Je vertrek voorbereiden of je verzekering afsluiten bij studie, stage of onderzoek in het buitenland
Study or work abroad? check your insurance options with The JoHo Foundation
Outlined is a quick introduction mainly in the anatomy of the human brain and its functions. Much of the information in the introduction chapter is also covered in the following chapters about neuropsychological disorders, so these topics will not be discussed here.
Clinical neuropsychology is about the study of human behaviors, emotions, and thoughts and how they relate to the brain, particularly the damaged brain. A number of disciplines are closely related to clinical neuropsychology, with neurology at one end and cognitive psychology at the other end:
There is not a strict division between these disciplines and in practice, they often overlap considerably.
Neuroimaging is rapidly developing, and clinical neuropsychology has been one of the greatest beneficiaries. Different methods of neuroimaging are:
The brain can be divided into three major divisions:
The limbic system is involved in:
The brain has three coverings, called the meninges:
An inflammation of the meninges is called meningitis.
The ventricles are lakes of CSF located deep within the hemispheres. The CSF is formed by the choroid plexus and circulates through the ventricles and around the outside of the brain and spinal cord within the subarachnoid space. When there is a blockage of flow, this is called hydrocephalus.
The cerebrovascular system involves two pairs of cerebral arteries, which branches further into different arteries which supply different parts of the brain:
The Circle of Willis is a circle of arteries that supply blood to the brain. It is a frequent site of weakening on the artery wall, called aneurysms. If an aneurysm bursts, it expels blood around the brain in the subarachnoid space, causing a subarachnoid hemorrhage (see the chapter about cerebrovascular accidents).
The parietal, temporal and occipital lobes constitute the posterior cortex and are involved mainly in a person’s awareness, perception and integration of information from the outside world, although their connections to the limbic system ensure that the way that the world is experienced, is influenced by a person’s mood, motivation and past experiences. Each of these lobes can be divided into three zones:
The frontal lobes are concerned mainly with the acting on knowledge relayed to the posterior part of the cerebral cortex from the outside world. They can also be divided into three zones:
Each hemisphere of the brain can be divided into four lobes. The lobes have their specialized functions, but the brain operates as a whole. So the division is not as strict as it sometimes seems to be.
The three posterior lobes are:
The frontal lobes are the anterior lobes. They are concerned with motor functions and executive functions such as forming abstract concepts and planning and executing actions based on the information received from the posterior cortex. The left frontal lobe includes the speech area, Broca’s area. As the frontal lobes are so important in mediating and integrating many brain functions, lesions to the frontal lobes can cause personality change. They can be the onset of an apathetic, aspontaneous, or even mute state or an increase in aggression or the display of inappropriate behaviors.
There are a lot of terms that describe different disorders, syndromes, or symptoms. An understanding of the main one will improve your understanding of the deficits mentioned in the chapters about neuropsychological disorders, so a few are outlined:
Other terms thar are commonly used are:
This method involves the standardized use of a set of group, or battery, of tests. The results on these tests of brain-damaged patients are compared with the results of non-brain-damaged patients. The results are matched on several demographic factors like age, sex, socioeconomic group, culture and years of formal education. The advantage of this method is that it can be conducted by any trained psychometrist who does not necessarily need to understand the underlying concepts of the tests. A disadvantage of this method is, is that there is no room for qualitative inter-individual differences in brain-behavior relations.
This method emphasizes the uniqueness of every case. A hypothesis-testing approach is used for assessment by giving a subject a certain test, and depending on the results giving further specifying tests suited to the individual. The contextual factor are also taken in consideration, like emotional state or learning history. A disadvantage of this method is that the assessment can only be done by a trained neuropsychologist. The quality of the assessment also depends on the training and experience of the neuropsychologist. So differences in outcome might be seen when the assessment is done by another neuropsychologist.
This approach uses a flexible battery of different kinds of test like the Wechsler Adult Intelligent Scale (WAIS-III), the Wechsler Intelligence Scale for Children (WISC), and the Wechsler Memory Scale (WMS). These tests have been revised over the years. These tests consist of several subtests, which can be added or deleted to suit the individual. The tests batteries use standardized scores, so the measures can be compared with normative data.
There are different phases that can constitute the neuropsychological assessment process. The referral can come from any health professional and can have different aims. A few examples are to aid with diagnosis, to monitor a patient’s recovery or progression of disease, to provide an up-to-date picture of the patient or to provide a baseline measure of cognitive functioning before neurosurgery or drug treatment and a follow-up assessment.
After the referral the clinical interview takes place which aims to provide the neuropsychologist with a picture of the patient’s difficulties and intact abilities from the point of view of the patient. Sometimes family members are interviewed as well. Medical and psychological history are also taken into account, as well as psychological and contextual factors, like depression and suicide risk.
The next step is the actual assessment. This is described above. It is very important for the conditions and surroundings to be standardized during the assessment and comfortable for the patients. So the lighting should be good and the room should be quiet. Some patients’ conditions make it hard to undergo the assessment the standard way, so personalized procedures should be thought of. After the assessment the neuropsychologist writes a report for the referral agency. Many neuropsychologists also provide the patient himself with the report, preferably in a follow-up session so the results can be explained. Some patients require only one assessment, but other might require more. For example after brain surgery. This is called follow-up assessment. During assessment, cross-cultural factors should be taken into account. Some cultures evolve other specializations than other cultures. These differences in abilities should influence how we interpret impairments after brain damage. The form of an assessment and the manner in which they are given, should be suited to the client's culture, norms and values.
There are many hundreds of tests that can be used for assessment. The most commonly used tests will be described shortly.
The most commonly used test to measure general intellectual ability is the Wechsler Adult Intelligence Scale (WAIS). This test has been revised several times. It consists of various subtests and the sum of the subtests scores can be converted into IQ scores.
The WAIS is divided into different groups: Verbal IQ, which consists of general knowledge, vocabulary, comprehension and verbal abstract function; and Performance IQ, which consists of complex visuospatial function, perceptual organization, psychomotor speed, and bonus points are earned for fast performance on most of these tests.
In the WAIS-III there are three further supplementary tests, that are used when further information is needed. The Verbal IQ and Performance IQ combined form the Full Scale IQ. They all have a mean of 100 points and the standard deviation is 15 points. The WAIS-III goes beyond the previous versions by adding four index scores to the IQ scores, to be known: Verbal Comprehension, Perceptual Organization, Working Memory and Processing Speed.
Language is a very complex function of the human being and can therefore be damaged in many different ways. Language impairments include speech fluency, naming, repetition, comprehension, reading, spelling, and writing deficits. The Short Token Test is used to assess the basic auditory comprehension of the subject before starting the other tests. Two often used aphasia batteries are the Boston Diagnostic Aphasia Examination and the Neurosensory Center Comprehensive Examination For Aphasia. The Communicative Abilities in Daily Living is designed to assess the patient’s ability to communicate in normal living situations.
Next to some of the WIS subtests, the Rey Complex Figure is a commonly used test to assess complex spatial functions that are often impaired following brain damage. The Complex Figure should be copied, and the copy is then compared to the copy of a non-brain-damaged person. The maximum score is 36 points, and is compared to normative data.
When the frontal lobes of people are damaged, they will experience problems with executive functioning. The frontal lobes are often referred to as the executive lobes because their main function is to formulate goals, to organize and plan, to carry out goal-directed plans, and to solve problems. Some subtests of the WIS assess some executive functions, but many other tests are designed for this aim. An example is the Wisconson Card Sorting Test. In this test the rules are changed by the examiner, and the subject should change his sorting behavior consistent with the new rules. This test assesses a person's ability to change mental sets, to form abstract concepts, to problem solve, and to plan a strategy. People with frontal lobe damage often have great difficulty with these sorts of tests. Perseveration is often seen; they return to the previous strategy, even though they know the rule has changed. A more recently designed test battery to assess different aspects of executive functioning is the Behavioral Assessment of the Dysexecutive Syndrome. This test includes subtests that require the sort of initiative, problem-solving, planning and organization that are essential for day-to-day functioning.
Memory involves many different abilities like attention, sensory memory, concentration, short-term memory, working memory, encoding, long-term store, recall and recognition. Usually people with memory impairment have anterograde amnesia, which means that they have difficulty learning and retrieving or recalling new information. This affects information learned after the brain injury. Some people have retrograde amnesia, which means they have difficulty recalling memories learned and stored before the brain damage. Retrograde amnesia is more difficult to assess than anterograde amnesia, as retrograde amnesia involves remembering information from the past, before the brain injury happened. It’s difficult to make sure that the information provided by the subject is real.
Sometimes The Autobiographical Memory Interview is used to establish the richness and reliability of a person’s past memories. Family members can be asked for verification.
As memory involves many aspects, many tests are designed to assess the different functions of memory. One commonly used test is the Digit Span test, a subtest of the WAIS. This test assesses short-term memory by measuring the number of digits the subject can hold in memory over a period of about 7 seconds. The most commonly used test is the Wechsler Memory Scale (WMS) and its revised versions. The main verbal subtests of the WMS are Logical Memory, Paired Associations, and Learning a list of unrelated words.
Another often used memory test is the recall of the Rey Complex Figure. This is often used as a test of incidental learning, which means that the subject is not told to remember the figure. He will later be asked to recall it.
It is very essential to estimate a subject’s premorbid abilities to make a conclusive evaluation of the current functioning. If a patient scores average on the WIS, this will not necessarily have to mean that he is not impaired. For example, before the injury he might have been a professor scoring very superior. This taken in consideration, his score dropped quite dramatically. The National Adult Reading Test and its revised version (NART-R) are designed to assess premorbid (before the injury) IQ. They rely on the fact that the pronunciation of irregularly spelled English words will not deteriorate in most cases. The score on this test is thought to be highly correlated with the WIS IQs.
Amnesia is memory impairment. There are two kinds of amnesia:
A memory loss for facts and events for a certain period before the damage occurred. Often people with retrograde amnesia show a temporal gradient, which means that the longer ago an event took place or a fact was learned, the better it is remember. So more recent things are not remembered compared to thing a longer time ago.
Usually the intelligence of the subject is not impaired. The severe cases just ‘live in the moment’. They don’t remember what just happened to them and don’t know what is going to happen. This can be very useful in research though, because the same neuropsychological test can be done over and over again without the subject getting bored because he doesn’t remember he just did the test a few moments earlier as well.
Every type of memory impairment can cause severe ability, but usually the subject is able to live a normal life and compensate with the memory functions that are still intact. Global amnesia, is however a lot more severe. It involves every aspect of the victim’s life; it includes an inability to learn new information, whether verbal, nonverbal, visual, or auditory, and it also includes a period of retrograde amnesia (see above).
Impairments in new learning and memory can occur for verbal material after damage to the left medial temporal lobe. The left hemisphere is dominant for language. Damage to the right medial temporal lobe can cause, less severe though, memory impairment for nonverbal material. Global amnesia usually results from bilateral damage to particular structures on the internal aspects of the cerebral hemispheres. Included are the medial temporal structures and structures surrounding the ventricles, including the thalamus and the mamillary bodies of the hypothalamus. The medial temporal lobes (particularly the hippocampus and adjacent cortical structures) are very important for the encoding and storage of new explicit information.
Research has shown that with the exception of lexical decision task, most tasks requiring implicit learning, do not require the amygdalae and anterior hippocampus, whether the learning process assesses motor, perceptual, or cognitive skills. There is evidence that semantic information learning is more intact than episodic learning. Semantic learning might be a more implicit process. Semantic information like world facts are often better remember than personal episodes from the period covered by retrograde amnesia. Implicit learning is better preserved than explicit learning.
Survivers of herpes simplex encephalitis can also experience global amnesia, as well as sufferers of Korsakoff’s disease. Korsakoff’s is characterized by a thiamine deficiency, and in these people the mamillothalamic region is destroyed. Survivers of herpes simplex encephalitis can experience amnesia because the disease can destroy the medial temporal lobe structures bilaterally. Korsakoff’s amnesia seems to be very different from the global amnesia experienced by herpes simplex encephalitis and ‘normal’ global amnesia however. In the last two the amnesia is a ‘pure forgetting’ problem, and cues to assist remembering don’t help. In Korsakoff’s patients, cues can help to remember, but they have difficulty to use higher-order concepts to organize material to be remembered. This seems to be caused by the frontal-lobe atrophy, often seen in Korsakoff’s patients. Korsakoff’s patients often perseverate (repeat actions or word) and confabulate (produce unconsidered, inconsistent, and sometimes exotic explanations, perhaps to fill memory gaps). These symptoms may also be the consequence of the frontal-lobe atrophy.
Epilepsy is an umbrella term for a range of central nervous system disorders that include seizures as a symptom. The exact nature of the neural mechanisms triggering seizures is unknown. Research is being done and new hypotheses are being formed. Brain functioning can be understood as the outcome of electrochemical impulses traveling along neural pathways and being directed and coordinated by a process in which some neurons are activated by an impulse and some are inhibited by it. Sometimes, the balance between excitatory and inhibitory neurons is distorted, and because of this inbalance more and more neurons are activated, without any counteraction by inhibitory activity. At a certain point the threshold is reached, and the storm of electrical activity in the brain results in a seizure. Most of the times this causes a temporary loss of consciousness, accompanied by motor, sensory, cognitive or emotional changes. Brain seizures are most of the time idiopathic, which means they have no known cause. They can occur in many different types of brain injury, so all taken together, they happen quite often. A conservative estimation is that five in a thousand people will suffer from epilepsy. As the seizures cause brain damage or dysfunction, which can result in cognitive and personality disorders of impairments, most sufferers seek help.
As mentioned before, most seizures are idiopathic. Some, however, are symptomatic which means that they are caused by an identifiable brain pathology, for example Traumatic Brain Injury (TBI). Other seizures are called cryptogenic, which means that they have a hidden cause. These are almost always due to some form of cortical abnormality acquired during fetal development.
Seizures can be classified on the basis of clinical symptoms and typical EEG-patterns.
Partial seizures
Simple partial seizures are haracterized by an abnormal neural firing restricted to a focal brain area. The clinical signs shown depend on where in the brain the excessive neuronal discharges are taking place. A simple partial seizure endures from several seconds to a few minutes. The patient is alert and maintains awareness and memory for the entire event. During the seizure the person will experience motor movements (Jacksonian seizures).
Complex partial seizures (also called psychomotor seizures or temporal lobe seizures) differ from simple partial seizures by a decreased awareness, a lack of responsiveness and an absence of recall for events occurred during the seizure. Complex seizures usually arise in the temporal lobe, in particular in the hippocampus underlying the temporal lobe. A complex partial seizure lasts for several minutes and begins as a simple partial seizure.
It then progresses to an impairment of awareness. Sometimes the sufferer may experience an ‘aura’ preceding the seizure. This may be for example an unpleasant smell or a feeling of fear. The aura acts as a warning signal that the person is about to have a seizure. After the seizure the victim enters a ‘post-ictal period’. This is a two to ten minute period characterized by disorientation, inactivation, inactivity and headache. The post-ictal period resolves gradually. During the seizure the patient may experience hallucinations or perceptual distortions, alterations of mood, or obsessional thinking. Sometimes during the seizure, the person displays automatism, like lip smacking. This is not recalled afterwards.
Partial seizures can evolve into secondary generalized seizures.
Generalized tonic-clonic seizures (Grand Mal)
This type of seizure begins with an increase in tone across multiple muscle groups and upward deviations of the eyes and the victim often cries out. This lasts for about 10 to 30 seconds. This is called the tonic phase. Then the person enters the clonic phase, and for a duration of 30 to 90 seconds, he displays repeated, bilateral, symmetric jerking of the arms and legs. Then the muscles stiffen and relax. After this the person enters the post-ictal period. This one is more severe and takes longer than in a complex partial seizure. The person may wake gradually and passes through phases of coma to confusion to drowsiness. Sometimes, the patient may fall asleep for varying lengths of time. After the seizure the patient has no memory for what happened. Afterwards the patient will be tired and experience muscle soreness.
Epileptic seizures can be classified into known epileptic syndromes.
An epileptic syndrome is an epileptic disorder characterized by a cluster of signs and symptoms customarily occurring together.
There is no standard pattern of neuropsychological test results which is characteristic of specific epilepsy subtypes.
Drug therapy is the most common used treatment for epilepsy. With the exact right dosage of antiepileptic drugs (AED), seizures can sometimes be completely controlled. AEDs also affect normally acting neurons, and can thereby cause cognitive impairment. AEDs target speed of processing, attention, executive functions, memory, and language functions. The dosage is very precise however, as the drug can produce side effects of drowsiness or even toxicity. There are individual differences in experiencing side effects. Some people are very content with a certain drug, while other experience negative side effects. The use of several different drugs by one person is not recommended. Some drugs can be dangerous during pregnancy.
In some cases the cause of the seizures is very clearly found in a lesion in the brain. Often, this lesion can be safely removed and relieve the person of its symptoms or reduce the symptoms. There are also cases in which the seizure clearly arises from a particular brain area, like the temporal lobe or the hippocampus. In these cases the epilepsy is idiopathic and removal the brain tissue where the focus of the seizures is located can be very successful in relieving the symptoms. This is, however, quite a dramatic treatment. Surgery is especially effective for refractory epilepsy, which resists drug treatment.
An example of this is Medial Temporal Lobe Epilepsy (MTLE). In 80% of MTLE cases surgery is effective.
Before the surgery takes places, EEG and MRI are used for thorough investigation for the possible location of the lesion. EEG patterns are abnormal in 95% of cases. Also tests are being done to determine which hemisphere is dominant for language, as language might otherwise be impaired when not paid attention to this. An often used test for assessing the language hemisphere and how good the other hemisphere would do in case of removal of language areas, is the Wada test. In this test a drug, called sodium amytal, is injected into the carotid artery of one hemisphere of the brain while the patient is awake. Before the drug is administered, the psychologist gives the patient a number of baseline speech, object naming and memory tests. When the hemisphere is anesthetized, the psychologist gives some baseline speech tests again, to test the other, awake hemisphere in how well it copes with speech, object naming, and memory. If the items of the memory tests cannot be remembered after the other hemisphere wakes up again, the temporal lobe and hippocampus of the hemisphere that remained awake cannot mediate memory. So removing these will not cause amnesia. Removing the temporal lobe and hippocampus of the hemisphere that was anesthetized, will cause amnesic problems. The surgeon will not go ahead with the surgery or remove only minor parts of the temporal lobe leaving the hippocampus intact. This will not cure the epilepsy, but might reduce the frequency of the seizures. In some cases fMRI is used to visualize the origin of the seizures.
This is a more reliable and safer procedure. As the research outcomes of surgery are further improving, in the future surgery might be the preferred opposed to drug therapy.
Psycho education and cognitive behavioral therapy can reduce the epilepsy in some cases. Especially because the treatment compliance improves and factors like stress are reduced. Therapy can help people learn strategies to cope with their epilepsy and can help readjusting to a seizure-free life following successful surgery. Therapists often encourage sufferers and their families to take part in support groups, where they can receive emotional and practical support and education.
Neuropsychological impairments in people with epilepsy may be a result of the brain dysfunction or lesion that also causes the epilepsy. It can also be a result of the mediation or the surgery. But other psychological factors can also cause or exacerbate the neuropsychological impairment. Children can experience problems following poor school attendance and when at school, often experience concentration problems. Worry, stress, anxiety, low self-esteem and depression are all understandable consequences of epilepsy.
Sufferers of epilepsy can experience several emotional and personality problems. These problems are often bigger in symptomatic epilepsy compared to idiopathic epilepsy. Victims of Temporal Lobe Epilepsy suffer the most disturbing problems. Many people end up in an identity crisis or get a ‘temporal lobe personality’, which is characterized by an increased emotional intensity.
Patients can also develop psychosis- or psychotic-like conditions between two seizures. This may be a transient ictal phenomenon. Also aggression, depression, increased stress and stigma are seen.
Intellectual deterioration is related to the severity of the seizure disorder and the underlying etiology. However, overall it has been shown that many of the subtests that make up an IQ battery such as the Wechsler Intelligence Scales are not sensitive to the subtle impairments found in some people with epilepsy. But impairments are found. A few examples are: attention deficits, perceptuomotor impairments; speed of mental processing; reaction and response times. Also poor mathematical skills and reading difficulties have been found, but epileptic students are seen to be at an appropriate academic level in other areas of schooling. People whose seizures arise in the temporal lobe or the hippocampus of the hemisphere dominant for language, which is usually the left, tend to demonstrate impaired functioning on tests of new verbal learning and memory. But they display relatively normal functioning on test of visual, nonverbal memory.
Aphasia is an impairment of the language ability. Most aphasias are caused by strokes, discussed more in detail in the chapter about cerebrovascular accidents. The type of aphasia depends on the location of the stroke, so which part of the brain is damaged or died off after lack of oxygen. Many patients do not fit the exact parameters for one language function or fall somewhere between two classifications, as there are many subtle individual differences in the location of language functions in the brain. Two people with a lesion on the same location might present with different symptoms.
Broca’s aphasia was first described by Paul Broca in 1861. This syndrome is known as expressive, nonfluent, or motor aphasia. The third frontal gyrus is the area most frequently associated with expressive aphasia and is called Broca’s area. The other most important area, the precentral gyrus, lies adjacent to Broca’s area. This area contains the motor neurons for the tongue and lips. People with Broca’s aphasia display a severe nonfluency of speech. In the most extreme cases, people are mute. An inmelodic speech results from the ability to pronounce nouns and verbs, but an impairment of grammatical modifiers and prepositions. Words beginning with letters like p, b or m are easier to pronounce than words beginning with letters like s and t. So ‘talk’ is articulated like ‘palk’. Verbs are pronounced in the simplest way, so the person will say ‘Me go’ instead of ‘I am going’. As the lesions causing Broca’s aphasia might also involve the motor strip for the hand, the right hand is often paralyzed. Copying is easier for Broca patients than writing spontaneously or to dictation. Many patients also suffer from oral apraxia, which involves nonspeech movements, like licking. A person with severe oral apraxia might be unable to stick out his tongue or whistle on verbal command. The degree of speech loss is highly correlated with the degree of oral apraxia. Language comprehension is often impaired, as well as comprehension of numbers and symbols. People with Broca’s aphasia are alert, unconfused and keep their intelligence. Their nonverbal memory is unimpaired.
This type of aphasia is often associated with damage to the left posterior superior temporal lobe and was first described by the neurologist Carl Wernicke in 1874. Wernicke’s aphasia is known as sensory, receptive, or fluent aphasia and the main difficulty is in comprehending speech. The comprehension deficit involves both spoken and written language. Because the comprehension is impaired, the repetition is also impaired. Syntax is mostly preserved, so the speech sounds fluently. But it often does not make any sense. Words like ‘bell’ might be replaced with ‘dell, this is called phonemic paraphasia. Also neologism might occur, which are non-existent words. Loss of intelligent behavior is often seen, and the patient does not seem to notice or does not seem to be concerned about his problems. If able to be assessed, verbal memory would most likely be impaired.
Almost always, a visual-field defect affecting the upper right quadrant and sometimes the whole right field, is present.
This is the result when Wernicke’s and Broca’s area are separated from each other. The supramarginal gyrus, which connects the two speech areas, can be damaged. Verbal output is fluent, but with many phonemic paraphasias, and comprehension of speech is often relatively well preserved. Repetition is however severely impaired. Reading aloud is impaired, in contrast to reading in silence, which is unimpaired. Writing is somewhat disturbed.
Global aphasia is the result of a large lesion affecting both Broca’s and Wernicke’s area and is accompanied by right hemiplegia, which means that the right side of the body is paralyzed. Speech is nonfluent and comprehension, repetition and naming are severely impaired.
TMA seems to be the result of the separation of Broca’s area to nearby cortical areas that are necessary for speech and is characterized by halting, nonfluent speech, but unimpaired, fluent repetition of sentences. Reading aloud for comprehension and comprehension of speech are unimpaired. Naming and writing are often impaired. TMA is often accompanied by right hemiplegia.
This resembles Wernicke’s aphasia, but the patient is able to repeat spoken language. He is however unable to comprehend it.
Anomic aphasia. This is the most common form of aphasia and it most often seen as the form of aphasia after head injury or in Alzheimer’s Disease. The main problem is a word finding problem. Speech is fluent, and repetition and comprehension of spoken and written language is unimpaired.
Examples of reading and writing deficits are:
In some cases, a person will completely recover from aphasia without treatment. This type of spontaneous recovery usually occurs following a type of stroke in which blood flow to the brain is temporarily interrupted but quickly restored, called a transient ischemic attack. In these circumstances, language abilities may return in a few hours or days.
Aphasia therapy is aimed at improving the patients communicating abilities, compensate for language problems, and learning other methods to communicate. Family involvement is very important as they need to learn new and other communication skills as well to communicate with the affected relative.
Autotopagnosia is a rare disorder that is associated either with generalized brain damage or with lesions to the left parietal lobe. The main symptom is an inability to point on verbal command to human body parts, either one’s own or those on another person (or doll or picture of a human). There are individual variances in the deficit, and several hypotheses have been proposed to explain autotopagnosia. One of them is that it is mainly a naming disorder. This fits well with the damage in the posterior left language hemisphere seen in autotopagnosia patients. Another hypothesis proposes that the deficit is the result of a more generalized difficulty with pointing to the parts of any object. As this hypothesis has a visuospatial aspect, it fits well with the lesion in the (visuospatial) parietal lobe. The third hypothesis suggests that it is a distortion of the body image that is mediated systems in the region of the left parietal lobe. This hypothesis seems to be the less likely one.
The left hemisphere is not only involved in language, but also in many other important cognitive functions. No two brains are alike, and the relation between the site of the lesion and the cognitive impairments followed by the lesions can differ between people. neurotransmitter systems can also be of importance. Many people show different impairments after lesions, some examples are:
Apraxia is an inability to carry out learned skilled movements (waving, brushing one’s hair) despite good comprehension, full cooperation, and intact motor and sensory systems. These days the term is used to describe a range of disorders, among which are (see also the chapter about cerebrovascular accidents):
Four disorders make up Gerstmann’s Syndrome: agraphia, acalculia, right- left disorientation, and finger agnosia.
Difficulties in writing. Because writing is a complex skill requiring the cooperation of a number of abilities, agraphia can result from lesions in many different parts of the brain and a range of different deficits. The agraphia usually associated with Gerstmann’s Syndrome results in writing or printing that is well formed, but spelling and word order that are often incorrect and omissions (leaving something out) are frequent. Alexia, a reading impairment, is not present, so the patient is able to read his own poorly written sentences and often see that they are incorrect.
This is a deficit in calculating. Calculation is a very complex function and can be disturbed by lesions in many areas of the brain. For example right parietal lesions that result in a difficulty with manipulating the spatial positions of figures. Patients with left-hemispheric lesions are more likely to have difficulties with the logical grammatical relationships involved in, for example, ‘take away 3 from 7’. The biggest problem seems to be in interpreting ‘take away’.
This is a confusion in discriminating a rightward direction from a leftward direction. This can be viewed as a spatial disorder, but it is almost always consequent on a posterior left (or dominant) hemispheric lesion.
Finger agnosia is not knowing the fingers, so for example not knowing which one one’s thumb or index finger is. The person can also not point to a finger when the name is given. Also, he may not recognize which finger has been touched by the examiner.
There is considerable controversy if Gerstmann’s syndrome exists at all. It has been argued that this group of symptoms may be found simply because they are each mediated by anatomical systems that are physically close to one another, not because they are intrinsically or functionally bound together, perhaps because all the symptoms have some cognitive subcomponents in common. When the four Gerstmann symptoms coexist, the lesion is almost always in the posterior left lobe, often involving the parieto-occipital junction region.
Hemineglect is known under various names: hemineglect, hemispatial neglect, unilateral neglect, unilateral spatial neglect, and unilateral inattention. This spatial impairment quite commonly follows focal damage to one hemisphere of the brain in humans. The main symptom is an apparent unawareness or unresponsiveness to stimuli in the side of space opposite the brain damage. The stimuli may be in any modality, but in humans neglect of visual stimuli seems the be the most common form of the disorder. Also common is neglect of the limbs on the side of the body opposite the side of the damage. Both left- and right- hemispheric neglect can occur, but right-hemispheric neglect is usually more severe and lasting.
Curiously, patients with left-sided neglect from a right-sided lesion not uncommonly joke about their problems, and in cases where this is extreme or clearly inappropriate, it suggests a lack of awareness about the seriousness of their condition. This in itself seems to be the result of the right-hemispheric lesion. Some researchers have suggested that the right hemisphere is the depressive one and that the left hemisphere is the happy one. So when the left hemisphere is damaged, the depressive right hemisphere might dominate the emotional expression, resulting in catastrophic depressive reaction sometimes seen following left-hemispheric damage. When the right hemisphere is damaged however, the patient might underestimate his condition as it is not appropriately moderated by the damaged right hemisphere. In these cases the patients might even found their condition amusing.
Hemineglect is common following unilateral brain lesions. Researchers are very intrigued by these cases: How it is that patients do not overtly respond to the stimuli of their own limbs in their neglected hemispace, yet at another level demonstrate in various indirect ways that they are aware of their presence in that hemispace? Hemispace refers to the extracorporal (outside the body) space to the left or right of the body and head midline. It is distinct from the visual field and from the hand or ear receiving input. For example, if a person places his right arm across his body, his right hand will now be in his left hemispace. Only in the situation where a person aligns body and head visually fixates directly ahead do the left and right visual fields and left and right hemispaces coincide. If the head or eyes are moved to the left or right, the visual fields are displaced accordingly. The hemispaces are not, however, tied to eye movements, and they therefore will no longer coincide with the visual fields.
Hemineglect can occur in one or more modalities in the same patient. A patient with a right-hemispheric lesions and left-sided neglect often fails to complete the left side of drawings he is asked to copy, misses the words on the left side of a page he is reading, ignores people standing on his left, collides with the wall on his left when walking down a corridor, and in severe cases, eats only dinner on the right side of his plate and then complaints that he is hungry. The same is possible for left-hemispheric lesions and right-sided neglect.
When presented a stimulus in the visual field, the patient will be able to respond to stimuli in the right and the left side. When presented two stimuli simultaneously to the right and the left visual field, however, the person will only respond to the stimulus presented in the field on the side of his lesion.
Auditory neglect, anosognosia, misoplegia and anosodiaphoria are less common forms of neglect.
Recent studies using Magnetic Resonance Imaging (MRI) have enabled detailed topographical mapping of the lesions of patients with hemineglect. The scans show that the lesions of patients who have persisting hemineglect are large and usually involve two or more cortical or subcortical brain areas. The most common affected brain areas in hemiplegics are:
Sometimes the cingulated gyrus and thalamus result in neglect, but this is more uncommon. Lesions in all areas in the left hemisphere can cause hemineglect of the right hemispace or limbs, but the symptoms tend to be much less severe and recovery more rapid than when they have lesions in the right hemisphere. The most patients who require rehabilitation are patients with right-hemispheric damage and left-sided neglect.
Neglect is usually at its most dramatic immediately after the brain damage occurs. There are different causes of neglect, and often they have an individual path of recovery. Some causes of brain damage causing hemineglect are strokes and tumors.
There are different kinds of stroke possible:
There are different kinds of tumors possible:
To this day, no definitive theory has been put forward able to explain all aspects and forms of neglect. Most theories tend to fall into one of two categories:
In most case, spontaneous recovery is rapid, occurring within days to months of a stroke. The most rehabilitation interventions are aimed at attention. The patients need to become aware of their neglected hemispace or neglected side of the body. Also training in coping with the difficulties is very important. Rehabilitation interventions should begin early to ensure that the patient receives training that will stimulate appropriate synaptic reconnections and lessen the possibility of the patient developing behaviors and movements that foster faulty connections.
The family of cognitive disorders known as the agnosias includes a wide range of ‘not knowing’ impairments, many specific to one modality. So there are not only visual agnosias but also auditory and somatosensory (tactile) agnosias. Nosia means to know, and agnosia means not to know. A few examples of agnosias and subdivisions are:
Visual object agnosia means not to know objects by vision. This disorder has been known for over a hundred years and is quite uncommon, but not rare. It is considered one of the ‘classical’ neuropsychological disorders. Objects can be seen but not recognized. It is modality specific in that the object can be recognized via the other senses of touch, sound or smell. When the object is recognized through other ways, the person is able to name it, so visual object agnosia is not a disorder of naming.
Three types of visual agnosia have been described:
All these three types of visual object agnosia are usually associated with bilateral occipital damage.
Some patients with visual object agnosia also experience a loss of visual imagery, but this is not by far always the case. It may be that the individual differences in the ability to make visual images influence what happens after brain damage and that imagery may be mediated by more than one functional system in the brain. Also a loss of color perception, called achromatopsia, which is also associated with bilateral occipital damage, and a loss of color memory can occur.
Prosopagnosia is the inability to recognize familiar faces on sight and is usually, just like visual object agnosia, associated with bilateral occipital damage. Therefore it is often found in patients together with visual object agnosia. The system representing complex parts is like faces is very vulnerable because it so complex. So only mild damage is needed, to result in prosopagnosia, as recognizing faces is a very complex ability. More severe damage to this system not only results in prosopagnosia, but also in difficulties in recognizing complex objects. Object recognition is by far not as complicated as face recognition, so more severe damage is needed to cause visual object agnosia than to cause prosopagnosia. Some cases of visual object agnosia are related to alexia, an impairment of reading. The damage seems to be done in the ability to form whole words of separate letters, so integrating parts into meaningful wholes. This is a hypothesis, and if it correct, it suggests that different systems or pathways in the occipital lobes are concerned with different types of visual representation.
This once more underscores that the site of a brain lesion at best provides a guide to the type of impairments the patient might have, but only a careful neuropsychological assessment can tease apart the subtle differences between many higher cognitive processes.
Psychosurgery (brain surgery for the purpose of relieving psychiatric symptoms) decreased substantially from the 1950s on, although centers in some countries still practice modified procedures called leukotomies. In these operations, the frontal lobes are partially disconnected of the rest of the cortex by sectioning the thalamofrontal fibres in the lower medial quadrant of the frontal lobe. These and similar greatly modified operations are reported to provide relief from the psychiatric symptoms of psychiatric disorders, with minimal frontal-lobe symptoms.
Frontal-lobe impairments are, taken in all its forms, from mild to severe, probably the most common neuropsychological symptom cluster in the neurological population. There are many causes of frontal-lobe impairment, for example:
The assessment of frontal-lobe functioning is as integral a part of a basic neuropsychological assessment as is the assessment of verbal, visuospatial, and memory functions.
The term frontal-lobe syndrome is still sometimes used as an easy way to describe the range of impairment that can characterize frontal-lobe dysfunction. It has been labeled a syndrome because it comprises a range of cognitive and emotional deficits commonly associated to the prefrontal lobes. The deficits can be mild to significant, and different combinations of deficits occur in different patients. People at the severe end of the frontal-lobe dysfunction spectrum, often display unambiguously bizarre and debilitating behaviors. Frontal-lobe dysfunction is, however, often associated with subtle impairments, such as irritability, poor motivation, and a quickness to lose one’s temper. All these impairments can disrupt the life of the sufferer and his family.
Often no obvious damage to the frontal lobes is seen in people who display many frontal-lobe deficits.
There are many reasons for this, like:
The functions mediated by the frontal cortex are very complex and diverse. It is easy to ‘use’ frontal-lobe dysfunction to explain complex disorders that are otherwise too difficult to explain. An example of this is the frontal-lobe hypothesis of schizophrenia, which proposes that some of the symptoms of schizophrenia are related to frontal-lobe dysfunction, perhaps as a result of a neurotransmitter imbalance or as a side effect of the major tranquilizers taken by many people with schizophrenia.
The frontal lobes are the part of the brain most recently developed. Because of their large size in men relative to other primates, they are often viewed as the seat of the highest and most complex cognitive capacities. The frontal lobes have rich connections to all other parts of the brain and organize and perform purposeful and goal-directed behavior.
Modern neuropsychologists have labeled the frontal lobes the executive lobes because of their role in formulating, modifying, and executing plans of action. This results in patients having frontal-lobe dysfunction being able to perform well known, highly structured tasks, but having difficulties in performing unknown, unstructured tasks, that requires planning a strategy to initiate and complete the task. Also if this task involves thinking in terms of abstract concepts, the person with frontal-lobe dysfunction may well show deficits.
These problems in executive functions show in many tests, like the Block Design items of the revised Wechsler Adult Intelligence Scales (WAIS-R). To carry out these test successfully, the subject must be able to conceptualize how to break a pictured pattern into block-sized unit. Especially patients with frontal or parietal damage show difficulties. Frontal patients might improve with a little structured help, but parietal patients cannot do the task because they have visuospatial perceptual and construction problems. No one kind of instruction will help them overcome their difficulties.
Another task which is difficult for patients with executive impairment, is the Rey Complex Figure. When asked to copy this drawing, they often use a piecemeal approach, suggesting that their ability to plan a logical approach to this task is flawed. But if the figure is presented in consecutive stages, their performance improves greatly. Many people with focal prefrontal-lobe lesions perform normally when copying the Rey Figure, especially once they have recovered from the acute effects of their stroke or head injury.
Patients with executive deficits, often perform normally in intelligence tests. This is probably because these tests are in general highly structured. Working memory, prospective memory and the ability to think abstract are often impaired. The impact of impaired executive functions on everyday activities is often much more debilitating than the individual’s formal test performance would indicate. Planning, preparing, and serving a relatively simple meal can become impossible.
Frontal amnesia is a term often applied to people who do not suffer from true memory impairments in the sense of experiencing difficulties with registering, encoding, or retrieval, but who have apparent memory problems because of an inability to form plans that enable them to regulate the procedures and verify the outcomes of the various mental steps in the memory process.
Often, people with severe frontal-lobe damage, display personality changes. A few examples are:
People with frontal damage often have frontal amnesia. This sometimes results not only in apparent memory impairments but, perhaps of disinhibition, also encourages confabulation. This is the tendency to fill in memory gaps with self invented stories. Patients do not seem to be aware of this. Another symptom is perseveration. This is the stereotypical repetition of sentences and behaviors.
Traumatic brain injury (TBI), also known as intracranial injury, occurs when an external mechanical force traumatically injures the brain. TBI is evidenced by:
Head injuries can be classified into three types:
The damage that occurs in the first few seconds of an accident is sometimes called the first injury. In severe closed head injury, the neurological damage does not stop there. A second injury can occur if the person is trapped in a way that blocks breathing. Vomit can be a cause of this. The consequence is that the oxygen supply to the brain is reduced. The longer this takes, the more (irreversible) damage will be done. Another cause of second injury can be that the person looses a lot of blood, which can also reduce the oxygen supply to the brain. taken these risks into account, emergency treatment is of vital importance. Even third injury can occur. Many victims of closed head injuries do not die immediately, but days or sometimes even weeks later. Third injuries can be the cause, this includes swelling of the brain as the escaping fluids from damaged cells and blood from torn vessels cause a rise in intracranial pressure. After a while the pressure gets too high, preventing the blood from circulating, so the brain dies off.
The injury can be focal or diffuse. When it is focal, it has affected circumscribed regions of the brain or one region. When it is diffuse, the brain is affected in a widespread pattern. The injury can occur when a object strikes the head or when the brain comes into contact with the skull. The pathology in these cases is focal in nature and may include injury to the skull or even skull fracture, as well as surface contusions (bruise of the brain) and intracerebral hematomas, which are bleedings into the brain tissue.
Another cause of TBI can be acceleration of deceleration of the brain resulting from unrestricted movement of the head. This results in shear, tensile and compressive strain on the brain tissue. Bridging veins are torn, subdural hematomas grow and diffuse axonal and vascular injuries occur. In acceleration or deceleration injuries, contre-coup injuries are frequent. In contre-coup injury the side opposite to the side of impact gets damaged, because the brain bounces back and forth inside the skull after the impact.
Some important facts about TBI are:
One month after the injury the patients with the most severe injuries have impairment on most measures. The patients with less severe injury tend to have more selective impairments, like impairments of memory, cognitive flexibility and psychomotor speed. The premorbid characteristics and functional states are more predictive for outcome one year after injury than the severity of injury. The Glasgow Outcome Scale (GOS) can be used after injury, to measure the outcome. The outcome tends to get better with the passage of time.
The different measurements of the GOS are, from worse to better:
After the traumatic brain injury, some victims develop the Postconcussional Syndrome. This is the most psychological disturbance following TBI and is characterized by: unpleasant sensations and pain; cognitive disturbances; emotional changes; insomnia; reduced tolerance (e.g. for alcohol); preoccupation (e.g. hypochondrial concern).Six years after injury, 70% of victims still suffer from cognitive impairments, most frequently in learning and memory.
The risk of unemployment after TBI is higher in:
The severity of TBI can be assessed using different techniques. A way to measure injury severity is by time to follow commands. This is predictive for global outcome, neuropsychological functioning, personal independence and employment after TBI.
A frequently used assessment method is the Glasgow Coma Scale (GCS).
The GCS measures the depth of coma by assessing the level of responsiveness on:
A higher score indicates more intact functioning. The GCS is predictive for early important outcomes and later functional outcomes. The classification should be done within the first 24 hours after the TBI. The classification by score is as follows:
Many people with mild TBI do not seek treatment or are not hospitalized. Their cognitive deficits usually resolve in about three months. People with moderate to severe TBI are more likely to require inpatient or post-acute rehabilitation.
Another way of assessing the severity of the TBI is by measuring the coma duration since the injury, classified by:
Posttraumatic amnesia (PTA) is a phase of recovery during which the patient is responsive but confused, disoriented and unable to form and retain new memories. The duration of PTA is predictive for: neuropsychological outcome; independent living; return to work. The classification is as follows:
What can be confusing is that the GCS and PTA can have different outcomes. It’s a difficult decision which one to use as the official measurement.
Traumatic Brain Injury can be very dramatic, and emergence treatment is often necessary to prevent further damage. The emergency treatment is aimed at:
After the acute treatment, sub acute treatment is given to minimize the damage. The treatment goals are early detection of complications, facilitation of neurological and functional recovery, prevention of injury, like during PTA, as this is a period of confusion.
Different stages of recovery are the following:
The rehabilitation for head-injured people is far from straightforward. This acts against the establishment of successful programs. Head-injured people have organically based problems with memory, planning, and organization, impaired judgment, a poor ability to learn from their mistakes, poor motivation, and emotional mood swings as a result of diffuse shearing injuries, brain stem injuries, and focal damage to the frontal and temporal lobes. They also suffer from lowered self-esteem, a loss of confidence, and psychosocial problems that have an effect on every aspect of their daily life.
A cerebrovascular accident (CVA) is a general term that refers to a stroke or brain hemorrhage as a result of a blockage or rupture of an artery or vein. An infarct is an area of tissue death due to a local lack of oxygen, caused by obstruction of the tissue’s blood supply. A stroke is the rapidly developing loss of brain functions due to disturbance of the blood supply to the brain. This disturbance can be due to ischemia (lack of blood flow), or a hemorrhage (leakage of blood). A very important part of the vascular geography of the brain is seen in the Circle of Willis. Here each internal carotid artery supplies one hemisphere, it divides to form the anterior cerebral artery and the middle cerebral artery. The posterior cerebral artery arises from the basilar artery. There are different kinds of CVAs and one of them is the ischemic stroke. The ischemic stroke is characterized by an abrupt onset of a focal neurological deficit, like disruption of strength, speech, perception or cognition, which is consistent with the vascular distribution. An ischemic stroke lasts longer than 24 hours and the arteries are blocked or ruptured. This causes an insufficient oxygen supply to the brain, which in its turn causes cell death in the brain. There are several mechanisms that can be the underlying cause of the ischemic stroke:
Several ischemic strokes are possible, for example:
Another kind of CVA, in which the signs usually develop gradually, is the hemorrhagic stroke:
More men than women experience a stroke in their life but more women die after a stroke. The cognitive domains which are most effected by a stroke are memory, orientation, language and attention. Several deficits present depending on which of the hemispheres is affected.
When the left hemisphere is affected by an infarct, common symptoms are:
When the right hemisphere is affected, common symptoms are:
Often there is a comorbidity of psychiatric problems in the early phases of a stroke. Some persist into the chronic phase. About 33% of the affected experience depression, and about 20% experience anxiety. Other seen problems are: disinhibition, denial, mania, apathy and overt aggression.
The diagnosis of a CVA is very important, as time is brain. The more time has passed since the onset of the stroke, the more brain is damaged. Often a lumbar puncture is done, to detect blood in the cerebrospinal fluid (CSF). Blood in the CSF may indicate bleeding in the subarachnoid space of the brain, caused by a hemorrhagic stroke. When a stroke has taken place, two zones are distinguishable: the penumbra, which is the zone of reversible ischemia and can be saved by emergency stroke care; the core, which is in the zone in the middle, where irreversible damage is done.
There are different kinds of treatment possible, depending on the kind of stroke and the time passed since the onset:
The goals of the treatment of intracerebral hemorrhage are to stop the bleeding, to remove the cloth, and to relieve the pressure on the brain, this can be done a placing a shunt. When it’s not treated, the clot will be absorbed by the brain in weeks.
A subarachnoid hemorrhage (SAH) has a sudden onset and is a rare form of stroke that usually happens in previously healthy people. Most victims fall in the 45 to 60-year age range. Some people die immediately or lose consciousness and die over the next few days. Many remain awake but become confused and drowsy.
The onset of the hemorrhage is the feeling of an explosion in the head, in 77% of cases caused by the bursting of an aneurysm. In 7 to 25% of cases, cerebral angiography fails to reveal an aneurysm. These cases are called non-aneurysmal SAH. An aneurysm is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms have a genetic component. Other causes are head trauma, tumors, infections, or the rupture of an arteriovenous malformation (AVM), which is a congenital and abnormal tangle of blood vessels. Several risk factors have been identified for SAH. Among those are cigarette smoking, hypertension, a sudden rise intracranial pressure (for example caused by sneezing), a transient rise in blood pressure associated with physical strain, or sudden emotional shock. Recovery is very variable among victims. Some return to their previous state of functioning, while other sustain severe brain damage resulting in global cognitive deterioration and paralyzed limbs.
The subarachnoid space is a space filled with cerebrospinal fluid (CSF) where the brain lies against the layers at the inside of the skull. In SAH blood is released into the subarachnoid space, which causes increased pressure on the brain. To see if there is indeed blood in the subarachnoid space, a lumbar puncture is being performed.
Hydrocephalus is a lack of absorption, blockage of flow, or overproduction of CSF. In the area deprived of oxygen a stroke occurs. The pressure can be relieved by placing a shunt into the ventricle, which allows the excess CSF to drain safely into the abdominal or heart cavity.
The damage to the brain can be done by the blood around spilled by the ruptured aneurysm but also in the brain itself. The severity of a subarachnoid hemorrhage can be measured by the Hunt-Hess Grading Scale. The scales are as follows:
Next to the Hunt-Hess Grading, the Glasgow Coma Scale is often used to assess the severity of the head trauma.
Three to fourteen days after the subarachnoid hemorrhage the person can experience vasospasms, in which the arteries react to the blood around them by going into spasm, which can result in a loss of blood and oxygen (ischemia) to the area of the brain supplied by that artery, resulting in ischemic stroke if left untreated.
When people survived the initial hemorrhage, they undergo 2,5 to 4 hour neurosurgery to clip off the source of the bleeding, which is usually an aneurysm. In this procedure a microscopic clip is placed at the base of the aneurysm to prevent it from filling with blood.
Another possible surgical procedure is endovascular coiling. A tiny soft platinum coil is released into the aneurysm sac. The coils attract blood cells, platelets and fibrinogen, which results in clot formation. Clipping is more invasive, as it requires opening up the skull. This is not the case in coiling, but the downside of coiling is that the aneurysm is often not fully occluded. Clipping has a high success rate in permanently occluding the aneurysm.
Sometimes the aneurysm is not treated. This can be the case in people who are too sick, or the aneurysm might be very difficult to reach. Some aneurysms are very risky to treat, like a giant aneurysm over 25 mm in diameter in the tip of the basilar artery. The risk of rupturing and thereby causing death during clipping or coiling is very present. In these cases, people need to adjust their lifestyle in for example quitting smoking and reducing hypertension.
With surgery there’s always the risk of doing damage, independent of the kind of aneurysm treated.
Nowadays, more unruptured intracranial aneurysms (UIAs) are discovered because of the improvements in neuroimaging. UIAs are discovered in imaging and angiography following SAH and sometimes also in persons undergoing MRI for some other unrelated problem. When an UIA is discovered, the person needs to decide whether to get surgery or not. If he chooses not to, he will be followed up at regular intervals to ensure the aneurysm is not growing larger. Also he will be advised not to smoke and avoid risk factors for hypertension. In many people with an UIA, it will never rupture.
More than half of the victims of SAH die or become demented. The site of the rupture has not been found to correlate to the type or severity of cognitive impairment. Among the often reported neuropsychological problems after SAH are:
Commonly reported psychosocial symptoms by patients and their families after SAH are:
Because of all these problems most people who even had a good recovery find it very hard to return to their old job, especially if it involves concentration, long hours, or complex decision-making. Many start working at a lower level of shorter hours. It is very important for SAH patients to return to work, both financially and for their regaining of self-esteem. The poor motivation to return to work might be in part explained by the fatigue and the irritability experienced by the person when struggling with subtle and unrecognized cognitive impairments.
A few decades ago, people were not yet aware of the damaging effects of exposure to organic solvents that are widely used in industry in paints, glues, adhesives, and degreasing or cleaning agents and in the production of plastics, textiles, printing inks, polymers, dyers, agricultural products and pharmaceuticals. Many workers work with these solvents and long or intense exposure can result in Organic Solvent Neurotoxicity (OSN). In recent years health professionals have become increasingly aware of the debilitating symptoms that characterize OSN.
In the earlier days, protective clothing was not worn, but these days, more and more safety standard have to be followed. Most workers protect themselves very good now with protective clothes, but unfortunately lots of them also refuse to wear them, because the clothes can be uncomfortable to work in. The clothes might be hot or difficult to move around in. Typically, people who suffer from OSN type 2 (see below), are men in their 30s or older and are usually skilled or semiskilled trades people, like carpenters, pest controllers, or dry cleaners. It is often very hard for these people to quit their jobs once they start experiencing the effects of exposure to solvents. They often have a family to take care of, so money has to be earned.
OSN tends to have a slow and insidious onset; it can take a long time for the symptoms present. Usually ten years or more of exposure to solvent is necessary for the symptoms become apparent. Accidental intake of solvents into the bloodstream is either via direct absorption through the skin of via inhalation. Solvent abuse via inhalation is also common among young people. Solvents accidentally of purposefully ingested (suicide attemps9 are readily absorbed form the gastrointestinal tract. The immediate exposure level of the solvent can be measured in urine, blood, or exhaled air.
Among the acute symptoms of OSN are:
Not everyone displays these symptoms however. Some victims of OSN never had the acute symptoms, but do suffer from chronic OSN. Also some persons who did experience the acute symptoms, will not develop chronic OSN.
This can be because they stop working in the solvent environment after they have experienced the unpleasant acute symptoms, before irreversible neurological damage results.
Most of the acute symptoms resolve quickly, but will return again as soon as the person enters the solvent environment again. The solvent can often be detected on the victim's breath and skin for many hours and even days after they have left the solvent environment. The symptoms include psychological and psychiatric symptoms and impairment of cognitive functioning.
Because the onset is slow, most victims will not realize that the cause of their symptoms is the long exposure to solvent at their job. Years later they will be looking for help because they are aggressive, irritated, have chronic fatigue, poor memory or other problems. It will be very difficult then to identify OSN as the primary cause of the problems, and proving cause and effect beyond doubt is almost impossible. So it is very important for clinicians to become familiar with OSN syndrome as many victims will not realize the cause of the problems themselves.
A neurological examination or computed tomography (CT) usually will not reveal a lot, because the neurological damage resulting from neurotoxins tends to be diffuse or may, for example, involve a neurotransmitter balance. As the clearest indicator will be cognitive and psychological impairments, neuropsychological assessment will be the best method to diagnose chronic OSN. A neuropsychological assessment is also officially required to be used in diagnosis of OSN.
The individual differences between sufferers of chronic OSN are big, as several factors play a role. These include:
So victims with the same severity of OSN, might display different damage or might have been exposed to other (mixes of) solvents.
Three types of OSN are defined by the International Solvent Workshop:
Type 1 OSN. This is the least severe type of OSN and is reversible on removal from the solvent. The symptoms are subjective complaints of fatigue, irritability, depression, and episodes of anxiety. On neuropsychological tests, no impairments show.
Type 2 OSN. This type is more severe and chronic than type 1 and is not completely reversible. The severity may reduce as the time since the last exposure to solvents lengthens. This type of OSN requires neuropsychological and clinical assessments to demonstrate chronic symptoms of neurotoxicity and cognitive impairments. The diagnostic features include sustained personality and mood disturbances, fatigue, poor impulse control, poor motivation, impaired concentration, memory, learning, and psychomotor slowing. The recovery may be enhanced by appropriate counseling or rehabilitation.
Type 3 OSN. The third type of OSN is uncommon. It is a dementia and requires a global and progressive deterioration in memory, other intellectual functions, and emotion.
Commonly caused problems in the client’s daily activities are the result of fatigue, irritability, depression, anxiety, poor concentration, and memory impairments.
It is difficult to isolate the causes of depression, anxiety and irritability, but they might be seen as direct or indirect consequences of OSN. Indirect causes of depression and anxiety could include a poor memory, lowered sexual drive, fatigue, and low energy levels. These symptoms could result in marital stress, hypersensitivity to noise, constant headaches, and other physical symptoms that lower work capacity.
Other psychiatric symptoms include:
Physical symptoms are often present as well, these include:
The most often used battery for the assessment of OSN has been developed by the World Health Organization/Nordic Council. The Scandinavian countries are the research leaders in this field. The neuropsychological symptoms most commonly found in cases of OSN are those associated with diffuse cerebral encephalopathy. The picture painted by OSN sufferers often looks like mild to moderate closed head injury.
Neuropsychological test results reveal difficulties in vigilance, psychomotor speed, reaction time, memory for new material, and visual perception and memory.
More severe cases display deficits that are suggestive of possible frontal-lobe dysfunction:
Many clients benefit from therapy that help them express and resolve their understandable anger, resentment, frustration, and grief as they become aware that their occupation has lost them their health, job, and often their relationship. Perhaps most important of all is the task of rebuilding the clients self-esteem.
Multiple Sclerosis (MS) is an autoimmune inflammatory disease which is characterized by multiple attacks to the central nervous system (CNS) of a wide variety of neurological symptoms. There are many different types of symptoms; which symptom is showing, depends on which part of the CNS is affected.
Many symptoms are unpredictable and transient, which means that they are temporary. Often the first symptom is numbness in the extremities, which can spread gradually. MS is life long, but not fatal. 95% of sufferers have an abnormal brain and the majority has an abnormal spinal cord, shown in MRI.
The prevalence is about 100 cases per 100.000 people, affecting people primarily between age 20 and 40. Less than 10% of the MS sufferers are affected after age 55 or before puberty. If people are affected after their forties, the progression of the disease is more rapidly. This makes MS the most common nontraumatic neurological disease among young adults. Twice as many women as men are affected, and the prevalence also varies between cultures.
What is interesting, is that MS is much less common around the equator. It seems to be that the climate experienced before puberty, has an influence on whether one develops MS or not. The climate experienced after puberty does not have any influence. There seems to a heritable biological predisposition for MS. 15% of people suffering from MS, have a first-degree relative suffering from MS as well. Monozygotic twins also have a higher concordance rate than dizygotic twins.
MS is an autoimmune condition, which means that the immune system, which normally attacks infectious viruses, now attacks itself, which is called inflammation. The body mistakes its own tissue for foreign tissue, which results in damaged myelin sheaths which cover the nerve fibers. This process is called demyelination. Myelin is necessary for the quick transportation of signals along the nerves. This transportation is called salutatory conduction. This means that the electrical signal travels from one node of Ranvier to the next node of Ranvier and so on. When this process is distorted, the messages will travel very slowly along the nerve or do not get through at all. The damaged myelin sheaths form sclerotic plaques, which are mainly (75%) found in the white matter of the brain, especially around the lateral ventricles, the corpus callosum, the frontal lobes, the brainstem, the cerebellum and the optic nerves. Another neuropathological sign of MS is lesions in the brain, which develop at different moments over time or have progressed over some time. Sometimes axons are affected by inflammation as well. The CNS will try to compensate for this, but after a while the threshold will be reached, and the disability gets irreversible and progressive.
MS can be classified into four main types:
This is the most common type of MS and 85% of people suffering from MS ‘start’ with this type. Relapsing remitting MS is characterized by sudden attacks which increase over time but also often decrease after a while. This is followed by a period of remission without symptoms or with only mild symptoms. Complete remyelination is not always necessary for the recovery of functions. The next attack (relapse) will not be present for at least 30 days, and often even years. A relapse is caused by inflammation or demyelination and lasts at least 24 hours. A person has to have experienced two attacks or more to be diagnosed with MS. He also has to have evidence of two distinct areas where demyelination has taken place. A subgroup of people with this type of MS show a benign form, which is characterized by few attacks and little or no disability after 20 years of suffering from MS. Typical symptoms of relapsing remitting MS are a feeling of numbness, a disturbance or loss of vision, fatigue, depression and trigeminal neuralgia, which is characterized by unusual sensations such as electric shocks.
This type usually forms from the relapsing remitting type. The attacks often are not followed by periods of remission anymore, and each episode leaves some permanent deficit, which can also get worse without the presence of any more attacks.
This form is MS is not characterized by attacks, but by a slow and progressive accumulation of neurological symptoms. Very common are lesions in the spinal cord, which causes limb numbness in the lower part of the body, and because of this difficulties in walking. Urinary frequency and urgency is also common.
This is the least common form of MS. It starts with the primary progressive type of MS, but becomes accompanied by attacks which is accompanied by a steadier decline. If MS is left untreated, 50% of sufferers will have progressive MS in 10 to 15 years.
Fatigue is very common among MS sufferers. Many people also get depressed, which can be a reaction to the disease or can be caused by the underlying neurological processes of MS. Somatosensory symptoms are the most common ones in MS. Especially feelings of numbness in the extremities are very common. Also frequently seen are brainstem syndromes, characterized by vertigo, and cerebellar syndromes, characterized by gait and intention tremor. Many people also experience visual pathway syndromes, bowel and blabber difficulties and sexual dysfunction. There is a life time depression prevalence of 50% among MS-patients.
Depression is sometimes accompanied by behaviors like suicide alcohol abuse or social isolation. Anxiety is experienced by about 25% of the MS sufferers.
Mild to severe cognitive deficits are present among about half of MS-patients. Whether cognitive deficits are present depends on the type of MS and in particular on whether there are lesions in the white matter or not. The more lesions there are, the more cognitive deficits the sufferer shows. The location of the lesion and the form of cognitive deficits are related. The severity of the physical disabilities and the duration of the disease are not related to the severity of the cognitive deficits. Someone primarily having demyelination in the spinal cord may be physically dependant, but cognitively fine. Someone having white matter lesions will be more likely to have cognitive deficits. So cognitive impairment is less common among sufferers of primary progressive MS than among sufferers of secondary progressive MS. People presenting the same physical problems, might be presenting completely different cognitive problems. The most common cognitive problems are problems related to slowed information processing and executive functioning, like encoding and retrieval of new information and deficits in attention. Also difficulties with higher order visuospatial skills and deficits on verbal fluency are reported. Many people showing cognitive deficits report having a lower quality of life, are less engaged in social life and more dependent on others concerning activities of daily life (like household tasks).
There is no test which is able to conclusively diagnose MS and to this day, there is no cure for MS. Several medical treatments, called disease modifying agents (DMA’s), are given in some cases however, to treat the inflammation and the loss of immunity that characterizes MS. DMA’s slow down the progression of MS, reduce the frequency of attacks, and also reduce the severity of the attacks. For the DMA’s to be most profitable, early diagnosis and early start of treatment is very important. People on DMA’s show less lesions and less cortical atrophy on MRI scans. A positive effect of this is that they show less cognitive deficits than people not on DMA’s. Corticosteroids are an example of DMA’s. When the person is suffering from relapsing remitting MS, only the attacks can be treated. So the medication cannot be taken continuously. Much research is being done on finding better ways to treat MS and on developing better strategies to cope with MS.
Secondary symptoms like constipation and urinary tract infections can be treated with medication meant for these disabilities, like antibiotics. A personally suited diet can also be effective. Depression can be treated with antidepressants in severe cases. It is very important to take a multidisciplinary approach to the disease, as many different symptoms can show and should be treated in different but integrated ways. Finally, support groups for the sufferer and his or her family members can be very helpful in trying to cope with the disease and gaining more information about it.
Parkinson’s Disease (PD) is a subcortical dementia and is the second most common of neurodegenerative disorders. The most prominent symptoms in PD are motor symptoms, but PD sufferers also develop some cognitive deficits. About 10 to 15% of patients also becomes demented. PD is a result of dysfunction of the extrapyramidal system, which modulates movement and maintains muscle tone and posture. The onset is usually in the sixth decade of life, with 1 in 100 people in their sixties suffering from the disease. About 1 in 500 people in de population have PD and men are a little more often affected than women. Most PD patients will not have a reduced lifespan. Parkinson’s Disease might be more accurately called a syndrome, because it consists of several Parkinsonian symptoms. These are resting tremor, rigidity, bradykinesia and postural instability. The progression of the disease is mostly increasing in severity over time. It seems to be that the older the age of onset, the quicker the progression.
PD can be caused by several factors, but most cases are idiopathic, which means that the unset is sudden and the cause is unknown. Among the factors likely to be able to cause PD are environmental factors, genetic factor and a combination of the two, showed by a heritable vulnerability to PD. Toxic factors like pesticides and herbicides are risk factors as well.
In PD patients there is a loss of dopaminergic neurons in the substantia nigra, which results in a decrease of the neurotransmitter dopamine and because of this a dysfunctioning of the striatum. This causes dysfunctioning of the indirect and the direct route; two basal ganglia-thalamocortical routes. The direct pathway is thought to facilitate movement. This path is slowed because of the shortage of dopaminergic input. The indirect pathway, which is thought to inhibit unwanted movement, becomes more active as a consequence of less dopaminergic input. The process is not yet fully understood, however. Another finding in PD patients as well as in Alzheimer and Down Syndrome patients, is the presence of Lewy bodies in the substantia nigra. These might be responsible for the cell death, but this hypothesis is controversial.
As mentioned before, the most upfront symptoms of Parkinson’s Disease are motor symptoms. These show because of a dysfunctioning of the motor cortex, whose connections with the striatum are distorted because of the decrease of dopamine.
The most common motor symptoms are:
70% of PD sufferers show tremor. Tremor usually starts in the hand, but can spread out to other parts of the body. Very often rigidity is showing as the first symptom of PD and can cause painful muscular discomfort for the person. The person cannot get out of his chair, has difficulties buttoning his shirt or has troubles turning in bed. People often learn tricks to overcome their stiffness by warming up, waving their arms before they begin to walk. PD patients in a later stage fall quite often, have a monotone speech and start drooling. Often people show micrographia, which is bradykinesia of the hands. In these cases their writing is smaller and more unclear. All these motor symptoms are very exhausting for the patients’ muscles, so fatigue is a very common consequence of this.
40% of Parkinson’s Disease patients suffer from depression. This is more common in PD than in any other chronic, disabling disease. Depression is of course an understandable response to having PD, but often it is thought to be part of the organic disease process. One of the hypotheses is that depression is a consequence of the decrease of dopamine in the striatum; PD patients show less activity in the locus cerulues, thalamus, amygdala and the ventral striatum. Another hypothesis is that the level of the neurotransmitter serotonin in the cerebrospinal fluid is related to depression and that PD patients suffering from depression have lower levels of this neurotransmitter.
84% of PD patients will experience cognitive decline, which will get worse with progression of the disease. The frontal lobes of some PD patients might not function well, because dopamine mediates the many connections between the frontal lobe and the basal ganglia. A consequence of this is problems with executive functioning. Difficulties with organizing and planning ahead and carrying out cognitive and motor plans are often seen. In research people discovered that PD patients planned and executed tasks simultaneously instead of parallel. This causes problems in daily life for almost all of the PD patients and difficulties with visuospatial skills, which are reported in 60% of cases, might be a consequence of this as well. Task executing becomes slower as the disease progresses.
PD patients have problems with their temporal memory and shifting mental set. Impairments on memory appear when memory tests require spontaneous recall, but not on recognition tests. A hypothesis to explain this is that PD patients have a generalized difficulty with working memory, which is the limited-capacity system in which incoming information is manipulated and worked on before being processed into a longer-term store. Another possible symptom of PD is bradyphrenia, which means slowed thinking. It seems to be that this is a consequence of the motor impairments, which slows the thinking down. About 25 to 30% of Parkinson’s Disease patients become demented. 17% of these become demented in the first five years of the disease.
Until this day, there is no cure for PD. There are however, several methods to increase the dopaminergic input to the two (direct and indirect) basal ganglia-thalamocortical circuits. Medication is one of the possibilities and the treatment of first choice. Dopamine does not cross the blood-brain barrier, so levodopa, a precursor of dopamine, is used. Levodopa does cross the blood-brain barrier. Levodopa is often used in combination with carbidopa, which makes sure that more of the drug has crossed the blood-brain barrier before it is converted in the place where it is needed. The drug Sinemet combines levodopa and carbidopa. This drug is the most used one in PD. There are more drugs that can be used, and the most important aim of these drugs is to reduce the motor symptoms. There is evidence however, that they can also positively affect some of the cognitive symptoms.
A disadvantage of levodopa is that many PD patients become intolerant for the drug after about 5 to 10 years. They then experience the ON/OFF syndrome. This displays as follows: Usually not long after the patient took the drugs, the ON phase starts and is characterized by side effects of too much dopamine. The patient then suffers from severe dyskinesias (involuntary movements of the limbs). Sometimes these side effects occur twice: once when the drug is just taken and once again as the drug starts to wear off. The dyskinesias are now more likely to take the form of dystionias, which are painful flexions or extensios of the limbs. As the effect of the drugs wear off, the patient enters the OFF phase. In this phase the Parkinsonian symptoms become very severe and the patient experiences severe rigidity, akinesia, and tremor. If patients have the choice, they often prefer the ON phase rather than the OFF phase.
Another option to treat PD is surgery. Patients who can control for their symptoms with medication, are no candidates for surgery. There are several surgical procedures available. One of them is thalamotomy. Thalamotomy is placing a tiny radiofrequency lesion unilaterally in either the ventrointermediate nucleus of the thalamus or the globus pallidus interna. The aim of thalamotomy is relieving the tremor on the side of the body opposite the lesion. Another surgical option is called pallidotomy, which can reduce akinetic symptoms and dyskinesias, bradykinesia and rigidity, and to some extent tremor. Pallidotomy is probably the most used option of the above two. Sometimes both surgical interventions are executed at the same time and after a while again on the opposite side. It’s effects can last for at least two years. A new procedure is Deep Brain Stimulation (DBS). A pulse generator is surgically implanted under the skin and is connected to a multielectrode lead that is implanted into the ventrointermediate nucleus of the thalamus. The PD patient can switch it on and off by moving a magnet over the pulse generator. When the generator is turned on, it blocks the tremor. There are some side effects, so most people choose to turn the generator off at night, when the tremor is not disabling for them.
Research for other treatments is in full progress, especially genetic engineering will play a major role in the future treatment and cure of PD.
Huntington’s Disease (HD) is a progressive, hereditary disease with usually an adult onset. HD is typified by a number of motor abnormalities, especially the excessive, spontaneous irregular movements called chorea. Other motor disorders are also present, like rigidity. These motor symptoms are accompanied by a range of cognitive, psychiatric and behavioral disturbances. If the patient lives long enough, a progressive decline to a severe dementia is almost inevitable. HD is a subcortical dementia. The mean age of onset is 35 to 44 years. The mean age of death for sufferers is 50 to 60 years old, so survival length is about 13 to 17 years. In 10 – 15%, the age of onset is before age 20. Sometimes, age of onset of HD can be as young as 4 years old. This is called juvenile HD and it usually includes, from the early stages, rigidity, hypokinesia, and seizures, as well as choreic movements. In about 20% of cases, age of onset is after 50 years and sometimes even at 84 years old. Very late onset cases often present with chorea only and relatively little other disability. The diagnosis of HD is frequently stated after 8 to 10 years of the disease. The prevalence of HD varies from country to country. Even within countries variation can be present. All cases all over the world are a result of the same mutational mechanism: an identical type of CAG repeat expansion. It seems to be that all cases of HD arose from one small proportion of individuals, and now spreads out.
HD fits the criteria for Mendelian autosomal dominant inheritance, which are the following:
A lot of research has been done on Huntington’s Disease. All the efforts have resulted in the identification and isolation of the gene on which HD is situated and mutation. It also resulted in the ability to predict, with a high level of certainty, which asymptomatic members of a family with HD will go on to develop the disease. Further research is being done on prevention and cure of the disease.
HD can be divided into three clinical stages, each lasting about 5 years:
Each human being has about 35.000 genes. In 1 out of every 10.000 cases, the HD gene carries a mutation that results in the production of a toxic protein in the striatum, which kills the cells of the striatum. As mentioned before, Huntington’s Disease is an autosomal dominant hereditary disorder. One of the characteristics of this is that 50% of the offspring will develop HD if they live long enough. This is because the infected parent usually only carries the gene on one the alleles of the pair of genes. So the child will have a 50% chance of inheriting the gene and if inherited, the person will develop HD if he or she lives long enough. So HD appears to be close to 100% penetrant. In most cases, the parent is heterozygous for the HD gene mutation. In rare cases people are homozygous for the HD gene mutation. This means that they carry the gene on both alleles, so the offspring has a 100% chance of inheriting the gene. But the disease will not be more severe in these cases.
Before the gene was located, a genetic marker for HD was discovered. This genetic marker, called G8, was a functionless piece of DNA lying close to the HD gene on the chromosome. Because it lies to close to the HD, the chance of coinheriting the marker with the HD gene is much higher than 50%. The marker detects several restriction fragment length polymorphisms. The marker was a big discovery because it made it possible to test asymptomatic members of a HD family and as well as prenatal diagnosis of at risk pregnancies. After a lot more research, a mutation in the form of a CAG repeat was discovered. The length of this CAG repeat can vary, and the interesting thing is that all HD sufferers show an expansion of the repeat CAG sequence. This indicates that this expansion on this gene was the causative mutation involved in HD.
In normal people without HD, the CAG repeat ranges from 6 to 35. When an individual has the HD gene and mutation of 42+ CAG repeats, he has a 100% chance of developing HD, but when he has less than 35 repeats, he will not develop HD and won’t pass on the gene to the offspring.
HD sufferers have high numbers of CAG repeats, and the higher the number of CAG repeats, the younger the person will be at the onset of HD:
These data could help predict the age around which asymptomatic people will probably develop HD. The number of CAG repeats can increase or sometimes decrease when passed onto the next generation. Predictive testing is a very sensitive issue. It can change someone’s life dramatically, when the knowledge that he will develop HD is there. Many people with a parent with HD choose not to take the test when they’re still asymptomatic.
The testing procedure starts with two interviews to make sure that the person has enough time to consider or reconsider the implications of predictive testing. If the person is likely to be at risk for depression or suicide or some other mental illness once the results show that he will develop HD, the testing will not take place. Some parents chose to test their unborn child, which is possible at 9-12 weeks. This is of course a very controversial issue, as the parents might decide abortion when the unborn baby is found to have the HD gene.
The primary anatomic finding in HD is generalized shrinkage of the brain with mostly atrophy of the caudate nucleus and putamen, which are structures in the corpus striatum. Severe motor disorders result from the striatum cell loss. Also the cerebellum and the thalamic nuclei might be affected. As the disease progresses, cortical changes will probably take place. Because of the basal ganglia degeneration, neurotransmitter levels will be distorted. This includes reduced levels of the inhibitory neurotransmitter GABA, and an increase in excitatory neurotransmitters. These can have a neurotoxic effect at concentrated levels. As the disease progresses, so does the damage in the fronto-striatal circuits, and in addition, cortical trophy, especially to the frontal lobes, results in ever-worsening executive impairments. An example is this is difficulties in switching mental sets.
Chorea is the most prominent of the HD symptoms. It is also usually the first one to develop. Chorea is defined as a state of excessive, spontaneous, random, and abrupt movements, with a range of severity from restlessness with mild, intermittent exaggeration of gesture and expression; fidgeting movements of the hands: and an unstable, dancelike gait, to a continuous flow of disabling, violent movements. Choreic movements often don’t occur at night. In the later stages of HD, the person might be sleepy all day and awake at night. Other motor abnormalities include dystonias, which are sustained muscle contractions; rigidity, especially in advanced HD; bradykinesia, sometimes accompanied by freezing. Eye movement abnormalities are common, especially difficulties in initiating saccades within the field of vision and a decrease in saccade velocity.
Also often seen is dysarthria, which is a speech distortion, and dysphagia, which involves multiple abnormalities of ingestion, like inappropriate rate of eating. During the terminal stages, 20% of patients become incontinent. Motor impairment can be assessed using the Unified Huntington’s Disease Rating Scale (UHDRS).
The dementia involved in Huntington’s Disease is called subcortical dementia, just like dementia in Parkinson’s Disease. Dementia in Alzheimer’s Disease is called cortical dementia. The earliest and most prominent cognitive impairments are frontally mediated executive problems and problems associated with basal ganglia functioning. Symptoms like difficulty with planning ahead; difficulty in switching mental set; impaired facial recognition; impaired pattern recognition memory; lack of self-control; poor ability to foresee the consequences of ones actions are often seen. To screen dementia the Mini-Mental State Examination is often used.
Psychiatric symptoms are very common among HD patients. As much as 79% suffer from them. The depression rate is very high and is especially prominent in stage 1 of the disease, during this stage the patient is still fully aware of his condition and what is happening to him. Reported depression rates vary from 9 to 44%. Suicide rates are a few times higher than in the normal healthy population. 1/3 tot 2/3 of patients experience symptoms like dysphoria, agitation, irritability, apathy, anxiety, disinhibition and euphoria.
Disease duration and severity are not related to the severity of psychiatric symptoms. However, apathy might correlate with cognitive function. Further in the disease process, depression and apathy become less prominent because the disease awareness of the patients gets less because of the dementia. Many other symptoms can arise from the ones called above. A few examples are moodiness, aggression, violent behavior, marked self-neglect, lying and stealing. Psychiatric symptoms can be assessed using the Problem Behaviors Assessment for Huntington’s Disease (PBA-HD), which is specifically designed for HD.
The items are categorized into three subscales:
Functional capacity can be measured using the HD Functional Capacity Scale, which yields scores in the range of 0-13. The lower the score, the greater the impairment.
Unfortunately to this day, there is no cure for HD. There is a lot of research going on, mainly focusing on ways to turn the mutant gene off or to inject growth factors into the brain to block the toxic protein’s effect and inducing stem cells to divide and grow into new striatal cells to replace the died off one's. For chorea, pharmacological treatments are used. There are several neuroleptic drugs that block central dopamine receptors. One of these is haloperidol. This drug is effective for many patients. The downside however, is that these drugs can have considerable side effect, such as rigidity. Studies are being done on how to treat this rigidity in HD. As many HD sufferers will experience depression during their disease process, Selective Serotonin Reuptake Inhibitors (SSRIs) are used. They selectively block the reabsorption of the brain chemical serotonin. Of course, psychological counseling should first be tried to relieve the depression, before administering drugs. There is no medication yet which is effective for the memory en cognitive problems. Memory aids can be helpful though. As the living environment of the patient concerns, this should be stable and with regular routines. It is very important to provide emotional support to the family as well, as the emotional burden on them can be big.
During the years, people are getting older and older because of the improvement in medical health care, leading to longer life expectancy. Because families are getting smaller, the proportion of older people is also increasing. The chance of getting dementia increases with age; One new case per 100 people between 70 and 80 years old, and 2 new cases per 100 people in the 80+ age group. The prevalence of dementia doubles every 5 years after the age of 60 is reached. 1% of people in the 60-65 age group have dementia, and 35-40% in the 85+ age group. People with dementia live for about 5 years, so the prevalence is higher than the incidence. That is, more cases of dementia are added each year than people already dying from dementia. Researching the causes and treatment of dementia is very important, as it costs the community a lot of money.
Dementia is a general descriptive term for a brain disorder that produces widespread deterioration of mental functions and social capabilities. Dementia is a chronic disease and usually progressive. It affects memory, thinking, judgment and behavior. There are different kinds of dementia, the most common one is Alzheimer’s Disease (AD). More than half of the dementia cases are AD. There are however, 50 other diseases that result in dementia.
A few examples are:
Other prominent causes of dementia are:
AD and most other forms of dementia are irreversible, but when given the appropriate treatment, some are reversible. Because of this, the right diagnosis is very important. Overdiagnosis and misdiagnosis are common problems, as many other physical and psychiatric conditions can present as dementia. Depression is the psychiatric condition most often confused with dementia. When psychiatric conditions are confused with dementia, this is called pseudodementia.
Some forms of dementia, like PD and HD, primarily affect the extrapyramidal motor system. This is why PD and HD are called subcortical dementias. Dysfunction of the extrapyramidal motor system results in motor abnormalities. This can be in the decrease of spontaneous movement (akinesia), as seen in PD. In HD however, too much movement is displayed, such as the involuntary rapid jerking of the limbs and facial grimaces (chorea-form movements).
The diagnostic criteria for the most common dementias are listed in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) by the American Psychiatric Association. The neurobehavioral and clinical criteria for all types of dementia include:
To be diagnosed with dementia, these impairments should be severe enough to disturb daily life and normal functioning. This is why many cases of early dementia are missed in their early stages. It is important to exclude the possibility of delirium as a cause for the symptoms. Careful physical examination and laboratory tests are done to assess whether a specific organic factor is present that is judged to be etiologically related to the specific type of dementia. If such a cause is not found, it is important to make sure that the symptoms aren’t the consequence of another nonorganic mental disorder, like depression.
As Alzheimer’s Disease (AD) makes up more than half of the dementia cases, it will be discussed in detail. AD is a slow, progressive and irreversible disease and is not heritable. The pattern of functional regression is the inverse of the normal developmental stages. The time between onset and death is usually about 12 years. The onset is usually after age 65, and more women than men are affected. When the onset is after age 65, it is called senile AD. When the onset is before age 65, it is called presenile AD. Presenile AD is often characterized by a faster decline. The causes of AD are unknown, but several hypotheses have been formed:
The neuropathology of AD can only be confirmed by biopsy or autopsy postmortem (after death). Plaques and tangles are found in the brain of all aging people, but many more are found in AD patients. Plaques and tangles are associated with loss of nerve cells, which results in brain atrophy. An amyloid plaque is an extracellular deposit containing a dense core of β-amyloid protein surrounded by degenerating axons and dendrites. A neurofibrillary tangle is a dying neuron containing intracellular accumulations of twisted filaments of tau protein. The density of the tangles correlates with the degree of psychological disturbance before death. There is a typical distribution of plaques and tangles in advanced AD. In these patients they are primarily found in the:
The cause of most causes of AD is not known, but several risk factors have been proposed:
Luckily there are also protective factors for AD, which are: maybe the ApoE2 allele; higher linguistic ability; maybe higher education level; the use of vitamin E and other antioxidants; the use of inflammatory agents; reduction of ‘bad’ cholesterol with the use of statins, which are drugs that improve blood cholesterol levels.
Forgetfulness is usually the first symptom that shows in AD. This progresses quickly so soon it appears to be pathological instead of the normal forgetfulness that comes with aging. In the later stages, the patient will not even remember where he lives anymore, who his family is, what year it is, or even what his own name is. Speech and language are also affected, the patient may not be able to keep up with a conversation and even become mute in the later stages. For the screening of mental impairment, the Mini Mental State Examination (MMSE) is used. The scales show a regular 6-monthly or annual decline in cognitive functioning , particularly in memory functioning, with a more rapid decline as the disease progresses. The scores are as follows:
About 38% of the AD population shows symptoms of depression. These symptoms usually do not develop into major depressive disorders. As the disease progresses, the frontal lobes are more impaired, with a lack of insight as a consequence. By this time, many patients lose their concerns about their disease so depression numbers drop. At this stage, poor judgment, poor impulse control and disinhibited behaviors are common. This can cause some embarrassing situations for the family in front of others.
In the middle stage, personality changes become prominent, and the person can become apathetic, withdrawn and unspontaneous. Also emotional changes can occur, and the person might become aggressive. In about 22% of cases delusions occur.
There are different kinds of treatments used in AD patients, depending on the symptoms they display. The most useful pharmacological interventions work on the cholinergic system. Acetylcholinesterase inhibitors have a positive effect on measures of cognitive, behavioral and Activities of Daily Living (ADL). If the patient has depressions symptoms, he can be treated with antidepressants. Psychotic symptoms can be treated with antipsychotics. Especially in the early stages, when the patients still realizes very well what his future is going to look like, psychotherapy is very important to deal with the effects. Also caregivers are given training and support to deal with the consequences of their family member having AD. Vaccination against β-amyloid can be effective by slowing the progression of the disease, and by this a reduction of cognitive decline.
In split-brain surgery (commissurotomy), the larger fiber tract connecting the two hemispheres of the brain, the corpus callosum, is split. The first commissurotomy in humans performed was in the 1940s, in an attempt to control epilepsy. It is very interesting to assess subjects that underwent commissurotomy to investigate how the brain is lateralized and how well it is in coping without the interhemispheric connection. It is important to use subjects in which the corpus callosum has been completely split, as in some subject some fibers have been (accidentally) left intact during the surgery. In the normal state the two sides of our brain are connected of course, and they appear to act as one mind. It is only in the abnormal state when the two hemispheres are surgically separated that their potential for independence becomes apparent. It then takes special equipment and clever experimentation to trick the brain into revealing its two independent minds, because in everyday life, split-brain patients appear to think and behave exactly like everyone else. There are however many individual differences as well.
Another very interesting part of research in split-brain patients is investigating the involvement of the separate hemispheres in consciousness and intelligence. Language is very often found to be located in the left hemisphere, so the left hemisphere can talk just like any other normal person. But the right hemisphere seems to have very limited language skills or is even mute. An extreme point of view is that the right hemisphere is unintelligent as well as mute. These days this extreme view is no longer held by most researchers. The right hemisphere seems to be superior over the left hemisphere in its ability to perform some specialized, nonverbal, visuospatial skills.
In experimental animals, the corpus callosum connecting the two hemispheres is surgically cut along with the optic chiasm. In humans, the corpus callosum is split for therapeutic purposes: the patient has intractable and debilitating epileptic seizures that cannot be satisfactorily controlled by anticonvulsant medication. The seizures are diffuse or of mixed types and cannot be localized to a defined area within the cortex. Therefore, it is not possible to cut out the epileptic focus surgically. So the two hemispheres are disconnected in the hope of preventing the spread of seizures from one hemisphere to the other.
In humans, usually not only the corpus callosum is split, but also smalles commissures, like the anterior and hippocampal commissures. When only the corpus callosum is split, it is called callosotomy. This procedure seems to be less debilitating and has a smaller risk of postsurgical complications. In humans, the optic chiasm is not split.
The Acute Disconnection Syndrome (ADS) occurs in most patients immediately after the surgery and may last from a few days to several weeks. The patient is mute and can only use body language. They are often unable to perform purposeful movements with the left side of their body on verbal command (left-sided apraxia).
Other common symptoms are:
These symptoms will resolve in days to weeks, but rapid and highly coordinated movement remain impaired.
The most obviously bisected system of the commissurotomized brain is the visual system. As the optic chiasm is not split, all the visual information from the right eye is still projected to the left hemisphere. And the visual information from the left eye is still projected to the right hemisphere. Tactile and auditory stimuli are projected predominantly to the opposite side of the brain, but weak ipsilateral connections (to the same side of the brain) are also present. So the incoming information is still presented to the opposite hemisphere. But after this, the information will not be transmitted to the other hemisphere. So if a split-brain patient sees something in his right visual field, he will be able to say what it is, because the object is projected to his left verbal hemisphere. When the object is presented to his left visual field however, he will not be able to name the object. This is because the object is presented to his non-linguistic right hemisphere, and the information cannot get transmitted back (because the corpus callosum is split) to the left verbal hemisphere to name the object. If a word is flashed to the left hemisphere, the subject will deny having seen anything. If, however, he is shown an array of objects or printed words in free vision and asked to guess what was flashed in his left visual field, he will accurately point to the correct object or word with his right hand but not with his left hand. If an apple is flashed in the left visual field, the left hand will pick up an apple from a bowl of fruit in open view. When at the same time an orange is flashed in his right visual field, he will pick up an orange with his right hand. When asked what he has seen, he will only mention the orange, because only the image of the orange was available to his left verbal hemisphere.
When the subject is asked to write down the name of the object or pick it from a number of unseen object with the left hand, he will not be able to do this because the information cannot be transmitted to the right hemisphere, which controls the left hand. A strategy to overcome this problem, is cross-cuing: if the left hemisphere says the name of the object felt with the right hand, the right hemisphere might be able to understand the simple noun and then pick the corresponding object from an array of objects with the left hand. The neuropsychologist should be very aware of this strategy, as it can cause mixed results.
When an object is placed, unseen, in the left hand, the subject will not be able to say what the object is or pick it from an array of objects with his right hand, which is controlled by his left hemisphere. Only the right, mute, hemisphere has the information. If the subject is then shown an array of objects in free vision, however, he can point to the object with his left hand but not with his right hand. In these cases, the ipsilateral (to the same side) pathways of the brain are clearly inhibited by the more dominant contralateral pathways.
Other general findings following commissurotomy include normal writing with the right hand bur poor or absent writing with the left hand. The left hand can make good drawings of cubes and other, spatial, nonverbal pictures. The right hand makes these drawings poorly. So split-brain subjects usually have a right-hand drawing impairment and a left-hand writing impairment. The above might be indicating that the right hemisphere is specialized in visuospatial perception but also in manipulospatial skills. A right-hemispheric superiority will be more apparent when a visuospatial task has a motor component.
The bulk of evidence supports the idea that the right hemisphere is specialized for the higher cognitive functions involved in tasks requiring a nonverbal, holistic, visuospatial approach, regardless of whether there is a motor component. But the extent of the right hemisphere’s role in visuospatial cognition is still controversial. The specialization of the left hemisphere for language is no longer in doubt and is clearly demonstrated by the normal ability of the disconnected left hemisphere to perform all language tasks. The left hemisphere also seems to be the one with the calculative abilities. Calculation beyond simple addition is not possible for the right hemisphere. Most of the right-handed split-brain patients have a fairly good ability to comprehend single words that enter the right hemisphere via auditory, visual, or tactile routes. The disconnected right hemisphere can also make lexical decisions.
As the left hemisphere can speak for itself and express what it is doing, thinking and feeling. To assess the self-awareness of the right hemisphere, other measures are needed. The self-awareness of the two hemispheres was tested by showing photos to the separate hemisphere en measuring the emotional reactions to these. Each hemisphere seems to be equally good at recognizing photographs of relatives, pets, belonging, familiar scenes, and well-know historical, political, and entertainment figures.
The subjects’ answers to follow-up questions after recognition by his right hemisphere demonstrated that he not only recognized that the person or item was familiar but he also knew the personal or social context of the item. When a photograph of the subject himself was unexpectantly presented among unrelated items, in an inappropriate context, the subject demonstrated this by his emotional expression.
Hemispherectomy is the removal of one half of the brain. It is very interesting to study which of the functions can be taken over by the other half of the brain and which cannot be taken over. Many people who have half their brain removed are severely impaired, but usually these people were already mentally retarded before the hemispherectomy. Many other people are doing surprisingly well, and often it is not even noticed that there is ‘something different’ about them. In general it is thought that the damage to one side of the brain must have occurred in infancy if removal of that hemisphere is to improve the quality of life of that person. People who had a normally functioning brain in childhood and have one side removed after for example extensive damage in adulthood, will often experience deficits related to the damaged half. Recovery of the functions of the removed half, for example language functions, tends not to occur.
The usual reason to perform hemispherectomy is that one of the hemispheres is severely damaged, atrophied and substantially nonfunctional. Often the damaged hemisphere causes frequent and severe seizures. This also disrupts the functioning of the ‘good’ hemisphere. In most of the cases, the removal of the damaged hemisphere results in great relieve for the patient.
In about 96% of right handers and 70% of left handers, the left hemisphere is dominant for language functions, including verbal memory. A hypothesis has been proposed that favors earlier development of the left hemisphere as opposed to the right. The right hemisphere becomes ready for language development earlier than the right hemisphere. And once the language is established in the left hemisphere, it inhibits the right hemisphere from developing these functions.
The right hemisphere is dominant for visuospatial functions, including nonverbal memory and emotional expression. This division of specializations is not as clear as stated, but much evidence for the specialization is found in specific deficits following lesions in particular brain areas.
Recovery of specialized language and visuospatial abilities following massive damage to one of the hemispheres raises questions about the equipotentiality and plasticity of different brain areas and systems with respect to their ability to mediate and take over a range of functions. There is a little evidence that the recovery is better when the person is younger. This accounts especially for language functions. Children who sustain extensive damage to the left ‘speech’ hemisphere seem to develop normal language functions. But older children and adult often stay impaired. A possible explanation for this is that it takes long for undamaged brain areas to take over the lost functions. Adult subjects who sustain major brain injury do not have a long life expectancy in general.
Sometimes it seems to be that the functions of the right hemisphere become a little impaired when the right hemisphere needs to take over the functions of the left hemisphere.
Studies done on subjects who have had left hemispherectomies, found that when the right hemisphere takes over language function in infancy, it does so in a degraded form. The right hemisphere processes language in a quantitatively different way from the left hemisphere. One interesting finding is that left-hemispherectomized subjects had difficulty understanding passive-negative sentences (e.g. ‘the girl is not pushed by the boy’). But if the subjects are given enough time, they do understand the sentence. This means that their ability to understand these complex sentences is intact, but that their speed of processing is impaired. Impaired speed of processing is very often seen in brain damaged subjects, even after mild brain injury. It is not clear yet if one of the hemispheres is dominant for mediating memory, but research findings show that when the two hemispheres are disconnected from each other, so they cannot communicate anymore, recent memory is poor. This might indicate that the connection between the two hemispheres is important for mediating memory. One right-hemispheric function, prosody (the rhythm, stress, and intonation of speech), does not seem to be disadvantaged by the development of language in the right hemisphere, perhaps because prosody is so intimately tied in with speech. If the right hemisphere is the damaged one, language skills develop at a normal rate, and nonverbal skills are disadvantaged.
Je vertrek voorbereiden of je verzekering afsluiten bij studie, stage of onderzoek in het buitenland
Study or work abroad? check your insurance options with The JoHo Foundation
Add new contribution