Movement Disorders

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Movement disorders
Movement disorders include:

Akathisia (inability to sit still) Akinesia (lack of movement) Associated Movements (Mirror Movements or Homolateral Synkinesis) Athetosis (contorted torsion or twisting) Ataxia (gross lack of coordination of muscle movements) Ballismus (violent involuntary rapid and irregular movements) Hemiballismus (affecting only one side of the body) Bradykinesia (slow movement) Cerebral palsy Chorea (rapid, involuntary movement) Sydenham's chorea Rheumatic chorea Huntington's disease Dystonia (sustained torsion) Dystonia muscularum Blepharospasm Writer's cramp Spasmodic torticollis (twisting of head and neck) Dopamine-responsive dystonia (hereditary progressive dystonia with diurnal fluctuation or Segawa's disease) Geniospasm (episodic involuntary up and down movements of the chin and lower lip) Myoclonus (brief, involuntary twitching of a muscle or a group of muscles) Metabolic General Unwellness Movement Syndrome (MGUMS) Mirror movement disorder (involuntary movements on one side of the body mirroring voluntary movements of the other side) Parkinson's disease Paroxysmal kinesigenic dyskinesia Restless Legs Syndrome RLS (WittMaack-Ekboms disease) Spasms (contractions) Stereotypic movement disorder Stereotypy (repetition) Tardive dyskinesia Tic disorders (involuntary, compulsive, repetitive, stereotyped) Tourette's syndrome
Prepared by Kawal and Navjot, Mai Bhago College of Nursing, Tarn Taran
Tremor (oscillations) Rest tremor (4-8 Hz) Postural tremor Kinetic tremor Essential tremor (6-8 Hz variable amplitude) Cerebellar tremor (6-8 Hz variable amplitude) Parkinsonian tremors (4-8 Hz variable amplitude) Physiological tremor (10-12 Hz low amplitude) Wilson's disease
Tic disorder
Tic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic, stereotyped) [Classification

Transient tic disorder consists of multiple motor and/or phonic tics with duration of at least 4 weeks, but less than 12 months. Chronic tic disorder is either single or multiple motor or phonic tics, but not both, which are present for more than a year. Tourette syndrome is diagnosed when both motor and phonic tics are present for more than a year. Tic Disorder NOS is diagnosed when tics are present, but do not meet the criteria for any specific tic disorder.
Definition Tic disorders are characterized by the persistent presence of tics, which are abrupt, repetitive involuntary movements and sounds that have been described as caricatures of normal physical acts. The best known of these disorders is Tourette's disorder, or Tourette's syndrome. Characteristics Tics are sudden, painless, nonrhythmic behaviors that are either motor (related to movement) or vocal and that appear out of context for example, knee bends in science class. They are fairly common in childhood. Tics may be simple (using only a few muscles or simple sounds) or complex (using many muscle groups or full words and sentences). Simple motor tics are brief, meaningless movements like eye blinking, facial grimacing, head jerks or shoulder shrugs. They usually last less than one second.
Complex motor tics involve slower, longer, and more purposeful movements like sustained looks, facial gestures, biting, banging, whirling or twisting around, or copropraxia (obscene gestures). Simple phonic tics are meaningless sounds or noises like throat clearing, coughing, sniffling, barking, or hissing. Complex phonic tics include syllables, words, phrases, and such statements as "Shut up!" or "Now you've done it!" The child's speech may be abnormal, with unusual rhythms, tones, accents or intensities. The echo phenomenon is a tic characterized by the immediate repetition of one's own or another's words. Coprolalia is a tic made up of obscene, inappropriate or aggressive words and statements. Factors aggravates the condition Motor and vocal tics may be worsened by anxiety, stress , boredom, fatigue , or excitement. Tics are intensified by premenstrual syndrome, additives in food, and stimulants. The symptoms of tic disorders may be lessened while the patient is asleep. Cannabis (marijuana), alcohol, relaxation, playing a sport, or concentrating on an enjoyable task are also reported to reduce the severity and frequency of symptoms. Causes Emotional factors, biological, chemical and environmental factors. Both functional and structural abnormalities in the brains of people with tic disorders. Exact neurochemical cause is unknown Abnormal neurotransmitters (chemical messengers within the brain ) contribute to the disorders. The affected neurotransmitters are dopamine, serotonin, and cyclic AMP. Vulnerability to tic disorders appears to be genetic, or transmitted within families. Psychomotor stimulants as methylphenidate (Ritalin); pemoline (Cylert); amphetamines ; and cocaine. Some forms of tic may be triggered by the environment. A cough that began during an upper respiratory infection may continue as an involuntary vocal tic. Neuropsychiatric disorders, such as tic disorders and obsessive-compulsive disorder . The development of tics after head trauma, viral encephalitis or stroke .
Symptoms The diagnostic criteria of all tic disorders specify that the symptoms must appear before the age of 18, and that they cannot result from ingestion of such substances as stimulants, or from such general medical conditions as Huntington's disease. Tic disorders can be seen as occurring along
a continuum of least to most severe in terms of disruption and impairment, with transient tic disorder at one end and Tourette's disorder at the other. Tics increase in frequency when a person is under any form of mental or physical stress, even if it is of a positive nature (excitement about an upcoming holiday, for example). Some people's tics are most obvious when the person is in a relaxed situation, such as quietly watching television. Tics tend to diminish when the person is placed in a new or highly structured situation, such as a doctor's office a factor that can complicate diagnosis . When the symptoms of a tic are present over long time periods, they do not remain constant but will wax and wane in their severity. Transient tic disorder occurs in approximately 4%24% of schoolchildren. It is the mildest form of tic disorder, and may be underreported because of its temporary nature. In transient tic disorder, there may be single or multiple motor and/or vocal tics that occur many times a day nearly every day for at least four weeks, but not for longer than one year. If the criteria have been met at one time for Tourette's disorder or for chronic motor or vocal tic disorder, transient tic disorder may not be diagnosed. Chronic motor or vocal tic disorder is characterized by either motor tics or vocal tics, but not both. The tics occur many times a day nearly every day, or intermittently for a period of more than one year. During that time, the patient is never without symptoms for more than three consecutive months. The severity of the symptoms and functional impairment is usually much less than for patients with Tourette's disorder. For a diagnosis of Tourette's disorder, a patient must have experienced both multiple motor and one or more vocal tics at some time during the illness, though they do not have to occur at the same time. The tics occur many times a day, usually in bouts, nearly every day or intermittently for a period of more than one year. The patient is never symptom-free for more than three months at a time. Children and adolescents with Tourette's disorder frequently experience additional problems including aggressiveness, self-harming behaviors, emotional immaturity, social withdrawal, physical complaints, conduct disorders, affective disorders, anxiety, panic attacks, stuttering , sleep disorders , migraine headaches, and inappropriate sexual behaviors. Tics seem to worsen during the patient's adolescence, although some clinicians think that the symptoms become more problematic rather than more severe, because the patient experiences them as more embarrassing than previously. The symptoms do become more unpredictable from day to day during adolescence. Many teenagers may refuse to go to school when their tics are severe. Coprolalia often appears first in adolescence; this symptom causes considerable distress for individuals and their families.
Behavioral problems also become more prominent in adolescence. There is some evidence that temper tantrums, aggressiveness, and explosive behavior appear in preadolescence, intensify in adolescence, and gradually diminish by early adulthood. Interestingly, aggression appears to increase at approximately the same time that the tics decrease in severity. Diagnosis There are no diagnostic laboratory tests to screen for tic disorders. Except for the tics, the results of the patient's physical and neurological examinations are normal. A complete medical history including a detailed account of prenatal events, birth history, head injuries, episodes of encephalitis or meningitis, poisonings, and medication or drug use. The patient's developmental, behavioral, and academic histories are also important. Tic disorders can be differentiated from movement disorders by the following characteristics: they are suppressible; they tend to persist during sleep; they are preceded by sensory symptoms; they have both phonic and motor components; and they wax and wane. Treatments A holistic approach is recommended for the treatment of tic disorders. A multidisciplinary team should work together with the affected child's parents and teachers to put together a comprehensive treatment plan. Treatment should include the following:

Educating the patient and family about the course of the disorder in a reassuring manner. Completion of necessary diagnostic tests, including self-reports (by child and parents); clinician-administered ratings; and direct observational methods. Comprehensive assessment, including the child's cognitive abilities, perception, motor skills, behavior and adaptive functioning. Collaboration with school personnel to create a learning environment conducive to academic success. Therapy, most often behavioral or cognitive-behavioral, though other modalities may be appropriate. If necessary, evaluation for medication.
Behavioral and cognitive-behavioral therapy Massed negative practice has been one of the most frequently used behavioral therapy techniques in the treatment of children with tic disorder. The patient is asked to deliberately perform the tic movement for specified periods of time interspersed with brief periods of rest. Patients have shown some decrease in tic frequency, but the long-term benefits of massed negative practice are unclear.
Contingency management is another behavioral treatment. It is based on positive reinforcement , usually administered by parents. Children are praised and rewarded for not performing tics and for replacing them with alternative behaviors. Contingency management, however, appears to be of limited use outside of such controlled settings as schools or institutions. Self-monitoring consists of having the patient record tics by using a wrist counter or small notebook. It is fairly effective in reducing some tics by increasing the child's awareness. Habit reversal is the most commonly used technique, combining relaxation exercises, awareness training, and contingency management for positive reinforcement. This method shows a 64% 100% success rate. Adding a cognitive component to habit reversal involves the introduction of flexibility into rigid thinking, and confronting the child's irrational expectations and unrealistic anticipations. It has not been shown as of 2002 to increase treatment effectiveness. The specific cognitive technique of distraction, however, has been shown to help patients resist sensory urges and to restore the patient's sense of control over the tic. Medications Medications prescribed for patients with tic disorders include:
Typical neuroleptics (antipsychotic medications), including haloperidol (Haldol) and pimozide (Orap). Neuroleptics can have significant side effects, which include concentration problems, cognitive blunting, and rarely, tardive dyskinesia (a movement disorder that consists of lip, mouth, and tongue movements). Such side effects as stiffness, rigidity, tremor, sedation, and depression are common with haloperidol, but are less so with pimozide. Alpha-adrenergic receptor agonists, including clonidine (Catapres) and guanfacine (Tenex). Clonidine has fewer and milder side effects than the neuroleptics in general, with the most common being sedation. Sedation occurs in 10%20% of cases and can often be controlled through adjusting the dosage. The phenothiazines may be used when haloperidol or pimozide has proven ineffective. Atypical antipsychotics and other agents that block dopamine receptors include risperidone (Risperdal) and clozapine (Clozaril). Tetrabenazine is a promising new medication with fewer side effects than other typical neuroleptics. It can be used in combination with the older antipsychotic medications, allowing for lower doses of both medications with substantial relief. Selective serotonin reuptake inhibitors (SSRIs), which include such medications as fluoxetine (Prozac) and sertraline (Zoloft), can be used to treat the obsessive-
compulsive behaviors associated with Tourette's disorder. They can also be helpful with depression and impulse control difficulties, though they must be given at higher dosages for OCD than for depression. The SSRIs, however, can cause gastric upset and nausea. Benzodiazepines are used in some cases to lower the patient's anxiety level, but are often avoided because they can cause dependence and tolerance. Nicotine chewing gum appears to reduce tics when added to ongoing treatment with haloperidol, but is in need of further study.
Alternative therapies There is growing interest in dietary changes and nutritional supplements to prevent and manage the symptoms of tic disorders, although formal studies have not yet been conducted in this area. Some theorists have suggested that hidden food and chemical allergies or nutritional deficiencies may influence the development and maintenance of tic disorders. Recommendations include eating organic food and avoiding pesticides; taking antioxidants; increasing intake of folic acid and the B vitamins; eating foods high in zinc and magnesium; eliminating caffeine from the diet; and avoiding artificial sweeteners, colors and dyes. Prognosis There is presently no cure for tic disorders, and there is no evidence that early treatment alters prognosis. When a child is first evaluated, it is not possible to determine whether the tics will be chronic or transient, mild or severe. While the tics themselves may decline, however, the associated problems often continue into adult life. Obsessive-compulsive symptoms and other behavioral problems, as well as learning disabilities, may grow worse. Obsessive-compulsive behaviors become most pronounced at age 15 and remain at that level. Panic attacks, depression, agoraphobia and alcoholism are most significant in the early adult years, while a tendency toward obesity increases steadily with age, particularly in women. In adulthood, a patient's repertoire of tics is reduced and becomes predictable during periods of fatigue and heightened emotionality. Some studies suggest remission rates, with the complete cessation of symptoms, to be as high as 50%. Cases of total remission appear to be related to the family's treatment of the patient when he or she was a child. Persons who were punished, misunderstood and stigmatized experience greater functional impairment as adults than those who were supported and understood as children.
Prevention There are few preventive strategies for tic disorders. There is some evidence that maternal emotional stress during pregnancy and severe nausea and vomiting during the first trimester may affect tic severity. Attempting to minimize prenatal stress may possibly serve a limited preventive function. Similarly, because people with tic disorders are sensitive to stress, attempting to maintain a lowstress environment can help minimize the number or severity of tics (reducing the number of social gatherings, which can be anxiety-provoking, for example). This approach cannot prevent tics altogether, and must be undertaken with an awareness that it is neither healthful nor advisable to attempt to eliminate all stressful events in life.
Dystonia
Definition Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. Causes The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning (e.g., lead poisoning) or reaction to pharmaceutical drugs, particularly neuroleptics. Treatment is difficult and has been limited to minimizing the symptoms of the disorder, since there is no cure available. The causes of dystonia are not yet known or understood; however, they are categorized as follows on a theoretical basis: Primary dystonia is suspected to be caused by a pathology of the central nervous system, likely originating in those parts of the brain concerned with motor function, such as the basal ganglia, and the GABA (gamma-aminobutyric acid) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions. Secondary dystonia refers to dystonia brought on by some identified cause, usually involving brain damage, or by some unidentified cause such as chemical imbalance. Some cases of (particularly focal) dystonia are brought on after trauma, are induced by certain drugs (tardive dystonia), or may be the result of diseases of the nervous system such as Wilson's disease. Environmental and task-related factors are suspected to trigger the development of focal dystonias because they appear disproportionately in individuals who perform high precision hand
movements such as musicians, engineers, architects and artists. Chlorpromazine can also cause dystonia, which can be often misjudged as a seizure. Neuroleptic drugs often cause dystonia, including oculogyric crisis. Types of dystonia Generalized dystonia affects most or all of the body. Focal dystonia is localized to a specific part of the body. Multifocal dystonia involves two or more unrelated body parts. Segmental dystonia affects two or more adjacent parts of the body. Hemidystonia involves the arm and leg on the same side of the body. Torsion dystonia, previously called dystonia musculorum deformans or DMD, is a rare, generalized dystonia that may be inherited, usually begins in childhood, and becomes progressively worse. It can leave individuals seriously disabled and confined to a wheelchair. Genetic studies have revealed an underlying cause in many patients - a mutation in a gene named DYT1. And it has been discovered that this gene is related not only to generalized dystonia, but also to some forms of focal dystonia. Note, however, that most dystonia, of any type, is not due to this gene and has an unknown cause. Cervical dystonia, also called spasmodic torticollis, or torticollis, is the most common of the focal dystonias. In torticollis, the muscles in the neck that control the position of the head are affected, causing the head to twist and turn to one side. In addition, the head may be pulled forward or backward. Torticollis can occur at any age, although most individuals first experience symptoms in middle age. It often begins slowly and usually reaches a plateau. About 10 to 20 percent of those with torticollis experience a spontaneous remission, but unfortunately the remission may not be lasting. Blepharospasm, the second most common focal dystonia, is the involuntary, forcible closure of the eyelids. The first symptoms may be uncontrollable blinking. Only one eye may be affected initially, but eventually both eyes are usually involved. The spasms may leave the eyelids completely closed causing functional blindness even though the eyes and vision are normal. Cranial dystonia is a term used to describe dystonia that affects the muscles of the head, face, and neck. Oromandibular dystonia affects the muscles of the jaw, lips, and tongue. The jaw may be pulled either open or shut, and speech and swallowing can be difficult. Spasmodic dysphonia involves the muscles of the throat that control speech. Also called spastic dysphonia or laryngeal dystonia, it causes strained and difficult speaking or breathy and effortful speech. Meige's syndrome is the combination of blepharospasm and oromandibular dystonia and sometimes spasmodic dysphonia. Spasmodic torticollis can be classified as a type of cranial dystonia. Writer's cramp is a dystonia that affects the muscles of the hand and sometimes the forearm, and only occurs during handwriting. Similar focal dystonias have also been called typist's cramp, pianist's cramp, and musician's cramp. Dopa-responsive dystonia (DRD), of which Segawa's dystonia is an important variant, is a condition successfully treated with drugs. Typically, DRD begins in childhood or adolescence with progressive difficulty in walking and, in some cases, spasticity. In Segawa's dystonia, the
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symptoms fluctuate during the day from relative mobility in the morning to increasingly worse disability in the afternoon and evening as well as afterexercise. The diagnosis of DRD may be missed since it mimics many of the symptoms of cerebral palsy.
Generalized dystonias

Normal birth history and milestones Autosomal dominant Childhood on Starts in lower limbs and spreads upwards Also known as "idiopathic torsion dystonia" (old terminology "dystonia musculorum deformans")
Focal dystonias These are the most common dystonias and tend to be classified as follows: Name Location Description
Anismus
muscles of Causes painful defecation, constipation; the rectum complicated by encopresis.
may
be
Cervical dystonia muscles (spasmodic torticollis) the neck
of
Causes the head to rotate to one side, to pull down towards the chest, or back, or a combination of these postures.
Blepharospasm
muscles around theeyes
The sufferer experiences rapid blinking of the eyes or even their forced closure causing functional blindness.
Oculogyric crisis
An extreme and sustained (usually) upward deviation of the eyes often with convergence causing diplopia(double muscles of vision). It is frequently associated with backwards and eyes and head lateral flexion of the neck and either widely opened mouth or jaw clenching. Frequently a result of antiemetics such as
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the neuroleptics (e.g., prochlorperazine) or metoclopramide. Also can by Chlorpromazine
be
caused
Oromandibular dystonia
muscles of the jaw Causes distortions of the mouth and tongue. andmuscles of tongue
Spasmodic dysphonia/Laryngeal dystonia
muscles larynx
of Causes the voice to sound broken, become hoarse, sometimes reducing it to a whisper.
single muscle Focal hand dystonia or small (also known as group of musician's orwriter's muscles in cramp). the hand
It interferes with activities such as writing or playing a musical instrument by causing involuntary muscular contractions. The condition is sometimes "task-specific," meaning that it is generally apparent during only certain activities. Focal hand dystonia is neurological in origin, and is not due to normal fatigue. The loss of precise muscle control and continuous unintentional movement results in painful cramping and abnormal positioning that makes continued use of the affected body parts impossible.
The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or Meige's syndrome. Segmental dystonias Segmental dystonias affect two adjoining parts of the body: Hemidystonia affects an arm and foot on one side of the body. Multifocal dystonia affects many different parts of the body. Generalized dystonia affects most of the body, frequently involving the legs and back. Genetic / primary Name OMIM Gene Locus Alt Name
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DYT1 EOTD)
(or
128100
DYT1
9q34
early-onset torsion dystonia
DYT2
224500
unknown
unknown
autosomal dystonia
recessive
torsion
DYT3
314250
TAF1
Xq13
X-linked torsion dystonia
DYT4
128101
TUBB4[3]
19p13.12-13
autosomal dystonia
dominant
torsion
DYT5 DRD)
(or
128230
GCH1
14q22.1q22.2
Dopamine-responsive dystonia
DYT6
602629
THAP1
8p11.21
DYT7
602124
unknown
18p
Primary cervical dystonia
DYT8 (or 118800 PNKD1)
MR1
2q35
paroxysmal dyskinesia 1
nonkinesigenic
DYT9
601042
possibly KCNA3[4]
1p
episodic choreoathetosis/spasticity
DYT10 EKD1)
(or
128200
unknown
16p11.2q12.1
episodic kinesigenic dyskinesia 1
DYT11
159900taco SGCE
7q21
Myoclonic dystonia
13
DYT12
128235
ATP1A3
19q12-q13.2
DYT13
607671
unknown, D1S2667[5]
near 1p36.32p36.13
DYT14
See DYT5
DYT15
607488
unknown
18p11[6]
Myoclonic dystonia
DYT16
612067
PRKRA
2q31.3
DYT17
612406
unknown, D20S107[7]
near 20p11.2q13.12
DYT18
612126
SLC2A1
1p35-p31.3
DYT19 EKD2)
(or
611031
unknown
16q13-q22.1
episodic kinesigenic dyskinesia 2
DYT20 (or 611147 PNKD2)
unknown
2q31
paroxysmal dyskinesia 2
nonkinesigenic
There is a group called myoclonus dystonia or myoclonic dystonia, where some cases are hereditary and have been associated with a missense mutation in the dopamine-D2 receptor. Some of these cases have responded remarkably to alcohol. Signs and symptoms Hyperglycemia-induced involuntary movements which, in this case, did not consist of typical hemiballismus, but rather of hemichorea (dance-like movements of one side of the body; initial movements of the right arm in the video) and bilateraldystonia (slow muscle contraction in legs, chest and right arm) in a 62-year-old Japanese woman with type 1 diabetes. Symptoms vary according to the kind of dystonia involved.
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In most cases, dystonia tends to lead to abnormal posturing, particularly on movement. Many sufferers have continuous pain, cramping and relentless muscle spasms due to involuntary muscle movements. Other motor symptoms are possible including lip smacking.[10] Early symptoms may include Loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, and dropped items), Cramping pain with sustained use and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome. Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth, or symptoms similar to TMD. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping. Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a "mirror effect" is often observed in other body parts: use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms. Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and
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livelihood to a progressing disability. Side effects from treatment and medications can also present challenges in normal activities. Treatment Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side effects and risks. In some cases, botox is used. Physical intervention Physical therapy can be utilized to manage changes in balance, mobility and overall function that occur as a result of the disorder. A variety of treatment strategies can be employed to address the unique needs of each individual. Potential treatment interventions include splinting, therapeutic exercise, manual stretching, soft tissue and joint mobilization, postural training and bracing, neuromuscular electrical stimulation,constraint-induced movement therapy, activity and environmental modification, and gait training. Medication Different medications are tried in an effort to find a combination that is effective for a specific person. Not all people will respond well to the same medications. Medications that have had positive results in some include: diphenhydramine, benzatropine, anti-Parkinsons agents ( such as trihexyphenidyl), and muscle relaxers (such as diazepam). Anticholinergics Medications such as anticholinergics (benztropine), which act as inhibitors of the neurotransmitter acetylcholine, may provide some relief. In the case of an acute dystonic reaction, diphenhydramine is sometimes used (though this drug is well known as an antihistamine, in this context it is being used primarily for its anticholinergic role). In the case of Oculogyric crisis, diphenhydramine may be administered with excellent results with symptoms subsiding in a matter of minutes. Muscle relaxants Clonazepam, an anti-seizure medicine, is also sometimes prescribed. However, for most their effects are limited and side effects like mental confusion, sedation, mood swings and short-term memory loss occur. Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 36 months, depending on the kind of dystonia. Botox injections have the advantage of ready availability (the same form is used for cosmetic surgery) and the effects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking
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of the toxin into adjacent muscle groups causing weakness or paralysis in them. The injections have to be repeated as the effects wear off and around 15% of recipients will develop immunity to the toxin. There is a Type A and Type B toxin approved for treatment of dystonia; often those that develop resistance to Type A may be able to use Type B. Parkinsonian drugs Dopamine agonists: One type of dystonia, dopamine-responsive dystonia, can be completely treated with regular doses of L-DOPA in a form such as Sinemet (carbidopa/levodopa). Although this doesn't remove the condition, it does alleviate the symptoms most of the time. (In contrast, dopamine antagonists can sometimes cause dystonia.) Baclofen A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal cord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin. Cannabidiol Cannabidiol has been found to be effective in reducing symptoms of dystonia. This is a cannabinoid that is produced in cannabis. Surgery Surgery, such as the denervation of selected muscles, may also provide some relief; however, the destruction of nerves in the limbs or brain is not reversible and should only be considered in the most extreme cases. Recently, the procedure of deep brain stimulation (DBS) has proven successful in a number of cases of severe generalised dystonia. DBS as treatment for medicationrefractory dystonia, on the other hand, may increase the risk of suicide in patients. Unfortunately, reference data of patients without DBS therapy are lacking.
Chorea
Definition Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term chorea is derived from the Greek word (=dance; see choreia), as the quick movements of the feet or hands are comparable to dancing. The term hemichorea refers to chorea of one side of the body, such as chorea of one arm but not both (comparable to hemiballismus).
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Chorea: Types

Huntington's Chorea Sydenham chorea Drug-induced chorea
Chorea: Rare Types Rare types of medical conditions and diseases in related medical categories:
Brain & Neurological Disorders: Rare Types: o Adult ADHD -- Rare Types
o o o o o o o o
ADHD -- Rare Types Alzheimer Disease -- Rare Types Migraine -- Rare Types Concentration Disorders -- Rare Types Stroke -- Rare Types Bipolar Disorder -- Rare Types Schizophrenia -- Rare Types Epilepsy -- Rare Types
Presentation Chorea is characterized by brief, semi-directed, irregular movements that are not repetitive or rhythmic, but appear to flow from one muscle to the next. These 'dance-like' movements of chorea often occur with athetosis, which adds twisting and writhing movements. Walking may become difficult, and include odd postures and leg movements. Unlike ataxia, which affects the quality of voluntary movements, or Parkinsonism, which is a hindrance of voluntary movements, the movements of chorea and ballism occur on their own, without conscious effort. Thus, chorea is said to be a hyperkinetic movement disorder. When chorea is serious, slight movements will become thrashing motions; this form of severe chorea is referred to as ballism or ballismus. Causes Chorea can occur in a variety of conditions and disorders.
Chorea is a primary feature of Huntington's disease, a progressive neurological disorder.
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Twenty percent (20%) of children and adolescents with rheumatic fever develop Sydenham's chorea as a complication. Chorea gravidarum is rare type of chorea which is a complication of pregnancy. Chorea may also be caused by drugs (levodopa, anti-convulsants, anti-psychotics), metabolic disorders, endocrine disorders, and stroke. Wilson's disease, a genetic disorder that leads to toxic levels of copper in the body Transmissible spongiform encephalopathies: A group of neurodegenerative diseases such as Creutzfeldt-Jakob disease and Kuru, caused by prions. Neuroacanthocytosis, a genetic disorder that may affect the blood, brain, peripheral nerves, muscle and heart. Common features include peripheral neuropathy, cardiomyopathy and hemolytic anemia. Other features include limb chorea, facial tics, other oral movements (lip and tongue biting), seizures, a late-onset dementia and behavioral changes.
Treatment There is no standard course of treatment for chorea. Treatment depends on the type of chorea and the associated disease. Although there are many drugs that can control it, no cure has yet been identified. Form Treatment
Huntington'srelated
A common treatment is dopaminergic antagonists, although treatment is largely supportive. Tetrabenazine is the only FDA approved drug for the treatment of Huntington's Disease related chorea.
Haloperidol, carbamazepine and valproic acid. Usually Sydenham's chorea involves antibiotic drugs to treat the infection, followed by drug therapy to prevent recurrence.
haloperidol,[1][2][3] chlorpromazine alone or in combination with diazepam, Chorea gravidarum also pimozide can also be used.
Wilson's disease
Reducing levels of copper in the body using D-penicillinamine, trientine hydrochloride, tetrathiomolybdate, and other chelatingagents
Drug-induced
Adjusting medication dosages.
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chorea
Metabolic and endocrine-related Treated according to their causes. choreas
Wilson's disease Definition Wilson's disease is an inherited disorder in which there is too much copper in the body's tissues. The excess copper damages the liver and nervous system. Causes, incidence, and risk factors Wilson's disease is a rare inherited disorder. If both parents carry an abnormal gene for Wilson's disease, there is a 25% chance in each pregnancy that the child will have the disorder. Wilson's disease causes the body to take in and keep too much copper. The copper deposits in the liver, brain, kidneys, and the eyes. The deposits of copper cause tissue damage, death of the tissues, and scarring, which causes the affected organs to stop working correctly. This condition is most common in eastern Europeans, Sicilians, and southern Italians, but may occur in any group. Wilson's disease typically appears in people under 40 years old. In children, the symptoms begin to show by age 4. Symptoms

Abnormal posture of arms and legs Confusion or delirium Dementia Difficulty moving arms and legs, stiffness Difficulty walking (ataxia) Emotional or behavioral changes Enlargement of the abdomen (abdominal distention) Personality changes
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Phobias, distress (neuroses) Slow movements Slow or decreased movement and expressions of the face Speech impairment Tremors of the arms or hands Uncontrollable movement Unpredictable and jerky movement Vomiting blood Weakness Yellow skin (jaundice) or yellow color of the white of the eye (icterus)
Signs and tests A slit-lamp eye examination may show:

Limited eye movement Rusty or brown-colored ring around the iris (Kayser-Fleischer rings)
A physical examination may show signs of:
Damage to the central nervous system, including loss of coordination, loss of muscle control, muscle tremors, loss of thinking and IQ, loss of memory, and confusion (delirium or dementia) Liver or spleen disorders (including cirrhosis, splenomegaly, and liver necrosis)
Lab tests may include:

Complete blood count (CBC) Serum ceruloplasmin Serum copper Serum uric acid Urine copper
If there are liver problems, lab tests may find:

High AST and ALT High bilirubin High PT and PTT Low albumin
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Other tests may include:

24-hour urine copper test Abdominal x-ray Abdominal MRI CT scan of the abdomen Head CT scan Head MRI Liver biopsy
The gene that causes Wilson's disease has been found. It is called ATP7B. DNA testing is available for this gene. Talk to your health care provider or a genetic counselor if you would like to have gene testing performed. Treatment The goal of treatment is to reduce the amount of copper in the tissues. This is done by a procedure called chelation -- certain medications can bind to copper and help remove it through the kidneys or gut. Treatment must be lifelong. The following medications may be used:
Penicillamine (Cuprimine, Depen) binds to copper and leads to increased release of copper in the urine. Trientine (Syprine) binds (chelates) the copper and increases its release through the urine. Zinc acetate (Galzin) blocks copper from being absorbed in the intestinal tract.
Vitamin E supplements may also be used. Sometimes, medications that chelate copper (especially penicillamine) can affect the function of the brain and nervous system (neurological function). Other medications under investigation may bind copper without affecting neurological function. A low-copper diet may also be recommended. Foods to avoid include:

Chocolate Dried fruit Liver Mushrooms Nuts Shellfish
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You may want to drink distilled water because most tap water flows through copper pipes. Avoid using copper cooking utensils. Symptoms may be treated with exercise or physical therapy. People who are confused or unable to care for themselves may need special protective measures. A liver transplant may be considered in cases where the liver is severely damaged by the disease. Support Groups Wilson's disease support groups at www.wilsonsdisease.org and www.geneticalliance.org. Expectations (prognosis) Lifelong treatment is needed to control Wilson's disease. The disorder may cause fatal effects, especially loss of liver function and toxic effects of copper on the nervous system. In cases where the disorder is not fatal, symptoms may be disabling. Complications

can
be
found
Anemia (hemolytic anemia is rare) Central nervous system complications Cirrhosis Death of liver tissues Fatty liver Hepatitis Increased number of bone fractures Increased number of infections Injury caused by falls Jaundice Joint contractures or other deformity Loss of ability to care for self Loss of ability to function at work and home Loss of ability to interact with other people Loss of muscle mass (muscle atrophy)
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Psychological complications Side effects of penicillamine and other medications used to treat the disorder Spleen problems
Liver failure and damage to the central nervous system (brain, spinal cord) are the most common and dangerous effects of the disorder. If not caught and treated early, Wilson's disease is fatal. Signs and symptoms Liver disease Liver disease may present itself as tiredness, increased bleeding tendency or confusion (due to hepatic encephalopathy) and portal hypertension. Fulminant acute liver failure, often in the context of a hemolytic anemia (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by deranged coagulation) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products such as ammonia in the bloodstream. When these irritate the brain, the person develops hepatic encephalopathy (confusion, coma, seizures and finally life-threatening swelling of the brain). Neuropsychiatric symptoms Mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of parkinsonism (cogwheel rigidity, bradykinesia or slowed movements and a lack of balance are the most common parkinsonian features) with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body). Seizures and migraine appear to be more common in Wilson's disease. Cognition can also be affected in Wilson's disease. This comes in two, not mutually exclusive, categories: frontal lobe disorder (may present as impulsivity, impaired judgement, promiscuity, apathy and executive dysfunction with poor planning and decision making) and subcortical dementia(may present as slow thinking, memory loss and executive dysfunction, without signs of aphasia, apraxia or agnosia). Psychiatric symptoms are commonly seen in conjunction with neurological symptoms and are rarely manifested on their own. These symptoms are often poorly defined and can sometimes be attributed to other causes. Because of this, diagnosis of Wilson's disease is rarely made when only psychiatric symptoms are present. Other organ systems
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Medical conditions have been linked with copper accumulation in Wilson's disease:
Eyes: KayserFleischer rings (KF rings), a pathognomonic sign, may be visible in the cornea of the eyes, either directly or on slit lamp examination as deposits of copper in a ring around the cornea. They are due to copper deposition in Descemet's membrane. They do not occur in all people with Wilson's disease. Wilson's disease is also associated with sunflower cataracts exhibited by brown or green pigmentation of the anterior and posterior lens capsule. Neither cause significant visual loss. KF rings occur in approximately 66% of diagnosed cases (more often in those with neurological symptoms rather than with liver problems). Kidneys: renal tubular acidosis, a disorder of bicarbonate handling by the proximal tubules leads to nephrocalcinosis (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally aminoaciduria (loss of essential amino acids needed for protein synthesis). Heart: cardiomyopathy (weakness of the heart muscle) is a rare but recognized problem in Wilson's disease; it may lead to heart failure (fluid accumulation due to decreased pump function) and cardiac arrhythmias (episodes of irregular and/or abnormally fast or slow heart beat). Hormones: hypoparathyroidism (failure of the parathyroid glands leading to low calcium levels), infertility, and habitual abortion.
Genetics
Wilson's disease has an autosomal recessive pattern of inheritance. The Wilson's disease gene (ATP7B) has been mapped to chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta. The gene codes for a P-type (cation
25
transport enzyme) ATPase that transports copper into bile and incorporates it [1] into ceruloplasmin. Mutations can be detected in 90%. Most (60%) arehomozygous for ATP7B mutations (two abnormal copies), and 30% have only one abnormal copy. Ten per cent have no detectable mutation. A normal variation in the PRNP gene can modify the course of the disease by delaying the age of onset and affecting the type of symptoms that develop. This gene produces prion protein, which is active in the brain and other tissues and also appears to be involved in transporting copper.[7] A role for the ApoE gene was initially suspected but could not be confirmed. The condition is inherited in an autosomal recessive pattern. In order to inherit it, both of the parents of an individual must carry an affected gene. Most have no family history of the condition. People with only one abnormal gene are called carriers (heterozygotes) and may have mild, but medically insignificant, abnormalities of copper metabolism. Wilson's disease is the most common of a group of hereditary diseases that cause copper overload in the liver. All can cause cirrhosis at a young age. The other members of the group are Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis. These are not related toATP7B mutations: for example, ICC has been linked to mutations in the KRT8 and the KRT18 gene. Diagnosis
Location of the basal ganglia, the part of the brain affected by Wilson's disease Wilson's disease may be suspected on the basis of any of the symptoms mentioned above, or when a close relative has been found to have Wilson's. Most have slightly abnormal liver function tests such as a raisedaspartate transaminase, alanine transaminase and bilirubin level. If the liver damage is significant, albumin may be decreased due to an inability of damaged liver cells to produce this protein; likewise, the prothrombin time (a test of coagulation) may be prolonged as the liver is unable to produce proteins known as clotting factors.
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Alkaline phosphatase levels are relatively low in those with Wilson's-related acute liver failure. If there are neurological symptoms, magnetic resonance imaging (MRI) of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the T2 setting. MRI may also demonstrate the characteristic "face of the giant panda" pattern. There is no totally reliable test for Wilson's disease, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24-hour period, are together used to form an impression of the amount of copper in the body. The gold standard or most ideal test is a liver biopsy.[1] Ceruloplasmin
Ceruloplasmin Levels of ceruloplasmin are abnormally low (<0.2 g/L) in 8095% of cases.[1] It can, however, be present at normal levels in people with ongoing inflammation as it is an acute phase protein. Low ceruloplasmin is also found inMenkes disease and aceruloplasminemia, which are related to, but much rarer than Wilson's disease. The combination of neurological symptoms, KayserFleisher rings and a low ceruloplasmin level is considered sufficient for the diagnosis of Wilson's disease. In many cases, however, further tests are needed. Serum and urine copper Serum copper is paradoxically low but urine copper is elevated in Wilson's disease. Urine is collected for 24 hours in a bottle with a copper-free liner. Levels above 100 g/24h (1.6 mol/24h) confirm Wilson's disease, and levels above 40 g/24h (0.6 mol/24h) are strongly indicative.[1] High urine copper levels are not unique to Wilson's disease; they are sometimes observed in autoimmune hepatitis and in cholestasis (any disease obstructing the flow of bile from the liver to the small bowel).
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In children, the penicillamine test may be used. A 500 mg oral dose of penicillamine is administered, and urine collected for 24 hours. If this contains more than 1600 g (25 mol), it is a reliable indicator of Wilson's disease. This test has not been validated in adults Liver biopsy Once other investigations have indicated Wilson's disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. This is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. A level of 250 g of copper per gram of dried liver tissue confirms Wilson's disease. Occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of Wilson's. In the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas ofnecrosis (cell death). In more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration byinflammatory cells, piecemeal necrosis and fibrosis (scar tissue). In advanced disease, finally, cirrhosis is the main finding. In acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. Histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis. Genetic testing Mutation analysis of the ATP7B gene, as well as other genes linked to copper accumulation in the liver, may be performed. Once a mutation is confirmed, it is possible to screen family members for the disease as part of clinical genetics family counseling. Treatment Dietary In general, a diet low in copper-containing foods is recommended with the avoidance of mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Medication Medical treatments are available for Wilson's disease. Some increase the removal of copper from the body, while others prevent the absorption of copper from the diet. penicillamine is the first treatment used. This binds copper (chelation) and leads to excretion of copper in the urine. Hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. Penicillamine is not without problems: about 20% experience a side effect or complication of penicillamine treatment, such as druginduced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to
28
muscle weakness). In those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. A further agent with known activity in Wilson's disease is tetrathiomolybdate. This is regarded as experimental, though some studies have shown a beneficial effect.[1] Once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called Galzin) may be used instead of chelators to maintain stable copper levels in the body. Zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents their absorption and transport to the liver. Zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases. In rare cases where none of the oral treatments are effective, especially in severe neurological disease, dimercaprol (British anti-Lewisite) is occasionally necessary. This treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain. Physical therapy Physiotherapy is beneficial for patients with the neurologic form of the disease. The copper chelating treatment may take up to six months to start working, and physical therapy can assist in coping with ataxia, dystonia, and tremors, as well as preventing the development of contractures that can result from dystonia. Transplantation Liver transplantation is an effective cure for Wilson's disease but is used only in particular scenarios because of the risks and complications associated with the procedure. It is used mainly in people with fulminant liver failure who fail to respond to medical treatment or in those with advanced chronic liver disease. Liver transplantation is avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated. Prognosis Left untreated, Wilson's disease tends to become progressively worse and is eventually fatal. With early detection and treatment, most of those affected can live relatively normal lives. Liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent.
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Essential tremor
Definition Essential tremor is a type of involuntary shaking movement in which no cause can be identified. Involuntary means you shake without trying to do so. Causes, incidence, and risk factors Essential tremors are most common in people older than 65. The exact cause for essential tremor is unknown. Tremors occur when there is a problem with the nerves that supply certain muscles. Essential tremor can also occur with other brain and nervous system problems, such as dystonia, parkinsonism, and certain nerve conditions passed down through families. If an essential tremor occurs in more than one member of a family, it is called a familial tremor. This type of essential tremor is passed down through families (inherited), which suggests that genes play a role in its cause. Familial tremor is usually a dominant trait, which means that you only need to get the gene from one parent to develop the tremor. It often starts in early middle age, but may be seen in people who are older or younger. Symptoms The tremor is more likely to be noticed in the hands, but may affect the arms, head, eyelids, or other muscles. The tremor rarely affects the legs or feet. People with essential tremor may have trouble holding or using small objects such as silverware or a pen. The shaking most often involves small, rapid movements -- more than 5 times a second. Specific symptoms may include:

Head nodding Shaking or quivering sound to the voice if the tremor affects the voice box Problems with writing, drawing, drinking from a cup, or using tools if the tremor affects the hands
The tremors may:

Occur when you move (action-related tremor), and may be less noticeable with rest Come and go, but often get worse as you age
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Get worse with stress, caffeine, and certain medications Not affect both sides of the body the same way
Signs and tests Medical and personal history. A physical exam will show shaking with movement, usually small movements that are faster than 5 times per second. There are usually no problems with coordination or mental function. Further tests may be needed to rule out other reasons for the tremors. Other causes of tremors may include:

Smoking and smokeless tobacco Overactive thyroid (hyperthyroidism) Suddenly stopping alcohol after drinking a lot for a long time (alcohol withdrawal) Too much caffeine Use of certain medications
Blood tests and imaging studies (such as a CT scan of the head, brain MRI, and x-rays) are usually normal. Treatment Treatment may not be needed unless the tremors interfere with your daily activities or cause embarrassment. HOME CARE For tremors made worse by stress, try techniques that help you relax. For tremors of any cause, avoid caffeine and get enough sleep. For tremors caused or made worse by a medication, talk to your doctor about stopping the drug, reducing the dosage, or switching. Do NOT change or stop medications on your own. Severe tremors may make it harder to do daily activities. You may need help with these activities. Devices may help with everyday activities, such as: Buying clothes with Velcro fasteners, using button hooks Cooking or eating with utensils that have a larger handle Using straws to drink Wearing slip-on shoes and using shoehorns
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MEDICINES FOR TREMOR Medicines may help relieve symptoms. The most commonly used drugs include:

Propranolol, a beta blocker Primidone, a drug used to treat seizures
The drugs can have side effects.
Propranolol may cause fatigue, stuffy nose, or slow heart beat, and may make asthma worse Primidone may cause drowsiness, problems concentrating, nausea, and problems with walking, balance, and coordination.
Other medications that may reduce tremors include:

Antiseizure drugs such as gabapentin and topiramate Mild tranquilizers such as alprazolam or clonazepam Blood pressure drugs called calcium-channel blockers such as flunarizine and nimodipine
Botox injections, given in the hand, have been used to reduce tremors by weakening local muscles. SURGERY In severe cases, surgery may be tried. This may include:

Focusing high-powered x-rays on a small area of the brain (stereotactic radiosurgery) Implanting a stimulating device in the brain to signals the area that controls movement
Expectations (prognosis) An essential tremor is not a dangerous problem, but some patients find the tremors annoying and embarrassing. In some cases, it may be dramatic enough to interfere with work, writing, eating, or drinking. Complications Sometimes the tremors affect the voice box, which occasionally leads to speech problems.
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Multiple sclerosis
DEFINITION Multiple sclerosis (MS), also known as "disseminated sclerosis" or "encephalomyelitis disseminata", is aninflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. INCIDENCE Disease onset usually occurs in young adults, and it is more common in women. Causes Most likely MS occurs as a result of some combination of genetic, environmental and infectious factors, and possibly other factors like vascular problems. Genetics
HLA region of Chromosome 6. Changes in this area increase the probability of suffering MS.
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MS is not considered a hereditary disease. However, a number of genetic variations have been shown to increase the risk of developing the disease. Environmental factors Different environmental factors, both of infectious and non-infectious origin, have been proposed as risk factors for MS. Although some are partly modifiable, only further researchespecially clinical trialswill reveal whether their elimination can help prevent MS.[17] Decreased sunlight exposure has been linked with a higher risk of MS. Decreased vitamin D production and intake has been the main biological mechanism used to explain the higher risk among those less exposed to sun. Severe stress may be a risk factor although evidence is weak. Smoking has also been shown to be an independent risk factor for developing MS. Association with occupational exposures and toxinsmainlysolventshas been evaluated, but no clear conclusions have been reached. Vaccinations were investigated as causal factors for the disease; however, most studies show no association between MS and vaccines. Several other possible risk factors, such as diet and hormone intake, have been investigated; however, evidence on their relation with the disease is "sparse and unpersuasive". Gout occurs less than would statistically be expected in people with MS, and low levels of uric acid have been found in people with MS as compared to normal individuals.
Infections The association of several viruses with human demyelination encephalomyelitis, and induction of demyelination in animals through viral infection. Human herpes viruses are a candidate group of viruses linked to MS. Individuals who have never been infected by the Epstein-Barr virus have a reduced risk of having the disease, and those infected as young adults have a greater risk than those who had it at a younger age. Other diseases that have also been related with MS are measles,mumps, and rubella.
Progression of MS subtypes Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Societystandardized four clinical courses: 1. relapsing remitting, 2. secondary progressive, 3. primary progressive, and
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4. progressive relapsing. The relapsing-remitting subtype is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during attacks may either resolve or leave sequelae, the latter being more common as a function of time.
Nerve axon with myelin sheath Secondary progressive MS (sometimes called "galloping MS") describes around 65% of those with an initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The median time between disease onset and conversion from relapsingremitting to secondary progressive MS is 19 years. The primary progressive subtype describes the approximately 1015% of individuals who never have remission after their initial MS symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. The age of onset for the primary progressive subtype is later than for the relapsing-remitting, but similar to mean age of progression between the relapsing-remitting and the secondary progressive. In both cases it is around 40 years of age. Progressive relapsing MS describes those individuals who, from onset, have a steady neurologic decline but also suffer clear superimposed attacks. This is the least common of all subtypes. Pathophysiology
35
Demyelination in MS. On Klver-Barrera myelin staining, decoloration in the area of the lesion can be appreciated (Original scale 1:100). Autoimmunology MS is believed to be an immune-mediated disorder mediated by a complex interaction of the individual's genetics and as yet unidentified environmental insults. Damage is believed to be caused by the person's own immune system attacking the nervous system. Possible targets of the immune response include myelin basic protein (MBP) and proteolipid protein (PLP). The commonly prescribed MS drug Copaxone was designed to mimic MBP and therefore act as a decoy for autoreactive immune cells. Even so, the role of MBP in MS is controversial; it is buried within the myelin sheath (rather than on the surface), where immune cells would not be able to recognize it. Recent data suggest a role for myelin lipids in MS. Historically, researchers have assumed the myelin target was a protein, even though the myelin sheath is nearly 80% lipid. Furthermore, lipids are known to be the target of another prominent nervous system autoimmune condition, Guillain-Barre Syndrome. Whether the autoantigen is a protein or a lipid, autoimmunity may arise when immune cells recognizing a foreign antigen cross-react with self antigens. This process is known as molecular mimicry. Lesions The name multiple sclerosis refers to the scars (scleroses better known as plaques or lesions) that form in the nervous system. MS lesions most commonly involve white matter areas close to the ventricles of the cerebellum, brain stem, basal ganglia and spinal cord; and the optic nerve. The function of white matter cells is to carry signals between grey matter areas, where the processing is done, and the rest of the body. The peripheral nervous system is rarely involved More specifically, MS destroys oligodendrocytes, the cells responsible for creating and maintaining a fatty layerknown as the myelin sheathwhich helps the neurons carry electrical signals (action potentials). MS results in a thinning or complete loss of myelin and, as the disease advances, the cutting (transection) of the neuron's axons. When the myelin is lost, a neuron can no longer effectively conduct electrical signals. A repair process, calledremyelination, takes place in early phases of the disease, but the oligodendrocytes cannot completely rebuild the cell's myelin sheath. Repeated attacks lead to successively fewer effective remyelinations, until a scarlike plaque is built up around the damaged axons. Different lesion patterns have been described Inflammation Apart from demyelination, the other pathologic hallmark of the disease is inflammation. According to a strictly immunological explanation of MS, the inflammatory process is caused by T cells, a kind of lymphocyte. Lymphocytes are cells that play an important role in the body's defenses. In MS, T cells gain entry into the brain via disruptions in the bloodbrain barrier.
36
Evidence from animal models also point to a role of B cells in addition to T cells in development of the disease. The T cells recognize myelin as foreign and attack it as if it were an invading virus. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Further leaks form in the bloodbrain barrier, which in turn cause a number of other damaging effects such asswelling, activation of macrophages, and more activation of cytokines and other destructive proteins. Bloodbrain barrier breakdown The bloodbrain barrier is a part of the capillary system that prevents the entry of T cells into the central nervous system. However, it may become permeable to these types of cells because of an infection or a virus. When the bloodbrain barrier regains its integrity, typically after the infection or virus has cleared, the T cells are trapped inside the brain. Signs and symptoms
Main symptoms of multiple sclerosis A person with MS can suffer almost any neurological symptom or sign, including changes in sensation such as loss of sensitivity or tingling, pricking or numbness (hypoesthesia and paresthesia) muscle weakness, clonus,muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis including phosphenes,[8][9] ordiplopia),
37
fatigue, acute or chronic pain bladder and bowel difficulties. Cognitive impairment of varying degrees of depression or unstable mood are also common.
and
emotional
symptoms
Symptoms of MS usually appear in episodic acute periods of worsening (called relapses, exacerbations, bouts, attacks, or "flare-ups"), in a gradually progressive deterioration of neurologic function, or in a combination of both. Multiple sclerosis relapses are often unpredictable, occurring without warning and without obvious inciting factors. Symptoms vary, because the location and severity of each attack can be different. Episodes can last for days, weeks, or months. These episodes alternate with periods of reduced or no symptoms (remissions). Fever, hot baths, sun exposure, and stress can trigger or worsen attacks. It is common for the disease to return (relapse). However, the disease may continue to get worse without periods of remission. Because nerves in any part of the brain or spinal cord may be damaged, patients with multiple sclerosis can have symptoms in many parts of the body. Muscle symptoms:

Loss of balance Muscle spasms Numbness or abnormal sensation in any area Problems moving arms or legs Problems walking Problems with coordination and making small movements Tremor in one or more arms or legs Weakness in one or more arms or legs
Bowel and bladder symptoms:

Constipation and stool leakage Difficulty beginning to urinate Frequent need to urinate Strong urge to urinate Urine leakage (incontinence)
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Eye symptoms:

Double vision Eye discomfort Uncontrollable rapid eye movements Vision loss (usually affects one eye at a time)
Numbness, tingling, or pain

Facial pain Painful muscle spasms Tingling, crawling, or burning feeling in the arms and legs
Other brain and nerve symptoms:

Decreased attention span, poor judgment, and memory loss Difficulty reasoning and solving problems Depression or feelings of sadness Dizziness and balance problems Hearing loss
Sexual symptoms:

Problems with erections Problems with vaginal lubrication
Speech and swallowing symptoms:

Slurred or difficult-to-understand speech Trouble chewing and swallowing
Fatigue is a common and bothersome symptoms as MS progresses. It is often worse in the late afternoon. Diagnosis The most commonly used diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously as a contrast to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with symptoms at the moment of the evaluation.
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Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands of IgG on electrophoresis, which are inflammation markers found in 7585% of people with MS.
The nervous system of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials. Signs and tests Symptoms of MS may mimic those of many other nervous system disorders. The disease is diagnosed by ruling out other conditions. People who have a form of MS called relapsing-remitting may have a history of at least two attacks, separated by a period of reduced or no symptoms. The health care provider may suspect MS if there are decreases in the function of two different parts of the central nervous system (such as abnormal reflexes) at two different times. A neurological exam may show reduced nerve function in one area of the body, or spread over many parts of the body. This may include:

Abnormal nerve reflexes Decreased ability to move a part of the body Decreased or abnormal sensation Other loss of nervous system functions
An eye examination may show:

Abnormal pupil responses Changes in the visual fields or eye movements Decreased visual acuity Problems with the inside parts of the eye Rapid eye movements triggered when the eye moves
Tests to diagnose multiple sclerosis include:

Lumbar puncture (spinal tap) for cerebrospinal fluid tests, including CSF oligoclonal banding MRI scan of the brain and MRI scan of the spine are important to help diagnose and follow MS
40
Nerve function study (evoked potential test)
Treatment There is no known cure for multiple sclerosis at this time. However, there are therapies that may slow the disease. The goal of treatment is to control symptoms and help you maintain a normal quality of life. Medications used to slow the progression of multiple sclerosis are taken on a long-term basis, they include:
Interferons (Avonex, Betaseron, or Rebif), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), and natalizumab (Tysabri) Fingolimod (Gilenya ) Methotrexate, azathioprine (Imuran), intravenous immunoglobulin (IVIg) and cyclophosphamide (Cytoxan) may also be used if the above drugs are not working well
Steroids may be used to decrease the severity of attacks. Medications to control symptoms may include:
Medicines to reduce muscle spasms such as Lioresal (Baclofen), tizanidine (Zanaflex), or a benzodiazepine Cholinergic medications to reduce urinary problems Antidepressants for mood or behavior symptoms Amantadine for fatigue
For more information see:

Neurogenic bladder Bowel retraining
The following may also be helpful for people with MS:

Physical therapy, speech therapy, occupational therapy, and support groups Assistive devices, such as wheelchairs, bed lifts, shower chairs, walkers, and wall bars A planned exercise program early in the course of the disorder A healthy lifestyle, with good nutrition and enough rest and relaxation Avoiding fatigue, stress, temperature extremes, and illness
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Changes in what you eat or drink if there are swallowing problems Making changes around the home to prevent falls Social workers or other counseling services to help you cope with the disorder and get assistance (such as Meals-on-Wheels)
For more information about living with MS, see: Multiple sclerosis - at home Household changes to ensure safety and ease in moving around the home are often needed. Management Acute attacks During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses, while oral corticosteroids seem to have a similar efficacy and safety profile. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on longterm recovery. Consequences of severe attacks which do not respond to corticosteroids might be treated by plasmapheresis. Disease-modifying treatments Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 13 month intervals. The approved drugs are interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone(an immunosuppressant also used in cancer chemotherapy), natalizumab (a humanized monoclonal antibodyimmunomodulator), fingolimod and teriflunomide. The interferons and glatiramer acetate are delivered by frequent injections, varying from onceper-day for glatiramer acetate to once-per-week (but intra-muscular) for interferon beta-1a. Natalizumab and mitoxantrone are given by intravenous (IV) infusion at monthly intervals in the case of natalizumab and every three months in the case of mitoxantrone. Fingolimod and teriflunomide are taken through a daily single dose. Most drugs are approved only for the relapsing-remitting course (RRMS). Medications are modestly effective at decreasing the number of attacks in RRMS.[49] Management of the effects of MS Disease-modifying treatments reduce the progression rate of the disease, but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and disability. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, though neither influences disease progression. Some symptoms have a good response to medication,
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such as unstable bladder and spasticity, while management of many others is much more complicated. As for any person with neurologic deficits, a multidisciplinary approach is key to improving quality of life; however, there are particular difficulties in specifying a 'core team' because people with MS may need help from almost any health profession or service at some point. Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level. Due to the paucity of randomized controlled studies, there is limited evidence of the overall efficacy of individual therapy disciplines, though there is good evidence that specific approaches, such as exercise, psychology therapies, particularly cognitive behavioral approaches and energy conservation instruction are effective. Alternative treatments Many people with MS use complementary and alternative medicine. Depending on the treatments, the evidence is weak or absent. Examples are a dietary regimen, herbal medicine (including the use of medical cannabis), hyperbaric oxygenation and self-infection with hookworm (known generally ashelminthic therapy). Prognosis
The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, age, and initial symptoms; and the degree of disability the person experiences. The disease evolves and advances over decades, 30 being the mean years to death since onset. Female sex, relapsing-remitting subtype, optic neuritis or sensory symptoms at onset, few attacks in the initial years and especially early age at onset, are associated with a better course. The life expectancy of people with MS is 5 to 10 years lower than that of unaffected people. Symptoms Support Groups For additional information, see multiple sclerosis resources. Expectations (prognosis) The outcome varies, and is hard to predict. Although the disorder is chronic and incurable, life expectancy can be normal or almost normal. Most people with MS continue to walk and function at work with minimal disability for 20 or more years. The following typically have the best outlook:
Females
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People who were young (less than 30 years) when the disease started People with infrequent attacks People with a relapsing-remitting pattern People who have limited disease on imaging studies
The amount of disability and discomfort depends on:

How often you have attacks How severe they are The part of the central nervous system that is affected by each attack
Most people return to normal or near-normal function between attacks. Slowly, there is greater loss of function with less improvement between attacks. Over time, many require a wheelchair to get around and have a more difficult time transferring out of the wheelchair. Those with a support system are often able to remain in their home. Complications

Depression Difficulty swallowing Difficulty thinking Less and less ability to care for self Need for indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medications used to treat the disorder Urinary tract infections

Movement Disorders

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1

muscles of Causes painful defecation, constipation; the rectum complicated by encopresis.

Cervical dystonia muscles (spasmodic torticollis) the neck

muscles around theeyes

the neuroleptics (e.g., prochlorperazine) or metoclopramide. Also can by Chlorpromazine

Spasmodic dysphonia/Laryngeal dystonia

early-onset torsion dystonia

X-linked torsion dystonia

Primary cervical dystonia

DYT8 (or 118800 PNKD1)

episodic kinesigenic dyskinesia 1

episodic kinesigenic dyskinesia 2

DYT20 (or 611147 PNKD2)

Huntington's Chorea Sydenham chorea Drug-induced chorea

Chorea is a primary feature of Huntington's disease, a progressive neurological disorder.

Adjusting medication dosages.

Metabolic and endocrine-related Treated according to their causes. choreas

Signs and tests A slit-lamp eye examination may show:

A physical examination may show signs of:

Lab tests may include:

If there are liver problems, lab tests may find:

Other tests may include:

Chocolate Dried fruit Liver Mushrooms Nuts Shellfish

The tremors may:

Propranolol, a beta blocker Primidone, a drug used to treat seizures

The drugs can have side effects.

Other medications that may reduce tremors include:

Bowel and bladder symptoms:

Numbness, tingling, or pain

Other brain and nerve symptoms:

Problems with erections Problems with vaginal lubrication

Speech and swallowing symptoms:

Slurred or difficult-to-understand speech Trouble chewing and swallowing

An eye examination may show:

Tests to diagnose multiple sclerosis include:

Nerve function study (evoked potential test)

For more information see:

Neurogenic bladder Bowel retraining

The following may also be helpful for people with MS:

The amount of disability and discomfort depends on:

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