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CT scanning usually demonstrates cerebral atrophy and atrophy of the caudate nucleus in established cases MRI and positron emission tomography (PET) have shown reduced glucose utilization in an anatomically normal caudate nucleus
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4 Idiopathic Torsion Dystonia
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Differential Diagnosis
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Chorea developing with no family history of choreoathetosis should not be attributed to Huntington s disease, at least not until other causes of chorea have been excluded clinically and by appropriate laboratory studies Nongenetic causes of chorea include stroke, systemic lupus erythematosus and related disorders, paraneoplastic syndromes, infection with HIV, and various medications In younger patients, self-limiting Sydenham s chorea develops after group A streptococcal infections on rare occasions If a patient presents solely with progressive intellectual failure, it may not be possible to distinguish Huntington s disease from other causes of dementia unless there is a characteristic family history or a dyskinesia develops A clinically similar autosomal dominant disorder (dentatorubral-pallidoluysian atrophy), manifested by chorea, dementia, ataxia, and myoclonic epilepsy, is uncommon except in persons of Japanese ancestry It is due to a mutant gene mapping to 12p1331 Treatment is as for Huntington s disease
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Dystonic movements and postures Normal birth and developmental history No other neurologic signs Investigations (including CT scan or MRI) reveal no cause of dystonia
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Idiopathic torsion dystonia may occur sporadically or on a hereditary basis, with autosomal dominant, autosomal recessive, and X-linked recessive modes of transmission One responsible gene is located at 9q34 (and has been named DYT1) and involves a unique mutation consisting of a GAG deletion in the dominantly inherited disorder, and maps to the long arm of the X chromosome in the X-linked recessive form; the responsible gene in the autosomal recessive disorder is unknown Other autosomal dominant forms have also been recognized, with different or unidentified genetic loci Symptoms may begin in childhood or later and persist throughout life
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Treatment
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There is no cure for Huntington s disease; progression cannot be halted; and treatment is purely symptomatic The reported biochemical changes suggest a relative underactivity of neurons containing gamma-aminobutyric acid (GABA) and acetylcholine or a relative overactivity of dopaminergic neurons Treatment with drugs blocking dopamine receptors, such as phenothiazines or haloperidol, may control the dyskinesia and any behavioral disturbances Haloperidol treatment is usually begun with a dose of 1 mg once or twice daily, which is then increased every 3 or 4 days depending on the response Tetrabenazine, a drug that depletes central monoamines, is widely used in Europe to treat dyskinesia but is not available in the United States Reserpine is similar in its actions to tetrabenazine and may be helpful; the daily dose is built up gradually to between 2 and 5 mg, depending on the response
Clinical Findings
The disorder is characterized by the onset of abnormal movements and postures in a patient with a normal birth and developmental history, no relevant past medical illness, and no other neurologic signs Investigations (including CT scan) reveal no cause for the abnormal movements Dystonic movements of the head and neck may take the form of torticollis, blepharospasm, facial grimacing, or forced opening or closing of the mouth The limbs may also adopt abnormal but characteristic postures The age at onset influences both
CMDT 2008
8 (DYT6) and chromosome 18 (DYT7) has been reported in some instances of cervical or cranial dystonia Medical treatment is generally unsatisfactory A trial of the drugs used in idiopathic torsion dystonia is worthwhile, however, since a few patients do show some response In addition, with restricted dystonias such as blepharospasm or torticollis, local injection of botulinum A toxin into the overactive muscles may produce worthwhile benefit for several weeks or months and can be repeated as needed Both blepharospasm and oromandibular dystonia may occur as an isolated focal dystonia The former is characterized by spontaneous involuntary forced closure of the eyelids for a variable interval Oromandibular dystonia is manifested by involuntary contraction of the muscles about the mouth causing, for example, involuntary opening or closing of the mouth, roving or protruding tongue movements, and retraction of the platysma Spasmodic torticollis, usually with onset between 25 and 50 years of age, is characterized by a tendency for the neck to twist to one side This initially occurs episodically, but eventually the neck is held to the side Spontaneous resolution may occur in the first year or so The disorder is otherwise usually lifelong Selective section of the spinal accessory nerve and the upper cervical nerve roots is sometimes helpful if medical treatment is unsuccessful Local injection of botulinum A toxin provides benefit in most cases Writer s cramp is characterized by dystonic posturing of the hand and forearm when the hand is used for writing and sometimes when it is used for other tasks, eg, playing the piano or using a screwdriver or eating utensils Drug treatment is usually unrewarding, and patients are often best advised to learn to use the other hand for activities requiring manual dexterity Injections of botulinum A toxin are helpful in some instances
the clinical findings and the prognosis With onset in childhood, there is usually a family history of the disorder, symptoms commonly commence in the legs, and progression is likely until there is severe disability from generalized dystonia In contrast, when onset is later, a positive family history is unlikely, initial symptoms are often in the arms or axial structures, and severe disability does not usually occur, although generalized dystonia may ultimately develop in some patients If all cases are considered together, about onethird of patients eventually become so severely disabled that they are confined to chair or bed, while another one-third are affected only mildly
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