Abstract: Summary A consanguineous family affected by an autosomal recessive, progressive neurodegenerative Huntington-like disorder, was tested to rule out juvenile-onset Huntington disease (JHD). The disease manifests at ∼3–4 years and is characterized by both pyramidal and extrapyramidal abnormalities, including chorea, dystonia, ataxia, gait instability, spasticity, seizures, mutism, and intellectual impairment. Brain magnetic resonance imaging (MRI) findings include progressive frontal cortical atrophy and bilateral caudate atrophy. Huntington CAG trinucleotide-repeat analyses ruled out JHD, since all affected individuals had repeat numbers within the normal range. The presence of only four recombinant events (θ=.2) between the disease and the Huntington locus in 20 informative meioses suggested that the disease localized to chromosome 4. Linkage was initially achieved with marker D4S2366 at 4p15.3 (LOD 3.03). High-density mapping at the linked locus resulted in homozygosity for markers D4S431 and D4S394, which span a 3-cM region. A maximum LOD score of 4.71 in the homozygous interval was obtained. Heterozygosity at the distal D4S2366 and proximal D4S2983 markers defines the maximum localization interval (7 cM). Multiple brain-related expressed sequence tags (ESTs) with no known disease association exist in the linkage interval. Among the three known genes residing in the linked interval ( ACOX3, DRD5, QDPR ), the most likely candidate, DRD5, encoding the dopamine receptor D5, was excluded, since all five affected family members were heterozygous for an intragenic dinucleotide repeat. The inheritance pattern and unique localization to 4p15.3 are consistent with the identification of a novel, autosomal recessive, neurodegenerative Huntington-like disorder.

Abstract: Huntington's disease is characterised by hyperkinetic movements, mainly chorea, cognitive dysfunction, and psychiatric abnormalities. Non-dopa responsive parkinsonism occurs in the later stages of choreic disease or as the predominant feature of juvenile patients (Westphal variant). Late onset Huntington's disease presenting as levodopa responsive parkinsonism is rare. A series of four patients with late onset Huntington's disease presenting as levodopa responsive parkinsonism and cardiovascular dysautonomia, initially misdiagnosed as multiple system atrophy (MSA) in three patients, is reported. Levodopa treatment did not unmask significant chorea. These cases suggest the presence of a distinct phenotypic variant of Huntington's disease to be added to the differential diagnosis of other akinetic rigid syndromes.

Abstract: BACKGROUND: Movement disorders may appear during tuberculous meningitis (TbM).OBJECTIVE: To investigate the variety of movement disorders seen in TbM and consider possible pathogenic mechanisms.DESIGN: We established two diagnostic categories for TbM: definite and probable. All patients were examined clinically and with laboratory tests, computed tomographic scan, or magnetic resonance imaging.SETTING: A university hospital in Quite, Ecuador.RESULTS: Thirty of 180 consecutively studied patients with TbM developed movement disorders. Twenty-four months after treatment was completed, we determined a prognosis for the patients. Seven patients had chorea, three dystonia, and 20 tremor. One of the patients with tremor also had myoclonus and one with dystonia had tremor. The average age of the patients with chorea was lower than that of the patients with dystonia and tremor. Two patients with chorea, one with dystonia, and three patients with tremor died. The patients with chorea and dystonia had more severe disease. We found little correlation between the type, distribution, or severity of abnormal movements and the computed tomography scan or magnetic resonance image findings.CONCLUSIONS: Tremor is the most common movement disorder seen in the course of TbM. Chorea is more frequently found in young children. Deep vascular lesions are more common among patients with movement disorders.

Abstract: Neurologic complications of systemic lupus cerebritis are not as well known in children as in adults. Twenty-five children with neurologic complications were identified after reviewing the hospital medical records of 86 children with systemic lupus erythematosus. Seven children (28%) had neurologic symptoms at the time of initial diagnosis of systemic lupus erythematosus; median time between diagnosis of systemic lupus erythematosus and onset of neurologic complications was 1 month (range 0-5 years). Seizures were the most common neurologic symptoms overall, but headaches were the most frequent neurologic manifestation in children without a previous diagnosis of systemic lupus erythematosus. Sixteen children had seizures, and 12 children had seizures as the initial central nervous system involvement. Almost all children who developed seizures had an established diagnosis of systemic lupus erythematosus; only one child had seizures that led to the diagnosis of systemic lupus erythematosus. No patient had status epilepticus, and, in general, seizures were not difficult to control. In six children, headache was the initial symptom of central nervous system involvement. Five children had lupus cerebritis, three children had stroke, and two had isolated cranial neuropathies. Chorea was seen in only two cases, and three children had pseudotumor cerebri. Treatment with high-dose intravenous methylprednisolone led to a good response in 18 children; cyclophosphamide was required in 6 patients and plasmapheresis in 1 child. Outcome was generally good, although one child developed fulminant cerebritis with intracranial hypertension and died.

Abstract: INTRODUCTION AND METHOD The prototypic motor feature of Huntington's disease (HD) is chorea, but parkinsonism and involuntary movements such as dystonia and myoclonus can also be present. Pallidotomy has been shown to be an effective treatment for medically refractory Parkinson's disease (PD). We performed bilateral microelectrode guided-stereotactic pallidotomies targeted at globus pallidum internus (GPi) to treat a 13-year-old patient diagnosed with Westphal variant of HD with intractable generalized dystonia and parkinsonism. RESULTS Intraoperative microelectrode recordings of GPi cells showed a relatively low firing rate, 29 + 14 Hz, with most neurons showing pauses. Acutely, after surgery, limb dystonia mildly improved but trunk dystonia persisted. Postoperative follow up 3 months later showed minimal clinical improvement in dystonic features with marked worsening of spasticity. CONCLUSION In our case, bilateral pallidotomy produced modest palliative functional improvement in dystonic features. Cellular firing patterns were markedly different than in PD and were similar to those found in dystonia.

Abstract: Background In juvenile Huntington disease (HD), dystonia as well as parkinsonism and eye movement abnormalities may be the predominant motor signs rather than chorea. Several patients have come to our attention with adult-onset HD in whom there is prominent dystonia and minimal chorea (ie, an adult-onset form of HD that resembles juvenile HD). Objectives To estimate the prevalence of these cases of dystonia-predominant HD in a clinic and to study the relationship between the motor phenotype and age of onset in HD. Methods The Unified Huntington's Disease Rating Scale (UHDRS) was administered to 127 subjects during their initial visit to the Huntington's Disease Center at the New York State Psychiatric Institute, where dystonia, chorea, bradykinesia, rigidity, and eye movements were rated. The dystonia score was the mean UHDRS rating of dystonia in 5 body regions; the chorea score, the mean rating of chorea in 7 regions; the bradykinesia score, the mean rating of axial and limb bradykinesia; the rigidity score, the mean rating of rigidity in both arms; and the eye movement score, the mean rating of ocular pursuit, saccade initiation, and velocity. Dystonia-predominant HD was defined by the severity of dystonia relative to the severity of chorea. Results Fifteen (11.8%) of 127 subjects had dystonia-predominant HD. Age of onset correlated negatively ( r = −0.22, P = .02) with the dystonia score divided by the chorea score and negatively ( r = −0.28, P = .002) with the severity of dystonia, bradykinesia, and eye movement abnormalities relative to chorea (ie, [(dystonia score + bradykinesia score + eye movement score)/3] − chorea score), suggesting that subjects with younger ages of onset had more severe dystonia, bradykinesia, and eye movement abnormalities relative to chorea. Conclusions Cases of adult-onset HD with prominent dystonia and a paucity of chorea may represent 1 in 8 cases in specialty clinics. Age of onset was clearly associated with the motor phenotype. A younger age of onset was associated with more severe dystonia, bradykinesia, and eye movement abnormalities relative to chorea, supporting the notion that in adult-onset HD, the motor phenotype forms a continuum with respect to age of onset.

Abstract: The original Jones Criteria as proposed by Dr. T. Duckett Jones have been modified four times and the updated revised criteria were published in 1992. According to this latest publication major manifestations are carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules. Minor manifestations include fever, arthralgia and laboratory findings of elevated erythrocyte sedimentation rate, C-reactive protein and prolonged PR interval on ECG. For making a diagnosis of acute rheumatic fever, two major, or one major and two minor manifestations must be accompanied by supporting evidence of antecedent group A streptococcal infection in the form of positive throat culture or elevated or rising anti-streptolysin titre. The updated guidelines also highlighted a subgroup of “exceptions to Jones Criteria” for patients with chorea, indolent carditis and previous history of rheumatic fever or “rheumatic heart disease”. Role of echocardiography has not been defined in these modifications but may be important, as clinical detection of soft murmurs may be difficult due to tachycardia. Doppler and color flow mapping is more sensitive in picking up minor digress of valvular regurgitation. Several studies have confirmed that the yield of carditis with valvular regurgitation increased with use of echocardiography in patients with acute rheumatic fever. Also echocardiography is of great help in mixed valve lesions to determine the severity of each lesion. Other abnormalities detected on echocardiography in acute carditis include prolapse of the valve, focal nodular thickening of leaflets and pericardial effusion.

Abstract: The treatment of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) can be difficult and complex owing to the variety of nervous system manifestations that can occur, which include peripheral nerve disease, headaches, seizures, cerebrovascular disease, chorea, transverse myelitis, and psychiatric and cognitive disorders. Many of these manifestations can result from metabolic abnormalities or infection or as side effects of medications. Thus, in any patient with suspected NPSLE, it is crucial to exclude secondary causes of the presenting symptoms before assuming that they are due to NPSLE. It is especially important to exclude infection because this is a common cause of both morbidity and mortality in patients with systemic lupus erythematosus (SLE). Symptoms such as anxiety and depression may or may not be related to disease activity. Treatment decisions are based on accurate diagnosis of the specific NPSLE manifestation, which is usually made using tools such as brain imaging, electroencephalography, cerebrospinal fluid analysis, nerve conduction studies, or special serologic tests (eg, determination of antiphospholipid or antiribosomal P antibody levels). It is also important to assess the degree of other SLE- mediated systemic disease activity in a patient with neurologic manifestations to determine if activation of systemic disease activity is also occurring. This is done by measuring complement levels, anti-double-stranded DNA levels, complete blood count, and urinalysis. For some NPSLE manifestations (eg, infrequent seizures, headaches, depression, anxiety, or peripheral neuropathy) that appear without activation of systemic disease, symptomatic treatment is appropriate. For others (eg, psychosis, delirium, or transverse myelopathy without other obvious cause), treatment with high-dose glucocorticoids with or without cyclophosphamide is appropriate whether there is evidence of other systemic disease activity or not. In general, the activity and severity of the leading organ manifestations dictate pharmacologic treatment.

Abstract: A 73 year old man presented with progressive choreic movement and dementia. An antineuronal antibody that recognised a 68 kDa band on a western blot was found in the patient's serum; this antibody immunolabelled neuronal somata in rat brain. Postmortem examination showed a small cell lung cancer and severe neuronal loss with lymphocytic infiltration in the striatum that was more severe in the caudate head. This is thought to be the first pathologically proved case of paraneoplastic chorea with striatal encephalitis.

Abstract: Although Huntington's disease has existed since at least the seventeenth century, and although several physicians provided earlier descriptions of hereditary chorea, Huntington's disease was not generally recognized until the classic description by George Huntington (1850–1916) in 1872. This paper – on the sesquicentennial of Huntington's birth – reviews Huntington's original and later contributions to the description of this disorder, his professional presentations and correspondence on the topic, and his publications, as well as his background, medical training, and clinical practice. The characteristics of Huntington's disease recognized by George Huntington in 1872 – i.e., the distinct clinical profile, midlife onset, and autosomal dominant inheritance pattern – made the disease ideal for investigation by genetic linkage analysis a century after Huntington's description. Subsequent breakthroughs have identified the genetic defect as an unstable expanded CAG trinucleotide repeat mutation in a novel gen...

Abstract: Metabolite levels in cerebrospinal fluid from patients with Parkinson disease or Huntington chorea were compared with the levels in healthy controls using proton magnetic resonance spectroscopy. No significant differences were found for any metabolite measured in cerebrospinal fluid from patients with Parkinson disease compared to controls. Slight but significantly reduced levels of both lactate and citrate, however, were found in cerebrospinal fluid from patients with Huntington chorea compared to controls. This suggests possible impairment of both glycolysis and tricarboxylic acid cycle function. The reduction in lactate found in the present study may reflect neuronal loss. The decrease in citrate supports the theory of mitochondrial dysfunction in the brain of patients with Huntington chorea, but also suggests that there may be an important astrocytic component in this disease. If so, it would certainly have implications for neuronal function. J. Neurosci. Res. 60:779–782, 2000. © 2000 Wiley-Liss, Inc.

Abstract: Sydenham's chorea (SC) may occur in rheumatic fever (RF) patients without arthritis and carditis. In this study we typed HLA antigens and alleles in patients presenting with the distinct major clinical mani- festations of RF, i.e., chorea, carditis, or arthritis, in population and family studies. We evaluated 91 patients with RF for HLA-A, HLA-B, and HLA-DR antigens; of these, 33 had pure chorea, 26 pure carditis, 16 pure arthritis, and 16 carditis plus arthri- tis. We also typed 24 SC patients and their unaffected siblings for HLA- DRB1 and HLA-DQB1 alleles using molecular methods. HLA-B49 and HLA-DR1 antigens were overrepre- sented in the total group of patients with RF and in all the subgroups studied, excluding the SC subgroup in which the frequency of HLA-DR1 antigen was not increased. The fre- quencies of the HLA-DRB1 and HLA-DQB1 alleles in patients with pure chorea were not significantly different from those observed in con- trols. Similarly, the frequencies of HLA class II alleles in SC patients did not differ significantly from those observed in unaffected sib- lings. These findings show that im- munogenetic susceptibility to RF varies according to the major clinical manifestation presented by the pa- tient.

Abstract: Neurological manifestations occur frequently in polycythaemia. Chorea, however, is a rare complication of the disease. A case of chorea in a patient previously diagnosed with polycythaemia vera is reported. Choreic movements started after measurement of haematological variables showed deterioration. It was considered that this was caused by inappropriate treatment with iron because the chorea was markedly reduced after the two first venesections and normalisation of the packed cell volume and haemoglobin parameters.

Abstract: Paroxysmal dystonic choreoathetosis (PDC) is an unusual hyperkinetic movement disorder characterized by attacks of chorea, dystonia, and ballism with onset in childhood. We report a large British family with dominantly inherited PDC linked to chromosome 2q and describe the clinical features in 20 affected family members. Attacks were precipitated by a variety of factors, including caffeine, alcohol, or emotion, and could be relieved by short periods of sleep in most subjects. The clinical features in the family are compared with those of 11 other PDC families in the literature and a core phenotype for PDC suggested. CSF monoamine metabolites measured at baseline and during an attack in one subject were found to increase during the attack. Magnetic resonance spectroscopy of brain and basal ganglia performed both during and between attacks was normal. Positron emission tomography using the D2 receptor ligand, 11C-raclopride, showed no abnormalities.

Abstract: The clinical picture of Creutzfeldt-Jakob disease (CJD) includes various movement disorders such as myoclonus, parkinsonism, hemiballism, and dystonia. We report on a patient with CJD who manifested the alien hand sign. We suggest that CJD should be included in the differential diagnosis of diseases which present with an alien hand. Creutztfeldt-Jakob disease, one of the human prion diseases, is characterised by rapidly progressive mental and motor deterioration.1 Involuntary movements occur in above 90% of the patients in the course of the disease, the most common being myoclonus.1 Other movement disorders range from tremor to chorea, athetosis, dystonia, and hemiballism.1 We report on a patient with CJD who presented with an alien hand. Alien hand is a rare and striking phenomenon defined as “a patient's failure to recognise the action of one of his hands as his own”.2 One of the patient's hands acts as a stranger to the body and is uncooperative. Thus, there is loss of feeling of ownership but not loss of sensation in the affected hand. Originally described in callosal tumours,3 the aetiology of alien hand also includes surgical callosotomy,4 infarction of the medial frontal cortex, occipitotemporal lobe, and thalamus,1 5 infection,6 and corticobasal degeneration.5 7 A 70 year old, right handed Jewish man born in Argentina, living in Israel for the past 20 years, was …

Abstract: There is little experience of anaesthesia for patients with Huntington's chorea. These patients have an increased risk of intraoperative complications such as pulmonary aspiration. We present the successful anaesthetic management of a 17-yr-old patient suffering from Huntington's chorea requiring urgent appendectomy. After rapid-sequence induction with thiopental 400 mg and succinylcholine 100 mg, anaesthesia was maintained with sevoflurane. For maintenance of neuromuscular blockade mivacurium 10 mg was administered and repeated 15 min later. Except for a short episode of postoperative shivering, the perioperative course was uneventful. Sevoflurane and mivacurium were used safely and effectively in this patient.

Abstract: Senile chorea is a well recognised but poorly understood clinical entity characterised by a slowly progressive, generalised chorea in elderly people without mental deterioration or a clear underlying cause. The Hallervorden-Spatz syndrome is typically thought of as a paediatric condition with extrapyramidal features and dementia. However, it has been described in adults usually presenting with parkinsonism plus dementia. An elderly woman with slowly progressive chorea without dementia was found at postmortem to have the pathological features originally described by Hallervorden and Spatz. This association has not previously been reported.

Abstract: Moyamoya disease is a relatively uncommon, chronic cerebral vasculopathy of unknown aetiology that is characterised by unilateral or bilateral stenosis or occlusion of the proximal portion of the carotid arteries, together with an abnormal vascular network at the base of the brain. Most childhood cases manifest with the signs and symptoms of cerebral ischaemia or infarction, whereas intracerebral haemorrhage prevails in adults.1 2 We describe here a case of moyamoya disease in a 29 year old multiparous woman, who presented with involuntary limb movements induced by singing. A 29 year old woman, gravida two, para two, presented to the neurological outpatient clinic at Chungbuk National University Hospital with recurrent episodes of brief involuntary movements affecting her left hand and arm. The movements were characterised as unilateral, brief, coarse, irregular, and wavering. There was no history of neuroleptic drug therapy, or family history of involuntary movement. General physical, neurological, and neuropsychological examinations were unremarkable. Baseline blood tests, ECG, and …

Abstract: Huntington's disease is a fatal neurological disorder characterized by chorea and deterioration in cognitive and neuropsychiatric function. Primary pathological changes are found in the striatum, where GABAergic neurons undergo degenerative changes. Local interneurons are relatively spared. Here, we describe the rationale for clinical trials of fetal striatal tissue transplantation for the treatment of Huntington's disease. Specifically, the reasons for utilizing tissue derived from the far lateral aspect of the lateral ventricular eminence as a source of striatal tissue will be discussed.

Abstract: Computed tomography (CT) scans of lower leg muscles reveal a selective pattern of fat infiltration in the posterior compartment with spared gracilis, semitendinosus, and the lateral head of the gastrocnemius in both McLeod syndrome and chorea-acanthocytosis, which are disorders characterized by the presence of circulating acanthocytes. The selectivity of affected muscles indicates that late onset and slowly progressive muscular atrophy in both diseases could be a consequence of primary myopathy. Asymmetrical muscle involvement may be seen during the process of degeneration only in McLeod syndrome, however, and may be helpful in distinguishing this disease from chorea-acanthocytosis.

Abstract: Myoclonus and chorea are hyperkinetic movement disorders that confer a jerky appearance. Myoclonus involves a quick and simple jerk, whereas the jerking in chorea combines with other, slower movements in a continuous, flowing fashion. Both disorders have many different causes, and diagnosis requires knowledge of common clinical characteristics and directed ancillary testing. Symptomatic treatment is available, but reversal of the underlying cause should be considered first if possible. The potential benefits of treatment must be weighed against the risk of drug side effects.