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Chorea is an involuntary movement that appears along with many diseases, it is commonly described as a frequent, brief, sudden, and twitch-like movement that is manifested in various parts of the body in a chaotic pattern. Huntington disease (HD) is a representative neurodegenerative disorder that presents with chorea. Although HD is caused by a CAG-repeat expansion in the IT-15 gene which encodes huntingtin, a small group of patients showing the symptoms and signs of HD do not have the causative CAG-repeat expansion, thereby showing that autosomal-dominant chorea is genetically heterogeneous. Recent studies have demonstrated that such disorders include dentatorubral pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), and benign hereditary chorea (BHC). We recently identified 2 Japanese families with adult-onset benign chorea that was inherited in an autosomal-dominant pattern that was linked to chromosome 8q22.2-q23.3, and we named this disease "benign hereditary chorea type 2 (BHC2)". Chorea can also be caused by a wide range of other hereditary diseases and sporadic disease such as metabolic, infectious, inflammatory, vascular, and drug-induced syndromes. In this article, we have reviewed the clinical features of the disorders associated with chorea.

We described a 61-year-old man with diabetes mellitus who presented with hyperglycemia related paroxysmal kinesigenic dyskinesia (PKD) with sudden development of paroxysmal unilateral involuntary movements (IMs) of his neck and the left extremities. Ictal 99mTc-ethylcysteinate dimer SPECT (ECD-SPECT) revealed a hyperperfusion over the contralateral frontal cortex and a hypoperfusion over the contralateral basal ganglia. Immediate correction of hyperglycemia after admission resulted in a marked improvement of IMs and a return to normal cerebral blood flow on interictal ECD-SPECT imaging. These findings suggest that dysfunction of the indirect pathway through the basal ganglia lead to an imbalance of the cortico-striato-thalamo-cortical circuit and may have contributed to the cause of PKD in this case.

Paroxysmal kinesigenic choreoathetosis (PKC) is a rare and benign disorder with its onset in childhood. PKC generally improves with age, and its pathophysiology has not been revealed. We recorded both ictal and interictal SPECT in a 14-year-old girl with PKC. Ictal SPECT showed a significant decrease in blood flow in the caudate nucleus contralateral to the limb showing an involuntary movement. We also examined paired-pulse stimuli somatosensory evoked potential (SEP) of the same patient. Recovery pattern of P25 and N33 components was normal and comparable to 5 healthy volunteers, suggesting the absence of cortical hyperexcitability. These results suggest dysfunction or immaturity of the indirect pathway of basal ganglia in PKC, as well as the hyperexcitability of the descending pathway.

A 71-year-old woman was admitted to our hospital because of involuntary movement of the left upper extremity. MR image of the brain 15 days after the onset revealed the low intensity in right posterior limb of internal capsule. The lesion was surrounded by thalamus, subthalamic nucleus, and globus pallidus with enhancement by Gd-DTPA. Surface EMG revealed irregular grouped discharge in short duration and grouped discharge in long duration in the left upper extremity. Those features are compatible with one of choreoathetosis. Choreoathetosis due to cerebral infarction in acute phase is rare. We discussed pathophysiology of this involuntary movement due to lacunar infarction of posterior limb of internal capsule in acute phase.

We described a 41-year-old man with chorea-acanthocytosis, who presented severe choreoathetosis in all the limbs, neck, face and tongue. Especially, the oral area was affected most strikingly. He had difficulty in eating, because he pushed foods out of the mouth with the tongue. He received left posteroventral pallidotomy (PVP). His involuntary movements became much less enough for the patient to eat with a spoon in a sitting position by himself. Six months after the first operation, although involuntary movement on the right hand remained reduced, choreoballistic movement appeared on the left side. He received PVP on the right side. The choreoballistic movement was remarkably improved after the right PVP. No neurological aggravation has been found for 7 months after the second PVP. Bilateral PVP was fully effective as for the improvement of the activity of daily life. The output from the internal globus pallidus (GPi) is well-known to be inhibitory. Therefore, it is understandable that the coagulation of GPi results in improvement of hypokinesia and rigidity in patients with Parkinson's disease. However, some clinical reports, including ours, have described the significant reduction of hyperkinetic choreoballistic movement after PVP. The exact mechanism of these surgical effects has not been elucidated yet, and further clinical and basic studies are needed to answer this question.

Inhibitory control of basal ganglia output to thalamocortical projection plays an important role in normal cortical activity in the current model of the basal ganglia motor circuit. Hypokinetic and hyperkinetic movement disorders of basal ganglia origin can be explained by excess or collapse of the basal ganglia output. An abundance of evidence indicates that parkinsonian akinesia results from hyperactivity of the basal ganglia output. Reversal of akinesia by lesions of the internal division of the globus pallidus (GPi) or its excitatory source, the subthalamic nucleus, agrees with this pathological schema. Ballism associated with subthalamic lesions, and dopa-induced dyskinesia are regarded as hyperkinetic disorders resulting from suppressed subthalamopallidal projection. Decreased firing rate in GPi was reported in both disorders. However, pallidotomy has recently been postulated to abolish both ballism and dopa-induced dyskinesia. A possible mechanism for the effect of GPi destruction in these hyperkinetic disorders may be blockade of the generation or conduction of phasic neuronal activities driving choreic movements. Symptomatologically, dystonia has aspects of both hypokinetic and hyperkinetic disorders. Overactivity of the premotor cortices, which receive projections from the basal ganglia via the ventral thalamus, was found both at rest and on movement in idiopathic dystonia. This abnormal cortical activity may arise from underactivity of basal ganglia output; however, the amelioration of dystonia with pallidotomy suggests a complex pathomechanism of the pallidothalamic system in dystonia.

Supplementary motor seizure (SMS) and paroxysmal kinesigenic choreoathetosis (PKC) appear similar, but are generally considered to represent different disease entities. We report a case that shared the clinical features of both disorders. A 62-year-old woman presented with attacks consisting of brief tonic posturing of four limbs, more prominent on the right side. The attack started at age 59 and subsequently began to occur about 20 times daily. Her consciousness was preserved during the attack. The attack lasted 5-15 sec. The attacks were often evoked by sudden initiation of movement, but also occurred spontaneously and even during sleep. She had never experienced generalized convulsion. Ictal scalp EEG showed high amplitude beta activity appearing a few seconds before the attacks around the vertex. Otherwise EEG was within normal limits. The response to anti-convulsant medication was poor and a combination of three kinds of drugs was needed. An almost identical case was reported as "PKC" by Lombroso. His case showed unequivocal epileptiform discharges arising from the supplementary motor area. Accordingly, our case is considered kinesigenic SMS. It seems important to examine similar cases to elucidate the relationship between SMS and PKC, or between the kinesigenic and non-kinesigenic types of these disease entities.

An endocrinological study was performed dopaminergic regulation of the hypothalamic-pituitary axis of 3 patients with familial chorea-acanthocytosis (females, 38 to 47 years of age). All 3 patients exhibited low basal levels of triiodo-thyronine (T3), and 2 patients had a slightly elevated baseline plasma prolactin (PRL) level. The patients had a delayed plasma thyroid stimulating hormone (TSH) response and plasma PRL excessive response to thyrotropin releasing hormone (TRH), and a low plasma growth hormone releasing hormone (GRF) response to L-dopa. These TSH, PRL and GRF responses represent a secretion pattern due to a hypothalamic disorder, suggesting impaired regulation of hormone secretion by the dopaminergic system, primarily in the hypothalamus. In addition, an increased growth hormone (GH) response secretion following TRH (paradoxical response) was observed in 2 patients, suggesting that the pituitary was also involved. An oral glucose tolerance test (75g-OGTT) revealed a diabetic pattern in all 3 patients, indicating frequent association with impaired glucose tolerance.

Chorea is a hyperkinetic involuntary movement disorder characterized by a random pattern of irregular muscle jerks. This movement may involve any parts of the body. Emotional stress or voluntary movements may exacervate chorea and sleep abolish it. Luys body and striatum are the most important anatomical sites to evoke chorea. The lesion of inner segment of pallidum or ventrolateral thalamus may abolish chorea. Measurements of neurotransmitter changes of Huntington's disease show diminution of striatal GABA neurons and preserving nigrostriatal dopamine neurons. Dopamine antagonists can reduce chorea because doperminergic hyperactivity contribute to exacervate chorea. Precise pathophysiological mechanism of chorea is controversial, therefore its classification is not established. On the clinical point of view, classification according to heredity is useful to make diagnosis because hereditary diseases are easily confirmed by family history or specific biochemical markers. There are two groups of underlying diseases of non hereditary chorea. One is unilateral chorea usually due to contralateral hemispheric lesions to chorea. Another is bilateral chorea usually due to degenerative, metabolic or toxic brain diseases. Recent identification of abnormal DNA structure (trinucleotide repeat) in Huntington's disease may greatly contribute to classify underlying diseases of chorea.

We report a 72-year-old woman who showed marked orolingual dyskinesia and choreoathetoid movements of the neck, with rolling and nodding of the head. She had been treated for postural tremor and other complaints with multiple drugs, including trihexyphenidyl HCl (THP) 6 mg/day for about two years. Moreover, two months before admission to our hospital, a doctor added tricyclic antidepressant, dosulepin HCl (DL) because of her state of anxiety. Two weeks following DL administration, the persistent dyskinesia described above appeared. Suspecting the dyskinesia to be induced by anticholinergics, we withdrew THP, which decreased the intensity of the dyskinesia. Then, when DL was ceased the dyskinesia almost completely disappeared, slightly recurring only during calculating, when excited or writing. In order to confirm that anticholinergics were the cause of the dyskinesia, we administered THP 6 mg/day again. In a few days the same dyskinesia reappeared, disappearing following THP withdrawal. In this case the overlap of anticholinergics might have resulted in the dyskinesia, because both THP and DL have anticholinergic effects. It should be stressed that inappropriate administration of anticholinergics could cause severe dyskinesia in the elderly.

Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Choreic movement is one of the most attractive involuntary movements in terms of searches for the underlying mechanisms. Huntington's disease is a most popular disorder exhibiting choreic movements, in which the rather selective striatal degeneration is postulated to be responsible for the generation of choreic movements. In this respect, we have recently produced an experimental model of choreic movements in monkey by combined methods of kainic acid injection into the unilateral striatum and the oral administration of L-DOPA. The purpose of this paper is to summarize our experiment and to review the previous papers on experimental model of choreic movements in order to shed light on the underlying mechanisms of choreic movements. There are at least following three possible mechanisms in the generation of choreic movement. 1) A massive loss of GABAergic inhibitory neurones in the striatum induces disinhibitory effects on nigral dopaminergic neurones, which causes activation of dopaminergic neurones and choreic movements. However, a loss of GABA in the nigra does not always correlate with the generation of choreic movements. 2) A hypersensitive receptors for dopamine in the striatum may cause choreic movements. In fact, however, dopamine receptors are decreased or normal rather than increased not only in Huntington's disease but also in monkey models. 3) A massive loss of neurones in the striatum causes a loss of post-synaptic components of dopaminergic terminals. This may further cause rearrangements and compensatory changes in dopaminergic terminals in the spared striatum. These changes may activate pre-synaptic dopaminergic components which are further activated by the administration of L-DOPA. This hypothesis is mainly derived from the experimental model in monkey.

Whether the basal ganglia have a cognitive function or not is a worldwide dispute. We have examined 13 parkinsonian patients and 12 age-matched non-parkinsonian controls using the Modified Wisconsin Card Sorting Test (MCST). All 12 controls could achieve all 6 sets of categories which were successively changed. On the other hand, in the parkinsonians, 9 patients could achieve all 6 sets, but 4 patients could do only 4 to 0 sets. The difference between the two groups was statistically significant. These 4 patients who showed poor achievement on MCST had tendency showing higher percentage of perseverative errors. Taking the proportion of perseverative error (PE) to total error (TE) revealed that the parkinsonian group had a peak ranged from 55% to 65% which meant higher occurrence of perseverative errors. When the 4 parkinsonians whose proportion of PE/TE on MCST was over 55% were excluded, a comparison of the parkinsonians with the controls showed no significant difference statistically in both groups. There were no clinical differences based upon Yahr's classification between the 4 parkinsonians with poor MCST score and those with the normal score. Among these parkinsonians whose proportion of PE/TE ranged from 55% to 65%, 3 cases showed apparent frontal lobe signs and 3 mild dementia on Wechsler Intelligence Scale for Adults. Two patients with chorea-acanthocytosis and showing a marked atrophy of the caudate nucleus were also examined. They showed excellent results on MCST.(ABSTRACT TRUNCATED AT 250 WORDS)

Seven cases in a family of hereditary spino-cerebellar degeneration (SCD) similar to dentatorubro-pallido-Luysian atrophy (DRPLA) were reported. The clinical features of these cases were disturbance of ocular movement (limitation of ocular movement and slow eye movement (SEM], remarkable amyotrophy, choreoathetosis, dementia and sleep apnea. The brain CT's revealed marked atrophy in pons and cerebellum. Amyotrophy had been reported in the case of DRPLA, particular ataxo-choreoathetoid form (by Hirayama). Muscle biopsy was performed in these cases, which showed scattered small angulated fiber, severe atrophic fiber with pyknotic nuclear clump, fiber type grouping and small rounded fiber were mixed. These findings indicates neurogenic change of radiculoneuropathy type (by Tanabe). In many reported cases of DRPLA and SCD with amyotrophy, this type of muscle biopsy had not been recognized. In SCD with amyotrophy, a main lesion had existed on peripheral nerve. In this case, there was no definite clinical findings (sensory disturbance, delay of conduction nerve velocity, peripheral neuropathy in nerve biopsy). In recent years, several unclassified cases of SCD with amyotrophy had been reported, which had multi-system degeneration involving peripheral neuropathy. This case is similar to these cases, which is speculates multi-systemic lesions, not only DRPLA but also peripheral nerve involvement. On neuro-otological study, velocity of saccade was slow and persuit was reserved in proband case. In younger onset case, disturbance of saccade and pursuit was mild. In older progressive case, disturbance of saccade and pursuit was progressive and accompanied with severe limitation of ocular movement. Several autopsy cases of SEM had been reported.(ABSTRACT TRUNCATED AT 250 WORDS)