Involuntary Movement Disorders Research Articles

Decreased striatal dopamine receptor binding in primary focal dystonia: A D2 or D3 defect?

Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular, dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role. We have demonstrated with positron emission tomography that patients with primary focal cranial or hand dystonia have reduced putamenal specific binding of [(18)F]spiperone, a nonselective D2-like radioligand with nearly equal affinity for serotonergic 5-HT(2A) sites. We then repeated the study with [(18)F]N-methyl-benperidol (NMB), a more selective D2-like receptor radioligand with minimal affinity for 5-HT(2A). Surprisingly, there was no decrease in NMB binding in the putamen of subjects with dystonia. Our findings excluded reductions of putamenal uptake greater than 20% with 95% confidence intervals. The analysis of the in vitro selectivity of NMB and spiperone demonstrated that NMB was highly selective for D2 receptors relative to D3 receptors (200-fold difference in affinity), whereas spiperone has similar affinity for all three of the D2-like receptor subtypes. These findings when coupled with other literature suggest that a defect in D3, rather than D2, receptor expression may be associated with primary focal dystonia.

The PtdIns(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic neuronal death

Phosphorylated derivatives of phosphatidylinositol, collectively referred to as phosphoinositides, occur in the cytoplasmic leaflet of cellular membranes and regulate activities such as vesicle transport, cytoskeletal reorganization and signal transduction. Recent studies have indicated an important role for phosphoinositide metabolism in the aetiology of diseases such as cancer, diabetes, myopathy and inflammation. Although the biological functions of the phosphatases that regulate phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) have been well characterized, little is known about the functions of the phosphatases regulating the closely related molecule phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P(2)). Here we show that inositol polyphosphate phosphatase 4A (INPP4A), a PtdIns(3,4)P(2) phosphatase, is a suppressor of glutamate excitotoxicity in the central nervous system. Targeted disruption of the Inpp4a gene in mice leads to neurodegeneration in the striatum, the input nucleus of the basal ganglia that has a central role in motor and cognitive behaviours. Notably, Inpp4a(-/-) mice show severe involuntary movement disorders. In vitro, Inpp4a gene silencing via short hairpin RNA renders cultured primary striatal neurons vulnerable to cell death mediated by N-methyl-d-aspartate-type glutamate receptors (NMDARs). Mechanistically, INPP4A is found at the postsynaptic density and regulates synaptic NMDAR localization and NMDAR-mediated excitatory postsynaptic current. Thus, INPP4A protects neurons from excitotoxic cell death and thereby maintains the functional integrity of the brain. Our study demonstrates that PtdIns(3,4)P(2), PtdIns(3,4,5)P(3) and the phosphatases acting on them can have distinct regulatory roles, and provides insight into the unique aspects and physiological significance of PtdIns(3,4)P(2) metabolism. INPP4A represents, to our knowledge, the first signalling protein with a function in neurons to suppress excitotoxic cell death. The discovery of a direct link between PtdIns(3,4)P(2) metabolism and the regulation of neurodegeneration and involuntary movements may aid the development of new approaches for the treatment of neurodegenerative disorders.

Reconnaître les symptômes psychiatriques iatrogènes liés aux antipsychotiques

This article proposes a review of atypical multicentre studies for drug-induced movement disorders (and related psychiatric symptoms) and supersensitivity psychosis. A well-conducted antipsychotic treatment consists of regular attempts to reduce the dose by finding the minimal therapeutic dose. To achieve optimal antipsychotic treatment, it is important to distinguish psychiatric symptoms associated with drug-induced movement disorder(s) (DIMD) or supersensitivity psychosis from true relapse. Persistent DIMD have been found to be a predictor of supersensitivity psychosis or tardive dyskinesia (DT). DIMD-associated psychiatric symptoms can be classified into three types: directly induced by DIMD; resulting from confounding DIMD with psychiatric symptoms; and supersensitivity symptoms associated with DIMD. Without this distinction, the beneficial effects of antipsychotics are masked by emergent DIMD psychiatric symptoms (as was confounded in the CATIE study). A constant decline in the prevalence of TD (hyperkinetic, involuntary and purposeless movement disorder) has been observed since the introduction of atypical antipsychotics. The neurotoxic effects of classical antipsychotics are well documented and their discontinuation is required. However, the risk of TD still exits with atypical antipsychotics and continued surveillance of emerging cases is very important for clinicians. Moreover, a regular evaluation of DIMD and associated psychiatric symptoms is crucial. It is important to underline the fact that DIMD persists with antipsychotics, with significantly higher total PANSS scores than in patients without DIMD. Supersensitivity psychosis is a drug-induced psychotic relapse (6 weeks following the decrease or withdrawal of an antipsychotic). Discontinuation syndromes can produce psychiatric symptoms (and be confounded with true relapse), but can be improved more quickly after reintroduction of treatment. Interestingly, various data suggest that lower doses of antipsychotics could prevent such symptoms. Anticonvulsants can be efficient adjuvants in the treatment of psychosis. In the United States, many patients received valproate or gabapentin treatment. These adjuvants, by antikindling effect, can facilitate minimal maintenance drug treatment and be efficient for anxiety. Resistant schizophrenia can be related to supersensitivity psychosis; gabapentin and lamotrigine are effective in this case.

Psychotropic Medication-Induced: Rabbit syndrome

Rabbit syndrome (RS) is an involuntary movement disorder characterized by rapid, fine movements of an individual's mouth, similar to the chewing movements of a rabbit, and has most frequently been associated with the use of antipsychotic medications. RS is often unrecognized or misdiagnosed as tardive dyskinesia or pseudoparkinsonism. Although rare, RS is easily treatable if recognized. It is essential that nurses are able to distinguish this syndrome from other movement disorders; however, a lack of information exists in the nursing literature about this syndrome. The aims of this article are to describe the clinical symptoms of RS, its prevalence and etiology, and recommended treatment. Clinical and education implications regarding RS are also provided.

CNE Quiz

Rabbit syndrome (RS) is an involuntary movement disorder characterized by rapid, fine movements of an individual's mouth, similar to the chewing movements of a rabbit, and has most frequently been associated with the use of antipsychotic medications. RS is often unrecognized or misdiagnosed as tardive dyskinesia or pseudoparkinsonism. Although rare, RS is easily treatable if recognized. It is essential that nurses are able to distinguish this syndrome from other movement disorders; however, a lack of information exists in the nursing literature about this syndrome. The aims of this article are to describe the clinical symptoms of RS, its prevalence and etiology, and recommended treatment. Clinical and education implications regarding RS are also provided.

Unraveling of the E-helices and Disruption of 4-Fold Pores Are Associated with Iron Mishandling in a Mutant Ferritin Causing Neurodegeneration

Mutations in the coding sequence of the ferritin light chain (FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy, which is characterized by the presence of intracellular inclusion bodies containing the mutant FTL polypeptide and by abnormal accumulation of iron in the brain. Here, we describe the x-ray crystallographic structure and report functional studies of ferritin homopolymers formed from the mutant FTL polypeptide p.Phe167SerfsX26, which has a C terminus that is altered in amino acid sequence and length. The structure was determined and refined to 2.85 A resolution and was very similar to the wild type between residues Ile-5 and Arg-154. However, instead of the E-helices normally present in wild type ferritin, the C-terminal sequences of all 24 mutant subunits showed substantial amounts of disorder, leading to multiple C-terminal polypeptide conformations and a large disruption of the normally tiny 4-fold axis pores. Functional studies underscored the importance of the mutant C-terminal sequence in iron-induced precipitation and revealed iron mishandling by soluble mutant FTL homopolymers in that only wild type incorporated iron when in direct competition in solution with mutant ferritin. Even without competition, the amount of iron incorporation over the first few minutes differed severalfold. Our data suggest that disruption at the 4-fold pores may lead to direct iron mishandling through attenuated iron incorporation by the soluble form of mutant ferritin and that the disordered C-terminal polypeptides may play a major role in iron-induced precipitation and formation of ferritin inclusion bodies in hereditary ferritinopathy.

Two cases of hemichorea-hemiballism with nonketotic hyperglycemia: a new point of view

Hemichorea-hemiballism (HCHB) is an usually continuous, nonpatterned, involuntary movement disorder caused by basal ganglia dysfunction, commonly due to a vascular lesion, described in nonketotic hyperglycemic patients. Particular computed tomography and magnetic resonance imaging findings have been described. The pathogenic mechanism of chorea arising during hyperglycemia and the nature of neuroimaging findings are unclear. In this paper we describe two elderly women with onset of HCHB during a hyperglycemic episode. The symptoms persisted in one of them after recovery of normal glycemia. The pathophysiological mechanism of the disease is discussed in the light of clinical and neuroradiological follow-up.

Deep Brain Stimulation Devices: A Brief Technical History and Review

Deep brain stimulation (DBS)--a broadly accepted therapeutic modality with tens of thousands of patients currently implanted--is the application of implantable electrical stimulation devices to treat neurological disorders. Approved indications include involuntary movement disorders; investigational applications include epilepsy, selected psychiatric disorders, and other conditions. DBS differs fundamentally from functional electrical stimulation and sensory prosthetics in that DBS therapies do not substitute for or replace injured tissues, organs, or body functions. DBS--targeted to particular brain nuclei or pathways that are specific for the disorder under treatment--influences brain function and behavioral output in ways that can relieve symptoms and improve the overall functioning of the patient. We will briefly review the history and present status of DBS from a technical and device-oriented perspective, with an eye toward future advances.

Functional and Neuroreceptor Imaging of the Brain in Bicuculline-Induced Dystonic Rats

Dystonia is an involuntary movement disorder dominated by sustained muscle contractions that frequently cause twisting, repetitive movements, and postural changes. The purpose of this study was to determine the mechanism causing dystonia. We therefore employed a rat model of dystonia, which was induced by injecting (-)-bicuculine methiodide (BM), a gamma-aminobutyric acid A (GABA(A)) receptor antagonist, stereotaxically into the ventrolateral thalamic nuclei. Cerebral glucose metabolism reflecting cerebral activities and densities of central benzodiazepine and adenosine A(1) receptors that play an inhibitory role in neural excitation were evaluated in the brain by ex vivo autoradiography using appropriate (14)C/(18)F- or (11)C-labeled tracers. The dystonic signs were accompanied by increased glucose metabolism in the thalamus, substantia nigra, globus pallidus, and striatum. However, central benzodiazepine receptor density was not altered, and adenosine A(1) receptor density was reduced in the hippocampus. These results indicate the activation of a basal ganglia-thalamo-cortical motor circuit, which consists of the thalamus, substantia nigra, globus pallidus, and striatum. In this context, the activation of the above circuit has been reported in human dystonia patients. The decreased adenosine A(1) receptor density in the hippocampus might be related to a transient hippocampal dysfunction due to an acute type of dystonia. In conclusion, we have succeeded in generating a rat model of dystonia, and observed the activation of the basal ganglia-thalamo-cortical motor circuit that is related to dystonia.

Treatment of Tardive Dyskinesia by tetrabenazine, clonazepam and vitamin E

Byline: Himanshu. Sharma Sir, The term tardive dyskinesia has been used to refer to a group of delayed-onset abnormal involuntary movement disorders that present with rapid, repetitive, stereotypic choreoathetoid movements mostly involving the oral, buccal, and lingual areas or the trunk (oro-bucco-lingual variety ).[sup] [1] The word Tardiv e means late appearing movements which start after 3months of neuroleptic exposure.[sup] [2] The annual rate is estimated at 5% for the early years, the cumulative rates over 5 years being between 20-26%.[sup] [3] Most patients with TD have schizophrenia but it can develop in-patients with depression or anxiety. Risk factors for TD are age over 40 years, affective disorder, Negroes, prolonged use and use of high potency neuroleptics in high doses, early occurrence of drug-induced Parkinson's disease, and female gender and smoking, chronic use of anticholinergic drugs and diabetes mellitus.[sup] [1],[3],[4] Of the various pathogenic mechanisms proposed, dopamine receptor hypersensitivity, damage to GABA containing -neurons and free radical formation from catecholamine metabolism are the most widely accepted.[sup] [5] Following are some of the proposed guidelines for its treatment: 1) minimal dose of the causative antipsychotic or switching over to clozapine, after tapering off the offending antipsychotic drug slowly.[sup] [1] 2) Dopamine-depleting drugs -Reserpine (1 to 8 mg/day), Tetrabenazine (25 to 150 mg/day).[sup] [4],[6] 3) GABA-enhancing drugs Clonazepam (1 to 4 mg/day), Valproate, Vigabatrin, Baclofen, 4) Antioxidants: Vitamin E 800 IU/bid.[sup] [1],[7] A 34-year-old male was referred to the Psychiatry OPD of our hospital with complaints of involuntary movement of orofacial region along with difficulty in breathing and swallowing, pain in nuchal region and backache. A detailed examination revealed that the patient had complex repetitive movements of orofacial region including forehead and eyebrows raising, eye closure, puckering of lips, to and fro movements of head and neck, protrusion of and twisting and darting out movement tongue in between the parted lips and repeated clenching of teeth. The patient reported that 3 years ago he had faced some financial loss as result of which he suffered from a bout of depression for which he consulted a private psychiatrist who prescribed him Trifluoperazine 10 mg along with T.Citalopram 20mg and T. Trihexyphenidyl 2mg and T. Propranolol 10-mg tid. After 2 years the patient developed TD. Patient was nonalcoholic but chronic smoker and tobacco chewer since 15 years. His baseline assessment of abnormal involuntary movement scale (AIMS)[sup] [8] revealed a score of 21 qualifying for diagnosis of Tardive Dyskinesia (TD) . All psychotropic drugs were tapered off and a course of Tetrabenazine 25mg 1/2 hs bid was started which was increased to 25mg bid and then tid after 2 weeks. In addition to this Clonazepam 0.5 mg I hs and Cap Vit E 400 mg 1 OD were added. The patient reported a dramatic improvement within first 2 weeks of starting the treatment (AIMS score-13) and finally achieving a score of AIMS - 10 at the end of four weeks. …

Iron-mediated Aggregation and a Localized Structural Change Characterize Ferritin from a Mutant Light Chain Polypeptide That Causes Neurodegeneration

Nucleotide insertions in the ferritin light chain (FTL) polypeptide gene cause hereditary ferritinopathy, a neurodegenerative disease characterized by abnormal accumulation of ferritin and iron in the central nervous system. Here we describe for the first time the protein structure and iron storage function of the FTL mutant p.Phe167SerfsX26 (MT-FTL), which has a C terminus altered in sequence and extended in length. MT-FTL polypeptides assembled spontaneously into soluble, spherical 24-mers that were ultrastructurally indistinguishable from those of the wild type. Far-UV CD showed a decrease in α-helical content, and 8-anilino-1-naphthalenesulfonate fluorescence revealed the appearance of hydrophobic binding sites. Near-UV CD and proteolysis studies suggested little or no structural alteration outside of the C-terminal region. In contrast to wild type, MT-FTL homopolymers precipitated at much lower iron loading, had a diminished capacity to incorporate iron, and were less thermostable. However, precipitation was significantly reversed by addition of iron chelators both in vitro and in vivo. Our results reveal substantial protein conformational changes localized at the 4-fold pore of MT-FTL homopolymers and imply that the C terminus of the MT-FTL polypeptide plays an important role in ferritin solubility, stability, and iron management. We propose that the protrusion of some portion of the C terminus above the spherical shell allows it to cross-link with other mutant polypeptides through iron bridging, leading to enhanced mutant precipitation by iron. Our data suggest that hereditary ferritinopathy pathogenesis is likely to result from a combination of reduction in iron storage function and enhanced toxicity associated with iron-induced ferritin aggregates.

Analysis of genetic variations in the RGS9 gene and antipsychotic‐induced tardive dyskinesia in schizophrenia

Some patients treated chronically with antipsychotics develop tardive dyskinesia (TD), an abnormal involuntary movement disorder. Typical antipsychotics block D(2) dopamine receptors (D(2)DR) and produce D(2)DR supersensitivity. On contrary, regulators of G-protein signaling (RGS) can enhance the signal termination of G-protein-coupled D(2)DR. Besides, after prolonged inhibition of dopaminergic transmission, dopaminergic agonists induced severe dyskinesia only in RGS9 knock-out mice but not in normal mice. Therefore, variety in the human RGS9 gene may be related to susceptibility to TD. In this study, schizophrenic inpatients receiving long-term antipsychotic treatment were assessed using the Abnormal Involuntary Movement Scale twice over a 3-month interval. Only patients in whom abnormal involuntary movements were absent (non-TD group) and those who showed persistent TD (TD group) were enrolled. There were 407 patients in the study sample (TD = 252; non-TD = 155) and seven single nucleus polymorphisms (SNPs) in the RGS9 gene were genotyped for each subject. Genotype and allelic distributions of SNPs did not differ between the TD and non-TD groups in this study, with the exception that a weak trend of allelic association was seen with rs4790953 (P = 0.0399). In the haplotype analysis, a significant association of the AGG haplotype (rs8077696-rs8070231-rs2292593) of the RGS9 gene was found (permutation P = 0.007), and this is worthy of replication and further study.

A case of an intraventricular inflammatory pseudotumor presumably caused by Epstein-Barr virus infection

Background Inflammatory pseudotumor primarily affecting the CNS is an extremely rare lesion with uncertain etiology in most cases. Case Description A 67-year-old man developed involuntary movement disorder of the left upper extremity. On MRI, a solid homogeneously-enhanced tumor was noted in the right lateral ventricle adjacent to the thalamus. He had histories of right thalamic hypertensive hemorrhage and recurrent chronic nasal sinusitis associated with an orbital mass lesion, presumably an IP. Partial removal of the tumor yielded a diagnosis of IP associated with EBV infection. Conclusion The simultaneous occurrence of multiple IPs was presumably because of an exaggerated immune process after EBV infection. Inflammatory pseudotumor should be considered in any case of intraventricular mass lesion.

Pathway-based association analysis of genome-wide screening data suggest that genes associated with the γ-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia

Neuroleptic-induced tardive dyskinesia (TD) is an involuntary movement disorder that develops in patients who have undergone long-term treatment with antipsychotic medications, and its etiology is unclear. In this study, a genome-wide association screening was done to identify the pathway(s) in which genetic variations influence susceptibility to neuroleptic-induced TD. Screening with Sentrix Human-1 Genotyping BeadChip (Illumina, San Diego, California, USA) was done for 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD. A total of 40 573 single nucleotide polymorphisms that were not in linkage disequilibrium with each other and were located in the exonic and intronic regions of 13 307 genes were analyzed. After gene-based corrections, P values for allelic associations were subjected to canonical pathway-based analyses with Ingenuity Pathway Analysis software (Ingenuity Systems, Inc., Redwood City, California, USA). Eight genes (ABAT, ALDH9A1, GABRA3, GABRA4, GABRB2, GABRAG3, GPHN, and SLC6A11) contained polymorphisms with gene-based corrected allelic P values of less than 0.05. They were aggregated significantly in 33 genes belonging to the gamma-aminobutyric acid (GABA) receptor signaling pathway (P=0.00007, corrected P=0.01). Associations were replicated in an independent sample of 36 patients with TD and 136 patients without TD for polymorphisms in SLC6A11 (GABA transporter 3) (P=0.0004 in the total sample), GABRB2 (beta-2 subunit of GABA-A receptor) (P=0.00007 in the total sample), and GABRG3 (gamma-3 subunit of GABA-A receptor) (P=0.0006 in the total sample). The results suggest that the GABA receptor signaling pathway may be involved in genetic susceptibility to treatment-resistant TD, at least in a subgroup of Japanese patients with schizophrenia. The present results suggest that benzodiazepines may be considered as possible treatment option for TD.

Re: Preferential Aggregation of Obsessive—Compulsive Spectrum Disorders in Schizophrenia Patients with OCD

Dear Editor: Dr Michael Poyurovsky and coauthors1 reported on an interesting study in which they assessed the rates of psychiatric disorders in schizophrenia patients with and without obsessive-compulsive disorders (OCD) and pure OCD patients. Body dysmorphic disorder, tic disorders (TD), and anxiety disorders were found in higher frequencies in the schizo-obsessive group when compared to pure schizophrenia. The findings support the notion that the schizo-obssesive group may be an intermediate phenotype between schizophrenia and OCD. We would like to comment on the specific findings of TD. Curiously, the authors found no cases of Tourette syndrome in the schizo-obsessive group, while the odds of having chronic motor tics in the schizo-obsessive group (16%) were 4 times higher than those of the schizophrenia group (4%). In the OCD group, the frequency of TD was the classical 34.3% found in the literature.2 The intermediate frequency of TD in the schizo-obsessive group speaks for a continuum between these disorders. One explanation for these higher frequencies of obsessive spectrum disorders could be the presence of common vulnerability genes. There are few reports of Tourette patients who later developed schizophrenia and also few reports of TD in schizophrenia.3-5 The low frequency of TD in schizophrenia could be owing to a real low incidence of tic disorders in schizophrenia, the use of antipsychotics in schizophrenia patients that would mask tics when present, and tics that may be misdiagnosed as Stereotypie behaviors, tardive diskinesia, and other extrapiramidal symptoms that might also lead to an underestimation of TD frequencies.6 To rule out these factors, the authors could have informed medication use in the 3 groups of patients as well as the diagnostic criteria used to differentiate between several involuntary movement disorders. The age of onset of the disorder, used as a covariable, showed no difference between OCD and schizo-obsessive patients. This is another important factor that reinforces the hypothesis that schizo-obsessive, have a place between schizophrenia and OCD, sharing specific comorbidity patterns with both.

Motor impairment after severe traumatic brain injury: A longitudinal multicenter study

Neuromotor impairment is a common sequela of severe traumatic brain injury (TBI) but has been understudied relative to neurocognitive outcomes. This multicenter cohort study describes the longitudinal course of neurological examination-based motor abnormalities after severe TBI. Subjects were enrolled from the four lead Department of Veterans Affairs and Defense and Veterans Brain Injury Center sites. The study cohort consisted of 102 consecutive patients (active duty, veteran, or military dependent) with severe TBI who consented during acute rehabilitation for data collection and completed all follow-up evaluations. Paresis, ataxia, and postural instability measures showed a pattern of improvement over time, with the greatest improvement occurring between the inpatient (baseline) and 6-month follow-up assessments. Involuntary movement disorders were rare at all time points. Two years following acute rehabilitation, more than one-third of subjects continued to display a neuromotor abnormality on basic neurological examination. Persistence of tandem gait abnormality was particularly common.

The Physiological Effects of Pallidal Deep Brain Stimulation in Dystonia

Dystonia is an involuntary movement disorder characterized by muscle contractions causing abnormal postures and spasms, affecting part or all of the body. Dystonia may be primary where an abnormal gene, most commonly DYT1, may be identified, or secondary to structural brain lesions or heredodegenerative disorders. The underlying defect is believed to be abnormal basal ganglia modulation of cortical motor pathways, and various motor and sensory physiological abnormalities have been demonstrated. The failure of medical treatment in many patients with the more severe and generalized forms of dystonia has led to renewed interest in neurosurgical treatment approaches. In recent years, deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for dystonia, particularly patients with primary generalized dystonia, where remarkable improvement may occur. In contrast to Parkinson's disease, the beneficial effects of DBS in dystonia are not immediate but progressive over weeks to months. Physiological and imaging studies in dystonia patients with GPi DBS have demonstrated both short and long-term effects of GPi DBS on motor cortex and subcortical circuits including progressive normalization of spinal and brainstem excitability after GPi DBS which correlate with clinical improvement. These effects, in light of existing physiological data in dystonia, suggest that GPi DBS acts primarily by major modification of basal ganglia output to brainstem, thalamus, and cortex resulting in neural reorganization, which may explain the characteristic progressive improvement in dystonia after GPi DBS.

Myoklonien

Myoclonus, an involuntary movement disorder reveals itself with a wide variety of short muscle twitches or jerks, and may cause severe disability. From a clinical perspective, it is sometimes difficult to discriminate myoclonus from other central movement disorders. Moreover, myoclonus has a spectrum of causes including rare neurological syndromes and uncommon manifestations of systemic disease. Its pathogenesis is only partially understood. Neurophysiologic investigations suggest a close relationship between certain types of myoclonic jerking and epilepsy. The use of anticonvulsants for treatment of myoclonus has its basis in such observations and empirical evidence. Often high doses or a combination of drugs, or both are required, with, however, serious side effects.

3. AAV/AADC Gene Therapy for Parkinson's Disease(LS1-4 Surgical Management of Involuntary Movement Disorders, The 27^<th> Annual Meeting of The Japanese Congress of Neurological Surgeons)

3. AAV/AADC Gene Therapy for Parkinson's Disease(LS1-4 Surgical Management of Involuntary Movement Disorders, The 27^<th> Annual Meeting of The Japanese Congress of Neurological Surgeons)

1. 大脳基底核の構造と機能(LS1-4 不随意運動疾患の外科治療, 第27回 日本脳神経外科コングレス総会)

1. 大脳基底核の構造と機能(LS1-4 不随意運動疾患の外科治療, 第27回 日本脳神経外科コングレス総会)