Onset Of Movement Disorder Research Articles

Onset and progression of dystonia in Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS) may lead to movement disorders (MDs) in some patients. Reliable information on the nature, chronology and clinical determinants of MDs in CRPS patients is lacking but could provide better insight in to the underlying pathophysiological mechanism. We retrospectively evaluated the clinical and temporal characteristics of MDs in patients with CRPS. Cox’s proportional hazards model was used to evaluate factors influencing the onset of MDs. One-hundred and eighty-five patients suffered CRPS in one or more extremities. MDs occurred in 121 patients, with dystonia (91%) being the most prevalent. Sixty-two percent of these patients displayed dystonia in multiple extremities. Patients with dystonia were on average 11 years younger and more often had CRPS in multiple extremities. The interval between the onset of CRPS and dystonia in the first affected extremity varied from less than 1 week in 26% of the patients to more than 1 year in 27%. The hazard of developing dystonia in subsequent extremities increased with the number of extremities affected by dystonia. We conclude that dystonia in CRPS shows highly variable onset latency and is associated with younger age at onset and increased risk of developing dystonia in other extremities. The delayed onset and progression of dystonia in CRPS may indicate the involvement of a different underlying mechanism, possibly associated with maladaptive neuroplasticity.

PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease

Mutations in the pantothenate kinase 2 gene ( PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G → A transition at base 1238 (G411R) and a C → A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5–1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation.

Case report: Severe acute Parkinsonism associated with streptococcal infection and antibasal ganglia antibodies

We report the case of a young man who presented with a severe acute akinetic-rigid disorder 2 weeks after complete recovery from an episode of pharyngitis. Magnetic resonance imaging scan abnormalities strikingly localized to the basal ganglia were accompanied by serological evidence of recent streptococcal infection and the presence of anti-basal ganglia antibodies in the serum. The case represents an unusually clear example in the spectrum of inflammatory neurological disorders associated with streptococcal infection, an etiology that should be considered in the differential diagnosis of all acute onset movement disorders.

Anti-basal ganglia antibodies in patients with atypical dystonia and tics: a prospective study.

Anti-basal ganglia antibodies (ABGA) are associated with movement disorders in children, but have not been assessed in adult onset movement disorders. In a prospective assessment ABGA were positive in 65% of a group of 65 patients with atypical movement disorders, but were very rare in healthy adults and adults with idiopathic dystonia. An autoimmune mechanism may underlie a proportion of cases of atypical movement disorders.

Mitochondrial defects in neurodegenerative disease.

Over the past 12 years, a wide variety of neurodegenerative diseases has been linked to mutations in mitochondrial genes located in either the mitochondrial DNA (mtDNA) or the nuclear DNA (nDNA). These disorders encompass an array of unorthodox inheritance patterns and a plethora of symptoms ranging from lethal neonatal multi-symptom disorders to later onset myopathies, cardiomyopathies, movement disorders, and dementias. The bases for the genetic and phenotypic variability of mitochondrial diseases lie in the multiplicity of the mitochondria genes dispersed across the human genome and the variety of cellular pathways and functions in which the mitochondria play a central role.

Delayed Movement Disorders after Carbon Monoxide Poisoning

Of 242 patients with carbon monoxide (CO) poisoning examined between 1986 and 1996, delayed movement disorders were diagnosed in 32 (13.2%). There were 15 men and 17 women. Ages at insult ranged from 9 to 69 years (mean 45.3 years). Of the 32 patients with delayed movement disorders, 23 (71.9%) had parkinsonism, 5 dystonia, 3 chorea and 1 myoclonus. All were associated with delayed CO encephalopathy. The median latency between CO poisoning and the onset of movement disorders was 4 weeks for parkinsonism, 51 weeks for dystonia, 4 weeks for chorea and 8 weeks for myoclonus. The latency of dystonia onset after CO poisoning was longer than that of other types of movement disorders. The CT findings in delayed movement disorders after CO poisoning were variable, and there was no correlation between the sites of imaging and the development of movement disorders. Abnormal dyskinesias disappeared within 8 weeks, and patients recovered from parkinsonism within 6 months. In conclusion, delayed movement disorders after CO poisoning are not rare, and usually appear as a part of delayed CO encephalopathy. The prognosis is good.

Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene.

Iraqi-Jewish optic atrophy plus is an autosomal recessive condition characterized by infantile optic atrophy, an early onset movement disorder, and 3-methylglutaconic aciduria. Other features include spastic paraplegia, mild ataxia, mild cognitive deficiency and dysarthria. This disorder was identified in inbred Iraqi-Jewish kindreds in which relationships between most of the affected individuals were unknown. In this study we identify linkage to chromosome 19q13.2-q13.3 by using a DNA pooling strategy to perform a genome wide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial genome wide screen. A significantly high positive lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene. The existence of multiple recombinant individuals indicates the disease interval can be further narrowed with additional markers. Linkage disequilibrium was seen in six polymorphic markers across a 1 Mb interval. This region is well characterized and contains several candidate genes.

Delayed-onset progressive movement disorders after static brain lesions.

We studied 53 patients (64% females) with static brain lesions who developed progressive movement disorders. Of these, 50 (94%) had dystonia, 17 (32%) tremor, eight (15%) parkinsonism, seven (13%) myoclonus, and three (6%) chorea. The precipitating insults included perinatal hypoxia/ischemia in 22 (42%), stroke in 12 (23%), head injury in eight (15%), encephalitis in eight (15%), and carbon monoxide poisoning, kernicterus, and radiation necrosis in one patient (2%) each. Among the 30 patients with initial insult occurring at age 2 years or younger (Infant group), distribution of dystonia at follow-up was focal in three (10%), segmental in eight (27%), unilateral in 10 (33%), and generalized in nine (30%). The mean latency between the original injury and onset of movement disorder was 25.5 +/- 16.7 years. Among the nine patients who developed dystonia after an insult occurring between ages 6 and 17 (Childhood group), the distribution of dystonia at follow-up was segmental in two (33%) and unilateral in seven (78%); the mean latency of dystonia onset was 4.9 +/- 7.8 years. Of the 14 patients in the Adult group (injury at age 25 or older), 11 developed dystonia, two developed parkinsonism, and one had carbon monoxide encephalopathy and parkinsonism. The distribution of dystonia in the 11 patients at follow-up was segmental in three (27%) and unilateral in eight (73%). The mean latency of movement disorder onset in the 14 patients of the Adult group was 2.5 +/- 4.9 years. No individuals in the Childhood or Adult groups became left-hand dominant; by comparison, nine of the 30 individuals in the Infant group became left-handed. In conclusion, brain injury at a young age is associated with a longer latency to onset of subsequent movement disorder, a greater tendency to development of generalized dystonia, and a greater probability of altered handedness. These tendencies may result from differences in age-related neuroplasticity.

Mitochondrial dysfunction in movement disorders.

A major theory regarding the mechanism of neuronal degeneration in several movement disorders is that mitochondrial defects may play a role. Biochemical studies in Parkinson's disease, Huntington's disease, multiple system atrophy, and idiopathic dystonia have shown defects in enzymes of oxidative phosphorylation in postmortem brain tissue, platelets, muscle, or lymphocytes. The basal ganglia and substantia nigra are also particularly susceptible to the accumulation of age-dependent mitochondrial DNA deletions, which may contribute to the delayed onset of movement disorders. The 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine model of Parkinson's disease involves conversion to 1-methyl-4-phenylpyridinium, which then inhibits complex I of the electron transport chain. Our studies show that the complex II inhibitor 3-nitropropionic acid can closely replicate the neurochemical, histologic, and clinical features of Huntington's disease. The mechanism of neuronal death in both these models may be slow excitotoxicity. Both direct biochemical studies and animal models of movement disorders therefore suggest that mitochondrial dysfunction may play a direct role in their pathogenesis.

Antineuronal Antibodies in Movement Disorders

To determine whether children with recent onset of movement disorders (Tourette syndrome, motor and/or vocal tics, chorea, choreiform movements) show evidence of serological antibodies directed against the human central nervous system as previously documented in research on Sydenham's chorea. Serum antibodies against previously frozen human caudate nucleus sections were analyzed using a blinded design and immunofluorescent staining methods. The sera of one group of 50 children referred for evaluation of attention deficit hyperactivity disorder, behavior disorders, and learning disabilities (24 with an associated movement disorder) seen between June 1989 and June 1990 were analyzed. The study was replicated in 33 children (21 with an associated movement disorder) seen between June 1990 and November 1990. In the original sample of 50 children, those with movement disorders were significantly more likely to have evidence of antineuronal antibodies than were those without movement disorders (odds ratio [OR] 4.80, 95% confidence interval [CI] 2.58 to 8.93). Results of the replication were similar (OR 6.00, 95% CI 2.56 to 14.03). For the total group, the OR was 5.50, (95% CI 3.54 to 8.99), which is highly significant. The percentage of children with a movement disorder whose sera were strongly positive for antineuronal antibodies (44%) was very similar to that previously found in children with Sydenham's chorea (46%). Children with movement disorders were also more likely than children without movement disorders to have at least one antistreptococcal titer elevated. The data strongly suggest an association between antecedent group A beta-hemolytic streptococcal infection as inferred from elevated antistreptococcal titers and the presence of serum antineuronal antibodies, which may, in turn, be linked to childhood movement disorders.

Quantitative light microscopic demonstration of increased pallidal and striatal met 5-enkephalin-like immunoreactivity in rats following chronic treatment with haloperidol but not with clozapine: Implications for the pathogenesis of neuroleptic-induced movement disorders

Acute and late onset movement disorders frequently complicate the treatment of psychosis with typical neuroleptic drugs like haloperidol, but not with atypical neuroleptic drugs like clozapine. Although the neural mechanisms underlying neuroleptic-induced movement disorders remain unknown, alterations in basal ganglia function are likely involved. A potential role for the endogenous opiate peptides in neuroleptic-induced movement disorders is suggested by the immunocytochemical localization of met 5-enkephalin (ME) in the striatopallidal projection pathway, and by the increased levels of ME measured by radioimmunoassay in the rat caudate-putamen nuclei (CPN) following haloperidol treatment. We sought to determine whether met 5-enkephalin-like immunoreactivity (MELI) in terminal fields within globus pallidus and in perikarya in CPN was differentially altered in rats chronically treated with haloperidol or clozapine. Acrolein-fixed forebrain sections were collected from cohorts of adult rats receiving 21-day oral administration of haloperidol, clozapine, or water. Sections from the three treatment groups were collectively processed for immunocytochemical labeling using varying dilutions of ME antiserum and the avidin-biotin peroxidase method. In globus pallidus, densitometry measures revealed significantly increased levels of immunoperoxidase labeling for ME in haloperidol-treated, but not in clozapine-treated animals. In CPN, optical densitometry as well as cell counting measurements also showed a significant increase in MELI only in the haloperidol-treated group. These results support the concept that alterations in endogenous opiate peptides in basal ganglia may contribute to movement disorders seen in patients receiving typical neuroleptic drugs. A hypothesis is advanced to suggest how alterations in the enkephalin containing striatopallidal pathway may contribute to both the acute hypokinetic disorder (parkinsonism) and the late onset hyperkinetic disorder (tardive dyskinesia).

Delayed onset movement disorders as a complication of central pontine myelinolysis

This report describes a case of central pontine myelinolysis occurring after a rapid correction of profound hyponatremia. Delayed-onset generalized dystonia and choreoathetosis then appeared. A small pontine myelinolysis was demonstrated by magnetic resonance images, but striatal myelinolysis could not be established. Aspects of movement disorders associated with the osmotic demyelination syndrome are briefly reviewed and discussed.

Neurologic Approach to Drug-Induced Movement Disorders

Of 125 patients with neuroleptic (dopamine blocking) drug-induced movement disorders who had been referred to a specialized clinic to differentiate the predominant movement disorder, 63% had tardive dyskinesia, 30% had parkinsonism, 24% had dystonia, 7% had akathisia, and 2% had isolated tremor. Two or more movement disorders coexisted in 31 patients (25%). Functional disability was more severe in patients with akathisia than in other patients. Women outnumbered men at a ratio of 4:1, except for tardive dystonia which affected both sexes equally. The average at onset was 56 years (range, 13 to 87); 69 patients (55%) had onset of movement disorder in the sixth decade. While tardive dystonia was distributed relatively evenly in all age groups, almost a third of patients with parkinsonism had it in the eighth decade. Haloperidol was implicated in 47 patients (37%), followed by amitriptyline/perphenazine in 30%, thioridazine in 27%, and chlorpromazine in 20%. Metoclopramide-induced movement disorders were found in 10 (8%). Most patients (101 or 81%) had history of psychiatric illnesses, but of these only 44 had psychosis. Neuroleptic drugs had been prescribed for 33 patients (26%) who had gastrointestinal problems. It is important to recognize and differentiate various drug-induced movement disorders because such differentiation has pathophysiologic and therapeutic implications. Many patients could have been treated with less potent drugs.

Metoclopramide-Induced Movement Disorders

• Metoclopramide, a dopamine-2 receptor antagonist used for various gastrointestinal disorders, may cause or exacerbate a variety of extrapyramidal movement disorders. To draw attention to the frequent occurrence of metoclopramide-induced movement disorders, we identified and studied 16 patients who had been exposed to this neuroleptic. The average age at onset was 63 years (range, 24 to 85 years), and women outnumbered men 3 to 1. Tardive dyskinesia was the most common movement disorder (n=10 [63%]). Five patients had metoclopramide-induced parkinsonism, 1 patient had tardive dystonia, and 1 patient had akathisia. The average duration of exposure prior to onset of movement disorders was 12 months (range, 1 day to 4 years). Therapy was continued for an average of 6 months (range, 1 day to 2 years) after the onset of symptoms, reflecting clinical nonrecognition of the movement disorder and its relationship to metoclopramide. To prevent persistent and disabling movement disorders, long-term use of metoclopramide should be avoided, and patients should be carefully observed for potential neurologic reactions. (<i>Arch Intern Med.</i>1989;149:2486-2492)

Metoclopramide-induced movement disorders. Clinical findings with a review of the literature.

Metoclopramide, a dopamine-2 receptor antagonist used for various gastrointestinal disorders, may cause or exacerbate a variety of extrapyramidal movement disorders. To draw attention to the frequent occurrence of metoclopramide-induced movement disorders, we identified and studied 16 patients who had been exposed to this neuroleptic. The average age at onset was 63 years (range, 24 to 85 years), and women outnumbered men 3 to 1. Tardive dyskinesia was the most common movement disorder (n = 10 [63%]). Five patients had metoclopramide-induced parkinsonism, 1 patient had tardive dystonia, and 1 patient had akathisia. The average duration of exposure prior to onset of movement disorders was 12 months (range, 1 day to 4 years). Therapy was continued for an average of 6 months (range, 1 day to 2 years) after the onset of symptoms, reflecting clinical nonrecognition of the movement disorder and its relationship to metoclopramide. To prevent persistent and disabling movement disorders, long-term use of metoclopramide should be avoided, and patients should be carefully observed for potential neurologic reactions.

INDUCTION OF INVOLUNTARY MOVEMENTS BY PERIPHERAL TRAUMA: AN ANALOGY WITH CAUSALGIA

Ten patients are described in whom various involuntary movement disorders developed after trauma that was predominantly or entirely peripheral. The interval between injury and onset of movement disorder ranged from 48 hours to 3 years; the injured and painful part was the area initially affected by involuntary movements, although more widespread involvement subsequently occurred. These clinical features resemble the phenomena experienced by some patients with causalgia and suggest the possibility of common mechanisms.