Psychogenic tremor: long-term outcome.

INTRODUCTION: Psychogenic disorders, also referred to as somatoform, conversion, somatization, hysteria, and medically unexplained symptoms, are among the most challenging disorders to diagnose and treat. Psychogenic movement disorders are increasingly encountered in specialized clinics, and represent approximately 15% of all patients evaluated in the Baylor College of Medicine Movement Disorders Clinic. OBJECTIVE: To characterize psychogenic tremor and provide data on prognosis and long-term outcome in a large group of patients with psychogenic tremor followed in a movement disorders clinic. METHODS: Patients evaluated at the Baylor College of Medicine Movement Disorders Clinic in Houston, Texas, between 1990 and 2003 with the diagnosis of psychogenic movement disorder (PMD), who consented to be interviewed, were administered a structured questionnaire designed to assess current motor and psychological function. RESULTS: psychogenic tremor is the most common PMD, accounting for 4.1% of all patients evaluated in our clinic. We were able to obtain clinical information on a total of 228 of 517 (44.1%) patients with PMD, followed for a mean of 3.4+/-2.8 years. Among the 127 patients diagnosed with psychogenic tremor, 92 (72.4%) were female, the mean age at initial evaluation was 43.7+/-14.1 years, and the mean duration of symptoms was 4.6+/-7.6 years. The following clinical features were considered to be characteristic of psychogenic tremor: abrupt onset (78.7%), distractibility (72.4%), variable amplitude and frequency (62.2%), intermittent occurrence (35.4%), inconsistent movement (29.9%), and variable direction (17.3%). Assessment of long-term outcome showed that 56.6% of patients reported improvement in their tremor. Factors predictable of a favorable outcome were elimination of stressors and patient's perception of effective treatment by the physician. CONCLUSION: This largest longitudinal study of patients with psychogenic tremor provides data on the clinical characteristics and natural history of this most common PMD. The accurate diagnosis of psychogenic tremor is based not only on exclusion of other causes but is also dependent on positive clinical criteria, the presence of which should avoid unnecessary investigation. The prognosis of psychogenic tremor may be improved with appropriate behavioral and pharmacologic management.

Long-term prognosis of patients with psychogenic movement disorders.

Psychogenic movement disorders (PMD) are hyper- or hypokinetic movement disorders associated with underlying psychological or psychiatric disorders. Structured telephone interview was administered to 228 patients with PMD seen in our clinic between 1990 and 2003. The mean age of the subjects was 42.3+/-14.3 years (range 14-70 years), mean duration of symptoms was 4.7+/-8.1 years (range 2-14 years), and mean duration of follow-up was 3.4+/-2.8 years (6 months-12 years). Improvement of symptoms was noted in 56.6% patients; while 22.1% were worse, and 21.3% remained the same at the time of follow-up. In this longitudinal study of patients with PMD we found that indices of strong physical health, positive social life perceptions, patient's perception of effective treatment by the physician, elimination of stressors, and treatment with a specific medication contributed to a favorable outcome.

Evaluating factors that can influence spirography ratings in patients with essential tremor.

Spirograph drawings are used in most comprehensive assessments of essential tremor (ET). Nevertheless, several different paradigms are used and no effort has been made to compare these. We used two different cohorts to assess different aspects of spiral rating. In the first, we had subjects simulate different levels of effort by writing (1) 'normally', (2) 'slowly and carefully', (3) 'softly', and (4) 'rapidly' using both their dominant and non-dominant hands. In the second, subjects (1) drew in between the lines of two drawn spirals, (2) traced a previously drawn spirograph, and (3) drew freehand. Subjects drew each with both 'supported' (regular writing) and 'unsupported' writing. The spirals were coded, randomized and blindly rated on a 0-9 scale. Unsupported drawings were consistently rated as worse than supported spirals, and the dominant hand was generally better than the non-dominant hand. Spiral drawn freehand spirals were consistently rated with the lowest scores. Inter-rater and intra-rater reliability were also best for unsupported drawings and tended to be best for 'freehand'. 'Effort' had little effect on ratings. Based on our results, we recommend that assessment of ET include unsupported, freehand spirals.

Glabellar and palmomental reflexes in Parkinsonian disorders.

The authors examined the glabellar reflex and the palmomental reflex in 100 subjects, including patients with Parkinson disease (n = 41), patients with progressive supranuclear palsy (n = 12), patients with multiple system atrophy (n = 7), and healthy, age-matched, controls (n = 40). The study provides evidence that these reflexes, particularly glabellar reflex, are relatively sensitive signs of parkinsonian disorders, but they lack specificity as they do not differentiate among the three most common parkinsonian disorders.

Neurodegenerative disease and iron storage in the brain.

PURPOSE OF REVIEW: Iron is very important for normal regulation of various metabolic pathways. Neurons store iron in the form of ferrous ion or neuromelanin. In specific disorders the axonal transport of iron is impaired, leading to iron deposition which in the presence of reactive oxygen species results in neurodegeneration. RECENT FINDINGS: Recent developments in genetics, including the finding of mutations in the pantothenate kinase gene and ferritin light chain gene, have demonstrated a direct relationship between the presence of a mutation in the iron-regulatory pathways and iron deposition in the brain resulting in neurodegeneration. These two disorders now add to our understanding of the mechanism of disease due to dysfunction of iron-regulatory pathways. In addition to these disorders there may be several other mutations of iron-regulatory genes or related genes that are yet to be found. The animal models of disease have also added value to this area. SUMMARY: In this review we provide a summary of recent developments in the field of movement disorders with abnormalities in iron transport, and the current evidence in neurodegenerative disorders such as Parkinson's disease.

Minocycline in Huntington's disease: a pilot study.

Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase (iNOS), and has been shown to delay disease progression in the mouse model R6/2 of Huntington's disease (HD). This safety and tolerability study included 30 patients with HD who were given minocycline over a 6-month period and underwent assessments every 2 months with laboratory studies, the Abnormal Involuntary Movements Scale, the Unified Huntington's Disease Rating Scale, and the Mini-Mental State Examination. Minocycline was well tolerated during this study period and no serious adverse events were noted.

Psychogenic movement disorders: diagnosis and management.

Psychogenic movement disorders (PMDs) are best defined as hyper- or hypo-kinetic movement disorders, often associated with gait disorders, that cannot be directly attributed to a lesion or dysfunction of the nervous system and which are derived in most cases from psychological or psychiatric causes. There are a variety of PMDs including tremor, dystonia, parkinsonism, gait disorders and, even, unusual forms including paroxysmal dyskinesias. As has been recognised in the recent literature, PMDs cannot be strictly classified into clearly defined psychiatric disorders such as somatoform, dissociative or conversion disorders. In this review, we discuss the diagnosis of various PMDs (including hyper- and hypo-kinetic disorders; and current evidence for underlying comorbid disorders) and the current therapeutic approach to them. The therapy of PMDs is not well established, is very challenging to the clinician, and a better outcome can be achieved in the setting of a team approach involving movement disorders specialists, psychiatrists and therapists who specialise in cognitive-behavioural techniques. Current pharmacological and non-pharmacological approaches to treatment focus on therapy of underlying comorbid psychiatric and psychological issues, although compliance is a major concern.

Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration.

Hallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3-p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase-associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 (PANK2) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult-onset patients whereas dystonia seems more frequent in the earlier-onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome.

Clinical gait and balance scale (GABS): validation and utilization.

Gait and Balance Scale (GABS) consists of historical information and examination of 14 different gait and balance parameters designed to assess the severity of these functional domains. Thirty-five patients with Parkinson's disease (PD), Hoehn and Yahr stages 1-3, were tested during their "off" period. GABS items were compared to quantitative data from two computerized gait analysis instruments, GAITRite and Pro Balance Master. Intra-class correlation coefficients were calculated to establish reliability. Intra-rater test-retest reliability was determined using Cohen's Kappa statistic. Concurrent validity was derived using the Spearman's rho test with the items from GABS, GAITRite and Balance Master. Intra-rater reliability was high with k>0.41 (k=kappa statistic) for 17 items, 6 had k>0.61. When performing validity measurements, a number of items on the GABS had a correlation coefficient significant at p<0.01 (2-tailed). Posture, pull test, balance during stance, single limb stance, tandem stance, turning, toe walking and functional reach had significant correlation with Balance Master data (R=0.46-1). Gait, arm swing, gait speed, steps/5 m, 'up-and-go test', modified performance oriented assessment of gait scale and provocative testing had significant correlation with the GAITRite items (R=0.51-0.83). GABS is an easy-to-use comprehensive clinical scale with high intra-rater and internal item reliability. We have shown concurrent validity with two computerized gait analysis instruments. We expect GABS to have a particular utility in clinical trials designed to modify functional impairment associated with abnormalities in gait and balance.

Tetrabenazine treatment for Huntington's disease-associated chorea.

Tetrabenazine (TBZ), a monoamine depleter and dopamine receptor blocker, is used to treat a variety of hyperkinetic movement disorders. The objective was to study the efficacy and tolerability of TBZ for chorea associated with Huntington's disease (HD). Nineteen patients (12 female), mean age 56.3 +/- 12.4 years (range 37-76 years) diagnosed with HD were prospectively evaluated at initial and follow-up visits using a modified Abnormal Involuntary Movement Scale (AIMS). Patients were videotaped, and the randomized videotapes were rated with the motor subset of the AIMS by two investigators who were blinded to treatment assignment. Eighteen patients completed and were rated after 5.9 +/- 3.3 months (range 2-11) at a final mean TBZ dose of 62.5 +/- 37.4 mg/day (range 25-150). The blinded videotaped motor scores showed that 15 were better on TBZ, 2 were better before TBZ, and 1 was unchanged (p < 0.001, Wilcoxon signed rank test). The mean score improved from 16.2 +/- 4.8 to 12.8 +/- 4.4. Adverse events included akathisia, insomnia, constipation, depression, drooling, and subjective weakness. All 18 of these patients have continued to take TBZ since completion of the study. TBZ was well tolerated and resulted in a significant improvement in modified AIMS scores in HD patients. These results support the use of TBZ for chorea in patients with HD.