M. Netravathi

Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) in movement disorders: A review

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable adjunctive therapeutic modality in movement disorders. It is a non-invasive technique of repeated stimulation of the cerebral cortex by a train of magnetic pulses. The therapeutic effect of rTMS was first noted in depression. Later several researchers have investigated the role of rTMS in various movement disorders, notably Parkinsons disease, dystonia, Tourettes syndrome etc. The rTMS protocols used in these studies vary widely, lacks uniformity and often the results are not consistent. The optimal rTMS parameters for each disorder are yet to be established. This review discusses the current knowledge on the therapeutic applications of rTMS in various movement disorders.

A clinical profile of 103 patients with secondary movement disorders: correlation of etiology with phenomenology.

Background and purpose:  Studying patients with secondary movement disorders (SMD) provides a unique opportunity to determine the correlation between the etiology and phenomenology of movement disorders.

Spinocerebellar ataxias types 1, 2 and 3 : Age adjusted clinical severity of disease at presentation correlates with size of CAG repeat lengths

OBJECTIVE The objective of this study was to determine the correlation, if any, between the clinical rate of disease progression at presentation with the CAG repeat size in patients with spinocerebellar ataxias 1, 2 and 3 (SCA1, SCA2 and SCA3). METHODS The severity of ataxia was measured using the International Cooperative Ataxia Rating Scale (IARS) in 31 patients of SCA1 (mean+/-SD age: 35.1+/-12.6 years; age at onset (AAO): 29.9+/-10.7 years), 25 patients of SCA2 (age: 34.9+/-14.9 years; AAO: 29.7+/-14.0 years) and 15 patients of SCA3 (age: 40.9+/-8.6 years; AAO: 36.9+/-10.1). The rate of disease progression at presentation was measured by the age adjusted IARS (IARS/Age). For each SCA, correlations of AAO, raw scores of IARS, age adjusted IARS and duration adjusted IARS (IARS/Duration) with the CAG repeat size were determined. RESULTS The number of CAG repeats of the abnormal allele ranged from 42 to 67 in SCA1, 38 to 66 in SCA2, and 69 to 79 in SCA3. In all the three types of SCAs, there were significant inverse correlations of AAO with CAG repeat size (SCA1: r=-0.9, p<0.0001; SCA2: r=-0.7, p<0.0001; SCA3:-0.8, p=0.0003) and significant positive correlations of IARS/Age with CAG repeat size (SCA1: r=0.6, p=0.0015; SCA2: r=0.9, p<0.0001; SCA3:0.7, p=0.0057). However, the raw IARS scores and the duration adjusted IARS scores did not correlate significantly with the CAG repeat sizes. CONCLUSIONS These data suggest that the rate of clinical disease progression at presentation, especially in SCA2, is dependent on the CAG repeat size, and may commence linearly from birth.

Profile of extrapyramidal manifestations in 85 patients with spinocerebellar ataxia type 1, 2 and 3

This study aimed to determine the prevalence and type of extrapyramidal signs (EPS) in spinocerebellar ataxia (SCA) type 1, 2 and 3. Eighty-five patients with genetically confirmed SCA (SCA1=40, SCA2=28, SCA3=17) were evaluated for the prevalence and types of EPS. Forty-one SCA patients (48.2%) had one or more types of EPS. The prevalence of EPS was 60.7% in SCA2, 52.9% in SCA3, and 37.5% in SCA1. Among SCA2 patients, bradykinesia was the most frequent (35.3%), followed by reduced facial expression, postural tremor and dystonia (29.4% each), rest tremor, titubation and rigidity (23.5% each), and lip/jaw tremor and chorea (11.8% each). In SCA3 the common EPS were bradykinesia (44.4%), staring look, postural tremor and dystonia (33.3% each), and reduced facial expression and rigidity (22.2% each). In SCA1, staring look was the most common (53.3%), followed by dystonia and bradykinesia (33.3% each), and postural tremor (26.7%). In all three groups, there was no significant difference in the mean length of repeat of the abnormal allele between those with and without EPS. To conclude bradykinesia, staring look, dystonia and postural tremor were the most frequent EPS observed in SCA. In SCA1, these signs were seen more often in younger patients with early onset of symptoms.

Reversible parkinsonism following ventriculoperitoneal shunt in a patient with obstructive hydrocephalus secondary to intraventricular neurocysticercosis

Parkinsonism with evidence of midbrain dysfunction has been reported in a few patients with aqueductal stenosis after placement of ventriculoperitoneal (VP) shunt. The response to levodopa is variable. We report a patient with neurocysticercosis of the fourth ventricle who developed transient parkinsonism without evidence of midbrain dysfunction after placement of a VP shunt. The frequency of tremor was 5-5.5 Hz. Though the response to levodopa was initially slow, later it was significant, and after 3 months he was asymptomatic without levodopa. The exact pathophysiology of parkinsonism in our patient remained obscure.

Clinical and imaging characteristics of 16 patients with autoimmune neuronal synaptic encephalitis.

OBJECTIVES Autoimmune neuronal synaptic encephalitis (AIE) encompasses a heterogeneous group of disorders characterized by immune-mediated neuronal cell destruction. In this study, we aim to study the clinical features, imaging profile and treatment outcome of patients with AIE. METHODS This is a chart review of 16 (M: F-3:13) patients with AIE from 2011 to 2015. RESULTS Among the patients, 10 had anti-NMDA, 4 had anti-TPO, and 2 had anti-VGKC antibody positivity. Cognitive impairment and seizures were the predominant symptoms present in nearly all patients, followed by psychiatric disturbances (87.5%), mutism (62.5%), movement disorders (62.5%), myoclonic jerks (37.5%) and visual hallucinations (18.75%). Magnetic resonance imaging (MRI) of the brain was available in 15 patients; it was abnormal in 53.3% patients. Abnormalities were seen in all patients with anti-VGKC positivity; and, 60% of patients with anti-NMDA positivity. Imaging was normal in 26.7% of the patients (3: anti-NMDA; and, 1: anti-TPO positivity); and, diffuse cerebral atrophy was noted in rest of the 20% (3: anti-TPO positivity) patients. All patients improved gradually with immunomodulation. CONCLUSIONS All patients with anti-VGKC, anti-NMDA and anti-TPO antibody positivity presented with a triad of behavioral changes, impaired cognition and seizures. Mutism was a predominant symptom in patients with an anti-NMDA antibody positivity, which may help in the early identification of this disorder. MRI brain showed changes restricted to limbic structures in anti-NMDA and anti-VGKC antibody positivity. An early diagnosis and treatment of autoimmune encephalitis is essential for a better outcome and for prevention of long-term sequel.

Does lesioning surgery have a role in the management of multietiological tremor in the era of Deep Brain Stimulation

INTRODUCTION Surgical management of tremor has evolved over the years with Deep Brain Stimulation (DBS) gradually supplanting lesioning as the mainstay in treatment. In this article, the largest of its kind from our country, we present our experience in the use of lesioning in the management of patients with multietiological tremors. These include not only common indications like Parkinson disease and essential tremor but also rare causes such as Pantothenate kinase associated neurodegeneration (PKAN), multiple sclerosis (MS) and Wilson disease. MATERIALS AND METHODS Patients with medically refractory tremor who underwent surgery were included in the analysis. A comprehensive clinical and radiological evaluation was performed which was repeated 3 months postoperatively and at successive visits. Video documentation of was obtained at all visits. RESULTS A total of 21 patients (18 men, 3 women) with an average age 37.7 years (range 21-65 years) underwent stereotactic thalamotomy/subthalamotomy at our institute between 2008 and 2013, for the treatment of medically refractory tremor of varying etiologies. The mean preoperative duration of symptoms was 11 years (range 10 months to 34 years). The median time to onset of improvement was 2 months (range 1 week to 8 months). Analyzing the improvement on the modified FTM scale, in part 1 the scores improved from 21.7 to 1.5, the part II subset improved from an average of 9.2 to 3.2 while the part III subset improved from an average of 14.1 to 4.1 postoperatively. This implied an excellent response in tremor while the other 2 components had a very good response. DISCUSSION In this study we have for the first time objectively analyzed the tremor improvement with a modified FTM scale and have produced excellent results. We have also shown that tremor of various etiologies respond extremely well to lesioning surgery. While DBS continues to remain the treatment of choice in various types of bilateral tremor, lesioning is very successful in a carefully selected cohort of patients. We are of the opinion that in predominantly unilateral tremor or when the patient cannot afford DBS especially in a country like ours, lesioning surgery is an important tool in the armamentarium of the functional neurosurgeon.

Long-term efficacy and limitations of cyclophosphamide in myasthenia gravis.

Myasthenia gravis (MG) is a chronic autoimmune disorder with a fluctuating clinical course. The aim of immunotherapy is to bring about long-term remission. We evaluated the safety and efficacy of cyclophosphamide in generalized MG. We also highlight the limitations of cyclophosphamide therapy in inducing long-term remission. Data from 22 patients with generalized MG who received cyclophosphamide therapy were analyzed in terms of its safety and outcome. Twelve patients completed at least six pulses of intravenous cyclophosphamide therapy, and all improved symptomatically at 6 months. At 1 year, only seven patients reported sustained benefit and five had discontinued oral pyridostigmine. During a follow-up period of 56.67 months, all but one patient relapsed and required alternative immunomodulatory therapy. The average time to remission after the initiation of intravenous pulse cyclophosphamide (n=12) was 3.6 months (standard deviation [SD] 1.6 months, range 1-6 months), while the mean duration of remission was 20.3 months (SD 8.8 months, range 12-39 months). Forty-six adverse events were documented in 11 patients over 127 cyclophosphamide pulses. Most of the adverse events were managed symptomatically. In four patients, cyclophosphamide had to be discontinued due to adverse events. Intravenous pulse cyclophosphamide is effective in the management of MG; however remission may be short, necessitating long-term follow-up and alternative immunomodulation. Careful monitoring for adverse events should be mandatory.

Movement disorders of probable infectious origin.

Background: Movement disorders (MDs) associated with infections remains an important debilitating disorder in the Asian countries. Objectives: The objective of the following study is to report the clinical and imaging profile of a large cohort of patients with MDs probably associated with infection. Materials and Methods: This was a chart review of 35 patients (F:M-15:20) presenting with MD in the Neurology services of National Institute of Mental Health and Neurosciences, India. The demographic profile, type of infection, time from infection to MD, phenomenology of MD and magnetic resonance imaging (MRI) findings were reviewed. Results: The mean age at presentation was 22.6 ± 13.3 years, (5-60), age of onset of MD was 15.7 ± 15 years, and duration of symptoms was 6.9 ± 8.1 years (42 days to 32 years). The mean latency of onset of MD after the infection was 5.9 ± 4.2 weeks. The phenomenology of MD were: (1) Pure dystonia-28.6%, (2) dystonia with choreoathetosis-22.9%, (3) Parkinsonism-14.6%, (4) pure tremor, hemiballismus, myoclonus and chorea-2.9% each, and (5) mixed MD-22.9%. Most often the MD was generalized (60%), followed by right upper limb (31.4%) and left upper limb (8.6%). A viral encephalitic type of neuroinfection was the most common infection (85.7%), which was associated with MD. Abnormalities of brain MRI, seen in 79.2%, included signal changes in (1) thalamus-52.0%, (2) putamen and subcortical white matter-16% each, (3) pons-12%, (4) striatopallidum, striatum and grey matter-8% each, and (5) caudate, cerebellum, lentiform nucleus, midbrain and subthalamic nucleus-4.0% each. Conclusions: MDs associated with infection were the most often post-encephalitic. Dystonia was the most common MD, and thalamus was the most common anatomical site involved.

Subacute sclerosing pan encephalitis with HIV: two rare case reports

Case Reports Two children, a 10 year old boy and an 11 year old girl, both HIV-1 seropositive following perinatally acquired infection, presented with strikingly different clinical symptoms to Neurology OPD, NIMHANS. The boy presented with deterioration in scholastic performance over a four month duration with generalized tonic clonic seizures of 1 month duration. Vision was normal. The girl was found to have evidence of bilateral blindness, altered gait with dysarthric speech and severe truncal ataxia. Both children were unvaccinated for measles and gave a definitive history of Measles at the age of 8 months and 6 years. The latent period between Measles infection and SSPE was 9 and 5 years respectively. Clinically both were staged at Jabbour Stage II and Gascon stage III. The CD4 counts were 554/mm and 130//mm respectively. In both patients, progressive cognitive decline, reduction in scholastic performance, regression of milestones and inability to walk with loss of self care occurred in 12 and 4 weeks respectively following onset.