Nitish Kamble

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.

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.

Gender and Age Determinants of Psychogenic Movement Disorders: A Clinical Profile of 73 Patients.

BACKGROUND Psychogenic movement disorders (PMD) is a group of disorders that cannot be attributed to any structural or biochemical abnormality, but has an underlying psychiatric illness. The profile of PMD varies according to country and socioeconomic factors. METHODS The present study reports the clinical profile of patients with PMD from India. Seventy-three patients with documented or clinically established PMD were seen over a period of 14 years with detailed neurological and psychiatric examinations. RESULTS The mean age at presentation was 29.1±15.1 years (women, 51%). Approximately 30% were ≤18 years of age (boys, 63.6%). The onset of symptoms was abrupt in 61.6% and the initial body part most often affected was right upper limb (adults, 29.4%; children, 31.8%). Tremor was observed in 31.4% of adults and 9% of children, whereas myoclonus was more common in children (36.4%). Tremors were more often seen in women (42.3%) than in men (20%), whereas myoclonus was almost equally prevalent in girls (37.5%) and boys (35.7%). Depression was the most common psychiatric comorbidity (men, 16%; women, 15.4%). About 42.5% required hospital admission and 57.5% had significant reduction or complete cessation of PMD after counseling, antidepressants, and/ or placebo. CONCLUSIONS PMD was equally prevalent among women and men. Tremor was most often observed in adults, whereas myoclonus was most often observed in children. Electrophysiology and placebo were useful supplementary tools for diagnosing PMD.

Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients.

BACKGROUND Huntingtons disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse. OBJECTIVE Objective of this study is to determine the differences in the demographic and genetic characteristics of patients with behavioral symptom at the onset of HD from those with motor symptoms. METHODS A chart review of 92 patients with HD who had attended the neurology outpatient clinics of National Institute of Mental Health and Neurosciences, India was done. Demographic and genetic characteristics of HD patients with onset of the disease with initial behavioral symptoms (HD-iB) were compared with patients with onset of the disease with initial motor symptoms (HD-iM). RESULTS The principal findings in our study were (i) higher proportion of patients with HD-iB had a positive family history of HD, (ii) maternal inheritance of HD was more frequent among those with HD-iB, and (iii) There is no significant difference between the CAG repeat length between HD-iB and HD-iM groups. CONCLUSION Presence of family history of HD especially inheritance of HD from mother may be associated with behavioral symptoms at the onset of HD. CAG repeat length in patients with HD-iB does not differ from those with HD-iM.

Electrophysiological evaluation of psychogenic movement disorders.

Psychogenic movement disorders (PMD) include a group of neurological symptoms which cannot be explained by any organic syndrome. The diagnosis of PMD is challenging for both neurologist and psychiatrist. Electrophysiological examination is a useful tool to evaluate and support a diagnosis PMD. It includes a set of tests which are chosen appropriate to the clinical setting that provides objective criteria for the diagnosis of PMD. The various tests available include accelerometry, surface electromyography, electroencephalography, jerk locked back averaging and pre-movement potentials, somatosensory evoked potentials, transcranial magnetic stimulation (TMS) etc. Electrophysiologically psychogenic tremors display features of variability, entrainability, coactivation, distractibility and increase in the amplitude and frequency on mass loading. Movement related cortical potentials such as Bereitschaftspotential is seen in psychogenic myoclonus. Presence of triphasic contraction of muscles and absence of co-contraction suggests psychogenic myoclonus. Latency of C-reflex is longer in psychogenic myoclonus as compared to organic myoclonus. The role of TMS to differentiate psychogenic from organic dystonia is still not clear. In conclusion, electrophysiological tests are most useful for tremor, followed by jerks and least for dystonia. In patients with long-standing PMD or those with mixed pathology, electrophysiological tests may not be very useful.

Tremor syndromes: A review

Among the involuntary movement disorders, tremor is a common phenomenology seen in clinical practice. The important factors that need to be determined while assessing a patient with tremor include the phenomenology of tremor, presence or absence of other neurologic signs, and the effect of medications or alcohol. Tremor can broadly be classified based on the circumstances under which it occurs, i.e., rest or action. The basal ganglia-cerebello-thalamic and dentate-olivary circuits are involved in the generation of tremor. Experimental data have suggested the olivocerebellar system as the site of the central oscillator in essential tremor. Generation of tremor in Parkinsons disease results from loss of dopaminergic neurons of the retrorubral area causing dysfunction of the globus pallidus, which finally leads to abnormal firing pattern of the ventrolateral posterior neurons of the thalamus. Involvement of the cerebello-thalamic pathways leads to orthostatic tremor. Palatal tremor is thought to be generated by the cells of the inferior olive. Holmes tremor usually results from the disruption of the dentate-rubro-thalamic circuit and also the nigro-striatal circuit. Multiple drugs can cause tremors. Demyelinating neuropathies are associated with tremors. Involvement of the deep cerebellar nuclei, cerebellar outflow tracts and the cerebrocerebellar loops has been postulated in the cerebellar tremor production. Electrophysiological methods are valuable in characterizing tremors. In addition to the pharmacological therapy including botulinum toxin therapy, surgical therapies in form of DBS or lesional surgeries are beneficial in reducing the symptoms.

Abnormalities of white and grey matter in early multiple system atrophy: comparison of parkinsonian and cerebellar variants

ObjectiveMultiple system atrophy (MSA) is a neurodegenerative disorder with progressive motor and autonomic dysfunction. There is a paucity of information on the early neurostructural changes in MSA, especially its subtypes, MSA-P (patients with predominant parkinsonism) and MSA-C (patients with predominant cerebellar signs). This study investigates the abnormalities of grey matter (GM) and white matter (WM) in early MSA and its subtypes using multi-modal voxel-based analysis.Materials and methodsTwenty-six patients with MSA with duration of symptoms ≤ 2.5 years (mean duration: 1.6 ±0.9 years) were assessed clinically and with 3T MRI. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to identify the structural changes in MSA and its subtypes. The GM changes and diffusion parameters of WM tracts were correlated with the clinical scores. The results were compared with MRI of 25 age- and gender-matched healthy controls.ResultsThe early structural changes in MSA included GM loss of the cerebellum and subcallosal gyrus with widespread involvement of supratentorial and infratentorial WM fibres. In MSA-C, GM loss was limited to the cerebellum with WM changes predominantly affecting the infratentorial WM and association tracts. In contrast, MSA-P did not demonstrate any GM loss and the WM involvement was mainly supratentorial. There was no significant correlation between structural changes and clinical severity score.ConclusionIn early MSA, WM microstructure was more affected than GM. These changes were greater in MSA-C than in MSA-P, suggesting variable deterioration in the subtypes of MSA.Key Points• Structural changes in early multiple system atrophy were evaluated using multi-modal neuroimaging.• White matter was more affected than grey matter in early MSA.• Clinical variables did not correlate with early structural changes.

Evaluation of Cognition and Cortical Excitability in Huntington’s Disease

BACKGROUND Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntingtons disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. OBJECTIVES Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. METHODS The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. RESULTS The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. CONCLUSIONS TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Prescribing Pattern for Parkinson’s Disease in Indian Community before Referral to Tertiary Center

BACKGROUND Several factors determine the choice of medications in patients with Parkinsons disease (PD). We aimed to analyze the pattern of prescription of drugs in patients with PD before attending a tertiary-care center. METHODS The study included chart review of 800 PD patients attending the Department of Neurology of the National Institute of Mental Health and Neurosciences in Bangalore, India. RESULTS The mean age at onset was 51.1±11.8 years. The mean duration of illness was 41.7±43.6 months. At first visit, 79.4% (group 1, n=635) of patients were on medications, 10% (group 2, n=80) were on medications but later discontinued, and 10.6% (group 3, n=85) were drug-naïve. Overall, levodopa was prescribed in 94.8%, trihexyphenidyl in 40.4%, dopamine agonists in 23.2%, and amantadine in 17.2% either as monotherapy or in combination. In group 1, 37.8% were on monotherapy, with levodopa being the most commonly used agent (33.1%), followed by trihexyphenidyl (2.2%), dopamine agonists (1.6%), and amantadine (0.6%). Among those on polytherapy, levodopa plus trihexyphenidyl was the preferred combination (23.9%). In group 2, levodopa monotherapy was also most common (72.5%), followed by trihexyphenidyl monotherapy (7.5%). CONCLUSIONS Levodopa and trihexyphenidyl were the most commonly prescribed drugs in our patients. A higher use of trihexyphenidyl could be due to its easy availability, low cost, and better tolerability in our patients, who were relatively young at the time of onset of their disease. The choice of antiparkinsonian medications at the primary and secondary care levels in India may be inappropriate, and newer guidelines tailored to the Indian context are warranted.

Impaired frontal lobe functions in patients with Parkinson’s disease and psychosis

INTRODUCTION Patients with Parkinsons disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). METHODOLOGY This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinsons disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. RESULTS The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). CONCLUSION Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up.