Modulatory effect of continuous theta burst stimulation in patients with essential tremor.

INTRODUCTION: We aimed to study the cortical and intracortical functions in patients of ET using transcranial magnetic stimulation (TMS) and to evaluate the effect of continuous theta burst stimulation (cTBS) on the tremor characteristics. METHODS: Ten ET and 20 healthy controls were included in the study. All the participants were evaluated with TMS with recording of resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Subsequently only ET patients underwent cTBS of the motor cortex (M1) followed by repeat TMS. RESULTS: The mean age of the patients (46.5 ± 17.2 years) was comparable to healthy controls (55.4 ± 9.2 years; p = 0.16). There was a non-significant increase in RMT in ET patients (44 ± 12.5%) when compared to healthy controls (40.9 ± 6.9%; p = 0.48). There was a significant reduction of cSP in the ET group (102.03 ± 15.26 msec) compared to healthy controls (116.1 ± 15.2, p = 0.03). In addition, a significant reduction in ICF was observed in ET patients (0.9 ± 0.7) compared to healthy controls (1.8 ± 0.8, p = 0.01). Following cTBS there was a significant reduction in the tremor scores [FTMRS (Pre-cTBS: 29.3 ± 18.7, Post-cTBS: 25.3 ± 16.8; p < 0.001) and TETRAS (pre-cTBS: 34.4 ± 16.2, post-cTBS: 29.8 ± 12.1; p = 0.01)] and improvement (increase) of the duration of cSP (pre-cTBS: 102.03 ± 15.3 msec., post-cTBS: 119.4 ± 12.03 msec; p = 0.05). CONCLUSIONS: Patients with ET have GABAergic and glutaminergic dysfunction as demonstrated by reduced cSP and ICF. However, only the cSP improved following cTBS of M1 region, with a corresponding improvement of tremor severity suggesting the effect of cTBS on the cerebello-thalamo-cortical network.

Knowledge, Attitude, and Perceptions about Deep Brain Stimulation for Parkinson's Disease: Observations from a Single Indian Center.

OBJECTIVE: Willingness to undergo deep brain stimulation (DBS) among patients with Parkinson's disease (PD) and their overall satisfaction with the procedure is highly dependent upon expectations, which are based on the core concepts of knowledge, attitude and perceptions. The present study aims to evaluate these factors in patients and caregivers with PD from a single tertiary care hospital in India. METHODS: A structured questionnaire designed to assess the knowledge, attitude and perceptions about DBS in PD was administered to 400 patients with PD and their caregivers. RESULTS: A very small proportion of patients and caregivers were aware of DBS. Even those who claimed to be aware of DBS were inadequately informed and had incorrect knowledge, which led to wrong attitudes and perceptions. CONCLUSION: There are very significant knowledge gaps and misconceptions regarding DBS among patients with PD and caregivers. Adequate and appropriate education is necessary to clarify these misconceptions to avoid the development of unrealistic expectations and poor satisfaction.

Study of Clinicoradiological Profile and Prognosis of Longitudinally Extensive Transverse Myelitis from a Single Tertiary Center in Eastern India.

CONTEXT: Longitudinally extensive transverse myelitis (LETM) is defined as a hyperintense spinal cord lesion extending over three or more vertebral levels on sagittal T2-weighted spinal magnetic resonance imaging (MRI). Among the different causes of LETM, neuromyelitis optica (NMO) is the most common and associated with bad prognosis. AIMS: We aimed to study the clinicoradiological profile, etiology, and prognosis of LETM. SETTINGS AND DESIGN: This is a hospital-based cross-sectional prospective study. SUBJECTS AND METHODS: The study included 37 patients who presented with paraplegia/paresis or quadriplegia/paresis with MRI spine showing LETM. They were analyzed for their clinical features, routine blood parameters, MRI findings, serum aquaporin 4 (AQP4) antibodies. All patients were followed up for 1 year for prognosis. STATISTICAL ANALYSIS USED: Data analysis was performed using SPSS software (version 17, SPSS Inc.; Chicago, IL, USA). The different groups were compared with each other using Chi-square test. RESULTS: The mean age in our series was 35.97 ± 13.2 years. There was a slight female predominance of LETM in our series with a female: male ratio of 1.05:1. Thoracic spinal cord segments were the most commonly (56.76%) affected. The tendency to involve three to five segments is more common (40.54%). Serum AQP4 antibody (Ab) test was done in 26 patients with LETM. Among them, AQP4 Ab was found positive in nine patients (34.62%). A total of 22 patients (59.46%) were clinically diagnosed as NMO, 4 patients as postinfectious myelitis, 1 each in tuberculous myelitis and subacute combined degeneration, and 9 were idiopathic LETM. Prognosis of LETM in the form of Expanded Disability Status Scale at 1 year was poor in patients with NMO particularly those with positive AQP4 Ab. CONCLUSION: NMO is the most common cause of LETM. Because of poor prognosis of LETM in patients with NMO, particularly those with positive AQP4 Ab, it is very essential for early and accurate diagnosis of etiology of LETM, so that appropriate treatment can be provided to the patient.

Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

Hemichorea Secondary to Non-Ketotic Hyperglycemia as the Presenting Manifestation of Diabetes Mellitus.

Nonketotic hyperglycemia is an unusual and rare cause of hemichorea. Hemichorea though rare may be the initial manifestation of diabetes mellitus. Correction of the hyperglycemia usually results in total resolution of the signs and symptoms. We present the case of a 71 yr old female, who presented with subacute onset of choreiform movement of left upper and lower extremities over 8 days. Her serum glucose level was 416 mg/dl and urine ketone bodies were absent. Computed tomography of brain showed right caudate nucleus and right lentiform nucleus hyperdensity suggesting hyperglycemia related hemichorea syndrome. Restoration of euglycemia along with treatment with haloperidol and tetrabenazine led to eventual resolution of all symptoms. So, nonketotic hyperglycemia should be kept as a differential diagnosis in a patient with hemichorea.

Concurrent intramedullary spinal cord and multiple intracranial tuberculomas with tuberculous optic neuritis: A rare case report.

Tuberculosis (TB) remains a worldwide burden, with a large majority of new active TB cases occurring in underdeveloped and developing countries. Tuberculous meningitis (TBM) is one of the common infections of central nervous system. Other manifestations include intracranial tuberculoma, tubercular brain abscess, spinal tuberculoma, and granulomatous arachnoiditis. Visual impairment in TBM may be due to optic neuritis, optochiasmatic arachnoiditis (OCA), tuberculoma in the chiasmatic region or in the optic pathways, chorioretinitis, secondary to hydrocephalus and increased intracranial pressure, and finally due to ethambutol toxicity. We report a case of young girl with concurrent spinal cord intramedullary tuberculoma and multiple intracranial tuberculomas with TBM and bilateral visual impairment due to tuberculous optic neuritis.

Study of Seminal Fluid Parameters and Fertility of Male Sickle Cell Disease Patients and Potential Impact of Hydroxyurea Treatment.

INTRODUCTION: Male Sickle cell disease (SCD) patients often have moderate to severe hypogonadism resulting in abnormal seminal fluid parameters due to testicular dysfunction. Hydroxyurea (HU), the only drug found to be effective in preventing morbidity and mortality in sickle cell disease patients has been found to further aggravate the testicular dysfunction. MATERIAL AND METHODS: This was a prospective study done at a tertiary care hospital over 26 months between September 2011 to October 2013. 100 male sickle cell disease patients of age group 15 to 45 years were recruited in the study. We evaluated seminal fluid indices in all patients and the effect of hydroxyurea on seminal fluid parameters. Hydroxyurea was given at low dose of 10mg/kg/day orally to patients with frequent vaso-occlusive crisis and frequent need of blood transfusion. Seminal fluid analysis was done according to WHO criteria before starting hydroxyurea and every 3 months after initiation of hydroxyurea. Patients with abnormal seminal parameters before hydroxyurea therapy were not given hydroxyurea therapy. Patients with abnormal sperm parameters were subjected for FNAC of testis. In sickle cell disease patients with hydroxyurea therapy, who developed abnormal seminal fluid parameters, hydroxyurea was stopped for 3 months and seminal fluid parameters were re-evaluated. Patients who had recovery of seminal indices after hydroxyurea cessation were restarted with hydroxyurea therapy at low dose. RESULTS: Among Sickle cell disease patients without hydroxyurea therapy, 18% of patients developed oligospermia and 4% developed azoospermia. Among sickle cell disease patients with hydroxyurea therapy, 20% of patients developed oligospermia and 10% developed azoospermia. Seminal fluid parameters reverted back to normal after stoppage of hydroxyurea for 3 months in 73% of patients. CONCLUSIONS: Alteration of sperm parameters is seen in a significant number of sickle cell disease patients. Also, alterations of seminal fluid parameters are exacerbated by hydroxyurea treatment even with low dose. Therefore, treatment with hydroxyurea in adolescent and adult male sickle cell disease patients should be preceded by routine assessment of seminal fluid parameters and followed up regularly every 3 months for any change in seminal fluid parameters for evidence of hydroxyurea toxicity.

Chorea and Orofaciolingual Dystonia in a 40 Year Old Male.

Neuroacanthocytosis is a heterogeneous group of disorders which result in progressive neurodegeneration, predominantly of the basal ganglia, and erythrocyte acanthocytosis. We report a case of neuroacanthocytosis with typical phenotype of choreoacanthocytosis. A 40 year male presented with features of chorea with orofaciolingual dystonia producing eating and speech difficulties. There were features of self mutilation in form of lip and tongue biting. Peripheral blood smear examination revealed acanthocytes in our patient. Neuroimaging showed bilateral caudate atrophy and nerve conduction study showed motor axonal neuropathy. This case report describes the typical features and investigations to diagnose this rare disorder which is usually underdiagnosed.

Glutaric Aciduria Type I: A Rare Metabolic Disorder Mimicking as Choreoathetoid Cerebral Palsy.

Glutaric aciduria type I (GA I) is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme glutaryl-CoA dehydrogenase. This disorder is characterized by progressive dystonia, choreoathetosis, and dyskinesia. It is often misdiagnosed as athetoid cerebral palsy. Laboratory evaluation usually demonstrates increased urinary excretion of gluataric acid and 3-hydroxyglutaric acid. We report a case of a 7-year-old boy presenting with choreoathetosis and dystonia, mimicking as choreoathetoid cerebral palsy. The presence of characteristic neuroimaging and biochemical studies led to the diagnosis of GA I.

Low and fixed dose of hydroxyurea is effective and safe in patients with HbSß(+) thalassemia with IVS1-5(G→C) mutation.

BACKGROUND: Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSß(+) -thalassemia with IVS1-5(G→C) mutation. PROCEDURE: We registered 318 patients with HbSß(+) -thalassemia with IVS1-5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group-I: 37 children and Group-II: 67 adults) with ≥2 years of hydroxyurea treatment were studied. RESULTS: The rate of vaso-occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group-I and 3 to 0, 1 to 0 and 0.5 to 0 in Group-II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum-bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function. CONCLUSION: In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSß(+) -thalassemia in resource poor setting.