Movement disorders are one of the important neurological manifestations of inherited metabolic disorders. Important clues to the presence of an underlying inborn error of metabolism are early onset, presence of neuroregression or degeneration, parental consanguinity, sibling affection, paroxysmal events, waxing and waning course, skin or hair changes, absence of a perinatal insult or any structural cause, and presence of identifiable triggers. It is particularly important to recognize this class of movement disorders as several of them are eminently treatable and may often need disease-specific therapy besides symptomatic treatment. The current review focusses on the movement disorders associated with inherited metabolic defects in children, with emphasis on treatable disorders.

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Stroke is a serious neurological complication observed during the ongoing COVID-19 (coronavirus associated disease 2019) pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome, corona virus 2) and includes both ischemic stroke and intracerebral haemorrhage. We reviewed factors that could potentially contribute to the occurrence of stroke among patients with COVID-19. There could be an interaction between the conventional risk factors of stroke, infection, systemic inflammatory response and plaque destabilisation. Inflammatory markers, D-dimer elevation and increased cytokine activity have all been observed in patients with COVID-19. Other probable contributing factors include cardiac injury leading to embolism, a prothrombotic state and a possibility of direct neuroinvasive potential causing vasculopathy. Data from stroke patients gathered in large multicentric cohorts could help shed more light on the occurrence, behaviour, aetiology, pathophysiology, biomarkers and outcomes of stroke occurring during the ongoing pandemic.

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Background: Parkinson's disease (PD) is the second-most common neurodegenerative disorder known primarily by its motor symptomatology. These motor manifestations are also hypothesised to affect the respiratory muscular function of PD patients contributing to restrictive pattern of ventilatory dysfunction. Previous reports attempting to detect these abnormalities through spirometric assessments have been inconclusive. Attempts at reversal of the restrictive abnormalities by levodopa therapy too, have yielded conflicting results. Objectives: This study aims to classify spirometric abnormalities in asymptomatic PD patients after levopopa withdrawal and document changes after levodopa replacement. Methods: Thirty-six non-smoker PD patients without pre-existing respiratory abnormalities were enrolled. Their standard spirometric values- FEV1, FVC and FEV1/FVC, were noted before and after their morning levodopa dose. Results: Nineteen patients had abnormal PFT values at baseline - 14 restrictive and 5 obstructive defects. Fourteen patients showed improvement in their pulmonary performances after dopamine administration with 6 showing complete reversibility. Statistically significant improvement in the post-levodopa FVC values was seen in patients with restrictive disorder (P value=0.04) but not for obstructive disorders. Discussions: This pilot study characterised that 39% of PD patients had restrictive ventilatory defects prior to morning dopamine administration. Of these, 40% showed improvement after levodopa administration. Conclusion: Restrictive defects are common in PD patients which are evident on routine spirometric screening. These defects are reversible on levodopa administration.

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Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS), first described in 1984 is a rare disorder. Generally, it presents at adulthood with dementia, motor impairment, extrapyramidal abnormalities, and epilepsy. Definitive diagnosis is made by brain biopsy. Neuroimaging studies have revealed confluent white matter lesions predominantly in the frontal lobes, corpus callosum, and corticospinal tracts on conventional magnetic resonance imaging. Only a few reports showed diffusion restriction in the cerebral white matter; furthermore, rarer reports emphasized persistent foci of diffusion restriction as a diagnostic imaging marker. Objective: Herein, we have aimed to illustrate the first biopsy-proven Turkish HDLS pedigree consisting of 18 persons in 3 generations which contained 4 affected individuals. Materials and Methods: Four individuals in the pedigree of HDLS [two affected patients (patient III-1 and patient III-2) and two unaffected individuals (patient II-4 and patient III-5)] were investigated with conventional MRI and Diffusion-weighted imaging (DWI) using 1.5 Tesla (T) scanner. All four individuals were evaluated via neurological examinations and Mini-Mental State Examination. Brain biopsy study was performed on patient III-2. Finally, an extensive literature review involving pathology investigations and neuroimaging studies of HDLS patients was conducted. Results: DWIs of two investigated patients showed deep white matter lesions with persistent diffusion restriction. Computed tomography imaging showed punctate mineralization in the lesions. Biopsy specimens of patient III-2 demonstrated axonal spheroids which were typical for HDLS. Conclusions: Via the presentation of our pedigree and literature review, we suggest HDSL as a first-line differential diagnosis in patients with undiagnosed adult-onset familial leukoencephalopathy, in particular, those with MRI lesions of frontal white matter and centrum semiovale associated with foci of diffusion restriction and mineralization. Finally, we think that the persistence of the diffusion restriction in deep white matter lesions should be kept in mind as a crucial neuroimaging sign for HDLS.

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Objective: Onabotulinum toxin A (botulinum A toxin) is utilized to extend flexed extremities in spastic hemiparesis. Injection points are important to obtain a better effect. Injecting botulinum A toxin into the forearm muscles is a standard method for flexed wrist and fingers; however, we developed new injection points in the intrinsic muscles of the hand to acquire more reliable effect. Methods: The authors injected botulinum A toxin into the palmar side of the proximal and middle phalanx of each finger and thenar muscles. Eight patients with poststroke flexed wrist and fingers were treated by this method. Results: In all patients, the spasticity improved to 0 or 1 from 3 or 4 in Modified Modified Ashworth Scale 1 month after the treatment. They were satisfied with our treatment because they could keep their affected fingers hygienic by washing fingers cleanly after the treatment. Conclusions: Our botulinum A toxin injection points for finger spastic paralysis are accurate spots producing great effect to flexed fingers.

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Context: The amplitude ratio of sural radial sensory nerve action potential is used as a sensitive measure for the diagnosis of an early distal axonal peripheral neuropathy. There is no age-stratified reference data available. Aim: To establish age-stratified sural radial amplitude ratio (SRAR) reference data in healthy Indian subjects. Study Setting and Design: The study was conducted in the electrodiagnostic laboratory of a tertiary city hospital and is an analytical, prospective, and field trial study. Materials and Methods: A prospective study was conducted on 146 healthy volunteers between 18 and 86 years, stratified into 6 groups, a = 18–30 years, b = 31–40 years, c = 41–50 years, d = 51–60 years, e = 61–70 years, and f = >70 years. Sural: Radial amplitude ratio was calculated. Statistical Methods: Stata 12.1 statistical program was used. Lower limit of SRAR was obtained (mean-2SD of transformed data). ANOVA defined the intergroup variability, and linear regression and Pearson's correlation assessed the statistical significance. Results: The lower limit of normal SRAR, for each age group is as follows: a: 0.30, b: 0.23, c: 0.20, d: 0.17, e: 0.17, and f: 0.08. SRAR of groups a, b, c was significantly different from groups e and f. Similarly, SRAR was significantly different between groups d and f but not between groups d and e or a, b, c, d. Conclusion: This study provides age-stratified reference data for SRAR. There is evidence to suggest that SRAR varies with age; hence, a single value of SRAR should not be used when diagnosing a peripheral neuropathy based on this criterion.

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Movement disorders in childhood comprise a heterogeneous group of conditions that lead to impairment of voluntary movement, abnormal postures, or inserted involuntary movements. Movement disorders in children are frequently caused by metabolic disorders, both inherited and acquired. Many of these respond to vitamin supplementation. Examples include infantile tremor syndrome, biotinidase deficiency, biotin-thiamine-responsive basal ganglia disease, pyruvate dehydrogenase deficiency, aromatic amino acid decarboxylase deficiency, ataxia with vitamin E deficiency, abetalipoproteinemia, cerebral folate deficiency, and cobalamin metabolism defects. Recognition of these disorders by pediatricians and neurologists is imperative as they are easily treated by vitamin supplementation. In this review, we discuss vitamin-responsive movement disorders in children.

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Context: Parkinson's disease (PD) is a neurodegenerative disease characterized by traditional motor features. Non-motor symptoms (NMS) are also seen in PD, which inevitably emerge through the disease progression and are often under-recognized and untargeted. Aims: We studied the prevalence of NMS in PD and their impact on health-related quality of life (HRQoL). Materials and Methods: A cross-sectional observational study from January 2017 to July 2017 of PD patients (n = 100) was done. NMS and HRQoL are measured using NMS scoring scale; PD questionnaire-39 and Hoehn and Yahr scale, respectively. Motor symptoms were assessed using scales for outcome in Parkinson's disease (SCoPA) - motor scoring scale. Statistical Analysis: Descriptive statistics calculated for NMS' prevalence. Continuous variables were assessed by two-tailed t-test and discrete and categorical variables by chi-square test. Multiple linear regression analysis was done among scoring scales to identify the influence on 39-item Parkinson's disease questionnaire (PDQ-39) scoring scale. All statistical data collected are analyzed with SSPS software version- 20 for windows. Results: In 100 study population, 66 were males and 34 females. The mean age was 68.35 years and median onset of duration of PD was 3.49 with 64.6% on treatment. Fatigue, pain, and lightheadedness were more prevalent NMS with 78%, 75%, and 69%, respectively. With regression analysis, strongest predictor was NMSS score (P = 0.000), with each unit increase, it is associated with nearly 0.65 increase in PDQ-39 score. Conclusion: Though motor symptoms define the disease, NMS have a larger impact on HRQoL in PD and on caregiver's life. Understanding the pattern and effect of NMS is needed for targeted treatment strategies.

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Objective: The objective of the study is to establish normative values of cortical evoked response audiometry (CERA) in a heterogeneous Indian population and correlate CERA threshold with pure tone audiometric (PTA) threshold values. Materials and Methods: A prospective study was carried out on 31 volunteers (n = 62) who had no otological or neurological complaints. Two study groups were formed; Group 1 with individuals from 20 to 40 years (mean age of 29.1 years) and Group 2 with individuals from 41 to 60 years (mean age of 46.2 years). The latencies and amplitudes of the waves of P1, N1, and P2 at threshold and 70 dBnHL were measured. Results: Twenty-nine participants (94% of the ears) had CERA threshold within 20 dB of true behavioral threshold with only 6% having a difference of >20 dB with their PTA thresholds. There was a significant difference (P < 0.05) at 70 dB in amplitudes for waves P1, N1, and P2 at 2 kHz and additionally at 1 kHz for N1 between the two groups. Conclusion: Normative values for CERA in a heterogeneous Indian population at 70 dB nHL using tone burst stimulus was found to have an average latency of 46.5, 90.1, and 155.5 ms for P1, N1, and P2, respectively. The average amplitude of P1 at 70 dB nHL was 4.3 μV, N1, was 6.5 μV and P2 was 3.2 μV. Hearing threshold obtained with CERA gave a good indication of the actual behavioral hearing threshold of the normal controls, and the age of an individual had a significant effect on the values obtained during CERA testing with N1 being significantly larger at 1 kHz and 2 kHz in older adults when compared to young adults.

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Background and Aims: Intracranial atherosclerotic disease (ICAD) is common in the Asian population, but less studied in South Asians compared to East Asians. We compared risk factors, treatments, and outcomes among consecutive patients with symptomatic ICAD from India with a mixed-ethnic cohort from Chicago, Illinois. Methods: Consecutive patients with symptomatic ICAD were enrolled at 2 academic medical centers in Kerala, India and Chicago, United States. Data on demographics, risk factors, initial stroke severity (National Institute of Health Stroke Scale score [NIHSS]), recurrent stroke, and 3-month functional outcome (modified Rankin Scale [mRS]) were prospectively collected. Recurrent stroke was defined as symptomatic recurrence of focal neurologic deficits associated with radiographic evidence of new cerebral infarction within 3 months of index admission. Results: 329 patients (117 from Kerala, 212 from Chicago) were included. Indian patients were younger (61 vs. 68, P < 0.001), less frequently had prior stroke history (15.4 vs. 32.5%, P = 0.001) and coronary artery disease (11.1 vs. 22.2%, P = 0.013) but had higher initial NIHSS score (median 6 vs. 3, P < 0.001). Both groups received reperfusion therapy in similar proportions (8.5 vs. 7.1%, P = 0.630) but at discharge, 90.6% of Indian patients compared to 59.0% of Chicago patients were treated with dual antiplatelet therapy. More recurrent strokes occurred in Chicago patients (21.7 vs. 1.9%, P < 0.001) but functional outcome did not differ significantly. Conclusion: Compared to patients in US with symptomatic ICAD, Indian patients were younger and had more severe strokes. However, Indian patients had lower rates of recurrent stroke, perhaps due to greater use of dual antiplatelet therapy.

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Guanidinoacetate methyltransferase (GAMT) deficiency is the second most common defect in the creatine metabolism pathway resulting in cerebral creatine deficiency syndrome (CCDS). We report three patients from two unrelated families, diagnosed with GAMT deficiency on next-generation sequencing. All the probands had happy predisposition as a predominant manifestation in addition to the reported features of global developmental delay, seizures, and microcephaly. This further expands the phenotype of CCDS. The workup for creatine deficiency disorder should be included in the diagnostic algorithm for children with nonsyndromic intellectual disability, especially in those with a happy demeanor. These cases exemplify the utility of magnetic resonance spectroscopy of the brain in the workup of nonsyndromic intellectual disability to diagnose a potentially treatable disorder. In addition, documentation of low serum creatinine may be supportive. Early diagnosis and treatment is essential for better prognosis.

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Background and Aims: Brain abscess is a serious and dreadful disease presenting at tertiary centre. The objective of this study was to look into the clinical profile, predisposing conditions, microbiology and outcome of children suffering from brain abscess. Methods: 30 children up to 18 years with clinical and imaging evidence of brain abscess were taken for study. Patients were stabilized as per unit protocol. Necessary investigations were carried out. Neuroimaging (CT or MRI) was used to confirm the diagnosis. All parameters (clinical, investigation, outcome) were recorded in predesigned performa. Neurosurgery consultation was sought in patients with multiple abscesses, posterior fossa abscesses, abscess with air-fluid level and causing midline shift. Results: There were 16 males with 13 patients in age group (5-10 years). Mean duration of stay in hospital was 14.8 days. Most common predisposing factor was chronic suppurative otitis media (n-15). Typically, patients presented with fever, headache and seizures. On examination, motor deficits were the most common followed by signs of meningitis. Computerized tomography confirmed the diagnosis in most cases. Temporal lobe (n-11) was the commonest intracranial site for the abscess. Methicillin resistant staphylococcus and proteus mirabilis were the common pathogen isolated from blood and pus. Blood culture positivity rate was 16.7% and pus culture positivity rate was 25%. All cases were managed with intravenous antibiotics and aspiration (n-10) and excision (n-6). There were 5 deaths. There was complete immediate recovery in 13 cases with residual motor deficit in 12 cases. Conclusion: Brain abscess is a rare but serious entity in children. Late diagnosis and improper management leads to poor outcome. Early surgical intervention is helpful. Threshold for diagnosis should be low in children with chronic ear infection and congenital heart diseases.

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Background: Recent respiratory infection including SARS-CoV-2 is an independent risk factor for acute cerebrovascular disease. Purpose: There have been reports linking haemorrhagic strokes to SARS-CoV-2 infection during this pandemic, which lead us to evaluate if SARS-CoV-2 infection could be associated with increased risk of intracerebral haemorrhage (ICH). Methods: A retrospective observational study evaluating all stroke cases admitted in our centre in the past one month. Results: More than half (56%) had ICH, compared to 22% last year. Two patients with ICH were SARS-CoV-2 positive and they had no or mild respiratory symptoms and had higher occurrence of renal dysfunction. Conclusion: There could be possible association between ICH and SARS-CoV-2 infections. However, a prospective study with larger sample size is needed to elucidate the pathogenesis.

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Introduction: This study aimed to establish whether there is a relationship between the Monocyte to High-Density Lipoprotein Cholesterol (HDL-C) ratio (MHR) and severity of disease, and whether it can be used as a new marker for predicting disability in Multiple Sclerosis (MS), a chronic disease, which is usually contracted in early adolescence. Methods: 184 patient subjects who had been definitively diagnosed with MS, based on the McDonald criteria, and 105 healthy subjects with a similar age and gender profile were included in the study. The patients' Expanded Disability Status Scale (EDSS) scores, MS subtypes, length of time with the disease and demographics were captured. Blood samples were collected for hematologic and biochemical testing. The MHR values were calculated and statistically compared with those of the control group. Results: The average age of the MS patients was 38.3 ± 8.6 years and their average EDSS score was 2.5 [0-7.5]. The patient arm consisted of 118 (64.1%) females and 66 (35.9%) males. In the patients with MS, the MHR was 15.01 ± 0.63 compared to 9.61 ± 0.25 in the controls. This difference was statistically significant (P < 0.001). In the MS patients, the MHR cut-off value was 12.95 compared to controls, which was statistically significant (P < 0.001). Also, a statistically-significant (r: 0.297, P < 0.001) positive correlation was found between the MHR and EDSS score. Conclusion: The Monocyte to High-Density Lipoprotein Cholesterol ratio is associated with disease severity and disability in MS patients, and may be used as an independent marker for predicting disability. However, broader-scale studies are needed for more conclusive results.

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The interpretation of the results of clinical trials should be done by examining the finer prints of extraneous factors such as stopping rules, interim analysis, intricacies of patient selection, and the rationale of decisions that lead to non-prespecified termination. This can be done only by critical education in the art and science of interpretation of evidence emerging from clinical trials. The pioneering pivotal studies, namely, NINDS rtPA and ECASS III trials, hold disproportionate influence in determining the contours of the subsequent fate of clinical trials and treatment guidelines. It needs to be recognized that the pooling of studies using dissimilar trial designs, notwithstanding similar patient profiles, would undermine the positive signal emerging from the studies that have used better selection methodologies to homogenize the study population.

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Background and Aims: Palliative care is an important area of intervention in neurodegenerative diseases. The aim of this study is to understand the relationship between Palliative Care Needs and Caregiver Burden among persons diagnosed with neurodegenerative diseases. Methods: A cross-sectional study design was adopted to explore the research problem. A prospective sample of 120 participants (60 Patient Caregiver dyads) of Motor Neurone Disease (MND) and Parkinson's disease (PD) were recruited for the study based on inclusion and exclusion criteria from a quaternary referral care centre for neurology in south India. Patients seeking care were recruited for the study consecutively. Palliative care outcome scale and Zarit Burden Interview scale were administered to understand the relationship. Results: It was found that Palliative care outcomes score was positively correlated with caregiver burden (r = 0.597), showing that there is a bi-directional relationship between palliative care needs and caregiver burden. Conclusion: Irrespective of the differences in illness characteristics, the study found that palliative care needs are high among chronic neurological conditions which requires a noncategorical psychosocial approach in ensuring care.

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Thyroid storm (TS) is a rare hyperthyroidism associated multisystem decompensation and can mimic a systemic inflammatory response syndrome. It is diagnosed in the presence of fever with cardiovascular, central nervous system, and gastrointestinal complications. Only a few reports of acute flaccid quadriplegic thyrotoxic myopathy (TM) with TS have been reported. However, muscle magnetic resonance imaging (MRI) findings in TM have not been yet been reported. Our patient underwent muscle MRI and showed some unusual features. These are discussed in this article.

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Background: Multiple system atrophy is an adult-onset, sporadic, neurodegenerative disorder with parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes. Objective: We aimed to elucidate differences in prognostic factors between MSA subtypes. Methods: The study population comprised 45 probable MSA patients (MSA-P = 22; MSA-C = 23) and 45 healthy controls. Clinical parameters, heart rate variability (HRV), and conventional cardiac autonomic function testing (AFT) were the study tools. Results: Mean age of onset of MSA was 54.7 ± 9 years for MSA-P and 51.9 ± 7 years for MSA-C subgroups. Median disease duration was 2 years in both subgroups. A greater percentage of MSA-P patients (45.5%) had beneficial response to levodopa (P < 0.01). Patients in both subgroups reported significant autonomic disturbances, such as postural symptoms, bladder disturbances, and erectile dysfunction. MSA-P patients had a trend for a greater number of falls and bladder disturbances than MSA-C patients (P = 0.05). Cardiac AFT showed that in MSA-P, 22.2% had definitive and 77.7% had severe autonomic dysfunction, whereas in MSA-C, 9.5% had early, 28.5% had definitive, and 57.1% had severe autonomic dysfunction. HRV analysis showed significant reduction in overall HRV, sympathetic activity, and parasympathetic activity in MSA patients as compared with controls (P < 0.0001). The sympathetic limb was more severely affected in MSA-P patients as compared with MSA-C patients (P < 0.05). Conclusion: Autonomic dysfunction and postural instability, negative prognostic markers, were relatively more common in the MSA-P than in the MSA-C patients. This implies that MSA-P patients have poorer prognosis as compared with MSA-C. Dopaminergic medications can be beneficial in MSA-P patients.

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L-2 Hydroxyglutaric aciduria is a rare metabolic disorder which is autosomal recessive in inheritance. It is characterised by the increased urinary excretion of L-2 hydroxyglutaric acid and the diagnosis is based on the increased levels of the L-2 hydroxy glutaric acid in the urine, serum & CSF. This is a neurometabolic disorder which is associated with slowly progressive psychomotor delay since childhood. We report a case of an 18 –year old female who presented at the emergency department with seizures, fever and on imaging show classic features.

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Objective: To study the effect of dual tasking and deep brain stimulation frequency parameters on gait in advanced Parkinson's disease Materials and Methods: This is an open label interventional study evaluating 40 post STN-DBS patients with gait disturbances. All patients were diagnosed as PD by a movement disorder specialist using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria. Patients underwent bilateral subthalamic deep brain stimulation by a qualified neurosurgeon. Patients were managed on a combination of dopamine replacement therapy as well as deep brain stimulation. Patients were assessed by stand walk sit (SWS) test for a 5 meter distance and FOG scoring during medication 'ON' state and device “ON” state, at four frequencies 180, 130, 90, 60 HZ and device “OFF” state. Results: Out of 40 patients, 38 patients showed a significant improvement in gait at a single frequency (best response frequency) which is different for each patient. The mean FOG score showed significant improvement at all stimulation frequencies when compared to OFF stimulation (P < 0.05). The mean number of steps was 18.9 at best response frequency and 21.48 at 130 Hz (P < 0.0001). Number of freezing episodes also were significantly less with best frequency when compared to 130 Hz stimulation (0.28 and 0.65 respectively, (P < 0.0001). The mean FOG score was 6.45 at best frequency and 9.48 at 130 Hz (P < 0.0001). Mean Dual tasking score was 3.53 at best frequency and 5.15 at 130 Hz (P < 0.0002). Conclusion: Optimization of frequency setting for each patient can improve gait and that each patient may have a different optimal frequency.

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