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1.  More on epilepsy before I sign off! 
PMCID: PMC3271457  PMID: 22346007
2.  Living longer living happier: My journey from clinical neurology to complexities of brain 
The present article is a treatise on the illuminating voyage of a Neurophysician along the fascinating horizons and frontiers of neurosciences. During the career as a clinical neurologist, some very interesting and intriguing cases and issues were dealt with and documented scientifically. The working of the brain and its operational architectonics came up for critical analysis, opening up new vistas in the appreciation and management of various neurological disorders. Issues regarding the working of the mind and the guidelines for health and happiness became apparent, and some very interesting generalizations with far-reaching consequences on the general well-being and health have been formulated and put forward for a healthy and happy future for mankind. A paradigm shift is warranted for a closer and better appreciation of neural dynamics at all levels of the brain, namely microscopic, mesoscopic and macroscopic levels!
PMCID: PMC3271458  PMID: 22346008
Happiness; Brain-Mind-Body; Longevity
3.  Altered RNA metabolism and amyotrophic lateral sclerosis 
Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. Typically, patients with ALS develop progressive weakness resulting, eventually, in respiratory muscle paralysis and death in 3-5 years after the onset of the disease. No definite therapy currently exists for ALS. The biologic basis of the disease is unknown. However, ALS research has taken a dramatic turn over the last 3 years. Landmark discoveries of mutations in the transactive response DNA-binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) as causative of ALS and demonstration that abnormal aggregation of these proteins is the proximate cause of motor neuron loss in familial and sporadic ALS have initiated a paradigm shift in understanding the pathogenic mechanism of this disease. TDP-43 and FUS/TLS are DNA/RNA-binding proteins with striking structural and functional similarities. This article reviews the current direction of research efforts toward understanding the role of RNA (ribonucleic acid) processing regulation in ALS and possible therapeutic pathways in this fatal disease.
PMCID: PMC3271459  PMID: 22346009
Amyotrophic lateral sclerosis; fused in sarcoma/translocated in liposarcoma; RNA metabolism; TDP-43
4.  Repetitive transcranial magnetic stimulation in psychiatry 
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and relatively painless tool that has been used to study various cognitive functions as well as to understand the brain–behavior relationship in normal individuals as well as in those with various neuropsychiatric disorders. It has also been used as a therapeutic tool in various neuropsychiatric disorders because of its ability to specifically modulate distinct brain areas. Studies have shown that repeated stimulation at low frequency produces long-lasting inhibition, which is called as long-term depression, whereas repeated high-frequency stimulation can produce excitation through long-term potentiation. This paper reviews the current status of rTMS as an investigative and therapeutic modality in various neuropsychiatric disorders. It has been used to study the cortical and subcortical functions, neural plasticity and brain mapping in normal individuals and in various neuropsychiatric disorders. rTMS has been most promising in the treatment of depression, with an overall milder adverse effect profile compared with electroconvulsive therapy. In other neuropsychiatric disorders such as schizophrenia, mania, epilepsy and substance abuse, it has been found to be useful, although further studies are required to establish therapeutic efficacy. It appears to be ineffective in the treatment of obsessive compulsive disorder. There is a paucity of studies of efficacy and safety of rTMS in pediatric and geriatric population. Although it appears safe, further research is required to optimize its efficacy and reduce the side-effects. Magnetic seizure therapy, which involves producing seizures akin to electroconvulsive therapy, appears to be of comparable efficacy in the treatment of depression with less cognitive adverse effects.
PMCID: PMC3271460  PMID: 22346010
Long-term potentiation; long-term depression; neuropsychiatry; repetitive transcranial magnetic stimulation
5.  Patient's Invoice 
PMCID: PMC3271461  PMID: 22346011
6.  Correlates of parental stress and psychopathology in pediatric epilepsy 
Chronic conditions like epilepsy in a child can affect his/her entire family. The failure of the family members to adapt adequately to the unique demands of this childhood chronic illness can be considered as an important risk factor for development of psychopathology.
The objectives of this study were to study the profile of parenting stress in parents of children with epilepsy and its correlates; and, to examine the correlates of psychopathology in these children.
Material and Methods:
Twenty three epileptic children and their families were subjected to Parenting Stress Index (PSI), Scores for indices such as The Children's Depression Inventory (CDI), Benton Visual Retention test, Spence anxiety scale for children, The Child Behavior Checklist (CBCL) and Wechsler Intelligence Scale for Children were calculated.
Mean verbal and performance IQ score was 94, while the mean total IQ score was 95. Mean scores for all Wechsler IQ Scores as well as Benton Visual retention test were within the average range. Means for total internalizing CBCL t scores (M, Mean=70; Standard Deviation, SD=4.4), total externalizing CBCL t scores (M=60, SD=9.6), and total behavior problems CBCL t scores (M=67, SD=5.2) were above the standard cut off levels of 65 for clinical behavioral problems. Mean score on CDI was 42 ± 2. Scores of the PSI equal to or higher than 85th percentile were considered pathologically high.
The results of our study indicated that pediatric patients with epilepsy, specifically with intractable cases, are correlated with high levels of parental stress.
PMCID: PMC3271462  PMID: 22346012
Epilepsy; parental stress; pediatric; psychopathology
7.  Translation and validation of International Restless Leg Syndrome Study Group rating scale in Hindi language 
The objective of this study is to translate and validate the International Restless Leg Syndrome Study Group rating scale (IRLS) in Hindi language.
Materials and Methods:
Thirty one consecutive patients diagnosed of Restless Leg Syndrome (RLS) were included in the study. Control group comprised of 31 subjects not having any symptom of RLS. The scale was procured from MAPI research trust; and, permission for the translation was sought. The translation was done according to the guidelines provided by the publisher. After translation, final version of the scale was applied in both the groups to find out the reliability and clinical validity.
RLS group had a predominance of females, and they were younger than the male counterparts (Age=36.80 ± 10.46 years vs 45.18 ± 8.34 years; t=2.28; P=0.03). There was no difference in the mean age between groups (RLS=39.77 ± 10.44 years vs Non RLS=38.29 ± 11.29 years; t=-0.53; P=0.59). IRLS scores were significantly different between both groups on all items (P<0.001). Translated version showed high reliability (Cronbach's alpha=0.86). IRLS scores were significantly different between both groups on all items (P<0.001).
Hindi version of IRLS is reliable and a clinically valid tool that can be applied in Hindi speaking population.
PMCID: PMC3271463  PMID: 22346013
Hindi translation; International Restless Leg Syndrome Study Group rating scale; Restless Leg Syndrome; translation; validation
8.  Mortality in mechanically ventilated patients of Guillain Barré Syndrome 
The mortality of patients with Guillain Barré syndrome (GBS) has varied widely with rates between 1-18%. Death results from pneumonia, sepsis, adult respiratory distress syndrome (ARDS) and less frequently due to autonomic dysfunction or pulmonary embolism. There are only few studies which have used a large sample and have in detail analyzed the circumstances relating to death and the prognostic factors for the same in a cohort, including only mechanically ventilated patients.
The objective of our study was to analyze the circumstances and factors related to mortality in mechanically ventilated patients of GBS.
Materials and Methods:
Case records of patients of GBS, satisfying National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria, and requiring mechanical ventilation from 1984 to 2007, were analyzed.
A total of 273 GBS patients were managed with ventilatory support (190 men and 83 women) during the period. Besides symmetrical paralysis in all patients, bulbar palsy was present in 186 (68.1%), sensory involvement in 88 (32.2%) and symptomatic autonomic dysfunction in 72 (26.4%) patients. The mortality was 12.1%. The factors determining mortality were elderly age group (P=0.03), autonomic dysfunction (P=0.03), pulmonary complications (P=0.001), hypokalemia (P=0.001) and bleeding (P=0.001) from any site. Logistic regression analysis showed the risk of mortality was 4.69 times more when pneumonia was present, 2.44 times more when hypokalemia was present, and 3.14 times more when dysautonomia was present. The odds ratio for age was 0.97 indicating that a higher age was associated with a higher risk of mortality.
Ventilator associated pulmonary complications, bleeding and hypokalemia especially in elderly patients require optimal surveillance and aggressive therapy at the earliest for reducing the mortality in this group of GBS patients.
PMCID: PMC3271464  PMID: 22346014
Guillain Barré syndrome; intensive care; mechanical ventilation; mortality
9.  Factors predicting surgical outcome of thymectomy in myasthenia gravis: A 16-year experience 
To assess the surgical outcome of myasthenia gravis (MG) following thymectomy and to determine the outcome predictors to such therapeutic approach.
Materials and Methods:
This study is a retrospective review of 80 consecutive thymectomies performed for MG over a 16-year period.
There were 41 females and 39 males (mean age, 34.32 years) with mean disease duration of 17.45 months prior to surgery. Stagewise distribution of the patients revealed 2.5% in stage I, 48.7% in stage IIA, 33.8% in stage IIB, 8.7% in stage III, and 6.3% in stage IV. The surgical approach was either trans-sternal (n=67) or video-assisted thoracoscopic route (n=13). Follow-up was obtained in 91.2% (n=73) of patients with mean duration of 67.7 months. At their last follow-up, 26.0% were in complete remission, 35.6% were asymptomatic on decreased medications, and 17.8% had clinical improvement on decreased medications. Overall, 79.4% of patients benefited from surgery, 8.2% had unchanged disease status, and 12.3% worsened clinically. Factors influencing favorable outcome include sex, disease stage, gland weight, and preoperative medication with anti-cholinesterase (P<0.05). There was one death in the perioperative period due to septicemia. Two patients died at fourth and seventh month following thymectomy.
Thymectomy for MG is safe and effective. Certain influencing factors may shape treatment decisions and target higher risk patients.
PMCID: PMC3271465  PMID: 22346015
Myasthenia gravis; thymectomy; video-assisted thymectomy
10.  Neurological complications of dengue fever: Experience from a tertiary center of north India 
Dengue, an acute viral disease transmitted by Aedes mosquitoes, is highly endemic in many tropical and subtropical areas of the world. Neurological complications of dengue infection have been observed more frequently in the recent past and some studies highlighted varied neurological complications arising in the course of dengue illness. In this retrospective study, we report various neurological complications observed during the last 2 years in patients of dengue fever.
Materials and Methods:
The patients presenting with neurological complications with positive serology (IgM antibody) for dengue infection were consecutively recruited from the Department of Neurology/Medicine from a tertiary center of Lucknow, India. These patients were subjected to a detailed clinical evaluation, laboratory assessment including blood count, hematocrit, coagulation parameters, biochemical assays, serology for dengue fever, enzyme-linked immunosorbent assay for human immunodeficiency virus and other relevant investigations.
Twenty-six patients with neurological complications associated with confirmed dengue infection were observed during the last 2 years. Eighteen of these patients were male. Of the 26 patients, 10 patients were suffering from brachial neuritis, four patients had encephalopathy, three patients were consistent with the diagnosis of Guillain Barre syndrome, three patients had hypokalemic paralysis associated with dengue fever and two patients had acute viral myositis. Opsoclonus-myoclonus syndrome was diagnosed in two patients, myelitis in one patient and acute disseminated encephalo-myelitis also in one patient.
Dengue fever was associated with widespread neurological complications. Brachial neuritis and opsoclonus-myoclonus syndrome were observed for the first time in this study.
PMCID: PMC3271466  PMID: 22346016
Brachial neuritis; dengue fever; hypokalemic paralysis; myositis; neurological complications
11.  Quality of life in children with epilepsy 
Epilepsy is a chronic medical condition with many co-morbid features. It has been observed that children with epilepsy (CWE) have a compromised quality of life (QOL).
To assess the QOL in CWE and to study the various factors affecting QOL among CWE.
Materials and Methods:
The sample consisted of 102 CWE aged 5–15 years of either sex. QOL was measured by Quality of Life in Childhood Epilepsy (QOLCE) questionnaire, a 76-item, parent-reported questionnaire. Cronbach alpha was used to determine the internal consistency of the subscales and Pearson correlation to determine construct validity. The t-test and analysis of variance were used to compare mean QOLCE scores.
Factors affecting QOL included age, place of residence, socioeconomic condition, maternal education, seizure type and frequency and number of antiepileptic drugs.
CWE have a relatively compromised QOL and comprehensive care needs to go beyond the attempt of controlling seizures.
PMCID: PMC3271467  PMID: 22346017
Children with epilepsy; health related quality of life; quality of life in childhood epilepsy questionnaire; quality of life
12.  Risk factors of childhood epilepsy in Kerala 
We aimed to identify the risk factors for epilepsy in children.
Materials and Methods:
This case–control retrospective study was carried out in the pediatric neurology outpatient service of the Trivandrum Medical College. All children (1–12 years) with epilepsy satisfying the selection criteria were included, after obtaining consent from parents. Those with single seizures or febrile seizures were excluded. Controls were children without epilepsy attending the same hospital. Parents were interviewed and clinical data were obtained from medical records. Statistical analysis included chi-square test, odds ratio (OR), and logistic regression.
There were 82 cases and 160 controls whose mean age was 6.9 + 3.6 and 5.2 + 3.1, years respectively. On univariate analysis, family history of epilepsy, prolonged labor, cyanosis at birth, delayed cry after birth, admission to newborn intensive care unit, presence of congenital malformations, neurocutaneous markers, incessant cry in the first week, delayed developmental milestones, meningitis, encephalitis, and head trauma were found to be significant. On logistic regression, family history of epilepsy (OR 4.7), newborn distress (OR 8.6), delayed developmental milestones (OR 12.6), and head trauma (OR 5.8) were found to be significant predictors. Infants who had history of newborn distress are likely to manifest epilepsy before 1 year if they are eventually going to have epilepsy (OR 3.4).
Modifiable factors such as newborn distress and significant head trauma are significant risk factors for childhood epilepsy. Newborn distress is a risk factor for early-onset (<1 year age) epilepsy.
PMCID: PMC3271468  PMID: 22346018
Epilepsy; Kerala; risk factor
13.  Design, data analysis and sampling techniques for clinical research 
Statistical analysis is an essential technique that enables a medical research practitioner to draw meaningful inference from their data analysis. Improper application of study design and data analysis may render insufficient and improper results and conclusion. Converting a medical problem into a statistical hypothesis with appropriate methodological and logical design and then back-translating the statistical results into relevant medical knowledge is a real challenge. This article explains various sampling methods that can be appropriately used in medical research with different scenarios and challenges.
PMCID: PMC3271469  PMID: 22346019
Design; study; sampling
14.  De novo development of artistic creativity in Alzheimer's disease 
The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed.
PMCID: PMC3271470  PMID: 22346020
Alzheimer's disease; artistic creativity; fronto-temporal dementia
15.  Atypical clinical and imaging manifestation in neurocysticercosis 
A 20-year-old man presented with left-sided headache and seizures of three years duration. Conglomerate ring-enhancing lesions were seen in the first magnetic resonance imaging study. He was initially treated with anticonvulsants for two years. Because the symptoms and the lesions were persisting, antitubercular treatment was added. He was asymptomatic after antitubercular treatment despite persisting lesion. Lesion showed exuberant ring enhancement with increased perfusion. Because the lesion was persisting even after 24 months of antitubercular treatment, excision was considered. Lesionectomy was done and histopathology reported meningoencephalitis secondary to neurocysticercosis. The case report highlights the difficulty in differentiating cysticercosis from tuberculoma in patients from countries where both the conditions are endemic.
PMCID: PMC3271471  PMID: 22346021
Chronic meningoencephalitis; magnetic resonance imaging; neurocysticercosis; perfusion magnetic resonance imaging
16.  Cortical blindness after contrast-enhanced CT scan in a patient of sarcoidosis – Is it related to posterior reversible encephalopathy syndrome? 
Transient cortical blindness (TCB) is a well known but rare complication of administration of contrast agent. In this case report, we present a 53-year-old woman who is a follow-up case of sarcoidosis and developed TCB with focal neurological symptoms following contrast-enhanced computed tomography scan. Magnetic resonance imaging revealed bilateral T2/Flair hyperintensities in parieto-occipital, high frontal, and cerebellar hemispheres with involvement of corpus callosum. Clinically and radiologically patient improved significantly in 4 days. The exact mechanism is still speculative and its possible relationship with posterior reversible encephalopathy syndrome is briefly discussed. The patient's symptoms were presumed to be exacerbated by presence of hypertension, underlying autoimmune disorder, sepsis, and high osmolality of contrast agent. Though there is no definite evidence to suggest that a certain treatment regimen improves the natural history of this disease but control of risk factors can possibly prevent this rare but devastating complication.
PMCID: PMC3271472  PMID: 22346022
Sarcoidosis; posterior reversible encephalopathy syndrome; contrast; cortical blindness
17.  Posterior circulation ischemic stroke following Russell's viper envenomation 
Ischemic stroke following viper bite is rare. We report a case of posterior circulation ischemic infarction following viper bite in a previously healthy woman. Soon after being bitten by the snake on the left leg, she developed local redness, echymosis and one hour later became drowsy. On examination she had skew deviation of eyes and down gaze preference, generalized hypotonia. A CT scan of brain showed infarcts in cerebellar hemispheres and occipital lobes on both sides and that was confirmed on magnetic resonance imaging of brain. Her coagulation profile was deranged. Most common and serious central nervous system complication following snake bite is intracranial hemorrhage. Ischemic stroke commonly involves anterior circulation. Bilateral cerebellar and occipital infraction is not yet reported in literature. Exact cause for the development of infarction is not clear. The possible mechanisms of infarction in this scenario are discussed. Patient was treated with anti-snake venom and showed a good recovery. Early imaging and early treatment with anti-snake venom is important for a favorable outcome.
PMCID: PMC3271473  PMID: 22346023
Viper envenomation; ischemic stroke; posterior circulation
18.  An unusual case of Takayasu's arteritis: Evaluation by CT angiography 
Takayasu's arteritis is a chronic, idiopathic, medium and large vessel vasculitis involving aorta and its main branches. Frequent neurological manifestations include postural syncope, seizures, and blindness. Stroke, as presenting feature of Takayasu's arteritis, is unusual. CT angiography reveals characteristic involvement of aortic arch and its branches. Involvement of intracranial vasculature is rather unusual. We are describing an unusual patient of Takayasu's arteritis who presented with recurrent disabling syncopal attacks and had extensive involvement of intracranial vasculature. CT angiography revealed severe involvement of aortic arch. There was near complete occlusion at origins of both subclavian arteries, distal flow was maintained by collateral vessels along the chest wall. There was near total occlusion (at origin) of right common carotid with normal flow in distal part. The left common carotid was more severely involved showing greater than 80% narrowing in proximal half of the vessel. CT angiography also revealed involvement of left internal carotid artery, narrowing of left middle cerebral artery and involvement of cortical vessels. Patient was treated with oral corticosteroids. She improved remarkably after two and half months of follow up.
PMCID: PMC3271474  PMID: 22346024
Takayasu's arteritis; vasculitis; stroke
19.  Moroccan consanguineous family with Becker myotonia and review 
Myotonia congenita is a genetic muscle disorder characterized by clinical and electrical myotonia, muscle hypertrophy, and stiffness. It is inherited as either autosomal-dominant or –recessive, known as Thomsen and Becker diseases, respectively. These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness and pain. Mutations in the muscular voltage-dependent chloride channel gene (CLCN1), located at 7q35, have been found in both types. We report here the case of a Moroccan consanguineous family with a myotonic autosomal-recessive condition in two children. The molecular studies showed that the patients reported here are homozygous for mutation p.Gly482Arg in the CLCN1 gene. The parents were heterozygote carriers for mutation p.Gly482Arg. This diagnosis allowed us to provide an appropriate management to the patients and to make a genetic counselling to their family.
PMCID: PMC3271475  PMID: 22346025
Autosomal recessive; CLCN1gene; myotonia congenital
20.  A case of leukoencephalopathy, cerebral calcifications and cysts 
Triad of leukoencephalopathy, cerebral calcifications and cysts (LCC) is a recently reported rare disease named ‘Labrune syndrome’ after the first case was reported in 1996 by Labrune et al. Herein, we report a case of a 36-year-old man with mild right-sided weakness and seizures for 5 years. CT of brain revealed extensive calcification involving bilateral basal ganglia, right thalamus and bilateral deep cerebellar nuclei. A supratentorial cystic lesion with blood fluid level was seen in left occipitotemporal region. MRI examination revealed diffuse symmetric white matter hyperintensity suggesting leukoencephalopathy. On follow-up, patient reported improvement in the weakness and no further seizure episodes. However, follow-up of MRI revealed persistence of lesions. Differential diagnosis considered were parasitic infections (hydatid, cysticercosis), Coat's plus disease and causes of diffuse cerebral calcification like Fahr's disease and post-radiotherapy/chemotherapy. Serology for parasitic infections was negative. No history of radiotherapy or chemotherapy in the past could be elicited in the history. Another close differential is Coat's plus disease which can mimic LCC pathologically.
PMCID: PMC3271476  PMID: 22346026
Calcification; cerebral cysts; labrune syndrome; leukoencephalopathy; cerebral calcifications and cysts
22.  Paroxysmal dystonic choreoathetosis with symptomatic seizures secondary to hypoglycemia caused by insulinoma 
Neurological syndromes are not an uncommon presentation with insulinomas. Recurrent hypoglycemia associated with it can present with a variety of neurological symptoms that may include disturbances of consciousness, seizures, stroke-like presentation, movement disorder, dementia and chronic neuropathy. The myriad of presentations, resemblance with other neurological conditions and episodic nature often lead to misdiagnosis and a delay in definitive treatment. Rare cases of insulinoma presenting as combination of abnormal movements have been described. We report a patient who presented with both hypoglycemia induced symptomatic seizures and paroxysmal non-kinesiogenic dystonic choreoathetosis. Insulinoma is a potentially treatable disorder and early definitive intervention can prevent long term neurological disability in patients.
PMCID: PMC3271477  PMID: 22346027
Hypoglycemia; insulinoma; movement disorder; seizures
23.  Coexistence of primary sclerosing cholangitis in a patient with myasthenia gravis 
Myasthenia gravis (MG) is an immune-mediated disease that compromises the postsynaptic membrane of the neuromuscular junction. Primary sclerosing cholangitis (PSC) is considered an immune-mediated cholestatic liver disease. Both MG and PSC include an autoimmune pathogenesis, so there is some evidence that patients with MG or PSC have a higher risk of developing autoantibodies and other immune disorders than normal controls, but the coexistence of these two disorders has never been documented. We report a 40-year-old woman who presented with MG when she was 20 years old and developed PSC 20 years after a thymectomy. Liver biochemistry revealed cholestasis. Magnetic resonance imaging showed multifocal strictures and beads involving the intrahepatic bile ducts. A liver biopsy confirmed sclerosing cholangitis. Serological analysis demonstrated positive autoantibodies (Anti-nuclear antibodies, anti-smooth muscle antibodies). Repetitive stimulation had a decremental response, and antibodies to acetylcholine receptors were detectable. To our knowledge, this is the first case of PSC in a patient with MG. The main characteristics of both MG and PSC combination are discussed.
PMCID: PMC3271478  PMID: 22346028
Autoimmune diseases; myasthenia gravis; sclerosing cholangitis; thymectomy
24.  Dementia in Parkinsonism 
Annals of Indian Academy of Neurology  2011;14(Suppl1):S21-S24.
PMCID: PMC3152156  PMID: 21847324
25.  Initiation of treatment in early PD (evidences based) 
Annals of Indian Academy of Neurology  2011;14(Suppl1):S6-S10.
PMCID: PMC3152157  PMID: 21847330

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