Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome.

Isaacs syndrome is a disease characterized by nerve hyperexcitability and pseudomyotonia and treated with immunomodulatory and symptomatic therapy approaches. Here, we report a case of anti-(leucine-rich glioma-inactivated 1) antibody-positive patient diagnosed as Isaacs syndrome and accomplished a nearly complete response to only four sessions of therapeutic plasma exchange (TPE). Our experience suggests that TPE along with other immunomodulatory agents may be beneficial and well-tolerated approach in patient with Isaacs syndrome.

Identification of Taenia solium DNA by PCR in blood and urine samples from a tertiary care center in North India.

BACKGROUND: NCC is a neglected zoonotic disease with high endemicity and disease burden. Neurocysticercosis is a frequent cause of seizures in endemic countries. Early diagnosis and therapy helps in reducing morbidity and DALYs (daily adjusted life years) lost. Definite diagnosis still relies on neuroimaging identification of scolex or by histopathological examination. Molecular method such as PCR (Polymerase Chain Reaction) is an emerging modality to supplement or complement these Gold standard methods. AIM: To determine the utility of PCR in detecting Taenia Solium DNA in NCC patients. METHODS: A total of 100 blood samples of cases of NCC and 50 control blood samples, 58 urine samples of NCC cases and 24 control samples were collected. Repetitive element PTsol9 of the Taenia Solium was targeted. RESULTS: The sensitivity and specificity of PCR in blood samples was 57% and 94%, while sensitivity and specificity in urine samples was 64% and 87%. CONCLUSION: PCR assay can be used as an adjunct for the diagnosis of NCC especially in ambiguous cases, this is relatively rapid and non-invasive diagnostic modality.

Use of rituximab in muscle-specific tyrosine kinase antibody-positive myasthenia gravis: Preliminary observations from a tertiary care center in Northern India.

OBJECTIVES: Approximately 10%-15% of patients with myasthenia gravis (MG) are refractory to standard treatment. A sizable chunk of these patients is due to muscle-specific tyrosine kinase (MuSK) antibody-positive MG which often runs a severe course with frequent relapses and poor response to conventional treatment. We report six patients with refractory MuSK-positive MG who responded well to the treatment with rituximab. PATIENTS AND METHODS: In this prospective institute-based observational study, we report six MuSK antibody-positive MG patients, who did not achieve remission with standard treatment and were later started on rituximab infusion. RESULTS: There was a significant clinical improvement in all patients after starting rituximab. CONCLUSION: Rituximab is an effective immunomodulatory therapy in MuSK antibody-positive MG patients who are not responding to the standard treatment.

Sorting out difficulties in immunological diagnosis of neurocysticercosis: Development and assessment of real time loop mediated isothermal amplification of cysticercal DNA in blood.

PURPOSE OF THE STUDY: Among various immunological tests available for diagnosis of neurocysticercosis (NCC), only EITB (Electroimmunotransfer blot for detection of anticysticercal antibodies) had gained widespread acceptance. However EITB is not available widely and is costly (Indian rupees 15,000/- approximately). We evaluated utility of Loop mediated isothermal amplification (LAMP) assay for detection of Taenia solium cox1 gene in blood of patients with NCC. PATIENTS AND METHODS: Current study included 100 consecutive patients of NCC at a tertiary teaching hospital in Northern India. All the patients underwent detailed history and examinations as well as gadolinium enhanced magnetic resonance imaging of brain. LAMP assay was performed in all the patients. The results were compared with 50 controls. RESULTS: LAMP detected Taenia Solium cox1 gene in 74% of all blood samples in patients of NCC.T he overall sensitivity of LAMP assay for detection of cox1 gene was 74% in all patients with NCC, 71.8% in patients with intraparenchymal brain cysts only and 86.7% of patients with extraparenchymal brain cysts with or without intraparenchymal brain cysts. The overall specificity of LAMP assay was 90% in all these three subgroups. The positive predictive value of real time LAMP assay was close to 93% for almost all forms of NCC- both solitary and multiple while negative predictive value ranged from 57 to 64%. CONCLUSION: Real time LAMP assay of blood for detection of Taenia solium cox1 gene appears to be a promising toll for diagnosis of NCC.

Prevalence of Epilepsy and its Association with Exposure to Toxocara canis: A Community Based, Case-control Study from Rural Northern India.

OBJECTIVES: Many community-based and hospital-based studies across the world have yielded contradictory results regarding association of positive Toxocara canis serology and epilepsy. The present study was planned to analyze disease burden of epilepsy in rural community of North India and its association with exposure to T. canis in this part of the world. METHODS: A door-to-door screening survey was carried out in the rural community using a validated questionnaire for epilepsy by trained field workers, which was finally confirmed by trained neurologists. The risk factors for epilepsy and for predisposing infections were also enquired. The results were compared with an equal number of age- and sex-matched healthy controls enrolled from the same community. Serologic evaluation was carried out to detect antibodies against T. canis. RESULTS: A total of 41,973 persons from the rural community in 49 villages were enrolled in the study. Two hundred and eleven persons were confirmed to be suffering from active epilepsy, resulting in a crude prevalence of 5 per 1000 population. More than 50% of people with epilepsy were in the second or third decade of life. The prevalence of antibodies to T. canis was similar in people with epilepsy (13.7%; 29 of 211 individuals) and controls (9.95%; 21 of 211 individuals). Of the 151 persons with epilepsy, who underwent CT scan, 34 people (22.3%) had evidence of inflammatory granuloma, thereby confirming high incidence of this infestation in rural Northern India. SIGNIFICANCE: Our study does not support the association between epilepsy and exposure to T. canis in rural Northern Indian population.

Hypothalamic and pituitary dysfunction is common in tubercular meningitis: A prospective study from a tertiary care center in Northern India.

INTRODUCTION: Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS: Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS: 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION: Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.

Management of myasthenia gravis during pregnancy.

The management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and fetus. MG often affects women in second and third decades of life during the childbearing age. Exacerbations of MG are likely to occur during the first trimester and postpartum period. The treatment of MG during pregnancy needs to be individualized depending on the severity of MG as well as the efficacy of various treatment modalities and their possible harmful effects on pregnancy. In addition, special attention has to be given to avoid drugs and other factors (such as urinary tract infections) which may worsen MG. The key to successful outcome during pregnancy in myasthenic women lies in multidisciplinary care involving obstetricians, neurologists, anesthetist as well as neonatologist. In this review, we discuss various therapeutic options available for the management of MG during pregnancy and provide recommendations based on the current best evidence.

Progressive myoclonic epilepsy and horizontal gaze palsy: a rare aetiology.

Gaucher's disease is a rare autosomal recessive, potentially fatal disorder but most common type among lysosomal storage disorders. The disease's incidence is around 1/40 000 to 1/60 000 births in the general population. A 32-year-old man, born out of non-consanguineous union, presented with generalised tonic-clonic seizures and myoclonus since 17 years of age. Seizures were noted to be resistant to multiple epileptic drugs. He developed gait imbalance, intentional tremor and dysarthria. Detailed examination revealed hepatosplenomegaly, bilateral pancerebellar signs with normal power, reflexes and sensory system. He had major cognitive impairment with impaired frontal and temporal lobar functions. Bone marrow evaluation revealed Gaucher cells, confirming the diagnosis.

Role of Plasma Clusterin in Alzheimer's Disease-A Pilot Study in a Tertiary Hospital in Northern India.

OBJECTIVE: To evaluate the role of plasma clusterin in Alzheimer's disease (AD). BACKGROUND: Plasma clusterin is a promising biomarker as various studies have shown it to be associated with AD. But other studies have shown that plasma clusterin levels were not related to Alzheimer's disease or presymptomatic AD. Hence the diagnostic value of plasma clusterin is still not conclusive. METHODS: Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD were used for establishing the diagnosis of MCI, AD or Vascular dementia. The CSF control group included patients who were having knee or hip surgery and plasma control group included the spouses of patients. RESULTS: Forty-six patients who gave consent for CSF examination and FDG PET brain were included in the study along with 19 control samples. Alzheimer's group had 34 patients and Vascular group had 12 patients. Both had a significantly lower value of clusterin than the control samples (p<0.01). The median plasma clusterin level was 84.38 µg/ml in control group, 57.98µg/ml in Alzheimer's group and 49.93µg/ml in the vascular group. Alzheimer and Vascular group did not differ in plasma clusterin levels. Moreover there was no correlation of plasma clusterin with AD severity. The sensitivity and specificity of plasma clusterin was low for any significance for clinical use. CONCLUSION: Our pilot study shows that plasma clusterin is lower in Alzheimer's disease with respect to control population. Plasma clusterin levels and severity of Alzheimer's disease had no significant correlation. There was no difference in plasma clusterin between Alzheimer's disease and Vascular Dementia. The sensitivity and specificity of plasma clusterin is low for any use in clinical practice. More studies are required to ascertain the utility of plasma clusterin as a biomarker in Alzheimer's disease.

The Diagnostic Dilemma of Neurolymphomatosis.

Neurolymphomatosis (NL) defined as infiltration of the central nervous system or the peripheral nervous system (PNS) by malignant lymphoma cells is a rare clinical entity. However, the increasing use of fluorodeoxyglucose positron-emission tomography (FDG-PET) and magnetic resonance imaging in evaluating PNS disorders is resulting in; this condition being recognized more frequently. Here; we report five NL patients and review the current literature. We report five patients with non-Hodgkin's lymphoma (NHL) and NL, all of whom were men aged 47-69 years. The clinical presentation varied from symmetrical peripheral neuropathy to mononeuropathy. Peripheral neuropathy was the presenting manifestation of a systemic lymphoma in two patients (40%). Neuroimaging as well as whole-body FDG-PET helped in determining the correct diagnosis in all of the patients. NL is an unusual presentation of NHL resulting from infiltration of the PNS by malignant lymphomatous cells. While evaluating peripheral neuropathy, a high degree of suspicion of NL is required since the presenting symptoms vary, conventional radiology has only modest sensitivity, and a pathological diagnosis is often difficult. FDG-PET helps in the early diagnosis and treatment of this condition.

Which Classification of Cavernous Sinus Syndrome is Better - Ishikawa or Jefferson? A Prospective Study of 73 Patients.

INTRODUCTION: Ishikawa and Jefferson are the two most commonly used systems used for the classification of cavernous sinus syndrome (CSS). However, relative utilities of these two classification systems have not been evaluated in detail in developing countries. In this study, we compared relative utilities of these two classification schemes in the evaluation of CSS. OBJECTIVE: To compare the utility of Jefferson and Ishikawa classifications in the evaluation of CSS. PATIENTS AND METHODS: A total of 73 consecutive patients of CSS were prospectively classified using either Ishikawa or Jefferson classification and relative utility of these two classification schemes in determining etiology of CSS was compared. RESULTS: While only 46.6% of patients could be classified using Jefferson classification, 95.5% of patients could be classified using Ishikawa scheme. CSS was classified as anterior, middle, and posterior in 17.8%, 21.9%, and 8.2% of patients, respectively, as per the Jefferson classification. As per the Ishikawa classification, 37% of patients each showed anterior and posterior CSS, 16.4% showed middle CSS, whereas 4.1% had whole CSS. Middle CSS was significantly associated with the presence of fungal infections (P = 0.045) as per Jefferson classifications, and anterior CSS was significantly associated with a vascular etiology (P = 0.005) as per Ishikawa classification. Overall, inflammatory causes were the most common cause for anterior CSS, while tumors accounted for maximum cases of posterior CSS. CONCLUSION: Although more number of patients could be classified using Ishikawa classification, there was no advantage of Ishikawa classification over Jefferson with regard to determination of etiology of CSS.