A Study on Evaluation of Motor, Cognitive and Behavioral Manifestations of Basal Ganglia Infarcts.

Isolated basal ganglia infarcts are rare. Basal ganglia infarcts are often associated with infarcts in other structures like cerebral cortex, thalamus and fronto parietal white matter. Clinical consequences of basal ganglia infarcts are often masked by infarcts in other areas. When basal ganglia infarct extends into the adjacent internal capsule, more concern and priority will be given to the hemiplegia and associated behavioral and cognitive features may be overlooked. Several studies have been conducted to analyze the clinical consequences of isolated basal ganglionic infarcts. Most of the studies were conducted in several countries outside India. So, we decided to analyze the clinical consequences of isolated basal ganglia infarcts in our patient population. Normal functions of many neurological structures were identified by the consequences of destruction of these structures. The pathologies that damage the human brain are rarely restricted to single anatomical structures. Stroke, trauma and tumour do not respect functional anatomical boundaries. Modern imaging techniques such as CT and MRI have dramatically improved the demonstration of the extent of brain damage caused by many pathologies. Of course, such techniques do not establish the full extent of anatomical pathology, and even more importantly do not show the distant functional effects (diaschisis) of such lesions. Motor, cognitive and behavioral consequences of basal ganglia infarcts are more common than expected. The current concepts of basal ganglia organization and physiology do not fully explain the disorders observed in man when the striatum and globus pallidus are damaged by crude pathology like infarction. In our study, dystonia was the most common movement disorder observed in patients with basal ganglionic infarcts, followed by chorea. Mild to moderate depression and apathy is very common in basal ganglionic infarcts; it should be identified and treated effectively to improve the quality of life. Reduced attention span, impaired verbal memory recall and executive dysfunction was the common cognitive impairments identifies which signifies the important role of frontal basal ganglionic subcortical circuitry in higher cognition like executive function and basic cognition like attention and memory. Patients with caudate infarcts developed more of behavioral and cognitive abnormalities like apathy and executive dysfunction than movement disorders except chorea. Patients with infarcts in the lentiform nucleus developed movement disorders frequently; behavioral disorders were rare in these patients. While infarcts in the basal ganglia are producing behavioral and movement disorders, many more cases with basal ganglia infarcts are encountered in which similar lesions have no such effects. The reasons for such discrepancies are unknown, but challenge simplistic concepts of basal ganglia motor physiology

An interesting case of Leigh-like syndrome

A 12-year-old female child with motor developmental delay presented with persistent vomiting, recurrent falls and unsteadiness in dark since 2 years of age. There was decline in scholastic performance, bulbar symptoms and aggravation of symptoms during intercurrent illness. Clinically, she had frontal and parietal lobar dysfunction, dysarthria, optic atrophy and LMN VII, IX, X, XII cranial nerve involvement. There was generalized hypotonia, distal muscle wasting, weakness, cerebellar signs and impaired vibration/position sense in distal extremities. Biochemical investigations revealed elevated serum/cerebrospinal fluid (CSF) lactate and CSF lactate pyruvate ratio. Neuroimaging demonstrated bilateral symmetrical T2 hyperintensities in basal ganglia, subcortical white matter, cerebellar hemispheres and posterior aspect of spinal cord. As certain atypical features like bilateral symmetrical T2 hyperintensities in subcortical white matter were also seen, metachromatic leukodystrophy was considered in differential diagnosis but ruled out by nerve biopsy. This case is reported for the presence of atypical neuroimaging features that are rarely found in Leigh′s disease

Tenofovir induced Fanconi syndrome: A rare cause of hypokalemic paralysis

We report a 55-year-old female who presented to the emergency department with acute onset quadriparesis. She was diagnosed to have acquired immunodeficiency syndrome 7 years ago and was on tenofovir based anti-retroviral therapy for past 10 months. As the patient also had hypophosphatemia, glucosuria and proteinuria Fanconi syndrome (FS) was suspected. She improved dramatically over next 12 h to regain normal power and also her renal functions improved over next few days. Tenofovir induced FS presenting as hypokalemic paralysis is very rare complication and is the first case reported from India

Mercury toxicity following unauthorized siddha medicine intake – A mimicker of acquired neuromyotonia - Report of 32 cases

Context: Mercury is used extensively in the preparation of Siddha medicines, after purification. In this study, we present 32 patients of mercury toxicity following unauthorized Siddha medicine intake who mimicked neuromyotonia clinically. We analyzed the clinical features of these patients, the role of autoimmunity in etiopathology, and compared it with acquired neuromyotonia. Subjects and Methods: This is a retrospective study to analyze inpatients in a tertiary care center, admitted with mercury toxicity following Siddha medicine intake from August 2012 to October 2016. We analyzed the clinical features, laboratory data including mercury, arsenic and lead levels in blood, and serum voltage-gated potassium channels (VGKC)-CASPR2 Ab in selected patients. Results: Thirty-two patients who had high blood mercury levels following Siddha medicine intake were included in the study. All patients (100%) had severe intractable neuropathic pain predominantly involving lower limbs. Twenty-six (81.25%) patients had fasciculations and myokymia. Fifteen patients (46.86%) had autonomic dysfunction (postural hypotension and resting tachycardia). Nine (28.12%) patients had encephalopathic features such as dullness, apathy, drowsiness, or delirium. Anti-VGKC Ab was positive in 12 patients with myokymia. All the patients in the study consumed Siddha medicines obtained from unauthorized dealers. Conclusions: Mercury toxicity following Siddha medicine intake closely mimics acquired neuromyotonia; severe intolerable neuropathic pain is the hallmark feature; Positive VGKC-CASPR2 antibody in some patients must be due to triggered autoimmunity secondary to mercury toxicity due to Siddha medicine intake. The government should establish licensing system to prevent distribution of unauthorized Siddha medicines

Hepatotoxicity and Liver-Related Mortality in Women of Childbearing Potential Living With Human Immunodeficiency Virus and High CD4 Cell Counts Initiating Efavirenz-Containing Regimens.

BackgroundSevere hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens.MethodsIn the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation.ResultsAmong 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70]).ConclusionsSevere hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age

A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area. </p

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

BackgroundRandomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.MethodsWe randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety.ResultsThe median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P&gt;0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P&lt;0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P&lt;0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART.ConclusionsAntenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .)