Autonomic Function Tests, Heart Rate Variability, and Electrophysiological Evaluation in Patients With a Primary Episodic Headache: An Observational Study.

PURPOSE: Cranial autonomic symptoms are typically associated with the trigeminal autonomic cephalalgias and also present in substantial cases of migraine. Autonomic nervous system dysfunctions are also been reported in headache disorders and postulated to promote headache attacks. This study was aimed to evaluate the parasympathetic and sympathetic autonomic functions tests in patients with a episodic primary headache and to investigate, if any, electrophysiological abnormalities in the blink reflex test and sympathetic skin response test in these patients. METHODS: In this cross-sectional study, a total of 100 patients, 50 patients each of migraine and tension-type headache attending the neurology OPD and fulfilling the diagnostic criteria of headache disorders were enrolled. Autonomic functions tests were performed in the Department of Physiology, whereas electrophysiological tests were powered by the Editorial Manager and ProduXion Manager from Aries Systems Corporation performed in the Department of Neurology. RESULTS: Significant association ( P < 0.05) was observed in "blood pressure response to sustained handgrip" (sympathetic activity) and "heart rate response to Valsalva maneuver" (parasympathetic activity) among patients with migraine. Although the mean sympathetic skin response latency of patients with migraine was within the normal range, it was significantly prolonged in comparison with the control group. "Blood pressure response to sustained handgrip" and "heart rate variability" were found to be significantly ( P < 0.05) different in patients with a tension-type headache. The blink reflex test was observed to be normal in all patients with a headache. Patients with migraine showed a significant dysautonomia in category three of the Ewing battery for autonomic functional disability. CONCLUSIONS: Autonomic functional abnormality, both sympathetic and parasympathetic, does exist in patients with a primary episodic headache.

A Comparative Study of Regional Cerebral Blood Flow Asymmetry Index in Stroke Patients with or without Poststroke Depression Using 99m Tc-ECD Single-Photon Emission Computed Tomography.

Introduction Stroke is a major cause of death and disability around the globe. The development of depression following a stroke further increases the disability and impairs functional recovery. In recent decades, despite the advancement in structural and nuclear medicine imaging, the pathophysiologic basis of poststroke depression (PSD) is not well understood. Etiopathogenesis of PSD is multifactorial and afflictions of the frontal lobe, hippocampus, limbic region, and basal ganglia projections are implicated. Aim The aim of this study was to assess the regional cerebral blood flow (rCBF) using 99m Tc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) in patients with (PSD + ) or without PSD (PSD-). Materials and Methods To evaluate the hemispheric asymmetry, the percentage of asymmetry index (AI) was calculated for frontal, temporal, parietal, occipital, putamen, caudate, and thalamic regions of brain and compared between PSD+ and PSD-. The correlation between AIs over the different brain regions was also established in patients of PSD+ and PSD-. Our study cohort included 122 patients between 6 weeks and 1 year of stroke. Depression was present in 52 (42.6%) patients, assessed by hospital anxiety and depression scale (HADS) and general health questionnaire-28 items (GHQ-28) scale. The 28 patients with PSD+ and 18 PSD- gave consent for SPECT study. Results Our results are based on 46 patients who underwent SPECT study. In patients with PSD+ and PSD-, the HADS and GHQ-28 scores were 8.93 ± 2.77 vs. 3.94 ± 2.15 ( p = 0.001) and 40.96 ± 9.48 vs. 17.72 ± 5.38 ( p = 0.001), respectively. A significant difference in rCBF AI was found in the temporal lobe ( p = 0.03) between patients of PSD+ and PSD-. On logistic regression analysis, the odds ratio of rCBF AI for temporal lobe was 0.89 (95% confidence interval [CI]: 0.80-0.99; p = 0.04) and caudate nucleus was 0.85 (95% CI: 0.73-0.98; p = 0.03), which were statistically significant. PSD correlated with AI in temporal region ( r = -0.03; p = 0.03) but did not show significant correlation with other regions of brain between PSD+ and PSD-. Conclusion The presence of temporal lobe rCBF AI on SPECT is significantly associated with PSD. This may reflect the dysfunction of the limbic system and contribute to the occurrence of PSD.

High resolution ultrasonography of peripheral nerves in diabetic patients to evaluate nerve cross sectional area with clinical profile.

OBJECTIVES: The aim of this observational study was ultrasound evaluation of peripheral nerves cross-sectional area (CSA) in subjects with probable diabetic peripheral sensorimotor neuropathy (DPN). CSA was analyzed with reference to clinical and nerve conduction study's (NCS) parameters for early diagnosis and pattern of involvement. METHODS: A total of 50 patients with probable DPN due to Type 2 diabetes and 50 age-matched healthy controls underwent sonographic examinations of ulnar nerve at the lower arm, median nerve proximal to carpal tunnel, the common peroneal nerve proximal to fibular head, tibial nerve proximal to the tarsal tunnel, and sural nerve at lower third leg. RESULTS: CSA was increased in cases of DPN as compared to healthy controls. Area changes were more marked with demyelinating pattern. Probable DPN cases with normal NCS had significantly higher number of peripheral nerves showing increased CSA as compared to healthy control. A cut-off of >4 nerve thickening showed a sensitivity of 86 %, and specificity of 56%. The neuropathy pattern in the lower limb was axonal, whereas in the upper limb, it was demyelinating with the majority showing sonographic feature of associated compressive neuropathy. CONCLUSION: There is an increase in CSA of peripheral nerve in diabetic patients. It can be used as a morphological marker for classifying DPN with changes being picked up earlier to NCS abnormality. Clinical neurological presentation in probable DPN can also be due to compressive neuropathy in early phases, and ultrasound can be a useful tool. ADVANCES IN KNOWLEDGE: Early pick up of DPN cases shall be useful for early therapy and motivating the patients to actively participate in the treatment. Morphological changes on ultrasonography precedes the electrodiagnostic change in DPN. Symptoms of DPN is not only due to metabolic changes but also compressive neuropathy.

Classification and comparative analysis of psychogenic nonepileptic seizures (PNES) semiology based on video-electroencephalography (VEEG).

BACKGROUND: Multiple classification systems for psychogenic nonepileptic seizures (PNES) based on semiological features have been described. We sought to compare the efficiency of four PNES classification systems. METHODS: We retrospectively analyzed medical and video-electroencephalography (VEEG) records of patients with PNES with at least one typical event recorded on VEEG. Semiology of PNES events was stringently classified using Hubsch, Dhiman, Wadwekar, and Asadi-Pooya's classification systems. RESULTS: We studied 248 patients with PNES (78% females, mean age 23.1 ±â€¯10.3 years) and reviewed 498 PNES events. Using Hubsch's scheme, we classified events into: dystonic attacks with primitive gestural activity (5.2%), paucikinetic attacks with preserved responsiveness (9.7%), pseudosyncope (59.8%), hyperkinetic prolonged attacks (16.2%) and axial dystonic prolonged attacks (1.6%), and unclassified (7.5%). Using Dhiman's classification, events were: abnormal motor (hypermotor [10.4%]/ partial motor [12.7%]), dialeptic type (58.6%), mixed patterns (17.3%), and unclassified (1%). Using Wadwekar's classification: dystonic attacks with primitive gestural activity (5.2%), paucikinetic attacks with preserved responsiveness (9.6%), pseudosyncope with/without hyperventilation (65.1%), hyperkinetic prolonged attacks involving limbs ±â€¯trunk (18.5%), and axial dystonic prolonged attacks (1.6%). Using Asadi-Pooya's classification, events were: hypermotor (30.1%), non-motor (62.9%), and mixed (7.0%). All events could be classified via Wadwekar and Asadi-Pooya systems. CONCLUSION: In our study, pseudosyncope/dialeptic/non-motor semiology emerged as most frequent. Most of our patients with PNES had stereotyped semiology. All events could be classified using the schemes by Asadi-Pooya and Wadweker et al. Dhiman et al. scheme could classify 99% and 7.5% remained unclassified using Hubsch et al. scheme.

Clinical value of perilesional perfusion deficit measured by Technetium-99m-ECD single-photon emission computed tomography in hypertensive intracerebral hemorrhage.

Pathological and experimental studies indicate the existence of a "penumbra" of progressive tissue damage and edema in regions immediately surrounding a hematoma in patients of intracerebral hemorrhage (ICH). This zone of oligemia surrounding ICH has a potential for perfusion recovery. Improved understanding of the pathophysiology of perilesional blood flow changes and brain injury after ICH may result in improved treatment strategies. The aim was to study perilesional blood flow changes in ICH by perfusion deficit (PD) measured by single-photon emission computed tomography (SPECT) and to correlate it with the severity of ICH and outcome. Forty-four patients of computed tomography (CT) documented nonlobar deep ICH suggestive of hypertensive hematoma of <7 days duration were subjected to 99mTc-ethylene diacetate SPECT scans of the brain. Patients with significant midline shift (0.5 cm) or global blood flow reduction were excluded from the analysis. SPECT scan of the brain was analyzed by segmental analysis, a semi-quantitative method of cerebral blood flow. A difference of radiotracer uptake of >10% between the region of interest of ICH cases and the ratio between the two ROI below 0.9 was taken as a significant PD. A correlation of PD was analyzed with that of various parameters such as the severity of stroke, duration from onset of ictus, and imaging including CT scan of the brain and SPECT scan. A statistically significant difference in the percentage of radiotracer uptake on comparison of ipsilateral and contralateral to ICH (P < 0.001) was observed, suggesting a significant hypoperfusion in the perilesional area in patients with ICH. A statistically significant correlation was noted between the severity of stroke and PD indicated by various parameters such as the National Institutes of Health Stroke Scale (NIHSS) score at admission (r = 0.328, P = 0.016), Glasgow Coma Scale (GCS) score at admission (r = -0.388, P = 0.005), and ICH score at admission (r = 0.314, P = 0.020). This study demonstrated more severe hypoperfusion in clinically severe ICH which is a possible explanation of poor outcomes in severe ICH cases. We observed hypoperfusion on SPECT study in 25 of 34 (73.5%) patients with subacute ICH and 5 of 10 patients (50%) with acute ICH. The mean time from the onset of ictus to SPECT scan done was 5.04 ± 1.75 days with a range of 1-7 days, suggesting the persistence of hypoperfusion in subacute stages too. This finding may be of clinical importance for identifying the salvageable area surrounding ICH for any possible intervention in future to improve the outcome. This study demonstrates that perilesional PD occurs in acute and subacute cases of ICH. This hypoperfusion is possibly time related and appears to be more severe in patients having major ICH with poor clinical and imaging parameters. This area of hypoperfusion or ischemic penumbra is a potential site for perfusion recovery to improve clinical outcomes and to reduce long-term neurological deficits.

Brain-derived neurotrophic factor levels in acute stroke and its clinical implications.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has a very important role in repairing intact and injured brain, also known as neuroplasticity. Risk factors may affect neuroplasticity. OBJECTIVES: In this study, our aim was to delineate the levels of BDNF in acute stroke with different etiology and impact of risk factors on its levels. METHODS: In this prospective study, 208 patients with first-ever stroke, between 18 and 75 years, were included. All individuals were assessed for severity and type of stroke, risk factors, levels of BDNF in the acute stroke, and its association with outcome of stroke. RESULTS: The mean age of the patients in our study was 55.29 ± 11.6 years. Compared to healthy controls, a significant decline in the levels of BDNF was observed after stroke (P < 0.01). Patients with National Institutes of Health Stroke Scale (NIHSS) <6 on the 1st day of stroke had significantly higher levels of BDNF than those with NIHSS >6 (9.8 ng/ml ± 3.8; P < 0.01). A significant difference in the levels of BDNF was observed on comparing the stroke patients and healthy individuals of age <55 and >55 years (<55 years: 10.4 ng/ml ± 3.2; >55 years: 9.8 ng/ml ± 4.5 and in healthy individuals <55 years: 22.97 ± 3.8, >55 years: 15.4 ± 4.9; P < 0.01). Risk factors have negative impact on levels of BDNF (diabetics, P = 0.001; alcoholics, P = 0.003; both diabetes mellitus + hypertension, P = 0.002; smokers, P = 0.001). The difference was not significant between hypertensives and nonhypertensives (P = 0.06). CONCLUSION: BDNF level is significantly reduced in acute stroke. The presence of risk factors further affects its level.

Post-stroke BDNF concentration changes following proprioceptive neuromuscular facilitation (PNF) exercises.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in repairing normal as well as in the injured brain. Physical exercise may have a positive impact on the release of BDNF. OBJECTIVE: PNF is a neurophysiological approach that facilitates the stimulation of central and peripheral nervous systems. In this study, our aim was to assess the levels of BDNF as well as functional recovery before and after the intervention of PNF in patients with acute stroke. METHODS: A total of 208 patients with first time confirmed stroke were recruited and assessed for stroke severity, type, mini-mental state exam (MMSE), functional independence measure scale, and BDNF levels before and after PNF intervention. BDNF levels were also assessed in healthy individuals for control values. RESULTS: A significant decline in levels of BDNF was observed after in stroke. BDNF levels in patients (with different risk factors) with diabetes, hypertension and DM+ HTN, alcohol, and smoking history were 8.8 ± 4.04 ng/mL, 8.86 ± 4.68 ng/mL, 8.65 ± 3.26 ng/mL, 8.51 ± 4.26 ng/mL, and 8.9 ± 3.4 ng/mL, respectively. A decline in BDNF levels was observed in accordance with the severity of stroke in both ischemic and hemorrhagic stroke with the least level being in severe stroke (NIHSS >15 and ICH >3). Despite the type of stroke and the presence of risk factors, a significant improvement in BDNF levels and FIM scale scores was seen in all subjects who received PNF exercises. CONCLUSION: Thus, PNF is efficient in improving functional level in acute stroke irrespective of the type of stroke and risk factors.

Depression impedes neuroplasticity and quality of life after stroke.

BACKGROUND AND PURPOSE: Depression following a stroke/poststroke depression (PSD) has been newly recognized as one of the most common complications after stroke. PSD may affect neuroplasticity and quality of life. The purpose of present study was to find out effects of depression on functional recovery, quality of life and neuroplasticity in patients with acute stroke. METHODS: A total of 76 cases were recruited for the study and out of which 44 were available for the analysis after six months. Patients were divided into three groups according to severity of depression: Group A (without depression), Group B (mild-to-moderate depression), and Group C (severe depression) on the basis of Patient Health Questionnaire-9 (PHQ-9) scale scores. All patients were assessed for depression by PHQ-9, and for quality of life by Stroke Specific Quality of Life (SSQOL) scale. Neuroplasticity was assessed by measuring levels of serum brain-derived neurotrophic factor. RESULTS: Quality of life was observed to be significantly affected by depression (P ≤ 0.05). The most commonly affected characteristics were energy, family roles, mobility, self-care, social roles, upper extremity function, and work productivity. Serum BDNF levels were also affected significantly by depression (P ≤ 0.05). CONCLUSION: PSD is a serious complication, affecting quality of life and neuroplasticity (BDNF) in patients. Decreased neuroplasticity further may affect functional improvement.

De novo nose-pinching stereotypy with somnolence: Clues to autoimmune encephalitis.

Autoimmune encephalitis (AE) is being increasingly recognized as a cause of new-onset movement disorders. Movement disorders in AE are diverse and range from hyperkinetic conditions such as oromandibular dyskinesias, tremors and chorea to hypokinetic ones such as bradykinesia and parkinsonism. Stereotypies have been described in association with anti-NMDAR encephalitis. Similarly, sleep dysfunction is an underrecognized feature in many AE subtypes, prominently anti-IgLON5 although the correlation of phenotype of sleep dysfunction with a particular antibody subtype in AE is unclear. Despite the recognition of both these features as part of an overreaching spectrum in any patient with AE, seldom are they the sole presenting manifestations. Additionally, the challenge is further compounded in a patient who has seronegative AE since neither sleep disturbances nor stereotypies have been well characterized with this condition yet, and the diagnosis is conditional to exhausting a list of ancillary supportive features. In this brief communication, we describe the case of a young man who presented with hypersomnolence and an unusual focal nose-pinching stereotypy of subacute onset who lacked the presence of other typical clinical characteristics such as cognitive/memory impairment and seizures and had negative autoimmune antibodies but responded to immune therapy dramatically. We propose that the presence of de novo hypersomnolence and stereotypy should inform a potential diagnosis of AE.

Diabetes mellitus type 2 impedes functional recovery, neuroplasticity and quality of life after stroke.

OBJECTIVES: The recovery after stroke depends on the resolution of brain edema and neuroplasticity. The comorbidities associated with stroke such as type 2 diabetes mellitus (T2DM) may increase the chances of unfavorable outcome and delay the recovery from stroke and needs further investigation. SUBJECTS AND METHODS: The study dealt with 208 patients. The neurological status of the patients was assessed by Glasgow Coma Scale and the severity of stroke was assessed by the National Institute of Health Stroke Scale. Patients were divided into two groups: T2DM in group 1 and without T2DM in group 2. We assessed functional improvement by Functional Independence Measure (FIM) Scale, quality of life by Stroke Specific Quality of Life (SSQOL) Scale, and serum levels of brain-derived neurotrophic factor (BDNF) for assessing neuroplasticity. RESULTS: We observed lower levels of BDNF in diabetic stroke patients. There was significant improvement in FIM scale scores and SSQOL scale scores in non-diabetic stroke patients after 6 months (P < 0.05). The relative risk (RR) of poor functional recovery (FIM) in the diabetic group was 1.34 [95% confidence interval (CI) 1.0-1.8] and the odds ratio (OR) was 1.8 (95% CI 1.03-3.12). Diabetes is an independent risk factor for poor BDNF recovery (serum BDNF < mean value, i.e. 10.07 ± 3.8 ng/mL) (RR 2.40; 95% CI: 1.36-4.21 and OR 1.6; 95% CI: 1.15-2.13] and poor quality of life (RR 1.56; 95% CI: 1.13-2.16 and OR 2.83; 95% CI: 1.14-7.0). CONCLUSION: Diabetes is not only a risk factor for stroke occurrence but also delayed recovery after stroke.

Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy.

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit-skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit-skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.

Chalcone Based Homodimeric PET Agent, 11C-(Chal)2DEA-Me, for Beta Amyloid Imaging: Synthesis and Bioevaluation.

Homodimeric chalcone based 11C-PET radiotracer, 11C-(Chal)2DEA-Me, was synthesized, and binding affinity toward beta amyloid (Aß) was evaluated. The computational studies revealed multiple binding of the tracer at the recognition sites of Aß fibrils. The bivalent ligand 11C-(Chal)2DEA-Me displayed higher binding affinity compared to the corresponding monomer, 11C-Chal-Me, and classical Aß agents. The radiolabeling yield with carbon-11 was 40-55% (decay corrected) with specific activity of 65-90 GBq/µmol. A significant ( p < 0.0001) improvement in the binding affinity of 11C-(Chal)2DEA-Me with synthetic Aß42 aggregates over the monomer, 11C-Chal-Me, demonstrates the utility of the bivalent approach. The PET imaging and biodistribution data displayed suitable brain pharmacokinetics of both ligands with higher brain uptake in the case of the bivalent ligand. Metabolite analysis of healthy ddY mouse brain homogenates exhibited high stability of the radiotracers in the brain with >93% intact tracer at 30 min post injection. Both chalcone derivatives were fluorescent in nature and demonstrated significant changes in the emission properties after binding with Aß42. The preliminary analysis indicates high potential of 11C-(Chal)2DEA-Me as in vivo Aß42 imaging tracer and highlights the significance of the bivalent approach to achieve a higher biological response for detection of early stages of amyloidosis.

Evaluation of polymerase chain reaction in nerve biopsy specimens of patients with Hansen's disease.

BACKGROUND: Pure neuritic variety of leprosy (PNL) presents as peripheral neuropathy with absent skin lesions and negative skin smears. Diagnosing PNL is an uphill task as most of these patients have nonspecific changes on nerve biopsy. In such circumstances, additional molecular diagnostic tools like polymerase chain reaction (PCR) has proven to be useful in diagnosing leprosy. The present study was planned to evaluate the role of PCR in nerve biopsy specimens of patients with PNL. METHODS: Patients attending the neuromuscular clinic from January 2013 to June 2014 with mononeuropathy multiplex underwent detailed diagnostic evaluation to ascertain the cause of neuropathy. Patients where this evaluation failed to establish an etiology underwent a nerve biopsy. RESULTS: Nerve biopsy was done in 52 patients, of which 35 were diagnosed as pure neuritic leprosy. Definite leprosy with positive wade fite staining for lepra bacilli was seen in 13 patients and 22 biopsies revealed a probable leprosy without lepra bacilli being identified. PCR for M. leprae was positive in 22 patients (62%). 12 of the 13 cases with definite leprosy on histopathology were PCR positive while in the AFB negative group, PCR was positive in 10 cases. PCR had a sensitivity of 92.3%, specificity of 54.5%. The positive and negative predictive value of PCR was 54.5% and 92.3% respectively. CONCLUSIONS: PCR helps in diagnosing PNL in doubtful cases. A positive PCR increases the sensitivity of detection of M. leprae especially in cases of probable PNL group where AFB cannot be demonstrated on histopathology.

Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

BACKGROUND: Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). METHODS: The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). RESULTS: The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R2 of 0.97 and Q2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R2 of 0.80 and Q2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. CONCLUSION: On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples.

Nerve biopsy in Indian patients with mononeuropathy multiplex of undetermined etiology.

INTRODUCTION: A diagnosis of mononeuropathy multiplex (MM) requires detailed evaluation to determine etiology. We performed nerve biopsy on patients with MM in whom the etiology could not be established via other investigations. METHODS: Sixty-eight patients with MM seen between January 2013 and June 2014 underwent detailed diagnostic evaluation. Those in whom the investigations failed to establish an etiology underwent nerve biopsy. RESULTS: A diagnosis of leprosy was confirmed in 14 patients and was highly probable in 17 others. Eleven patients had vasculitic neuropathy, and in 1 patient there were amyloid deposits on nerve biopsy. CONCLUSIONS: In 43 of 68 Indian patients (63%) with MM, nerve biopsy identified a definite (26 patients) or probable (17 patients) etiology. Nerve biopsy is a valuable investigation in MM that frequently results in a diagnosis of leprosy in India. Muscle Nerve, 2016 Muscle Nerve 55: 23-27, 2017.

Subacute Sclerosing Panencephalitis in a Child with Human Immunodeficiency Virus Co-Infection.

Subacute sclerosing panencephalitis is a fatal infectious disease of childhood caused by persistence of the measles virus in the brain. The effect of human immunodeficiency virus (HIV) co-infection on subacute sclerosing panencephalitis remains elusive and rare. We report a child who developed subacute sclerosing panencephalitis following a short latency period and a rapidly progressive course with HIV co-infection.

Visual pathway abnormalities in tuberculous meningitis.

Ophthalmological complications are common and disabling in patients with tuberculous meningitis. We aimed to study the visual pathway abnormalities in patients with tuberculous meningitis. Forty-three patients with tuberculous meningitis were subjected to visual evoked responses (VER) and neuroophthalmologic assessment. Neuroophthalmologic assessment revealed abnormalities in 22 (51.3%) patients. VER were found to be abnormal in 27 (62.8%) patients. The VER abnormalities included prolonged P100 latencies with relatively normal amplitude and significant interocular latency differences. Visual pathways abnormalities are common in patients with tuberculous meningitis and are often subclinical. Pathophysiologic explanations for electrophysiological abnormalities on VER in these patients are incompletely understood and needs further exploration.

Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas.

The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind (99m)Tc. The radiolabeled complex, (99m)Tc-(EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/µmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 µM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERß and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy.