Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Vogt-Koyanagi-Harada Syndrome - A Neurologist's Perspective.

Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with "complete" or "incomplete" syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.

Clinical Profile and Treatment Response in Patients with CASPR2 Antibody-Associated Neurological Disease.

BACKGROUND: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. AIMS: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. METHODS: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. RESULTS: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. CONCLUSION: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.

Emerging behavioral and neuroimaging biomarkers for early and accurate characterization of autism spectrum disorders: a systematic review.

The possibility of early treatment and a better outcome is the direct product of early identification and characterization of any pathological condition. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication, restricted, and repetitive patterns of behavior. In recent times, various tools and methods have been developed for the early identification and characterization of ASD features as early as 6 months of age. Thorough and exhaustive research has been done to identify biomarkers in ASD using noninvasive neuroimaging and various molecular methods. By employing advanced assessment tools such as MRI and behavioral assessment methods for accurate characterization of the ASD features and may facilitate pre-emptive interventional and targeted therapy programs. However, the application of advanced quantitative MRI methods is still confined to investigational/laboratory settings, and the clinical implication of these imaging methods in personalized medicine is still in infancy. Longitudinal research studies in neurodevelopmental disorders are the need of the hour for accurate characterization of brain-behavioral changes that could be monitored over a period of time. These findings would be more reliable and consistent with translating into the clinics. This review article aims to focus on the recent advancement of early biomarkers for the characterization of ASD features at a younger age using behavioral and quantitative MRI methods.

Pigmented variant of pleomorphic xanthoastrocytoma - A rare long-term epilepsy associated neoplasm.

Pleomorphic xanthoastrocytoma (PXA) is an uncommon, long-term epilepsy associated tumor of young adults. Its pigmented variant is exceedingly rare, with only five previously reported cases on record. We report the sixth case of pigmented PXA in a 24-year-old lady presenting with long-standing seizures. The MRI revealed a solid cystic lesion located in the right medial temporal lobe. Histopathologically, the superficially located tumor showed typical features of PXA with melanin-laden astrocytic component and was negative for V600E-mutant BRAF. The histogenesis is discussed.

Pediatric opsoclonus-myoclonus-ataxia syndrome: Experience from a tertiary care university hospital.

BACKGROUND: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder; there is limited experience regarding its clinical course and therapeutic response. AIMS AND OBJECTIVES: To describe the clinical profile, investigations, and therapeutic outcome in pediatric OMAS. PATIENTS AND METHODS: Fourteen children (age: 27.1 ± 7 months; male: female = 1:2.3) suffering from OMAS seen over a period of 10 years (2006-2015) were included in the study. Their clinicodemographic profile, investigations, therapeutic outcome at follow-up, and relapses were reviewed. RESULTS: Ten children reported antecedent events (respiratory infection: 7; gastrointestinal infection: 1; vaccination: 2). The most common referral diagnosis was acute cerebellitis (n = 8). Hypotonia (n = 9), abnormal behavior (n = 10), and neuroregression (n = 6) were also the frequent manifestations. Brain magnetic resonance imaging, cerebrospinal fluid, and urinary vanillylmandelic acid were normal in all the patients. Seven patients had an underlying tumor (abdomen: 4; thorax: 2; neck: 1) detected by ultrasound (n = 2/14), computed tomography (CT) (n = 6/12), and fluorodeoxyglucose - positron emission tomography (n = 2/2). CT scan identified the tumor in 2 patients where metaiodobenzylguanidine scintigraphy was negative. All patients received steroids for 22.3 ± 20 months (3 months to 5 years). Eight required prolonged immunomodulation (>12 months). Complete remission after follow-up of 31.3 ± 19 months (7 months to 5 years) was noted in 5 patients, whereas the rest had persisting behavioral and cognitive abnormalities. Relapses were noted in 6 patients related to intercurrent infections (n = 5) and discontinuation of steroids (n = 1). The patients presented with isolated symptoms of the full-blown syndrome during their relapses. CONCLUSION: OMAS in children runs an indolent course requiring careful monitoring and long-term immunomodulation. An abnormal behavior is common and the outcome is variable.

Preoperative functional magnetic resonance imaging in patients undergoing surgery for tumors around left (dominant) inferior frontal gyrus region.

BACKGROUND: Preoperative functional magnetic resonance imaging (fMRI) helps to preserve neurological function and ensure maximal tumor tissue excision. We studied the lateralization and localization of speech centers in select cases of tumors around the left (dominant) inferior frontal gyrus (IFG). METHODS: Twenty-three right-handed patients, harboring tumors involving the left (dominant) IFG or causing mass effect or edema extending onto the left IFG, were recruited over 17 months. Preoperatively, all patients underwent language and speech assessment followed by MRI and fMRI with paradigm (picture naming). Normative data for language fMRI was taken from the institute's imaging data bank. RESULTS: The study included 23 patients [mean age: 38.9 (±11.9) years; M: F = 16:7; 9 - normal speech, 14 - abnormal speech]. Group analysis of controls showed significant activation in the region of interest (ROI) - left Brodmann's areas (BAs) 44,45. Group analysis of patients with normal speech showed no activation in the left BAs 44,45; however, activation was noted in the immediate adjacent areas, left BAs 13,47 and contralateral prefrontal cortex. Group analysis of patients with impaired speech showed no activation in BAs 44,45 or in the immediate adjacent areas. CONCLUSIONS: Neuroplasticity in the brain may enable functional language areas to shift to adjoining or distant regions in the brain when the primary areas are involved by intrinsic tumors. This phenomenon is more likely in slow-growing compared to fast-growing tumors. Preoperative language fMRI may help us in identifying and protecting these areas during surgery.

Palatal Tremor Revisited: Disorder with Nosological Diversity and Etiological Heterogeneity.

This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature. We highlight salient magnetic resonance imaging features, electrophysiological observations, and diverse etiologies in a large cohort of palatal tremor.

A Single Session of rTMS Enhances Small-Worldness in Writer's Cramp: Evidence from Simultaneous EEG-fMRI Multi-Modal Brain Graph.

Background and Purpose: Repetitive transcranial magnetic stimulation (rTMS) induces widespread changes in brain connectivity. As the network topology differences induced by a single session of rTMS are less known we undertook this study to ascertain whether the network alterations had a small-world morphology using multi-modal graph theory analysis of simultaneous EEG-fMRI. Method: Simultaneous EEG-fMRI was acquired in duplicate before (R1) and after (R2) a single session of rTMS in 14 patients with Writer's Cramp (WC). Whole brain neuronal and hemodynamic network connectivity were explored using the graph theory measures and clustering coefficient, path length and small-world index were calculated for EEG and resting state fMRI (rsfMRI). Multi-modal graph theory analysis was used to evaluate the correlation of EEG and fMRI clustering coefficients. Result: A single session of rTMS was found to increase the clustering coefficient and small-worldness significantly in both EEG and fMRI (p < 0.05). Multi-modal graph theory analysis revealed significant modulations in the fronto-parietal regions immediately after rTMS. The rsfMRI revealed additional modulations in several deep brain regions including cerebellum, insula and medial frontal lobe. Conclusion: Multi-modal graph theory analysis of simultaneous EEG-fMRI can supplement motor physiology methods in understanding the neurobiology of rTMS in vivo. Coinciding evidence from EEG and rsfMRI reports small-world morphology for the acute phase network hyper-connectivity indicating changes ensuing low-frequency rTMS is probably not "noise".

Imaging biomarker correlates with oxidative stress in Parkinson's disease.

BACKGROUND: While oxidative stress (OS) may be one of the crucial factors determining the initiation and progression of Parkinson's disease (PD), its correlation with gray matter (GM) atrophy is not known. AIMS: To determine the GM volume (GMV) changes using voxel-based morphometry (VBM) and correlation with OS marker serum malondialdehyde (MDA) in PD. MATERIALS AND METHODS: Seventy-two patients with PD were clinically evaluated and underwent magnetic resonance imaging (MRI) on a 3T MRI scanner using a 32-channel head coil. Lipid peroxidation product MDA levels were measured by spectrophotometry. MDA levels and regional GM differences using VBM were compared with 72 healthy controls. RESULTS: The mean age of the patients was 51.3 ± 10.6 years and that of controls was 50.8 ± 10.4 years. The mean age of onset of symptoms in PD was 45.2 ± 11.3 years. In PD, serum MDA level was significantly higher than that in controls (0.592 ± 0.89 µmol/l vs. 0.427 ± 0.055 µmol/l; P < 0.0001). Compared to controls, patients had greater regional GM atrophy in all the brain lobes (P < 0.001, uncorrected). A significant positive correlation was found between GMV and MDA in the caudate nucleus (CN) and posterior cingulate gyrus (PC) in the patient group (P < 0.001, uncorrected). CONCLUSIONS: We observed GM atrophy in all major brain lobes of patients when compared to controls. Only in the patient group, a significant positive correlation was observed in CN and PC with MDA. These findings suggest that, even though the whole brain is affected in PD, some of the non-substantia nigra regions of the brain, such as CN, may have some differential compensatory mechanism, which are preserved from oxidative damage.

Fatal Morvan Syndrome Associated With Myasthenia Gravis.

INTRODUCTION: Morvan syndrome is a rare and complex autoimmune disorder affecting multiple sites of neuraxis. CASE REPORT: We present fulminant Morvan syndrome, developing on a background of chronic myasthenia gravis. A 54-year-old gentleman presented with fluctuating ophthalmoplegia and proximal muscles weakness of 7 years duration that remitted with pyridostigmine and prednisolone. He developed insomnia of 2 months duration, worsening of myasthenic symptoms and respiratory distress, dysautonomia, encephalopathy, and peripheral nerve hyperexcitability. Antibodies against contactin-associated protein (CASPR) 2 were detected in serum. Computed tomography of thorax showed a thymic mass. He received intravenous methyl prednisolone and plasmapheresis. Antibodies against CASPR and thymic lesion reduced with immunotherapy. However, he developed persistent hypotension and expired after 11 weeks of hospital stay. CONCLUSIONS: Clinical clues for diagnosis of Morvan syndrome and therapeutic changes faced by the treating team are highlighted in this report. Increased awareness and prompt testing for CASPR2 antibody is warranted so that early immunotherapy can be initiated.

Temporal Dynamics of the Default Mode Network Characterize Meditation-Induced Alterations in Consciousness.

Current research suggests that human consciousness is associated with complex, synchronous interactions between multiple cortical networks. In particular, the default mode network (DMN) of the resting brain is thought to be altered by changes in consciousness, including the meditative state. However, it remains unclear how meditation alters the fast and ever-changing dynamics of brain activity within this network. Here we addressed this question using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to compare the spatial extents and temporal dynamics of the DMN during rest and meditation. Using fMRI, we identified key reductions in the posterior cingulate hub of the DMN, along with increases in right frontal and left temporal areas, in experienced meditators during rest and during meditation, in comparison to healthy controls (HCs). We employed the simultaneously recorded EEG data to identify the topographical microstate corresponding to activation of the DMN. Analysis of the temporal dynamics of this microstate revealed that the average duration and frequency of occurrence of DMN microstate was higher in meditators compared to HCs. Both these temporal parameters increased during meditation, reflecting the state effect of meditation. In particular, we found that the alteration in the duration of the DMN microstate when meditators entered the meditative state correlated negatively with their years of meditation experience. This reflected a trait effect of meditation, highlighting its role in producing durable changes in temporal dynamics of the DMN. Taken together, these findings shed new light on short and long-term consequences of meditation practice on this key brain network.

Recovery of resting brain connectivity ensuing mild traumatic brain injury.

Brains reveal amplified plasticity as they recover from an injury. We aimed to define time dependent plasticity changes in patients recovering from mild traumatic brain injury (mTBI). Twenty-five subjects with mild head injury were longitudinally evaluated within 36 h, 3 and 6 months using resting state functional connectivity (RSFC). Region of interest (ROI) based connectivity differences over time within the patient group and in comparison with a healthy control group were analyzed at p < 0.005. We found 33 distinct ROI pairs that revealed significant changes in their connectivity strength with time. Within 3 months, the majority of the ROI pairs had decreased connectivity in mTBI population, which increased and became comparable to healthy controls at 6 months. Within this diffuse decreased connectivity in the first 3 months, there were also few regions with increased connections. This hyper connectivity involved the salience network and default mode network within 36 h, and lingual, inferior frontal and fronto-parietal networks at 3 months. Our findings in a fairly homogenous group of patients with mTBI evaluated during the 6 month window of recovery defines time varying brain connectivity changes as the brain recovers from an injury. A majority of these changes were seen in the frontal and parietal lobes between 3 and 6 months after injury. Hyper connectivity of several networks supported normal recovery in the first 6 months and it remains to be seen in future studies whether this can predict an early and efficient recovery of brain function.

Ictal Generalized EEG Attenuation (IGEA) and hypopnea in a child with occipital type 1 cortical dysplasia - Is it a biomarker for SUDEP?

An interesting association of ictal hypopnea and ictal generalized EEG attenuation (IGEA) as possible marker of sudden unexpected death in epilepsy (SUDEP) is reported. We describe a 5-years-old girl with left focal seizures with secondary generalization due to right occipital cortical dysplasia presenting with ictal hypopnea and IGEA. She had repeated episodes of the ictal apnoea in the past requiring ventilator support and intensive care unit (ICU) admission during episodes of status epilepticus. The IGEA lasted for 0.26-4.68 seconds coinciding with the ictal hypopnea during which both clinical seizure and electrical epileptic activity stopped. Review of literature showed correlation between post-ictal apnoea and post ictal generalized EEG suppression and increased risk for SUDEP. The report adds to the growing body of literature on peri-ictal apnea, about its association with IGEA might be considered as a marker for SUDEP. She is seizure free for 4 months following surgery.

Hot water epilepsy: Phenotype and single photon emission computed tomography observations.

We studied the anatomical correlates of reflex hot water epilepsy (HWE) using multimodality investigations viz. magnetic resonance imaging (MRI), electroencephalography (EEG), and single photon emission computed tomography (SPECT). Five men (mean age: 27.0 ΁ 5.8 years) with HWE were subjected to MRI of brain, video-EEG studies, and SPECT scan. These were correlated with phenotypic presentations. Seizures could be precipitated in three patients with pouring of hot water over the head and semiology of seizures was suggestive of temporal lobe epilepsy. Ictal SPECT showed hyperperfusion in: left medial temporal - one, left lateral temporal - one, and right parietal - one. Interictal SPECT was normal in all five patients and did not help in localization. MRI and interictal EEG was normal in all the patients. The clinical and SPECT studies suggested temporal lobe as the seizure onset zone in some of the patients with HWE.