Localisation of eloquent cortex using magnetoencephalography and its clinical implications.

OBJECTIVES: This study aimed to localise the eloquent cortex and measure evoked field (EF) parameters using magnetoencephalography in patients with epilepsy and tumours near the eloquent cortex. METHODS: A total of 41 patients (26 with drug-refractory epilepsy and 15 with tumours), with a mean age of 33 years, were recruited. Visual evoked field (VEF), auditory evoked field (AEF), sensory evoked field (SSEF), and motor-evoked field (MEF) latencies, amplitudes, and localisation were compared with those of a control population. Subgroup analyses were performed based on lobar involvement. Evoked Field parameters on the affected side were compared with those on the opposite side. The effect of distance from the lesion on nearby and distant evoked fields was evaluated. RESULTS: AEF and VEF amplitudes and latencies were reduced bilaterally (p < 0.05). Amplitude in the ipsilateral SSEF was reduced by 29.27% and 2.16% in the AEF group compared to the contralateral side (p = 0.02). In patients with temporal lobe lesions, the SSEF amplitude was reduced bilaterally (p < 0.02), and latency was prolonged compared with controls. The MEF amplitude was reduced and latency was prolonged in patients with frontal lobe lesions (p = 0.01). EF displacement was 32%, 57%, 21%, and 16% for AEF, MEF, VEF, and SSEF respectively. Patients in the epilepsy group had distant EF abnormalities. CONCLUSIONS: EF amplitude was reduced and latency was prolonged in the involved hemisphere. Distant EF amplitudes were more affected than latencies in epilepsy. Amplitude and distance from the lesion had negative correlation for all EF. EF changes indicated eloquent cortical displacement which may not be apparent on MRI.

Exploring immunoreactivity of TTF-1 and AVP in hypothalamic hamartoma.

INTRODUCTION: Hypothalamic hamartoma (HH) is a rare developmental disorder presenting with gelastic seizures or precocious puberty attributed to gonadotrophin-releasing hormone expression by the hamartoma. The histogenesis of HH is uncertain, and diagnosis of HH is difficult in small biopsies due to its close resemblance to normal hypothalamic nuclei. TTF-1 and arginine vasopressin (AVP) are associated with gonadotropin-releasing hormone release. MATERIALS AND METHODS: In this study, we explored the expression pattern of TTF-1 and AVP in HH and its utility, if any, in diagnosis. We reviewed the clinical, radiologic, and histopathological features of 23 HH diagnosed over the past decade at our Institute. RESULTS: The age at presentation ranged from 11 months to 34 years with gelastic seizures (82.6%), precocious puberty (17.4%), and developmental delay (8.7%) as presenting symptoms. On imaging, all the lesions (n = 9) involved the posterior and tuberal group of hypothalamic nuclei, while 5 cases involved the anterior hypothalamus. Anatomically, the lesions involved mammillary body, arcuate and periventricular nuclei. On histopathology, 52% cases revealed nodular arrangement of small neurocytic cells separated by glial stroma. TTF-1 and AVP immunoreactivity was absent in all the cases, whereas in normal hypothalamus, AVP was expressed in periventricular nuclei. CONCLUSION: Our results suggest that immunoexpression of TTF-1 is absent in HH, particularly in those arising from the posterior hypothalamus, and this can be used in small biopsies to distinguish from a normal hypothalamus as well as from posterior pituitary tumors.

Posterior Quadrant Disconnection for Childhood Onset Sub-Hemispheric Posterior Head Region Epilepsy: Indications in an Indian Cohort and Outcome.

BACKGROUND: Posterior quadrant disconnection (PQD) is an under-utilized surgical technique in the management of refractory epilepsy. There is a dearth of data pertinent to post-PQD seizure outcomes. METHODS: This retrospective study analyzed patients with drug-resistant childhood-onset epilepsy who underwent PQD at our center from 2009 to 2018. The clinical, imaging, and electrophysiological data were reviewed. The seizure outcome was noted from the latest follow-up in all patients. RESULTS: Fifteen patients underwent PQD, with a mean age at onset of epilepsy of 3.3 ± 4.6 years. All patients had seizure onset in childhood with focal onset of seizures, and in addition, 5 had multiple seizure types. All cases underwent presurgical workup with MRI, video-EEG, psychometry, while PET/MEG was done if required. Engel Ia and ILAE I outcomes were considered to be favorable. The histology of the specimen showed 9 patients (60%) had gliosis, 4 (26.7%) had focal cortical dysplasia (FCD), while 1 patient had nodular heterotopia and another had polymicrogyria-pachygyria complex. Postoperative follow-up was available in 14 cases. One patient was lost to follow-up. Mean follow-up duration for the cohort was 45 + 24 months. At last, follow-up (n = 14), 66.7% (10 cases) had favorable outcome (Engel Ia). At the end of 1-year follow-up, up to 73% (n = 11) of the patients were seizure-free. Four patients developed transient hemiparesis after surgery which improved completely by 3-6 months. CONCLUSIONS: Gliosis was more common etiology requiring PQD in our series than Western series, where FCD was more common. PQD is a safe and effective surgical modality in childhood-onset epilepsy with posterior head region epileptogenic focus.

Magnetoencephalography imaging of high frequency oscillations strengthens presurgical localization and outcome prediction.

In patients with medically refractory epilepsy, resective surgery is the mainstay of therapy to achieve seizure freedom. However, ∼20-50% of cases have intractable seizures post-surgery due to the imprecise determination of epileptogenic zone. Recent intracranial studies suggest that high frequency oscillations between 80 and 200 Hz could serve as one of the consistent epileptogenicity biomarkers for localization of the epileptogenic zone. However, these high frequency oscillations are not adopted in the clinical setting because of difficult non-invasive detection. Here, we investigated non-invasive detection and localization of high frequency oscillations and its clinical utility in accurate pre-surgical assessment and post-surgical outcome prediction. We prospectively recruited 52 patients with medically refractory epilepsy who underwent standard pre-surgical workup including magnetoencephalography (MEG) followed by resective surgery after determination of the epileptogenic zone. The post-surgical outcome was assessed after 22.14 ± 10.05 months. Interictal epileptic spikes were expertly identified, and interictal epileptic oscillations across the neural activity frequency spectrum from 8 to 200 Hz were localized using adaptive spatial filtering methods. Localization results were compared with epileptogenic zone and resected cortex for congruence assessment and validated against the clinical outcome. The concordance rate of high frequency oscillations sources (80-200 Hz) with the presumed epileptogenic zone and the resected cortex were 75.0% and 78.8%, respectively, which is superior to that of other frequency bands and standard dipole fitting methods. High frequency oscillation sources corresponding with the resected cortex, had the best sensitivity of 78.0%, positive predictive value of 100% and an accuracy of 78.84% to predict the patient's surgical outcome, among all other frequency bands. If high frequency oscillation sources were spatially congruent with resected cortex, patients had an odds ratio of 5.67 and 82.4% probability of achieving a favourable surgical outcome. If high frequency oscillations sources were discordant with the epileptogenic zone or resection area, patient has an odds ratio of 0.18 and only 14.3% probability of achieving good outcome, and mostly tended to have an unfavourable outcome (χ2 = 5.22; P = 0.02; φ = -0.317). In receiver operating characteristic curve analyses, only sources of high-frequency oscillations demonstrated the best sensitivity and specificity profile in determining the patient's surgical outcome with area under the curve of 0.76, whereas other frequency bands indicate a poor predictive performance. Our study is the first non-invasive study to detect high frequency oscillations, address the efficacy of high frequency oscillations over the different neural oscillatory frequencies, localize them and clinically validate them with the post-surgical outcome in patients with medically refractory epilepsy. The evidence presented in the current study supports the fact that HFOs might significantly improve the presurgical assessment, and post-surgical outcome prediction, where it could widely be used in a clinical setting as a non-invasive biomarker.

Epilepsy surgery for focal cortical dysplasia: Seizure and quality of life (QOLIE-89) outcomes.

AIM: Surgery for drug resistant epilepsy (DRE) with focal cortical dysplasia (FCD) often requires multiple non-invasive as well as invasive pre-surgical evaluations and innovative surgical strategies. There is limited data regarding surgical management of people with FCD as the underlying substrate for DRE among the low and middle-income countries (LAMIC) including India. METHODOLOGY: The presurgical evaluation, surgical strategy and outcome of 52 people who underwent resective surgery for DRE with FCD between January 2008 and December 2016 were analyzed. The 2011 classification proposed by Blumcke et al., was used for histo-pathological categorization. The Engel classification was used for defining the seizure outcome. The surgical outcome was correlated with the preoperative clinical presentation, video encephalogram (VEEG) recording, magnetic resonance imaging (MRI), invasive monitoring, surgical findings as well as histopathology and the quality of life in epilepsy (QOLIE)- 89 scores. RESULTS: Fifty-two patients underwent resective surgery for FCD (mean age at onset of seizure: 7.94 ± 6.23 years; duration of seizures prior to surgery: 12.95 ± 9.56 years; and, age at surgery: 20.88 ± 12.51 years). The following regional distribution was found; temporal-24 (language-13), frontal-15 (motor cortex- 5), parietal-5 (sensory cortex-4), occipital-1 and multilobar-7. Forty-seven percent of the cases had FCD in the right hemisphere and 53% had FCD in the left hemisphere. Invasive monitoring was performed for identification of the epileptogenic zone (EZ) as well as eloquent cortex in 7 cases and an intra-operative electro-corticography (ECoG) was used in 32 cases. Histopathology revealed the following distribution; FCD IA-4, IB- 1, IC-5, IIA-8, IIB-18, IIIA-13, IIIB -1, IIIC-1 and IIID-1. After a median follow up of 3.7 years after surgery, 84% of patients had Engel's Ia outcome. QOLIE-89 scores improved from 38.33 ± 4.7 (31.14-49.03) before surgery to 75.21 ± 8.44 (56.49-90.49) after surgery (P < 0.001). The younger age of the patient (<20 years) at surgery (P = 0.013), a lower pre-operative score (<9) on seizure severity scale (P = 0.012), focal discharges without propagation on ictal VEEG (P < 0.001), absence of acute post-operative seizures (P < 0.001) and Type II FCD (P = 0.045) were the significant predictors for a favorable seizure outcome. CONCLUSION: Surgical management of people with DRE and FCD is possible in countries with limited resources. Meticulous pre-surgical evaluation to localize the epileptogenic zone and complete resection of the focus and lesion can lead to the cure or control of epilepsy; and, improvement in the quality of life was observed along with seizure-free outcome.

A preliminary study of natural history of mild traumatic brain injury by using multidimensional approach.

BACKGROUND & OBJECTIVES: Spectrum of post-traumatic symptoms is frequent among mild traumatic brain injury (mTBI) patients. They account for symptoms in 30-80 per cent of patients during 3-4 months and 20-30 per cent of patients six months post-injury. There are no studies from India in this area. The present longitudinal study was conducted to evaluate the natural recovery of post-traumatic symptoms in mTBI patients. METHODS: Twenty five mTBI patients presenting with initial Glasgow coma scale score of 15 were recruited initially 2-3 wk post-injury. All patients were followed up twice, after 3-4 and 6-7 months. The patients were evaluated with neuropsychological test, post-traumatic symptoms and quality of life after injury. RESULTS: Sustained attention and sensory registration were first to improve. Memory and executive domains improved partially until three months and then after complete recovery. However, a few facets of learning/memory did not improve even at six months. The post-traumatic symptoms decreased since baseline from 76 to 52 per cent at 3-4 months and further to 28 per cent at 6-7 months. The quality of life improved partially from baseline till 3-4 months and much more by 6-7 months. INTERPRETATION & CONCLUSIONS: The study findings showed the course of changes in cognition, traumatic symptoms and quality of life since the time of injury till 6-7 months post-injury. Though majority of post-traumatic symptoms recovered after mTBI without any intervention, but residuals were not uncommon.

Preservation of cognitive and musical abilities of a musician following surgery for chronic drug-resistant temporal lobe epilepsy: a case report.

Mesial temporal lobe epilepsy (TLE) affects a range of cognitive functions and musical abilities. We report a 16-year-old boy diagnosed with drug-resistant right-medial TLE. He is a professional musician, trained in Carnatic classical music. Clinical, electrophysiological, magnetic resonance imaging (MRI) and positron emission tomography evaluation localized the seizure focus to the right medial temporal lobe. Patient underwent detailed neuropsychological evaluation and functional MRI (fMRI) for musical abilities prior to surgery. He underwent an awake craniotomy and tailored resection of lateral neocortex as well as amygdalohippocampectomy under guidance of cortical stimulation and clinical monitoring. The superior temporal gyrus where activation was revealed on task-based fMRI was preserved. At 16-month follow-up, there was no seizure recurrence and his cognitive functions including musical abilities did not deteriorate with surgery. The task-based fMRI while listening to music revealed bilateral frontotemporal activation. There was evidence of increased left frontotemporal connectivity during the postsurgical period in the resting state fMRI. It is hypothesized that the intact neuropsychological and musical abilities might be as a result of intense musical training from an early age despite the illness leading to functional and neural adaptation of the brain might have contributed to his preserved cognitive functions and musical skills. Intense musical training at a young age perhaps not only honed a range of cognitive functions but also resulted in functionally more efficient cognitive networks despite the surgical resection.

Role of the thalamus in natural recovery of cognitive impairment in patients with mild traumatic brain injury.

INTRODUCTION: Patients with mild traumatic brain injury (mTBI) may have normal neuroimaging but manifest with a broad-spectrum of cognitive-deficits, which may resolve eventually. The function of the thalamus in the process of natural-recovery remains elusive. The current study investigates the role of the thalamus in natural-recovery of cognitive-deficits in patients with mTBI. METHODS: Twenty-one patients with mTBI were evaluated with an initial MRI scan, within 36 hours of injury and assessed with neuropsychological tests(NPT) at 3-4 weeks after injury. First and second follow-up MRI and NPT were performed at 3-4 months and 6-7 months, respectively. The volume and tensor measures of the thalamus and cognitive-scores were analysed at each assessment using repeated-measures of variance. The association of cognitive-scores with corresponding period imaging measures was analysed using bivariate-correlation. RESULTS: Serial evaluation showed that all the cognitive-domains improved significantly. During this period there was a significant increase in mean thalamic volume (p = 0.049, effect-size = 0.18). After 3-4 months there was emergence of anisotropic thalamo-cortical connections. At 2-3 weeks and 6-7 months after injury, the alterations in diffusivity values were positively associated with improvement in memory-scores. Improvement in attention-scores correlated significantly with changes in tensor values at the 6-7 months after-injury. CONCLUSION: The correlation between improvement in cognitive-scores and changes in thalamic tensor and volume measures reflect the role of the thalamus in natural-recovery after mTBI.

Magnetoencephalography Profile of Patients with Drug-Resistant Focal Epilepsy and Normal MRI.

BACKGROUND AND OBJECTIVES: Magnetoencephalography (MEG) could be a valuable tool in the presurgical evaluation of drug-resistant epilepsy (DRE), especially when the initial evaluation is inconclusive. In this retrospective study, we describe the profile of MEG in patients with DRE and normal magnetic resonance imaging (MRI). METHODS: We included patients with focal epilepsy and normal MRI who underwent presurgical evaluation for DRE. MEG profiles of these patients, including the frequency of spikes, density of clusters, number of clusters, and concordance with video electroencephalography (VEEG), were analyzed. RESULTS: Of the 73 patients included, magnetic source imaging (MSI) provided localizing information in 51 (69.9%) patients. Among patients with localizing MEG findings, localizing information on VEEG too was noted in 42 (57.5% of the whole cohort). Thirty-one (42.5%) patients had concordant findings with region-specific localization, six (8.2%) patients had partial concordance, and five (6.8%) subjects showed discordant findings. There was a moderate agreement for the presumed epileptogenic zone in comparing findings derived from MEG and VEEG (kappa value of 0.451, P < 0.001). The agreement was lower when MEG localized to the frontal lobe (kappa value of 0.379, P = 0.001) than the temporal lobe (kappa value 0.442, P = 0.002). CONCLUSIONS: MEG can provide localizing information in most patients with a normal MRI. A moderate degree of agreement between localization by MEG and VEEG was noted. These findings highlight the usefulness of MSI in the presurgical evaluation of MRI-negative DRE.

Yield of video electro encephalography for phase 1 pre-surgical evaluation of drug resistant epilepsy in 1200 adults: retrospective study from a tertiary center situated in a lower-middle-income country.

INTRODUCTION: Video Electroencephalography (VEEG) is crucial for presurgical evaluation of Drug Refractory Epilepsy (DRE). The yield of VEEG in large volume centers, particularly those situated in Low-and Middle-Income countries (LMIC) is not well studied. METHODOLOGY: We studied 1200 adults with drug resistant focal epilepsy whose seizures were recorded during VEEG in the epilepsy monitoring unit. VEEG review and analysis was done independently by trained epileptologists. Video EEG and MRI data were examined for concordance in order to generate a hypothesis for the presumed epileptogenic zone. RESULTS: Analysis of seizure semiology provided information on the symptomatogenic zone in most cases except for 33 (2.75%) patients. A total of 1050 (87.5%) patients showed interictal epileptiform discharges (IEDs) with most (58.3%) showing unilateral IEDs. Most patients (n = 1162, 96.83%) showed ictal EEG discharges of which 951(81.8%) had unilateral ictal onset. Abnormal MRI was seen in 978 (81.5%) patients. Concordance of electroclinical data obtained by analysis of VEEG with MRI abnormality could be established in most patients (63%). Concordance was higher for patients with ictal onset from temporal regions (83.71%) as compared to posterior cortex (55.4%) and frontal regions (43.5%.) CONCLUSION: This study highlights the high yield of VEEG in phase 1 presurgical evaluation in DRE. Systematic evaluation of data from VEEG provided lateralizing and localizing information in most cases. Concordance between VEEG and MRI findings was noted in most patients. These findings support steps to increase referral for pre-surgical evaluation in DRE.

Effects of an 18-Week Integrated Yoga Program on Cardiac Autonomic Function in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Cardiotoxicity is a commonly observed adverse effect seen in breast cancer (BC) patients undergoing chemotherapy with attributes toward cardiac autonomic dysfunction (CAD). Yoga, a mind-body system of medicine that has been shown to improve cardiac autonomic nervous system (ANS) activity in various health conditions, could be an effective adjuvant approach in addressing CAD. OBJECTIVE: This study aims to investigate the protective effects of Integrated Yoga Therapy (IYT) on ANS functioning, assessed using Heart rate variability (HRV) in breast cancer patients undergoing chemotherapy. METHODS: A total of 68 (stage I-III) BC patients were randomly assigned into 2 groups: Treatment as Usual group (TAU) and TAU with Yoga Therapy group (TAUYT). All patients underwent anthracycline-based adjuvant chemotherapy for a total of 6 cycles with 21 days/cycle. During chemotherapy, the TAUYT group received IYT 5 days a week for 18 weeks, compared with usual care alone in the TAU group. Resting heart rate (RHR) and HRV, measured in both the time and frequency domains, were used to assess the cardiac ANS function of each patient before and after 6 cycles of chemotherapy. RESULTS: A total of 30 subjects in the TAU group and 29 subjects in the TAUYT group were included in the analysis. At baseline (before chemotherapy), there were no significant differences between the TAU and TAUYT groups in terms of RHR and HRV indices. However, after chemotherapy, patients in the TAU group had a significantly higher average RHR (P < .02) and lower HRV indices with reduced parasympathetic indices: RMSSD (P < .01), pNN50% (P < .04), high-frequency power (P < .001) and increased sympathetic indices: low-frequency power (P < .001) with sympathovagal imbalance: LF/HF (P < .001) compared with patients in the TAUYT group. CONCLUSION: The study showed the protective effects of yoga therapy on CAD in patients receiving anthracycline-based chemotherapy for BC, proposing yoga as a potential adjuvant intervention in improving cardiac health and preventing cardiovascular-related morbidities. TRIAL REGISTRATION: This trial is registered with the Clinical Trials Registry-India (CTRI) database (CTRI/2020/10/028446; October 16, 2020).

Corpus Callosotomy for Non-Localizing Drug Resistant Epilepsy with Drop Attacks.

BACKGROUND: Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls. METHODS: We performed a retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated. RESULTS: During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range [IQR] = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency. CONCLUSIONS: Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks.

Resting-State Functional MRI/PET Profile as a Potential Alternative to Tri-Modality EEG-MR/PET Imaging: An Exploratory Study in Drug-Refractory Epilepsy.

Objective The study explores whether the epileptic networks associate with predetermined seizure onset zone (SOZ) identified from other modalities such as electroencephalogram/video electroencephalogram/structural MRI (EEG/VEEG/sMRI) and with the degree of resting-state functional MRI/positron emission tomography (RS-fMRI/PET) coupling. Here, we have analyzed the subgroup of patients who reported having a seizure on the day of scan as postictal cases and compared the findings with interictal cases (seizure-free interval). Methods We performed independent component analysis (ICA) on RS-fMRI and 20 ICA were hand-labeled as large scale, noise, downstream, and epilepsy networks (Epinets) based on their profile in spatial, time series, and power spectrum domains. We had a total of 43 cases, with 4 cases in the postictal group (100%). Of 39 cases, 14 cases did not yield any Epinet and 25 cases (61%) were analyzed for the final study. The analysis was done patient-wise and correlated with predetermined SOZ. Results The yield of finding Epinets on RS-fMRI is more during the postictal period than in the interictal period, although PET and RS-fMRI spatial, time series, and power spectral patterns were similar in both these subgroups. Overlaps between large-scale and downstream networks were noted, indicating that epilepsy propagation can involve large-scale cognition networks. Lateralization to SOZ was noted as blood oxygen level-dependent activation and correlated with sMRI/PET findings. Postoperative surgical failure cases showed residual Epinet profile. Conclusion RS-fMRI may be a viable option for trimodality imaging to obtain simultaneous physiological information at the functional network and metabolic level.

A Pilot Study of Perspective Taking and Emotional Contagion in Mental Health Professionals: Glass Brain View of Empathy.

Background: Empathy plays a fundamental role in the context of psychotherapy. Mental health professionals (MHP) are required to express empathy on a daily basis. "Perspective taking" (cognitive empathy) and "emotional contagion" (affective empathy) are elements of empathy that are both innate and acquired. This study aimed to explore the underlying neural correlates of empathy using functional magnetic resonance imaging (fMRI). Method: A total of six healthy subjects from MHP and other professionals (OP) were recruited in a single-assessment study design. Subjects were screened using the Mini-International Neuropsychiatric Interview and the Standard Progressive Matrices. Behavioral measures such as cognitive and affective empathy, interpersonal reactivity, and emotional and social quotient were assessed. Perspective taking was examined with the fMRI face recognition task and the reading mind through eyes task. Emotional contagion was examined by the negative, positive, and pain emotions task. The fMRI was conducted in a 3T Siemens Magnetom Skyra scanner, using a block design paradigm. Results: Activation was noted in the following areas: cingulate and thalamus for positive and negative emotions, precuneus for negative emotion and pain, inferior parietal lobe for reading mind task and negative emotion, declive for reading mind and pain, and precuneus and frontal gyrus for reading mind task and facial recognition. Conclusions: There was no significant difference between MHP and OP groups on the behavioral measures. However, there were variations in cerebral and cerebellar activation in the functional imaging parameters.

Impact of integrated yoga therapy on cognitive impairment and cardiac dysfunction in relation to quality of life in breast cancer patients undergoing chemotherapy: Study protocol for a two-arm randomized controlled trial.

Background: Chemotherapy-related cognitive impairment (CRCI) and cardiac dysfunction (CRCD) are common adverse effects seen in breast cancer patients undergoing chemotherapy. Even though these effects significantly influence daily functioning and overall quality of life, effective strategies to avoid and/or mitigate these adverse effects remain elusive. Yoga as a Mind-body intervention has been used increasingly by cancer patients and has undergone empirical investigations as a potential intervention for patients with cancer. Furthermore, yoga is associated with improved cognition and cardiac functioning in healthy older adults and subjects with cognitive and cardiac impairments. Accordingly, in the current study, yoga holds promise as an intervention to prevent/manage CRCI and CRCD with improved overall QOL in women receiving chemotherapy for breast cancer. Methods: The study is a two-arm, randomized controlled trial. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy will be recruited from a tertiary care center in Bangalore, India. Following recruitment, subjects are randomized to the intervention group (integrated yoga therapy intervention during chemotherapy) or the control group (standard care during chemotherapy). The study's primary outcome is to measure the quality of life (cognitive domain) using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The other primary objectives will include cognitive functioning using neuropsychological test battery and cardiac autonomic function testing using heart rate variability. Secondary outcomes are Brain-derived neurotrophic factor (BDNF), brain function (functional MRI), Echocardiography, serum cortisol, Functional assessment of cancer therapy-cognition (FACT-Cog V3), perceived stress scale and Ryff Scales of Psychological Well-Being. Assessments take place before, during and after chemotherapy; 16-weeks post chemotherapy and 1-year post-baseline. Discussion: Yoga is a promising intervention for preventing and/or managing chemotherapy-related adverse effects (CRAE) and enhancing the quality of life among breast cancer patients. The findings from this study may also help understand the inner mechanisms involved in the protective and restorative effects of yoga on CRAE and support the use of yoga prophylactically for breast cancer patients. In addition, the results of this study could help chemotherapy-exposed individuals with other solid cancer types who have cognitive and cardiac issues. Ethics and Dissemination: The study is approved by the ethics committee of the HealthCare Global Enterprises Ltd. Hospital (EC/434/19/01) and National Institute of Mental Health and Neurosciences (NIMH/DO/ETHICS SUB-COMMITTEE (BS&NS) 9th MEETING/2018). Clinical Trial Registration: http://ctri.nic.in/Clinicaltrials/advancesearchmain.php, identifier CTRI/2020/10/028446.

Disrupted structural connectome and neurocognitive functions in Duchenne muscular dystrophy: classifying and subtyping based on Dp140 dystrophin isoform.

OBJECTIVE: Neurocognitive disabilities in Duchenne muscular dystrophy (DMD) children beginning in early childhood and distal DMD gene deletions involving disruption of Dp140 isoform are more likely to manifest significant neurocognitive impairments. MRI data analysis techniques like brain-network metrics can provide information on microstructural integrity and underlying pathophysiology. METHODS: A prospective study on 95 participants [DMD = 57, and healthy controls (HC) = 38]. The muscular dystrophy functional rating scale (MDFRS) scores, neuropsychology batteries, and multiplex ligand-dependent probe amplification (MLPA) testing were used for clinical assessment, IQ estimation, and genotypic classification. Diffusion MRI and network-based statistics were used to analyze structural connectomes at various levels and correlate with clinical markers. RESULTS: Motor and executive sub-networks were extracted and analyzed. Out of 57 DMD children, 23 belong to Dp140 + and 34 to Dp140- subgroup. Motor disabilities are pronounced in Dp140- subgroup as reflected by lower MDFRS scores. IQ parameters are significantly low in all-DMD cases; however, the Dp140- has specifically lowest scores. Significant differences were observed in global efficiency, transitivity, and characteristic path length between HC and DMD. Subgroup analysis demonstrates that the significance is mainly driven by participants with Dp140- than Dp140 + isoform. Finally, a random forest classifier model illustrated an accuracy of 79% between HC and DMD and 90% between DMD- subgroups. CONCLUSIONS: Current findings demonstrate structural network-based characterization of abnormalities in DMD, especially prominent in Dp140-. Our observations suggest that participants with Dp140 + have relatively intact connectivity while Dp140- show widespread connectivity alterations at global, nodal, and edge levels. This study provides valuable insights supporting the genotype-phenotype correlation of brain-behavior involvement in DMD children.

Cognitive Retraining in Traumatic Brain Injury: Experience from Tertiary Care Center in Southern India.

Objective Traumatic brain injury (TBI) is a leading cause of mortality and chronic disability across the globe. This study aimed to understand the effects of cognitive retraining (CR) intervention on neuropsychological functions, symptom reporting, and quality of life in patients with moderate to severe TBI. Materials and Methods The present single-group intervention study with a pre-post design included 12 patients diagnosed with moderate to severe TBI within 3-24 months post injury. Outcome measures included National Institute of Mental Health and Neuro Sciences (NIMHANS) Neuropsychology Battery, Perceived Stress Scale, Rivermead Post-Concussion Symptom Questionnaire, World Health Organization Quality of Life Scale-Brief, and Visual Analogue Scale. All patients underwent a total of 20 sessions of hospital-based CR, spanning over a period of 2 months. The CR included tasks targeting to enhance processing speed, attention, executive function, learning, and memory. Outcome assessments were conducted at baseline and immediately at post intervention. Statistical Analysis Mean, standard deviation, frequency, and percentage were used as measures of descriptive statistics. Pre- and post-intervention scores were compared using Wilcoxon signed-rank test. Results The results showed that at post intervention, significant improvements were found in processing speed, working memory, planning, visuo-spatial construction, visual memory, and verbal encoding. Subjective symptom reporting, perceived stress, and quality of life in psychological domain also improved. Conclusion CR can be helpful in improving not only cognition but also symptom reporting and quality of life in moderate to severe TBI.

The Triad of Cognition, Language, and Communication in Traumatic Brain Injury: A Correlational Study.

Objectives Traumatic brain injury (TBI) is associated with deficits in cognition, language, and communication along with physical and psychosocial consequences. This study aimed at evaluating the association between cognition, language, and communication in a cohort of patients with TBI in southern India using standardized language specific assessment tools. Materials and Methods The present correlational study included 30 patients with TBI of any severity, that is, mild, moderate, and severe within the postinjury period of 6 to 36 months. Comprehensive evaluation of cognition, language, and communication was done using National Institute of Mental Health and Neurosciences Neuropsychology Battery, Indian adapted versions of Western Aphasia Battery and La Trobe Communication Questionnaire (LCQ) respectively. Data Analysis Measures of descriptive statistics, that is, mean, median, percentages, and frequencies, were used. Raw scores, that is, aphasia quotient (AQ), and subdomain scores for LCQ, that is, LCQ-quality, quantity, relation, manner, and cognition, were calculated. Composite scores for the three neuropsychological domains, that is, attention and processing speed, executive function, learning and memory, were evaluated. Partial correlation was computed for identifying the association between the three variables by controlling for age, education, duration, and severity of injury. Results A significant correlation was found between AQ and measures of attention and executive functioning and all measures of LCQ except LCQ-manner. Further, a significant correlation was found between executive functioning and LCQ-total, LCQ-quantity, and LCQ cognition. No correlation was found between measures of attention and memory with communication. Conclusion A good language and executive functioning are associated with better communication abilities in patients with TBI thus emphasizing on the importance of a multidisciplinary team for the management of cognitive-communication impairments following a TBI.

Magnetic source imaging in presurgical evaluation of paediatric focal drug-resistant epilepsy and its predictive value of surgical outcome in lesional cases: A single-centre experience from South India.

OBJECTIVE: This study aims to evaluate the utility of magnetoencephalography in presurgical planning and in predicting post-surgical seizure outcome. METHODS: This study included a cohort of 231 children (1-18 years) with focal drug-resistant epilepsy who underwent MEG as a part of their presurgical workup. Characteristics of MEG observations were described in all children. The concordance and agreement of Magnetic Source Imaging (MSI) of interictal discharges (IED) was estimated with either of the 3 subgroups - MRI lesion; presumed epileptogenic zone (EZ); or resection cavity. In operated children group, MEG dipole characteristics between good and poor outcome groups were assessed. RESULTS: A total of 153 cases (66.2%) showed frequent IEDs (60 spikes/60 min). Of the 173 cases where MSI showed clusters (74.9%), 151 had lesions and 22 were non-lesional. amongst patients with lesional epilepsy and MEG clusters, class I concordance (MEG localization either completely included or overlapped at least 60% with the MRI lesion) was seen in 60.92% with a Cohen's kappa of 0.608. In non-lesional epilepsy, class I concordance of MEG with presumed EZ was found in (81.81%) with an agreement of 0.317. Fifty-three children underwent surgery of whom 39 (73.58%) showed a good outcome (Engel I). In operated children, concordance between MEG focus and resection cavity was observed in 23 (58.97%) with good outcome and in 12 (86.72%) with poor outcome with no significant difference (p>0.05). However, MEG cluster regular organization and clusterectomy are associated with good seizure outcome postoperatively (p< 0.05). Presence of scatters were associated with poor outcome (p<0.05) in children with focal cortical dysplasia. CONCLUSIONS: MEG provides useful information that can serve as a biomarker for prognosticating the surgical outcome in paediatric epilepsy. Cluster removal and regular cluster organization shows predictive power in post-surgical prognostication in children and the presence of scatters predicts poor outcome in children with focal cortical dysplasia.

Neuropathological spectrum of drug resistant epilepsy: 15-years-experience from a tertiary care centre.

Neuropathology of drug resistant epilepsy (DRE) has direct bearing on the clinical outcome. Classification of the most common pathologies, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) have undergone several revisions and studies on the surgical pathology of DRE employing the updated ILAE classification are scarce. Here, we report the neuropathological spectrum of 482 surgically treated cases of DRE from a single institute using the latest ILAE classifications along with clinicoradiologic correlation. Majority of the cases (324, 67.2%) had temporal lobe epilepsy (TLE), with 158 (32.8%) having extratemporal seizure focus. Among TLE, HS was most common (n = 208, 64.2%), followed by neoplasms (42, 13%), FCD (26, 8%) and dual pathology (23, 7%). Less frequent were vascular malformations (cavernoma-3, arteriovenous malformation-1), mild malformation of cortical development (mMCD, 3), gliotic lesions (5), cysticercosis (2), double pathology (2) and polymicrogyria (1). Among extratemporal epilepsies, FCD was most common (46, 29.1%), followed by neoplasms (29, 18.3%), gliotic lesions (27, 17.1%), Rasmussen encephalitis (18, 11.4%), hypothalamic hamartoma (12, 7.6%), malformations of cortical development (10, 6.3%) and vascular malformations (6, 3.8%). Less frequent were double pathology (2, cysticercosis + FCD type IIb, DNET + FCD type IIb), mMCD (2), cysticercosis (1) and dual pathology (1). No underlying pathology was detected in 12 cases (2.5%). Radiopathological concordance was noted in 83%. In 36 cases (7.5%), histopathology detected an unsuspected second pathology that included FCD type III (n = 16) dual pathology (n = 18) and double pathology (n = 2). Further, in four MRI negative cases, histopathology was required for a conclusive diagnosis.