The evaluation of frequency and predictors of delirium and its short-term and long-term outcomes in hospitalized older adults'.

BACKGROUND: Delirium is a common complication in hospitalized older adults with multifactorial etiology and poor health outcomes. AIM: To determine the frequency and predictors of delirium and its short-term and long-term outcomes in hospitalized older adults. METHODS: A prospective observational study was performed in patients aged ≥60 years consecutively admitted to geriatric ward. Potential risk factors were assessed within 24 hours of hospital admission. Delirium screening was performed on admission and daily thereafter throughout the hospital stay using Confusion Assessment Method (CAM). Patients were followed up at 1-year post-discharge. RESULTS: The study included 200 patients with mean age 73.1 ± 8.83 years. Incidence and prevalence rate of delirium were 5% and 20% respectively. Multivariable regression analysis revealed emergency admission (OR= 5.12 (1.94-13.57), p=0.001), functional dependency (Katz index of Independence in Activities of Daily Living (Katz-ADL) score <5) 2 weeks before admission (OR= 3.08 (1.30-7.33), p=0.011) and more psychopathological symptoms (higher Brief Psychiatric Rating Scale (BPRS) total score) (OR=1.12 (1.06-1.18), p=0.001) to be independently associated with delirium. Patients in delirium group had significantly high in-hospital mortality (OR= 5.02 (2.12-11.8), p=0.001) and post-discharge mortality (HR= 2.02 (1.13-3.61), p=0.017) and functional dependency (Katz-ADL score <5) (OR= 5.45 (1.49-19.31), p=0.01) at 1-year follow up. CONCLUSION: Delirium is quite frequent in geriatric inpatients and is associated with high in-hospital and post-discharge mortality risk and long-term functional dependency. Emergency admission, pre-hospitalization functional dependency, and more general psychopathological symptoms are independently associated factors. Hence, earliest identification and treatment with early implementation of rehabilitation services is warranted.

Novel intervention of high-frequency repetitive transcranial magnetic stimulation in patients with somatic symptom disorder and its safety and outcome.

Somatic Symptom disorders (SSDs) are characterised by the presence of persistent somatic symptoms associated with excessive thoughts, feelings and behaviours related to the symptoms. However, current treatment modalities are non-specific with modest effects. We aim to explore the safety and outcome of high-frequency transcranial magnetic stimulation at medial Prefrontal Cortex in ten such patients. Patient Health Questionnaire-15, Hamilton Rating Scale for Depression and Hamilton Anxiety Rating Scale were applied to ten patients with Somatic Symptom Disorder. 15 sessions of 15Hz TMS using a double cone coil with 2500 pulses/session were administered. All patients completed their sessions except one. Eight of the nine patients reported significant improvement with a reduction of 33%-80% from their baseline PHQ-15 scores. One patient reported significant adverse effects. Double cone coil TMS at medial Prefrontal Cortex appears to be a safe therapeutic intervention with potentially good outcomes in SSDs.

Need to rethink tDCS protocols for the treatment of alcohol use disorder: Insights from a randomized sham-controlled clinical trial among detoxified inpatients.

OBJECTIVES: Alcohol use disorder (AUD) is a chronic disorder with various health problems. Reduced functioning of the Dorsolateral Prefrontal Cortex (DLPFC) is associated with impaired regulation of alcohol-seeking behaviors and increased cravings in individuals with AUD. This study aimed to investigate whether 10 add-on sessions of tDCS, over the left DLPFC in detoxified inpatients with AUD could reduce cravings and increase abstinence rates at three months. METHODS: Detoxified inpatients with AUD were randomly assigned to either treatment as usual (TAU) plus ten sessions of active tDCS over left DLPFC, or TAU plus ten sessions of sham tDCS treatment twice daily for five consecutive days. RESULTS: The results from the generalized linear mixed model (GLMM) revealed that time had a significant effect on OCDS scores, but neither treatment nor interaction between these two factors had a significant effect on OCDS scores The Chi-square test in the intention- to- treat analysis did not show a significant difference in complete abstinence rates between the active treatment group and the sham treatment group. CONCLUSIONS: we found that adding ten sessions of active tDCS over left DLPFC tDCS to the treatment as usual for AUD did not result in improved abstinence rates or reduced craving.

Individualized closed-loop TMS synchronized with exoskeleton for modulation of cortical-excitability in patients with stroke: a proof-of-concept study.

Background: Repetitive TMS is used in stroke rehabilitation with predefined passive low and high-frequency stimulation. Brain State-Dependent Stimulation (BSDS)/Activity-Dependent Stimulation (ADS) using bio-signal has been observed to strengthen synaptic connections. Without the personalization of brain-stimulation protocols, we risk a one-size-fits-all approach. Methods: We attempted to close the ADS loop via intrinsic-proprioceptive (via exoskeleton-movement) and extrinsic-visual-feedback to the brain. We developed a patient-specific brain stimulation platform with a two-way feedback system, to synchronize single-pulse TMS with exoskeleton along with adaptive performance visual feedback, in real-time, for a focused neurorehabilitation strategy to voluntarily engage the patient in the brain stimulation process. Results: The novel TMS Synchronized Exoskeleton Feedback (TSEF) platform, controlled by the patient's residual Electromyogram, simultaneously triggered exoskeleton movement and single-pulse TMS, once in 10 s, implying 0.1 Hz frequency. The TSEF platform was tested for a demonstration on three patients (n = 3) with different spasticity on the Modified Ashworth Scale (MAS = 1, 1+, 2) for one session each. Three patients completed their session in their own timing; patients with (more) spasticity tend to take (more) inter-trial intervals. A proof-of-concept study on two groups-TSEF-group and a physiotherapy control-group was performed for 45 min/day for 20-sessions. Dose-matched Physiotherapy was given to control-group. Post 20 sessions, an increase in ipsilesional cortical-excitability was observed; Motor Evoked Potential increased by ~48.5 µV at a decreased Resting Motor Threshold by ~15.6%, with improvement in clinical scales relevant to the Fugl-Mayer Wrist/Hand joint (involved in training) by 2.6 units, an effect not found in control-group. This strategy could voluntarily engage the patient. Conclusion: A brain stimulation platform with a real-time two-way feedback system was developed to voluntarily engage the patients during the brain stimulation process and a proof-of-concept study on three patients indicates clinical gains with increased cortical excitability, an effect not observed in the control-group; and the encouraging results nudge for further investigations on a larger cohort.

Clinical potential and neuroplastic effect of targeted virtual reality based intervention for distal upper limb in post-stroke rehabilitation: a pilot observational study.

PURPOSE: A library of Virtual Reality (VR) tasks has been developed for targeted post-stroke rehabilitation of distal upper extremities. The objective of this pilot study was to evaluate the clinical potential of the targeted VR-based therapeutic intervention in a small cohort of patients specifically with chronic stroke. Furthermore, our aim was to explore the possible neuronal reorganizations in corticospinal pathways in response to the distal upper limb targeted VR-intervention. METHODOLOGY: Five patients with chronic stroke were enrolled in this study and were given VR-intervention of 20 sessions of 45 min each. Clinical Scales, cortical-excitability measures (using Transcranial Magnetic Stimulation): Resting Motor Threshold (RMT), and Motor Evoked Potential (MEP) amplitude, task-specific performance metrics i.e., Time taken to complete the task (TCT), smoothness of trajectory, relative % error were evaluated pre- and post-intervention to evaluate the intervention-induced improvements. RESULTS: Pre-to post-intervention improvements were observed in Fugl-Meyer Assessment (both total and wrist/hand component), Modified Barthel Index, Stroke Impact Scale, Motor Assessment Scale, active range of motion at wrist, and task-specific outcome metrics. Pre-to post-intervention ipsilesional RMT reduced (mean ∼9%) and MEP amplitude increased (mean ∼29µV), indicating increased cortical excitability at post-intervention. CONCLUSION: VR-training exhibited improved motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes observed in terms of improved cortical-excitability might be a consequence of plastic reorganization induced by VR-intervention.IMPLICATIONS FOR REHABILITATIONPost-stroke rehabilitation of distal upper extremities is crucial and needs targeted intervention to rehabilitate in the chronic phase of recovery.Virtual reality (VR) has emerged as a supplemental approach in post-stroke rehabilitation. However, its customization as per clinical need is still under research.This pilot study provides preliminary evidence of the clinical utility of the developed VR tasks targeted for distal upper extremities.

Post-Stroke Rehabilitation of Distal Upper Limb with New Perspective Technologies: Virtual Reality and Repetitive Transcranial Magnetic Stimulation-A Mini Review.

Upper extremity motor impairment is the most common sequelae in patients with stroke. Moreover, its continual nature limits the optimal functioning of patients in the activities of daily living. Because of the intrinsic limitations in the conventional form of rehabilitation, the rehabilitation applications have been expanded to technology-driven solutions, such as Virtual Reality and Repetitive Transcranial Magnetic Stimulation (rTMS). The motor relearning processes are influenced by variables, such as task specificity, motivation, and feedback provision, and a VR environment in the form of interactive games could provide novel and motivating customized training solutions for better post-stroke upper limb motor improvement. rTMS being a precise non-invasive brain stimulation method with good control of stimulation parameters, has the potential to facilitate neuroplasticity and hence a good recovery. Although several studies have discussed these forms of approaches and their underlying mechanisms, only a few of them have specifically summarized the synergistic applications of these paradigms. To bridge the gaps, this mini review presents recent research and focuses precisely on the applications of VR and rTMS in distal upper limb rehabilitation. It is anticipated that this article will provide a better representation of the role of VR and rTMS in distal joint upper limb rehabilitation in patients with stroke.

Low-Frequency Repetitive Transcranial Magnetic Stimulation for Chronic Tension-Type Headache: A Randomized Controlled Study.

BACKGROUND: Nearly 1-3% of the population is affected by chronic tension-type headaches (CTTH). However, it is still difficult to treat owing to the lack of knowledge of the disease's pathophysiology. Available literature suggests a role for pericranial muscle activity and abnormal modulation of central pain. Repetitive transcranial magnetic stimulation (rTMS) therapy done at the dorsolateral prefrontal cortex (DLPFC) can help modulate pericranial muscle overactivity and central pain modulation in subjects with CTTH. AIM: This randomized controlled study aimed to assess the effect of rTMS used in the low-frequency dorsolateral prefrontal cortex on pain and muscle activity in subjects with a chronic tension-type headache. MATERIALS AND METHODS: The present randomized controlled clinical study was commenced in a health care center on 20 subjects with chronic tension-type headaches who were given either sham or low-frequency repetitive transcranial magnetic stimulation at the right dorsolateral prefrontal cortex. The therapy effect was evaluated statistically using Welch's corrected t-test. RESULTS: The study results depicted that daily use of rTMS therapy for two weeks led to a considerable reduction in the intensity of the pain, the activity of pericranial muscles, and headache impact, along with an increase in the nociceptive excitability thresholds in subjects with CTTH, with p=0.001 compared to the sham group. CONCLUSION: Considering its limitations, the present study depicts that rTMS is an efficacious management tool for reducing pain associated with CTTH and can serve as the cornerstone for additional investigations.

Role of nuclear energy in carbon mitigation to achieve United Nations net zero carbon emission: evidence from Fourier bootstrap Toda-Yamamoto.

In this communication, the time series data of three major countries USA, France, and Japan from 1965 to 2020 for CO2 emission, GDP, and nuclear energy (NE) are evaluated. It also analyzed and validated the EKC hypothesis while using nuclear energy for electricity generation. Fourier ARDL is used to investigate the hypothesis criteria, and the Fourier bootstrap Toda-Yamamoto (FBTY) causality test is used for causal linkage between the variables as well as the wavelet coherence; it is also presented the time and frequency dependency of the variables. The CO2 mitigation by using the NE is also assessed for all three countries and assessed that the France, Japan, and USA mitigated the CO2 per year is 0.0463 million metric ton (MMT), 0.0239 and 0.0728 MMT per year respectively. Similar to that the SO2 is reduced by using the NE is 24.322, 43.527, and 132.592 MMT/year, and NOx is reduced by approximately 0.2847, 0.147, and 0.4478 MMT/year by France, Japan, and USA respectively by applying the NE for power generation. The evidence of the EKC, Fourier bootstrap and Toda-Yamamoto clarifies the important role of nuclear energy in terms of carbon mitigation to achieve UN net zero carbon emission by 2050. Hence, in order to meet the UN target of net zero carbon emission by 2050, the USA and Japan should increase the production of nuclear energy as France meets its 74.1% energy demand through NE by validating the EKC hypothesis; on the other hand, all the three countries should increase the production of tidal energy due to their geographical location as tides are much more predictable than wind and sun keeping in consideration to the expenses incurred and a full proof plan for disposing NE residuals in a safe place as NE residuals are highly radioactive and contains traces of thorium and uranium.

Longitudinal assessment of disability amongst patients of bipolar and unipolar depressive disorders presenting to a tertiary care center in North India.

OBJECTIVES: To assess and compare the changes in disability scores associated with Bipolar Depression (BD) and Unipolar Depression (UD) over 1 year. METHODS: A longitudinal study was taken up in adults diagnosed with unipolar or bipolar depressive disorder with current depressive episode. Diagnosis was made according to Schedule for Clinical Assessment in Neuropsychiatry. Severity scoring was done using Hamilton's Depression (HAM-D) rating scale and Hamilton's Anxiety (HAM-A) rating scale. Disability was assessed using Indian Disability Evaluation and Assessment Scale (IDEAS) and London handicap Scale (LHS) at baseline, 6 and 12 months. RESULTS: Sixty participants were recruited (42 UD and 18 BD). No significant differences were seen in socio-demographic parameters, except higher education levels and males being overrepresented in UD. Significant differences at baseline were seen in HAM-D (p = .001) and HAM-A (p = .003) scores. The extent of disability was seen to correlate with severity of illness only in case of BD at baseline. No significant differences were seen in the IDEAS scores at baseline. IDEAS score improved at each follow-up assessment (p < .001). LHS showed significant improvement over time in UD (p < .001), but not BD (p = .076). Percentage individuals meeting cut-off for benchmark disability (>40%) were comparable at baseline but were significantly more in the BD at 12-months (p = .049). CONCLUSION AND IMPLICATIONS: Disability in psychiatry occurs equally amongst unipolar and bipolar depressive disorders and tends to improve over time, although the level of improvement may differ. It may not always correspond to severity of illness. These factors should be considered while certifying disability.

Spinocerebellar Ataxia 12 Patients have better Quality of Life than Spinocerebellar Ataxia 1 and 2.

Background: Spinocerebellar ataxia is a neurodegenerative disease. Information on comparative assessment of quality of life (QoL) among SCAs, particularly SCA 12, is scarce. We aimed to compare health-related QoL in SCA 1, 2 and 12. Methods: We conducted a cross-sectional study among individuals with genetically-confirmed SCAs. Ataxia severity was assessed using Brief Ataxia Rating Scale (BARS), independence in activities of daily living (ADL) using Katz index (Katz ADL) and depression using Beck's Depression Inventory-II (BDI-II). QoL was assessed via Short Form Health Survey version 2.0 (SF-36). Results: We enrolled 89 individuals (SCA1 = 17, SCA2 = 43, SCA12 = 29; 56% males). Mean age at onset (41.0 ± 11.6 for SCA12 versus 24.9 + 7.0 for SCA1 and 28.8 ± 9.8 years for SCA2) was significantly higher among SCA12. SCA12 had lower BARS (mean score 4.1 ± 4.5 versus 10.6 ± 4.6 for SCA1 and 12.5 ± 4.5 for SCA2). SCA12 scored better on all SF-36 subdomains including Physical (PCS) and Mental Component Summary (MCS) scores. PCS score amongst SCA12 was 44.4 ± 9.0 versus 30.4 ± 9.1 for SCA1 and 33.3 ± 8.9 for SCA2. MCS score for SCA12 was 51.4 ± 11.4 versus 41.8 ± 11.5 for SCA1 and 41.8 ± 11.2 for SCA2. SCA12 had lower mean BDI scores (5.0 ± 6.0) versus SCA1 (9.5 ± 11.6) and SCA2 (10.9 ± 10.3). BARS and BDI emerged as significant predictors of most SF-36 subdomains. Conclusions: Our study suggests that despite older age and comparable disease duration, SCA12 patients experience better QoL, less severe depression and ataxia versus SCA1 and SCA2. Severity of ataxia and depression are significant predictors of QoL among the three SCA types.

A novel perspective of associativity of upper limb motor impairment and cortical excitability in sub-acute and chronic stroke.

Background: The global inclination of stroke onset in earlier years of life and increased lifespan have resulted in an increased chronic post-stroke-related disability. The precise and simplistic approach such as the correlation of Fugl-Meyer Assessment (FMA) with Transcranial Magnetic Stimulation (TMS) parameters, Resting Motor Threshold (RMT) and Motor Evoked Potential (MEP), in patients with stroke might play a critical role, given the prognostic value of MEP, a measure of cortical excitability, and might be the key point in prescribing appropriate therapeutic strategies. Objective: The study aimed to determine the correlation of FMA-based impairment in the upper extremity function specifically of the wrist and hand with respect to the neurophysiological parameters of corticospinal tract integrity. Materials and methods: The Institutional Review Board approved the study and 67 (n) patients with stroke were enrolled in the Department of Neurology, AIIMS, New Delhi, India. The motor assessment was performed on patients by the upper extremity subset of Fugl-Meyer Assessment (FMA) and the clinical history was obtained. RMT and MEP of Extensor Digitorum Communis (EDC) muscle were measured via TMS. Results: A significant positive correlation was observed between Fugl-Meyer Assessment Wrist/Hand (FMA W/H) and MEP scores (r = 0.560, <0.001). Also, Fugl-Meyer Assessment Upper Extremity (FMA UE) scores demonstrated a moderate positive association with MEP responsiveness (r = 0.421, <0.001). Conclusion: MEP of the EDC muscle was found to be associated with sensorimotor control as measured by FMA. Moreover, FMA W/H score values might be a better prognostic indicator of EDC MEP responsiveness. Interestingly, a novel element comprising the range of FMA UE and FMA W/H components was observed to be a potential indicator of MEP responsiveness and could also indicate establishing FMA as a surrogate for TMS in resource-limited settings for prognostification.

Clinical Effectiveness of Non-Immersive Virtual Reality Tasks for Post-Stroke Neuro-Rehabilitation of Distal Upper-Extremities: A Case Report.

A library of non-immersive Virtual Reality (VR) tasks were developed for post-stroke rehabilitation of distal upper extremities. The objective was to evaluate the rehabilitation impact of the developed VR-tasks on a patient with chronic stroke. The study involved a 50-year-old male patient with chronic (13 month) stroke. Twenty VR therapy sessions of 45 min each were given. Clinical scales, cortical-excitability measures, functional MRI (fMRI), and diffusion tensor imaging (DTI) data were acquired pre-and post-therapy to evaluate the motor recovery. Increase in Fugl-Meyer Assessment (wrist/hand) by 2 units, Barthel Index by 5 units, Brunnstrom Stage by 1 unit, Addenbrooke's Cognitive Examination by 3 units, Wrist Active Range of Motion by 5° and decrease in Modified Ashworth Scale by 1 unit were observed. Ipsilesional Motor Evoked Potential (MEP) amplitude (obtained using Transcranial Magnetic Stimulation) was increased by 60.9µV with a decrease in Resting Motor Threshold (RMT) by 7%, and contralesional MEP amplitude was increased by 56.2µV with a decrease in RMT by 7%. The fMRI-derived Laterality Index of Sensorimotor Cortex increased in precentral-gyrus (from 0.28 to 0.33) and in postcentral-gyrus (from 0.07 to 0.3). The DTI-derived FA-asymmetry decreased in precentral-gyrus (from 0.029 to 0.024) and in postcentral-gyrus (from 0.027 to 0.017). Relative reduction in task-specific performance metrics, i.e., time taken to complete the task (31.6%), smoothness of trajectory (76.7%), and relative percentage error (80.7%), were observed from day 1 to day 20 of the VR therapy. VR therapy resulted in improvement in clinical outcomes in a patient with chronic stroke. The research also gives insights to further improve the overall system of rehabilitation.

Magnitude of psychiatric comorbidity in patients with obesity in Northern Indian population.

BACKGROUND AND AIMS: To determine the prevalence of different psychiatric comorbidities in patients with obesity and study their relationship with the degrees of obesity. METHODS: This cross-sectional study included 151 patients with a BMI≥25 kg/m2. Subjects with diagnosed psychiatric illness, type 2 diabetes mellitus, coronary artery disease or any neurological illness were excluded. Prevalence of psychiatric comorbidities was assessed by MINI screening tool for all major axis 1 disorders including anxiety, eating and mood disorders. The WHOQOL-BREF was used for assessment of well-being, in the four domains, physical, psychological, social and environmental. RESULTS: Females constituted 68.6% of the study population. Lifetime diagnosis of any psychiatric illness was present in 24%, higher in females than males [31% vs 9%, p = 0.003]. The WHOQOL-BREF average scores of psychological, physical and environmental domains were significantly lower (p < 0.001) in patients diagnosed with depression as compared to those without. The WHOQOL-BREF average score of only the physical domain were significantly lower in individuals with BMI ≥30 kg/m2 as compared to those with BMI <30 kg/m2. CONCLUSIONS: The burden of undiagnosed psychiatric comorbidity in patients with obesity decreases the quality of life. There is need to screen for psychiatric comorbidities for effective management of obesity.

A Case Report: Effect of Robotic Exoskeleton Based Therapy on Neurological and Functional Recovery of a Patient With Chronic Stroke.

Background: In this study, a novel electromechanical robotic exoskeleton was developed for the rehabilitation of distal joints. The objective was to explore the functional MRI and the neurophysiological changes in cortical-excitability in response to exoskeleton training for a 9-year chronic stroke patient. Case-Report: The study involved a 52-year old female patient with a 9-year chronic stroke of the right hemisphere, who underwent 20 therapy sessions of 45 min each. Cortical-excitability and clinical-scales: Fugl-Mayer (FM), Modified Ashworth Scale (MAS), Brunnstrom-Stage (BS), Barthel-Index (BI), Range of Motion (ROM), were assessed pre-and post-therapy to quantitatively assess the motor recovery. Clinical Rehabilitation Impact: Increase in FM wrist/hand by 6, BI by 10, and decrease in MAS by 1 were reported. Ipsilesional Motor Evoked Potential (MEP) (obtained using Transcranial Magnetic Stimulation) was increased by 98 µV with a decrease in RMT by 6% and contralesional MEP was increased by 43 µV with a decrease in RMT by 4%. Laterality Index of Sensorimotor Cortex (SMC) reduced in precentral- gyrus (from 0.152 to -0.707) and in postcentral-gyrus (from 0.203 to -0.632). Conclusion: The novel exoskeleton-based training showed improved motor outcomes, cortical excitability, and neuronal activation. The research encourages the further investigation of the potential of exoskeleton training.

Evidence of neuroplasticity with robotic hand exoskeleton for post-stroke rehabilitation: a randomized controlled trial.

BACKGROUND: A novel electromechanical robotic-exoskeleton was designed in-house for the rehabilitation of wrist joint and Metacarpophalangeal (MCP) joint. OBJECTIVE: The objective was to compare the rehabilitation effectiveness (clinical-scales and neurophysiological-measures) of robotic-therapy training sessions with dose-matched conventional therapy in patients with stroke. METHODS: A pilot prospective parallel randomized controlled study at clinical settings was designed for patients with stroke within 2 years of chronicity. Patients were randomly assigned to receive an intervention of 20 sessions of 45 min each, five days a week for four weeks, in Robotic-therapy Group (RG) (n = 12) and conventional upper-limb rehabilitation in Control-Group (CG) (n = 11). We intended to evaluate the effects of a novel exoskeleton based therapy on the functional rehabilitation outcomes of upper-limb and cortical-excitability in patients with stroke as compared to the conventional-rehabilitation. Clinical-scales- Modified Ashworth Scale, Active Range of Motion, Barthel-Index, Brunnstrom-stage and Fugl-Meyer (FM) scale and neurophysiological measures of cortical-excitability (using Transcranial Magnetic Stimulation) -Motor Evoked Potential and Resting Motor threshold, were acquired pre- and post-therapy. RESULTS: No side effects were noticed in any of the patients. Both RG and CG showed significant (p < 0.05) improvement in all clinical motor-outcomes except Modified Ashworth Scale in CG. RG showed significantly (p < 0.05) higher improvement over CG in Modified Ashworth Scale, Active Range of Motion and Fugl-Meyer scale and FM Wrist-/Hand component. An increase in cortical-excitability in ipsilesional-hemisphere was found to be statistically significant (p < 0.05) in RG over CG, as indexed by a decrease in Resting Motor Threshold and increase in the amplitude of Motor Evoked Potential. No significant changes were shown by the contralesional-hemisphere. Interhemispheric RMT-asymmetry evidenced significant (p < 0.05) changes in RG over CG indicating increased cortical-excitability in ipsilesional-hemisphere along with interhemispheric changes. CONCLUSION: Robotic-exoskeleton training showed improvement in motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes in RG could most likely be a consequence of plastic reorganization and use-dependent plasticity. Trial registry number: ISRCTN95291802.

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.

Robotic Guided Bilateral Anterior Cingulate Radiofrequency Ablation for Obsessive-Compulsive Disorder.

BACKGROUND: Bilateral anterior cingulotomy (BAC) constitutes the most commonly performed procedure for treatment of refractory OCD. Evolution of stereotactic procedures has rekindled the interest in the effective management of refractory psychiatric disorders, especially OCD with utmost safety and excellent outcomes. OBJECTIVE: The aim of this study was to demonstrate the technique of performing BAC under robotic guidance using radiofrequency ablation with an operative video. PROCEDURE: A 23-year-old gentleman diagnosed with symptoms of OCD for a duration of 8 years and was refractory to conventional therapy. The trajectories for BAC were planned on the robotic platform (ROSA, Zimmer-Biomet, Warsaw, Indiana, USA). The target point was selected on the anterior cingulate, approximately 2 cms posterior to the anterior most point of the frontal horn, 2-3 mm above the corpus callosum and 7 mm lateral to the midline. Pre coronal (1 cm anterior and 3 cms lateral to midline) holes of 2.5 mm diameter were made using pneumatic handheld drill. Radiofrequency (RF) thermocoagulation of the anterior cingulum was performed using an RF probe of 2.2 mm diameter and 4 mm uninsulated tip under robotic guidance after confirming the position with intraoperative O-arm imaging bilaterally. RESULTS: The surgery was uneventful and the patient had a significant improvement following surgery, with the Yale Brown Obsessive Compulsive Scale of 18 at 1 year follow-up compared to the preoperative score of 36. CONCLUSION: Robotic-guided BAC is a safe and effective technique for the treatment of drug-refractory OCD. Intraoperative O arm CT augments the precision of the lesions created.

Psychiatric co-morbidities and factors associated with psychogenic non-epileptic seizures: a case-control study.

PURPOSE: Psychogenic non-epileptic seizures (PNES) offer an immense diagnostic and therapeutic challenge. We sought to determine socioeconomic, psychological and demographic factors in PNES compared to age and gender matched epilepsy patients as well as healthy controls. We also examined psychiatric co-morbidities in PNES and epilepsy patients. METHODS: We conducted a case-control study at a tertiary centre in India with three groups including PNES only, age and gender matched epilepsy only and healthy participants. Factors including marital status, family type, education level and psychiatric comorbidities etc. were compared between the three groups. Details of PNES semiology, duration of event and disease were collected. Psychiatric assessment included MINI International Diagnostic Interview based on DSM-IV criteria and Holmes-Rahe Social Readjustment Scale for stress evaluation. The modified Kuppuswamy scale was used to assess socio-economic status. RESULTS: We enrolled 100 PNES patients (mean age 26.1 ± 10.8 years), 100 epilepsy patients (23.5 ± 9.6 years) and 100 healthy controls (28.9 ± 11.0 years). Ninety per cent of participants were female. Significant factors associated with PNES included family history of epilepsy [OR 20.3 (2.6-155.6) (p = 0.004)], low education including literate/illiterate status [OR 14.1 (2.5-78.9) (p = 0.003)], interpersonal conflict [OR 2.4 (1.1-6.0) (p = 0.05)] and presence of psychiatric comorbidity [OR 60.5 (24.1-152.2) (p < 0.001)] of which major depression was the most common. The current suicide risk was significantly elevated in PNES compared to epilepsy patients (p < 0.001). PNES disease duration correlated with presence of current depression, dysthymia and suicidality but not with other psychiatric comorbidities. CONCLUSIONS: Our results highlight that several socio-economic and demographic factors are associated with occurrence of PNES. High rates of psychiatric comorbidities including current suicide risk emphasise the need for a collaborative neuropsychiatric approach.