Ceftriaxone-induced encephalopathy in a patient with multicentric glioma.

Background: Ceftriaxone is a commonly used antibiotic in a wide range of local and systemic infections. Encephalopathy is a rare complication of ceftriaxone, often seen in older adults and those with renal insufficiency. Case Description: A 73-year-old lady with prior history of hypertension and dyslipidemia presented with the complaints of slurred speech, gait imbalance, nocturnal vomiting, and progressively worsening headache. A magnetic resonance imaging of the brain revealed two intracerebral lesions involving the right frontal and temporal lobes, suggestive of multicentric glioma. She underwent craniotomy and excision of these lesions. The biopsy was reported as intra-axial tumors with features suggestive of the WHO Grade IV glioma. Postoperatively, she did not wake up. An electroencephalogram demonstrated triphasic waves suggestive of encephalopathy. The probable diagnosis of ceftriaxone-induced encephalopathy was made after ruling out other causes of delayed awakening after surgery. Ceftriaxone was discontinued and the patient improved within 2 days of withdrawal of ceftriaxone. Conclusion: Drug-induced encephalopathy should be considered in the differential diagnosis of patients with delayed awakening after surgery. Discontinuation of the drug leads to the recovery of these patients.

A real world multi center study on efficacy and safety of natalizumab in Indian patients with multiple sclerosis.

BACKGROUND: Natalizumab (NTZ) is increasingly being used in Indian multiple sclerosis (MS) patients. There are no reports on its safety and efficacy, especially with respect to the occurrence of progressive multifocal leukoencephalopathy (PML). OBJECTIVES: To describe the patient characteristics, treatment outcomes, and adverse events, especially the occurrence of PML in NTZ-treated patients. METHODS: A multicentre ambispective study was conducted across 18 centres, from Jan 2012 to Dec 2021. Patients at and above the age of 18 years treated with NTZ were included. Descriptive and comparative statistics were applied to analyze data. RESULTS: During the study period of 9 years, 116 patients were treated with NTZ. Mean age of the cohort was 35.6 ± 9.7 years; 83/116 (71.6%) were females. Relapse rate for the entire cohort in the year before NTZ was 3.1 ± 1.51 while one year after was 0.20±0.57 (p = 0.001; CI 2.45 -3.35). EDSS of the entire cohort in the year before NTZ was 4.5 ± 1.94 and one year after was 3.8 ± 2.7 (p = 0.013; CI 0.16-1.36). At last follow up (38.3 ± 22.78 months) there were no cases of PML identified. CONCLUSIONS: Natalizumab is highly effective and safe in Indian MS patients, with no cases of PML identified at last follow up.

Reversible Hemichorea with Severe Carotid Stenosis.

Background: We report a 74-year-old lady with hemichorea of 6 months duration due to severe carotid stenosis without cerebral infarction. Electroencephalography and single-photon emission computed tomography studies suggested hemispheric abnormality. Hemichorea resolved following carotid endarterectomy. Discussion: Hemichorea is the commonest movement disorder following acute stroke. It is rarely reported in association with severe carotid stenosis without evident infarction. In the absence of corresponding structural abnormalities on magnetic resonance imaging in hemichorea, vascular imaging is critical in establishing the diagnosis. Hemichorea in setting of carotid or vascular stenosis is often resistant to medical treatment and best responds to reperfusion. Conclusion: Hemichorea due to critical hemispheric ischemia is a well-described rare entity that best responds to reperfusion strategies. Awareness is essential to identify this entity and manage appropriately.

Knowledge gap exists among caregivers of adults compared to caregivers of children with epilepsy: A comparative analysis from a low resource setting.

Caregivers of adults (CG-A) and caregivers of children (CG-C) may differ in their knowledge, attitude and behavior and hence their education requirements during epilepsy counseling could vary. This study compares the current knowledge, attitudes, behavior during a seizure, presence of myths surrounding epilepsy and ability to recognize seizures among a sample of CG-A and CG-C. Caregivers of children and adult patients with minimum 6 months history of epilepsy were enrolled. Information was collected using a questionnaire about clinical and demographic details and five domains (KAP-plus); knowledge, attitude, behavior, presence of myths and a video data for identification of focal impaired awareness seizures (FIAS) and generalized tonic-clonic seizures (GTCS). There were 132 CG-A and 127 CG-C. CG-C were younger and better educated compared to CG-A (formal education of 64.6% vs 44.7% p = 0.001). CG-A and CG-C were comparable in the knowledge and attitude domains. CG-A scored less than CG-C in the domains of behavior (15.5 vs 16.8 p = <0.001), myths (15.4 vs 16.2 p = 0.002), video recognition of FIAS and GTCS (0.7 vs 0.94 p = 0.001) and KAP-plus score (22.9 vs 24.6 p = 0.017). The knowledge-behavior or knowing-doing gap, knowledge-faith gap and knowledge-recognition gaps existed more among CG-A compared to CG-C. Focused education strategies are required to bridge the gap among CG-A.

COVID-19 outcomes in persons with multiple sclerosis treated with rituximab.

BACKGROUND: Outcomes of COVID-19 in PwMS (persons with Multiple Sclerosis) on immunosuppressive therapies, particularly B-cell depletors, can be unpredictable. There has been a concern for postponing or avoiding use of Rituximab (RTX) during the COVID-19 pandemic. We report the course and outcomes of COVID-19 in PwMS receiving RTX. METHODS: PwMS receiving RTX who contracted COVID-19 were closely monitored by tele-consultation and/or evaluated during hospital visits. Those requiring hospitalization for oxygen therapy or admission to ICU or expiring due to COVID-19 were considered to have severe disease. Those without desaturation and manageable at home were considered to have mild disease. Disease course and outcomes were noted. RESULTS: Twelve out of 62 (19.4%) PwMS on RTX therapy developed COVID-19. Four (age 35-49 years; mean 43.5) had severe COVID; three of whom had Secondary Progressive MS (SPMS). One PwMS expired. Two had prolonged fever lasting >1 month. One demonstrated features of SARS-CoV-2 reactivation. Interval from last RTX infusion (average dose 750 mg) to COVID-19 onset ranged 1-4 (mean 3.7) months. Eight PwMS had mild COVID-19 (age 26-54 years; mean 37.7); six had RRMS and two SPMS. RTX dose was lower (average dose 625 mg) and infusion to COVID-19 onset duration was longer, ranging 4-20 (mean 9.5) months. Four patients, two each from mild and severe COVID-19 groups had neurological deterioration, but none had true relapses. CONCLUSION: RTX treated PwMS may have unpredictable disease outcomes if they contract COVID-19, but may be at risk of severe disease and persistent infection. In our series higher age, SPMS, shorter interval from RTX infusion to COVID-19 onset and higher dose of RTX were noted amongst those developing severe disease. RTX should be use cautiously during the COVID-19 pandemic and if unavoidable, less frequent and lower doses should be considered. Patients receiving RTX must be counselled to follow strict COVID-19 preventive measures.

Clarithromycin-induced Seizures and Status Epilepticus.

Clarithromycin is a commonly used antibiotic. Neuropsychiatric adverse effects are recognized, but the occurrence of seizures and status epilepticus (SE) has been rarely reported. We report the case of an elderly patient who developed generalized tonic-clonic seizures (GTCS) followed by nonconvulsive status epilepticus (NCSE), 2 days after starting clarithromycin. Other causes of seizures were excluded by magnetic resonance imaging (MRI) of the brain, CSF analysis, and routine laboratory studies, thus establishing the causal role of clarithromycin. Clarithromycin was stopped and parenteral antiepileptic drugs started, which controlled the status. In the elderly, symptoms like delirium, drowsiness, confusion, or seizures can occur due to an underlying systemic disease, brain pathology, or adverse effects of medications, all of which must be correctly differentiated. This case illustrates the occurrence of seizures and SE due to clarithromycin. Awareness about this possibility will help physicians recognize and treat such situations promptly. How to cite this article: Seetharam R, Iyer RB, Nooraine J, Ramachandran J. Clarithromycin-induced Seizures and Status Epilepticus. Indian J Crit Care Med 2021;25(8):945-947.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a widespread disease with an apparently focal epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently recognized, highly epileptogenic, distinct histopathological entity in drug-resistant epilepsy that primarily involves the frontal lobes. Surgical outcomes in MOGHE are variable. Although the diagnosis is based on histopathology, high-resolution MRI helps to differentiate MOGHE preoperatively from other forms of cortical malformations (i.e., mMCD II and FCD IIa). We discuss the clinical, electrographic, radiological and histopathological characteristics of MOGHE in two patients who underwent evaluation for drug-resistant epilepsy followed by electrocorticography-based resection. Both patients presented with childhood-onset refractory frontal lobe epilepsy with a high seizure burden. Interictal epileptiform discharges were widespread. PET abnormalities were disproportionate to the MRI findings. Cognitive impairment, persistent epileptiform discharges on post-resection electrocorticography and sub-optimal surgical outcomes suggest that MOGHE is a widespread pathology in focal epilepsy.

Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system.

Objective.This study aimed at investigating a novel fully implantable deep brain stimulation (DBS) system and its ability to modulate brain metabolism and behavior through subthalamic nucleus (STN) stimulation in a hemiparkinsonian rat model.Approach.Twelve male rats were unilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fully implantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests to analyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery but before stimulation onset and an ON test under DBS. To visualize brain glucose metabolism in the awake animal, two [18F]FDG scans were conducted in the OFF and ON condition. At least 4 weeks after surgery, an [18F]FDOPA scan was used to check for dopaminergic integrity.Main results.In general, STN DBS increased [18F]FDG uptake ipsilesionally and decreased it contralesionally. More specifically, bilateral orbitofrontal cortex, ipsilateral caudate putamen, sensorimotor cortex and nucleus accumbens showed significantly higher tracer uptake in ON compared to OFF condition. Contralateral cingulate and secondary motor cortex, caudate putamen, amygdala, hippocampus, retrosplenial granular cortex, superior colliculus, and parts of the cerebellum exhibited significantly higher [18F]FDG uptake in the OFF condition. On the behavioral level, stimulation was able improve use of the contralesional affected front paw suggesting an effective stimulation produced by the implanted system.Significance.The fully implantable stimulation system developed by us and presented here offers the output of arbitrary user-defined waveforms, patterns and stimulation settings and allows tracer accumulation in freely moving animals. It is therefore a suitable device for implementing behavioral PET studies. It contributes immensely to the possibilities to characterize and unveil the effects and mechanisms of DBS offering valuable clues for future improvements of this therapy.

COVID-19-related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India.

BACKGROUND: COVID-19-related strokes are increasingly being diagnosed across the world. Knowledge about the clinical profile, imaging findings, and outcomes is still evolving. Here we describe the characteristics of a cohort of 62 COVID-19-related stroke patients from 13 hospitals, from Bangalore city, south India. OBJECTIVE: To describe the clinical profile, neuroimaging findings, interventions, and outcomes in COVID-19-related stroke patients. METHODS: This is a multicenter retrospective study of all COVID-19-related stroke patients from 13 hospitals from south India; 1st June 2020-31st August 2020. The demographic, clinical, laboratory, and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT-PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. RESULTS: During the three-month period, we had 62 COVID-19-related stroke patients, across 13 centers; 60 (97%) had ischemic strokes, while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ± 13.20 years, with 34 (77.4%) males. Twenty-six percent (16/62) of patients did not have any conventional risk factors for stroke. Diabetes mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8%, and atrial fibrillation in 4.8%. Baseline National Institutes of Health Stroke Scale score was 12.7 ± 6.44. Stroke severity was moderate (National Institutes of Health Stroke Scale 5-15) in 27 (61.3%) patients, moderate to severe (National Institutes of Health Stroke Scale 16-20) in 13 (20.9%) patients and severe (National Institutes of Health Stroke Scale 21-42) in 11 (17.7%) patients. According to TOAST classification, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion, and 5% had cardioembolic strokes. Three (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/kg and 3 (5%) underwent mechanical thrombectomy, two endovascular and one surgical. Duration of hospital stay was 16.16 ± 6.39 days; 21% (13/62) died in hospital, while 37 (59.7%) had a modified Rankin score of 3-5 at discharge. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality. A comparison to 111 historical controls during the non-COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality, and higher morbidity in COVID-19-related stroke patients. CONCLUSION: COVID-19-related strokes are increasingly being recognized in developing countries, like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of COVID-19-related strokes. COVID-19-related strokes were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation, and higher baseline National Institutes of Health Stroke Scale scores were associated with increased mortality.

Affordability, availability and tolerability of anti-seizure medications are better predictors of adherence than beliefs: Changing paradigms from a low resource setting.

OBJECTIVES: Anti-seizure medication (ASM) non-adherence contributes to treatment gap and increases mortality and morbidity associated with epilepsy. Beliefs about medications are considered better predictors of ASM non-adherence than clinico-demographic factors. We aimed to look into ASM non-adherence rates among adults with epilepsy (AWE), identify the contributing barriers and determine whether medication beliefs were more powerful predictors than clinico-demographic factors. METHODS: This was a cross-sectional study of AWE receiving ASMs. Participants (n = 304) were assessed by validated questionnaires, for non-adherence (8-item Morisky Medication Adherence Scale) and perceptions of ASMs (Beliefs about Medicines Questionnaire) along with clinico-demographic details. RESULTS: Our group with high literacy and low-income had a high non-adherence rate (55 %) despite having positive beliefs (Mean necessity-concern differential [NCD] = 2.86). Among the beliefs, ASM non-adherence was significantly associated with ASM-concern (t = 4.23, p < 0.001) and NCD (t = -4.11, p < 0.001). Stepwise multiple linear regression analysis showed that non-adherence was significantly associated with per-capita income (ß -0.215, p < 0.001), ASM side effects (ß 0.177, p = 0.001), high seizure frequency (ß 0.167, p = 0.002), ASM availability (ß -0.151, p = 0.004), ASM costs (ß -0.134, p = 0.013 and NCD (ß -0.184, p = 0.001). NCD accounted for 2.9 % of the variance in non-adherence whereas the other clinico-demographic variables together accounted for 14.6 %. CONCLUSION: We describe a paradigm shift in AWE with high non-adherence to ASMs, wherein clinico-demographic variables emerge as better predictors of non-adherence than beliefs. High literacy facilitates the perception of need for ASMs whereas costs and side effects hamper adherence.

Apomorphine: The Initial Indian Experience in Relation to Response Tests and Pumps.

BACKGROUND: Apomorphine is an option for continuous dopaminergic therapy in Parkinson's disease (PD). However, its effects in varied populations are limited due to its availability. OBJECTIVE: To assess the efficacy and outcomes of apomorphine in Indian patients. MATERIALS AND METHODS: Retrospective analysis of PD patients who underwent apomorphine response test (ART), along with the subset, who went on to apomorphine pumps. RESULTS: Twenty-nine confirmed PD patients underwent ART and all PD patients showed good clinical response. 19 subjects developed adverse events which included: nausea (n-15, 51.7%), vomiting (n-10, 34.4%), sleepiness (n-08; 27.5%), yawning (n-07, 24.1%), postural hypotension (n-03, 10.3%), dizziness (n-03, 10.3%), and profuse sweating (n-01, 3.4%). Apomorphine pumps were initiated in six subjects, with significant clinical improvement. Adverse events on pump included subcutaneous nodules, nausea, hypersexuality. Two among them subsequently discontinued the pump primarily due to financial constraints. CONCLUSIONS: Apomorphine adds up to the armamentarium for treatment of PD patients in India with good clinical responses.

Bilateral independent periodic lateralised epileptiform discharges at presentation followed by rapid recovery: novel observations from a case of Epstein-Barr virus encephalitis.

Bilateral independent periodic lateralised epileptiform discharges (BIPLEDs) in electroencephalograms (EEGs) are commonly caused by anoxic encephalopathy and central nervous system infections. They are associated with coma and high mortality and are thus markers of poor prognosis. We present a case of encephalitis who presented with BIPLEDs in EEG. Though the clinical, EEG and MRI features closely resembled herpes simplex encephalitis, further investigations proved it to be Epstein-Barr virus (EBV) encephalitis. Despite the presence of BIPLEDs in the EEG, the patient had a rapid clinical response to therapy with acyclovir. We emphasise that BIPLEDs may not always indicate poor prognosis especially in the setting of EBV encephalitis.

'Enemy within': an interesting cause for anemia during warfarin therapy for atrial fibrillation.

The oral anticoagulant warfarin is a vitamin K antagonist and is considered the first line anticoagulant in valvular atrial fibrillation. However prothrombin time should be closely monitored, drug interactions checked and compliance regarding diet ensured when the patient is on warfarin therapy. Anaemia should be looked for, evaluated for the cause and corrected since it is an independent predictor of bleeding and thrombotic episodes during warfarin therapy for atrial fibrillation We present an interesting case of anaemia which developed during warfarin therapy for atrial fibrillation. The patient was on amiodarone and was consuming leafy vegetables resulting in frequent raise in prothrombin time during which time she developed bleeding into the right femoral pseudoaneurysm which had developed following catheterisation for thrombectomy. Surgical correction of pseudoaneurysm was done, comedication was changed and diet compliance ensured which resulted in the subsequent maintenance of prothrombin time in the therapeutic range and steady haemoglobin levels.

Is it safe to treat cerebral venous thrombosis with oral rivaroxaban without heparin? A preliminary study from 20 patients.

OBJECTIVES: Newer oral anticoagulants like rivaroxaban are increasingly becoming the mainstay of treatment in systemic thrombosis. However cerebral venous thrombosis (CVT) is conventionally treated with heparin followed by oral vitamin K antagonists. Currently very little information is available about the use of rivaroxaban in CVT. Rivaroxaban has been used only after the initial treatment with heparin in the available studies. PATIENTS & METHODS: All patients with CVT between January 2017 and June 2017 were initiated directly on oral rivaroxaban. Critically ill patients including those requiring surgical intervention were excluded. The modified Rankin scale was used to assess clinical severity and a scale of 0-1 was defined as excellent outcome. Recanalization was assessed at 3 months follow-up with MR angiography. Complications of the drug including bleeding episodes during treatment and at follow-up were noted. RESULTS: Twenty patients were initiated on rivaroxaban and followed up for a mean duration of 6 months. Eighty percent (16/20) were males and the mean age was 34.1 years. Associated cerebral hemorrhagic infarcts were seen in 11(55%).Outcome was excellent in 19(95%). Complete recanalization was noted in 12(60%) and partial recanalization in 8(40%). No complications emerged out of the drug use. CONCLUSIONS: In clinically stable CVT rivaroxaban is safe and effective and may be used without previous heparin therapy. This can shorten the duration of hospitalization thereby decreasing the costs of treatment.

Trapped ipsilateral lateral ventricle: a delayed complication of hemispherotomy for Rasmussen's encephalitis.

Hemispherotomy is the currently preferred surgical treatment option for refractory unihemispheric epilepsies. The incidence of hydrocephalus is greatly reduced in this disconnective procedure when compared with the resective procedure of anatomical hemispherectomy. We describe the occurrence of ipsilateral trapped lateral ventricle months after hemispherotomy for Rasmussen's encephalitis. There is enough evidence to suggest that this rare and interesting complication is due to the local inflammatory changes associated with the surgical trauma.