Noninvasive Ventilation in Myasthenia Gravis.

BACKGROUND: Myasthenic crisis (MC) is mainly managed by invasive ventilation (IV) which is associated with prolonged intubation and ventilation and respiratory complication. AIM: To report the characteristics of patients who can be managed by noninvasive ventilation (NIV) and also predictors of NIV in myasthenia gravis (MG). PATIENTS AND METHODS: In a retrospective study at tertiary care hospital in India during 2013-2015, patients with MG were evaluated. MG was diagnosed by clinical, repetitive nerve stimulation, and acetylcholine receptor antibodies. Patients were intubated based on arterial blood gas criteria. Demographic variables, Myasthenia Gravis Foundation of America (MGFA) score, and clinical examination were done. NIV success was defined if patient did not need mechanical ventilation (MV) in the management or for 72 h after extubation and was considered unsuccessful if patients required MV during this period. RESULTS: Twenty three out of 68 MG patients had MC, 16 patients were given NIV, and 16 IV. Median intensive care unit stay was 18 (4-94) days. Predictors of crisis were infection, bulbar weakness, MGFA > 2b, and history of crisis. NIV was the only respiratory support in 7 patients and reintubation was prevented in 3 patients. NIV failed in 9 patients. Comparison of NIV success and failure did not reveal any difference. CONCLUSION: With NIV, intubation was prevented in 7 and reintubation in 3 patients. NIV has lower incidence of complications. NIV should be tried in patients with impending MC.

Predictors and outcome of status epilepticus in cerebral venous thrombosis.

We report the clinico-radiological characteristics of SE in the patients with cerebral venous thrombosis (CVT), and compare the relative risk of SE in determining death and disability compared with those patients with and without self-limiting seizures. Consecutive patients with magnetic resonance venography (MRV) confirmed CVT, admitted during 2006-2017, were included. Their clinical details, risk factors, and magnetic resonance imaging and MRV findings were noted. Duration of SE, Status Epilepticus Severity Score (STESS), Glasgow Coma Scale score, and response to antiepileptic drugs were noted. 6-month outcomes were noted using the modified Rankin Scale. Of 153 CVT patients, 28 (18.3%) had SE, 62 (40.5%) self-limiting seizures, and 63 (41.2%) did not have seizures or SE. The SE group had a higher incidence of focal motor deficit (71.4% vs. 33%, P = 0.006) and supratentorial lesions (93% vs 55.5%, P = 0.003) than the no-seizure group. Multivariate analysis of SE and no-SE group (includes self-limiting and no seizure) did not indicate any significant predictor, but multivariate analysis of SE and no-seizure group indicated that supratentorial lesion only predicted SE (odds ratio 5.65, 95% confidence interval 1.11-28.76; P = 0.03). Patients with SE and self-limiting seizure had similar clinical and MRI findings. In total, 17.8% had refractory SE; refractoriness was related to the pretreatment duration of SE (P < 0.001). The death and disability were not significantly different between the three groups. At 6 months, 84% patients with SE, 92.3% with self-limiting seizure, and 94.8% in no-seizure group had good recovery.

Evaluation of optic nerve functions in subacute combined degeneration using visual evoked potential and diffusion tensor imaging-a pilot study.

OBJECTIVE:: To evaluate optic nerve involvement in subacute combined degeneration (SACD) using diffusion tensor imaging (DTI) and visual evoked potential (VEP) studies, and their changes following cobalamine treatment. METHODS:: Six patients with SACD and six healthy matched controls were included. Visual acuity, field of vision, and color vision were tested. Pattern shift VEP was done, and P100 latency and amplitude were measured. Optic nerve MRI, and DTI of optic nerve to muscle ratio were measured, and fractional anisotropy ratio (FAR), axial diffusivity ratio (ADR), radial diffusivity ratio (RDR), and mean diffusivity ratio (MDR) were calculated. The patients received hydroxyl cobalamine 1000 µg intramuscularly and their clinical examination, VEP and DTI studies were repeated at 3 months. RESULTS:: The age of the patients ranged between 16 and 60 years and two were females. Their visual acuity, field of vision, and color vision were normal. P100 latency was prolonged in five patients (10 eyes) and amplitude was reduced in one (1 eye). The SACD patients had reduced FAR (1.94 ± 0.55 vs 2.81 ± 0.42; p = 0.01) and increased MDR (1.00 ± 0.04 vs 0.95 ± 0.01; p = 0.01) and RDR (0.96 ± 0.03 vs 0.89 ± 0.01; p = 0.002) compared to the controls. The FAR value correlated with P100 latency (r = -0.88). At 3 months, FAR value increased which was associated with improvement in P100 latency. CONCLUSION:: In SACD patients, optic nerve FAR is reduced and correlates with P100 latency. Both these parameters improve on cobalamine treatment. ADVANCES IN KNOWLEDGE:: Subclinical VEP abnormalities are common in SACD but conventional MRI sequence of optic nerve is normal. DTI of optic nerve reveals reduced fractional anisotropy (FA) values which improve after cobalamine treatment. FA values correlate with prolongation of P100 latency. DTI and VEP abnormalities suggest subclinical optic nerve myelin dysfunction.

A Study of Super Refractory Status Epilepticus from India.

BACKGROUND: Super refractory status epilepticus (SRSE) is an important and recently recognized neurological emergency. PURPOSE: In view of paucity of studies on SRSE, we report the frequency, etiology and outcome of SRSE. METHODS: In a hospital-based observational study during 2013 to 2016, consecutive patients with SRSE [persistence of status epilepticus (SE) for 24 h or more, or recurrence of SE on weaning of intravenous anesthetic] were included. The demographic, clinical, and laboratory data were obtained and the severity of SE was defined using Status Epilepticus Severity Score (STESS). The outcome was defined as control of SE, hospital death, and functional status at the time of discharge. RESULTS: Fourteen (13%) patients developed SRSE. Their median age was 27.5 (2-70) years and four were below 18 years of age. The etiology of SRSE was metabolic encephalopathy and encephalitis in five patients each, cerebral venous sinus thrombosis in one and miscellaneous disorders in three patients. Six (43%) patients died. The patients with SRSE had higher admission STESS (p = 0.04), and longer intensive care unit (p < 0.01) and hospital (p = 0.004) stay compared to non-SRSE group. The patients with treatable etiology had better outcome. CONCLUSION: SRSE occurred in 13% patients with SE and 43% of them died. The SRSE patients with treatable etiology had a better outcome.

Comparison of lacosamide versus sodium valproate in status epilepticus: A pilot study.

PURPOSE: The purpose of this study was to compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant SE. METHODS: Patients with LOR-resistant SE were randomized to intravenous LCM 400mg at the rate of 60mg/kg/min or SVA 30mg/kg at the rate of 100mg/min. The SE severity score (STESS), duration of SE and its etiology, and MRI findings were noted. Primary outcome was seizure cessation for 1h, and secondary outcomes were 24h seizure remission, in-hospital death, and severe adverse events (SAE). RESULTS: Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One-hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs 69.7%; P=0.79). Twenty-four-hour seizure freedom was insignificantly higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%). Death (10 vs 12) and composite side effects (4 vs 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (1 patient), and SVA with liver dysfunction (6). CONCLUSION: In patients with LOR-resistant SE, both LCM and SVA have comparable efficacy and safety.

Spectrum and Predictors of Refractory Status Epilepticus in a Developing Country.

OBJECTIVE: Refractory status epilepticus (RSE) can influence the outcome of status epilepticus (SE). In the present study, we report the aetiology and predictors of outcomes of RSE in a developing country. METHODS: This is a prospective hospital-based study of SE patients (continuous seizures for five minutes or more). Those who had SE persisting after two antiepileptic drugs were defined as having RSE. We present the demographic information, duration, and type of SE, and we note its severity using the status epilepticus severity score (STESS), its aetiology, comorbidities and imaging findings. The outcome of RSE was defined as cessation of seizures and the condition upon discharge, as assessed by the modified Rankin Scale. RESULTS: A total of 35 (42.5%) of our 81 patients had RSE. The median duration of SE before starting treatment was 2 hours (range=0.008-160 h). The most common causes of RSE were stroke in 5 (14.3%), central nervous system (CNS) infections in 12 (34.3%) and metabolic encephalopathies in 13 (37.1%) patients. Some 21 (60%) patients had comorbidities, and the STESS was favourable in 7 (20%) patients. A total of 14 (20%) patients died, but death was directly related to SE in only one of these. Some 10 patients had super-refractory status epilepticus, which was due to CNS infection in 5 (50%) and metabolic encephalopathy in 3 (30%). On multivariate analysis, an unfavourable STESS (p=0.05) and duration of SE before treatment (p=0.01) predicted RSE. Metabolic aetiology (p=0.05), mechanical ventilation (p60 years (p=0.003) were predictors of poor outcomes. CONCLUSIONS: RSE was common (42.5%) among patients with SE in a tertiary care center in India. It was associated with high mortality and poor outcomes. Age above 60 years and metabolic aetiology were found to be predictors of poor outcomes.

Status epilepticus: Refractory and super-refractory.

Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent. RSE occurs in 23%-48% of the patients and SRSE in approximately 22% of the patients with SE. In general, RSE occurs in patients with new-onset seizures rather than in patients with chronic epilepsy. The etiology of RSE in developing countries is dominated by central nervous system (CNS) infections and head injury compared to stroke and drug withdrawal in the developed countries. The treatment of RSE and SRSE is not evidence based. Following benzodiazepines, the second line antiepileptic drugs include sodium valproate, phenytoin, levetiracetam, and anesthetic drugs such as midazolam, phenobarbital, and propofol. Most intravenous anesthetic drugs produce hypotension and respiratory suppression; therefore, patients with RSE are managed in intensive care units (ICUs). In RSE patients, electroencephalogram (EEG) burst suppression with interburst interval of 2-20 s or even flat EEG has been tried. Recently, concerns have been raised on the safety of burst suppression in RSE and SRSE. The paucity of ICUs in developing countries limits the use of these management protocols. There is a need to explore intravenous AEDs with safer cardiovascular and respiratory profile for the management of SE.

A randomized controlled trial of lacosamide versus sodium valproate in status epilepticus.

OBJECTIVE: To compare the efficacy and safety of lacosamide (LCM) and sodium valproate (SVA) in lorazepam (LOR)-resistant status epilepticus (SE). METHODS: Patients with LOR-resistant SE were randomized to intravenous LCM 400 mg at a rate of 60 mg/kg/min or SVA 30 mg/kg at a rate of 100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and magnetic resonance imaging (MRI) findings were noted. Primary outcome was seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission, in hospital death and severe adverse events (SAEs). RESULTS: Sixty-six patients were included, and their median age was 40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their demographic, clinical, STESS, etiology, and MRI findings were not significantly different. One hour seizure remission was not significantly different between LCM and SVA groups (66.7% vs. 69.7%; p = 0.79). Twenty-four hour seizure freedom was higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%), but this difference was not statistically significant. Death (10 vs. 12) and composite side effects (4 vs. 6) were also not significantly different in LCM and SVA groups. LCM was associated with hypotension and bradycardia (one patient), and SVA with liver dysfunction (six patients). SIGNIFICANCE: In LOR-resistant SE patients, both LCM and SVA have comparable efficacy and safety. SVA resulted in slightly better 24 h seizure remission.

Direct and indirect cost of myasthenia gravis: A prospective study from a tertiary care teaching hospital in India.

Myasthenia gravis (MG) requires lifelong treatment. The cost of management MG is very high in developed countries but there is no information on the cost of management of MG in the developing countries. This study reports the direct and indirect cost and predictors of cost of MG in a tertiary care teaching hospital in India. In a prospective hospital based study, from a tertiary hospital in India 66 consecutive patient during 2014-2015 were included. The age of the patients ranged between 6 and 75years. The severity of MG was assessed by myasthenia gravis foundation association (MGFA) class (MGFA) I-V. The patient data was collected s and their direct cost was calculated from the computerized Hospital information system. The indirect cost was calculated from patient's memory, checking the bills of transportation and wages loss by the patient or the care giver. Total annual cost of MG ranged between INR (4560-532227) with median INR 61390.5 (US$911.64). The median cost of outpatient department (OPD) consultation of 16 patients was INR 20439.9 (US$303.53), of 50 admitted patients was INR 44311.8 (US$658.03) and 21 intensive care unit (ICU) patients was INR 59574.3 (US$ 884.6) and the direct cost of thymectomy was INR 45000 (US$ 668.25). Direct cost was related to indirect cost (r=0.55; p=0.0001). Predictors of patient outcome were severity of MG, ICU admission, and thymectomy. The total median cost for management of myasthenia gravis was INR 61390.5 (4560-532227, US$911.64) per year, and the cost was mainly determined by the severity of MG.

Cost of status epilepticus in a tertiary care hospital in India.

PURPOSE: Status epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. METHODS: SE was defined as continuous seizure for ≥ 5 min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. RESULTS: Fifty-five patients aged 8-90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3-6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1-72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600-574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. CONCLUSION: Acute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation.