Balancing between apoptosis and survival biomarkers in the patients with tuberculous meningitis.

BACKGROUND: The balancing factor of apoptosis, survival, inflammatory and oxidative stress biomarkers may determine the clinico-radiological severity and death in the patients with tuberculous meningitis (TBM). AIM: We report the relationship of death [caspase-3, malondialdehyde (MDA), tumor necrosis factor-α (TNFα), interleukin 6 (IL6)] and survival biomarkers [X-linked inhibitory apoptotic protein (XIAP), IL10, glutathione (GSH) and catalase] in TBM, and its role in determining disease severity and death. METHODS: The diagnosis of TBM was based on clinical, MRI and cerebrospinal fluid (CSF) findings. Their clinical and MRI findings were noted. The severity of TBM was categorized as stages I to III. Serum and CSF caspase-3 and XIAP were measured by ELISA, and TNFα, IL6 and IL10 gene expression in peripheral blood mononuclear cells using RT-PCR (reverse-transcriptase polymerase chain reaction). Plasma MDA, GSH and catalase were measured by spectrophotometer. RESULTS: There were 40 patients with TBM whose mean age was 31.6 years and 50% were females. TBM patients had higher expression of death (caspase-3, TNFα, IL6, and MDA) and suppression of survival biomarkers (XIAP, catalase and GSH) compared to the healthy controls. Caspase-3 positively correlated with TNFα, IL6 and MDA, and negatively with XIAP, GSH and catalase. Patients with longer duration of illness and definite TBM had higher expression of caspase-3. Patients who died has higher expression of caspase-3 and suppression of XIAP compared to those who survived. CONCLUSION: It can be concluded from this study that there is up-regulation of death signals and suppression of survival signals in TBM.

Oxidative stress and ER stress are related to severity of tubercular infection.

To report the markers of oxidative stress and endoplasmic reticulum (ER) stress in tuberculosis of differing severity. Ninety patients with tuberculosis, 30 each with pulmonary tuberculosis (PTB), Pott's spine (PS) and tuberculous meningitis (TBM) were included. The diagnosis and severity of the respective group was based on pre-defined criteria. Six-months outcome and complications (Hyponatremia, paradoxical worsening and Drug induced hepatitis(DIH)) were recorded. Serum Melanodehyde (MDA) , glutathione (GSH), total antioxidant capacity (TAC), ER stress markers ATF-4,GRP-78 and CHOP, were measured using spectrophotometry and real time PCR. The oxidative and ER stress markers were correlated with different subgroups, severity of TBM, complications and outcome. The severity of TBM correlated with alteration in oxidative and ER stress markers. MDA was related to hyponatremia (P = 0.045), paradoxical worsening (P = 0.035) and DIH (P = 0.038), TAC correlated with paradoxical worsening (P = 0.047) and DIH (P = 0.015). In PS, MDA correlated with paradoxical worsening (P = 0.032) and DIH (P = 0.032); and in PTB, MDA correlated with hyponatremia (P = 0.025) and DIH (P = 0.037). Changes in stress marker levels were more marked in TBM compared to PS and PTB. Outcome of TBM correlated with MDA (P = 0.002), PS to MDA(P = 0.004), TAC(P = 0.05) CHOP(P = 0.004), GRP78(P = 0.001), ATF4(P = 0.045) and PTB to MDA(P = 0.0450), TAC(P = 0.014), CHOP(P = 0.025) and GRP78(P = 0.035). Oxidative and ER stress markers seem to be related to severity of TB, its complications and outcome.

Outcome of Guillain-Barré syndrome following intravenous immunoglobulin compared to natural course.

BACKGROUND AND PURPOSE: Intravenous immunoglobulin (IVIg) is recommended in Guillain-Barré syndrome (GBS), but its efficacy may vary in different subtypes. We report the outcomes of patients with GBS following IVIg treatment compared to the natural course (NC). We also compare the effect of IVIg treatment in different subtypes of GBS. METHODS: From a cohort of 528 GBS subjects, we have extracted 189 patients who received IVIg and compared their outcomes with 199 age- and peak disability-matched patients who did not receive IVIg, plasmapheresis, or corticosteroid. Disability was assessed using the 0-6 Guillain-Barré Syndrome Disability Scale (GBSDS). Clinical and neurophysiological subtypes were recorded. The primary outcome was functional disability at 6 months, which was categorized as complete (GBSDS ≤ 1), partial (GBSDS 2-3), or poor (GBSDS > 3). The secondary outcomes were in-hospital death, duration of hospitalization, and mechanical ventilation. RESULTS: In-hospital death (2.6% vs. 2%, p = 0.74) and 3-month poor recovery (20.7% vs. 18%) were similar in the IVIg and NC groups. At 6 months, however, a lesser proportion of patients in the IVIg group had poor recovery (2.2% vs. 8.3%, p = 0.026). The outcomes of IVIg and NC were compared in 72 acute motor axonal neuropathy (AMAN) and 256 acute inflammatory demyelinating polyradiculoneuropathy (AIDP) patients. IVIg therapy did not alter the outcome in AMAN but resulted in a lesser proportion of poor recovery at 6 months in AIDP (0.8% vs. 6.6%, p = 0.03). CONCLUSIONS: IVIg is beneficial in AIDP variants of GBS but not in the AMAN subtype. A customized treatment may be cost-effective until a randomized controlled trial is conducted in AMAN.

Renin, antidiuretic hormone (ADH), and ADH receptor levels in cerebral salt wasting associated with tuberculous meningitis.

BACKGROUND: To evaluate serum antidiuretic hormone (ADH), its receptors, and renin levels in cerebral salt wasting (CSW) in tuberculous meningitis (TBM). METHODS: Patients diagnosed with definite (n = 30) or probable TBM (n = 47) who developed hyponatremia (CSW, SIADH, or miscellaneous causes) were included. Sequential measurement of serum ADH, ADH-R, and renin activity by enzyme-linked immunosorbent assay was done and correlated with serum sodium level, urinary output, and fluid balance. RESULTS: Out of 79 TBM patients, CSW was observed in 36, SIADH in four, and miscellaneous hyponatremia in eight patients. CSW patients had a longer hospital stay (P < 0.001), lower GCS score (P < 0.007), higher MRC grade (P < 0.007), and a lower serum Na (P < 0.001) compared to non-CSW TBM patients. In severe CSW patients, serum ADH and ADH-R were correlated with hyponatremia and returned to baseline on correction; however, serum renin levels remained elevated. Serum ADH was related to hyponatremia but ADH-R and renin were not. ADH-R and renin levels did not significantly differ in CSW and SIADH. CONCLUSION: CSW is the commonest cause of hyponatremia in TBM and correlates with disease severity. ADH is related to hyponatremia, but ADH receptor and renin are not.

Phonophobia and brainstem excitability in migraine.

Phonophobia in migraineurs may be due to lower hearing threshold (HT) and higher brainstem neuronal excitability. We report the correlation of phonophobia in migraineurs with HT, brain stem auditory evoked potential (BAEP) findings, and auditory triggers. Sixty-one migraineurs and 101 controls were included for HT, of whom 59 migraineurs and 31 controls had BAEP studies. Clinical details, migraine triggers, and headache frequency were noted. Hearing threshold was measured, and amplitudes of waves I to V of BAEP studies were measured. Migraineurs had lower HT compared with controls (41.61 ± 5.25 versus 45.39 ± 6.26 dB; p < 0.001) especially in chronic migraine (40.24 ± 4.81; p < 0.001). Hearing threshold correlated with headache frequency (p < 0.05) and auditory, visual, and tactile (p < 0.05) triggers. Hearing threshold was lower during headache (p < 0.001). Wave II, III, and IV amplitudes of BAEP were higher in migraineurs than the controls. Wave II (p < 0.05) and III (p < 0.05) amplitudes correlated with HT. Migraineurs have lower HT, especially in those having chronic migraine, ictal HT recording, and multiple sensory triggers. Higher amplitudes of BAEP waves in migraineurs and their relationship with the frequency of headache and HT suggest the sensitization of brainstem auditory neurons.

Rest or 30-Min Walk as Exercise Intervention (RESTOREX) in Myasthenia Gravis: A Randomized Controlled Trial.

INTRODUCTION: There is a lack of evidence about the usefulness of exercise or rest in myasthenia gravis (MG). This study is aimed to evaluate the efficacy and safety of exercise or rest in MG. METHODS: In a single-center open-labeled randomized controlled trial, the patients with mild to moderate MG were randomized to 30-min walk or rest in addition to the standard treatment. The primary endpoint was 50% improvement in the MG Quality of Life (MG-QOL15), and secondary endpoints were change in the Myasthenic Muscle Score (MMS), MG Activities of Daily Living (MGADL), grip strength, dose of acetylcholine esterase inhibitor and prednisone, 6-min walk test (6MWT), decrement in trapezius on the low-rate repetitive nerve stimulation test, and adverse events. The outcomes were defined at 3 months, by >50% improvement in these outcome parameters. RESULTS: Forty patients with MG were randomized to the exercise or rest arm. The 2 arms were matched for demographic and clinical parameters. The patients in the exercise arm had significantly better QOL evidenced by MG-QOL15 (p = 0.02). The secondary endpoints, distance covered in 6MWT (p = 0.007), were also better in the exercise arm without any adverse event. CONCLUSION: Regular exercise for 30 min in mild and moderate MG improves quality of life and walking distance compared to rest and is safe. CLINICAL TRIAL REGISTRATION: The clinical trial registration number is CTRI/2019/11/021869.

Role of IV Immunoglobulin in Indian Children With Guillain-Barré Syndrome.

OBJECTIVES: To evaluate the outcome of Indian children with Guillain-Barré syndrome who received IV immunoglobulin compared with those who did not receive any specific therapy. DESIGN: Single center, prospective cross-sectional study. SETTING: Tertiary care neurology teaching hospital. PATIENTS: Children (≤ 18 yr old) with Guillain-Barré syndrome were included from a prospectively maintained Guillain-Barré syndrome registry from January 2008 to April 2017. Children were classified into acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and inexcitable motor nerves based on nerve conduction study. INTERVENTIONS: Out of 138 pediatric Guillain-Barré syndrome, 50 received IV immunoglobulin and another 50 age and peak disability matched controls (who did not receive IV immunoglobulin or plasmapheresis) were selected from the same registry for comparison. MEASUREMENTS AND MAIN RESULTS: Outcome at 3 and 6 months was defined on the basis of a 0-10 Clinical Grading Scale into complete (Clinical Grading Scale < 3), partial (Clinical Grading Scale 3-5), and poor (Clinical Grading Scale > 5) recovery. The primary outcome was proportion of patients with complete recovery at 3 and 6 months in IV immunoglobulin and non-IV immunoglobulin groups. Secondary outcomes included in-hospital deaths, duration of mechanical ventilation, and hospital stay. Subgroup analysis was done in acute motor axonal neuropathy and acute inflammatory demyelinating polyradiculoneuropathy groups. The baseline characteristics were similar except for shorter duration of illness and higher proportion of facial palsy in IV immunoglobulin group. Hospital deaths, duration of mechanical ventilation, hospital stay, and outcome at 3 and 6 months were not different between the two groups. Children with acute motor axonal neuropathy had better recovery at 6 months on IV immunoglobulin (58.3% vs 11.1%; p = 0.03), but not those with acute inflammatory demyelinating polyradiculoneuropathy (58.3% vs 72.2%; p = 0.22). In nonambulatory Guillain-Barré syndrome children, complete recovery at 6 months was similar in IV immunoglobulin and non-IV immunoglobulin group (57.4% vs 57.1%; p = 0.98). CONCLUSIONS: In Indian children with Guillain-Barré syndrome, the outcome at 6 months in IV immunoglobulin treated group was similar to non-IV immunoglobulin group. Children with acute motor axonal neuropathy responded better to IV immunoglobulin.

Cerebral Venous Sinus Thrombosis Score and its Correlation with Clinical and MRI Findings.

BACKGROUND: It is plausible that extent of cerebral venous sinus thrombosis (CVST) may determine clinical severity, magnetic resonance imaging (MRI) lesion, and outcome, therefore this study was undertaken. METHODS: A total of 160 CVST patients were included and their clinical details, risk factors, Glasgow Coma Scale score, and parenchymal lesion on MRI were noted. The extent of venous sinus thrombosis on magnetic resonance venography was assessed by using CVST score which was computed giving 1 point for each thrombosed sinus and 3 points to superior sagittal sinus (SSS). Death and outcome at 6 months were assessed using modified Rankin Scale (mRS) as good (≤2) and poor (mRS 3-5). RESULTS: Their median age was 29.5 years, and 76 (47%) were females. The median CVST score was 3 (range 1-9). CVST score did not correlate with clinical severity and risk factors. Insignificantly higher proportion of patients had parenchymal lesion with a CVST score of more than 2 (76.5% versus 64.2%). Superficial venous system thrombosis, however, correlated with seizure, papilloedema, and frontal lobe lesion. Frontal, temporal lesion correlated with SSS thrombosis, frontal and temporal with transverse sinus, temporal and cerebellar involvement in sigmoid, and basal ganglia and thalamus in straight sinus thrombosis. Seventeen patients (11%) died, and at 6 months, 132 (82%) had good and 11 (7%) poor recovery. Death and 6 months outcomes were not related to CVST score. CONCLUSIONS: Extent of CVST does not determine clinical severity, MRI lesion, and outcome. The location of parenchymal lesion however is related to thrombosis of draining sinus.

Prospective comparison of acute motor axonal neuropathy and acute inflammatory demyelinating polyradiculoneuropathy in 140 children with Guillain-Barré syndrome in India.

INTRODUCTION: There have been few reports on subtypes of Guillain-Barré syndrome (GBS) in children. We compared clinical and laboratory findings of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). METHODS: One hundred forty children with GBS were included. Based on nerve conduction study (NCS) findings, patients were subclassified as AIDP, AMAN, acute motor sensory axonal neuropathy (AMSAN), and equivocal. RESULTS: Clinically, 72.1% of patients had pure motor, 24.3% motor sensory, and 3.4% Miller Fisher syndrome. Based on NCS, 67.8% of patients had AIDP, 23.6% had AMAN, and 4.3% had AMSAN. By 3 months, 2.1% patients had died, 47.1% had complete recovery, and 24.3% had poor recovery (wheelchair-bound). Children with AMAN had more frequent lower limb weakness (P = 0.02) and a lower probability of complete recovery (P = 0.01) at 3 months than children with AIDP (56% vs. 30%). DISCUSSION: AIDP is the most common GBS subtype in children. It is characterized by better recovery at 3 months when compared with AMAN. Muscle Nerve 57: 761-765, 2018.

A study of oxidative stress in migraine with special reference to prophylactic therapy.

OBJECTIVE: The role of oxidative stress markers in migraine and effect of treatment on these has been reported. SUBJECTS AND METHODS: One hundred and fifty patients having > four attacks of migraine headache/month were included. Headache severity, Migraine Index (MI) and frequency of headache were noted. 120 patients received repetitive transcranial magnetic stimulation (rTMS) therapy and 30 patients received Amitriptyline (AMT). Recovery was defined by 50% improvement in frequency, severity or reduction in MI. Oxidative stress and antioxidant markers have been estimated in patients before and after treatment and correlate the clinical and outcome parameters. RESULTS: Glutathione (GSH) (P < 0.001), glutathione-S-transferase (GST) (P = 0.049) and total antioxidant activity (TAC) (P < 0.001) level were significantly reduced in migraine patients. GSH (P = 0.02), GST (P = 0.05) and TAC (P < 0.001) were reduced in ictal migraineurs compared to controls. GSH (P < 0.001) and TAC (P = 0.003) levels increased after treatment compared to the base line. There is an increase in GSH levels in the patients who had improved following rTMS (P = 0.003); placebo (P = 0.001) and AMT (P = 0.013). TAC levels were also increased following rTMS (P = 0.009) and AMT (P = 0.020). CONCLUSION: There is evidence of oxidative stress in migraine pathophysiology. Following treatment, oxidative stress declined following both pharmacological and rTMS.

Pellets in the Eye: Cerebral Aneurysm and Encephalomyeloneuropathy as Presenting Syndromes.

Lead poisoning following retained gunshot pellets resulting in recurrent episodes of encephalomyeloneuropathy is rare and association of intracranial aneurysm with lead poisoning is interesting. The case report describes about a 58-year ayurvedic doctor who was hospitalized for recurrent abdominal pain and limb weakness appearing spontaneously and improving in a few days to weeks. He had 20 such attacks in last 30 years starting at 25 years after the gunshot wound that resulted in retention of 2 lead pellets in his skull. Cranial imaging demonstrated left posterior communicating aneurysm. His initial blood lead level was 206.10 µg/dl, and following chelation with oral d-penicillamine, the lead level declined and was asymptomatic. After 4-year follow-up, he developed subarachnoid hemorrhage, which was managed with intravascular coiling of the ruptured aneurysm. The gunshot pellets are generally not removed, especially, if they are in inaccessible location. Our patient highlights that such cases should be closely monitored.

Evaluation of cerebral arterial and venous system in tuberculous meningitis.

BACKGROUND: Central nervous system infection especially pyogenic results in cerebral venous sinus thrombosis. Tuberculous meningitis (TBM) although associated with infarctions but there is no comprehensive study evaluating the role of CVST contributing in infarction. PURPOSE: To evaluate cerebral arterial and venous system using MR angiography (MRA) and MR venography (MRV) in TBM, and correlate with clinical and MRI findings. MATERIALS AND METHODS: Consecutive patients with TBM were evaluated clinically and their consciousness was assessed by using Glasgow Coma scale. Cerebrospinal fluid analysis was done. Patients were subjected to MRI, MRA and MRV studies. The severity of TBM was categorized as grades I to III. Presence of infarction on MRI and its cause as arterial or venous was noted based on MRA and MRV abnormalities. RESULTS: Twenty-six patients were included whose median age was 23 years. Seven (26.9%) patients had stage I, 12 (46.2%) stage II and 7 (26.9%) stage III TBM. MRI revealed infarction in 13 (50%) patients and were in tubercular zone (caudate, lentiform nuclei, anterior limb and genu of internal capsule, and anterior thalamus) in all except one. MRA was abnormal in 11/25 (42.3%) patients; 7 had middle cerebral artery, 2 both posterior cerebral artery and middle cerebral artery, and 2 had narrowing of all intracranial vessels. MRV however did not reveal any evidence of CVST although revealed variation in normal anatomy in 14 (53.8%) patients, commonest being hypoplastic transverse sinus. CONCLUSION: In TBM, infarction occurs in 50% patients, and is of arterial in origin. Cerebral venous system is usually spared in TBM.

Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies.

Tuberculous meningitis (TBM) remains a major cause of death and disability in tuberculosis-endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of TBM clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrollment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention TBM studies should improve the quality of future research outputs, can facilitate multicenter studies and meta-analyses of pooled data, and could provide the foundation for a global TBM data repository.

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.

Effect of high rate rTMS on somatosensory evoked potential in migraine.

Background Sensitization and impaired habituation of cortical neurons have been reported in migraineurs. Repetitive transcranial magnetic stimulation (rTMS) may change these phenomena and be the basis of therapeutic response. We report the effect of 10 Hz rTMS on sensitization and habituation of median somatosensory evoked potential (SEP) in migraineurs, and correlate these changes with clinical response. Methods Migraineurs having four or more episodes of headache per month were included and their clinical details were noted. Three sessions of 10 Hz rTMS, 600 pulses in 412.4 seconds were delivered on the left frontal cortex corresponding to the hot spot of right abductor digiti minimi, on alternate days. Median SEP was done before and 30 minutes after the third rTMS session. Sensitization (block I N20 amplitude) and impaired habituation (if N20 amplitude of block 2 or 3 were not suppressed compared to block I) were noted. The reduction in frequency and severity of headache in the next month were noted and correlated with SEP changes. Results Ninety-four migraineurs were included; 56 received true rTMS and 38 sham stimulation. Following stimulation, reduction in N20 amplitude of block 1 correlated with a reduction in frequency and severity of headache at one month. The impaired habituation significantly improved in the true rTMS group compared to sham stimulation, and correlated with a reduction in the severity of headache but not with frequency. Conclusion In migraineurs, 10 Hz rTMS improves habituation and may be the biological basis of headache relief.

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.

Clinical significance of magnetic resonance imaging findings in chronic low backache.

BACKGROUND & OBJECTIVES: Magnetic resonance imaging (MRI) is frequently done for the evaluation of chronic low backache (CLBA), however, its significance in Indian patients has not been evaluated. We report here the MRI findings in patients with CLBA and their sensitivity and specificity with clinical evidence of radiculopathy and localized CLBA as well as correlate these with pain severity and disability. METHODS: Seventy two patients with CLBA aged 20-70 yr without trauma, infection, tumour, metastasis and vascular malformation were included in the study. Their demographic characteristics, lifestyle, education and employment were noted. Lumbosacral MRI was carried out and 19 MRI parameters at six levels (D12-L1-L5-S1) were noted. The severity of pain was assessed by Numeric Rating Scale (NRS, 0-10) and disability by Oswestry Disability Index (ODI). RESULTS: MRI was abnormal in all patients, the most common being disc desiccation (90.3%) followed by facet joint arthropathy (FJA; 75%) and nerve root compression (NRC; 72.2%). Endplate changes and high-intensity zone were noted in 58 and 50 per cent of patients, respectively. One-third patients with FJA, however, were below 30 yr of age. NRC on MRI had 61.3 per cent sensitivity and 10 per cent specificity with clinical radiculopathy. FJA had 60.7 per cent sensitivity and 15.9 per cent specificity with localized CLBA. None of the MRI parameters and MRI sum score correlated with NRS and ODI. On multivariate analysis, NRS was independent predictor of ODI (odds ratio 0.58, 95% confidence interval 0.35-0.98, P=0.04). INTERPRETATION & CONCLUSIONS: In patients with CLBA, NRC on MRI showed poor specificity with corresponding clinical radiculopathy and FJA with localized backache. None of the MRI abnormality correlated with the severity of pain or disability.

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.