How safe is bone health in patients on newer or enzyme inhibitor antiepileptic drugs?

BACKGROUND: Data on the effect of enzyme inhibitors and newer anti-epileptic drugs (AEDs) on bone health is limited with conflicting results. AIM: We compared the effects on bone health of patients exposed to enzyme inducer versus enzyme inhibitor AEDs and newer versus older AEDs. METHODS: We prospectively studied 51 patients on AEDs for more than two years and equal age and sex matched controls from March 2017 to September 2018. Biochemical bone mineral markers and bone mineral density (BMD) were measured and analysed between patients versus controls and between various sub-groups based on enzymatic effect, generation and number of AEDs. RESULTS: Of 51 patients,11(21.5%) had osteopenia and 3(5.9%) had osteoporosis. T-score (-0.75 ±â€¯1.22 versus 0.004 ±â€¯1.0, p < .001) and Z-score at femur neck (-0.38 ±â€¯1.08 versus0.002 ±â€¯0.81, p < .001) were found to be significantly lower in patients compared to controls. Relative risk for low BMD was higher in patients on polytherapy compared to monotherapy (RR = 1.37,CI = 0.69-2.74).Higher relative risk for low BMD was noted with; clobazam (RR = 1.51,CI = 0.82-2.78), oxcarbazepine (RR = 1.33,CI = 0.68-2.59), phenobarbitone (RR = 1.31,CI = 0.26-6.7) and leviteracetam (RR = 1.18,CI = 0.45-3.06) mono or polytherapy and valproate monotherapy (RR = 3.5,CI = 1.09-11.29). No significant difference was noted with regards to mean dosage or metabolic or radiological markers of bone health between patients on enzyme inducer versus inhibitors and newer versus older AEDs. A significant negative correlation was found between cumulative drug load and femur T-score (r2 = -0.27, p = .04). CONCLUSION: Bone health in epilepsy is adversely affected by chronic exposure to AEDs; irrespective of the enzymatic effect or generation of AEDs. Complex pharmacodynamic mechanisms of AEDs as well as pharmacokinetic interactions between various AED polytherapies affects bone health.

Status epilepticus in pregnancy - Can we frame a uniform treatment protocol?

BACKGROUND: There is lack of uniform treatment protocol for status epilepticus (SE) in pregnancy, with majority of data being limited to individual cases or case series. Devising a uniform treatment protocol will facilitate prompt control of SE in pregnancy and reduce adverse maternal and fetal outcomes. METHODS: Literature search was done in various databases including PubMed, CINAHL, EMBASE, TRIP, and the gray literature, including relevant organizational websites, for the topics "Status Epilepticus" and "Pregnancy". English language original research articles, case reports, and systematic reviews that were published in the last 18 years (2000-2018) and addressed SE in relation to pregnancy (i.e., antepartum, labor, or postpartum) were considered for inclusion. RESULTS: Over the past 15 years, a total of seven articles reporting 29 cases of SE related to pregnancy, satisfying the inclusion criteria were analyzed. The most common cause of SE was posterior reversible encephalopathy syndrome (PRES)/reversible cerebral vasoconstriction syndrome (RCVS) spectrum (n = 11, 38%), followed by cortical venous sinus thrombosis (CVT) and autoimmune encephalitis (n = 5, 17%). Twenty-three out of 29 cases (79%) had good maternal outcomes in terms of recovery to baseline. Seventeen fetuses (58%) were delivered at term and seven at preterm (2.4%). First-line agent used was lorazepam in 15 patients (52%) and midazolam in two patients (7%). The most common antiepileptic drug (AED) and anesthesia used for treatment of SE and refractory SE were phenytoin/fosphenytoin (n = 21, 72%) and midazolam (n = 12, 52%), respectively. In all cases due to eclampsia (n = 5), magnesium sulfate was the preferred first-line drug. CONCLUSION: Management of SE in pregnancy is influenced by etiology of SE and duration of pregnancy. It carries a good prognosis if detected early and treated appropriately. Large-scale multicentric studies are warranted for formulating definite guidelines for management of SE in pregnancy. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Status epilepticus related to pregnancy: Devising a protocol for use in the intensive care unit.

BACKGROUND: Status epilepticus (SE) related to pregnancy is rare and carries a significant risk to both the mother and the fetus. OBJECTIVES: We conducted this study to devise a protocol for the management of SE related to pregnancy in a cohort of female patients admitted with SE during pregnancy. MATERIALS AND METHODS: All women who developed SE related to pregnancy (gestation, labor, and puerperium) between January 2000 and December 2016 were included. Data was collected using a structured proforma. RESULTS: There were 17 women who had SE related to pregnancy, of whom 10 had refractory SE. The various causes of refractory SE were eclampsia (N = 2), posterior reversible encephalopathy syndrome (PRES) due to various causes other than eclampsia (N = 3), cortical venous thrombosis (CVT) [N = 3], subarachnoid hemorrhage (SAH) [N = 1], and N-methyl-D-aspartate (NMDA) receptor antibody-mediated encephalitis (N = 1). Six out of 10 women with refractory SE (60%) and five out of 10 fetuses (50%) had a good outcome. CONCLUSION: There is a dearth of literature with regards to SE related to pregnancy and little or no guidelines exist for its management. Awareness about the diverse etiologies other than eclampsia is important. A protocol-based approach to the diagnosis and management of SE is necessary to ensure best outcomes.

Status epilepticus in pregnancy: Etiology, management, and clinical outcomes.

BACKGROUND: Status epilepticus (SE) in pregnancy carries significant risk to both mother and fetus. There is limited literature available on SE occurring in pregnancy world-over, with majority being from obstetric centers. METHODS: All women who developed SE related to pregnancy (gestation, labor, or puerperium) between January 2000 and December 2016 were included in the study. Data were collected from our SE registry, maintained, and archived in the institute. The variables influencing the maternal and fetal outcome were compared using Student's t-test for continuous variables and Fisher's exact test for discrete variables. RESULTS: During the 16-year study period, a total of 348 SE events were recorded in 294 patients. Among these, there were 138 women, of which 17 had SE related to pregnancy. The etiology of SE was remote symptomatic in two and acute symptomatic in 15 patients. The various causes detected after initial evaluation for acute symptomatic SE were eclampsia (n=4), posterior reversible encephalopathy syndrome due to various causes other than eclampsia (n=6), cortical venous thrombosis (n=3), subarachnoid hemorrhage (n=1), and NMDA receptor antibody-mediated encephalitis (n=1).13 of 17 women with SE (76%) had good outcome. Majority of the fetuses had good outcomes, i.e., Category 1 (n=9, 57%). Duration of intensive care unit stay (p=0.029) and Status Epilepticus Severity Score (p=0.0324) at admission, were found to be significantly associated with poor outcomes. CONCLUSION: In any patient presenting with SE occurring in pregnancy, though eclampsia is presumed to be the most common overall cause; it is relevant to consider other etiologies such as posterior reversible encephalopathy syndrome, cortical venous thrombosis, and autoimmune encephalitis especially in cases presenting with refractory SE. Posterior reversible encephalopathy may occur in pregnancy due to diverse etiologies other than eclampsia.

An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome.

Bilateral--otitis media, dacroadenitis, parotitis and left sided infranuclear facial palsy: unusual manifestations of Wegener's granulomatosis.

Wegener's granulomatosis is a systemic vasculitis of unknown aetiology. Although it classically involves the upper respiratory tract, lungs and kidneys, virtually any organ may be affected. We report a rare case of a 45 year old female who presented with bilateral-dacroadenitis, otitis media, parotid enlargement and left sided lower motor neuron type of facial palsy as the initial manifestations of Wegener's granulomatosis.