The IN-MIDAZ study - Intranasal midazolam in aborting seizures - An epilepsy monitoring unit based randomized controlled trial for efficacy.

OBJECTIVE: To compare efficacy and safety of Intranasal and Intramuscular routes of midazolam administration in terminating seizures. METHOD: This was an open label Randomized controlled trial (RCT). People with drug resistant epilepsy (DRE) undergoing Video Electroencephalogram (VEEG) monitoring, were randomized in a 1:1 ratio to receive either Intranasal (IN) or Intramuscular (IM) midazolam, for prolonged seizures: longer than 5 min for focal, and longer than 2 min for focal to bilateral tonic-clonic. Outcome assessor was blinded to the allocation arm. Primary outcome was time to electrographic seizure termination after administration of midazolam. All adverse events in both the groups were noted. RESULT: A total of 1108 seizures were recorded in 130 subjects, of which 110 (65 seizures in 23 subjects in IN group; 45 seizures in 18 subjects in IM group) seizures required midazolam administration and were included in final analysis. Mean time to electrographic seizure termination after midazolam administration was 45.1 ± 23.8 s in the IM group and 90.4 ± 59.0 s in the IN group (p = 0.0014); mean time to clinical seizure termination was 53.9 ± 25.8 s in IM group and 104.3 ± 66.4 s in the IN group (p = 0.002). Local side effects were more in IN group; hypotension as serious adverse event was noted in the IM group. SIGNIFICANCE: Though mean time to electrographic and clinical seizure termination was significantly lesser in Intramuscular group for both adults and pediatric population, it was still under 2 min in the Intranasal midazolam group.IN midazolam is a useful option for terminating seizures.

Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring.

OBJECTIVE: Antiepileptic drugs (AEDs) are routinely withdrawn during long-term video-electroencephalography (EEG) monitoring (LTM), to record sufficient number of seizures. The efficacy of rapid and slow AED taper has never been compared in a randomized control trial (RCT), which was the objective of this study. METHODS: In this open-label RCT, patients aged 2-80 years with drug-resistant epilepsy (DRE) were randomly assigned (1:1) to rapid and slow AED taper groups. Outcome assessor was blinded to the allocation arms. Daily AED dose reduction was 30% to 50% and 15% to <30% in the rapid and slow taper groups, respectively. The primary outcome was difference in mean duration of LTM between the rapid and slow AED taper groups. Secondary outcomes included diagnostic yield, secondary generalized tonic-clonic seizure (GTCS), 4- and 24- hour seizure clusters, status epilepticus, and need for midazolam rescue treatment. The study was registered with Clinical Trial Registry-India (CTRI/2016/08/007207). RESULTS: One hundred forty patients were randomly assigned to rapid (n = 70) or slow taper groups (n = 70), between June 13, 2016 and February 20, 2017. The difference in mean LTM duration between the rapid and slow taper groups was -1.8 days (95% confidence interval [CI] -2.9 to -0.8, P = .0006). Of the secondary outcome measures, time to first seizure (2.9 ± 1.7 and 4.6 ± 3.0 days in the rapid and slow taper groups respectively, P = .0002) and occurrence of 4-hour seizure clusters (11.9% and 2.9% in the rapid and slow taper groups, respectively, P = .04) were statistically significant. None of the other safety variables were different between the 2 groups. LTM diagnostic yield was 95.7% and 97.1%, in rapid and slow taper groups respectively (P = .46). SIGNIFICANCE: Rapid AED tapering has the advantage of significantly reducing LTM duration over slow tapering, without any serious adverse events.

Can home video facilitate diagnosis of epilepsy type in a developing country?

OBJECTIVES: The study aimed to evaluate the feasibility and yield of semiological features from home videos and compare them to those inferred from history provided by the caregiver of a person with epilepsy (PWE). A comparison of the accuracy of classification of epilepsy based on home videos and medical history was also done. METHODS: We enrolled PWEs who were awaiting admission for video electroencephalography (VEEG) to the epilepsy monitoring unit (EMU) in this prospective observational study. In phase I of the study, we encouraged caregivers to make home videos which were analyzed. A structured questionnaire dealing with 29 different semiological features was completed based on the information gathered from home videos. In phase II of the study, the questionnaire was administered to the patient's caregivers. In phase III the patients underwent VEEG recording, and the semiology from VEEG was analyzed to complete the same questionnaire. We also classified epilepsy type using home videos and medical history and compared it to that using VEEG finding. The information gathered from VEEG was considered the gold standard. Accuracy was calculated for the different semiological signs comparing medical history to VEEG findings. RESULTS: A total of 340 PWE fulfilled the inclusion and exclusion criteria, and their caregivers completed the questionnaire. Home videos were collected from 312 patients and 624 seizures were analyzed. The mean number of signs of semiology recorded after analysis of home videos was 3.3±2.2, and from the medical history was 2.1±1.1 (P<0.01). A total of 572 seizures in 282 patients admitted in the EMU were evaluated on VEEG. Bilateral generalized clonic movements of limbs, motor movement around mouth, fear, visual phenomenon, hemisensory phenomenon, and post-ictal unilateral weakness had the highest accuracy. The overall agreement of semiological signs inferred from medical history versus VEEG was 0.75 and between home video recordings versus VEEG was 0.92. A larger number of patients were correctly categorized into the focal epilepsy group when home videos were used to classify compared to when medical history was used. CONCLUSIONS: Home videos are more reliable in picking up semiological signs and classifying epilepsy type than history provided by caregivers of PWEs. Home videos are a complementary tool in a developing country like India.

A case of recurrent status epilepticus and successful management with progesterone.

Catamenial epilepsy (CE) is a commonly observed phenomenon among women with epilepsy, the management of which is both hormonal and non-hormonal. Progesterone therapy has been tried in these patients, as the possible mechanism of CE is withdrawal of progesterone and a higher oestrogen/progesterone ratio in the perimenstrual and periovulatory periods. Here, we describe a 24-year-old lady with multiple seizure types since childhood, which were refractory to adequate antiepileptic drug therapy after menarche with catamenial clustering of seizures. She went on to have several episodes of non-convulsive status epilepticus also with similar periodicity, which would abate only with midazolam infusion, without the need for ventilatory support. She was tried on acetazolamide, progesterone vaginal pessaries, and maximum tolerated doses of antiepileptic medications, but finally responded to intramuscular and oral progesterone, and has been seizure-free for more than a year.