Ovarian teratoma-associated anti-NMDA receptor encephalitis with severe features.

Anti-N-methyl-D-aspartame receptor (NMDAR) encephalitis is an uncommon clinical entity for the general intensivist or neurologist. Diagnosis can be made by the presence of cerebrospinal fluid IgG antibody against the GluNR1 and GluNR2 subunits of the NMDAR. We present a case of anti-NMDAR encephalitis in a young woman with an ovarian teratoma treated with surgical resection and multiple immunomodulatory therapies.

Measuring vagal activity in postictal bradycardia.

Alterations to cardiac electrical conduction are some of the most frequently observed systemic complications of seizures, with autonomic dysregulation cited as the principal driver for these alterations. In this prospective study, we use 6-lead continuous ECG monitoring in hospitalized patients with epilepsy to trend heart rate patterns in the postictal period. A total of 117 seizures in 45 patients met the criteria for analysis. There was a postictal heart rate increase of 61% (n = 72 seizures), and a decline in heart rate (deceleration) following 38.5% (n = 45). Using 6-lead ECGs for waveform analysis revealed that there was PR prolongation accompanying those seizures that were associated with postictal bradycardia.

Synergistic effect of sleep depth and seizures correlates with postictal heart rate.

Our objective was to determine the effect of sleep on heart rate following a recorded seizure. We prospectively acquired heart rate data in hospitalized epilepsy monitoring unit patients. We analyzed heart rate trends for multiple seizures (n = 101) in patients (n = 42) with electroencephalographically confirmed events. The patient's sleep state was scored for the 5 min preceding each seizure and correlated with the postictal nadir heart rate (PINHR). The depth of sleep during the 5 min before a seizure correlated (correlation coefficient [CC] = -.229, p < .05) with PINHR. This result was more significant and strengthened (CC = -.272, 95% confidence interval = -.392 to -.152, p < .001) when adjusted for covariates of age, generalized tonic-clonic seizures, and baseline heart rate. Sleep depth is an independent predictor of the change in heart rate following a seizure. Diminished heart rate following a seizure in the setting of sleep is likely secondary to non-rapid eye movement sleep's synergistic effect on parasympathetic tone.

Time of day is an inaccurate surrogate marker for sleep-wake state in an epilepsy monitoring unit.

OBJECTIVE: To assess the correlation between time of day and sleep-wake state prior to seizure onset for seizures recorded in an inpatient epilepsy monitoring unit. METHODS: We prospectively enrolled a consecutive series of patients undergoing inpatient epilepsy monitoring. For each epileptic seizure recorded, continuous EEG data preceding seizure onset was reviewed and scored as W, N1-3, or REM in ten 30-second epochs. Time of day was divided into four 6-h phases (0600-1159, 1200-1759, 1800-2359, 0000-0559). The preictal sleep-wake state was then correlated to nocturnal (0000-0559) versus diurnal (0600-2359) times of day. RESULTS: A total of 102 seizures from 42 patients met enrollment criteria over a period of 19 months. Eighty-five seizures occurred during the diurnal phase, and 17 seizures occurred during the nocturnal phase. Thirty-six percent of all seizures (n = 37) were preceded by at least 1 epoch of sleep. The proportion of patients sleeping prior to a seizure within each 6-h phase varied significantly from the overall distribution only during nocturnal phase. Seventy-six percent of nocturnal seizures and 28 % of diurnal seizures were preceded by sleep. Therefore, the nocturnal time window from 0000-0559 had a sensitivity of 0.65 (95 % confidence interval 0.48-0.78), a specificity of 0.06 (0.02-0.15), a positive predictive value of 0.28 (0.20-0.39), and a negative predictive value of 0.24 (0.10-0.39) in association with sleep-onset seizures. SIGNIFICANCE: The time of day is an inaccurate surrogate for preictal sleep-wake state in the epilepsy monitoring unit despite a correlation between nocturnal period and sleep. Diurnal sleep is a common phenomenon in the inpatient unit.

The SAMUKeppra study in prehospital status epilepticus: lessons for future study.

In the Lancet Neurology article "Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial" the authors conducted a prehospital, randomized controlled study to determine which treatment is more effective for status epilepticus (SE): benzodiazepine alone, or in combination with levetiracetam (LEV). Although the study had negative results, several aspects of the trial design likely masked any added effect that LEV may have had in controlling SE, including: higher doses of benzodiazepines, lower thresholds for determining cessation of SE, and a smaller sample size. Regardless, the study reaffirms the effectiveness and importance of early and adequate benzodiazepine dosing and helps guide us in designing future studies for treatment of SE.

Severe hemispatial neglect as a manifestation of seizures and nonconvulsive status epilepticus: utility of prolonged EEG monitoring.

PURPOSE: Seizures and status epilepticus causing hemispatial neglect syndromes are seldom diagnosed, in part because, without motor signs, EEGs are not performed. Also, nonconvulsive seizures are often intermittent and missed on a single EEG. Two patients had severe neglect syndromes thought due to strokes. Correct diagnosis of epileptic seizures required longer-term EEG monitoring. METHODS: Review of clinical history, neurologic examination, imaging, and findings on prolonged EEG monitoring. RESULTS: A patient with a new onset of a profound left neglect had normal strength and language use, with no obvious clinical seizures. A right hemisphere embolic stroke was diagnosed, but MRI with diffusion-weighted imaging showed no evidence of ischemia. The initial EEG showed marked right parietal voltage suppression, with subsequent brief electrographic seizures and later, right parietal periodic discharges. The second patient had an earlier right subdural hematoma and focal motor seizures but was admitted with a new neglect syndrome and no clear clinical seizures. Head computed tomography showed no new lesion. EEG showed frequent right parieto-temporal epileptiform discharges and electrographic seizures. The neglect syndromes resolved with anticonvulsant treatment, but in both cases, electrographic seizures were intermittent, and there was no strict correlation between the clinical deficit and EEG manifestations of seizures. CONCLUSIONS: Infrequently, the sudden onset of new hemispatial neglect can be caused by nonconvulsive seizures and nonconvulsive status epilepticus, even when there is no weakness and no clear clinical seizure activity. Nonconvulsive status epilepticus can cause primarily perceptual and cognitive syndromes. The correlation between the clinical deficits and seizure activity on the EEG, however, is imprecise. A single EEG may miss seizure activity, and repeated or prolonged EEG recording may be necessary to make the diagnosis.

Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy.

OBJECTIVE: The cardiac component of risk for sudden unexpected death in epilepsy (SUDEP) and alterations in cardiac risk by vagus nerve stimulation (VNS) are not well understood. We determined changes in T-wave alternans (TWA), a proven noninvasive marker of risk for sudden cardiac death in patients with cardiovascular disease, and heart rate variability (HRV), an indicator of autonomic function, in association with VNS in patients with drug-resistant focal epilepsy. METHODS: Ambulatory 24-h electrocardiograms (N = 9: ages 29-63, six males) were analyzed. RESULTS: Mean TWA during the interictal period was 37 ± 3.1 µV (mean ± SEM) in lead V1 for nine patients monitored following implantation of the VNS system (n = 7) or battery change (n = 2). Of these, six patients also monitored prior to implantation (n = 5) or battery change (n = 1) showed abnormally high TWA levels pre-VNS (60.0 ± 4.3 µV), which were significantly reduced by 24.3 µV (to 35.7 ± 4.8 µV, p = 0.02) after VNS settings were adjusted for desired clinical response. TWA in four (67%) of the six patients was reduced in association with VNS to levels below the 47-µV cut point of abnormality. The decrease in TWA was correlated with VNS intensity (r = 0.88, p < 0.02). In addition, low-frequency HRV was reduced by 60% (805.61 ± 253.96 to 323.49 ± 102.74 msec(2) , p = 0.05) and low-to high-frequency HRV ratio by 32% (3.34 ± 0.57 to 2.26 ± 0.31, p = 0.025), indicating a change in autonomic balance in favor of parasympathetic dominance. SIGNIFICANCE: This is the first report that elevated levels of TWA in patients with drug-refractory partial-onset seizures were reduced in association with VNS, potentially by improving sympathetic/parasympathetic balance. VNS may have a cardioprotective role at stimulation settings typically used for seizure control. These findings indicate the utility of TWA for tracking improvement in cardiac status in this population.

Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism.

Coenzyme Q10 (CoQ10) is a promising agent for neuroprotection in neurodegenerative diseases. We tested the effects of various doses of two formulations of CoQ10 in food and found that administration in the diet resulted in significant protection against loss of dopamine (DA), which was accompanied by a marked increase in plasma concentrations of CoQ10. We further investigated the neuroprotective effects of CoQ10, reduced CoQ10 (ubiquinol), and CoQ10 emulsions in the (MPTP) model of Parkinson's disease (PD). We found neuroprotection against MPTP induced loss of DA using both CoQ10, and reduced CoQ10, which produced the largest increases in plasma concentrations. Lastly, we administered CoQ10 in the diet to test its effects in a chronic MPTP model induced by administration of MPTP by Alzet pump for 1 month. We found neuroprotective effects against DA depletion, loss of tyrosine hydroxylase neurons and induction of alpha-synuclein inclusions in the substantia nigra pars compacta. The finding that CoQ10 is effective in a chronic dosing model of MPTP toxicity, is of particular interest, as this may be more relevant to PD. These results provide further evidence that administration of CoQ10 is a promising therapeutic strategy for the treatment of PD.