Deepti Zutshi

Sensitivity of quantitative EEG for seizure identification in the intensive care unit

Objective: To evaluate the sensitivity of quantitative EEG (QEEG) for electrographic seizure identification in the intensive care unit (ICU). Methods: Six-hour EEG epochs chosen from 15 patients underwent transformation into QEEG displays. Each epoch was reviewed in 3 formats: raw EEG, QEEG + raw, and QEEG-only. Epochs were also analyzed by a proprietary seizure detection algorithm. Nine neurophysiologists reviewed raw EEGs to identify seizures to serve as the gold standard. Nine other neurophysiologists with experience in QEEG evaluated the epochs in QEEG formats, with and without concomitant raw EEG. Sensitivity and false-positive rates (FPRs) for seizure identification were calculated and median review time assessed. Results: Mean sensitivity for seizure identification ranged from 51% to 67% for QEEG-only and 63%–68% for QEEG + raw. FPRs averaged 1/h for QEEG-only and 0.5/h for QEEG + raw. Mean sensitivity of seizure probability software was 26.2%–26.7%, with FPR of 0.07/h. Epochs with the highest sensitivities contained frequent, intermittent seizures. Lower sensitivities were seen with slow-frequency, low-amplitude seizures and epochs with rhythmic or periodic patterns. Median review times were shorter for QEEG (6 minutes) and QEEG + raw analysis (14.5 minutes) vs raw EEG (19 minutes; p = 0.00003). Conclusions: A panel of QEEG trends can be used by experts to shorten EEG review time for seizure identification with reasonable sensitivity and low FPRs. The prevalence of false detections confirms that raw EEG review must be used in conjunction with QEEG. Studies are needed to identify optimal QEEG trend configurations and the utility of QEEG as a screening tool for non-EEG personnel. Classification of evidence review: This study provides Class II evidence that QEEG + raw interpreted by experts identifies seizures in patients in the ICU with a sensitivity of 63%–68% and FPR of 0.5 seizures per hour.

Tardive Syndromes are Rarely Reversible after Discontinuing Dopamine Receptor Blocking Agents: Experience from a University-based Movement Disorder Clinic

Background Several studies have examined reversibility of tardive syndromes (TS), primarily in psychotic patients who are maintained on dopamine receptor blocking drugs. The results have varied widely. However, few have assessed remission rates after discontinuing the offending agents. This study evaluated reversibility of TS in patients who permanently withdrew the causative agent(s). We also examined for any possible clinical predictors of reversibility. Methods A retrospective cohort of 108 TS patients was studied. Most of the patients were not psychotic; most patients were being treated either for a mood disorder with atypical antipsychotics or for a gastrointestinal disturbance with metoclopramide. Patients were stratified on the basis of reversibility, and statistical tests were used for subgroup comparisons of relevant clinical variables. Logistic regression was undertaken to identify clinical variables predictive of reversibility. Results Only 13% of the cohort experienced reversibility of the TS, 2% without medical intervention. When stratified by reversibility, there were no significant differences in any study variables between subgroups. None of the study variables predicted reversibility in the logistic regression. Discussion Our study demonstrated a low remission rate for TS in a cohort of psychiatric and non-psychiatric patients seen in a movement disorder clinic after the offending agents were completely withdrawn. Such a finding has significant prognostic implications. It is possible that limitations of the retrospective design may have resulted in an underestimation. There is a clear need for prospective, multicenter, clinical trials in populations that can be safely withdrawn from dopamine receptor blocking agents so that true remission rates can be measured.

Negative results of a phase II study of hyperbaric oxygen therapy for amyotrophic lateral sclerosis

Dear Sir, We reported the results of a phase I study of hyperbaric oxygen therapy (HBOT) in amyotrophic lateral sclerosis (ALS) in this journal in 2004 (1). Although that report described a pilot study of only five patients, a statistically significant improvement over baseline measurements was seen in maximum voluntary isometric contraction (MVIC) testing of muscles. This improvement occurred during the four weeks following the completion of four weeks of HBOT. No change was noted in any other parameter of ALS function. We now report the negative results of a phase II single-blind placebo-controlled study of HBOT in patients with ALS. In order to determine if longer HBOT might improve ALS parameters in addition to MVIC, the duration of the treatment phase was doubled to eight weeks compared to the phase I study, and the follow-up period was extended to 12 weeks (i.e. to week 20). The study compared two groups of five patients with ALS, one of which received active HBOT and the other sham HBOT. The principle investigator (WGB), the MVIC evaluator (JS) and the HBOT technicians were aware of the treatment being received by each group, but the patients were blinded throughout the study and for the follow-up testing period after completion of the HBOT. Patients were recruited into two groups of five. Treatment was randomly allocated by the flip of a coin that resulted in the first group receiving active HBOT and the second group sham treatment. Patients included in the study met the El Escorial criteria for definite ALS (2) had a forced vital capacity of w60% at screening, were able to move into the HBOT chamber and perform a Valsalva maneuver, and had no history of congestive heart failure, significant lung disease, or prior experience with scuba diving or HBOT. The active treatment group (four males and one female, median age 62 years) received 100% oxygen at 2 ATA (equivalent to a dive of 33 feet) for one hour using the same type of plastic hood and rubber neck collar described in our earlier paper (1). The placebo group (three males and two females, median age 55 years) received hyperbaric treatments using oscillating pressures to a maximum of 1.3 ATA (equivalent to a dive of 10 feet). Subjects in the placebo group received room air through a facemask. For both groups, treatments lasted one hour and were administered five days a week for eight weeks (40 total treatments). Data on ALS function, as described in our earlier paper (1) were collected at baseline and every four weeks up to 20 weeks from the initiation of the trial. In the active study group, one patient was unable to complete all HBOT treatments due to injuries from a fall not associated with the study. Some patients in both treatment groups did not complete all the treatments and evaluations due to disease-related problems. However, sufficient data were available to make a meaningful analysis of HBOT versus sham HBOT. A survey of each treatment group was conducted at the end of the study to determine if the patients could identify whether they had received placebo or active treatment. This demonstrated that neither subject group was able to guess their treatment any better than chance. A full analysis of the data was performed after the active treatment group had completed all data gathering, and after the sham treatment group had received eight weeks of treatment followed by four weeks of follow-up. The analysis was undertaken before the end of the planned 12-week follow-up

Alpha 3 ganglionic acetylcholine receptor antibody associated refractory status epilepticus

Autoimmune encephalitides are a group of syndromes that may present with subacute onset of disorientation, personality changes, memory loss and most prominently seizures. Earlier reports of this entity were from patients with paraneoplastic limbic encephalitis, however autoimmune etiologies have also been described in patients with non-paraneoplastic encephalitis [1]. The Alpha 3 ganglionic acetylcholine receptor autoantibody (a3-AChR Ab) mainly causes autoimmune dysautonomia that is either subacute or insidious in onset. A direct relationship betweenantibody titer and severity of dysautonomia occurs in both experimental animals and patients [2]. Most of these cases have been paraneoplastic (mainly adenocarcinomas) however a few cases have been linked to other autoimmune disorders such as systemic lupus erythematosus (SLE) and Sjogren’s syndrome. Patients who are seropositive for a3-AChR Ab may present with less common neurological manifestations such as peripheral neuropathies, encephalopathy and subacute neuropsychiatric presentations. This report presents a unique case of refractory new-onset status epilepticus associated with a3-AChR antibody which responded to immunotherapy.

Medication-Induced Seizures and Status Epilepticus

Drug-induced seizures (DIS) were first described in the literature in the 1950s after the psychotropic drugs chlorpromazine and imipramine were observed to cause secondarily generalized tonic-clonic seizures [1]. In the mid-twentieth century, stimulants such as pentylenetetrazol and penicillin, which were described to have caused seizures in humans, were also used to create animal models for epilepsy research [2]. DIS are not considered to be epilepsy. The myriad of causes can be due to direct medication effect on brain receptors, withdrawal effects from antiepileptic medications and benzodiazepines, and medications causing electrolyte disturbances.

Effects of Marijuana on Ictal and Interictal EEG Activities in Idiopathic Generalized Epilepsy

Summary: Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series, and clinical trials. However, literature on their EEG effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy treated with cannabis. We blindly reviewed 3 long-term EEGs—a 24-hour study while only on antiepileptic drugs, a 72-hour EEG with Cannabis indica smoked on days 1 and 3 in addition to antiepileptic drugs, and a 48-hour EEG with combination C indica/sativa smoked on day 1 plus antiepileptic drugs. Generalized spike–wave discharges and diffuse paroxysmal fast activity were categorized as interictal and ictal, based on duration of less than 10 seconds or greater, respectively. Data from three studies concatenated into contiguous time series, with usage of marijuana modeled as time-dependent discrete variable while interictal and ictal events constituted dependent variables. Analysis of variance as initial test for significance followed by time series analysis using Generalized Autoregressive Conditional Heteroscedasticity model was performed. Statistical significance for lower interictal events (analysis of variance P = 0.001) was seen during C indica use, but not for C indica/sativa mixture (P = 0.629) or ictal events (P = 0.087). However, time series analysis revealed a significant inverse correlation between marijuana use, with interictal (P < 0.0004) and ictal (P = 0.002) event rates. Using a novel approach to EEG data, we demonstrate a decrease in interictal and ictal electrographic events during marijuana use. Larger samples of patients and EEG, with standardized cannabinoid formulation and dosing, are needed to validate our findings.