Do vaccines cause epilepsy? Review of cases in the National Vaccine Injury Compensation Program.

OBJECTIVE: The National Childhood Vaccine Injury Act of 1986 created the National Vaccine Injury Compensation Program (VICP), a no-fault alternative to the traditional tort system. Since 1988, the total compensation paid exceeds $5 billion. Although epilepsy is one of the leading reasons for filing a claim, there has been no review of the process and validity of the legal outcomes given current medical information. The objectives were to review the evolution of the VICP program in regard to vaccine-related epilepsy and assess the rationale behind decisions made by the court. METHODS: Publicly available cases involving epilepsy claims in the VICP were searched through Westlaw and the US Court of Federal Claims websites. All published reports were reviewed for petitioner's theories supporting vaccine-induced epilepsy, respondent's counterarguments, the final decision regarding compensation, and the rationale underlying these decisions. The primary goal was to determine which factors went into decisions regarding whether vaccines caused epilepsy. RESULTS: Since the first epilepsy case in 1989, there have been many changes in the program, including the removal of residual seizure disorder as a vaccine-related injury, publication of the Althen prongs, release of the acellular form of pertussis, and recognition that in genetic conditions the underlying genetic abnormality rather than the immunization causes epilepsy. We identified 532 unique cases with epilepsy: 105 with infantile spasms and 427 with epilepsy without infantile spasms. The petitioners' experts often espoused outdated, erroneous causation theories that lacked an acceptable medical or scientific foundation and were frequently criticized by the court. SIGNIFICANCE: Despite the lack of epidemiological or mechanistic evidence indicating that childhood vaccines covered by the VICP result in or aggravate epilepsy, these cases continue to be adjudicated. After 35 years of intense litigation, it is time to reconsider whether epilepsy should continue to be a compensable vaccine-induced injury.

Microelectrode recordings in human epilepsy: a case for clinical translation.

With their 'all-or-none' action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system-level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single-unit data, microelectrode recordings also record local field potentials and high-frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarize the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilized, principles of how to record and process microelectrode data and insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single-unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.

Mechanisms Responsible for Cognitive Impairment in Epilepsy.

Epilepsy is often associated with cognitive and behavioral impairments that can have profound impact on the quality of life of patients. Although the mechanisms of cognitive impairment are not completely understood, we make an attempt to describe, from a systems perspective, how information processing is affected in epilepsy disorders. The aim of this review is to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs). We conclude that these mechanisms are likely to be important and deserve more detailed scrutiny in the future.

Hippocampal volume loss following childhood convulsive status epilepticus is not limited to prolonged febrile seizures.

PURPOSE: Childhood convulsive status epilepticus (CSE), in particular prolonged febrile seizures (PFS), has been linked with mesial temporal sclerosis (MTS). Previous studies have shown that hippocampal injury occurs in the acute phase immediately following CSE, but little is known about the longer term evolution of such injury. This study aimed to investigate the longer term outcome of childhood CSE with sequential magnetic resonance imaging (MRI) looking for progressive hippocampal injury during the first year post-CSE. METHODS: Eighty children (0.18-15.5 years) underwent brain MRI 1 month post-CSE, 50 with a repeat MRI at 6 months and 46 with repeat MRI at 12 months post-CSE. Thirty-one control subjects without neurologic problems had a single brain MRI for comparison. Hippocampal volumes were measured from each MRI scan by two independent observers, and hippocampal growth rates were estimated in each patient with suitable imaging. KEY FINDINGS: Hippocampal volume loss was found in 20-30% of patients and was not associated with the etiology or clinical features of CSE, including seizure duration or focality. A borderline association was found between a history of previous seizures (p = 0.063) and the number of previous febrile seizures (p = 0.051), suggesting that multiple insults may be important in the pathogenesis of progressive hippocampal injury. SIGNIFICANCE: It is apparent that progressive hippocampal damage can occur after CSE of any etiology and is not limited to PFS. Repeated seizures may play an important role, but further follow-up is needed to determine any other risk factors and proportion of children showing initial volume loss progress to clinical MTS and temporal lobe epilepsy.

Outcome of frontal lobe epilepsy surgery.

PURPOSE: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well-established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. METHODS: Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. KEY FINDINGS: Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. SIGNIFICANCE: Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients.