Forensic antiepileptic drug levels in autopsy cases of epilepsy.

A 1-year retrospective coroner-based forensic examination of causes of death among persons with a history of epilepsy was conducted at the Allegheny County Coroner's Office to evaluate the phenomenon of sudden unexplained/unexpected death in epilepsy (SUDEP), a diagnosis of exclusion. All cases at the Coroner's Office from January 1, 2001 through December 31, 2001, were examined. Review of a total of 1200 autopsied deaths revealed 12 cases with a past medical history of seizure disorder on the death certificate, which listed seizure disorder as the immediate cause of death or contributory cause of the death.

A nationwide survey of the extent of autopsy in sudden unexplained death in epilepsy.

Sudden unexplained death in epilepsy is a catastrophic event that requires autopsy for definitive diagnosis. Lack of awareness of sudden unexplained death in epilepsy as an important cause of death in epilepsy has been observed among coroners and pathologists. This survey study of US coroners and medical examiners (MEs) assesses their postmortem examinations of persons with epilepsy who had died suddenly without obvious cause.

New perspectives on community-acquired pneumonia in 388 406 patients. Results from a nationwide mandatory performance measurement programme in healthcare quality.

Background: The database of the German programme for quality in healthcare including data of every hospitalised patient with community-acquired pneumonia (CAP) during a 2-year period (n = 388 406 patients in 2005 and 2006) was analysed.

Methods: End points of the analysis were: (1) incidence; (2) outcome; (3) performance of the CRB-65 (C, mental confusion; R, respiratory rate >or=30/min; B, systolic blood pressure <90 mm Hg or diastolic blood pressure or=65 years) score in predicting death; and (4) lack of ventilatory support as a possible indicator of treatment restrictions. The CRB-65 score was calculated, resulting in three risk classes (RCs).

Verbal autopsies and SUDEP.

There is a problem in defining the occurrence of sudden unexplained death in persons with epilepsy (SUDEP). The diagnosis of SUDEP in the United States is under-used as many do not use the term on the death certificate. SUDEP is found to be more prevalent worldwide than assumed.

The mystery of sudden death: mechanisms for risks.

This review addresses the possible overlapping mechanisms that may apply to the risk of sudden unexpected death occurring in epilepsy and in cardiac disease. It explores the interaction between the central and peripheral autonomic nervous systems and the cardiopulmonary systems. Included is a discussion of the potential interactive role of genetically determined subtle cardiac risk factors for arrhythmias with a predisposition for seizure-related cardiac arrhythmias.

Stress and sudden death.

Cardiac patients, psychiatric patients, and certain ethnic groups experiencing acute stressful circumstances are at risk for unexpected sudden death. Although stress is associated with changes in autonomic neural function, its role as a potential risk factor for sudden unexpected death in epilepsy (SUDEP) is not known. The association of epilepsy with cardiac abnormalities, such as neurogenic arrhythmias and microscopic perivascular and interstitial fibrosis, and with depression and anxiety indicates that emotional stress should be evaluated as a potential risk factor for SUDEP.

Pica with paradichlorobenzene mothball ingestion associated with toxic leukoencephalopathy.

This is a case report of central nervous system toxicity associated with paradichlorobenzene (PDCB) ingestion. The patient had ingested mothballs composed of 99.99% PDCB for a period of 7 months.

Coroner and medical examiner documentation of sudden unexplained deaths in epilepsy.

Background: Prevalence data for sudden unexplained death in epilepsy (SUDEP) are hampered by its underuse as a final diagnosis on death certificates in appropriate cases. Few data exist about how coroners (COs) and medical examiners (MEs) in the United States use the diagnosis of SUDEP.

Methods: A survey instrument that addressed demographics, professional background, annual cases of epilepsy, seizure history, percentage of post-mortem examinations, cause of death, and use of SUDEP as a diagnosis was sent to all COs and MEs in the United States.

Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios.

Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages over the "old" drugs. The second purpose is to teach those interested in clinical pharmacology about the use of Web-based information access to answer a neurology/clinical pharmacology problem: to compare the efficacy and side effects of topiramate versus lamotrigine versus phenobarbital using odds ratios.

A new goldfish model to evaluate pharmacokinetic and pharmacodynamic effects of drugs used for motion sickness in different gravity loads.

This paper proposes a new goldfish model to predict pharmacodynamic/pharmacokinetic effects of drugs used to treat motion sickness administered in differing gravity loads. The assumption of these experiments is that the vestibular system is dominant in producing motion sickness and that the visual system is secondary or of small import in the production of motion sickness. Studies will evaluate the parameter of gravity and the contribution of vision to the role of the neurovestibular system in the initiation of motion sickness with and without pharmacologic agents.

Treatment of chronic plaque-stage psoriasis and psoriatic arthritis with mycophenolate mofetil.

Mycophenolate mofetil (MMF), a widely used immunosuppressant in organ transplantation, is a recent addition to the therapeutic armamentarium of autoimmune and inflammatory skin disorders in dermatology. We describe 5 patients with moderate to severe chronic plaque psoriasis and 6 patients with psoriatic arthritis that was refractory to conventional systemic and/or topical antipsoriatic treatment who were treated with MMF monotherapy (2 g/d) in a 10-week study. Although MMF was tolerated well in all patients, only patients with moderate psoriasis and psoriatic arthritis improved with therapy, whereas patients with severe psoriasis did not respond to MMF.

Sudden unexplained death in epilepsy: observations from a large clinical development program.

Purpose: The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database.

Methods: A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP.

Clinical pharmacology of antiepileptic drug use: "clinical pearls about the perils of patty".

This Clinical Pharmacology Problem Solving (CPPS) Unit is for use with fourth- or fifth-year pharmacy students and third- or fourth-year medical students during conferences held when they are taking either a rotation in Neurology or Clinical Pharmacology. It may also be used for house staff teaching of residents in Neurology, Pediatrics, Internal Medicine, and Family Practice and fellows in Clinical Pharmacology. This material was prepared for a Teaching Clinic in Clinical Pharmacology taught by Claire M.

Experience-based teaching of therapeutics and clinical pharmacology of antiepileptic drugs. Sudden unexplained death in epilepsy: do antiepileptic drugs have a role?

The contents of this paper have been written to be used in a teaching program specifically designed for medical postgraduate education of resident physicians and fellows in training interested in the clinical pharmacology of antiepileptic drugs and their role in the treatment of epilepsy and/or in the prevention of sudden unexpected death associated with this disease. With some modifications, such as a specific lecture to provide an overview of the numerous concepts presented in the text, the article could be used when teaching fourth-year medical students. The format of the paper is a combination of didactic review and eight case reports in a self-learning format.

The spectrum of syncope.

Syncope is a loss of consciousness and postural tone. Although arising suddenly from prolonged recumbency or returning from weightlessness to Earth's gravity can result in syncope from orthostatic or vasovagal effects, there are many other possible causes. These causes can be divided into several groups.

Reflex sympathetic dystrophy associated with antiepileptic drugs.

Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEDs. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement.

Evaluation of the mechanisms of antiepileptic drug-related chronic leukopenia.

Antiepileptic drug (AED)-related chronic leukopenia [white blood cell (WBC) count < 4,000/microliters] is a dilemma, especially when the AED is effective in controlling seizures. We evaluated the possible mechanisms of leukopenia in 7 patients. Mean WBC count was 3,000/microliters with a mean of 42% polymorphonuclear leukocytes (PMN).

The effect of phenobarbital on autonomic function and epileptogenic activity induced by the hippocampal injection of penicillin in cats.

This study addressed whether penicillin-induced epileptiform discharges in the right hippocampus produced associated autonomic dysfunction. The study also examined the effect of phenobarbital on the heart rate and blood pressure changes that were induced by the epileptiform discharges. The delay in onset of epileptiform activity at the site of injection ranged from 1 second to 16 minutes, and consisted of interictal discharges or ictal discharges.

Combined ambulatory electroencephalographic and electrocardiographic recordings for evaluation of syncope.

Evaluation of patients with syncope often includes a battery of noninvasive tests. In this study, 45 patients (26 with suspected neurologic and 19 with suspected cardiac syncope) were evaluated with simultaneous 24-hour electroencephalographic (EEG) and 2-channel electrocardiographic (ECG) recordings. Isolated cardiac rhythm abnormalities were noted in 21 patients, but none of these was symptomatic and no definitive arrhythmias occurred.

Paroxysmal autonomic dysfunction, epileptogenic activity and sudden death.

Transient abnormalities of autonomic nervous system function are observed during almost every generalized tonic-clonic seizure and include disruptions in blood pressure, cardiac arrhythmias and apnea. An increasing body of literature indicates that epileptogenic discharges, even without accompanying clinical seizure activity, can produce a spectrum of autonomic abnormalities. Marked changes in blood pressure and cardiac rhythm occur in patients paralyzed with neuromuscular blocking agents and subjected to electrical shock or intravenous pentylenetetrazol.

Synchronization of cardiac autonomic neural discharge with epileptogenic activity: the lockstep phenomenon.

Autonomic dysfunction has been implicated in the sudden, unexplained deaths which account for 5-17% of mortality in persons with epilepsy. This study was designed to determine if epileptogenic activity is associated with changes in the pattern of autonomic cardiac neural discharge and the development of arrhythmias. Nine cats, anesthetized with alpha-chloralose, received pentylenetetrazol (PTZ) 10, 20, 50, 100, 200 and 2000 mg/kg, i.

Review of autonomic dysfunction, cardiac arrhythmias, and epileptogenic activity.

Similarities in autonomic dysfunction associated with arrhythmias and death in animal models for digitalis toxicity, myocardial infarction, psychotropic toxicity, and epileptogenic activity are reviewed. When intravenous (IV) pentylenetetrazol was given to anesthetized cats, autonomic dysfunction was associated with both interictal and ictal epileptogenic activity. The autonomic dysfunction was manifested by the fact that autonomic cardiac nerves did not always respond in a predictable manner to changes in blood pressure, the development of a marked increase in variability in mean autonomic cardiac nerve discharge, and the appearance of a very large increase in the variability of the discharge rate of parasympathetic nerves first and then secondly in sympathetic discharge.