Mark C. Spitz

New onset geriatric epilepsy: A randomized study of gabapentin, lamotrigine, and carbamazepine

Objective: To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy. Methods: This was an 18-center, randomized, double-blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed seizures. Patients were randomly assigned to one of three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/day. The primary outcome measure was retention in trial for 12 months. Results: Mean age was 72 years. The most common etiology was cerebral infarction. Patients had multiple medical conditions and took an average of seven comedications. Mean plasma levels at 6 weeks were as follows: GBP 8.67 ± 4.83 μg/mL, LTG 2.87 ± 1.60 μg/mL, CBZ 6.79 ± 2.92 μg/mL. They remained stable throughout the trial. Early terminations: LTG 44.2%, GBP 51%, CBZ 64.5% (p = 0.0002). Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008. Terminations for adverse events: LTG 12.1%, GBP 21.6%, CBZ 31% (p = 0.001). Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p = 0.015. There were no significant differences in seizure free rate at 12 months. Conclusions: The main limiting factor in patient retention was adverse drug reactions. Patients taking lamotrigine (LTG) or gabapentin (GBP) did better than those taking carbamazepine. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures.

Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective Study.

BACKGROUND Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING Commission of European Affairs of the International League Against Epilepsy.

Ictal hypoventilation contributes to cardiac arrhythmia and SUDEP: report on two deaths in video-EEG-monitored patients.

Sudden unexplained death in epilepsy (SUDEP) is a common cause of death in patients with epilepsy, with cardiorespiratory dysfunction and a primary cessation of cerebral function proposed as causes. We report two cases of SUDEP in patients with intractable temporal lobe epilepsy undergoing video‐EEG (electroencephalography) telemetry at two centers. Both had secondarily generalized convulsions. EEG, electrocardiography (ECG), and respiratory changes in these two patients are reported herein. Ictal/postictal hypoventilation may contribute to SUDEP with the resulting hypoxemia and acidosis leading to failure of recovery of cortical function and eventual cardiac failure.

Central nervous system effects of chronic toluene abuse—Clinical, brainstem evoked response and magnetic resonance imaging studies

We describe the results of neurological evaluation, magnetic resonance imaging (MRI) of the brain and brainstem auditory evoked response (BAER) testing in 11 chronic toluene vapor abusers. Neurological abnormalities were seen in four of 11 individuals and included cognitive, pyramidal, cerebellar and brainstem findings. MRI of the brain was abnormal in three of 11 individuals and revealed the following abnormalities: 1) Diffuse cerebral, cerebellar, and brainstem atrophy; 2) Loss of differentiation between the gray and white matter throughout the CNS; and 3) Increased periventricular white matter signal intensity on T2 weighted images. BAERs were abnormal (control mean +/- 3 S.D.) in five of 11 individuals. As a group, the latency of V (p less than 0.01), the III-V interpeak (p less than 0.05) and the I-V interpeak latencies were prolonged compared to controls. All three individuals with abnormal MRI scans also had abnormal neurological examinations and BAERs. Two of five individuals with abnormal BAERs, however, had normal neurological examinations and MRI scans. Our data support previous findings of diffuse white matter involvement in chronic toluene abusers and suggest that BAERs may detect early CNS injury from toluene inhalation even at a time when neurological examination and MRI scans are normal. BAERs, therefore, may be a sensitive screening test to monitor individuals at risk from toluene exposure (either abusers or industrially exposed individuals) for early evidence of CNS injury.

Familial tic disorder, parkinsonism, motor neuron disease, and acanthocytosis A new syndrome

We report two brothers who were of consanguineous parents and who displayed a unique association of motor and vocal tics, parkinsonism, distal muscular atrophy, and acanthocytosis. In the older brother, leg weakness and muscle wasting started at age 13, and he became wheelchair bound at 40. Electrophysiologic studies and muscle biopsy confirmed diffuse denervation. Involuntary vocalizations and facial tics began at age 36, but within 5 years the tics were replaced by progressive parkinsonism with supranuclear ophthalmoparesis. CSF studies implied impaired central dopamine and serotonin turnover. In the younger brother, orofacial tics started at age 36, vocalizations and fasciculations in the legs began 1 year later, and parkinsonian findings were present at age 40. This is the first report of an association of Tourettism, parkinsonism, motor neuron disease, and acanthocytosis occurring as an autosomal recessive syndrome.

Practice Guideline Summary: Sudden Unexpected Death in Epilepsy Incidence Rates and Risk Factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society

Objective: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. Methods: Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus. Results: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0–17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16–0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64–2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). Recommendations: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Risk Factors for Burns as a Consequence of Seizures in Persons with Epilepsy

Summary: To explore the risk factors and circumstances for burns in a population of persons with epilepsy, we surveyed 244 University of Colorado Health Sciences Center Seizure Clinic patients. Twenty‐five had at least one seizure‐related burn requiring medical attention (12 were hospitalized), 21 reported burns requiring medical attention not related to seizure activity, and 199 reported no burns. All patients with seizure‐related burns had alteration of consciousness during most seizures. Statistical models with logistic regression indicated that a useful model for assessing risk of seizure‐related burns in this population of patients could be constructed using three significant variables: lifetime total number of seizures experienced by the patient, the presence of interictal neurologic impairment, and gender. The remainder of the variables studied (percentage of seizures that occurred nocturnally, percentage of seizures preceded by a simple partial seizure (SPS) warning, self‐care status, number of seizures in adult life, seizure type, patient age, age of onset of seizure disorder, and presence of burns not associated with seizure) were either not significantly correlated with seizure‐related burns or did not significantly improve the success of the statistical model in light of the other variables studied. Most injuries occurred in the home during activities that might have been avoided. They included 10 burns incurred while cooking, 5 incurred while showering (with a plumbing system that permitted exposure to scalding water), and 3 caused by exposed room heaters. A subset of epileptic patients are at increased risk for burns and should minimize situations in which they can be burned.

Injuries and death as a consequence of seizures in people with epilepsy

People with epilepsy should be encouraged to live as normal a life as possible. However, many persons with seizure disorders must take special precautions because of seizure-related injuries. The literature on the morbidity and mortality that occurs as a result of accidents in people with epilepsy is reviewed, and a set of guidelines based on these data is presented. Although driving is a specific risk in people with epilepsy, it has already been studied extensively (1-3) and is not covered in this article.

Topiramate in older patients with partial-onset seizures: A pilot double-blind, dose-comparison study

Purpose: Pharmacokinetics of antiepileptic drugs (AEDs) can be altered by age‐related changes in physiology, thereby altering clinical effects, especially tolerability, in older adults. We compared two dosages of topiramate (TPM) in a pilot study of patients ≥60 years of age with partial‐onset seizures.

Severe Burns as a Consequence of Seizures in Patients with Epilepsy

Summary: We report 10 seizure‐related thermal injuries severe enough to require hospitalization in patients with epilepsy. Eight of the ten incidents were with patients who had had seizures with impaired consciousness two or more times a month. This suggests that seizure frequency is a risk factor and implies the importance of striving for optimal seizure control. Two burns each occurred from an electric iron, a hand‐held hair dryer, and stove‐top cooking. Minimizing these activities, especially in patients with frequent consciousness‐altering seizures, may be useful. Three burns occurred while showering; these resulted in the most severe injuries, with hospital stays of 29, 30, and 41 days. Simple plumbing devices may have prevented these injuries.