Ruth B. Loewenson

Seizure Recurrence after a First Unprovoked Seizure

We studied 244 patients (of all ages) who presented with a first unprovoked seizure and were followed for a median of 22 months in order to ascertain the risk of subsequent seizures. The cumulative risks of recurrence were 16 per cent at 12 months, 21 per cent at 24 months, and 27 per cent at 36 months after the initial seizure. The risk of recurrence in patients with a history of prior neurologic insult was 34 per cent; all recurrences in this group were observed within the first 20 months. Only 17 per cent of patients without such a history (classified as idiopathic) had a recurrence by 20 months; recurrence in this group was 26 per cent by 36 months. Patients with no recurrence for 36 months did not have a recurrence after that time. Among idiopathic cases the risk of recurrence was increased in patients with generalized spike-wave electroencephalograms (50 per cent at 18 months) and in those who had a sibling with seizures (35 per cent at four months). Age at first seizure, sex, seizure type, onset with status epilepticus, or abnormality on neurologic examination did not affect the risk of recurrence.

Influence of Pancreas Transplantation on Cardiorespiratory Reflexes, Nerve Conduction, and Mortality in Diabetes Mellitus

Cardiorespiratory reflexes (CRR) were studied by measuring heart-rate variation during 6 breaths/min respiration and a Valsalva maneuver in 232 insulin-dependent diabetic subjects. Abnormalities were found in 175 patients. During a 7-yr follow-up, 41 (23.4%) patients with abnormal and 2 (3.5%) with normal CRR tests died. The mortality rates of diabetic patients with abnormal autonomie function tests were 17% at 2.5 yr, 33% at 5 yr, and 40% at 7 yr, significantly higher (P < 0.002) than in patients with normal tests (rates of 4.6, 4.6, and 13.8% at the respective intervals). Nerve conduction studies (NCS) were indicative of somatic neuropathy in 148 of 205 patients. Mortality rates were higher in patients with abnormal NCS than in those with normal results (P < 0.025). Among patients with abnormal autonomie function, patients with a functioning pancreas transplantation (PTx) had better survival rates than patients with a failed PTx (P < 0.005) and, on long-term follow-up, better rates than patients without PTx. Similar results were found comparing the same group of patients who had abnormal NCS.

Neurologic prognosis after cardiopulmonary arrest III. Seizure activity

Nineteen (30%) of 63 adult survivors of cardiopulmonary arrest had seizures after admission to the hospital. Eleven of 19 had more than one type of seizure. Myoclonic seizures began within 12 hours of the arrest in eight patients, and after 3 or more days in four patients. Only two (17%) patients with myoclonic seizures survived. Partial seizures usually began within 12 hours of the arrest and were controllable with anticonvulsants; 4 of 12 patients survived. Two of four patients with generalized tonic-clonic seizures survived; one of four with “shivering” lived. Overall, patients with seizures had a survival rate of 32% (6 of 19), compared with 43% for patients without seizures. None of the survivors had recurrent seizures within 6 months after hospital admission.

Migration and risk of multiple sclerosis

A study of multiple sclerosis (MS) frequency among immigrants to Israel revealed that those from Afro-Asian countries, where MS is rare, had a low prevalence of MS, while European immigrants had a relatively high prevalence of the disease. On the other hand, native-born Israelis had a high rate of the disease, like European immigrants, regardless of the region of origin of their forebears. Age-specific incidence rates plotted for different age-at-immigration cohorts and based only on the most rigidly defined cases suggested that Afro-Asians who immigrated very early in life had rates similar to European immigrants. Among immigrants who came to Israel at an older age, Europeans had higher age-specific incidence rates of MS than Afro-Asians. Although the number of patients available for analysis in the youngest age-at-immigration cohort was small, and the age groups for which specific incidence rates could be plotted were still few, the results indicated that migration modifies risk only among those who migrate early, before adolescence. Over the next decade, as this immigration cohort ages, the validity of this result can be verified. If correct, it would mean that MS can be acquired in the brief interval between infancy and preadolescence.

Nonepileptic Events in Childhood

Summary: The medical records of 27 children admitted to the MINCEP Epilepsy Program for evaluation of intractable epilepsy but later shown to have nonepileptic events by EEG with simultaneous video monitoring were reviewed. Four groups were identified: pure psychogenic events (5 patients), psychogenic events plus epileptic seizures (3 patients), pure nonepileptic physiologic events (5 patients), and nonepileptic physiologic events plus seizures (14 patients). Historical data, physical examinations, and neurodiagnostic evaluations (including previous EEGs, neuroradiologic evaluations, and neuropsychologic testing) were reviewed. Children in all groups, except for those with pure psychogenic seizures, had a history of multiple seizure types identified by parents or caretakers. A history of status epilepticus was obtained in 64% (of 22 patients), including 11 of 14 patients with physiologic events plus seizures. Abnormal findings on neurologic examination were common, especially in children with nonepileptic physiologic events. AH but two patients had a history of interictal epileptiform abnormalities on previous routine EEGs. Based on identification of nonepileptic events, antiepileptic drugs (AEDs) were discontinued completely in eight patients (30%) and the total number of AEDs was reduced in nine others (33%). A diagnosis of nonepileptic events should be considered in all children with refractory seizures or multiple seizure types. Abnormal findings on routine (interictal) EEG may actually confound the diagnosis. Intensive neurodiagnostic EEG‐video recording is the preferred method for distinguishing nonepileptic from epileptic seizures.

The design of clinical studies to assess therapeutic efficacy in multiple sclerosis

Poorly designed trials of therapy for multiple sclerosis (MS) can waste time and money, and may lead either to false hopes or to the overlooking of a potentially effective treatment. A well-designed trial may well develop useful scientific information even if the putative therapy fails to show any therapeutic effect. The diagnosis, clinical course, and definitions of the stages of MS are discussed as they relate to trials of therapy. The goals of such trials include favorable modification of an exacerbation, favorable modification or prevention of future exacerbations, effective treatment of the progressive stage, and improvement of function in the stable-deficit stage. There should be an orderly progression from a small preliminary trial to a modest pilot trial and, when indicated, a full trial. All types of trials require careful organization and management, appropriate selection of patients, and properly planned and recorded observations. The treatment contrast-how the new treatment will be evaluated-provides the essential structure of the trial. The hypothesis being examined, the treatment contrast, and the observations being made in the designed clinical trial will govern the form of the analysis and the nature of the interpretations. Each goal requires that specific strategies and design considerations be applied to preliminary, pilot, and full trials.

Thalassemia major (homozygous beta-thalassemia). A survey of 138 cases with emphasis on neurologic and muscular aspects.

FORTY-FIVE Y ARS AGO Cooley and Lee defined a specific disorder characterized by anemia with decreased r e d cell osmotic fragil i ty, hepatosplenomegaly, pigmentary skin changes, and thickening of the long bones and skull. Cenetic studies 2 ~ 3 established that Cooley’s anemia, or thalassemia, represents the homozygous state of a partially dominant autosomal gene, with the heterozygous state usually represented by a clinically mild anemia. Cooley’s anemia has been extensively reviewed in recent years. 4-6 There are two categories of thalassemias, corresponding to inherited depression in synthesis of either alpha or beta polypeptide chains of the globin molecule, with failure to produce red cells with normal adult hemoglobin (Hb) content. In alpha-thalassemia there is decreased synthesis of alpha polypeptide chains, resulting in decreased amounts of adult and fetal hemoglobin. In beta-thalassemia there is failure in production of beta chains with a resulting decrease in the synthesis of the major adult hemoglobin fraction, HbA (a,P,); the minor fraction, HbA, (a,s,), and fetal hemoglobin, HbF (a ,y , ) , which do not contain beta chains, go into a compensatory overproduction. The homozygous state of beta-thalassemia, referred to as homozygous beta-thalassemia or simply thalassemia major, corresponds to the clinical condition of Cooley’s anemia. Symptoms in homozygous beta-thalassemia

The electroencephalogram of elderly subjects revisited

The EEGs of 98 elderly volunteers were compared with those of 84 patients with a recent cerebral infarction who had achieved a stable clinical course. All subjects were uniformly evaluated according to a special protocol. The elderly volunteers were accepted for the study if they had no history, signs or symptoms of central nervous system disease. The EEGs were found to be significantly different between the two groups of subjects in several aspects. These included not only possible abnormalities, focal or diffuse, but also some normal features, such as alpha frequency and responses to photic stimulation and to hyperventilation. Groups of these differentiating features were analyzed. Using the single variable of ER (evoked response), discrimination of 80% was achieved. The variables that distinguish the volunteers from the patients may be used in the future to determine whether they are helpful in differentiating normals from patients with conditions other than stroke.

Neurologic prognosis after cardiopulmonary arrest; II. Level of consciousness

Sixty-three patients with isolated global anoxic-ischemic injury were prospectively evaluated after cardiopulmonary arrest (CPA); 25 (40%) survived, 16 to an excellent recovery, 8 to a good recovery, and 1 with severe deficits. Forty-six percent of the patients achieved full alertness, and only patients who did so survived. Seventy-five percent of patients arousable or initially alert (level of consciousness [LOC] ≥ 4) survived, all but two with excellent outcomes. Twenty-eight percent of patients initially in deep coma (LOC ≤ 3) survived, all with excellent or good outcomes. Ninety percent of patients who became fully alert did so within 72 hours. The likelihood of alerting is correlated with the LOC at given intervals after CPA. Reliable predictions of survival and outcome can often be based upon LOC alone within 2 days after CPA.

A Comparative Study of Cerebral Atherosclerosis in Males and Females

An evaluation of the influence of sex upon cerebral atherosclerosis was carried out in 5,033 consecutive autopsies studied by a special well-standardized coding technique. A sex difference in frequency of cerebral atherosclerosis appears from the fourth to the sixth decade. During this period the percentage of female cases with no atherosclerosis lags behind the percentage of male cases by a 15-year period. After the sixth decade, the frequency of cerebral atherosclerosis increases more rapidly in females, so that beyond the age of 65 years the frequency of cerebral atherosclerosis is equal in the two sexes. Furthermore, younger males show a higher degree of cerebral atherosclerosis than females of the same age and a reverse trend appears in the oldest age groups. Diabetic females have more cerebral atherosclerosis than nondiabetic males, and beyond the fourth decade they have at least as much involvement as the diabetic males.