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All cases fulfilling stated criteria for encephalitis and aseptic meningitis in Olmsted County, Minnesota, for the period 1950 through 1981 were identified. This is, to our knowledge, the first such incidence and trend study in a delineated population, providing rates per 100,000 person-years of 7.4 for encephalitis (189 cases) and 10.9 for aseptic meningitis (283 cases). These are about twelve and six times higher, respectively, than the rates reported by the Centers for Disease Control. The rates have been stable over successive 5- or 10-year periods except for a recent increase in aseptic meningitis. Both conditions were more common in the summer months, in childhood, and among males. Viral identification using conventional laboratory tests has improved with time; in the period 1970 through 1981, virus type was specified in about one-fourth of the cases. The most common agents identified were California and mumps viruses in encephalitis, and entero and mumps viruses in aseptic meningitis. Antecedent and/or concurrent infections were noted in 42 and 35% of encephalitis and aseptic meningitis cases, respectively. No case due to mumps, measles, or rubella viruses has occurred since 1972, reflecting the impact of immunizations. Recovery was reported at the end of the acute phase in 95% of patients with aseptic meningitis, and there were no deaths. Seventy-eight percent of encephalitis patients recovered completely; the case fatality rate was 3.8%. Of the encephalitis cases, 2% were diagnosed initially postmortem.

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] greater than or equal to 4) survived, all but two with excellent outcomes. Twenty-eight percent of patients initially in deep coma (LOC less than or equal to 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.

In a longitudinal study of patients with epilepsy in Rochester, Minnesota, we found that the probability of being in remission (at least 5 consecutive years seizure-free, and continuing) at 20 years after diagnosis was 70%. The rates for remission we encountered were generally higher than those previously reported. We believe that the better prognosis in our series results from inclusion of all incidence cases in a defined population, beginning at the initial diagnosis of epilepsy. Prognosis for remission of epilepsy is poor in patients with associated neurologic dysfunction identified from birth. Patients with idiopathic seizures and survivors of postnatally acquired epilepsy have better prospects for eventual remission. The probability of remission is highest in patients with generalized-onset seizures diagnosed before 10 years of age. Prognosis is less favorable for those with partial complex seizures and adult-onset epilepsy.

There is ample evidence for genetic and other heterogeneity in the mechanisms leading to epilepsy. Animal models of epilepsy show that genetic factors can influence the hypersensitivity of neurons. In the human, there are over 140 Mendelian traits (including disorders of amino acids, enzymes, hormones, and vasculature) that increase the risk of seizures. Furthermore, systems with an intermediate optimum (such as blood clotting and blood glucose) involve a number of mechanisms under independent genetic control, and it is reasonable to assume that the same principle applies to neuronal excitability. Finally, genetic variation can be expected in any of the factors that are altered in the origin of seizures: neuronal inhibition, inactivation of excitatory neurotransmitters, feedback control, and seizure generalization. One goal of future research is to define etiological subtypes on the basis of biochemical data or other factors. Meanwhile, it is possible to analyze currently available indicators of phenotypic variability (age at onset of seizures, family history of seizures, seizure type, EEG pattern, and history of antecedent factors such as fever or trauma) to address the following questions: Do any phenotypic groups have different sibling risks for seizures? How much phenotypic variability is seen among affected siblings of each defined group of probands (index cases)? Do any groups of probands show significant biochemical differences? Within a specific group, do isolated and familial cases show the same phenotype? Within a presumed single entity, will linkage marker studies show further heterogeneity? With such data in hand, certain strategies can be recommended. Complex segregation analysis of family data will permit a test of alternative models for genetic transmission. Linkage studies of selected large families (using recombinant DNA probes) will establish the genetic map location of any single-locus major factor. Selected samples of multiplex families (with several affected siblings) will concentrate the likelihood of genetic factors and will permit the detection of biochemical factors that might be significant in only a few families. Biochemical and other hypotheses can be tested in a panel of twin pairs concordant or discordant for epilepsy. The search for genetic heterogeneity clearly has implications for diagnosis, prognosis, therapy, and genetic counseling, as well as for other research studies on the basic mechanisms of the epilepsies.(ABSTRACT TRUNCATED AT 400 WORDS)

If the patterns of seizure disorders in parents and offspring could be assessed accurately, some insight might be gained into the relative role of genetic and environmental factors in the development of convulsive disorders. In this study 908 children born in a Rochester, Minnesota hospital from 1922 through 1972 whose mother or father had a verified and classified diagnosis of seizure have been followed from birth for evidence of any convulsive episode or seizure disorder. The observed numbers of various types of convulsions in the offspring are compared to the expected the number based on local age-specific incidence rates. The outstanding finding was that a higher than expected number of children whose mothers had epilepsy also suffered from seizures (epilepsy or febrile convulsions), whereas no such increase was detected among the children of affected fathers.

Studies of patient compliance with medical regimens reveal that one-quarter to one-half of patients act at variance with their physician's suggestions. Using anthropological methods of long-term participant observation, seven epileptic patients were intensively studied for ten months in a variety of social contexts, including visits to health resources. Their conceptions of proper management of epilepsy were elicited, and their communication of these conceptions to providers of health care was observed. Although most of these patients were noncompliant, no single pattern of noncompliance encompassed their behavior as a group, and some of them had more than one drug consumption strategy. Furthermore, some patients were found to be noncompliant with biomedical regimens, yet actively and consistently pursuing alternative regimens. A range of such alternative therapies were identified both for low-income and middle-income patients. These case histories suggest that patients actively assess the quality of care given by their providers of health care. From the patient's point of view, biomedical strategies form one facet of many coping mechanisms in the management of epilepsy.

The clinical findings and laboratory results from 18 patients with clear-cut transient global amnesia (TGA) were compared with the results from 90 nonischemic neurological control patients using case-control analysis. A prior episode of cerebral ischemia, generally in the posterior circulation, was the most significant risk factor for TGA. Other risk factors for cerebrovascular disease were more prominent in the TGA group, but this association became less significant when cerebral ischemia was controlled for. Migraine, epilepsy, and psychiatric disorders were not significantly associated with TGA. In 5 of 13 patients, computed tomography showed focal thalamic and temporal lobe abnormalities. The recurrence rate was 7.0% for both TGA and subsequent cerebral ischemia. We conclude that TGA is closely linked to cerebrovascular disease. Further, prior damage to anatomical structures critical to memory may be necessary for the expression of this syndrome.

The course of seizures was reviewed in all 306 residents of Rochester, Minnesota who had epilepsy diagnosed between 1935 and 1978, lived in the region greater than or equal to 5 years after diagnosis, and had an electroencephalogram (EEG). The life-table probability of having achieved 5 years seizure-free (FYSF) by 20 years after diagnosis was 75%. In a multivariable proportional hazards model, these three variables predicted a significantly higher rate of achieving FYSF: no early-life brain damage (remission rate ratio = 2.27, p less than 0.01), no generalized epileptiform activity (rate ratio = 1.58, p less than 0.05), and never having had a generalized tonic-clonic seizure (rate ratio = 1.4, p less than 0.05). The same three variables, plus age at diagnosis, were descriptors of the rate of reaching FYSF off medication. Gender, family history, type of seizure, and EEG findings other than generalized epileptiform activity were not significantly related to either end point. The predictor set did 15% better than prior probabilities in forecasting FYSF. Although informative about group experience, these predictors are weak clinical discriminators, singly or in a set. FYSF occurred in high proportion of even those persons whose history, clinical examination, or EEG findings placed them in a less favorable stratum of one or more predictors.

A cohort of 666 children who had convulsions with fever were followed to determine the risks of subsequent epilepsy. High risks were found in children with preexisting cerebral palsy or mental retardation. Other major risk factors were atypical features of the febrile convulsions (such as focal seizures) and duration of febrile seizures for 10 minuts or more. The risk of developing epilepsy by age 20 was about 6 percent for all children who had experienced febrile convulsions. However, this risk figure consisted of a combination of 2.5 percent of children without prior neurologic disorder or atypical or prolonged seizures, and 17 percent of those with such complications.