Mapping and positional cloning of common idiopathic generalized epilepsies: juvenile myoclonus epilepsy and childhood absence epilepsy.

Among the 40 to 100 million persons with epilepsy worldwide and the 2 to 2.5 million persons with epilepsies in the United States, approximately 50% have generalized epilepsies. Among all epilepsies, the most common are juvenile myoclonus epilepsy (JME) with 10% to 30% of cases, childhood absence epilepsy (CAE) with 5% to 15% of cases, and pure grand mal on awakening with 22% to 37% of cases. In the last decade, six different chromosomal loci for common generalized epilepsies have been identified. These include two separate loci for JME in chromosomes 6p and 15q. The epilepsy locus in chromosome 6p expresses the phenotypes of classic JME, pure grand mal on awakening, and possibly JME mixed with absences. Two separate loci also are present for pyknoleptic CAE, namely, CAE that evolves to JME in chromosome 1p and CAE with grand mal in chromosome 8q24. Pandolfo et al. from the Italian League Against Epilepsy have reported two other putative susceptibility loci for idiopathic generalized epilepsies, namely, grand mal and generalized spike waves 35l in chromosome 3p and generalized epilepsies with febrile convulsions, grand mal, JME, absences, and electroencephalographic spike waves in 8q24. This chapter reports on the debate concerning whether there may be two separate epilepsy loci in chromosome 6p, one in the HLA region and one below HLA. The chapter then discusses the progress made in our laboratories as a result of the Genetic Epilepsy Studies (GENES) International Consortium. We discuss (a) the 2 to 6 cM critical region for classic JME located some 20 cM below HLA in chromosome 6p, (b) the 7-cM area for pyknoleptic CAE that evolves to JME in chromosome 1p, and (c) the 3.2 cM area for pyknoleptic CAE with grand mal and irregular 3 to 4 Hz spike waves in chromosome 8q24. We discusses efforts underway to refine the genetic map of JME in chromosome 6p11 and the advances in physical mapping and positioning of candidate genes, such as the gamma-aminobutyric acid receptor gene, the potassium channel gene of the long-QT family (KvLQT), named KCNQ3, and the human homologue of the mouse jerky gene for CAE in chromosome 8q24 and JME in chromosome 6p11.

Cognitions in generalized anxiety disorder and panic disorder patients.

Forty-three patients with generalized anxiety disorder (GAD) and 44 patients with panic disorder (PD) were given a standardized interview about thoughts and images during times of anxiety. The two groups differed significantly regarding the ideational content of anxiety. GAD patients experienced more thoughts focusing on themes of mental catastrophes and other catastrophes when suffering from anxiety or anxiety attacks, while PD patients mostly described the theme of physical catastrophes. Only 34% (n = 30) of the total sample reported experiencing images when feeling anxious/having panic. For PD patients (70%) onset of anxiety or panic attacks was precipitated by somatic symptoms (a physical feeling). GAD patients reported that onset of anxiety was precipitated by all three alternatives given: a physical feeling (42%), anxious thoughts (37%), or "it all came at once" (21%). The implications of these results are discussed.

Misinterpretation of body sensations in panic disorder.

Cognitive accounts of panic predict that panic disorder patients will be particularly prone to misinterpret autonomic sensations. Several studies have produced results consistent with this prediction, but each is open to alternative interpretation. To clarify matters, 2 studies administered the Body Sensations Interpretation Questionnaire (BSIQ) to panic patients and controls. Panic patients were more likely to interpret ambiguous autonomic sensations as signs of immediately impending physical or mental disaster and were more likely than other anxiety disorder patients and nonpatients to believe these interpretations. In a 3rd study, a brief version of the BSIQ was shown to have satisfactory test-retest reliability, to change with treatment, and to discriminate treatments that varied in their effects on panic.

Cognitive bias in panic disorder patients and changes after cognitive-behavioral treatments.

The aim of this study was to investigate cognitive biases in panic disorder patients via a questionnaire originally developed by Clark and co-workers [Clark, Salkovskis, Gelder, Koehler, Martin, Anastasiades, Hackman, Middleton & Jeavons, (1988). In Hand, I. & Wittchen, H.-U. (Eds) Panic and Phobias 2] to assess interpretations of ambiguous internal (bodily sensations) and external events. The results showed that, compared to normal controls, panic disorder patients interpreted bodily sensations in a more threatening fashion, while there was no difference concerning external events. Cognitive-behavioral treatments normalized this bias, and Cognitive Behavior Therapy and Applied Relaxation were equally effective in this respect. Moreover, compared to panicking patients, panic-free patients had reduced their cognitive threat bias at post-treatment and follow-up to a significantly larger extent. The results support the cognitive theory of panic disorder.

Applied relaxation vs cognitive behavior therapy in the treatment of panic disorder.

The present study investigated the efficacy of a coping-technique, applied relaxation (AR) and cognitive behavior therapy (CBT), in the treatment of panic disorder. Thirty-eight outpatients fulfilling the DSM-III-R criteria for panic disorder with no (n = 30) or mild (n = 8) avoidance were assessed with independent assessor ratings, self-report scales and self-observation of panic attacks before and after treatment, and at a 1-yr follow-up. The patients were treated individually for 12 weekly sessions. The results showed that both treatments yielded very large improvements, which were maintained, or furthered at follow-up. There was no difference between AR and CBT on any measure. The proportion of panic-free patients were 65 and 74% at post-treatment, and 82 and 89% at follow-up, for AR and CBT, respectively. There were no relapses at follow-up, on the contrary 55% of the patients who still had panic attacks at post-treatment were panic-free at follow-up. Besides affecting panic attacks the treatments also yielded marked and lasting changes on generalized anxiety, depression and cognitive misinterpretations. The conclusion that can be drawn is that both AR and CBT are effective treatments for panic disorder without avoidance.

Applied relaxation, exposure in vivo and cognitive methods in the treatment of panic disorder with agoraphobia.

Forty-five psychiatric outpatients with DSM-III-R diagnosis of panic disorder with agoraphobia were assessed with a battery of self-report, behavioral and cognitive measures before and after therapy, and at a 1 yr follow-up. They were randomly assigned to either Applied Relaxation (AR; n = 15), Exposure in vivo (E; n = 15) or Cognitive Treatment (CT; n = 15) and received 12 individual therapy sessions, once weekly. All patients also had self-exposure instructions. The three treatments yielded significant improvements that were maintained at follow-up. One criterion of clinically significant improvement was fulfilled by 87% of the AR-, 80% of the E- and 60% of the CT-patients at the end of treatment, and 85, 79 and 67%, respectively, at follow-up. Between-group differences were observed on two measures only, both showing better results for AR than for CT. The conclusion that can be drawn is that the three treatments, focussed on different anxiety components, are about equally effective, and the results are maintained 1 yr after the end of treatment.

Utilization of health care resources after stroke. A population-based study of 258 hospitalized cases followed during the first year.

In a prospective population-based study the cumulative utilization of health care resources (and the rehabilitation outcome) was followed in consecutive stroke patients 3, 6 and 12 months after the onset of the disease. The study group comprised 258 patients diseased during the period February 1st 1986-January 31th 1987. The pattern of various forms of hospital beds and non-hospital facilities in open care utilized during the first post-stroke year was analysed at 1986 year's cost level. The mean utilization of acute hospital beds during the initial phase was 15 days; at an expenditure cost of 26,670 SEK ($3,683). The mean utilization of acute hospital and of geriatric beds during the first year was 19 and 59 days respectively. Thus the total hospital bed days amounted to a mean of 78 days; at a mean expenditure of 87,0000 SEK ($12,000); 70% of the patients were discharged from hospital care to independent living after 36 days. The acute care hospital provided 36% and geriatric care 64% of the beds needed before discharge. The expenditure of non-hospital facilities was mean 19,000 SEK ($2600); thus total expenditure for health care amounted to 106,000 SEK ($14,600). The relation between non-hospital and hospital care was approximately 1 to 5. Severity of the stroke influenced markedly the pattern and the total utilization of both hospital and non-hospital care. Patients with major stroke utilized health care resources at an expenditure 3.5 times that used by patients with minor stroke. Age of the patient also influenced health care utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Rehabilitation and achieved health quality after stroke. A population-based study of 258 hospitalized cases followed for one year.

In a prospective population-based study rehabilitation outcome and achieved health quality was followed in consecutive hospitalized stroke patients after 3, 6 and 12 months. The study group comprised 258 patients (125 men and 133 women) admitted during the period February 1st 1986-January 31st 1987. Most (76%) had major stroke and 24% had minor stroke. Stroke occurred predominantly among the elderly; 74% were greater than or equal to 70 years and 38% greater than or equal to 80 years. The case-fatality rate was 11% during the acute phase and 27% after one year. Of all patients 49% returned to their own homes, 2% moved into an old people's home and 38% were referred to institutions. Age of the patient and severity of the stroke influenced on the survival rates and on the discharge pattern. The amount of patients living in their own homes increased steadily with time. At discharge and after 3, 6 and 12 months 49, 54, 58, 56% of all patients and 54, 66, 73 and 77% of the survivors respectively were living at home, whereas 38, 22, 15 and 10% of all patients and 43, 27, 19 and 14% of the survivors were in institutions at the corresponding time periods. The remaining survivors were living in an old people's home. The major recovery of functional ability occurred within the first 3-6 months. At 3, 6 and 12 months 80, 82 and 81% of the surviving patients were able to walk indoors independently.

Survival following stroke. A prospective population-based study of 438 hospitalized cases with prediction according to subtype, severity and age.

In a prospective population-based study analyses were performed to estimate the survival prognosis following stroke, in relation to age of the patient as well as to subtype, severity and occurrence of the stroke diagnosis. The statistical technique of stepwise regression analysis was used to discriminate the isolated importance of these factors on survival outcome. A total of 438 patients, consecutively admitted to the Department of Neurology during the period Feb. 1st 1986-September 30th 1987 were followed 15 days, 3, 6, and 12 months after the acute stroke. The one-year survival rate was 75% compared with 93% for a control group matched for age, sex, residence and calendar year. Mortality after stroke occurred predominantly within the first 3 months, after 3 months survival prognosis was no different from that of the general population. Statistical analysis identified 2 factors that gave significant isolated prediction on survival outcome. These factors were in order of importance age and severity of stroke diagnosis, whereas sex, subtype and occurrence of stroke were of no discriminative value.

Outcome after stroke in patients discharged to independent living.

In a prospective, population-based study, we evaluated rehabilitation outcome, place of residence, and functional ability 3, 6, and 12 months after stroke onset in 129 consecutive patients discharged from the hospital to independent living, either in their own homes or in an old people's home. The study group comprised 50% of all patients admitted for acute stroke between February 1, 1986, and January 31, 1987. Of the 129 patients, 125 returned to their own homes and four moved into an old people's home. Once they returned home, only minor changes occurred in the patients' place of residence or functional capacity. The majority of the patients (90%) were still living in their own homes after 12 months; 99% could walk independently indoors, 92-95% could climb a staircase, and 90% could manage their daily hygiene. Eight patients (6%) died during follow-up, and one fourth of the patients were hospitalized again. The average number of days of rehospitalization during the 12 months was 23. Our study may serve as a guide to the planning of stroke programs and to a more effective and efficient use of available health resources.

Nature of the penetration barrier in Escherichia coli K-12: effect of macromolecular inhibition of penetrability in strains containing the envA gene.

The envA mutation in Escherichia coli K-12, which maps at 1.5 min, was previously shown to mediate sensitivity to gentian violet as well as to several antibiotics. Moreover, strains containing the envA gene were recently found to be lysed by lysozyme in the absence of ethylenediaminetetraacetate. It is here reported that the envA mutation mediates an increased uptake of gentian violet. The uptake of the dye was markedly affected by growth with different antibiotics interfering with macromolecular synthesis. Amino acid starvation of a strain containing envA with a stringent control of ribonucleic acid (RNA) synthesis resulted in a decreased uptake of gentian violet. However, no decrease in dye uptake was found during starvation in an envA transductant with a relaxed control of RNA synthesis. Inhibition of deoxyribonucleic acid (DNA) synthesis by nalidixic acid decreased the uptake of gentian violet of envA cells and, in addition, rendered the cells insensitive to the lytic action of lysozyme. Chloramphenicol treatment increased penetrability in wild-type and starved envA cells. In most instances, this effect of chloramphenicol was prevented by selectively interfering with DNA or RNA synthesis. A coordinate regulation of nucleic acid synthesis and penetrability is suggested.