Rebecca Rausch

A HEALTH-RELATED QUALITY OF LIFE INSTRUMENT FOR PATIENTS EVALUATED FOR EPILEPSY SURGERY

The goals of surgery in treating intractable epilepsy are to eliminate seizures and improve quality of life. This report describes the development of the Epilepsy Surgery Inventory (ESI)-55, a 55-item measure of health-related quality of life for epilepsy patients. The ESI-55 includes the following scales (number of items in parentheses): health perceptions (9), energy/fatigue (4), overall quality of life (2), social function (2), emotional well-being (5), cognitive function (5), physical function (10), pain (2), and three separate scales of role limitations due to emotional, physical, or memory problems (5 items each). Also included is one change in health item. The ESI-55 was completed by 89% of 224 adults who had undergone a protocol evaluation for epilepsy surgery since 1974. Alpha internal consistency reliability coefficients ranged from 0.76 to 0.88 except for social function (alpha = 0.68). Multitrait scaling analyses supported item discrimination across scales. Factor analysis confirmed previously identified mental and physical health factors, and yielded a third factor defined by cognitive function and role limitations scales. Construct validity was supported by correlations of the ESI-55 with a mood profile instrument. Analysis of ESI-55 scale scores by seizure classification showed that the 44 patients who were seizure-free following surgery scored higher than did 55 patients who continued to have seizures (P<0.05 for all comparisons); 43 patients having seizures without loss of consciousness scored in between. Results of this study indicate that the ESI-55 is reliable, valid, and sensitive to differences in seizure status.

Psychological Status Related to Surgical Control of Temporal Lobe Seizures

Summary: Patients who underwent temporal lobe surgery with diagnosis aided by stereoelectroencephalography (SEEG) were evaluated psychosocial^ before surgery and at one month and one year after surgery. Patients who were not operated on but who also had been evaluated by SEEG served as controls. These patients were evaluated at time periods comparable to those of the operated cases. At one year after surgery, patients whose seizures had been relieved had improved in Degree of Dependency, Work Performance, and Non‐Family Relationships. Patients whose seizures were not controlled by surgery and nonoperated patients did not show any significant change in psychosocial measurements one year postoperatively. Psychosocial improvements were seen regardless of the side of the brain operated. While patients whose seizures were reduced experienced memory deficits of the type associated with side of the temporal lobe resection, the data suggested that there was improvement in intellectual scores and, in the case of right‐sided surgery patients, memory functions associated with the contralateral, intact hemisphere.

Local cerebral metabolism during partial seizures

Intericta1 and ictal fluorodeoxyglucose scans were obtained with positron CT from four patients with spontaneous recurrent partial seizures, one with epilepsia partialis continua, and one with a single partial seizure induced by electrical stimulation of the hippocampus. Ictal metabolic patterns were different for each patient studied. Focal and generalized increased and decreased metabolism were observed. Ictal hypermetabolism may exceed six times the interictal rate and could represent activation of excitatory or inhibitory synapses in the epileptogenic region and its projection fields. Hypometabolism seen on ictal scans most likely reflects postictal depression and may indicate projection fields of inhibited neurons. No quantitative relationship between alterations in metabolism and EEG or behavioral measurements of ictal events could be demonstrated.

Outcomes in 248 patients who had diagnostic evaluations for epilepsy surgery

Surgery for intractable epilepsy is a widely used treatment that is not readily assessed by randomised trials. We evaluated the impact of epilepsy surgery on seizures, medication use, employment, and the quality of life in 248 adults and adolescents consecutively referred to one medical centre between 1974 and 1990. Outcomes were determined through self-administered questionnaire and medical record review for 202 surgery and 46 non-surgery patients whose treatment was usually determined by the presence or absence of an epileptogenic focus. Surgery and non-surgery patients differed at baseline only in median monthly seizure frequency (surgery lower than non-surgery). After adjustment for baseline covariates, surgery patients at follow-up had greater decline in average monthly seizure frequency (-11.9 vs - 1.5; difference -10.4, 95% CI -20.5, -0.3) and took fewer antiepileptic medications (average number 1.4 vs 2.0; difference -0.67, 95% CI -0.94, -0.40). Although quality-of-life scores were higher (p < 0.05) with surgery on 5 of 11 scales that were administered only at follow-up, there were no significant differences in employment status or prospectively assessed quality of life. Relative to a non-surgery group, patients treated surgically had better seizure control with less antiepileptic medication. The impact of epilepsy surgery on quality of life and employment needs to be assessed in larger prospective studies.

Quality of Life of Epilepsy Surgery Patients as Compared with Outpatients with Hypertension, Diabetes, Heart Disease, and/or Depressive Symptoms

Summary: Health‐related quality of life (HRQOL) of 166 adults who had previously undergone surgical treatment for intractable epilepsy was compared with that of outpatients with hypertension, diabetes, heart disease, andlor depressive symptoms. Eight self‐reported HRQOL domains were evaluated and compared by the RAND 36‐Item Health Survey 1.0: emotional well‐being, social function, role limitations due to emotional problems, energy/fatigue, pain, role limitations due to physical problems, physical function, and general health perceptions. A pictorial item on overall QOL was also administered, for a total of 9 HRQOL domains. With adjustment made for age, gender, education, and comorbid conditions, 55 completely seizure‐free patients scored higher (i.e., better health) than patients with hypertension in 6 of 9 domains, higher than diabetic patients in 8 of 9, higher than those with heart disease in all 9, and higher than those with depressive symptoms in all 9 (all p < 0.05). Sixty‐seven patients still having seizures with impaired consciousness scored worse than hypertensive patients in 5 domains, worse than diabetic patients in 3, and worse than heart disease patients in 2; for all 3 conditions, these domains included emotional well‐being and overall QOL (p < 0.05). These 67 patients, however, scored better than patients with depressive symptoms in all 9 domains, better than those with heart disease in 2, and better than those with diabetes in 1 (all p < 0.05). Forty‐four other patients had only simple partial seizures (SPS); their scores were comparable to those of diabetic and heart disease patients on mental and social health scales but were higher (“better”) than those of these patients on physical health scales. HRQOL among patients who have undergone “curative” epilepsy surgery is better than that of patients who have hypertension, diabetes, heart disease, or depressive symptoms. Patients who have continued seizures with altered consciousness are worse off in terms of emotional well‐being and overall QOL than all other patients, except for those with depressive symptoms.

Olfactory memory in patients with anterior temporal lobectomy.

Right and left temporal lobectomy patients, matched in age and intelligence, made more errors in odor recall than a control group. Patients with right temporal lobe excisions recalled significantly fewer odors correctly than patients with left temporal lobe excisions. Olfactory memory scores were not related to other memory deficits associated with left or right temporal lobe dysfunction or to intelligence or lesion size. However, in patients with right temporal lobectomy, percent of odors recalled correctly correlated positively with a general memory index. The findings presented are consistent with previous reports that the right temporal lobe is more involved with nonverbal memory than the left temporal lobe.

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease

Loss‐of‐function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known.

APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease

IMPORTANCE Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature. OBJECTIVE To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD. DESIGN, SETTING, AND PARTICIPANTS We studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene. MAIN OUTCOMES AND MEASURES Nine variables derived from 7 psychometric tests. RESULTS The APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10(-6); corrected P [Pc] = 6.0 × 10(-5)), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10(-5); Pc = 9 × 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests. CONCLUSIONS AND RELEVANCE Our data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.

Neurons in the human basolateral amygdala and hippocampal formation do not respond to odors

Extracellular action potentials were recorded from human hippocampal, hippocampal gyrus, and basolateral amygdala neurons during passive and active olfactory stimulation. Introduction of an odor into a continuous stream of air passing over the olfactory mucosa resulted in no detectable change in firing. Actively sniffing from an odorous flask, whether or not the odor was detected or recognized, also failed to elicit an immediate unit response. However, after a latency of 10-15 sec, the slight hyperventilation inherent in sniffing did induce a strong change in firing by many neurons. In contrast to these unit responses, a short-latency EEG spindle was recorded in the amygdala that appeared directly related to mechanical stimulation of the olfactory mucosa.

Changes in intelligence following temporal lobectomy: relationship to EEG activity, seizure relief, and pathology.

Summary: Pre‐ and posttemporal lobectomy measures of intelligence and memory in 36 patients with medically refractory complex partial seizures were compared with (1) various aspects of presurgical ictal and interictal EEG activity derived from surface and deep electrodes, (2) postlobectomy seizure relief, and (3) pathological findings in the resected lobe. With respect to interictal EEG data, bilaterally synchronous surface spikes (accompanied or unaccompanied by simultaneous deep spikes) and sharp waves were significantly correlated with lower prelobectomy intelligence scores and a drop in these scores following lobectomy. With respect to ictal EEG data, bilaterally synchronous and multifocal onsets were significantly correlated with a postlobectomy drop in intelligence scores. Patients with poor postlobectomy seizure relief tended to have lower presurgical intelligence scores and a drop in intelligence scores following lobectomy. The patients most likely to show a postlobectomy drop in intelligence were those demonstrating some combination of poor seizure relief, an absence of pathology in the resected specimen, or EEG signs indicative of poor seizure relief. Postlobectomy changes in intellectual status are therefore not necessarily exclusively attributable to the amount of postlobectomy seizure relief experienced by these patients, but might be due to a combination of factors.