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Biomedical subjects

M R Sperling

Publications and source records attributed to M R Sperling.

At least 37 records · Page 2Linked to original sources
PubMed2000

EKG abnormalities during partial seizures in refractory epilepsy.

PURPOSE: This study assessed the frequency and character of ictal cardiac rhythm and conduction abnormalities in intractable epilepsy. Sudden unexpected death in epilepsy (SUDEP) is a major cause of excess mortality in people with refractory epilepsy, and cardiac arrhythmias during seizures may be responsible. The frequency of cardiac abnormalities during seizures in patients with refractory epilepsy must be determined. METHODS: Fifty-one seizures in 43 patients with intractable partial epilepsy were analyzed prospectively from CCTV-EEG monitoring with one ECG channel. Arrhythmias, repolarization abnormalities, and PR and QTc intervals were determined for preictal (3 min), ictal, and postictal (3 min) periods for one or more seizures per patient. Parametric statistics were used for continuous variables, and nonparametric statistics were used for categoric variables. RESULTS: Of the patients, 39% had one or more abnormalities of rhythm and/or repolarization during or immediately after seizures. Abnormalities included asystole (one), atrial fibrillation (one), marked or moderate sinus arrhythmia (six), supraventricular tachycardia (one), atrial premature depolarizations (APDs; eight), ventricular premature depolarizations (VPDs; two), and bundle-branch block (three). Mean seizure duration was longer in patients with abnormalities than in those without (204 vs. 71 s; p < 0.001). Generalized tonic-clonic seizures were also associated with increased occurrence of ictal ECG abnormalities (p = 0.006) as compared with complex partial seizures. There were no clinically significant differences in mean preictal and ictal/postictal PR and QTc intervals. CONCLUSIONS: Cardiac rhythm and conduction abnormalities are common during seizures, particularly if they are prolonged or generalized, in intractable epilepsy. These abnormalities may contribute to SUDEP.

Adolescent↗
PubMed2000

Relationships between seizure severity and health-related quality of life in refractory localization-related epilepsy.

PURPOSE: To evaluate relationships between self-report measures of seizure severity and health-related quality of life (HRQOL) in people with refractory localization-related epilepsy. METHODS: A sample of 340 adults enrolled in a seven-center, prospective study of resective epilepsy surgery completed baseline questionnaires that included the Quality of Life in Epilepsy (QOLIE)-89 and a seven-item adaptation of the National Hospital Seizure Severity Scale. Associations between QOLIE-89 summary measures and both the total seizure severity scale score and individual seizure severity items were assessed, after adjustment for seizure frequency. RESULTS: The seizure severity measure had adequate scale score variability and reliability in this sample. Correlations between individual items in the scale did not exceed 0. 43. Product-moment partial correlations between the seizure severity scale and QOLIE-89 summary measures ranged from -0.17 to -0.29 (all p values <0.01). Of the seven seizure severity items, the average time before individuals perceived they were "really back to normal" after their seizures was broadly related to all domains of HRQOL (r values ranged from -0.16 to -0.30; p values <0.01). Severity of injury during seizures was the only other item having more than minimal associations with HRQOL, and it was selectively related to the physical health measure. Higher frequency of falls during seizures was modestly related to less employment. CONCLUSIONS: This seizure severity measure assesses constructs that are generally distinct from HRQOL, except for moderate and broad associations between HRQOL and patient's perceptions of the average duration of recovery time after seizures. Recovery time may potentially be a useful clinical indicator of seizure severity that reflects meaningful impairment of HRQOL in adults with frequent seizures.

Adolescent↗
PubMed2000

Psychiatric aspects of temporal lobe epilepsy before and after anterior temporal lobectomy.

OBJECTIVES: Psychopathology has been reported to be prevalent both before and after surgical treatment for medically intractable temporal lobe epilepsy. Individual patients were evaluated prospectively to assess the effect of anterior temporal lobectomy (ATL) on prevalence and severity of psychiatric disease. METHODS: Psychiatric status was assessed in a consecutive series of epilepsy patients before and 6 months after ATL using a structured psychiatric interview, psychiatric rating scales, and self report mood measures. RESULTS: A DSM-III-R axis I diagnosis was present in 65% of patients before and after surgery. The most common diagnoses were depression, anxiety, and organic mood/personality disorders. There was a trend for major psychiatric diagnoses to be more common in patients with right compared to left temporal lobe seizure focus, both before and after surgery. The apparent stability in the overall rate of psychiatric dysfunction concealed onset of new psychiatric problems in 31% of patients in the months shortly after surgery, and resolution of psychiatric diagnoses in 15% of patients. In the group as a whole, the severity of psychiatric symptoms was lower at 6 months postsurgery than before temporal lobectomy. CONCLUSIONS: The overall prevalence of psychiatric dysfunction was comparably high before and after ATL, but individual changes in psychiatric status and changes in severity of symptoms occurred in many patients in the 6 months after surgery.

Adult↗
PubMed1999

Seizure control and mortality in epilepsy.

Mortality rates are increased among people with epilepsy, and may be highest in those with uncontrolled seizures. Because epilepsy surgery eliminates seizures in some people, we used an epilepsy surgery population to examine how seizure control influences mortality. We tested the hypothesis that patients with complete seizure relief after surgery would have a lower mortality rate than those who had persistent seizures. Three hundred ninety-three patients who had epilepsy surgery between January 1986 and January 1996 were followed after surgery to assess long-term survival; 347 had focal resection or transection, and 46 had anterior or complete corpus callosotomy. A multivariate survival analysis was performed, contrasting survival in those who had seizure recurrence with survival of those who remained seizure free. Standardized mortality ratios and 95% confidence intervals were calculated. Overall, seizure-free patients had a lower mortality rate than those with persistent seizures. This was true for the subset of patients with localized resection or multiple subpial transection. No patients died among 199 with no seizure recurrence, whereas of 194 patients with seizure recurrence, 11 died. Six of the deaths were sudden and unexplained. Most patients who died had a substantial reduction in postoperative seizure frequency. The standardized mortality ratio for patients with recurrent seizures was 4.69, and the risk of death in these patients was 1.37 in 100 person-years, whereas among patients who became seizure free, there was no difference in mortality rate compared with the age- and sex-matched population of the United States. Elimination of seizures after surgery reduces mortality rates in people with epilepsy to a level indistinguishable from that of the general population, whereas patients with recurrent seizures continue to suffer from high mortality rates. This suggests that uncontrolled seizures are a major risk factor for excess mortality in epilepsy. Achieving complete seizure control with epilepsy surgery in refractory patients reduces the risk of death, so the long-term risk of continuing medical treatment appears to be higher than the risk of epilepsy surgery in suitable candidates.

Adolescent↗
PubMed1999

Depression in temporal lobe epilepsy before epilepsy surgery.

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.

Adolescent↗
PubMed1999

Hippocampal cell density and subcortical metabolism in temporal lobe epilepsy.

PURPOSE: Correlations between hippocampal cell density and subcortical metabolism in patients with temporal lobe epilepsy (TLE) were studied to explore possible links between subcortical function and the regulation of hippocampal excitability. METHODS: Resected hippocampal cell densities were correlated with cortical and subcortical regional cerebral metabolic rate for glucose (CMRglu), as measured by [18F]-fluorodeoxyglucose positron emission tomography (18-FDG-PET), in 39 patients with intractable TLE who underwent anterior temporal lobectomy (ATL). CMRglu was measured ipsilateral and contralateral to the resected temporal lobe. Linear regression techniques were used for statistical analysis. RESULTS: Hilar cell densities correlated positively and significantly with CMRglu in the bilateral thalamus, putamen and globus pallidus, and the ipsilateral caudate. Dentate granule cell densities correlated positively and significantly with CMRglu in the bilateral thalamus and putamen. There was no significant correlation between cell densities and CMRglu in any cortical region, including the hippocampus. CONCLUSIONS: We postulate that hippocampal cell loss results in decreased efferent synaptic activity to the thalamus and basal ganglia, causing decreased neuronal activity in these structures with consequent hypometabolism. This synaptic activity has a significant bilateral component. Subcortical hypometabolism in patients with TLE may reinforce the epileptogenic potential of mesial temporal lobe discharges.

Amygdala↗
PubMed1999

The ketogenic diet for intractable epilepsy in adults: preliminary results.

PURPOSE: Little is known concerning the efficacy and adverse effects of the ketogenic diet in adults with refractory epilepsy. This review reports preliminary results in 11 adults prospectively treated with the diet who had previously failed to gain seizure control with two or more medications and/or surgery. METHODS: Eleven patients nine women, two men), median age, 32.2 years (range, 19-45 years) were treated with the ketogenic diet with a 4:1 ratio with fluid restriction. Six patients had symptomatic partial epilepsy, and five had symptomatic generalized epilepsy. The diet was administered in addition to antiepileptic medication by a multidisciplinary team geared exclusively to adult patients. Medications were not changed while on the diet. Seizure frequency at 8-month follow-up was compared with frequency during a baseline period. RESULTS: At 8 months of follow-up, three patients had a 90% seizure decrease, three patients had a 50-89% decrease in seizure frequency, one patient had <50% seizure decrease, and four patients discontinued the diet. Of the four patients who discontinued the diet, two had no appreciable change in their seizures despite high ketone levels. Two patients were unable to maintain persistent ketosis at home, despite having done so in the hospital. All seizure types responded to the diet. Common adverse effects included constipation and menstrual irregularities in women. Most patients reported a subjective improvement in concentration. Serum cholesterol and triglycerides increased while on the diet as well as cholesterol high-density lipoprotein (HDL) ratios. CONCLUSIONS: The ketogenic diet shows promise in both adult generalized and partial epilepsy. Persistent ketosis was possible in adults, and the diet was tolerable for most patients. Further study assessing the efficacy of the ketogenic diet, and the cognitive and long-term effects is ongoing.

Adult↗
PubMed1999

Marital status after epilepsy surgery.

PURPOSE: To characterize features influencing marital status in a group of patients with refractory epilepsy before and after epilepsy surgery and to assess the effect of seizure control on marital status after epilepsy surgery. METHODS: We analyzed marital status in 430 epilepsy surgery patients and in a subset with temporal lobe epilepsy. Marital status was assessed in relation to gender and age of epilepsy onset and compared with marital rates for the U.S. population. Patients who had > or =4 years of postsurgical follow-up were examined for change in marital status after surgery. Those patients who changed marital status were then evaluated for change in employment. RESULTS: Marital rates were lower than expected in men. Men with onset of epilepsy by age 11 years were less likely to be married than men whose seizures began after age 11 or women whose seizures began at any age. Men and women with temporal lobe epilepsy had higher marriage rates than those with extratemporal lobe epilepsy. More than 4 years after epilepsy surgery (n = 190), patients who had no recurrent seizures were more likely to change marital status (28 of 124, 23%), than those who had recurrent seizures (five of 66, 8%). Seizure-free women were more likely to divorce (n = 9) than were seizure-free men (n = 1). Most men who married were employed (77%), whereas women who divorced were usually unemployed (67%). CONCLUSIONS: The age at which seizures begin influences later marital status in men, who have reduced marriage rates. The abolition of seizures by epilepsy surgery creates new opportunities for changing social relationships. Location of the epileptic focus may influence psychosocial function.

Adult↗
PubMed1999

The EEG and prognosis in status epilepticus.

PURPOSE: To examine the relation between specific EEG features and clinical outcome, determine whether a predictable sequence of EEG patterns exists during status epilepticus (SE), and examine the relation between periodic epileptiform discharges (PEDs) and SE. METHODS: EEG records of 50 patients with SE admitted to Graduate Hospital between January 1990 and July 1995 were reviewed. Ictal EEGs were available in 72%; 28% had only postictal EEGs. Poor outcome was defined as death or persistent vegetative state, and good outcome as all others. Fisher's Exact test, chi2, and t tests were performed for data analysis. RESULTS: Of 50 patients, 72% had a good outcome and 28%, a poor outcome. If PEDs were present at any time during or after SE, outcome tended to be worse (p = 0.053). With PEDs, eight (44%) of 18 had a poor outcome; without PEDs, six (19%) of 32 had a poor outcome. Etiologies for SE did not substantially differ in patients with or without PEDs, and structural abnormalities were not more associated with the presence of PEDs. PEDs were seen both early and late, during and after SE. Other EEG characteristics (lateralized vs. bilateral symmetric ictal EEG, discrete vs. continuous ictal activity, and postictal focal slowing) did not relate to outcome. No predictable sequence of EEG changes was found during SE. CONCLUSIONS: PEDs are the only EEG feature related to outcome in SE and are associated with poor outcome independent of etiology.

Adolescent↗
PubMed1999

Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy.

The presence of paroxysmal discharges in the epileptic human dentate gyrus provides a physiologic basis for hyperexcitability that may initiate seizure discharges during the development of epilepsy. Although these responses can occur with single orthodromic stimulation, data obtained under conditions that weaken synaptic inhibition (e.g., 1 Hz stimulation or bicuculline disinhibition) suggest that paroxysmal discharges may be a more common feature of tissue from temporal lobe epileptic patients than has been reported previously. Hilar cell loss and weakened synaptic inhibition may provide conditions favorable for the activation of N-methyl-D-aspartate acid (NMDA) receptors that would allow triggering of paroxysmal discharges that normally never are evoked in dentate granule cells in nonepileptic humans. As the dentate gyrus in normal animal tissue is not susceptible to intrinsic bursting behavior and is characterized by a relatively short duration excitatory postsynaptic potential even under pharmacologic disinhibition, paroxysmal discharges in the epileptic human dentate gyrus may provide an important clue to understanding the prerequisite conditions for seizure discharge.

Animals↗
PubMed1998

Strong paired pulse depression of dentate granule cells in slices from patients with temporal lobe epilepsy.

Recurrent, feedback excitation by sprouted mossy fibers may contribute to the hyperexcitability observed in human temporal lobe epilepsy. Observations in rodent models of epilepsy mimic the findings in human tissue and reveal that dentate granule cells sprout axons which innervate fibers in their own dendritic layer. However, recent evidence in rodents suggest that these sprouted fibers may form connections which cause inhibition of dentate granule cells, not excitation. Thus, the net effect of sprouting in human epileptic tissue may not only be recurrent excitation. We analyzed paired pulse depression in dentate slices from 9 patients with temporal lobe epilepsy and found evidence for strong feedback inhibition. We also noted failure of high frequency stimulation induced inhibition in our human specimens. These data challenge the concept that human epileptic dentate granule cells are excited by recurrent mossy fiber sprouting.

Adolescent↗
PubMed1997

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy.

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.

Adolescent↗
PubMed1997

Clinical challenges in invasive monitoring in epilepsy surgery.

Invasive monitoring aids in selecting patients for epilepsy surgery. This article reviews the methods employed to obtain intracranial EEG, data interpretation, and problems that arise during intracranial investigations. The relative merits of depth, subdural, epidural, and foramen ovale electrodes are reviewed, and a strategy for their use is suggested. Characteristic interictal and ictal EEG findings are summarized, and the problems encountered in interpreting data are discussed.

Brain Mapping↗
PubMed1997

Seizures in temporal lobe epilepsy: I. Reliability of scalp/sphenoidal ictal recording.

We determined both (1) the reliability (reproducibility) of seizure onset location in patients with temporal lobe recorded with extracranial EEG and (2) if interictal spike (IIS) location influences that reliability. EEGs were recorded with the 10-20 system and sphenoidal electrodes. Between 1985 and 1993, 166 patients with suspected temporal lobe epilepsy were eligible for inclusion with a total of 734 seizures recorded. Each seizure onset was classified as either localized, lateralized, or nonlocalized. Individual patients were then grouped according to interictal spike location (i.e., unilateral, bilateral, or none) as well as by ictal onset reproducibility patterns (i.e., concordant, semiconcordant, conflicting, or nonlocalized) based on each patient's monitoring session. Seizure onset location was reproducible in 68% of the cases and variable patterns of seizure onset were seen in 32% of patients. Patients with unilateral IIS (68%) were more likely to have consistent ictal onset patterns than patients with bilateral IIS (27%). The first seizure more often predicted subsequent seizure onset patterns when it was localized than when it was nonlocalized. Of 18 patients with conflicting temporal lobe seizures, up to four seizures were necessary to detect independent bilateral temporal lobe seizures.

Adolescent↗
PubMed1997

A cost-effectiveness analysis of anterior temporal lobectomy for intractable temporal lobe epilepsy.

Patients with medically intractable temporal lobe epilepsy are potential candidates for anterior temporal lobectomy (ATL), in which epileptogenic temporal lobe tissue is localized and surgically removed. This surgical approach can eliminate or drastically reduce seizures in the majority of patients. The authors used a decision-analysis model to examine the cost-effectiveness of a surgical evaluation and treatment protocol for medically intractable temporal lobe epilepsy. This model compared a cohort treated with the new protocol with a continuation of their immediate preoperative medical management and projected these differences over the patient's lifetime. The Markov model incorporated postoperative seizure status, patient quality of life, death from surgical and natural causes, discounting, and the direct medical costs associated with outpatient evaluation, hospitalization, surgery, antiepileptic drugs, and lifetime outpatient treatment. The intent-to-treat analysis included patients who underwent evaluation but were not eligible for ATL. Sensitivity analyses were also performed on the variables in the model. Data from the baseline model indicated that evaluation for ATL provided an average of 1.1 additional quality-adjusted life years (QALYs) compared with continued medical management, at an additional cost of $29,800. Combining the clinical and economic outcomes yielded a cost-effectiveness ratio of $27,200 per QALY. This value is comparable to other accepted medical or surgical interventions, such as total knee arthroplasty ($16,700/QALY) or coronary artery balloon angioplasty ($40,800/QALY). Sensitivity analyses demonstrate that the results are critically dependent on postoperative seizure status and improvement in quality of life. Although further work is necessary to quantify the improvement in quality of life after epilepsy surgery better, the present data indicate that ATL for treatment of intractable temporal lobe epilepsy is a cost-effective use of medical resources.

Adult↗
PubMed1997

Epilepsy management. Issues in medical and surgical treatment.

After a single seizure, about 40% of patients have recurrence. The main features correlating with recurrence are cause, seizure type, EEG findings, family history of seizures and, possibly, the presence of a prior febrile seizure, Todd's paresis, and other abnormal neurologic findings. A number of medications are available for treatment. Withdrawal from medication is successful in 60% to 70% of patients. Several factors favor successful drug taper. These include a seizure-free status for at least 2 years during drug therapy, a single type of seizure (partial or generalized), young age at seizure onset, and an epilepsy syndrome with a tendency to remit. Surgery can be considered in certain patients with surgically remediable syndromes. Candidates typically have seizures that impair consciousness, that cause falling with injury, that have adverse psychosocial or social effects, and that persist after trials of three appropriate medications. A multidisciplinary evaluation should take place at a surgery center with experience and documented success. Favorable results from surgery can be expected in a large proportion of patients.

Anticonvulsants↗
PubMed1997

Mossy fiber reorganization and its possible physiological consequences in the dentate gyrus of epileptic humans.

It is unlikely that MF reorganization is the cause of epilepsy, but it may affect the progression of the disease, i.e., the frequency or severity of seizures. We propose that early events, yet undiscovered, lead to an increased likelihood of excitability. This hyperexcitability, which initially may not be manifested in overt seizures, may erode vulnerable hilar neurons that serve an important inhibitory function, as illustrated in Fig. 6-15. As inhibition is lost, hyperexcitability reaches the level of clinically manifested seizures that are severe enough to lead to substantial loss of hilar neurons. When the loss of these cells is sufficiently high, MF reorganization occurs, first to neighboring hilar neurons and later to dendrites of granule cells (Fig. 6-15). Thus, the functional consequence of MF reorganization may provide a compensatory form of inhibition, as well as a circuit for feedback excitation. Although definitive evidence indicating that MF reorganization contributes to the acceleration or progression of epilepsy is missing, the findings to date are consistent with this hypothesis. In the event that reorganization contributes to the epileptic condition, treatments that reduce indicators of neuropathology may lead to a reduction of seizure frequency and severity. Evidence suggests that reorganization in the dentate gyrus may follow the pathways of neuronal processes of hilar neurons that have died. Thus, further study of the events that guide MF reorganization may hold important clues for developing methods for targeting regenerating axons following central nervous system injury.

Dentate Gyrus↗