Acneiform follicular mucinosis.

Follicular mucinosis is a rare chronic inflammatory disease of unknown aetiology, presenting as mucin deposits around the follicles and sebaceous glands. It can progress to alopecia of the scalp and other hairy areas. Follicular mucinosis may be a benign primary idiopathic disorder or secondary to malignant lymphoproliferative disorders. It can present with shiny papules or sharply marginated infiltrated erythematous scaling plaques, with follicular accentuation on the scalp, neck, trunk and limbs. There are many local and systemic treatments. This paper discusses the case of an adult with an uncommon acneiform follicular mucinosis controlled with systemic corticosteroids.

Early and late cognitive changes following temporal lobe surgery for epilepsy.

OBJECTIVE: To evaluate early and late postoperative cognitive changes in adult patients who had a standardized temporal lobe resection for control of intractable complex partial seizures and to relate quality of life measures at the long-term follow-up to seizure control and a verbal memory skill. METHODS: Patients in this longitudinal study had intractable epilepsy and had cognitive tests at the initial surgical evaluation, 1 year later, and at a long-term follow-up (at least >9 years later). Mean follow-up was 12.8 years. Participants were 44 patients who had an en bloc left (LTL) or right (RTL) temporal lobe resection and 8 nonsurgical patients with epilepsy. RESULTS: Patients with LTL surgery showed selective early decreases in verbal memory. At the long-term follow-up, further decreases in verbal memory and visual memory scores were seen for all patient groups. In general, the nonmemory scores remained stable over time. LTL surgery and initial high scores were predictors of verbal memory decreases seen at the early follow-up. Late memory declines were predicted by higher 1-year scores. LTL surgery was an additional predictor of late decline on a verbal memory task sensitive to the integrity of the left hippocampus. Higher quality of life scores of patients at the long-term follow-up were associated with both better seizure control and a higher everyday verbal memory skill: prose recall. CONCLUSIONS: Surgery-induced verbal memory deficits following LTL surgery continue 13 years after surgery. Late, possibly age-related, declines in multiple memory scores are seen in patients with temporal lobe surgery and nonsurgical patients with epilepsy. Patients with LTL surgery may be at risk for a more rapid decline in selective verbal memory skills. Evaluations of treatments for intractable epilepsy that compromise memory functions should consider the further quality of life impact of late age-related memory declines.

Occurrence of seizure clusters and status epilepticus during inpatient video-EEG monitoring.

OBJECTIVE: To investigate the occurrence of status epilepticus and seizure clusters, and the duration until first seizure at epilepsy monitoring units in the United States. METHODS: The authors examined the inpatient video-EEG monitoring reports of 514 consecutive patients admitted to five comprehensive epilepsy centers during the year 2000. Time to first seizure, seizure clustering, and seizure duration were ascertained from reports and entered into a database. RESULTS: In 169 admissions with complex partial seizures (CPSs) or secondarily generalized tonic-clonic (2GTC) seizures, there were 5 (3.0%) patients with status epilepticus, 30 (17.8%) with 4-hour seizure clusters, and 82 (48.5%) with 24-hour seizure clusters. There were no statistically significant differences between centers, except that seizure clusters were observed to be less common at the one center with a formal drug withdrawal protocol. The average time to CPS or 2GTC seizure was 2.1 days; the average number of days to nonepileptic event was 1.2 days (p = 0.001). CONCLUSIONS: Although status epilepticus is uncommon at epilepsy monitoring units, clusters of seizures are common. Intensive monitoring with drug withdrawal must be performed in a highly supervised, hospitalized setting. Inpatient video-EEG monitoring is efficient, with recording of the first epileptic or nonepileptic events in 2 days or less.

Sleep deprivation does not affect seizure frequency during inpatient video-EEG monitoring.

OBJECTIVE: To determine whether acute sleep deprivation facilitates seizures during inpatient monitoring in a controlled protocol. METHODS: Eighty-four patients with medically refractory partial epilepsy undergoing inpatient monitoring were assigned in consecutive blocks to either sleep deprivation every other night or to normal sleep. In both groups, subjects were requested to stay awake during the day, from 6 AM to 10 PM. In the sleep deprivation group, patients also stayed awake between 10 PM and 6 AM every other night beginning with Day 2. Patients were removed from sleep deprivation if they had two or more secondarily generalized seizures within 24 hours. Patients were removed from the normal sleep group and were sleep deprived if they did not have a complex partial or secondarily generalized seizure by Day 6 of monitoring. In these patients removed from sleep deprivation or from normal sleep, data were analyzed up to and including the day of removal from the protocol. RESULTS: The sleep deprivation and normal sleep subjects did not differ in age, sex, seizure localization, or percent dosage reduction in antiepileptic drugs from baseline at days 1 to 3 of monitoring. Protocol duration was 6.5 +/- 2.4 days (mean +/- SD) for the sleep deprivation group and 5.8 +/- 2.0 days for the normal sleep group. Seizures per day for complex partial, secondarily generalized, and combined complex partial and secondarily generalized, calculated from admission until end of protocol, did not differ significantly between the two groups. CONCLUSION: Acute sleep deprivation did not affect seizure frequency during inpatient monitoring in our patients with intractable complex partial seizures with secondary generalization.

Outpatient seizure identification: results of 502 patients using computer-assisted ambulatory EEG.

Patients with epilepsy may not always be able to identify their seizures. Epilepsy management relies on patient reporting to validate whether seizures occur during treatment. The goal of this study was to assess the frequency of unreported seizures recorded during routine outpatient ambulatory EEG recording. The authors reviewed 552 records from 502 patients who underwent outpatient 16-channel computer-assisted ambulatory EEG monitoring (CAA-EEG). Seizure identification was evaluated by assessing push-button activation. Partial seizures were seen most commonly. A total of 47 of 552 records (8.5%) had partial seizures recorded on CAA-EEG, with 29 of 47 (61.7%) with electroclinical seizures identified by push-button activation. Seizures on EEG without push-button activation were analyzed separately and compared with a self-reported written diary to verify lack of recognition. A total of 18 of 47 records (38.3%) had some partial seizures that were unrecognized by the patient, and 11 of 47 records (23.4%) had seizures recognized only by the computer. The authors conclude that patients frequently have seizures outside of the hospital that go unrecognized. Underreporting of seizure frequency occurs in the outpatient setting and impacts optimal diagnosis and treatment for patients with epilepsy.

Seizure semiology and neuroimaging findings in patients with midline spikes.

PURPOSE: Midline epileptiform discharges are rare compared with discharges at other scalp locations. Neuroimaging results and semiologic seizure characteristics of patients with midline spikes are not adequately described. The aim of this study was to describe the neuroimaging findings and detailed seizure semiologies in patients with midline spikes. METHODS: We reviewed the EEG database of the University of Michigan Medical Center and identified 35 patients with midline spikes. Information about seizure types and neuroimaging results was obtained from a review of medical records. The seizures were classified according to the International League Against Epilepsy (ILAE) criteria and semiologic classification. RESULTS: Twenty-nine (83%) patients had a history of seizures. Complex partial seizures and simple partial seizures were the most common seizure types, experienced by 66% of patients. The age at seizure onset was within the first 10 years in 90% of patients. According to the semiologic seizure classification, automotor seizures and tonic seizures were the most common seizure types. Neuroimaging studies were abnormal in 45% of patients. When focal abnormalities were detected, they were lateralized to one of the frontal lobes in all cases. CONCLUSIONS: Our results indicate that in the majority of patients, midline spikes represent focal epileptiform activity rather than fragments of generalized discharges, and are most commonly associated with seizures of partial onset. Automotor seizures and tonic seizures are the most common semiologies. Focal radiologic abnormalities tend to be lateralized to one of the frontal lobes.

A direct brain interface based on event-related potentials.

Cross-correlation between a trigger-averaged event-related potential (ERP) template and continuous electrocorticogram was used to detect movement-related ERP's. The accuracy of ERP detection for the five best subjects (of 17 studied), had hit percentages >90% and false positive percentages <10%. These cases were considered appropriate for operation of a direct brain interface.

Identification of electrocorticogram patterns as the basis for a direct brain interface.

This study reports on the first step in the development of a direct brain interface based on the identification of event-related potentials (ERPs) from an electrocorticogram obtained from the surface of the cortex. Ten epilepsy surgery patients, undergoing monitoring with subdural electrode strips and grid arrays, participated in this study. Electrocorticograms were continuously recorded while subjects performed multiple repetitions for each of several motor actions. ERP templates were identified from action-triggered electrocorticogram averages using an amplitude criterion. At least one ERP template was identified for all 10 subjects and in 56% of all electrode-recording sets resulting from a subject performing an action. These results were obtained with electrodes placed solely for clinical purposes and not for research needs. Eighty-two percent of the identified ERPs began before the trigger, indicating the presence of premovement ERP components. The regions yielding the highest probability of valid ERP identification were the sensorimotor cortex (precentral and postcentral gyri) and anterior frontal lobe, although a number were recorded from other areas as well. The recording locations for multiple ERPs arising from the performance of a specific action were usually found on close-by electrodes. ERPs associated with different actions were occasionally identified from the same recording site but often had noticeably different characteristics. The results of this study support the use of ERPs recorded from the cortical surface as a basis for a direct brain interface.

Detection of event-related potentials for development of a direct brain interface.

The study presented here is part of an ongoing effort to develop a direct brain interface based on detection of event-related potentials (ERPs). In a study presented in a companion article, averaged ERP templates were identified from electrocorticograms recorded during repetition of voluntary motor actions. Here the authors report on the detection of individual motor ERPs within the electrocorticogram using cross-correlation. An averaged ERP template was created from the first half of each electrocorticogram and then cross-correlated with the continuous electrocorticogram from the second half. Points where the cross-correlation value exceeded an experimentally determined detection threshold were considered to be detection points. A detection point was considered to be a valid "hit" if it occurred between 1 second before and 0.25 second after the recorded time of a voluntary action. The difference between the hit and false-positive percentages (HF-difference) was used as a metric of detection accuracy. HF-differences greater than 90 were found for 5 of 15 subjects, HF-differences greater than 75 were found for 8 of 15 subjects, and HF-differences greater than 50 were found for 12 of 15 subjects. The three other subjects with HF-differences less than 50 had electrode locations not well suited for recording movement-related ERPs. Recordings from sensorimotor and supplementary motor areas produced the highest yield of channels with HF-difference greater than 50; however, a number of channels with good performance were found in other areas as well. The results demonstrate the likely prospect of using ERP detection as the basis of a single-switch direct brain interface and that furthermore, there is a good possibility of obtaining multiple control channels using this approach.

Relation of surgical volume to outcome in eight common operations: results from the VA National Surgical Quality Improvement Program.

OBJECTIVE: To examine, in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity. SUMMARY BACKGROUND DATA: In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial. METHODS: The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression, and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA). RESULTS: Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found. CONCLUSIONS: In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care.

Deletion of chromosome 1 predicts prognosis in pancreatic endocrine tumors.

Endocrine tumors, such as parathyroid adenomas and pheochromocytomas, frequently have deletions of chromosome 1, suggesting that inactivation of a tumor suppressor gene from chromosome 1 is important in their tumorigenesis. We hypothesized that deletion of chromosome 1 may contribute to pancreatic endocrine tumor formation. Twenty-nine sporadic and MEN1 pancreatic endocrine tumors were studied for loss of heterozygosity (LOH) with 12 chromosome 1 microsatellite markers. LOH on chromosome 1 was identified in 10 of 29 (34%) tumors studied. Allele loss occurred more frequently in tumors with hepatic metastases (7 of 8) than tumors without metastases (3 of 21) (P = 0.004). Tumors in patients with lymph node involvement and patients with multiple endocrine neoplasia type 1 did not demonstrate LOH for chromosome 1 markers. These data suggest that loss of chromosome 1 is associated specifically with the development of hepatic metastases in patients with sporadic pancreatic endocrine tumors.

Seizures in Klinefelter's syndrome.

This study describes the clinical spectrum of patients with Klinefelter's syndrome and seizures. Klinefelter's syndrome is a sex chromosomal abnormality and the most common cause of male hypogonadism. It is characterized by cognitive dysfunction, hypogonadism, and abnormalities of physical maturation. Neurologic impairment has been recognized, but seizures have received little attention. The authors describe three American patients and discuss nine additional patients from two European centers previously reported with Klinefelter's syndrome and seizures. The most common profile of patients with Klinefelter's syndrome and seizures includes mental retardation, behavior problems, epileptiform electroencephalograms (EEGs), and generalized tonic-clonic seizures. The seizures of six of 11 patients with epilepsy were well controlled with antiepileptic drugs. One patient had a single seizure and was not treated with medication. In patients with Klinefelter's syndrome and recurrent seizures, the electroclinical spectrum is heterogenous and outcome with antiepileptic drug treatment is favorable.

The Department of Veterans Affairs' NSQIP: the first national, validated, outcome-based, risk-adjusted, and peer-controlled program for the measurement and enhancement of the quality of surgical care. National VA Surgical Quality Improvement Program.

OBJECTIVE: To provide reliable risk-adjusted morbidity and mortality rates after major surgery to the 123 Veterans Affairs Medical Centers (VAMCs) performing major surgery, and to use risk-adjusted outcomes in the monitoring and improvement of the quality of surgical care to all veterans. SUMMARY BACKGROUND DATA: Outcome-based comparative measures of the quality of surgical care among surgical services and surgical subspecialties have been elusive. METHODS: This study included prospective assessment of presurgical risk factors, process of care during surgery, and outcomes 30 days after surgery on veterans undergoing major surgery in 123 medical centers; development of multivariable risk-adjustment models; identification of high and low outlier facilities by observed-to-expected outcome ratios; and generation of annual reports of comparative outcomes to all surgical services in the Veterans Health Administration (VHA). RESULTS: The National VA Surgical Quality Improvement Program (NSQIP) data base includes 417,944 major surgical procedures performed between October 1, 1991, and September 30, 1997. In FY97, 11 VAMCs were low outliers for risk-adjusted observed-to-expected mortality ratios; 13 VAMCs were high outliers for risk-adjusted observed-to-expected mortality ratios. Identification of high and low outliers by unadjusted mortality rates would have ascribed an outlier status incorrectly to 25 of 39 hospitals, an error rate of 64%. Since 1994, the 30-day mortality and morbidity rates for major surgery have fallen 9% and 30%, respectively. CONCLUSIONS: Reliable, valid information on patient presurgical risk factors, process of care during surgery, and 30-day morbidity and mortality rates is available for all major surgical procedures in the 123 VAMCs performing surgery in the VHA. With this information, the VHA has established the first prospective outcome-based program for comparative assessment and enhancement of the quality of surgical care among multiple institutions for several surgical subspecialties. Key features to the success of the NSQIP are the support of the surgeons who practice in the VHA, consistent clinical definitions and data collection by dedicated nurses, a uniform nationwide informatics system, and the support of VHA administration and managerial staff.

Mutation of the MENIN gene in sporadic pancreatic endocrine tumors.

Pancreatic endocrine tumors occur both sporadically and as part of the multiple endocrine neoplasia type 1 (MEN1) syndrome. MEN1 is an autosomal dominant disease characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. The MEN1 gene called MENIN maps to chromosome 11q13 and is thought to function as a tumor suppressor gene. We previously demonstrated loss of heterozygosity (LOH) at 11q13 in approximately 40% of sporadic pancreatic endocrine tumors and hypothesize that MENIN is involved in the development of these tumors. Thirty-one sporadic pancreatic endocrine tumors were analyzed for mutation of MENIN by nonradioactive single-stranded conformation polymorphism. Twelve mutations were detected in 31 sporadic pancreatic endocrine tumors (34%). Twelve of these 31 tumors previously demonstrated loss of heterozygosity at 11q13. Of the tumors with LOH, seven contained mutations of the MENIN gene (58%). The majority of the MENIN mutations occurred within exon 2. Two independent mutations in MENIN were detected in a gastrinoma that also revealed LOH, leading to the possibility of another tumor suppressor gene locus at 11q13. Mutations were present in both benign and malignant pancreatic endocrine tumors, suggesting that a MENIN gene mutation is a frequent and early event in the tumorigenesis. The high incidence of truncating mutations in tumors with LOH at 11q13 support the hypothesis that MENIN is a tumor suppressor gene.

Deletion mapping of endocrine tumors localizes a second tumor suppressor gene on chromosome band 11q13.

Multiple endocrine neoplasia type 1 syndrome (MEN1, MIM 131100), an autosomal dominant disease, is characterized by parathyroid hyperplasia, pancreatic endocrine tumors, and pituitary adenomas. These tumors also occur sporadically. Both the familial (MEN1) and the sporadic tumors reveal loss of heterozygosity (LOH) for chromosome band 11q13 sequences. Based on prior linkage and LOH analyses, the MEN1 gene was localized between PYGM and D11S460. Recently, the MEN1 gene (menin) has been cloned from sequences 30-kb distal to PYGM. We performed deletion mapping on 25 endocrine tumors (5 MEN1 and 20 sporadic) by using 21 polymorphic markers on chromosome band 11q13. Of these, two (137C7A, 137C7B) were derived from PYGM-containing BAC (bacterial artificial chromosome-137C7) sequences, one from INT2-containing cosmid sequences and the marker D11S4748, a (CA)20 repeat marker that was developed by us. The LOH analysis shows that the markers close to the MEN1 (menin) gene were not deleted in three of the tumors. These tumors, however, showed LOH for distal markers. Thus, the data suggest the existence of a second tumor suppressor gene on chromosome band 11q13.

Risk adjustment of the postoperative mortality rate for the comparative assessment of the quality of surgical care: results of the National Veterans Affairs Surgical Risk Study.

BACKGROUND: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality rates for surgical services in Veterans Health Administration. STUDY DESIGN: This cohort study was conducted in 44 Veterans Affairs Medical Centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measure was all-cause mortality within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. Risk-adjusted surgical mortality rates were expressed as observed-to-expected ratios and were compared with unadjusted 30-day postoperative mortality rates. RESULTS: Patient risk factors predictive of postoperative mortality included serum albumin level, American Society of Anesthesia class, emergency operation, and 31 additional preoperative variables. Considerable variability in unadjusted mortality rates for all operations was observed across the 44 hospitals (1.2-5.4%). After risk adjustment, observed-to-expected ratios ranged from 0.49 to 1.53. Rank order correlation of the hospitals by unadjusted and risk-adjusted mortality rates for all operations was 0.64. Ninety-three percent of the hospitals changed rank after risk adjustment, 50% by more than 5 and 25% by more than 10. CONCLUSIONS: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of risk-adjusted postoperative mortality rates after major noncardiac operations. Risk adjustment had an appreciable impact on the rank ordering of the hospitals and provided a means for monitoring and potentially improving the quality of surgical care.

Risk adjustment of the postoperative morbidity rate for the comparative assessment of the quality of surgical care: results of the National Veterans Affairs Surgical Risk Study.

BACKGROUND: The National Veterans Affairs Surgical Risk Study was designed to collect reliable, valid data on patient risk and outcomes for major surgery in the Veterans Health Administration and to report comparative risk-adjusted postoperative mortality and morbidity rates for surgical services in the Veterans Health Administration. STUDY DESIGN: This was a cohort study conducted at 44 Veterans Affairs Medical Centers closely affiliated with university medical centers. Included were 87,078 major noncardiac operations performed under general, spinal, or epidural anesthesia between October 1, 1991, and December 31, 1993. The main outcomes measures in this report are 21 postoperative adverse events (morbidities) occurring within 30 days after the index procedure. Multivariable logistic regression risk-adjustment models for all operations and for eight surgical subspecialties were developed. RESULTS: Patient risk factors predictive of postoperative morbidity included serum albumin level, American Society of Anesthesia class, the complexity of the operation, and 17 other preoperative risk variables. Wide variation in the unadjusted rates of one or more postoperative morbidities for all operations was observed across the 44 hospitals (7.4-28.4%). Risk-adjusted observed-to-expected ratios ranged from 0.49 to 1.46. The Spearman rank order correlation between the ranking of the hospitals based on unadjusted morbidity rates and risk-adjusted observed-to-expected ratios for all operations was 0.87. There was little or no correlation between the rank order of the hospitals by risk-adjusted morbidity and risk-adjusted mortality. CONCLUSIONS: The Department of Veterans Affairs has successfully implemented a system for the prospective collection and comparative reporting of postoperative mortality and morbidity rates after major noncardiac operations. Risk adjustment had only a modest effect on the rank order of the hospitals.