Prospective study: Long-term outcome at 12-15 years after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have poor outcome. Studies on outcome beyond 1 year post-aSAH are few, and late recovery is poorly investigated, initiating this prospective outcome study on patients 12-15 years after an aSAH. We hypothesized to find; functional improvement > 1 year post-ictus; increased long-term mortality in aSAH patients vs matched controls, and finally to present; predictors of long-term favorable outcome (GOS 4-5). METHODS: We prospectively investigated patients, admitted 2000-2003 to the Sahlgrenska University Hospital, 1 year post-ictus using Glasgow Outcome Scale (GOS). The patients were revalidated 12-15 years post-aSAH by structured-telephone interviews (GOS), followed by statistical analysis. RESULTS: A total of 158 patients were included, (women n = 114, men n = 44), with a mean age of 55 years at aSAH. Patients treated with surgical clipping had lower mortality. At the follow-up 12-15 years post-aSAH, all 103 survivors (65.2%) were categorized as having; good recovery (39.9%), moderate disability (15.2%), or severe disability (10.1%). Within the patient cohort, 23.6% improved GOS over time. Fifty-five patients died, median at 4 years post-ictus. aSAH patients had 3.5 times increased mortality 12-15 years post-ictus vs matched controls (P < .0001). Patients with favorable outcome at 1 year (67.3%, n = 101) had similar survival probability as control patients. Prognostic indicators of long-term favorable outcome were low age and high GOS at 1-year follow-up, (AUCROC, 0.79). CONCLUSIONS: Individual functional improvement was found >1 year post-ictus. Patients with favorable outcome at 1 year had similar long-term life expectancy as the general population. Indicators of long-term favorable prognosis were low age at ictus and high GOS at 1-year follow-up.

A prospective outcome study observing patients with severe traumatic brain injury over 10-15 years.

BACKGROUND: Severe traumatic brain injury (sTBI) can be divided into primary and secondary injuries. Intensive care protocols focus on preventing secondary injuries. This prospective cohort study was initiated to investigate outcome, including mortality, in patients treated according to the Lund Concept after a sTBI covering 10-15 years post-trauma. METHODS: Patients were included during 2000-2004 when admitted to the neurointensive care unit, Sahlgrenska University Hospital. Inclusion criteria were: Glasgow coma scale score of ≤8, need for artificial ventilation and intracranial monitoring. Glasgow Outcome Scale (GOS) was used to evaluate outcome both at 1-year and 10-15 years post-trauma. RESULTS: Ninety-five patients, (27 female and 68 male), were initially included. Both improvement and deterioration were noted between 1- and 10-15 years post-injury. Mortality rate (34/95) was higher in the studied population vs. a matched Swedish population, (Standard mortality rate (SMR) 9.5; P < 0.0001). When dividing the cohort into Good (GOS 4-5) and Poor (GOS 2-3) outcome at 1-year, only patients with Poor outcome had a higher mortality rate than the matched population (SMR 7.3; P < 0.0001). Further, good outcome (high GOS) at 1-year was associated with high GOS 10-15 years post-trauma (P < 0.0001). Finally, a majority of patients demonstrated symptoms of mental fatigue. CONCLUSION: This indicates that patients with severe traumatic brain injury with Good outcome at 1-year have similar survival probability as a matched Swedish population and that high Glasgow outcome scale at 1-year is related to good long-term outcome. Our results further emphasise the advantage of the Lund concept.

How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.

INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI). SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively. RESULTS: During daytime the patients took fewer steps (p < 0.001) and their total energy expenditure (TEE) was lower (p < 0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery. CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

How should sensory function in the oropharynx be tested? Cold thermal testing: a comparison of the methods of levels and limits.

OBJECTIVE: Several studies indicate an upper airway peripheral neuropathy in obstructive sleep apnea syndrome (OSAS). The sensation of cold, as measured by cold detection thresholds (CDT), in the oropharynx has been shown to be compromised in patients with sleep apnea and, to a lesser extent, habitual snoring. To reveal whether this neuropathy is part of the pathogenetic process of OSAS, longitudinal studies of snorers are needed. The objective of the present study was to establish the test-retest repeatability for the two most commonly used thermal testing methods: the reaction time exclusive method of levels (MLE) and the method of limits (MLI). METHODS: Forty non-snoring subjects were tested at the soft palate and the lip at two separate occasions (mean interval 45days) using a Medoc TSA - 2001 equipment with an intra-oral thermode. RESULTS: With MLE mean CDT's were lower for both the lip and soft palate than with MLI. However, MLI showed a better test-retest repeatability (r=2.2 vs. 2.6) for the soft palate. CONCLUSIONS: MLI should be used in longitudinal studies. The performance of this method is also faster. SIGNIFICANCE: We have established a quick, safe and reliable method suitable for longitudinal studies of peripheral neuropathy in sleep apnea pathogenesis.

Polyneuropathy associated with IgM vs IgG monoclonal gammopathy: comparison between clinical and electrophysiological findings.

OBJECTIVE: The neuropathy associated with IgM monoclonal gammopathy (IgM-MG) is regarded as a sensorimotor, mainly demyelinating neuropathy. It is not fully known whether the neuropathy in IgG-MG is caused by the same mechanisms and shows the same electrophysiological characteristics. We aimed at making a comparison between clinical and neurophysiological findings in these two conditions. PATIENTS AND METHODS: Twenty-seven patients with IgM-associated neuropathy [18 with anti-myelin-associated glycoprotein (anti-MAG) antibodies] were compared with 15 age-matched patients with IgG-associated neuropathy. RESULTS: Patients with IgM-associated neuropathy (especially those with anti-MAG antibodies) had significantly clinically more severe disabilities with involvement of both motor and sensory functions compared with patients with IgG-associated neuropathy in whom clinical sensory disturbances were more prominent than motor dysfunction. Motor and sensory conduction velocities were significantly lower and distal latencies significantly longer in the IgM group than in the IgG group concerning the median, ulnar and peroneal nerves. Fifty-four per cent of the patients in the IgM group did not present a sensory response of the median nerve vs 13% in the IgG group. There was also a significant difference concerning absent responses from the peroneal and sural nerves in the IgM vs IgG group (peroneal: 48% vs 13%, sural: 88% vs 27%). CONCLUSION: Polyneuropathy associated with IgM-MG, especially when associated with anti-MAG antibodies, appears to have more of a demyelinating involvement that meets the criteria for demyelination. This was not as clear in those associated with IgG. The IgG neuropathy showed less and milder deficit in the electrophysiological studies.

Cheyne-Stokes respiration and supine dependency.

The influence of position during sleep on central apnoeas during Cheyne-Stokes respiration has not previously been studied systematically. The current authors aimed to study the effect of body position and sleep stages on central sleep apnoeas during Cheyne-Stokes respiration. A total of 20 consecutive patients with cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration were investigated using nocturnal polysomnography, including a body position sensor mounted on the patient's sternum. The mean central apnoea-hypopnoea index was significantly higher in the supine position than in nonsupine positions (41+/-13 versus 26+/-12). The central apnoea-hypopnoea index was highest in sleep stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In every sleep stage, central apnoeas and hypopnoeas were more prevalent in the supine position compared with nonsupine positions. In conclusion, sleep in the supine body position increases the frequency of apnoeas and hypopnoeas in patients with Cheyne-Stokes respiration.

Polysomnography in chronic neuromuscular disease.

BACKGROUND: Sleep is a risk factor for respiratory failure in patients with chronic neuromuscular diseases (NMD). OBJECTIVE: To explore the diagnostic value of monitoring sleep parameters in addition to nocturnal respiratory parameters. METHODS: Thirty-one patients with chronic NMD underwent whole-night polysomnograms including EMG from accessory respiratory muscles. RESULTS: Sleep macrostructure was normal on average. The number of respiratory arousals per hour of sleep was above the upper limit observed in a control group (>2.1) in 71% of the patients, but was moderate in most cases. Nadir oxygen saturation <85% was the most common finding indicating respiratory dysfunction and was present in 80% of the patients. Noninvasive blood gas monitoring identified all but 2 patients with respiratory-induced sleep abnormalities. The respiratory arousal rate was correlated with the oxygen desaturation index, but otherwise there were no significant correlations between sleep and nocturnal respiratory parameters. Vital capacity was significantly positively correlated with obstructive apnea index and daytime base excess to nadir oxygen saturation. Inspiratory activity in accessory respiratory muscles was present during REM sleep and/or slow wave sleep in 70% of the patients. CONCLUSION: The severity of nocturnal respiratory dysfunction is not reflected in the extent of sleep impairment in patients with chronic neuromuscular diseases.

Inclusion body myositis--sensory dysfunction revealed with quantitative determination of somatosensory thresholds.

In order to evaluate sensory function in inclusion body myositis (IBM), nine patients were subjected to sensibility screening and quantitative determination of somatosensory thresholds. Data were compared with results from electrophysiological examination and muscle biopsy. On sensibility screening all but one of the IBM patients had abnormal findings in hands and/or feet mostly affecting thermal sensibility. Vibratory thresholds were abnormal in five and thermal thresholds in four of the patients. Mean vibratory thresholds were significantly (P < 0.05) higher in the IBM patients when compared with the controls. Significantly increased heat pain thresholds were found in hands and feet when compared with the controls while thermal thresholds were normal. Nerve conduction velocities were decreased in three patients, EMG showed both myopathic and neuropathic abnormalities in six patients. Eight patients had neuropathic abnormalities on muscle biopsy. The sensory dysfunction found suggests an affection of peripheral nerves in IBM mainly affecting large diameter myelinated nerve fibres corroborating earlier findings of a peripheral neuropathy in IBM.

Voice quality after radiofrequency volumetric tissue reduction of the soft palate in habitual snorers.

OBJECTIVE: To evaluate whether radiofrequency volumetric tissue reduction of the soft palate is causing voice changes as a result of velopharyngeal insufficiency in patients with heavy snoring. STUDY DESIGN: A prospective study of 16 habitual snorers (oxygen desaturation index, <6 in all cases) were investigated concerning nasopharyngeal competence before and, at minimum, 2 months after the procedure (mean period, 165 d). Speech evaluation was made objectively with a nasal-oral ratio meter and also was made subjectively by a trained speech-language pathologist. The patients received a mean of three Somnoplasty radiofrequency volumetric tissue reduction treatments of 1200 J each (600 J in the midline and 300 J on each side of the soft palate). RESULT: Comparison between preoperative and postoperative nasal-oral ratio meter analysis of hypernasality revealed no significant change. Neither did listener judgment of hypernasality, nasal escape, or pharyngeal snort reveal any influence on velopharyngeal function by the surgical procedures. Snoring was somewhat successfully treated, as evaluated by spouses; snoring score was reduced from 8.2 +/- 2.9 to 4.1 +/- 2.5 (P <.01) on a 10-grade rating scale. Maximum nocturnal decibel levels were also reduced in 79% of the cases. CONCLUSION: Radiofrequency volumetric tissue reduction in the soft palate as a treatment for snoring did not show any significant adverse effect on nasopharyngeal function.

The accuracy of subjective sleep time in sleep apnoea recordings.

Total sleep time is important in investigations of obstructive sleep apnoea, since the diagnosis is usually based on the average number of apnoeas per hour of sleep. Sleep estimates instead of exact EEG-recorded total sleep time is often used in the clinical setting. However, an overestimated sleep time would underestimate the degree of the disease and vice versa. The purpose of this study was to investigate the accuracy of subjective sleep time and time-in-bed as sleep estimates. One hundred patients undergoing diagnostic polysomnography for suspected obstructive sleep apnoea were asked to estimate their sleep time in a questionnaire. Seventy-five patients were diagnosed as suffering from obstructive sleep apnoea syndrome. The mean difference between self-scored and EEG-recorded total sleep time was 4 +/- 74 min. However, 30% scored with a difference greater than 1 h. The intra-class correlation coefficient was fair (0.58, CI: 0.43-0.70). Fifty-three patients overestimated their sleep time and 47 patients underestimated it. All but four patients underestimated their number of awakenings (P<0.001). The mean difference between time-in-bed and EEG-recorded total sleep time was 110 +/- 63 min. This difference was significantly larger than the difference between subjective sleep time and EEG-recorded total sleep time (P<0.001). The intra-class correlation coefficient was poor (0.38, CI: 0.20-0.54). Mean AHI was 27 +/- 27 using subjective sleep time and did not change significantly compared with the mean AHI of 25 +/- 21 based on EEG-recorded total sleep time. Mean AHI decreased significantly to 20 +/- 17 (P<0.001) when time-in-bed was used. In conclusion, 'time-in-bed' time is a poor predictor of total sleep time and should not be used when calculating the apnoea-hypopnoea index. Subjective sleep time is better as an approximation, but the individual differences are large.

Snoring, pregnancy-induced hypertension, and growth retardation of the fetus.

STUDY OBJECTIVE: Our purpose was to study the relationship between snoring and pregnancy-induced hypertension and growth retardation of the fetus. DESIGN: Retrospective, cross-sectional, consecutive case series. SETTING: The Department of Gynecology and Obstetrics, University Hospital, Umeâ, Sweden. PARTICIPANTS AND MEASUREMENTS: On the day of delivery, 502 women with singleton pregnancies completed a questionnaire about snoring, witnessed sleep apneas, and daytime fatigue. Data concerning medical complications were taken from the women's casebooks. RESULTS: During the last week of pregnancy, 23% of the women reported snoring every night. Only 4% reported snoring before becoming pregnant. Hypertension developed in 14% of snoring women, compared with 6% of nonsnorers (p < 0.01). Preeclampsia occurred in 10% of snorers, compared with 4% of nonsnorers (p < 0.05). An Apgar score < or = 7 was more common in infants born to habitual snorers. Growth retardation of the fetus, defined as small for gestational age at birth, had occurred in 7.1% of the infants of snoring mothers and 2.6% of the remaining infants (p < 0.05). Habitual snoring was independently predictive of hypertension (odds ratio [OR], 2.03; p < 0.05) and growth retardation (OR, 3.45; p < 0.01) in a logistic regression analysis controlling for weight, age, and smoking. CONCLUSIONS: Snoring is common in pregnancy and is a sign of pregnancy-induced hypertension. Snoring indicates a risk of growth retardation of the fetus.

Diabetic neuropathy in elderly Type 2 diabetic patients: effects of insulin treatment.

OBJECTIVES: To study the occurrence of diabetic neuropathy and the effect of insulin treatment in elderly Type 2 diabetic patients. MATERIAL AND METHODS: In 38 patients and 20 controls symptoms and neurophysiological examinations including electroneurography, vibration perception and temperature discrimination thresholds were investigated. Patients were randomized to insulin (n = 18) or sulfonylurea (n = 16) treatment and were re-investigated after 1 year. RESULTS: Neuropathy was present in 21/38 patients (56%). It was asymptomatic in 17/38 (45%) and symptomatic in 4/38 (11%). The occurrence of neuropathy was less common in healthy controls, 3/20 (15%) (P < 0.01). Temperature discrimination thresholds was the test that most often revealed pathology. The metabolic control after 1 year was significantly improved in the insulin treated group and unchanged in the sulfonylurea treated group. There were no changes as regards occurrence of neuropathy between or within the two treatment groups after 1 year. CONCLUSION: Diabetic neuropathy is common among elderly Type 2 diabetic patients. It is mostly asymptomatic. Improvement was not seen after 1 year of insulin treatment.

Children with nocturnal upper airway obstruction: postoperative orthodontic and respiratory improvement.

UNLABELLED: Twenty children, aged 4-9 years, underwent adeno/tonsillectomy because of unequivocal anamnestic nocturnal obstructive breathing. Preoperatively, apnea-hypopnea index was > 5 in 10 cases only, AI > 1 in 17. Nineteen children had signs of increased respiratory labour in movement recordings and inspiratory EMG-activity. Oxygen desaturation index was 0 in 7 children, and nadir SaO2 was > or = 90% in 10. Cephalometry and dentition study models initially revealed significant changes, chiefly lateral cross-bite (n = 11) and vertical growth direction of the mandible. Tonsillar size or duration of disease was not correlated with the severity of polysomnographic findings, nor were orthodontic variables. Symptoms disappeared promptly postoperatively. After one year, respiratory recordings were normalized or improved in the majority of children, and orthodontic variables normalized or improved in all children. CONCLUSION: Oximetry and airflow recordings may be normal in children who benefit from treatment of anamnestic nocturnal obstruction. Craniofacial deformities are common and improve significantly with surgical treatment of the airway obstruction.

Segregation of HLA genes in multicase narcolepsy families.

In the past 15 years, 411 sporadic narcolepsy patients have been diagnosed in the Hephata Klinik, Schwalmstadt, Germany. They were explored for presence or absence of excessive daytime sleepiness and narcolepsy in their relatives. A subset of 39 patients were explored for presence or absence of parasomnias. Six patients had more than one relative affected by narcolepsy-cataplexy. Forty-seven family members were investigated with the Stanford Center for Narcolepsy Sleep Inventory and a standardized parasomnia questionnaire. Twenty-four relatives had nocturnal polysomnographies and Multiple Sleep Latency Tests. HLA class I typing was performed in all sporadic and familial cases, class II and microsatellite typing was performed in all members of multicase families. Based on the Finnish prevalence study by Hublin et al., 1994, the relative risk for first degree relatives to develop narcolepsy-cataplexy was in our sample 16.5, 34.2 for excessive daytime sleepiness and 426.9 for parasomnias. Cataplexy, excessive daytime sleepiness and single narcoleptic symptoms in the multicase families segregate with the DRBI*1501, CARII:200, CARI: 103, DQBI*0602 haplotype. In two families, members with narcolepsy and isolated symptoms have inherited the DRBI*1501/DQBI*0602 haplotype from the nonaffected parent. The observed segregations in these two families may support the view that narcoleptic symptoms are expressed by DRBI*1501/DQBI*0602 carriers, independent of haplotype origin. Parasomnias do not segregate with a specific haplotype. The frequency of parasomnias in narcolepsy is much higher than in the general population. The empirical risk for first degree family members of narcolepsy patients to develop cataplexy seems to be low, whereas it is higher for EDS and highest for parasomnias.

Oxygen desaturations during exercise and sleep in fit tetraplegic patients.

OBJECTIVE: Tetraplegic patients are particularly at risk for respiratory deficiencies during sleep. In a previous study, it was found that several patients exhibited significant oxygen desaturations during arm ergometry tests. Therefore, the issue of whether patients who desaturate during exercise would be especially at risk for having nocturnal respiratory problems was raised. DESIGN: Respiratory recordings in connection with arm ergometry tests and during sleep. SETTING: Arm ergometry tests were performed in a hospital laboratory, and sleep recordings were performed in the patients' homes. PATIENTS: Nine C5-C6 tetraplegic patients, aged 22 to 42 years with body mass index of 15.2 to 24.2 kg/m2. MAIN OUTCOME MEASURES: Oximetry during exercise and sleep and sleep recordings. RESULTS: During exercise, six patients desaturated 6% to 20%. Only one patient had signs of a significant nocturnal respiratory problem with an average of eight desaturations per hour of sleep and an obstructive respiration movement pattern. Two additional patients (with normal oximetry during exercise) showed occasional desaturation below 89% during rapid eye movement sleep. CONCLUSION: In this study, the majority of tetraplegic patients desaturated during submaximal arm exercise but not during sleep. The reason could be that the patients in this study were all lean and physically active, which is at variance with previously published sleep studies.

Histological indications of a progressive snorers disease in an upper airway muscle.

The etiology of upper airway collapsibility in patients with snoring and obstructive sleep apnea (OSA) remains unclear. Local muscular abnormalities, including neurogenic lesions, could be a contributory factor. The aim of this study was to histologically evaluate the hypothesis of a progressive snorers disease. Biopsies of palatopharyngeal muscle were obtained from 21 patients with habitual snoring and different degrees of upper airway obstruction (10 patients with OSA) and 10 nonsnoring control subjects. Morphological abnormalities, including neurogenic signs (e.g., type grouping), were blindly quantified. The degree of abnormality was significantly increased in patients compared with control subjects. The individual score of abnormalities was significantly correlated to the percentage periodic obstructive breathing but not to oxygen desaturation index. Analyses of the individual fiber-size spectra demonstrated a significantly increased number of hypertrophied and/or atrophied fibers in patients compared with controls. The subjects were also divided into three groups according to their type of nocturnal breathing, i.e., nonsnorers, patients with < 20%, and patients with > or = 45% obstructive breathing. These groups correlated significantly with the degree of abnormality and pathological fiber-size spectra. In conclusion, these results support the hypothesis of a progressive local neurogenic lesion, caused by the trauma of snoring, as a possible contributory factor to upper airway collapsibility.

Melatonin secretion and excretion in patients with obstructive sleep apnea syndrome.

Melatonin (MT) secretion and excretion were investigated in patients with obstructive sleep apnea syndrome (OSAS). Nine men, mean age 55.1 years, mean body mass index 31.2, with a previously confirmed diagnosis of moderate to severe OSAS, were tested on two occasions: immediately before initiation of continuous positive airway pressure (CPAP) treatment and again after at least 4 weeks of continuous nocturnal use of CPAP. Serum MT concentrations were determined every second hour between 2000 and 0800 hours. Urine was collected between 2200 and 0700 hours for determination of urinary MT excretion. Sleep apnea recordings included ear oximetry, respiration and body movements, body position, and breathing sounds. Nine healthy male controls were tested on one occasion. We found that the MT secretion, as reflected by the area under the curve (AUC), among the OSAS patients did not differ from that found in healthy controls (MT AUC 1.68 vs. 1.92 nmol/l x h). Sleep apnea recordings were normalized during CPAP treatment. Moreover, the excessive daytime sleepiness disappeared in all patients. Neither MT secretion (MT AUC 1.68 vs. 1.56 nmol/l x h) nor urinary excretion of MT (0.122 vs. 0.108 nmol/9 h) changed significantly as a result of the CPAP treatment.

EEG frequency changes during sleep apneas.

To study the effect of transient, apnea-induced hypoxemia on electrocortical activity, five patients with severe obstructive sleep apnea syndrome (OSAS) were investigated during nocturnal sleep. Polysomnographic and simultaneous digitized electro encephalographic (EEG) recordings for topographic and compressed spectral array analysis were made. The EEG recordings were timed exactly to respiratory events. During nonrapid eye movement (NREM) apnea, delta band amplitude increased, starting on average 13 seconds after the apnea onset. Average differences were 268% between initial and maximal values and 202% between initial and final values. In contrast, significant increases in delta amplitudes between the onset and end of REM apneas did not occur, although some caused deep oxygen desaturations. Changes in delta activity were not correlated to NREM apnea duration or degree of desaturation. These results indicate that the increased delta activity during NREM apneas may not be caused by arterial hypoxemia. It could instead be due to either an arousal mechanism, since arousals may be preceded by slow waves in EEG, or to a breakthrough of slow-wave-sleep activity. The sleep disturbance in severe OSAS may create such a propensity for slow-wave sleep that stages pass much more rapidly than in normal persons.

Cortical benzodiazepine receptor changes are related to frequency of partial seizures: a positron emission tomography study.

Measurements of benzodiazepine (BZD) receptor density with positron emission tomography (PET) are a promising method of identifying and localizing epileptogenic regions. We investigated whether the pattern of BZD receptor changes depends on seizure frequency, studying 19 patients with matching seizure semiology but different rates of seizure occurrence, using [11C]flumazenil as the ligand. All patients had partial epilepsy and normal magnetic resonance imaging (MRI) of the brain. The visually determined PET focus, characterized by reduced BZD receptor density, corresponded to the epileptogenic focus/seizure onset region in all patients. The degree of BZD receptor reduction showed a positive correlation with seizure frequency. Patients with daily seizures differed from those with fewer seizures in two aspects: (a) the degree and extent of BZD receptor reduction was more pronounced, and (b) BZD receptors were also reduced in the primary projection areas of the focus. Flumazenil-PET reliably identifies epileptogenic brain regions in patients with partial seizures. In addition, flumazenil-PET can distinguish patients with frequent seizures. The method therefore is not only suitable for noninvasive localization of the seizure focus, but also may provide a biochemical marker of epileptogenicity.