Extending sleep to confirm insufficient sleep syndrome is challenging.

Insufficient sleep syndrome (ISS) is prevalent, but poorly studied. This descriptive study was performed to determine its diagnostic challenges and clinical characteristics in a large (n = 3,461) retrospective sample from a single sleep laboratory. Based on actigraphy, polysomnography and multiple sleep latency tests, we diagnosed "suspected insufficient sleep syndrome" in patients with chronic sleepiness, short time in bed, longer sleep duration during weekends or vacation, and without evidence of other causes of sleepiness. For the diagnosis of "definite insufficient sleep syndrome", we additionally required objectively confirmed resolution of sleepiness with actigraphy-documented extension of time in bed. We diagnosed "suspected insufficient sleep syndrome" in 300 subjects. In 94 subjects, extension of sleep time with consecutive relief of sleepiness was attempted, but only 37 subjects succeeded, often despite being offered several attempts. "Definite insufficient sleep syndrome" was confirmed in 36 patients. In these subjects, mean time in bed after sleep extension was above 8 hr per night and 84 min longer than at baseline. Narcolepsy-like findings were frequently observed before sleep extension, but no sleep onset rapid eye movement sleep on polysomnography. This study indicates that fulfilling the diagnostic criteria of ISS is challenging in clinical practice. It further corroborates the importance of actigraphy and polysomnography for correct diagnosis.

Slow-wave sleep and motor progression in Parkinson disease.

Growing evidence from Alzheimer disease supports a potentially beneficial role of slow-wave sleep in neurodegeneration. However, the importance of slow-wave sleep in Parkinson disease is unknown. In 129 patients with Parkinson disease, we retrospectively tested whether sleep slow waves, objectively quantified with polysomnography, relate to longitudinal changes in Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power of sleep slow waves was associated with slower motor progression, particularly of axial motor symptoms, over a mean time of 4.6 ± 2.3 years. This preliminary finding suggests that deeper sleep relates to slower motor progression in Parkinson disease. Ann Neurol 2019;85:765-770.

Exploring the impact of experimental sleep restriction and sleep deprivation on subjectively perceived sleep parameters.

We aimed to investigate the effect of increased sleep pressure and shortened sleep duration on subjective sleep perception in relation to electroencephalographic sleep measures. We analyzed the data from a study in which 14 healthy male volunteers had completed a baseline assessment with 8 hr time in bed, a sleep deprivation (40 hr of wakefulness) and a sleep restriction protocol with 5 hr time in bed during 7 nights. In this work, we assessed perception index, derived through dividing the subjectively perceived total sleep time, wake after sleep onset and sleep latency duration by the objectively measured one at each condition. We found that total sleep time was subjectively underestimated at baseline and shifted towards overestimation during sleep restriction and after deprivation. This change in accuracy of subjective estimates was not associated with any changes in sleep architecture or sleep depth. Wake after sleep onset was significantly underestimated only during sleep restriction. Sleep latency was always overestimated subjectively without any significant change in this misperception across conditions. When comparing accuracy of subjective and actimetry estimates, subjective estimates regarding total sleep time and wake after sleep onset deviated less from electroencephalography derived measures during sleep restriction and after deprivation. We conclude that self-assessments and actimetry data of patients with chronic sleep restriction should be interpreted cautiously. The subjectively decreased perception of wake after sleep onset could lead to overestimated sleep efficiency in such individuals, whereas the underestimation of sleep time and overestimation of wake after sleep onset by actimetry could lead to further underestimated sleep duration.

Insufficient sleep: Enhanced risk-seeking relates to low local sleep intensity.

OBJECTIVES: Chronic sleep restriction is highly prevalent in modern society and is, in its clinical form, insufficient sleep syndrome, one of the most prevalent diagnoses in clinical sleep laboratories, with substantial negative impact on health and community burden. It reflects every-day sleep loss better than acute sleep deprivation, but its effects and particularly the underlying mechanisms remain largely unknown for a variety of critical cognitive domains, as, for example, risky decision making. METHODS: We assessed financial risk-taking behavior after 7 consecutive nights of sleep restriction and after 1 night of acute sleep deprivation compared to a regular sleep condition in a within-subject design. We further investigated potential underlying mechanisms of sleep-loss-induced changes in behavior by high-density electroencephalography recordings during restricted sleep. RESULTS: We show that chronic sleep restriction increases risk-seeking, whereas this was not observed after acute sleep deprivation. This increase was subjectively not noticed and was related to locally lower values of slow-wave energy during preceding sleep, an electrophysiological marker of sleep intensity and restoration, in electrodes over the right prefrontal cortex. INTERPRETATION: This study provides, for the first time, evidence that insufficient sleep restoration over circumscribed cortical areas leads to aberrant behavior. In chronically sleep restricted subjects, low slow-wave sleep intensity over the right prefrontal cortex-which has been shown to be linked to risk behavior-may lead to increased and subjectively unnoticed risk-seeking. Ann Neurol 2017;82:409-418.

Diagnostic delay in narcolepsy type 1: combining the patients' and the doctors' perspectives.

Narcolepsy type 1 is a neurological disorder characterized by a unique syndrome, including the pathognomonic symptom of cataplexy. The diagnosis can be confirmed by objective measures, such as typical findings in the multiple sleep latency test, reduced or undetectable levels of orexin (hypocretin) in the cerebrospinal fluid, and linkage to a specific HLA haplotype. Nevertheless, the mean time that elapses from symptom onset to the correct diagnosis ranges between 10 and 20 years, and the causes and correlates of this delay are poorly understood. Diagnostic delay was assessed on 52 well-defined patients with narcolepsy type 1, evaluating clinical, electrophysiological and neurochemical parameters and the results of a 41-item questionnaire developed to obtain the patients' perspective on various aspects of the diagnostic process. The mean time gap between disease onset and first medical consultation was 3.2 ± 5.1 years; the mean diagnostic delay was 8.9 ± 11.0 years. Prior to correct diagnosis, patients received a wide variety of misdiagnoses. The self-ratings of the patients revealed that the undiagnosed symptoms caused high levels of anxiety and unjustified criticism by family, friends and employers. Multiple regression analysis identified higher cerebrospinal fluid orexin levels (ß = 0.311, P = 0.01), and a longer interval between the onset of excessive daytime sleepiness and cataplexy (ß = 0.368, P = 0.002) as independent associates of longer diagnostic delay. The diagnostic delay decreased over the last decades (ß = -0.672, P < 0.001). In conclusion, delayed diagnosis of narcolepsy type 1 is very common, associated with many adverse consequences, and requires educational efforts to improve awareness on narcolepsy among healthcare providers and the general population.

Topographic sleep EEG changes in the acute and chronic stage of hemispheric stroke.

After stroke, the injured brain undergoes extensive reorganization and reconnection. Sleep may play a role in synaptic plasticity underlying stroke recovery. To test this hypothesis, we investigated topographic sleep electroencephalographic characteristics, as a measure of brain reorganization, in the acute and chronic stages after hemispheric stroke. We studied eight patients with unilateral stroke in the supply territory of the middle cerebral artery and eight matched controls. All subjects underwent a detailed clinical examination including assessment of stroke severity, sleep habits and disturbances, anxiety and depression, and high-density electroencephalogram examination with 128 electrodes during sleep. The recordings were performed within 10 days after stroke in all patients, and in six patients also 3 months later. During sleep, we found higher slow-wave and theta activity over the affected hemisphere in the infarct area in the acute and chronic stage of stroke. Slow-wave, theta activity and spindle frequency range power over the affected hemisphere were lower in comparison to the non-affected side in a peri-infarct area in the patients' group, which persisted over time. Conversely, in wakefulness, only an increase of delta, theta activity and a slowing of alpha activity over the infarct area were found. Sleep slow-wave activity correlated with stroke severity and outcome. Stroke might have differential effects on the generation of delta activity in wakefulness and sleep slow waves (1-8 Hz). Sleep electroencephalogram changes over both the affected and non-affected hemispheres reflect the acute dysfunction caused by stroke and the plastic changes underlying its recovery. Moreover, these changes correlate with stroke severity and outcome.

Time perception in narcolepsy in comparison to patients with Parkinson's disease and healthy controls - an exploratory study.

The striatum and the prefrontal cortex play an important role in cognitive time processing, and time perception depends on sustained attention. Narcolepsy patients are unable to maintain sustained attention, due probably to deficient hypocretin signalling. Impaired time perception has been found in Parkinson's disease (PD) and attributed to a dysfunctional dopaminergic striatal pacemaker. We aimed to assess time perception in patients with narcolepsy and PD and to compare the outcome to healthy control participants. Seventeen narcolepsy patients, 12 PD patients and 15 healthy controls performed a short time production task, where they had to produce an interval of 1, 2 or 5 s. The accuracy of time production differed significantly according to task target duration, and there was a trend towards a group difference with narcolepsy patients tending to overproduce all target durations. Absolute variability was significantly different between groups, with narcolepsy patients showing higher absolute variability in comparison to controls and PD patients. The analysis of the temporal course of time estimation showed more pronounced overproduction of each target duration at the end of each trial in narcolepsy patients, whereas performance was more or less stable in controls and PD patients. Overproduction and higher variability of all time durations in narcolepsy indicate impaired short interval timing in the seconds range, while the scalar property of timing was preserved. The time-course of accuracy and variability of time production within sessions indicate an attention-related mechanism of impaired interval timing.

Actigraphic assessment of periodic leg movements in patients with restless legs syndrome.

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non-responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs-like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age-matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work-up. We examined 12 responders to dopaminergic treatment and 12 non-responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non-responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post-hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non-responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non-responders. PLMI day-to-day variability did not differ between responders and non-responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine-responsive restless legs syndrome.

Sleep-disordered breathing and periodic limb movements in narcolepsy with cataplexy: a systematic analysis of 35 consecutive patients.

BACKGROUND: Disturbed sleep is a core feature of narcolepsy with cataplexy (NC). Few studies have independently assessed sleep-disordered breathing (SDB) and periodic limb movements (PLMs) in non-homogeneous series of patients with and without cataplexy. We systematically assessed both SDB and PLMs in well-defined NC patients. METHODS: We analyzed the clinical and polysomnographic features of 35 consecutive NC patients (mean age 40 ± 16 years, 51% males, 23/23 hypocretin-deficient) to assess the prevalence of SDB (apnea-hypopnea index >5) and PLMs (periodic leg movements in sleep (PLMI) >15) together with their impact on nocturnal sleep and daytime sleepiness using the multiple sleep latency test. RESULTS: 11 (31%) and 14 (40%) patients had SDB and PLMs, respectively. SDB was associated with older age (49 ± 16 vs. 35 ± 13 years, p = 0.02), higher BMI (30 ± 5 vs. 27 ± 6, p = 0.05), and a trend towards higher PLMI (25 ± 20 vs. 12 ± 23, p = 0.052), whereas PLMs with older age (50 ± 16 vs. 33 ± 11 years, p = 0.002) and reduced and fragmented sleep (e.g. sleep efficiency of 82 ± 12% vs. 91 ± 6%, p = 0.015; sleep time of 353 ± 66 vs. 395 ± 28, p = 0.010). SDB and PLMs were also mutually associated (p = 0.007), but not correlated to daytime sleepiness. CONCLUSIONS: SDB and PLMs are highly prevalent and associated in NC. Nevertheless, SDB and PLMs are rarely severe, suggesting an overall limited effect on clinical manifestations.

Sleepiness at the time of testing impairs olfactory performance.

BACKGROUND: We aimed to investigate the differential roles of hypocretin versus dopamine dysfunction versus excessive daytime sleepiness (EDS) in the development of hyposmia. Olfaction in patients with Parkinson disease, restless leg syndrome, narcolepsy with cataplexy, EDS, and healthy controls was compared. METHODS: Sixty-six subjects participated in the study: 14 with PD, 13 with NC, 12 with RLS, 8 with EDS, and 20 healthy controls. Olfaction was tested using standardized Sniffin'Sticks test. Sleepiness was assessed using Karolinska, Stanford and Epworth sleepiness scales. RESULTS: Olfactory discrimination correlated negatively with subjective momentary sleepiness. A significant deficit in olfaction was found in PD patients with respect to all other groups in all olfactory domains. No significant differences were found between the other groups. CONCLUSION: We could not confirm decreased olfaction in patients with NC. Yet the significant correlation between momentary sleepiness and olfactory function suggests that sleepiness is a potential confounding factor in the assessment of olfaction, e.g. in NC. Furthermore, our results confirm that olfaction is impaired in PD, whereas it is normal in RLS.

Sleepwalking, REM sleep behaviour disorder and overlap parasomnia in patients with Parkinson's disease.

BACKGROUND/AIMS: In a questionnaire survey, we identified 36 (9%) of 417 Parkinson's disease (PD) patients with sleepwalking (SW); 72% of them also had a history of REM sleep behaviour disorder (RBD). We aimed to assess the clinical and polysomnographic characteristics of SW in PD and to compare them to patients with PD with and without a history of RBD. METHODS: We performed video-polysomnography and detailed clinical examination in 30 PD patients from the above-mentioned survey: 10 patients with a history of SW, 10 patients with a history of RBD, and 10 patients with no history of either SW or RBD. RESULTS: PD patients with SW had higher depression, anxiety and Hoehn & Yahr scores and lower activities of daily living scores than patients without a history of RBD but did not differ from patients with RBD. Patients with SW and RBD also had more often dyskinesia and hallucinations. By polysomnography, RBD was observed in 8 patients with SW and in all patients with a history of RBD. A total of 5 patients without a history of either SW or RBD had REM sleep without atonia without behavioural peculiarities. CONCLUSION: SW in PD is associated with depression, higher disease severity and functional disability. The simultaneous occurrence of SW and RBD (overlap parasomnia) in most patients suggests a common underlying disturbance of motor control during sleep in PD, with variable manifestations in different sleep stages.

How reliable is a simplified MSLT nap termination protocol?

OBJECTIVE: According to current practical guidelines, naps of the Mean Sleep Latency Test (MSLT) must be terminated 15 min after sleep onset, which requires ad hoc scoring. For clinical convenience, some sleep clinics use a simplified protocol with fixed nap lengths of 20min. Its diagnostic accuracy remains unknown. METHODS: A subset of MSLT naps of 56 narcolepsy type 1 (NT1), 98 Parkinson's disease (PD), 117 sleep disordered breathing (SDB), 22 insufficient sleep syndrome (ISS) patients, and 24 patients with idiopathic hypersomnia (IH), originally performed according to the simplified protocol, were retrospectively adjusted to standard protocol (nap termination 15min after sleep onset or after 20min when no sleep occurs). This was feasible in 60% of MSLT naps; in this subset, we compared sensitivity and specificity of both MSLT protocols for identification of patients with and without NT1. RESULTS: Sensitivity of classical MSLT criteria for NT1, i.e. mean sleep latency ≤8.0min and ≥2 sleep onset rapid eye movement periods (SOREMPs), did not differ between protocols (95%). Specificity, however, was slightly lower (88.1% vs. 89.7%) in the simplified nap termination protocol, with 3 SDB patients and 1 ISS patient having false-positive MSLT findings in the simplified but not in the standard protocol. CONCLUSIONS: The use of a simplified MSLT protocol with fixed nap duration had no impact on MSLT sensitivity for NT1, but the longer sleep periods in the simplified protocol increased the likelihood of REM sleep occurrence particularly in non-NT1 conditions, resulting in a slightly lower MSLT specificity compared to the standard protocol.

Cortical morphometry in narcolepsy with cataplexy.

The sleep-wake disorder narcolepsy with cataplexy is associated with the loss of hypocretin-(orexin-) producing neurons in the lateral hypothalamus. Several studies have reported abnormal cerebral activation in patients with narcolepsy with cataplexy. It remains unclear, however, whether these functional changes are related to structural alterations, particularly at the cortical level. To quantify structural brain changes associated with narcolepsy with cataplexy, we used high-resolution T1-weighted magnetic resonance imaging (MRI) in 12 patients compared with 12 healthy participants matched for age and gender. Subcortical and regional cortical volumes were measured using a method unbiased by non-linear registration. Further whole-brain analyses were conducted, measuring cortical characteristics, such as cortical thickness and gyrification, at thousands of points across each hemisphere using validated algorithms. Statistical analyses accounted for an effect of age and gender. We observed decreased cortical volume in the left paracentral lobule and increased cortical volume in the left caudal part of the middle frontal gyrus in narcoleptic patients compared with controls. Cortical thickness in prefrontal areas was inversely correlated with the severity of narcolepsy. Further, we observed several clusters of cortical thinning in patients with childhood or adolescent onset of narcolepsy compared with patients with adult onset of the disease. Our results suggest that specific anatomical changes may differentiate subgroups of narcolepsy patients with different clinical profiles (such as varying symptom severity or different age at onset). Future studies with larger groups of sleepy patients are required to assess whether distinct patterns of anatomical changes may distinguish narcolepsy from non-hypocretin-deficient hypersomnia disorders.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.

Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

OBJECTIVE: Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. METHODS: We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. RESULTS AND INTERPRETATION: Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

Reduced amygdala activity during aversive conditioning in human narcolepsy.

Narcolepsy with cataplexy is a sleep-wake disorder caused by a loss of hypothalamic hypocretins. Here we assessed the time course of amygdala activation during aversive conditioning in unmedicated patients with narcolepsy. Unlike healthy matched control subjects, narcolepsy patients had no enhancement of amygdala response to conditioned stimuli and no increase in functional coupling between the amygdala and medial prefrontal cortex. These findings suggest that human narcolepsy is accompanied by abnormal emotional learning, and that, in line with animal data, the hypocretin system and the amygdala are involved in this process.

REM sleep behavior disorder is not linked to postural instability and gait dysfunction in Parkinson.

To evaluate a potential association of REM-sleep behavior disorder (RBD) with gait and postural impairment in Parkinson's disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty-six patients with mild-to-moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age-matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits.

REM sleep behavior in Parkinson disease: Frequent, particularly with higher age.

This retrospective single-center polysomnography-based study was designed to assess the frequency of REM sleep behavior disorder (RBD) in consecutive patients with Parkinsonism, including Parkinson disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration. We observed RBD in 77% of 540 Parkinson patients, with rising frequency at higher age and regardless of sex, in >89% of 89 patients with dementia with Lewy bodies or multiple system atrophy, and in <15% of 42 patients with progressive supranuclear palsy or corticobasal degeneration. Thus, the prevalence of RBD in sporadic Parkinson disease might be higher than previously assumed, particularly in elderly patients.

Risk factors for the development of epilepsy in patients with brain metastases.

BACKGROUND: Current guidelines do not recommend primary prophylactic anti-epileptic drug (AED) therapy for patients with brain metastases (BM). Yet, subgroups of patients at high seizure risk might still benefit from prophylaxis. METHODS: We identified 799 patients diagnosed with BM by retrospective screening of our electronic chart system. Candidate risk factors for the development of epilepsy were tested by univariate and multivariate Cox regression models. RESULTS: Epilepsy was diagnosed in 226 of 799 patients (28%). Risk factors for epilepsy in non-operated patients were single BM (P = 0.002, hazard ratio [HR] 3.2, 95% CI: 1.5-6.6) and detection of tumoral hemorrhage (P = 0.008, HR 2.5, 95% CI: 1.3-4.9). Preoperative seizures occurred predominantly in patients with supratentorial BM (P = 0.003, HR 20.78, 95% CI: 2.8-153.4) and lung cancer (P = 0.022; HR 2.0, 95% CI: 1.1-3.6). Postoperative seizures were associated with supratentorial localization (P = 0.017, HR 5.8, 95% CI: 1.4-24.3), incomplete resection (P = 0.005, HR 4.6, 95% CI: 1.6-13.1), and by trend for multiple brain surgeries (P = 0.095, HR 1.9, 95% CI: 0.9-4.0). These risk factors were integrated into a predictive score model for postoperative epilepsy (score sum 0-8). A gradual increase of seizure rates along with higher sum score was confirmed post hoc (score 0 = no seizures; score 8 = 48% seizures). Receiver operating characteristic analysis supported diagnostic accuracy (P = 0.00001, area under the curve = 0.75). CONCLUSIONS: Here we have defined risk profiles for the development of BM-related epilepsy and derived a score which might help to estimate the risk of postoperative seizures and identify individuals at risk who might benefit from primary prophylactic AED therapy.

Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy.

STUDY OBJECTIVES: Proton resonance spectroscopy (1H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (ml), a glial marker and second messenger involved in the regulation of intracellular calcium. One 1H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, "regions of interest," thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae. DESIGN: We performed 1H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios. SETTING: The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich. PARTICIPANTS: 1H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning. MEASUREMENTS AND RESULTS: No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (ml)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and ml/Cr in the right amygdala (r = -0.89, P < 0.001), between ml/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = -63, P < 0.05) and between ml/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = -0.69, P < 0.05). CONCLUSION: Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy.