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Study Objectives: In young adults performing compulsory military service, fatigue and somnolence are common and presumably associated with objective or self-reported sleep deprivation. We aimed to find out whether objective sleep parameters from ambulatory polysomnography could explain their self-reported tiredness and sleepiness and whether habits were associated with sleep parameters or tiredness., Methods: Seventy (67 male, age 18-24 years) participants had their sleep assessed with polysomnography. Their self-reported symptoms and demographic data were obtained from online survey including Epworth Sleepiness Scale, Beck's Depression Inventory, items from Basic Nordic Sleep Questionnaire, Internet Addiction Scale, and lifestyle questions., Results: Snoring (audio recording, percentage of total sleep time) was associated with self-reported sleepiness ( P = .010) and tiredness ( P = .030) and snoring seemed to, partially, explain sleepiness ( P = .029). Twenty-six percent of the conscripts had self-reported sleep deprivation (mismatch between reported need for sleep and reported sleep). Self-reported sleep deprivation was significantly associated with somnolence ( P = .016) and fatigue ( P = .026). Smartphone usage, both average time ( P = .022) and frequency of usage ( P = .0093) before bedtime, was associated with shorter total sleep time. On average, objective sleep time was rather short (7 hours, 6 minutes), sleep efficiency high (94.9%), proportion of N3 sleep high (27.7%), and sleep latency brief (9 minutes)-suggesting that many of the conscripts might have chronic partial sleep deprivation., Conclusions: Snoring might predispose to tiredness in presumably healthy young adults. Conscripts may have partial sleep deprivation., Citation: Orjatsalo M, Toppila J, Heimola M, et al. Snoring was related to self-reported daytime sleepiness and tiredness in young adults performing compulsory conscript service. J Clin Sleep Med . 2023;19(2):243-251., (© 2023 American Academy of Sleep Medicine.)

Background: Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia-reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48-hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6-month neurological outcome., Methods: This is an observational, post hoc sub-study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU-treated adult OHCA survivors with initial shockable rhythm. We used grading of 48-hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6-month cerebral performance category (CPC) 1-2 as good and CPC 3-5 as poor long-term neurological outcome. We compared the prognostic value of biomarkers for 6-month neurological outcome to neurofilament light (NFL) measured at 48 h., Results: Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48-hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25-8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30-4.21) were independently associated with poor 48-hour cEEG in a multivariable logistic regression model. Poor 6-month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6-month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6-month outcome in a multivariable logistic regression model with 48-hour NFL., Conclusion: Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long-term prognostication compared to 48-hour NFL., (© 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: Levodopa-carbidopa-intestinal-gel (LCIG) infusion is an effective treatment for advanced PD with motor fluctuations. Polyneuropathy occurs as a complication in 10-15% of patients. We wanted to assess the frequency of polyneuropathy in Finnish advanced Parkinson's disease (PD) patients with continuous LCIG infusion, and the value of different clinical monitoring parameters during follow-up., Materials and Methods: Patient records of PD patients started on LCIG infusion at Helsinki University Hospital who received nerve conduction studies at baseline and 6 months after treatment initiation were reviewed for epidemiological information, mini mental state examination, baseline and 6 months' UPRDS-III, weight, body mass index, levodopa dose (LD), plasma homocysteine levels, folate, vitamin B6 and B12., Results: Out of 19 patients (n = 6 on B-vitamin substitution), two (10.5%) developed new-onset polyneuropathy after initiation of LCIG therapy (n = 0 with vitamin substitution). Neuropathy was associated with significant weight loss (BMI reduction > 1.5), but not with other monitoring parameters. Homocysteine rose significantly in patients not substituted with B-vitamin complex, but not in patients with B-vitamin substitution. Homocysteine changes correlated with LD changes in the absence of vitamin B substitution. After oral B-vitamin substitution, both patients' polyneuropathy remained electrophysiologically and clinically stable., Conclusions: Rates of polyneuropathy in Finnish PD patients with LCIG treatment are comparable to previous studies. Patients' weight should be included in regular follow up monitoring and can be used for patient self-monitoring. Vitamin B substitution appears to reduce coupling between levodopa dose and homocysteine and may be useful to prevent polyneuropathy related to LCIG., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury., Methods: A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TO x ) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TO x  > 0 indicating impaired reactivity and TO x  > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TO x was analysed in the 0-12, 12-24, 24-48 h time-periods and integrated over 0-48 h. The primary outcome was the association between TO x and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3-5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury., Results: In 108 patients with sufficient data to calculate TO x , 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TO x for 0-48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [- 1.17 to 2.94] vs. - 2.71 95% CI [- 4.16 to - 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, p = 0.042)., Conclusion: Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917 ., (© 2021. The Author(s).)

Aim of the Study: EEG slow wave activity (SWA) has shown prognostic potential in post-resuscitation care. In this prospective study, we investigated the accuracy of continuously measured early SWA for prediction of the outcome in comatose cardiac arrest (CA) survivors., Methods: We recorded EEG with a disposable self-adhesive frontal electrode and wireless device continuously starting from ICU admission until 48 h from return of spontaneous circulation (ROSC) in comatose CA survivors sedated with propofol. We determined SWA by offline calculation of C-Trend® Index describing SWA as a score ranging from 0 to 100. The functional outcome was defined based on Cerebral Performance Category (CPC) at 6 months after the CA to either good (CPC 1-2) or poor (CPC 3-5)., Results: Outcome at six months was good in 67 of the 93 patients. During the first 12 h after ROSC, the median C-Trend Index value was 38.8 (interquartile range 28.0-56.1) in patients with good outcome and 6.49 (3.01-18.2) in those with poor outcome showing significant difference (p < 0.001) at every hour between the groups. The index values of the first 12 h predicted poor outcome with an area under curve of 0.86 (95% CI 0.61-0.99). With a cutoff value of 20, the sensitivity was 83.3% (69.6%-92.3%) and specificity 94.7% (83.4%-99.7%) for categorization of outcome., Conclusion: EEG SWA measured with C-Trend Index during propofol sedation offers a promising practical approach for early bedside evaluation of recovery of brain function and prediction of outcome after CA., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: ITPR3, encoding inositol 1,4,5-trisphosphate receptor type 3, was previously reported as a potential candidate disease gene for Charcot-Marie-Tooth neuropathy. Here, we present genetic and functional evidence that ITPR3 is a Charcot-Marie-Tooth disease gene., Methods: Whole-exome sequencing of four affected individuals in an autosomal dominant family and one individual who was the only affected individual in his family was used to identify disease-causing variants. Skin fibroblasts from two individuals of the autosomal dominant family were analyzed functionally by western blotting, quantitative reverse transcription PCR, and Ca 2+ imaging., Results: Affected individuals in the autosomal dominant family had onset of symmetrical neuropathy with demyelinating and secondary axonal features at around age 30, showing signs of gradual progression with severe distal leg weakness and hand involvement in the proband at age 64. Exome sequencing identified a heterozygous ITPR3 p.Val615Met variant segregating with the disease. The individual who was the only affected in his family had disease onset at age 4 with demyelinating neuropathy. His condition was progressive, leading to severe muscle atrophy below knees and atrophy of proximal leg and hand muscles by age 16. Trio exome sequencing identified a de novo ITPR3 variant p.Arg2524Cys. Altered Ca 2+ -transients in p.Val615Met patient fibroblasts suggested that the variant has a dominant-negative effect on inositol 1,4,5-trisphosphate receptor type 3 function., Interpretation: Together with two previously identified variants, our report adds further evidence that ITPR3 is a disease-causing gene for CMT and indicates altered Ca 2+ homeostasis in disease pathogenesis., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Approximately two-thirds of the mortality following out of hospital cardiac arrest is related to devastating neurological injury. Previous small cohort studies have reported an impaired cerebrovascular autoregulation following cardiac arrest, but no studies have assessed the impact of differences in oxygen and carbon dioxide tensions in addition to mean arterial pressure management., Methods: This is a protocol and statistical analysis plan to assess the correlation between changes in cerebral tissue oxygenation and arterial pressure as measure of cerebrovascular autoregulation, the tissue oxygenation index, in patients following out of hospital cardiac arrest and in healthy volunteers. The COMACARE study included 120 comatose survivors of out of hospital cardiac arrest admitted to ICU and managed with low-normal or high-normal targets for mean arterial pressure, arterial oxygen and carbon dioxide partial pressures. In addition, 102 healthy volunteers have been investigated as a reference group for the tissue oxygenation index. In both cohorts, the cerebral tissue oxygenation was measured by near infrared spectroscopy., Conclusions: Cerebrovascular autoregulation is critical to maintain homoeostatic brain perfusion. This study of changes in autoregulation following out of hospital cardiac arrest over the first 48 hours, as compared to data from healthy volunteers, will generate important physiological information that may guide the rationale and design of interventional studies., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury., Methods: In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2 3 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65-75 mmHg) vs. high-normal (80-100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest., Results: We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p < 0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2-34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6-30.9 µg/L) in the high-normal MAP group, p = 0.522. We found no differences in the secondary outcomes., Conclusions: Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.

Purpose: We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO 2 ) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury., Methods: Using a 2 3 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO 2 and to normoxia (arterial oxygen tension [PaO 2 ] 10-15 kPa) or moderate hyperoxia (PaO 2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO 2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months., Results: In total 120 patients were included in the analyses. There was a clear separation in PaCO 2 (p < 0.001) and PaO 2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO 2 group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO 2 group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO 2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes., Conclusions: Both high-normal PaCO 2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected., Registration: ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.

Hereditary sensory neuropathy type 1 (HSAN1) may be the first genetic neuropathy amenable to a specific mechanism-based treatment, as L-serine supplementation can be used to lower the neurotoxic levels of 1-deoxysphingolipids (1-deoxySL) that cause the neurodegeneration. The treatment is so far untested in HSAN1C caused by variants in the serine palmitoyl transferase subunit 2 ( SPTLC2 ) gene. The aim of this study was to establish whether oral L-serine lowers 1-deoxySL in a patient with HSAN1C, to perform a dose escalation to find the minimal effective dose, and to assess the safety profile and global metabolic effects of the treatment. Our patient underwent a 52-wk treatment in which the L-serine dose was titrated up to 400 mg/kg/day. She was followed up by repeated clinical examination, nerve conduction testing, and skin biopsies to document effects on small nerve fibers. Serum was assayed for 1-deoxySL and metabolomics analysis of 111 metabolites. We found a robust lowering of 1-deoxySL, which correlated in a near-linear fashion with increased serum L-serine levels. Metabolomics analysis showed a modest elevation in glycine and a marked reduction in the level of cytosine, whereas most of the other assayed metabolites did not change. There were no direct side effects from the treatment, but the patient developed a transitory toe ulceration during the course of the study. The Charcot-Marie-Tooth neuropathy score increased by 1 point. We conclude that oral supplementation of L-serine decreases 1-deoxySL in HSAN1C without major global effects on metabolism. L-serine is therefore a potential treatment for HSAN1C., (© 2017 Auranen et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Arterial carbon dioxide tension (PaCO 2 ), oxygen tension (PaO 2 ), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists., Methods: The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low- or high-normal PaCO 2 , PaO 2 , and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 2 3 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO 2 , PaO 2 , and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest., Discussion: The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low- or high-normal PaCO 2 , PaO 2 , and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified., Trial Registration: ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy.

Background: The neonatal screening and early start of the dietary therapy have improved the outcome of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). The acute symptoms of LCHADD are hypoketotic hypoglycemia, failure to thrive, hepatopathy and rhabdomyolysis. Long term complications are retinopathy and neuropathy. Speculated etiology of these long term complications are the accumulation and toxicity of hydroxylacylcarnitines and long-chain fatty acid metabolites or deficiency of essential fatty acids., Aims: To study the possible development of polyneuropathy in LCHADD patients with current dietary regimen., Methods: Development of polyneuropathy in 12 LCHADD patients with the homozygous common mutation c.G1528C was evaluated with electroneurography (ENG) studies. The ENG was done 1-12 times to each patient, between the ages of 3 and 40 years. Clinical data of the patients were collected from the patient records., Results: The first sign of polyneuropathy was detected between the ages of 6-12 years, the first abnormality being reduction of the sensory amplitudes of the sural nerves. With time, progression was detected by abnormalities in sensory responses extending to upper limbs, as well as abnormalities in motor responses in lower limbs. Altogether, eight of the patients had polyneuropathy, despite good compliancy of the diet., Conclusions: This study is the first to report the evolution of polyneuropathy with clinical neurophysiological methods in a relative large LCHADD patient group. Despite early start, and good compliance of the therapy, 6/10 of the younger patients developed neuropathy. However, in most patients the polyneuropathy was less severe than previously described., (Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Recently, we have developed a simple method that uses two electro-oculography (EOG) electrodes for the automatic scoring of sleep-wake in normal subjects. In this study, we investigated the usefulness of this method on 284 consecutive patients referred for a suspicion of sleep apnea who underwent a polysomnography (PSG)., Method: We applied the AASM 2007 scoring rules. A simple automatic sleep-wake classification algorithm based on 18-45 Hz beta power was applied to the calculated bipolar EOG channel and was compared to standard polysomnography. Epoch by epoch agreement was evaluated., Result: Eighteen patients were excluded due to poor EOG quality. One hundred fifty-eight males and 108 females were studied, their mean age was 48 (range 17-89) years, apnea-hypopnea index 13 (range 0-96) /h, BMI 29 (range 17-52) kg/m(2), and sleep efficiency 78 (range 0-98) %. The mean agreement in sleep-wake states between EOG and PSG was 85% and the Cohen's kappa was 0.56. Overall epoch-by-epoch agreement was 85%, and the Cohen's kappa was 0.57 with positive predictive value of 91% and negative predictive value of 65%., Conclusions: The EOG method can be applied to patients referred for suspicion of sleep apnea to indicate the sleep-wake state.

We describe a founder mutation in the gene encoding ganglioside-induced differentiation associated-protein 1 (GDAP1), leading to amino acid change p.H123R, as a common cause of autosomal dominant axonal Charcot-Marie-Tooth (CMT2) neuropathy in Finland. The mutation explains up to 14 % of CMT2 in Finland, where most patients with axonal neuropathy have remained without molecular diagnosis. Only three families out of 28 were found to carry putative disease mutations in the MFN2 gene encoding mitofusin 2. In addition, the MFN2 variant p.V705I was commonly found in our patients, but we provide evidence that this previously described mutation is a common polymorphism and not pathogenic. GDAP1-associated polyneuropathy caused predominantly a mild and slowly progressive phenotype. Besides distal leg muscle weakness, most patients showed mild proximal weakness, often with asymmetry and pes cavus. Our findings broaden the understanding of GDAP1 mutations in CMT2 phenotypes and provide support for the use of whole-exome sequencing in CMT gene diagnostics.

The cyclic alternating pattern (CAP), that is, cyclic variation of brain activity within non-REM sleep stages, is related to sleep instability and preservation, as well as consolidation of learning. Unlike the well-known electrical activity of CAP, its cerebral hemodynamic counterpart has not been assessed in healthy subjects so far. We recorded scalp and cortical hemodynamics with near-infrared spectroscopy on the forehead and systemic hemodynamics (heart rate and amplitude of the photoplethysmograph) with a finger pulse oximeter during 23 nights in 11 subjects. Electrical CAP activity was recorded with a polysomnogram. CAP was related to changes in scalp, cortical, and systemic hemodynamic signals that resembled the ones seen in arousal. Due to their repetitive nature, CAP sequences manifested as low- and very-low-frequency oscillations in the hemodynamic signals. The subtype A3+B showed the strongest hemodynamic changes. A transient hypoxia occurred during CAP cycles, suggesting that an increased CAP rate, especially with the subtype A3+B, which may result from diseases or fragmented sleep, might have an adverse effect on the cerebral vasculature.

Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3-150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.

In order to study the role of endogenous somatostatin in the physiologic modulation of REM sleep (REMS), we measured the effect of intracerebroventricular (ICV) injection of somatostatin antagonist (SA) cyclo-(7-aminoheptanoyl-phe-d-trp-lys-thr(bzl)) on sleep in rats. The effect of ICV SA was also tested after 24-h REMS deprivation with the platform method. To study the role of locus coeruleus (LC) as a site of the sleep inducing action for somatostatin and galanin we microinjected SA, somatostatin, and galanin locally into LC. In all experiments, vigilance state was analyzed visually from 6 h post-injection EEG/EMG recording. Injection of 0.5 and 2 nmol of SA ICV reduced spontaneous REMS and 2 nmol dose reduced also rebound REMS after REMS deprivation when compared with controls (artificial cerebrospinal fluid vehicle). Microinjection of 0.25 nmol of SA into LC reduced REMS, whereas microinjection of somatostatin, galanin, and a combined injection of them were not effective to induce REMS. The results suggest that endogenous somatostatin may contribute to facilitation of REMS. Somatostatin receptors in the LC may be one possible mediator of this effect.

Molecular biological techniques combined with experimental sleep deprivation have revealed alterations in gene transcriptional activity of several proteins which may mediate the effects of prolonged wakefulness in the brain. During sleep deprivation gene transcription is altered in neuronal systems known to participate in the regulation of vigilance and sleep, ie the norardenergic and cholinergic systems, and several neuropeptides and cytokines. The study of immediate early genes during sleep deprivation has revealed increased transcriptional activity in those brain areas that are active during wakefulness. Systemic search for alterated levels of messenger RNA in sleep-deprived brain has revealed signal transduction proteins and metabolic enzymes which may mediate changes in neuronal function during prolonged wakefulness. The purpose of this article is to give a short overview of those genes whose transcription is affected by sleep deprivation according to the current literature, and to characterize the possible role of these genes in sleep regulation.

We studied the effect of sleep deprivation (SD) on the amount of somatostatin (SRIF) and growth hormone-releasing hormone (GHRH) mRNA in rat hypothalamic nuclei. According to earlier studies SRIF possibly facilitates REM sleep and GHRH slow-wave sleep. Adult male rats were sleep deprived by the gentle handling method either for 6 h during the first half of the light phase or for 12 h during the dark phase. Undisturbed rats sacrificed at the same time as the SD rats served as controls. After oligonucleotide in situ hybridization the amount of SRIF and GHRH mRNA was measured in brain sections by image analysis and cell count. SD increased the amount of SRIF mRNA in the arcuate nucleus (ARC). In the periventricular nucleus (PE) there was no effect. The amount of GHRH mRNA increased in the paraventricular nucleus (PA) in the 6 h SD group but no effect was detected in ARC. In the periventromedial hypothalamic area (pVMH) the amount of GHRH mRNA was higher in the control rats sacrificed in the morning (09.00 hours) than in the afternoon (15.00 hours), and SD had no effect. We conclude that SRIF cells in ARC and GHRH cells in PA are modulated by sleep loss, which is in accordance with the possible sleep regulatory function of these neuropeptides.

Growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) have been implicated as sleep factors. We studied how the hypothalamic SRIF/GHRH system is affected by possible feedback regulation resulting from REM sleep deprivation at the level of gene expression and how this is reflected in serum growth hormone (GH) content. Male rats were deprived of REM sleep on small platforms for 24 or 72 h, and one group was allowed a rebound sleep of 24 h after 72 h deprivation. Animals maintained on large platforms and animals taken directly from their home cages served as controls. In situ hybridization was made from 20 microm cryosections through the periventricular, paraventricular and arcuate hypothalamic nuclei using oligonucleotide probes for GHRH and SRIF. The number of cells expressing SRIF or GHRH was counted. Serum GH was measured by means of radioimmunoassay in similarly treated rats. Fewer cells expressed GHRH in the paraventricular nucleus of animals subjected to 24 and 72 h of REM sleep deprivation than in home control animals. A similar trend was observed in the arcuate nucleus. The number of cells expressing SRIF was elevated in the arcuate nucleus after 24 h of REM sleep deprivation but not after 72 h. In the periventricular nucleus the number of cells expressing SRIF was higher after 72 h of deprivation when compared to expression in animals maintained on large platforms. Serum GH levels were decreased in animals maintained on either small or large platforms. It is concluded that the expression of the SRIF and GHRH genes is modulated by REM sleep deprivation.

Rats were deprived of REM sleep for 24 h by keeping them on small platforms that were placed in a water bath (the platform method). Galanin coding mRNA was visualized using in situ hybridization, and cells expressing galanin mRNA were counted. In REM sleep-deprived animals the cell count was higher in the preoptic area and periventricular nucleus. Lesions of this area have been reported to induce wakefulness in cats and rats. Galanin administered into the lateral ventricle had no effect on sleep. We conclude that REM sleep deprivation can induce galanin gene expression in some brain areas, but galanin alone does not modify spontaneous sleep.

In order to evaluate the effect of a specific alpha 2-adrenoceptor antagonist, atipamezole, on vigilance, adult cats with implanted electrodes for polygraphy were tested in a double-blind Latin square design. The standard clinical dose (0.1 mg/kg i.m.) of the specific alpha 2-adrenoceptor agonist, medetomidine, promptly induced stuporous sedation. Atipamezole, given 30 min later at 0.2, 0.4 or 0.8 mg/kg i.m., reversed the sedation within 3 min, resulting in complete awareness of the animal. After the small dose of atipamezole, arousal with some motor excitation continued for 6 h, whereas after the larger doses, the physiological sleep-wake cycle returned earlier. Used alone, the preferred dose, 0.4 mg/kg atipamezole i.m., allowed physiological sleep within 33 +/- 9 min, compared to 22 +/- 3 min after saline. Atipamezole thus proved to be a most effective antagonist to sedation with alpha 2-adrenoceptor agonist drugs, without disturbing excitatory effects. Specific alpha 2-adrenoceptor modulating drugs have evident clinical application, as antidotes to overdosage of alpha 2-adrenoceptor agonists, or to terminate their effect after surgical procedures.