Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression.

BACKGROUND: Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS). METHODS: One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored. RESULTS: CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein. CONCLUSIONS: Measurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity.

Beta-amyloid and phosphorylated tau metabolism changes in narcolepsy over time.

PURPOSE: The aim od this study is to test whether metabolism of beta-amyloid and tau proteins changes in narcolepsy along with the disease course. METHODS: We analyzed a population of narcoleptic drug-naïve patients compared to a sample of healthy controls. Patients and controls underwent lumbar puncture for assessment of cerebrospinal fluid (CSF) beta-amyloid1-42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Moreover, based on the median disease duration of the whole narcolepsy group, the patients were divided into two subgroups: patients with a short disease duration (SdN, <5 years) and patients with a long disease duration (LdN, >5 years). RESULTS: We found significantly lower CSF Aß42 levels in the whole narcolepsy group with respect to controls. Taking into account the patient subgroups, we documented reduced CSF Aß42 levels in SdN compared to both LdN and controls. Even LdN patients showed lower CSF Aß42 levels with respect to controls. Moreover, we documented higher CSF p-tau levels in LdN patients compared to both SdN and controls. Finally, a significant positive correlation between CSF Aß42 levels and disease duration was evident. CONCLUSIONS: We hypothesize that beta-amyloid metabolism and cascade may be impaired in narcolepsy not only at the onset but also along with the disease course, although they show a compensatory profile over time. Concurrently, also CSF biomarkers indicative of neural structure (p-tau) appear to be altered in narcolepsy patients with a long disease duration. However, the mechanism underlying beta-amyloid and tau metabolism impairment in narcolepsy remains still unclear and deserves to be better elucidated.

Heidenhain variant in two patients with inherited V210I Creutzfeldt-Jakob disease.

OBJECTIVE: To report two members of the same family carrying the valine to isoleucine point mutation of the prion protein gene (PRNP) and presenting with visual symptoms as initial manifestation as in the "Heidenhain variant" of sporadic Creutzfeldt-Jakob disease (CJD). METHODS: Patients underwent neurological examination, electroencephalogram (EEG), brain magnetic resonance images (MRI) and cerebrospinal fluid (CSF) analysis including the Real Time Quaking Induced Conversion (RT-QuIC) test. Disease-specific mutations and polymorphism at codon 129 of the PRNP gene were also studied. RESULTS: Isolated visual symptoms characterized disease onset of both patients followed by progressive neurological signs, dementia and death in 3 (proband) and 9 (his aunt) months. RT-QuIC analysis of CSF samples of both patients revealed the presence of the pathological prion protein and DNA analysis the V210I point mutation of the PRNP and methionine homozygosity at the polymorphic codon 129. CONCLUSIONS: This report suggests to consider the diagnosis of V210I genetic CJD in patients presenting with the Heidenhain form of CJD and highlights the importance of genetic testing in all patients with isolated visual manifestations at onset followed by progressive neurological signs and dementia.

Cortical plasticity predicts recovery from relapse in multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is characterized by the occurrence of clinical relapses, followed by remitting phases of a neurological deficit. Clinical remission after a relapse can be complete, with a return to baseline function that was present before, but is sometimes only partial or absent. Remyelination and repair of the neuronal damage do contribute to recovery, but they are usually incomplete. OBJECTIVE: We tested the hypothesis that synaptic plasticity, namely long-term potentiation (LTP), may represent an additional substrate for compensating the clinical defect that results from the incomplete repair of neuronal damage. METHODS: We evaluated the correlation between a measure of LTP, named paired associative stimulation (PAS), at the time of relapse and symptom recovery, in a cohort of 22 newly-diagnosed MS patients. RESULTS: PAS-induced LTP was normal in patients with complete recovery, and reduced in patients showing incomplete or absent recovery, 12 weeks after the relapse onset. A multivariate regression model showed that PAS-induced LTP and age may contribute to predict null, partial or complete symptom recovery after a relapse. CONCLUSION: Synaptic plasticity may contribute to symptom recovery after a relapse in MS; and PAS, measured during a relapse, may be used as a predictor of recovery.

CSF beta-amyloid levels are altered in narcolepsy: a link with the inflammatory hypothesis?

Narcolepsy is characterized by hypocretin deficiency due to the loss of hypothalamic orexinergic neurons, and is associated with both the human leucocyte antigen DQB1*06:02 and the T cell receptor polymorphism. The above relationship suggests autoimmune/inflammatory processes underlying the loss of orexinergic neurons in narcolepsy. To test the autoimmune/inflammatory hypothesis by means of cerebrospinal fluid (CSF) levels of beta-amyloid1-42 and/or total tau proteins in a sample of narcoleptic patients, we analysed 16 narcoleptic patients and 16 healthy controls. Beta-amyloid1-42 CSF levels were significantly lower in narcoleptic patients compared with healthy controls. We also documented pathologically low levels of CSF beta-amyloid1-42 (<500 pg mL(-1) ) in six of 16 narcoleptic patients (37.5%). We hypothesize that the significant decrease of the CSF beta-amyloid1-42 levels in narcoleptic patients may support both the inflammatory/autoimmune hypothesis as the basis of the pathogenesis of narcolepsy and the prevalence of an 'amyloidogenic' pathway caused by the deficiency of the alpha-secretases enzymes.

Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study.

PURPOSE: The purpose of this study was to evaluate the effects of zonisamide (ZNS) as adjunctive therapy on sleep-wake cycle and daytime somnolence in adult patients affected by focal epilepsy. METHODS: Thirteen patients affected by focal epilepsy were recruited to undergo a 24-hour ambulatory polysomnography, Multiple Sleep Latency Test (MSLT), and a subjective evaluation of nocturnal sleep by means of the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by means of the Epworth Sleepiness Scale (ESS) before and after 3 months of treatment with ZNS as add-on therapy. RESULTS: Twelve patients completed the study. Zonisamide therapy reduced seizures by >50% in 8 out of 12 patients. Zonisamide did not induce any significant changes in nocturnal polysomnographic variables and in PSQI scores. In addition, mean sleep latency and ESS score were unmodified after treatment. CONCLUSION: Zonisamide seems to be effective and safe in focal epilepsy. Both subjective and objective sleep parameters showed no detrimental effects on nocturnal sleep and daytime somnolence in patients with focal epilepsy using ZNS. Since some AEDs induce sleep impairment, which is known to trigger EEG abnormalities and seizures and to worsen quality of life, our findings suggest a positive profile of ZNS.

Early treatment with high-dose interferon beta-1a reverses cognitive and cortical plasticity deficits in multiple sclerosis.

Acute inflammation is associated with cognitive deficits and alterations of cortical plasticity in multiple sclerosis (MS). We tested whether early treatment with high-dose interferon (IFN) beta-1a, known to reduce inflammatory activity, improves cortical function and cognitive deficits in MS. Eighty treatment-naïve relapsing-remitting MS (RRMS)patients received IFN beta-1a (44 mcg) subcutaneously three times per week. Cognitive performance and cortical plasticity were measured through the paced auditory serial addition test (PASAT) and intermittent theta burst stimulation (iTBS) before and up to two years af-ter IFN beta-1a initiation. Before treatment, patients with gadolinium-enhancing lesions (Gd+) on MRI performed worse on the PASAT,and showed lower iTBS-induced plasticity, compared with Gd- patients. Six months after treatment initiation both PASAT and iTBS-induced plasticity improved in Gd+ and remained stable in Gd- patients. These results suggest that cognitive and synaptic plasticity deficits may be rescued during high-doseIFN beta-1a treatment in newly-diagnosed RRMS patients with Gd+ lesions.

Cognitive profile and brain morphological changes in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is accompanied by neurocognitive impairment, likely mediated by injury to various brain regions. We evaluated brain morphological changes in patients with OSA and their relationship to neuropsychological and oximetric data. Sixteen patients affected by moderate-severe OSA (age: 55.8±6.7 years, 13 males) and fourteen control subjects (age: 57.6±5.1 years, 9 males) underwent 3.0 Tesla brain magnetic resonance imaging (MRI) and neuropsychological testing evaluating short- and long-term memory, executive functions, language, attention, praxia and non-verbal learning. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry (VBM) were performed. Patients and controls differed significantly in Rey Auditory-Verbal Learning test (immediate and delayed recall), Stroop test and Digit span backward scores. Volumes of cortical gray matter (GM), right hippocampus, right and left caudate were smaller in patients compared to controls, with also brain parenchymal fraction (a normalized measure of cerebral atrophy) approaching statistical significance. Differences remained significant after controlling for comorbidities (hypertension, diabetes, smoking, hypercholesterolemia). VBM analysis showed regions of decreased GM volume in right and left hippocampus and within more lateral temporal areas in patients with OSA. Our findings indicate that the significant cognitive impairment seen in patients with moderate-severe OSA is associated with brain tissue damage in regions involved in several cognitive tasks. We conclude that OSA can increase brain susceptibility to the effects of aging and other clinical and pathological occurrences.

High-resolution EEG techniques for brain-computer interface applications.

High-resolution electroencephalographic (HREEG) techniques allow estimation of cortical activity based on non-invasive scalp potential measurements, using appropriate models of volume conduction and of neuroelectrical sources. In this study we propose an application of this body of technologies, originally developed to obtain functional images of the brain's electrical activity, in the context of brain-computer interfaces (BCI). Our working hypothesis predicted that, since HREEG pre-processing removes spatial correlation introduced by current conduction in the head structures, by providing the BCI with waveforms that are mostly due to the unmixed activity of a small cortical region, a more reliable classification would be obtained, at least when the activity to detect has a limited generator, which is the case in motor related tasks. HREEG techniques employed in this study rely on (i) individual head models derived from anatomical magnetic resonance images, (ii) distributed source model, composed of a layer of current dipoles, geometrically constrained to the cortical mantle, (iii) depth-weighted minimum L(2)-norm constraint and Tikhonov regularization for linear inverse problem solution and (iv) estimation of electrical activity in cortical regions of interest corresponding to relevant Brodmann areas. Six subjects were trained to learn self modulation of sensorimotor EEG rhythms, related to the imagination of limb movements. Off-line EEG data was used to estimate waveforms of cortical activity (cortical current density, CCD) on selected regions of interest. CCD waveforms were fed into the BCI computational pipeline as an alternative to raw EEG signals; spectral features are evaluated through statistical tests (r(2) analysis), to quantify their reliability for BCI control. These results are compared, within subjects, to analogous results obtained without HREEG techniques. The processing procedure was designed in such a way that computations could be split into a setup phase (which includes most of the computational burden) and the actual EEG processing phase, which was limited to a single matrix multiplication. This separation allowed to make the procedure suitable for on-line utilization, and a pilot experiment was performed. Results show that lateralization of electrical activity, which is expected to be contralateral to the imagined movement, is more evident on the estimated CCDs than in the scalp potentials. CCDs produce a pattern of relevant spectral features that is more spatially focused, and has a higher statistical significance (EEG: 0.20+/-0.114 S.D.; CCD: 0.55+/-0.16 S.D.; p=10(-5)). A pilot experiment showed that a trained subject could utilize voluntary modulation of estimated CCDs for accurate (eight targets) on-line control of a cursor. This study showed that it is practically feasible to utilize HREEG techniques for on-line operation of a BCI system; off-line analysis suggests that accuracy of BCI control is enhanced by the proposed method.

Sleep-wake cycle and effects of cabergoline monotherapy in de novo Parkinson's disease patients. An ambulatory polysomnographic study.

OBJECTIVE: To investigate the sleep-wake cycle and the effects of cabergoline monotherapy in a homogenous group of de novo Parkinson's Disease (PD) patients without confounding comorbid factors. DESIGN AND PARTICIPANTS: Twelve de novo patients affected by idiopathic PD underwent two ambulatory polysomnographic (APSG)monitoring sessions. The first was performed at baseline, and the second recording one-month after stable treatment with cabergoline monotherapy. Subjective daytime sleepiness was evaluated by means of the Epworth Sleepiness Scale.Data obtained in PD patients at baseline were compared with those obtained in 12 age- and sex-matched healthy subjects. RESULTS: Diurnal sleep parameters did not show significant differences between controls and PD patients at baseline. In PD patients, no significant changes in diurnal sleep were observed between baseline and cabergoline treatment. Regarding nocturnal sleep, patients at baseline showed a significantly lower sleep efficiency and a significantly higher Wakefulness After Sleep Onset than controls. With respect to baseline, a significant increase in REM latency and a significant reduction in REM sleep were observed during cabergoline treatment. CONCLUSIONS: In the early stage of PD, the neurodegenerative process does not seem to be directly responsible for daytime somnolence, but it may be directly involved in the alteration of nocturnal sleep. Cabergoline monotherapy does not affect daytime sleep propensity and, despite clinical improvement, it may have negative effects on REM sleep.

Structure of the cortical networks during successful memory encoding in TV commercials.

OBJECTIVE: This work intends to evaluate the functional characteristics of the cerebral network during the successful memory encoding of TV commercials. METHODS: We estimated the functional networks in the frequency domain from a set of high-resolution EEG data in a group of healthy subjects during the showing of commercial spots within a neutral documentary. We evaluated the differences in the cortical network associated with later remembered and not-remembered commercials by calculating the global-E(g) and local-efficiency E(l) indexes. RESULTS: Successful encoding of TV spots significantly affects the functional communication among cortical areas irrespectively of the frequency band. During the visualization of the video-clips that will be forgotten (FRG), the cortical network exhibited high values of global- and local-efficiency, reflecting a small-world configuration. During the visualization of the video-clips that will be remembered (RMB), the same indexes appeared significantly lower. This difference was especially evident for E(l) in the alpha band and for E(g) in the beta and gamma bands. CONCLUSIONS: The presence of attentional and semantic processes during the RMB condition leads to a significant reduction of the network communication efficiency. SIGNIFICANCE: Such a reduction could represent a predictive measure of accurate recalls of TV spots.

Non-invasive brain-computer interface system: towards its application as assistive technology.

The quality of life of people suffering from severe motor disabilities can benefit from the use of current assistive technology capable of ameliorating communication, house-environment management and mobility, according to the user's residual motor abilities. Brain-computer interfaces (BCIs) are systems that can translate brain activity into signals that control external devices. Thus they can represent the only technology for severely paralyzed patients to increase or maintain their communication and control options. Here we report on a pilot study in which a system was implemented and validated to allow disabled persons to improve or recover their mobility (directly or by emulation) and communication within the surrounding environment. The system is based on a software controller that offers to the user a communication interface that is matched with the individual's residual motor abilities. Patients (n=14) with severe motor disabilities due to progressive neurodegenerative disorders were trained to use the system prototype under a rehabilitation program carried out in a house-like furnished space. All users utilized regular assistive control options (e.g., microswitches or head trackers). In addition, four subjects learned to operate the system by means of a non-invasive EEG-based BCI. This system was controlled by the subjects' voluntary modulations of EEG sensorimotor rhythms recorded on the scalp; this skill was learnt even though the subjects have not had control over their limbs for a long time. We conclude that such a prototype system, which integrates several different assistive technologies including a BCI system, can potentially facilitate the translation from pre-clinical demonstrations to a clinical useful BCI.

Performances evaluation and optimization of brain computer interface systems in a copy spelling task.

The evaluation of the performances of brain-computer interface (BCI) systems could be difficult as a standard procedure does not exist. In fact, every research team creates its own experimental protocol (different input signals, different trial structure, different output devices, etc.) and this makes systems comparison difficult. Moreover, the great question is whether these experiments can be extrapolated to real world applications or not. To overcome some intrinsic limitations of the most used criteria a new efficiency indicator will be described and used. Its main advantages are that it can predict with a high accuracy the performances of a whole system, a fact that can be used to successfully improve its behavior. Finally, simulations were performed to illustrate that the best system is built by tuning the transducer (TR) and the control interface (CI), which are the two main components of a BCI system, so that the best TR and the best CI do not exist but just the best combination of them.

How the NPX data format handles EEG data acquired simultaneously with fMRI.

There is a growing interest in combining EEG and (f)MRI data as they provide complementary information: EEG is characterized by a high temporal resolution but poor spatial one, while fMRI is characterized by a high spatial resolution but low temporal one. However, while a standard file format for storing EEG data is available since over a decade, it does not fulfill the needs of modern protocols and devices such as those involved in simultaneous EEG and fMRI recordings. The main reasons are the limited bit resolution, some difficulties encountered in handling and storing acquisition events or trace markers for off-line analyses and the impossibility to add some protocol-specific information that is not considered in the actual data formats. This, among others, hinders the release of free analysis software and makes it difficult to share data across different laboratories as every research unit develops its own tools according to its needs, stores data in proprietary formats and a lot of time is spent building software applications for converting data from one format to another. The NPX (NeuroPhysiological signals in eXtensible Markup Language) data format was defined to overcome these and other limitations, and here its main characteristics are reported as well as how some typical problems occurring in simultaneous EEG-fMRI recordings are also treated. Many tools based on the NPX technology can be freely downloaded, including a tool for removing artifacts occurring during simultaneous EEG-fMRI recordings.

Increasing cortical excitability: a possible explanation for the proconvulsant role of sleep deprivation.

STUDY OBJECTIVE: Sleep deprivation (SD) is known to facilitate both seizures and interictal epileptiform abnormalities. For this reason, it is often used in the routine diagnostic workup of epileptic patients as an activating procedure for eliciting epileptiform and/or seizure patterns in their EEGs. In order to evaluate the effects of SD on cortical excitability, we studied the effects of sleep loss on healthy subjects by transcranial magnetic stimulation (TMS). DESIGN AND PARTICIPANTS: Seven normal subjects underwent TMS examination in baseline condition and after total sleep deprivation. The TMS investigation included two protocols: a) the evaluation of motor evoked potential and silent period parameters recorded in response to single-pulse magnetic stimulation; and b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-6 ms. SETTING: Clinical neurophysiology laboratory in a general hospital. INTERVENTIONS: None. RESULTS: After SD, the principal finding observed using single-pulse TMS was a decrease of the silent period duration, whereas a reduction of the intracortical inhibition, in particular at inter-stimulus intervals 1 and 2 ms, was found, using the paired-pulse TMS. CONCLUSION: Our findings suggest that SD may modify cortical excitability, seen as the balance between inhibitory and excitatory cortical phenomena, which could reduce the epileptic threshold.

Rotigotine may improve sleep architecture in Parkinson's disease: a double-blind, randomized, placebo-controlled polysomnographic study.

BACKGROUND/OBJECTIVES: Growing evidence demonstrates that in Parkinson's Disease (PD) sleep disturbances are frequent and difficult to treat. Since the efficacy of rotigotine on sleep is corroborated by studies lacking polysomnography (PSG), this study explores the possible rotigotine-mediated impact on PSG parameters in PD patients. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group study to determine the efficacy of rotigotine vs placebo on PSG parameters in moderately advanced PD patients. An unusual protocol was utilized, since patches were maintained from 18:00 h to awakening, minimizing the possible diurnal impact on motor symptoms. All participants underwent sleep PSG recordings, subjective sleep questionnaires (Parkinson Disease Sleep Scale [PDSS], Pittsburgh Sleep Quality Index [PSQI]), and the assessment of early-morning motor disability. RESULTS: We evaluated 42 PD patients (Hoehn & Yahr stages 2 and 3) with sleep impairment randomly assigned to active branch (N =21) or placebo (N = 21). Rotigotine significantly increased sleep efficiency and reduced both wakefulness after sleep onset and sleep latency compared to placebo. Moreover, the mean change in REM sleep quantity was significantly higher in the rotigotine than placebo group. The improvement of PSG parameters corresponded to the amelioration of PDSS and PSQI scores together with the improvement of patient morning motor symptoms. CONCLUSIONS: This study demonstrated the significant effect of rotigotine on sleep quality and continuity in PD patients by promoting sleep stability and increasing REM. The effectiveness of rotigotine on sleep may be ascribed to its pharmacokinetic/pharmacodynamic profile directly on both D1 and D2 receptors.

Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer's disease.

The orexin system has been investigated in patients affected by mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by measuring orexin-A concentrations in the cerebrospinal fluid (CSF), and correlated to subjective and objective sleep parameters, quantified by questionnaires and polysomnography, respectively. Twenty drug-naïve patients with MCI due to AD were studied and compared with a population of 26 age and/or sex matched controls, divided into subgroups on the basis of the Pittsburgh Sleep Quality Index (PSQI) score. Increased CSF-orexin levels were detected in patients with MCI due to AD in comparison with controls (p < 0.05). In particular, CSF-orexin concentrations were higher in MCI patients suffering from sleep complaints (PSQI ≥5, n = 10) compared with MCI patients with a regular sleep-wake cycle (PSQI <5, n = 10, p < 0.001) and compared with both control groups (with sleep complaints, PSQI ≥5, n = 11, p < 0.001; without sleep complaints, PSQI <5, n = 15, p < 0.001). Moreover, REM sleep was reduced in MCI patients compared with controls (p < 0.01), and had a negative correlation coupled with a reciprocal influence at the multiple regression analysis with CSF-orexin levels (R = -0.65; ß = -8.90). REM sleep disruption and sleep fragmentation are related to higher CSF-orexin levels in patients with MCI due to AD, thus suggesting that the orexin system may be involved even in the earliest stages of AD, resulting in prolonged sleep latency, reduced sleep efficiency, and REM sleep impairment.

Optic Nerve Dysfunction in Obstructive Sleep Apnea: An Electrophysiological Study.

STUDY OBJECTIVES: The aim of this study was to evaluate the integrity of the visual system in patients affected by obstructive sleep apnea (OSA) by means of electroretinogram (ERG) and visual evoked potential (VEP). METHODS: We performed electrophysiological study of the visual system in a population of severe OSA (apnea-hypopnea events/time in bed ≥ 30/h) patients without medical comorbidities compared to a group of healthy controls similar for age, sex, and body mass index. Patients and controls did not have visual impairment or systemic disorders with known influence on the visual system. ERG and VEP were elicited by a reversal pattern generated on a television monitor at low (55') and high (15') spatial frequencies stimulation. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) in both patients and controls. RESULTS: In comparison with healthy controls (n = 27), patients with OSA (n = 27) showed a significant latency delay coupled with a significant amplitude reduction of P100 wave of VEP at all spatial frequencies in both eyes. No significant differences between groups were detected as concerning ERG components. No correlations were found between polygraphic parameters, ESS scores, or VEP and ERG components in OSA patients. CONCLUSIONS: This study documented that patients with OSA, without medical comorbidities, present VEP alteration as documented by lower amplitude and longer latency of the P100 component than healthy controls. These altered electrophysiological findings may be the expression of optic nerve dysfunction provoked by hypoxia, acidosis, hypercarbia and airway obstruction, frequently observed in patients with OSA. Hence, we hypothesize that OSA per se may impair optic nerve function.