Andrea Romigi

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.

Non-motor functions in parkinsonian patients implanted in the pedunculopontine nucleus: Focus on sleep and cognitive domains

Between 2005 and 2007, six patients affected by idiopathic Parkinsons disease (IPD) were submitted to the bilateral implantation (and subsequent deep brain stimulation - DBS) of the pedunculopontine nucleus (PPN) plus the subthalamic nucleus (STN). This review synthesizes the effects of PPN low-frequency stimulation on non-motor functions, focusing on patient sleep quality and cognitive performance. If not associated to STN-DBS, PPN-DBS promoted a modest amelioration of patient motor performance. However, during PPN-DBS, they experienced on the one hand a significant improvement in executive functions and working memory, on the other hand a beneficial change in sleep architecture. Overall, the limited sample hampers definite conclusions. Yet, although the PPN-DBS induced motor effects are quite disappointing (discouraging extended trials based upon the sole PPN implantation), the neuropsychological profile supports the contention by which in selected PD patients, with subtle cognitive deficits or vanished efficacy of previous implanted STN, PPN-DBS might still represent a reliable and compassionate option.

Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease.

IMPORTANCE Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness. OBJECTIVES To study cerebrospinal fluid levels of orexin in patients with AD, to evaluate the relationship of orexin cerebrospinal fluid levels with the degree of dementia and the cerebrospinal fluid AD biomarkers (tau proteins and β-amyloid 1-42), and to analyze potentially related sleep architecture changes measured by polysomnography. DESIGN, SETTING, AND PARTICIPANTS We conducted a case-control study from August 1, 2012, through May 31, 2013. We included 48 drug-naive AD patients referred to the Neurological Clinic of the University Hospital of Rome Tor Vergata. Based on the Mini-Mental State Examination score, 21 patients were included in mild AD group (score, ≥21), whereas 27 were included in the moderate to severe AD group (score, <21). The control group consisted of 29 nondemented participants of similar age and sex. EXPOSURE Laboratory assessment of cerebrospinal fluid levels of orexin, tau proteins, and β-amyloid 1-42 and polysomnographic assessment of sleep variables. MAIN OUTCOMES AND MEASURES Levels of orexin, tau proteins, and β-amyloid 1-42; macrostructural variables of nocturnal sleep (total sleep time, sleep efficiency, sleep onset and rapid eye movement [REM] sleep latencies, non-REM and REM sleep stages, and wakefulness after sleep onset); and Mini-Mental State Examination scores. RESULTS Patients with moderate to severe AD presented with higher mean (SD) orexin levels compared with controls (154.36 [28.16] vs 131.03 [26.55]; P < .01) and with more impaired nocturnal sleep with respect to controls and patients with mild AD. On the other hand, in the global AD group, orexin levels were positively correlated with total tau protein levels (r = 0.32; P = .03) and strictly related to sleep impairment. Finally, cognitive impairment, as measured by the Mini-Mental State Examination, was correlated with sleep structure deterioration. CONCLUSIONS AND RELEVANCE Our results demonstrate that, in AD, increased cerebrospinal fluid orexin levels are related to a parallel sleep deterioration, which appears to be associated with cognitive decline. Therefore, the orexinergic system seems to be dysregulated in AD, and its output and function appear to be overexpressed along the progression of the neurodegenerative process. This overexpression may result from an imbalance of the neurotransmitter networks regulating the wake-sleep cycle toward the orexinergic system promoting wakefulness.

Baroreflex Buffering of Sympathetic Activation During Sleep. Evidence From Autonomic Assessment of Sleep Macroarchitecture and Microarchitecture

Abstract—We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

Sleep-related changes in baroreflex sensitivity and cardiovascular autonomic modulation.

Objective We examined the effects of the various sleep stages on baroreflex sensitivity (BRS), and heart rate and blood pressure (BP) variability, and tested the hypothesis that there is a different behavior of the baroreflex control of the sinus node in response to hypertensive and hypotensive stimuli and in relation to different cycles of the overnight sleep. Design Polygraphic sleep recordings were performed in 10 healthy males. The BP and the RR interval were continuously recorded during sleep. Methods BRS was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate the RR-interval and BP variabilities. Results During rapid eye movement (REM) sleep BRS significantly increased in response to hypertensive stimuli in comparison with non-rapid eye movement (NREM) sleep and the awake state, whereas it did not change in response to hypotensive stimuli. In the first sleep cycle, BRS significantly increased during NREM in comparison with wakefulness, whereas during REM BRS in response to hypertensive stimuli did not show significant changes as compared with the awake state and/or with NREM. During REM occurring in the sleep cycle before morning awakening, BRS showed a significant increase in response to hypertensive stimuli in comparison with both NREM and the awake state. Conclusions During sleep, arterial baroreflex modulation of the sinus node is different in response to hypotensive and hypertensive stimuli particularly during REM. Furthermore, baroreflex control of the sinus node shows a non-uniform behavior during REM occurring in different nocturnal sleep cycles. These findings suggest that the arterial baroreflex is more effective in buffering the increased sympathetic activation associated with REM at the end of sleep than in the early night.

Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer's disease: a correlative study

OBJECTIVE To investigate the relationship between the electroencephalographic (EEG) power spectra features obtained by quantitative EEG (qEEG) and the hemodynamic parameters detected by dynamic susceptibility contrast-enhanced MR imaging (DSC MRI) in patients with Alzheimers disease (AD). METHODS Fourteen patients with probable AD and 15 elderly healthy controls were included in the study. All subjects underwent both EEG recording in a rest condition and perfusion MRI. Three EEG scalp areas were defined (anterior, central and posterior) and power spectra values were obtained from each scalp area. Relative values of temporoparietal and sensorimotor regional cerebral blood volume (rCBV) were measured bilaterally and successively averaged to obtain a total perfusion index. The brain atrophy index was calculated and used as a covariate to rCBV. Correlation analysis was performed between EEG variables and hemodynamic-morphological parameters. RESULTS qEEG power spectra of AD patients were characterized by an increase in mean relative power of theta (4-7.75 Hz) associated with a decrease in alpha (8-12.75 Hz) frequency bands with a topographic distribution over the central and posterior EEG scalp regions, when compared with controls; beta (13-31 Hz) frequency band also displayed a significant decrease over the anterior and posterior EEG scalp regions of AD patients with respect to controls. The DSC MRI revealed a bilateral reduction in the temporoparietal and sensorimotor rCBV with respect to controls. Correlation analysis showed that the total level of hypoperfusion selectively correlates with the EEG power spectra in theta and alpha frequency bands distributed over anterior/central and central region, respectively. Within AD patients, the lower the level of hypoperfusion, the higher the content of EEG power spectra in theta frequency band, and the lower the level of hypoperfusion, the lower the content of EEG power spectra in alpha band. CONCLUSIONS The combined qEEG and DSC MRI technology unveiled a selective correlation between neurophysiological and hemodynamical patterns in AD patients. Further investigations will ascertain the relevance of this multi-modal approach in the heterogeneous clinical context of AD.

Sleep disorders in adult-onset myotonic dystrophy type 1: a controlled polysomnographic study

Background:  Sleep disturbances and excessive daytime somnolence are common and disabling features in adult‐onset myotonic dystrophy type 1 (DM1).

Pedunculopontine nucleus stimulation influences REM sleep in Parkinson’s disease

OBJECTIVE: To investigate the sleep-wake cycle and the effects of cabergoline monotherapy in a homogenous group of de novo Parkinsons 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.

Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy.

Purpose:  The endocannabinoid system is involved in excitatory/inhibitory balance mechanisms within the central nervous system (CNS). Growing evidence shows that its perturbation leads to development of epileptic seizures in experimental models, thus indicating that endocannabinoids play an intrinsic protective role in suppressing pathologic neuronal excitability. Experimental data also demonstrate that the endocannabinoid anandamide (AEA) can antagonize epileptic discharges in hippocampal tissue. The objective of our study was to measure endocannabinoids levels in the cerebrospinal fluid (CSF) of drug‐naive patients affected by temporal lobe epilepsy (TLE).

Ketotic hyperglycemia and epilepsia partialis continua

Epilepsia partialis continua (EPC) may occur during nonketotic hyperglycemia but has not been described with diabetic ketoacidosis. The authors report a patient with EPC associated with ketotic hyperglycemia. Brain MRI showed two areas of abnormal signal intensity in the left precentral gyrus and in the right cerebellar hemisphere. Hyperglycemia may reduce seizure threshold because of the increase in γ-aminobutyric acid metabolism and may trigger epileptic discharges.