Heart rate variability in untreated newly diagnosed temporal lobe epilepsy: Evidence for ictal sympathetic dysregulation.

OBJECTIVE: To compare heart rate variability (HRV) parameters in newly diagnosed and untreated temporal lobe epilepsy (TLE) between the interictal, preictal, ictal, and postictal states. METHODS: HRV parameters were extracted from single-lead electrocardiography data collected during video-electroencephalography (EEG) recordings from 14 patients with newly diagnosed TLE in a resting, awake, and supine state. HRV parameters in the time and frequency domains included low frequency (LF), high frequency (HF), standard deviation of all consecutive R wave intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD). Cardiovagal index (CVI), cardiosympathetic index (CSI), and approximate entropy (ApEn) were also studied. RESULTS: Frequency domain analysis showed significantly higher preictal, ictal, and postictal LF/HF ratio compared to the interictal state. Similarly, the LF component increased progressively and was significantly higher during the ictal state compared to interictal and preictal states. RR interval values were lower in the ictal state compared to basal and preictal states and in the postictal state compared to the preictal state. Interictal RMSSD was significantly higher compared to all other states, and ictal SDNN was significantly higher compared to all other states. Ictal CSI was significantly higher compared to preictal and interictal states, whereas preictal CVI was lower than in basal and ictal states. In addition, ictal ApEn was significantly lower than interictal and preictal ApEn. Interictal CVI was lower in left TLE compared to right TLE. In addition, in left TLE, ictal CVI was higher than interictal CVI, whereas in right TLE, CVI was lower in the preictal state compared to all other states. SIGNIFICANCE: Our data suggest an ictal sympathetic overdrive with partial recovery in the postictal state. Higher sympathetic tone and vagal tone imbalance may induce early autonomic dysfunction and increase cardiovascular risk in patients affected by TLE.

Anterior Microsurgical Approach to Ventral Lower Cervical Spine Meningiomas: Indications, Surgical Technique and Long Term Outcome.

Ventral lower cervical spinal meningiomas with posterior displacement of the spinal cord are rare and anterior approach has been rarely reported in the literature. The authors present their experience about eight patients operated through anterior microsurgical approach. Exposure of meningiomas was achieved through one or two corpectomies, according to meningioma extension. Tumour removal was performed thanks to the aid of a dedicated ultrasonic aspirator, and intraoperative evoked potentials were employed. Particular care was taken with the materials adopted for reconstruction of the anterior dural plane, to avoid postoperative cerebrospinal fluid leak. Vertebral fusion and stabilization were achieved by tantalum cage or titanium graft in case of one or two corpectomies respectively; anterior titanium plate fixed with screws was applied in all patients. Extent of tumour removal was related to the presence of a conserved arachnoidal plane between the tumour and the spinal cord: total removal was achieved in 2 patients, while gross total removal in the other six ones. Postoperative neurological outcome, which was favourable in all patients, was related mostly to preoperative neurologic status. No recurrence after total removal and no remnant growth after gross total removal occurred during an average follow-up period of 6, 7 years.

Chronic dopaminergic treatment in restless legs syndrome: does it affect the autonomic nervous system?

OBJECTIVE: The link between the autonomic nervous system and restless legs syndrome (RLS) has been recently postulated. Since dopaminergic agents are used as first-line treatment for RLS, the purpose of our study is to verify whether chronic pramipexole treatment could influence the autonomic control of cardiovascular reflexes and heart rate variability (HRV) in RLS during wakefulness. METHODS: Consecutive drug naive RLS patients underwent polysomnography (PSG), subjective scales, and cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, handgrip and cold face before and after 3-month pramipexole therapy. HRV analysis was performed in the frequency domain using both autoregressive and fast Fourier transform algorithms in rest supine condition and during HUTT. RESULTS: Twenty RLS patients reported a significant reduction of RLS symptoms after pramipexole treatment, while PSG did not show significant improvements except for periodic limb movement index. Pramipexole induced a trend to a lower systolic blood pressure and a significant higher variation of systolic and diastolic blood pressure at HUTT. Cardiovascular responses to the other tests were unchanged. No significant differences in HRV spectral analysis between drug naive and treated patients were observed. Moreover, the within-group analysis of HRV between orthostatic and supine position did not show any significant change in sympathetic and parasympathetic components both in the drug naive and pramipexole groups. CONCLUSIONS: Chronic pramipexole treatment does not seem to affect autonomic balance during wakefulness. Considering that neither PSG data nor autonomic parameters are significantly modified by pramipexole, we hypothesize a non-dopaminergic autonomic dysfunction in RLS.

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 ß-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 ß-amyloid 1-42 and polysomnographic assessment of sleep variables. MAIN OUTCOMES AND MEASURES: Levels of orexin, tau proteins, and ß-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.

Is autonomic nervous system involved in restless legs syndrome during wakefulness?

OBJECTIVE: To investigate cardiovascular autonomic function in patients with restless leg syndrome (RLS) by means of cardiovascular reflexes and heart rate variability (HRV) during wakefulness. METHODS: Twelve RLS patients and 14 controls underwent cardiovascular function tests including head-up tilt test (HUTT), Valsalva maneuver, deep breathing, hand grip, and cold face. HRV analysis was performed in the frequency domain using both autoregressive (AR) and fast Fourier transform algorithms in rest supine condition and during HUTT. RESULTS: There was a significant increase in systolic blood pressure values in supine rest condition and a trend toward a lower Valsalva ratio in RLS patients with respect to controls. The significant and physiological changes of HRV at HUTT detected in healthy subjects were not found in RLS patients. CONCLUSION: RLS patients exhibit a tendency toward hypertension, reduced amplitude of both sympathetic and parasympathetic responses at HUTT, as well as blunted parasympathetic drive to blood pressure changes. These findings, if confirmed by more controlled studies, might support the hypothesis of autonomic nervous system involvement during wakefulness and consequently an enhanced cardiovascular risk in RLS.

Increased cortical excitability after selective REM sleep deprivation in healthy humans: a transcranial magnetic stimulation study.

BACKGROUND: REM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS). METHODS: Ten normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-10 ms. RESULTS: After SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL. CONCLUSIONS: SRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.

Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs.

PURPOSE: Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels. METHODS: Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control. RESULTS: Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm]. DISCUSSION: Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.

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.