Preliminary evidence that vortioxetine may improve sleep quality in depressed patients with insomnia: a retrospective questionnaire analysis.

Insomnia is a frequent symptom in depressed patients. It can present with difficulty in initiating and/or maintaining sleep. We retrospectively evaluated a group of 15 patients affected by major depressive disorder and complaining of insomnia, who started vortioxetine (VOR) treatment for their depressive symptoms. The following questionnaires were captured at baseline and follow-up: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Beck Depression Inventory. Pittsburgh Sleep Quality Index total score significantly decreased between follow-up and baseline (P < 0.01), and in several subitems related to sleep quality and continuity. Moreover, Epworth Sleepiness Scale decreased between follow-up and baseline (P < 0.01). Finally, Beck Depression Inventory reduction was also evident between follow-up and baseline (P < 0.01). This retrospective analysis showing the significant effect of VOR on both depressive symptoms and insomnia in patients showing comorbid major depressive disorder and insomnia invites further research in order to confirm this preliminary evidence. We hypothesize that the VOR mechanism of action may explain the improvement of subjective sleep, other than depressive symptoms.

Predicting seizures in untreated temporal lobe epilepsy using point-process nonlinear models of heartbeat dynamics.

Symptoms of temporal lobe epilepsy (TLE) are frequently associated with autonomic dysregulation, whose underlying biological processes are thought to strongly contribute to sudden unexpected death in epilepsy (SUDEP). While abnormal cardiovascular patterns commonly occur during ictal events, putative patterns of autonomic cardiac effects during pre-ictal (PRE) periods (i.e. periods preceding seizures) are still unknown. In this study, we investigated TLE-related heart rate variability (HRV) through instantaneous, nonlinear estimates of cardiovascular oscillations during inter-ictal (INT) and PRE periods. ECG recordings from 12 patients with TLE were processed to extract standard HRV indices, as well as indices of instantaneous HRV complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra) obtained through definition of inhomogeneous point-process nonlinear models, employing Volterra-Laguerre expansions of linear, quadratic, and cubic kernels. Experimental results demonstrate that the best INT vs. PRE classification performance (balanced accuracy: 73.91%) was achieved only when retaining the time-varying, nonlinear, and non-stationary structure of heartbeat dynamical features. The proposed approach opens novel important avenues in predicting ictal events using information gathered from cardiovascular signals exclusively.

Restless legs syndrome and post polio syndrome: a case-control study.

BACKGROUND AND PURPOSE: The aim was to investigate the prevalence of restless legs syndrome (RLS), fatigue and daytime sleepiness in a large cohort of patients affected by post polio syndrome (PPS) and their impact on patient health-related quality of life (HRQoL) compared with healthy subjects. METHODS: PPS patients were evaluated by means of the Stanford Sleepiness Scale and the Fatigue Severity Scale (FSS). The Short Form Health Survey (SF-36) questionnaire was utilized to assess HRQoL in PPS. RLS was diagnosed when standard criteria were met. Age and sex matched healthy controls were recruited amongst spouses or friends of PPS subjects. RESULTS: A total of 66 PPS patients and 80 healthy controls were enrolled in the study. A significantly higher prevalence of RLS (P < 0.0005; odds ratio 21.5; 95% confidence interval 8.17-57) was found in PPS patients (PPS/RLS+ 63.6%) than in healthy controls (7.5%). The FSS score was higher in PPS/RLS+ than in PPS/RLS- patients (P = 0.03). A significant decrease of SF-36 scores, including the physical function (P = 0.001), physical role (P = 0.0001) and bodily pain (P = 0.03) domains, was found in PPS/RLS+ versus PPS/RLS- patients. Finally, it was found that PPS/RLS+ showed a significant correlation between International Restless Legs Scale score and FSS (P < 0.0001), as well as between International Restless Legs Scale score and most of the SF-36 items (physical role P = 0.0018, general health P = 0.0009, vitality P = 0.0022, social functioning P = 0.002, role emotional P = 0.0019, and mental health P = 0.0003). CONCLUSION: Our findings demonstrate a high prevalence of RLS in PPS, and that RLS occurrence may significantly influence the HRQoL and fatigue of PPS patients. A hypothetical link between neuroanatomical and inflammatory mechanisms in RLS and PPS is suggested.

Cerebrospinal-fluid orexin levels and daytime somnolence in frontotemporal dementia.

Daytime somnolence and sleep-wake cycle disturbances are commonly encountered symptoms in Frontotemporal Dementia (FTD). Orexin-A (Hypocretin-1) is a hypothalamic neuropeptide regulating the sleep-wake rhythm. We investigated the cerebrospinal-fluid (CSF) orexin levels in a population of FTD patients and evaluated whether there is a relationship between daytime somnolence and CSF orexin concentrations. CSF orexin levels were measured in a sample of FTD patients (n = 11) compared to a population of non-demented controls (n = 13) similar for age and sex. Moreover, CSF orexin concentrations were correlated with daytime somnolence investigated by means of the Epworth Sleepiness Scale (ESS) in both FTD patients and controls. FTD patients showed CSF orexin concentrations (164.3 ± 66.45 vs 170.81 ± 42.73 pg/mL) and ESS scores (7.45 ± 4.36 vs 3.84 ± 1.82) not different from controls. However, three FTD patients showed pathological daytime sleepiness (ESS > 10) coupled with the lowest CSF orexin levels. In addition, we found a significant negative correlation between CSF orexin levels and ESS scores in the FTD population (R = -0.91; p < 0.0001), which was not evident in the control group (R = 0.16; p > 0.05). This is the first study investigating CSF orexin concentrations in FTD. We did not find differences in CSF orexin concentrations between FTD patients and controls. However, a significant negative correlation between daytime somnolence and CSF orexin levels was evident in FTD patients. Moreover, we have found that pathological daytime somnolence was evident in those FTD patients with the lowest CSF orexin levels. Based on these findings, we argued that lower orexin levels may be permissive for increased daytime somnolence in FTD.

Sleep disorders in myotonic dystrophy type 2: a controlled polysomnographic study and self-reported questionnaires.

BACKGROUND AND PURPOSE: There is a paucity of data available regarding the occurrence of sleep disorders in myotonic dystrophy type 2 (DM2). In this study the sleep-wake cycle and daytime sleepiness were investigated in DM2 patients and compared with results from healthy subjects and myotonic dystrophy type 1 (DM1) patients. METHODS: Twelve DM2 outpatients, 12 age- and sex-matched healthy controls and 18 DM1 patients were recruited. Subjective quality of sleep was assessed by means of the Pittsburgh Sleep Quality Index (PSQI). Both the Epworth Sleepiness Scale and the Daytime Sleepiness Scale were performed in order to evaluate excessive daytime sleepiness (EDS). All participants underwent polysomnographic monitoring over 48 h as well as the Multiple Sleep Latency Test. RESULTS: Sleep efficiency was < 90% in 12/12 DM2 patients, and significantly reduced when compared with controls or with DM1. Decreased sleep efficiency was associated with sleep-disordered breathing in seven out of 12 DM2 patients and/or periodic limbs movements of sleep (PLMS) in three out of eight patients. Six DM2 patients showed REM sleep without atonia, whereas none of the controls or DM1 patients showed REM sleep dysregulation. The global PSQI score was higher in DM2 patients than in controls and DM1 patients. CONCLUSIONS: Sleep quality in DM2 patients is poorer than in DM1 patients and controls. Sleep apnea is the most common sleep disorder in DM2 patients. Obstructive sleep apnea and sleep fragmentation may represent the main cause of EDS, whereas PLMS is a frequent finding in DM1.

Lacosamide as add-on treatment of focal symptomatic epilepsy in a patient with alcoholic liver cirrhosis.

The occurrence of epileptic seizures in the presence of hepatic disease is not uncommon in clinical practice. Selecting an appropriate AED for patients affected by liver failure who have new-onset epileptic seizures can be challenging. We describe a 64-year-old man affected by liver cirrhosis. The patient developed partial epilepsy with secondary generalization because of an intracerebral hemorrhage in the left parieto-occipital regions. After the neurosurgery procedure, seizures reappeared and were initially managed with levetiracetam. After one month, the patient experienced clusters of seizures while on stable treatment with levetiracetam. Pregabalin as add-on was not tolerated; therefore, he received a low dose of phenobarbital as add-on treatment. The patient developed hepatic encephalopathy. Phenobarbital was immediately stopped, and oral lacosamide was added. A rapid recovery of encephalopathy with a 6-month seizure freedom was obtained. The patient died 6 months later because of progressive impairment of liver function. Lacosamide may represent an alternative to other AEDs in patients with liver failure; however, further prospective evaluation of its efficacy and safety in this clinical setting is needed.

Spasticity as an ictal pattern due to excitotoxic upper motor neuron damage.

We describe the case of a man who presented with spasticity and aphasia related to continuous electroencephalographic epileptic activity in the left frontal-temporal regions. Magnetic resonance imaging (MRI) documented in diffusion-weighted images (DWI) two areas of restricted diffusion in the left frontal and temporal cortex. After starting treatment with levetiracetam 3000 mg/day there was progressive recovery of the clinical picture as well as the gradual disappearance of the electroencephalographic seizure activity and the vanishing of areas of restricted diffusion in brain MRI. Based on the clinical, EEG and MRI data, we hypothesized that both aphasia and spasticity represented ictal signs. To our knowledge, this is the first case report of ictal spasticity.

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). METHODS: Our study used questionnaires, ambulatory polysomnography and the multiple sleep latency test to evaluate sleep-wake cycle and daytime sleepiness in unselected adult-onset DM1 patients. We recruited 18 patients affected by adult-onset DM1 and 18 matched controls. RESULTS: Sleep efficiency was <90% in 16/18 patients, and it was significantly reduced when compared with controls. Reduced sleep efficiency was associated with abnormal respiratory events (5/18 patients) and/or periodic limb movements (11/18 patients). The Periodic Limb Movement Index was significantly increased in DM1 versus controls. A significantly lower mean MSLT sleep latency was detected in DM1 versus controls, but it did not reach pathological levels. CONCLUSIONS: Our controlled study demonstrated sleep alterations in unselected consecutive DM1 patients. Periodic limb movements in sleep are commonly associated with sleep disturbance in adult-onset DM1, and it may represent a marker of CNS neurodegenerative processes in DM1.

ICTAL aphasia as manifestation of partial status epilepticus in a long-lasting misdiagnosed symptomatic epilepsy: an emblematic case.

Magnetic Resonance Imaging (MRI) represents the procedure of choice for detection of anatomical lesions in epilepsy. Vascular malformations in central nervous system, such as cavernoma, can cause symptomatic epilepsy. We describe a case of ictal aphasia as manifestation of a partial status epilepticus probably due to a mutual interaction between a recent bleeding cavernoma and a concomitant reduction of antiepileptic treatment in a long-lasting misdiagnosed symptomatic epilepsy. We conclude that MRI is a mandatory diagnostic method to identify structural abnormalities underlying epilepsy in all patients affected by recurrent focal seizures independent of the duration of epilepsy.

Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study.

BACKGROUND AND PURPOSE: To evaluate the effects of pregabalin (PGB) adjunctive therapy on sleepwake cycle and daytime somnolence in adult patients affected by partial epilepsy. METHODS: Twelve patients affected by partial epilepsy underwent a 24-h ambulatory polysomnography and a subjective evaluation of daytime somnolence by means of the Epworth Sleepiness Scale (ESS), before and after 3 months treatment with PGB. RESULTS: Pregabalin therapy reduced seizures by >50% in 8 out of 12 patients. It induced a significant increase of REM sleep and a decrease of stage 2 NREM sleep (S2). A significant increase of the ESS score was observed without reaching the pathological cut-off value (mean ESS score <10). No statistical correlation between REM sleep and seizure frequency was observed. DISCUSSION: Pregabalin seems to be effective and safe in partial epilepsy. The increase of REM sleep may be indicative of an improvement of nocturnal sleep quality considering the involvement of REM sleep in learning and memory processes. REM sleep enhancement may be the result of both a direct effect of PGB on sleep generators and an indirect effect due to its clinical efficacy. The increase of ESS score within normal range suggests that daytime somnolence is a minor adverse effect of PGB.

Neuroradiological and neuropsychological study of a callosal infarct. A case report.

Corpus callosum infarcts are rare, constituing 0.6% of cerebral infarcts, most likely due to a rich blood supply from three main arterial systems. These infarcts may present with slowly evolving and non-localizing neurologic signs and symptoms that suggest the diagnosis of neoplasm rather than infarct. In addition, they may exhibit radiologic features more often associated with neoplasm, such as mass-like enhancement or extension across the midline. We describe a patient with corpus callosum infarct presenting with a non specific ataxia-like gait disorder, speech difficulty and left-side weakness. MR imaging disclosed an ischemic area in the body and splenium of the corpus callosum with extension to the right semiovalis centre. Neuropsychological study revealed constructive apraxia, attention reduction, motor programming and inhibiting control involvement. The atypical clinical presentation suggested involvement of the posterior circulation, while apraxia and attention impairment were in accordance with lesion localization. In-depth neuropsychological study is essential in patients with suspected corpus callosum involvement because the neurological signs and symptoms are confounding. The infarct localization in the body and semiovalis centre is an interesting neuroradiological feature.

Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study.

Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score (P < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.

Effect of cabergoline added to levodopa treatment on sleep-wake cycle in idiopathic Parkinson's disease: an open label 24-hour polysomnographic study.

Few studies focused on the effects of cabergoline on sleep-wake cycle in PD. Twelve patients affected by PD treated with levodopa as monotherapy underwent two 24-hour ambulatory polysomnographic (A-PSG) sessions twice: in baseline condition (levodopa as monotherapy) and after addition of cabergoline. In each condition, a subjective evaluation of sleep quality and daytime sleepiness was obtained by means of Parkinson's disease Sleep Scale (PDSS) and the Epworth Sleepiness Scale. The statistical analysis of sleep parameters revealed a significant increase of sleep efficiency and slow wave sleep under cabergoline. The PDSS total score showed a significant improvement of overall sleep quality after cabergoline. No significant changes in daytime sleepiness were observed. No patient referred and/or showed sleep attacks before and after addition of cabergoline. We hypothesize that the long-lasting effect of cabergoline may improve the objective quality of nocturnal sleep in PD patients complaining nocturnal motor disability without inducing daytime sleepiness.

Sleep episodes and daytime somnolence as result of individual susceptibility to different dopaminergic drugs in a PD patient: a polysomnographic study.

The association between excessive daytime somnolence (EDS) and idiopathic Parkinson's disease (PD) is often reported but still debated. The possible role of antiparkinsonian therapy or primarily of PD on excessive diurnal sleepiness is controversial. We describe the case of a 61-year-old patient affected by PD who experienced sleep episodes (SE) occurring during pramipexole plus L-Dopa therapy. Polysomnographic sleep studies and subjective evaluations of daytime sleepiness (Epworth Sleepiness Scale) were carried out under administration of pramipexole plus L-Dopa, L-Dopa monotherapy and cabergoline plus L-Dopa. The polysomnography revealed two sleep events during pramipexole plus L-Dopa. Moreover, the polysomnographic data showed an increase of both diurnal and nocturnal sleep under pramipexole plus L-Dopa compared with cabergoline plus L-Dopa and L-Dopa as monotherapy. In addition, while Epworth Sleepiness Scale (ESS) Score showed a mild sleepiness under pramipexole (ESS score=11), ESS scores were normal under both L-Dopa and cabergoline plus L-Dopa. Sleep episodes also disappeared under both L-Dopa and cabergoline plus L-Dopa (2- and 12-month follow-up). We hypothesize that an individual susceptibility to specific antiparkinsonian drug may play a significant role in the genesis of sleepiness in our PD patient.