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Papers by christian franceschini

Research paper thumbnail of Motor events during REM sleep in patients with narcolepsy–ocataplexy: A video-polysomnographic pilot study

Sleep Medicine

REM sleep behavior disorder Narcolepsy-cataplexy Video-PSG recording Simple and complex motor eve... more REM sleep behavior disorder Narcolepsy-cataplexy Video-PSG recording Simple and complex motor events REM sleep Vocalizations Dream enactment a b s t r a c t Objective: We carried out a systematic video-polysomnographic analysis of the number and type of motor events during REM sleep in narcolepsy-cataplexy patients with REM sleep behavior disorder (NC + RBD) but not clinical RBD (NC À RBD). Methods: Twelve NC + RBD and 10 NC À RBD male patients underwent video-polysomnography (video-PSG). Motor events of different type and complexity (i.e., elementary and complex movements and vocalizations) occurring during REM sleep were visually assessed, and indices of their frequency per hour of REM sleep were calculated. Subsequently, the index values were compared in NC + RBD versus NC À RBD patients. Results: Typical RBD behaviors observed in five NC + RBD patients were not included in any type of motor events. No objective conventional sleep parameter, including visual analysis of chin electromyographic (EMG) activity, significantly differed between the two groups of NC patients. NC + RBD patients showed higher occurrence of elementary movements (p = 0.034) during REM sleep compared with NC À RBD patients, but the occurrence of complex movements did not differ significantly. Conclusions: Video-analysis of motor events during REM sleep may improve the diagnosis of RBD in NC. RBD in NC patients is mainly characterized by elementary rather than complex movements, consistent with the view that RBD with NC patients displays a distinct phenotype with respect to other RBD patients.

Research paper thumbnail of O0069 Sympathetic activition during cataplexy in narcoleptic patients

Research paper thumbnail of Narcolepsy with cataplexy associated with holoprosencephaly misdiagnosed as epileptic drop attacks

Research paper thumbnail of Rhythmic movements and sleep paralysis in narcolepsy with cataplexy: A video-polygraphic study

Sleep Medicine, 2010

This section is a new feature of Sleep Medicine allowing readers to submit unique sleep related c... more This section is a new feature of Sleep Medicine allowing readers to submit unique sleep related cases with video segments as a way to enhance educational value in a manner unattainable through paper format. Please see our web site's (http://ees.elsevier.com/ sleep/) Guide for Authors for instructions. We hope this section will be enriched by the contributions of our colleagues who wish to offer stimulating opportunities for discussion and new insights into the field of sleep.

Research paper thumbnail of Behavioural and neurophysiological correlates of human cataplexy: A video-polygraphic study

Clinical Neurophysiology, 2010

Coherent motion perception was tested in nine adolescents with dyslexia and 10 control participan... more Coherent motion perception was tested in nine adolescents with dyslexia and 10 control participants matched for age and IQ using low contrast stimuli with three levels of coherence (10%, 25% and 40%). Event-related potentials (ERPs) and behavioural performance data were obtained. No significant between-group differences were found in performance accuracy and response latencies of correct responses, for early (P1, N1, and P2) or late (P3) ERP peaks. However, attenuated early ERPs in the 10% coherent condition correlated significantly with lower performance accuracy (r = −.66) and with the magnitude of literacy deficit (r = −.46).

Research paper thumbnail of P1.21 Analysis of heart rate variability demonstrates cardiac hypersympathetic tone at rest in narcolepsy with cataplexy

Autonomic Neuroscience-basic & Clinical, 2009

Research paper thumbnail of Errata: Narcolepsy with Cataplexy Associated with Holoprosencephaly Misdiagnosed as Epileptic Drop Attacks

Research paper thumbnail of Catathrenia under sodium oxybate in narcolepsy with cataplexy

Sleep and Breathing

Purpose This study aims to report on catathrenia occurring in narcolepsy with cataplexy (NC) pati... more Purpose This study aims to report on catathrenia occurring in narcolepsy with cataplexy (NC) patients under sodium oxybate (SO) treatment. Catathrenia is a parasomnia characterized by groaning and an abnormal respiratory pattern during sleep. Methods Fifty-one patients with NC and starting SO therapy underwent a baseline overnight polysomnography (PSG) to detect any sleep-related breathing disorders (SRBD). To avoid risks due to a possible central respiratory control depression by SO, all patients with concomitant obstructive sleep apnea (OSA) were treated with a nasal continuous positive airway pressure (nCPAP) device. After 2 months of treatment with SO, all patients underwent a follow-up overnight PSG to investigate possible newly occurring SRBD. They also underwent a semi-structured clinical interview to monitor other potential SO side effects. Results At baseline, four out of 51 patients showed simple snoring, and eight, mild to severe OSA. After a titration PSG night, patients with OSA received a nCPAP device. After 2 months of SO treatment, 28 patients (54.9%) showed SO-related side effects, including SRBD in 11 (21.6%). The follow-up PSG showed a respiratory pattern characteristic of catathrenia in seven patients (13.7%) as a newly observed and possibly benign SO side effect, and ruled out a worsening of OSA. Conclusions Catathrenia should be considered a possible side effect in NC patients under SO treatment and should be accurately identified to prevent unnecessary SO withdrawal.

Research paper thumbnail of Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy

Journal of Neurology, 2008

We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four childre... more We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four children with narcolepsy and cataplexy, in whom the early diagnosis and the extreme disease severity were indications for this potentially efficacious therapy. One of four patients showed an objective and persistent improvement in clinical features during and after IVIg treatment. Our data partially support the recent report of the efficacy of IVIg treatment in early diagnosed narcolepsy with cataplexy and support the need for a controlled multicenter clinical trial on IVIg in narcolepsy.

Research paper thumbnail of Medico-legal assessment of disability in narcolepsy: an interobserver reliability study

Journal of Sleep Research, 2008

Impairment because of narcolepsy strongly limits job performance, but there are no standard crite... more Impairment because of narcolepsy strongly limits job performance, but there are no standard criteria to assess disability in people with narcolepsy and a scale of disease severity is still lacking. We explored: (1) the interobserver reliability among Italian Medical Commissions making disability and handicap benefit decisions for people with narcolepsy, searching for correlations between the recognized disability degree and patients’ features; (2) the willingness to report patients to the driving licence authority and (3) possible sources of variance in judgement. Fifteen narcoleptic patients were examined by four Medical Commissions in simulated sessions. Raw agreement and interobserver reliability among Commissions were calculated for disability and handicap benefit decisions and for driving licence decisions. Levels of judgement differed on percentage of disability (P < 0.001), severity of handicap (P = 0.0007) and the need to inform the driving licence authority (P = 0.032). Interobserver reliability ranged from Kappa = −0.10 to 0.35 for disability benefit decision and from Kappa = −0.26 to 0.36 for handicap benefit decision. The raw agreement on driving licence decision ranged from 73% to 100% (Kappa not calculable). Spearman’s correlation between percentages of disability and patients’ features showed correlations with age, daytime naps, sleepiness, cataplexy and quality of life. This first interobserver reliability study on social benefit decisions for narcolepsy shows the difficulty of reaching an agreement in this field, mainly because of variance in interpretation of the assessment criteria. The minimum set of indicators of disease severity correlating with patients’ self assessments encourages a disability classification of narcolepsy.

Research paper thumbnail of Sleep Polygraphic Study of Children and Adolescents With Narcolepsy/Cataplexy

Developmental Neuropsychology, 2009

The alterations of the Cyclic Alternating Pattern (CAP) recently found in narcoleptic adult patie... more The alterations of the Cyclic Alternating Pattern (CAP) recently found in narcoleptic adult patients suggest the presence of an impaired modulation of the fluctuations of the arousal level during their non-rapid eye movement (NREM) sleep, possibly because of the persistence of neurophysiological mechanisms typical of rapid eye movement (REM) sleep. The same mechanism might play a role in the occurrence of leg movement (LM) activity during sleep characterized by low levels of periodicity. The aim of this study was to evaluate CAP and sleep LM activity in a group of children and adolescents with narcolepsy, to interpret the results under a developmental point of view and integrate this new information with data already available for adults. Thirteen young patients with narcolepsy/cataplexy were consecutively recruited for this study, together with 13 age- and sex-matched normal controls. Nocturnal polysomnography was carried out after a night of adaptation in a sleep laboratory room; sleep stages, CAP, and LMs were scored and evaluated following standard criteria. Narcoleptic patients showed shorter sleep onset and REM sleep latency, higher number of stage shifts and awakenings per hour of sleep, and higher percentage of wakefulness after sleep onset; CAP rate was found to be decreased in all NREM sleep stages (in particular CAP A1 subtypes) in narcoleptic patients who also showed significant higher values of all types of LMs (periodic or isolated), during both REM and NREM sleep; however, the most evident differences were found during REM sleep. The results of this study confirm that the sleep microstructure and LM activity changes observed in adulthood are already present and detectable in childhood and might have a role in the already known impaired prefrontal functioning of these subjects. The well-established orexin deficiency might be the unifying factor playing a major role in the modulation of CAP and LMs during sleep in children and adolescents with narcolepsy/cataplexy.

Research paper thumbnail of Overnight distribution and motor characteristics of REM sleep behaviour disorder episodes in patients with narcolepsy–cataplexy

Sleep Medicine, 2011

REM sleep behaviour disorder (RBD) Narcolepsy with cataplexy Videopolysomnographic recording Temp... more REM sleep behaviour disorder (RBD) Narcolepsy with cataplexy Videopolysomnographic recording Temporal distribution of RBD episodes Characteristics of dream-related motor activity REM without atonia (RWA) a b s t r a c t Objective: The study aimed to examine the temporal distribution of episodes of REM sleep behaviour disorder (RBD) over the night and their motor and polysomnographic (PSG) characteristics in patients with narcolepsy-cataplexy (NC). Methods: Full-night video-PSG recordings of a continuous series of 37 drug-naïve NC patients with clinically-documented RBD were examined to detect the occurrences of RBD episodes (disclosed in 27 patients) and to classify their related PSG and motor behaviour features. Results: RBD episodes occurred with comparable frequency in REM sleep periods of the first and second halves of the night, regardless of the length of REM periods, patients' age or disease duration. Vocalisations and pantomimes occurred in comparable proportions of RBD episodes in the two halves of the night, while aggressive-violent movements were significantly more frequent in RBD episodes of the second half of the night. No sleep parameter significantly differed in patients with RBD occurring in the first/second/ neither half of the night. Conclusions: RBD episodes (a) are not an every night phenomenon in NC patients with clinically documented RBD, regardless of their age or disease duration; (b) can occur in any period of REM sleep, regardless of length; and (c) display less violent-aggressive motor features when they occur in the first half of the night. Multi-night studies with dream-report collection may disclose whether this overnight variation in the violent-aggressive features in RBD episodes of NC patients is associated with a time-ofnight-related variation in dream content.

Research paper thumbnail of P15.1 Sympathetic activity during SOREMP in narcoleptic patients

Clinical Neurophysiology, 2011

14th ECCN / 4th ICTMS/DCS S127 Results: All patients presented a SOREMP and stages 1, 2 and 3 NRE... more 14th ECCN / 4th ICTMS/DCS S127 Results: All patients presented a SOREMP and stages 1, 2 and 3 NREM sleep whereas only 3 patients displayed stage 4 NREM sleep. The mean total time of SOREMP was 8.3±4.4 minutes whereas for stage 1, 2, 3 and 4 were 6.3±0.6, 12.6±9.3, 3.4±1.5 and 7.8±9.6 minutes respectively. Compared to wakefulness before sleep all patients showed a decrease of MSNA with unchanged BP and HR during SOREMP whereas during stages 1, 2, 3 and 4 MSNA, BP and HR showed a continuous further decrease. Conclusions: These preliminary findings showed that autonomic changes during SOREMP differ from normal REM sleep. These data suggested that SOREMP should not be simple considered as a REM sleep intrusion but the underlying pathogenetic mechanism is probably more complex.

Research paper thumbnail of Psychogenic nocturnal stridor in a child: A case report

Movement Disorders, 2009

References 1. Weber YG, Storch A, Wuttke TV, et al. GLUT1 mutations are a cause of paroxysmal exe... more References 1. Weber YG, Storch A, Wuttke TV, et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce haemolytic anemia by a cation leak. J Clin Invest 2008;118:2157-2168. 2. Suls A, Dedeken P, Goffin K, et al. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SCL2A1, encoding the glucose transporter, GLUT1. Brain 2008;131:1831-1844. 3. Windebank AJ, McEvoy KM. Diabetes and the nervous system. In: Aminoff MJ, editor. Neurology and general medicine. Philadelphia: Churchill Livingstone; 1995. p 349-381. 4. Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med 1999;106:307-310. 5. Winer J, Fish D, Sawyers D, Marsden CD. A movement disorder as a presenting feature of recurrent hypoglycaemia. Mov Disord 1990;5:176-177. 6. Shaw C, Haas L, Miller D, Delahunt J. A case report of paroxysmal dystonic choreoathetosis due to hypoglycaemia induced by an insulinoma. J Neurol Neurosurg Psychiatry 1996;61:194-195. 7. Tan NCK, Tan AKY, Sitoh YY, Loh KC, Leow MKS, Tjia HTL. Paroxysmal exercise-induced dystonia associated with hypoglycaemia induced by an insulinoma.

Research paper thumbnail of Spectral analysis of heart rate variability reveals an enhanced sympathetic activity in narcolepsy with cataplexy

Clinical Neurophysiology, 2010

To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest... more To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest and during orthostatic stress in narcolepsy with cataplexy (NC).Ten NC patients with a hypocretin deficit and 18 control subjects underwent head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing and cold face under controlled laboratory conditions. Heart rate variability (HRV) was analysed during supine rest and HUTT considering the normalized unit of LF and HF power (LFnu; HFnu), using autoregressive (AR) and fast Fourier transform (FFT) algorithms.Cardiovascular changes during HUTT, Valsalva manoeuvre, deep breathing, isometric handgrip and cold face were normal and comparable in the two groups. AR and FFT analysis showed an increased LF/HF ratio in NC patients during supine rest. As expected, LFnu increased and HFnu decreased in the control group during HUTT, but did not change in narcoleptics being comparable to values in the supine condition.NC patients showed an increased sympathetic drive on heart rate (HR) in the supine condition that did not further increase during HUTT.These results suggest the proper functioning of cardiovascular reflexes in NC but support an impairment of HR modulation at rest in favour of an enhanced sympathetic activity.

Research paper thumbnail of WO05 Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Clinical Neurophysiology, 2008

Research paper thumbnail of Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: An in vivo brain proton MR spectroscopy study

Brain Research Bulletin, 2009

Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscl... more Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscle tone triggered by emotions, termed cataplexy, disrupted nocturnal sleep and other dissociated rapid eye movement (REM) sleep phenomena. Narcolepsy has been linked to a loss of hypothalamic neurons producing hypocretins, neuropeptides implicated in the regulation of the arousal system. Neuroimaging and neurometabolic studies have shown the pathophysiological involvement of other brain structures such as cerebral cortex and thalamus, but, overall with inconsistent results. We investigated, by using an advanced quantitative MR technique, proton MR spectroscopy ((1)H-MRS), the distribution of brain neurochemical abnormalities in narcolepsy with cataplexy patients. Single voxel (1)H-MRS study was performed in the thalamus, hypothalamus, and parietal-occipital cortex of hypocretin deficient, narcolepsy with cataplexy patients, HLA-DQB1*0602-positive, drug free. No significant changes were detected in the thalamus and parietal-occipital cortex of the patients. On the other hand, the neuronal marker N-acetyl-aspartate was reduced in the hypothalamus of narcolepsy with cataplexy patients compared to controls. These (1)H-MRS findings further support that in narcolepsy with cataplexy patients, the hypothalamus is the primary site of neural lesions. The absence of (1)H-MRS neurodegenerative changes in the thalamus and cerebral cortex suggests that the abnormalities detected in these brain regions by other neuroimaging techniques are likely of functional nature.

Research paper thumbnail of Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy

Sleep Medicine, 2008

Background: Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form ... more Background: Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form of rapid eye movement (REM) sleep motor dyscontrol appearing during wakefulness and elicited by emotions. This study examined the relationship between the frequency of cataplectic attacks in patients with narcolepsy/cataplexy and (a) the clinical and behavioural characteristics of cataplectic attacks, including the emotional tone of trigger events, and (b) the polysomnographic characteristics of daytime sleepiness, nocturnal sleep structure and indices of motor disorders during sleep. Methods: A consecutive series of 44 first-diagnosed drug-naive patients with narcolepsy/cataplexy, fulfilling the International Classification of Sleep Disorders, 2nd edition (ICSD-2) clinical and polysomnographic diagnostic criteria, were interviewed to estimate the frequency and clinical characteristics of cataplectic attacks and the occurrence of REM sleep behaviour disorder (RBD). All patients also underwent a video-polysomnographic recording to assess their sleep parameters and indices of altered motor control during sleep. Results: Patients were divided into two groups on the basis of the frequency of cataplectic attacks, namely high-frequency (n = 30) or low-frequency (n = 14) depending on whether they estimated they had more or less than one attack per month. High-frequency patients (with a larger proportion of men) reported attacks more often affecting mainly the head, jaw and shoulder muscles and experienced more events among those listed as possible triggers of attacks. Sixty-one percent of patients reported RBD and 43% had an RBD episode at video-polysomnography regardless of the frequency of cataplectic attacks or gender. Lastly, the frequency of periodic leg movements (PLM) per hour was higher in men than women and increased with age. Conclusions: Patients with more than one cataplectic attack per month had more frequent involvement of head, jaw and shoulder muscles and were mainly men. The proportions of patients with clinically assessed RBD and an RBD episode documented by videopolysomnography, as well as conspicuous values of PLM per hour, are fairly consistent with those reported in recent small-group studies. Therefore, it seems legitimate to argue that RBD and PLM are nocturnal manifestations intrinsic to narcolepsy/cataplexy and that the gender-related differences in the frequency of attacks and the value of PLM per hour may be indicative of a larger difference in the clinical and polysomnographic characteristics of narcolepsy/cataplexy than hitherto suspected.

Research paper thumbnail of Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Journal of Sleep Research, 2008

Autonomic nervous system activity changes have been described during cataplexy as playing a role ... more Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin-deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro-oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co-activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.

Research paper thumbnail of Different sleep onset criteria at the multiple sleep latency test (MSLT): an additional marker to differentiate central nervous system (CNS) hypersomnias

Journal of Sleep Research, 2010

Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idi... more Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P < 0.0001) longer SusSL than SL (7.7 ± 2.5 versus 5.6 ± 1.3 min, respectively) compared to NwoC (5.8 ± 2.5 versus 5.3 ± 2.2 min) and NC patients (4.1 ± 3 versus 3.9 ± 3 min). A mean difference threshold between SusSL and SL ≥27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders.

Research paper thumbnail of Motor events during REM sleep in patients with narcolepsy–ocataplexy: A video-polysomnographic pilot study

Sleep Medicine

REM sleep behavior disorder Narcolepsy-cataplexy Video-PSG recording Simple and complex motor eve... more REM sleep behavior disorder Narcolepsy-cataplexy Video-PSG recording Simple and complex motor events REM sleep Vocalizations Dream enactment a b s t r a c t Objective: We carried out a systematic video-polysomnographic analysis of the number and type of motor events during REM sleep in narcolepsy-cataplexy patients with REM sleep behavior disorder (NC + RBD) but not clinical RBD (NC À RBD). Methods: Twelve NC + RBD and 10 NC À RBD male patients underwent video-polysomnography (video-PSG). Motor events of different type and complexity (i.e., elementary and complex movements and vocalizations) occurring during REM sleep were visually assessed, and indices of their frequency per hour of REM sleep were calculated. Subsequently, the index values were compared in NC + RBD versus NC À RBD patients. Results: Typical RBD behaviors observed in five NC + RBD patients were not included in any type of motor events. No objective conventional sleep parameter, including visual analysis of chin electromyographic (EMG) activity, significantly differed between the two groups of NC patients. NC + RBD patients showed higher occurrence of elementary movements (p = 0.034) during REM sleep compared with NC À RBD patients, but the occurrence of complex movements did not differ significantly. Conclusions: Video-analysis of motor events during REM sleep may improve the diagnosis of RBD in NC. RBD in NC patients is mainly characterized by elementary rather than complex movements, consistent with the view that RBD with NC patients displays a distinct phenotype with respect to other RBD patients.

Research paper thumbnail of O0069 Sympathetic activition during cataplexy in narcoleptic patients

Research paper thumbnail of Narcolepsy with cataplexy associated with holoprosencephaly misdiagnosed as epileptic drop attacks

Research paper thumbnail of Rhythmic movements and sleep paralysis in narcolepsy with cataplexy: A video-polygraphic study

Sleep Medicine, 2010

This section is a new feature of Sleep Medicine allowing readers to submit unique sleep related c... more This section is a new feature of Sleep Medicine allowing readers to submit unique sleep related cases with video segments as a way to enhance educational value in a manner unattainable through paper format. Please see our web site's (http://ees.elsevier.com/ sleep/) Guide for Authors for instructions. We hope this section will be enriched by the contributions of our colleagues who wish to offer stimulating opportunities for discussion and new insights into the field of sleep.

Research paper thumbnail of Behavioural and neurophysiological correlates of human cataplexy: A video-polygraphic study

Clinical Neurophysiology, 2010

Coherent motion perception was tested in nine adolescents with dyslexia and 10 control participan... more Coherent motion perception was tested in nine adolescents with dyslexia and 10 control participants matched for age and IQ using low contrast stimuli with three levels of coherence (10%, 25% and 40%). Event-related potentials (ERPs) and behavioural performance data were obtained. No significant between-group differences were found in performance accuracy and response latencies of correct responses, for early (P1, N1, and P2) or late (P3) ERP peaks. However, attenuated early ERPs in the 10% coherent condition correlated significantly with lower performance accuracy (r = −.66) and with the magnitude of literacy deficit (r = −.46).

Research paper thumbnail of P1.21 Analysis of heart rate variability demonstrates cardiac hypersympathetic tone at rest in narcolepsy with cataplexy

Autonomic Neuroscience-basic & Clinical, 2009

Research paper thumbnail of Errata: Narcolepsy with Cataplexy Associated with Holoprosencephaly Misdiagnosed as Epileptic Drop Attacks

Research paper thumbnail of Catathrenia under sodium oxybate in narcolepsy with cataplexy

Sleep and Breathing

Purpose This study aims to report on catathrenia occurring in narcolepsy with cataplexy (NC) pati... more Purpose This study aims to report on catathrenia occurring in narcolepsy with cataplexy (NC) patients under sodium oxybate (SO) treatment. Catathrenia is a parasomnia characterized by groaning and an abnormal respiratory pattern during sleep. Methods Fifty-one patients with NC and starting SO therapy underwent a baseline overnight polysomnography (PSG) to detect any sleep-related breathing disorders (SRBD). To avoid risks due to a possible central respiratory control depression by SO, all patients with concomitant obstructive sleep apnea (OSA) were treated with a nasal continuous positive airway pressure (nCPAP) device. After 2 months of treatment with SO, all patients underwent a follow-up overnight PSG to investigate possible newly occurring SRBD. They also underwent a semi-structured clinical interview to monitor other potential SO side effects. Results At baseline, four out of 51 patients showed simple snoring, and eight, mild to severe OSA. After a titration PSG night, patients with OSA received a nCPAP device. After 2 months of SO treatment, 28 patients (54.9%) showed SO-related side effects, including SRBD in 11 (21.6%). The follow-up PSG showed a respiratory pattern characteristic of catathrenia in seven patients (13.7%) as a newly observed and possibly benign SO side effect, and ruled out a worsening of OSA. Conclusions Catathrenia should be considered a possible side effect in NC patients under SO treatment and should be accurately identified to prevent unnecessary SO withdrawal.

Research paper thumbnail of Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy

Journal of Neurology, 2008

We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four childre... more We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four children with narcolepsy and cataplexy, in whom the early diagnosis and the extreme disease severity were indications for this potentially efficacious therapy. One of four patients showed an objective and persistent improvement in clinical features during and after IVIg treatment. Our data partially support the recent report of the efficacy of IVIg treatment in early diagnosed narcolepsy with cataplexy and support the need for a controlled multicenter clinical trial on IVIg in narcolepsy.

Research paper thumbnail of Medico-legal assessment of disability in narcolepsy: an interobserver reliability study

Journal of Sleep Research, 2008

Impairment because of narcolepsy strongly limits job performance, but there are no standard crite... more Impairment because of narcolepsy strongly limits job performance, but there are no standard criteria to assess disability in people with narcolepsy and a scale of disease severity is still lacking. We explored: (1) the interobserver reliability among Italian Medical Commissions making disability and handicap benefit decisions for people with narcolepsy, searching for correlations between the recognized disability degree and patients’ features; (2) the willingness to report patients to the driving licence authority and (3) possible sources of variance in judgement. Fifteen narcoleptic patients were examined by four Medical Commissions in simulated sessions. Raw agreement and interobserver reliability among Commissions were calculated for disability and handicap benefit decisions and for driving licence decisions. Levels of judgement differed on percentage of disability (P < 0.001), severity of handicap (P = 0.0007) and the need to inform the driving licence authority (P = 0.032). Interobserver reliability ranged from Kappa = −0.10 to 0.35 for disability benefit decision and from Kappa = −0.26 to 0.36 for handicap benefit decision. The raw agreement on driving licence decision ranged from 73% to 100% (Kappa not calculable). Spearman’s correlation between percentages of disability and patients’ features showed correlations with age, daytime naps, sleepiness, cataplexy and quality of life. This first interobserver reliability study on social benefit decisions for narcolepsy shows the difficulty of reaching an agreement in this field, mainly because of variance in interpretation of the assessment criteria. The minimum set of indicators of disease severity correlating with patients’ self assessments encourages a disability classification of narcolepsy.

Research paper thumbnail of Sleep Polygraphic Study of Children and Adolescents With Narcolepsy/Cataplexy

Developmental Neuropsychology, 2009

The alterations of the Cyclic Alternating Pattern (CAP) recently found in narcoleptic adult patie... more The alterations of the Cyclic Alternating Pattern (CAP) recently found in narcoleptic adult patients suggest the presence of an impaired modulation of the fluctuations of the arousal level during their non-rapid eye movement (NREM) sleep, possibly because of the persistence of neurophysiological mechanisms typical of rapid eye movement (REM) sleep. The same mechanism might play a role in the occurrence of leg movement (LM) activity during sleep characterized by low levels of periodicity. The aim of this study was to evaluate CAP and sleep LM activity in a group of children and adolescents with narcolepsy, to interpret the results under a developmental point of view and integrate this new information with data already available for adults. Thirteen young patients with narcolepsy/cataplexy were consecutively recruited for this study, together with 13 age- and sex-matched normal controls. Nocturnal polysomnography was carried out after a night of adaptation in a sleep laboratory room; sleep stages, CAP, and LMs were scored and evaluated following standard criteria. Narcoleptic patients showed shorter sleep onset and REM sleep latency, higher number of stage shifts and awakenings per hour of sleep, and higher percentage of wakefulness after sleep onset; CAP rate was found to be decreased in all NREM sleep stages (in particular CAP A1 subtypes) in narcoleptic patients who also showed significant higher values of all types of LMs (periodic or isolated), during both REM and NREM sleep; however, the most evident differences were found during REM sleep. The results of this study confirm that the sleep microstructure and LM activity changes observed in adulthood are already present and detectable in childhood and might have a role in the already known impaired prefrontal functioning of these subjects. The well-established orexin deficiency might be the unifying factor playing a major role in the modulation of CAP and LMs during sleep in children and adolescents with narcolepsy/cataplexy.

Research paper thumbnail of Overnight distribution and motor characteristics of REM sleep behaviour disorder episodes in patients with narcolepsy–cataplexy

Sleep Medicine, 2011

REM sleep behaviour disorder (RBD) Narcolepsy with cataplexy Videopolysomnographic recording Temp... more REM sleep behaviour disorder (RBD) Narcolepsy with cataplexy Videopolysomnographic recording Temporal distribution of RBD episodes Characteristics of dream-related motor activity REM without atonia (RWA) a b s t r a c t Objective: The study aimed to examine the temporal distribution of episodes of REM sleep behaviour disorder (RBD) over the night and their motor and polysomnographic (PSG) characteristics in patients with narcolepsy-cataplexy (NC). Methods: Full-night video-PSG recordings of a continuous series of 37 drug-naïve NC patients with clinically-documented RBD were examined to detect the occurrences of RBD episodes (disclosed in 27 patients) and to classify their related PSG and motor behaviour features. Results: RBD episodes occurred with comparable frequency in REM sleep periods of the first and second halves of the night, regardless of the length of REM periods, patients' age or disease duration. Vocalisations and pantomimes occurred in comparable proportions of RBD episodes in the two halves of the night, while aggressive-violent movements were significantly more frequent in RBD episodes of the second half of the night. No sleep parameter significantly differed in patients with RBD occurring in the first/second/ neither half of the night. Conclusions: RBD episodes (a) are not an every night phenomenon in NC patients with clinically documented RBD, regardless of their age or disease duration; (b) can occur in any period of REM sleep, regardless of length; and (c) display less violent-aggressive motor features when they occur in the first half of the night. Multi-night studies with dream-report collection may disclose whether this overnight variation in the violent-aggressive features in RBD episodes of NC patients is associated with a time-ofnight-related variation in dream content.

Research paper thumbnail of P15.1 Sympathetic activity during SOREMP in narcoleptic patients

Clinical Neurophysiology, 2011

14th ECCN / 4th ICTMS/DCS S127 Results: All patients presented a SOREMP and stages 1, 2 and 3 NRE... more 14th ECCN / 4th ICTMS/DCS S127 Results: All patients presented a SOREMP and stages 1, 2 and 3 NREM sleep whereas only 3 patients displayed stage 4 NREM sleep. The mean total time of SOREMP was 8.3±4.4 minutes whereas for stage 1, 2, 3 and 4 were 6.3±0.6, 12.6±9.3, 3.4±1.5 and 7.8±9.6 minutes respectively. Compared to wakefulness before sleep all patients showed a decrease of MSNA with unchanged BP and HR during SOREMP whereas during stages 1, 2, 3 and 4 MSNA, BP and HR showed a continuous further decrease. Conclusions: These preliminary findings showed that autonomic changes during SOREMP differ from normal REM sleep. These data suggested that SOREMP should not be simple considered as a REM sleep intrusion but the underlying pathogenetic mechanism is probably more complex.

Research paper thumbnail of Psychogenic nocturnal stridor in a child: A case report

Movement Disorders, 2009

References 1. Weber YG, Storch A, Wuttke TV, et al. GLUT1 mutations are a cause of paroxysmal exe... more References 1. Weber YG, Storch A, Wuttke TV, et al. GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce haemolytic anemia by a cation leak. J Clin Invest 2008;118:2157-2168. 2. Suls A, Dedeken P, Goffin K, et al. Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SCL2A1, encoding the glucose transporter, GLUT1. Brain 2008;131:1831-1844. 3. Windebank AJ, McEvoy KM. Diabetes and the nervous system. In: Aminoff MJ, editor. Neurology and general medicine. Philadelphia: Churchill Livingstone; 1995. p 349-381. 4. Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med 1999;106:307-310. 5. Winer J, Fish D, Sawyers D, Marsden CD. A movement disorder as a presenting feature of recurrent hypoglycaemia. Mov Disord 1990;5:176-177. 6. Shaw C, Haas L, Miller D, Delahunt J. A case report of paroxysmal dystonic choreoathetosis due to hypoglycaemia induced by an insulinoma. J Neurol Neurosurg Psychiatry 1996;61:194-195. 7. Tan NCK, Tan AKY, Sitoh YY, Loh KC, Leow MKS, Tjia HTL. Paroxysmal exercise-induced dystonia associated with hypoglycaemia induced by an insulinoma.

Research paper thumbnail of Spectral analysis of heart rate variability reveals an enhanced sympathetic activity in narcolepsy with cataplexy

Clinical Neurophysiology, 2010

To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest... more To test the autonomic control of cardiovascular reflexes and heart rate variability (HRV) at rest and during orthostatic stress in narcolepsy with cataplexy (NC).Ten NC patients with a hypocretin deficit and 18 control subjects underwent head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing and cold face under controlled laboratory conditions. Heart rate variability (HRV) was analysed during supine rest and HUTT considering the normalized unit of LF and HF power (LFnu; HFnu), using autoregressive (AR) and fast Fourier transform (FFT) algorithms.Cardiovascular changes during HUTT, Valsalva manoeuvre, deep breathing, isometric handgrip and cold face were normal and comparable in the two groups. AR and FFT analysis showed an increased LF/HF ratio in NC patients during supine rest. As expected, LFnu increased and HFnu decreased in the control group during HUTT, but did not change in narcoleptics being comparable to values in the supine condition.NC patients showed an increased sympathetic drive on heart rate (HR) in the supine condition that did not further increase during HUTT.These results suggest the proper functioning of cardiovascular reflexes in NC but support an impairment of HR modulation at rest in favour of an enhanced sympathetic activity.

Research paper thumbnail of WO05 Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Clinical Neurophysiology, 2008

Research paper thumbnail of Distribution of neurochemical abnormalities in patients with narcolepsy with cataplexy: An in vivo brain proton MR spectroscopy study

Brain Research Bulletin, 2009

Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscl... more Narcolepsy with cataplexy is characterised by excessive daytime sleepiness, sudden drops of muscle tone triggered by emotions, termed cataplexy, disrupted nocturnal sleep and other dissociated rapid eye movement (REM) sleep phenomena. Narcolepsy has been linked to a loss of hypothalamic neurons producing hypocretins, neuropeptides implicated in the regulation of the arousal system. Neuroimaging and neurometabolic studies have shown the pathophysiological involvement of other brain structures such as cerebral cortex and thalamus, but, overall with inconsistent results. We investigated, by using an advanced quantitative MR technique, proton MR spectroscopy ((1)H-MRS), the distribution of brain neurochemical abnormalities in narcolepsy with cataplexy patients. Single voxel (1)H-MRS study was performed in the thalamus, hypothalamus, and parietal-occipital cortex of hypocretin deficient, narcolepsy with cataplexy patients, HLA-DQB1*0602-positive, drug free. No significant changes were detected in the thalamus and parietal-occipital cortex of the patients. On the other hand, the neuronal marker N-acetyl-aspartate was reduced in the hypothalamus of narcolepsy with cataplexy patients compared to controls. These (1)H-MRS findings further support that in narcolepsy with cataplexy patients, the hypothalamus is the primary site of neural lesions. The absence of (1)H-MRS neurodegenerative changes in the thalamus and cerebral cortex suggests that the abnormalities detected in these brain regions by other neuroimaging techniques are likely of functional nature.

Research paper thumbnail of Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy

Sleep Medicine, 2008

Background: Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form ... more Background: Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form of rapid eye movement (REM) sleep motor dyscontrol appearing during wakefulness and elicited by emotions. This study examined the relationship between the frequency of cataplectic attacks in patients with narcolepsy/cataplexy and (a) the clinical and behavioural characteristics of cataplectic attacks, including the emotional tone of trigger events, and (b) the polysomnographic characteristics of daytime sleepiness, nocturnal sleep structure and indices of motor disorders during sleep. Methods: A consecutive series of 44 first-diagnosed drug-naive patients with narcolepsy/cataplexy, fulfilling the International Classification of Sleep Disorders, 2nd edition (ICSD-2) clinical and polysomnographic diagnostic criteria, were interviewed to estimate the frequency and clinical characteristics of cataplectic attacks and the occurrence of REM sleep behaviour disorder (RBD). All patients also underwent a video-polysomnographic recording to assess their sleep parameters and indices of altered motor control during sleep. Results: Patients were divided into two groups on the basis of the frequency of cataplectic attacks, namely high-frequency (n = 30) or low-frequency (n = 14) depending on whether they estimated they had more or less than one attack per month. High-frequency patients (with a larger proportion of men) reported attacks more often affecting mainly the head, jaw and shoulder muscles and experienced more events among those listed as possible triggers of attacks. Sixty-one percent of patients reported RBD and 43% had an RBD episode at video-polysomnography regardless of the frequency of cataplectic attacks or gender. Lastly, the frequency of periodic leg movements (PLM) per hour was higher in men than women and increased with age. Conclusions: Patients with more than one cataplectic attack per month had more frequent involvement of head, jaw and shoulder muscles and were mainly men. The proportions of patients with clinically assessed RBD and an RBD episode documented by videopolysomnography, as well as conspicuous values of PLM per hour, are fairly consistent with those reported in recent small-group studies. Therefore, it seems legitimate to argue that RBD and PLM are nocturnal manifestations intrinsic to narcolepsy/cataplexy and that the gender-related differences in the frequency of attacks and the value of PLM per hour may be indicative of a larger difference in the clinical and polysomnographic characteristics of narcolepsy/cataplexy than hitherto suspected.

Research paper thumbnail of Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Journal of Sleep Research, 2008

Autonomic nervous system activity changes have been described during cataplexy as playing a role ... more Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin-deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro-oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co-activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.

Research paper thumbnail of Different sleep onset criteria at the multiple sleep latency test (MSLT): an additional marker to differentiate central nervous system (CNS) hypersomnias

Journal of Sleep Research, 2010

Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idi... more Excessive daytime sleepiness (EDS) has different correlates in non-rapid eye movement (NREM) [idiopathic hypersomnia (IH) without long sleep time] and REM sleep [narcolepsy without cataplexy (NwoC) and narcolepsy with cataplexy (NC)]-related hypersomnias of central origin. We analysed sleep onset characteristics at the multiple sleep latency test (MSLT) applying simultaneously two sleep onset criteria in 44 NC, seven NwoC and 16 IH consecutive patients referred for subjective EDS complaint. Sleep latency (SL) at MSLT was assessed both as the time elapsed to the occurrence of a single epoch of sleep Stage 1 NREM (SL) and of unequivocal sleep [three sleep Stage 1 NREM epochs or any other sleep stage epoch, sustained SL (SusSL)]. Idiopathic hypersomnia patients showed significantly (P < 0.0001) longer SusSL than SL (7.7 ± 2.5 versus 5.6 ± 1.3 min, respectively) compared to NwoC (5.8 ± 2.5 versus 5.3 ± 2.2 min) and NC patients (4.1 ± 3 versus 3.9 ± 3 min). A mean difference threshold between SusSL and SL ≥27 s reached a diagnostic value to discriminate IH versus NC and NwoC sufferers (sensitivity 88%; specificity 82%). Moreover, NC patients showed better subjective sleepiness perception than NwoC and IH cases in the comparison between naps with or without sleep occurrence. Simultaneous application of the two widely used sleep onset criteria differentiates IH further from NC and NwoC patients: IH fluctuate through a wake-Stage 1 NREM sleep state before the onset of sustained sleep, while NC and NwoC shift abruptly into a sustained sleep. The combination of SusSL and SL determination at MSLT should be tested as an additional objective differential criterion for EDS disorders.