Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Clinical characteristics and outcome of patients with autoimmune encephalitis: clues for paraneoplastic aetiology.

BACKGROUND AND PURPOSE: Autoimmune encephalitis (AE) represents a complex syndrome with diverse clinical manifestations and therapeutic outcomes. The aim of this study was to report the clinical characteristics and the long-term outcome of patients with paraneoplastic and idiopathic AE. METHODS: All patients with subacute encephalopathy admitted to the Neurology Department of our Institution from January 2012 to May 2019 were consecutively enrolled. Patients' serum and cerebrospinal fluid were tested for neural-specific autoantibodies by indirect immunofluorescence assays on mouse brain, rat neurons, cell-based assays and immunoblots. Outcome was assessed by the modified Rankin Scale score. RESULTS: From 107 adult patients with subacute encephalopathy, 50 patients were finally diagnosed with AE. Neural antibodies (Abs) were detected in 45/50 patients (90%). Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent (6/50, 12%) Ab specific to neural surface antigens detected in adults with AE. Paraneoplastic encephalitis was diagnosed in 16/50 patients (32%). The presence of bilateral temporal lobe lesions on magnetic resonance imaging and cerebrospinal fluid restricted oligoclonal bands was associated with a higher probability to detect cancer at the time of AE diagnosis. All patients with Abs to neural surface antigens had a good outcome at last follow-up. Severe disability at AE onset and the lack of long-term immunosuppression predicted a poor outcome. CONCLUSIONS: Leucine-rich glioma-inactivated protein 1 immunoglobulin G was the most frequent Ab detected. Patients with bilateral temporal lobe lesions and oligoclonal bands have a higher probability to harbour an occult tumour. In these patients, a strict surveillance and monitoring for cancer detection is recommended.

The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.

BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

Psychological functioning measures in patients with primary insomnia and sleep state misperception.

OBJECTIVE: Sleep state misperception (SSM) is a term used in the International Classification of Sleep Disorders to indicate people who mistakenly perceive their sleep as wakefulness. SSM is a form of primary insomnia. The aim of this study was to record psychological functioning measures (anxiety, depression, ability to feel pleasure, obsessive-compulsive traits) in a population of patients with primary insomnia and to evaluate the relationship between these measures and the patients' perception of their sleep. MATERIALS AND METHODS: Seventy-six consecutive patients with primary insomnia were enrolled: 34 men and 42 women, mean age 53.9 ± 13.1. Sleep study included the following: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Berlin's Questionnaire and home-based polysomnography. Psychometric evaluation included the following: Self-Administered Anxiety Scale, Beck's Depression Inventory, Maudsley's Obsessive Compulsive Inventory, Snaith-Hamilton Pleasure Scale, Eating Attitude Test. RESULTS: All patients with insomnia had psychometric scores higher than the general population, but very few patients, in both groups, had anxiety or depression scores consistent with severe mood or anxiety disorders. Comparisons between subjective and objective scores confirmed that most sleep parameters were underestimated. Patients with SSM had lower anxiety scores as compared to patients without SSM. CONCLUSIONS: The study did not succeed in identifying any predictor of sleep misperception. We speculate that a group of patients, rather than being extremely worried by their insomnia, may have a sort of agnosia of their sleep.

Functional involvement of cerebral cortex in adult sleepwalking.

The pathophysiology of adult sleepwalking is still poorly understood. However, it is widely accepted that sleepwalking is a disorder of arousal. Arousal circuits widely project to the cortex, including motor cortex. We hypothesized that functional abnormality of these circuits could lead to changes in cortical excitability in sleepwalkers, even during wakefulness. We used transcranial magnetic stimulation (TMS) to examine the excitability of the human motor cortex during wakefulness in a group of adult sleepwalkers. When compared with the healthy control group, short interval intracortical inhibition (SICI), cortical silent period (CSP) duration, and short latency afferent inhibition (SAI) were reduced in adult sleepwalkers during wakefulness. Mean CSP duration was shorter in patients than in controls (80.9 +/- 41 ms vs. 139.4 +/- 37 ms; p = 0.0040). Mean SICI was significantly reduced in patients than in controls (73.5 +/- 38.4% vs. 36.7 +/- 13.1%; p = 0.0061). Mean SAI was also significantly reduced in patients than in controls (65.8 +/- 14.2% vs. 42.8 +/- 16.9%; p = 0.0053). This neurophysiological study suggests that there are alterations in sleepwalkers consistent with an impaired efficiency of inhibitory circuits during wakefulness. This inhibitory impairment could represent the neurophysiological correlate of brain "abnormalities" of sleepwalkers like "immaturity" of some neural circuits, synapses, or receptors.

Tensor veli palatini electromyography for monitoring Eustachian tube rehabilitation in otitis media.

BACKGROUND: The pathogenesis of otitis media is related to Eustachian tube dysfunction. The tensor veli palatini muscle actively opens the Eustachian tube and promotes middle-ear ventilation. This study describes a technique for paratubal electromyography that uses a surface, non-invasive electrode able to record tensor veli palatini muscle activity during swallowing. METHODS: Twenty otitis media patients and 10 healthy patients underwent tensor veli palatini electromyography. Activity of this muscle before and after Eustachian tube rehabilitation was also assessed. RESULTS: In 78.5 per cent of patients, the electromyography duration phase and/or amplitude were reduced in the affected side. The muscle action potential was impaired in all patients who underwent Eustachian tube rehabilitation. CONCLUSION: This study confirmed that Eustachian tube muscle dysfunction has a role in otitis media pathogenesis and showed that muscle activity increases after Eustachian tube rehabilitation therapy.

[Psychopathology in epilepsy and pseudoepilepsy: preliminary results in our experience]. / Psicopatologia nell'epilessia e nella pseudoepilessia: risultati preliminari nella nostra esperienza.

PURPOSE: Pseudoseizures or nonepileptic seizures (NES) are termed "nonepileptic psychogenic seizures" and account for approximately 20% of all intractable seizure disorders. These seizures are often misdiagnosed as true epilepsy, resulting in inappropriate, ineffective and costly treatment of many patients. Nowadays video-EEG monitoring have greatly improved the ability of specialists to correctly distinguish NES from epilepsy. Nevertheless, patients with NES do not always demonstrate obvious psychopathology. The aim of this study is to examine the complexity and severity of psychopathological features of patients with NES, in order to optimize strategies of intervention and appropriate long-term psychological and psychopharmacological treatment for these patients. MATERIALS AND METHODS: We evaluated three samples: patients with NES, patients with epilepsy and a control sample. Subjects with pseudoseizures and epileptic seizures have been randomly recruited from the Epilepsy Centre at the Neurology Institute of Catholic University of Sacred Heart of Rome. Seizures have been documented by the recording of spontaneous events with video-EEG, EEG, clinical observation and ictal examination. Each sample of patients has been tested using the Hamilton Rating Scale for Depression (HDRS), Dissociative Experience Scale (DES), Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Short Form Health Survey 36 (SF-36). RESULTS: 17 (4 M; 13 F) patients with NES, 13 (3 M; 10 F) patients with epilepsy and 16 (4 M; 12 F) control subjects were recruited. Our preliminary results confirm previous researches showing that NES typically manifest between 20 and 30 years of age and that approximately a three-quarters of all patients are women. Besides, they confirm that psychosocial, environmental and intrapsychic mechanisms interact in the aetiology of NES: in particular, our preliminary results are consistent with the hypothesis that traumatic experiences are important precursors to the development and expression of NES. CONCLUSIONS: This study has yielded promising results and confirm the necessity to improve our knowledge about psychopathology of patients with NES. Psychiatrists and neurologists should work in equipe to guarantee an adequate treatment for a pathology too long set aside and almost ignored from clinical research.

Evaluation of pharyngeal muscle activity through nasopharyngeal surface electromyography in a cohort of dysphagic patients with acute ischaemic stroke.

Oro-pharyngeal dysphagia is frequently present during the acute phase of stroke. The aim of the present study was to evaluate whether the recording of surface EMG using a nasopharyngeal (NP) electrode could be applied to evaluation of pharyngeal muscle activity in acute stroke patients and if this neurophysiological measure is related with clinical assessment of swallowing. Patients were examined and clinical severity was assessed with the National Institute of Health Stroke Scale (NIHSS) score; dysphagia was evaluated through bedside screening test using the Gugging Swallowing Scale (GUSS). Extension of the ischaemic lesion was measured by quantitative score, based on CT scan [Alberta Stroke Programme Early CT Score (ASPECTS)]. We analysed 70 patients; 50 were classified as dysphagic (Dys+), and 20 as non-dysphagic (Dys-). Each participant underwent a surface NP EMG recording performed with a NP electrode, made of a Teflon isolated steel catheter, with a length of 16 cm and a tip diameter of 1.5 mm. The electrode was inserted through the nasal cavity, rotated and positioned approximately 3 mm anteroinferior to the salpingo-palatine fold. At least four consecutive swallowing-induced EMG bursts were recorded and analysed for each participant. Swallowing always induced a repetitive, polyphasic burst of activation of the EMG, lasting around 0.25 to 1 sec, with an amplitude of around 100-600mV. Two parameters of the EMG potentials recorded with the NP electrode were analyzed: duration and amplitude. The duration of the EMG burst was increased in Dys+ patients with a statistically significant difference compared to Dys- patients (p < 0.001). The amplitude was slightly reduced in the Dys+ group, but statistically significant differences were not observed (p = 0,775). Nevertheless, the burst amplitude showed a significant inverse correlation with NIHSS [r(48) = -0.31; p < 0.05] and ASPECTS scores [r(48) = -0.27; p < 0.05], meaning that the burst amplitude progressively reduced with an increase of clinical severity (NIHSS) and topographic extension of brain lesions in CT (ASPECTS). These results suggest that NP recordings can give a semi-quantitative measure of swallowing difficulties originating from pharyngeal dysfunction, in fact, electromyographic findings suggest reduced pharyngeal motility.

Functional involvement of cerebral cortex in human narcolepsy.

The pathophysiology of human narcolepsy is still poorly understood. The hypoactivity of some neurotransmitter systems has been hypothesised on the basis of the canine model. To determine whether narcolepsy is associated with changes in excitability of the cerebral cortex, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in 13 patients with narcolepsy and in 12 control subjects. We used several TMS paradigms that can provide information on the excitability of the motor cortex. Resting and active motor thresholds were higher in narcoleptic patients than in controls and intracortical inhibition was more pronounced in narcoleptic patients. No changes in the other evaluated measures were detected. These results are consistent with an impaired balance between excitatory and inhibitory intracortical circuits in narcolepsy that leads to cortical hypoexcitability. We hypothesise that the deficiency of the excitatory hypocretin/orexin-neurotransmitter-system in narcolepsy is reflected in changes of cortical excitability since circuits originating in the lateral hypothalamus and in the basal forebrain project widely to the neocortex, including motor cortex. This abnormal excitability of cortical networks could be the physiological correlate of excessive daytime sleepiness and it could be the substrate for allowing dissociated states of wakefulness and sleep to emerge suddenly while patients are awake, which constitute the symptoms of narcolepsy.

Reduced sensorimotor inhibition in the ipsilesional motor cortex in a patient with chronic stroke of the paramedian thalamus.

OBJECTIVE: Unilateral or bilateral paramedian infarction in the region of the thalamus and upper midbrain may lead to hypersomnia. To determine whether unilateral infarction of the paramedian thalamus leads to changes in excitability of ipsilesional primary motor hand area (M1). METHODS: We describe a patient with chronic stroke of the right dorsomedian and intralaminar thalamic nuclei, who suffered from mild persistent hypersomnia. We studied the excitability of the right and left M1 with transcranial magnetic stimulation (TMS) in the patient, and in 10 healthy controls. RESULTS: In contrast to healthy controls, contralateral electrical stimulation of the median nerve failed to induce short-latency afferent inhibition (SAI) in the ipsilesional M1. Other measures of corticomotor excitability and somatosensory evoked potentials were normal. CONCLUSIONS: The selective loss of ipsilateral SAI in a patient with paramedian thalamic stroke suggests that during wakefulness, the intact paramedian thalamus facilitates the excitability of intracortical inhibitory circuits, which process thalamocortical sensory inputs in the ipsilateral M1. This preliminary finding suggests that measurements of SAI may provide a means of probing the integrity of some neural pathways, which are involved in the control of wakefulness and arousal. SIGNIFICANCE: In addition to the established role of the paramedian thalamus in arousal and memory, our observation suggests that thalamocortical projections from the paramedian thalamus contribute to the integration of sensory input at the cortical level during wakefulness.

[Orexin, sleep and appetite regulation: a review]. / Orexina, regolazione del sonno e dell'appetito: una rassegna.

Since 1998, two research groups independently reported the discovery of two novel hypothalamic neuropeptides, called hypocretin-1 and hypocretin-2, respectively many studies have been carried out about their possible functions. One group named these new peptides orexins (A and B) after the Greek word for appetite, since they found that central administration of orexins potently increased food intake in rats. However hypocretins/ orexins are involved in various hypothalamic mechanisms, such as energy homeostasis, neuroendocrine functions, appetite and satiety regulation, vigilance and defence behaviour, sleep and wake regulation. Here is a review of the recent literature, showing some recent discoveries about the link between orexin system, sleep regulation and appetite regulation.

Tensor veli palatini electromyography with surface electrode applied transnasally.

A new technique is proposed for paratubal electromyography, using a surface, non-invasive, electrode applied transnasally under nasopharyngoscope guidance. This electrode records activity of the tensor veli palatini muscle during swallowing. This technique is of interest for two reasons: endoscopic guidance offers the possibility to check correct positioning of the electrode recording at tensor veli palatini muscle level. Introduction of the non-invasive surface electrode is simple and not painful.

Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea.

Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 ± 2.8 versus 4.1 ± 2.2 (p < 0.05)], in mean AHI [(21.4 ± 6 events per hour versus 8.85 ± 6.9 (p < 0.05)] and in mean ODI [(18.6 ± 8 events per hour to 7 ± 5.8 (p < 0.05)]. We observed that the apnoea/hypopnoea index (AHI) improved by up to 50% from baseline in 71.4% of patients selected after DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as determined by the subject's initial AHI, but also by DISE findings combined with results of gentle mandibular advancement manoeuvre allowing direct view of the effects of mandibular protrusion on breathing spaces in obstruction sites, and showing good optimisation of selection of patients for oral device treatment.

Snoring and nocturnal oxygen desaturations in an Italian middle-aged male population. Epidemiologic study with an ambulatory device.

Recent studies have suggested that portable monitoring may be a valid means of finding respiratory disturbances in epidemiologic research on a large scale. The aim of this cross-sectional study was to evaluate by means of an appropriately validated portable instrument (MESAM 4) the nocturnal oxygen desaturations in a representative sample of adult male population in North Italy. We randomly chose 750 subjects: 399 subjects (53.2 percent) agreed to participate and a complete evaluation of nocturnal recording was possible in 349 subjects (87.5 percent). Seventeen percent of subjects were every-night snorers; a number of oxygen desaturations per hour (ODI) > 10 was found in 13.7 percent, and an ODI > 20 resulted in 4.8 percent. Age, neck circumference corrected for height, snoring time (measured by MESAM), and self-reported snoring were the variables best explaining ODI in our multivariate approach. This study reports the highest prevalence, using nocturnal oxygen desaturation indices as marker, of sleep-disordered breathing than any reported until now in a general population.

Is ESES/CSWS a strictly age-related disorder?

OBJECTIVES: We report on a case of ESES/CSWS observed in a patient of 21 years and still persisting at the age of 25. Cases of ESES/CSWS have never been previously described in adult patients. ESES/CSWS is considered to be related to the degree of maturation of the central nervous system, and therefore strictly age-related. METHODS: Our case of ESES/CSWS was observed in a 2 1 year old woman referred for cognitive and behavioral disorders. She had previously had epileptic fits, but was seizure free at that time. The patient underwent a full-night polygraphic recording , which showed typical ESES/CSWS pattern, with a Spike-and-Wave Index >8 5%. Polysomnography was repeated 9 times in a 4 year follow-up, during which the ESES/CSWS condition persisted, despite the pharmacological treatments. The patient also underwent cerebral magnetic resonance imaging and fludeoxyglucose F 18 positron emission tomography (PET). RESULTS: The PET study revealed reduced metabolic activity within the lower gyrus of the right parietal lobe, but no significant difference between subcortical structures and cortical mantle was seen. MRI scans were normal. CONCLUSIONS: This observation suggests that ESES/CSWS might not always be an age-related condition. Sleep EEG recordings should always be performed in patients with behavioral disorders and a history of epileptic fits.

Influence of cholinergic circuitries in generation of high-frequency somatosensory evoked potentials.

OBJECTIVE: High-frequency oscillations (HFOs) evoked by upper limb stimulation reflect highly synchronised spikes generated in the somatosensory human system. Since acetylcholine produces differential modulation in subgroups of neurons, we would determine whether cholinergic drive influences HFOs. METHODS: We recorded somatosensory evoked potentials (SEPs) from 31 scalp electrodes in 7 healthy volunteers, before and after single administration of rivastigmine, an inhibitor of central acetylcholinesterase. Right median nerve SEPs have been analysed after digital narrow bandpass filtering (500-700 Hz). Raw data were further submitted to Brain Electrical Source analysis (BESA) to evaluate the respective contribution of lemniscal, thalamic and cortical sources. Lastly, we analysed by Fast Fourier transform spectral changes after drug administration in the 10-30 ms latency range. RESULTS: Rivastigmine administration caused a significant increase of HFOs in the 18-28 ms latency range. Wavelets occurring before the onset latency of the conventional N20 SEP did not show any significant change. A similar increase concerned the strength of cortical dipolar sources in our BESA model. Lastly, we found a significant power increase of the frequency peak at about 600 Hz in P3-F3 traces after drug intake. CONCLUSIONS: Our findings demonstrate that the cortical component of HFOs is significantly enhanced by cholinergic activation. Pyramidal chattering cells, which are capable to discharge high-frequency bursts, are mainly modulated by cholinergic inputs; by contrast, acetylcholine does not modify the firing rate of fast-spiking GABAergic interneurons. We thus discuss the hypothesis that cortical HFOs are mainly generated by specialised pyramidal cells.

Snoring in twins.

Snoring is a prerequisite for obstructive sleep apnoea (OSA) and is known to run in families. Recent studies have provided sufficient evidence for a familial predisposition to OSA. In our study, 492 monozygotic and 284 dizygotic twins were contacted by telephone and asked to attend an interview which included questions of life habits, medical history, sleep habits and disorders, with particular emphasis on snoring. Our study showed that the probandwise concordance rate for habitual snoring was higher in monozygotic twins than in dizygotic ones, but the difference was not significant. The comparison of concordant pairs for habitual snoring vs. concordant pairs for non-snoring confirmed that habitual snoring is significantly associated with older age, male gender, higher body mass index (BMI), smoking and respiratory diseases. The multivariate analysis in the discordant groups confirmed that BMI is more strongly associated to habitual snoring in dizygotic twins than in the monozygotic ones. Our logistic analysis showed that other variables, such as smoking and respiratory diseases, are associated with habitual snoring in dizygotic pairs, but not in monozygotic ones. These findings suggest a genetic predisposition to habitual snoring.

Sleep disorders in Sanfilippo syndrome: a polygraphic study.

OBJECTIVE: A high prevalence of sleep disorders is reported in patients affected by Mucopolysaccharidosis III (Sanfilippo syndrome). These disorders have never been investigated by prolonged, objective, and instrumental evaluations. The present work is based on sleep duration and structure in Sanfilippo patients. STUDY DESIGN: The features of sleep/wake cycle in 6 Sanfilippo patients and 6 healthy controls were evaluated by means of sleep diaries and 48 hour ambulatory EEG and polygraphic recordings. Statistical analysis was performed by means of the U-test (Mann-Whitney). RESULTS: Four out of six Sanfilippo patients, the oldest patients in our sample, showed an extremely irregular sleep pattern, with several sleep episodes of inconstant duration, irregularly distributed along 24 hours. The two younger patients showed sleep maintenance insomnia with several nocturnal awakenings. CONCLUSIONS: These results suggest that sleep disruption in Sanfilippo syndrome consists of an irregular sleep/wake pattern, which at its onset might appear as a disorder of initiating or maintaining sleep. This could explain why same patients do not respond to conventional hypnotics. The present observation might suggest attempting therapies aimed at resynchronization, such as behavioral treatment, light therapy or melatonin.

[New perspectives in the diagnosis and therapy of narcolepsy]. / Nuove prospettive nella diagnosi e nella terapia della narcolessia.

Narcolepsy syndrome is a common, although often misdiagnosed, neurological disorder, whose clinical features are excessive daytime somnolence with sleep attacks, caplexy, sleep paralysis and hypnagogic hallucinations. The clinical manifestation have been interpreted as the expression of a sudden intrusion of dissociated REM phenomena in wakefulness. Sometimes the clinical manifestations may include only some of the symptoms: in particular, the cases in which the only symptom is excessive daytime somnolence may be difficult to diagnose. The etiopathogenesis of narcolepsy syndrome is still poorly understood. Recent experimental evidences suggest that a protein, called "orexin", which is supposed to play a role in the control mechanisms of both sleep and eating behaviour, is involved in its pathogenesis. The treatment of narcolepsy has been, up to now, exclusively symptomatic, and in some way empirical and unsatisfactory, especially regarding to daytime sleepiness. Recently, new pharmacological agents, acting on the serotoninergic and/or noradrenergic systems, allow a better control of the cataplectic attacks. The recent development of modafinil, a central nervous system stimulant, devoid of the serious side effects of amphetamines and other compounds, allows to hope in a better control of daytime somnolence and sleep attacks. The aim of the paper is to describe the recent advances in the diagnosis and treatment of narcolepsy.