Biomedical subjects
Publications and source records attributed to F Provini.
The previously unrecognised association of myoclonus in two patients with LHON with the 11778/ND4 pathogenic mutation is described. EEG failed to disclose epileptic figures, and a back averaging study suggested that myoclonus was cortical in origin in both patients.
The aim of this study was to validate some recurring definitions of excessive daytime sleepiness (EDS) obtained from descriptive epidemiological studies. We devised questions concerning concepts such as "tiredness", "resistible sleepiness", "irresistible sleepiness" and "sudden sleep attacks". The validation was done by comparing the answers with the results of the Multiple Sleep Latency Test (MSLT), considered the gold standard, or criterion measure, for the diagnosis of EDS. The sample study comprised 73 subjects, 57 outpatients referred to our Sleep Center complaining of daytime sleepiness, snoring or sleep apnea and 16 inpatients admitted to our Neurological Institute for causes other than sleep disorders. A moderate correlation (p = -0.38, 95% confidence interval -0.57 to -0.19) was found between "irresistible sleepiness" and mean sleep latency (MSL). The best combinations of sensitivity and specificity in identifying EDS, for 5- and 8-min MSL cutoffs, were observed for the questions concerning "sudden sleep attacks" and "irresistible sleepiness" (areas under the receiver-operating characteristic curves = 66 and 67%, respectively). The subitems exploring the frequency and situations of occurrence of these symptoms improved the validity in identifying EDS. The items regarding "tiredness" and "resistible sleepiness" were not related to the results of the MSLT. In subgroup analysis, irresistible sleepiness failed to identify pathologic MSLT in sleep-disordered breathing subjects. According to previous observations, we suggest that the concept of sleepiness includes various domains heterogeneously related with MSL and that questionnaires must be tailored to the different populations studied.
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Nocturnal paroxysmal dystonia (NPD) is the term used to describe motor attacks characterized by complex behavior, with dystonic-dyskinetic or ballic movements arising from NREM sleep. NPD together with paroxysmal arousals (PA), the briefest attacks, and episodic nocturnal wanderings (ENW), the most prolonged ones, constitute nocturnal frontal lobe epilepsy (NFLE). PA are sudden awakenings associated with stereotyped dystonic-dyskinetic movements, sometimes accompanied by screaming and a frightened expression. ENW are episodes of agitated ambulation, with complex, sometimes violent, motor behavior and dystonic postures involving head, trunk and limbs. NPD, PA and ENW coexist in most patients. NFLE is predominant in males and usually begins during adolescence. A familial recurrence of parasomnias in NFLE patients is much more common than in the general population. Autosomal dominant inheritance has been documented in 6% of our cases. Few patients present personal antecedents or positive neuroradiological findings. Seizures are frequent, occurring every or almost every night, many times per night. Interictal wake and sleep EEG tracings are often normal and ictal epileptic activity is recorded in a relatively small number of cases. Carbamazepine controls or significantly reduces seizures in about 70% of cases; the remainder are drug-resistant. Videopolysomnographic recordings, showing stereotyped abnormal movements during attacks, are mandatory to confirm the diagnosis of NFLE.
OBJECTIVE: To investigate the relationship between axial segmental myoclonus and propriospinal myoclonus. METHODS: A patient with a 3-year history of axial jerks evoked by physical effort and unexpected somesthetic and auditory stimulations was investigated. Polygraphy with multiple-channel axial and limb EMG recording was performed with off-line analysis. RESULTS: Spontaneous, somesthetic and acoustic evoked jerks always began in the left rectus abdominis muscle with a single or repetitive EMG burst that could spread to other rostral and caudal muscles without engagement of cranial nerve innervated muscles, consistent with propriospinal propagation. Spontaneous and evoked jerks could however also appear focally in abdominal muscles and remain localized without any diffusion to other muscle segments. CONCLUSION: Focal axial myoclonus and propriospinal myoclonus may coexist. Conceivably the same spinal generator responsible for a monomeric segmental myoclonus may, under conditions of heightened excitability, cause a multimeric propriospinally propagated muscular activation.
Nocturnal frontal lobe epilepsy (NFLE) has been delineated as a distinct syndrome in the heterogeneous group of paroxysmal sleep-related disturbances. The variable duration and intensity of the seizures distinguish three non-rapid eye movement-related subtypes: paroxysmal arousals, characterized by brief and sudden recurrent motor paroxysmal behaviour; nocturnal paroxysmal dystonia, motor attacks with complex dystonic-dyskinetic features; and episodic nocturnal wanderings, stereotyped, agitated somnambulism. We review the clinical and polysomnographic data related to 100 consecutive cases of NFLE in order to define the clinical and neurophysiological characteristics of the different seizure types that constitute NFLE. NFLE seizures predominate in males (7:3). Age at onset of the nocturnal seizures varies, but centres during infancy and adolescence. A familial recurrence of the epileptic attacks is found in 25% of the cases, while 39% of the patients present a family history of nocturnal paroxysmal episodes that fit the diagnostic criteria for parasomnias. A minority of cases (13%) have personal antecedents (such as birth anoxia, febrile convulsions) or brain CT or MRI abnormalities (14%). In many patients, ictal (44%) and interictal (51%) EEGs are uninformative. Marked autonomic activation is a common finding during the seizures. NFLE does not show a tendency to spontaneous remission. Carbamazepine completely abolishes the seizures in approximately 20% of the cases and gives remarkable relief (reduction of the seizures by at least 50%) in another 48%. VideoEEG recordings confirm that NFLE comprises a spectrum of distinct phenomena, different in intensity but representing a continuum of the same epileptic condition. We believe that the detailed clinical and videoEEG characterization of patients with NFLE represents the first step towards a better understanding of the pathogenic mechanisms and different clinical outcomes of the various seizure types that constitute the syndrome.
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OBJECTIVES: We describe two patients with hypothalamic hamartoma and gelastic seizures. METHODS: We performed ictal neurophysiological studies with polygraphic recordings of autonomic parameters and hormonal ictal plasma concentration measurements. RESULTS: Ictal recordings showed a stereotyped modification of autonomic parameters: increase in blood pressure and heart rate, peripheral vasoconstriction and modification of respiratory activity. At seizure onset, the norepinephrine plasma level was high and epinephrine unchanged, whereas prolactin and adrenocorticotropic hormone were increased in both cases. Growth hormone and cortisol plasma concentrations in each patient showed a different response to seizures. CONCLUSIONS: These data provide evidence that gelastic seizures are accompanied by an abrupt sympathetic system activation, probably due to the direct paroxysmal activation of limbic and paralimbic structures or other autonomic centres of the hypothalamus and medulla.
Ten patients with primary autonomic failure, followed up in a prospective clinical and laboratory study, were finally diagnosed as pure autonomic failure or multiple system atrophy with autonomic failure. Polysomnographic studies were performed in all patients. Whereas all four patients with multiple system atrophy complained of sleep related episodes suggesting REM sleep behaviour disorder (RBD) confirmed by polysomnography, RBD remained absent in the remaining six patients with pure autonomic failure. The data indicate that RBD is an important clinical feature, often heralding multiple system atrophy, but which is absent throughout the course of pure autonomic failure; its recognition can thus be useful in the prognostic evaluation of early primary autonomic failure syndromes.
Three patients, aged 71, 50, and 41 years, presented with myoclonic activity arising in the relaxation period preceding sleep onset and causing severe insomnia. Polygraphic studies showed that the myoclonic activity began in spinally innervated muscles, propagating at low speed to rostral and caudal muscular segments. Myoclonus arose whenever patients relaxed mentally and showed diffuse electroencephalographic alpha activity and was independent of posture. The jerks disappeared during sleep. Clonazepam afforded symptomatic improvement. Propriospinal myoclonus arising from a spinal generator may be facilitated by changes in supraspinal control related to vigilance levels. When arising during relaxation and drowsiness, it may cause severe insomnia.
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Recurring episodes of stupor in adults have been shown to be related to increased levels of endozepines, which are endogenous ligands for the GABAA receptors. We report here two children presenting with recurrent episodes of stupor associated with fast EEG activity who had increased levels of endozepine-4 in plasma. Mass spectroscopy did not reveal commercially available benzodiazepines. Interictal endozepine-4 levels were normal. In one of the patients, administration of flumazenil (0.25 mg i.v.), a benzodiazepine inverse agonist, induced improvement of consciousness and attenuation of EEG fast activity. In conclusion, children presenting with recurrent episodes of stupor and EEG fast activity should be evaluated for endozepine levels and can be effectively treated with i.v. flumazenil.
The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.
OBJECTIVE: A blunting of the nocturnal fall in arterial blood pressure is found in a minority of patients (nondippers) with essential hypertension. We tested whether sleep-disordered breathing (snoring and apnea or hypopnea) might explain such a finding for male patients, among whom its prevalence is much higher. SETTING AND PATIENTS: We studied 100 new cases of hypertension in men, observed consecutively by a local group of general practitioners and diagnosed essential hypertensives in a referral clinic. By using 24 h ambulatory blood pressure monitoring with a SpaceLabs 90207 device, 15 patients were classified initially nondippers (daytime ambulatory blood pressure > or = 136/87 mmHg; night-time decrease by < 10% of the daytime mean), but only 11 were confirmed to be nondippers by continuous blood pressure monitoring with a Finapres device. Ten dippers matched by age, body mass index and mean 24 h blood pressure were used as controls. MAIN OUTCOME MEASURES: Parameters of nocturnal polysomnography. RESULTS: During polysomnography, the nondippers exhibited a blunting of the sleep-related fall in blood pressure and an increased variability in blood pressure associated with sleep-disordered breathing (heavy snoring for all, with an apnea or hypopnea index > 10 in 10 cases). Six of the control patients breathed normally and four snored nonapneically. There was a normal fall in nocturnal blood pressure in all 10 cases. CONCLUSIONS: The nondipper condition appears to be associated with undiagnosed apneic snoring for an unselected population of previously untreated male subjects with a diagnosis of essential hypertension. Ambulatory blood pressure monitoring of such patients is of limited diagnostic value.
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We report the results of clinical and polysomnographic investigations on 39 consecutive multiple system atrophy (MSA) patients. Twenty-seven patients (69%) reported nocturnal motor paroxysmal episodes related to dreams, suggesting the clinical diagnosis of REM sleep behavior disorder (RBD). In 12 of them (44%), RBD preceded the clinical onset of the disease by more than 1 year. In seven (26%), the RBD onset was concomitant with and in eight (30%) was at least 2 years after the appearance of motor or autonomic symptoms. On polysomnographic recordings, 35 of 39 MSA patients (90%) had RBD. Other polysomnographic findings included nonclinical obstructive sleep apnea in 6 patients, laryngeal stridor in 8 patients, and periodic limb movements during sleep in 10 patients. Our data show that RBD represents the most common clinical sleep manifestation and polysomnographic finding in patients with MSA. RBD can frequently herald the appearance of other MSA symptoms by years. Extended polysomnographic montages are recommended in MSA sleep studies.
The organization of sleep activity in stages of different depth is reflected by consistent changes in blood pressure that account for the major part of the day-night blood pressure difference. On the other hand, different mechanisms may underlie dysregulation of nocturnal blood pressure. Cyclic variations in autonomic nervous system activity play an important role in the mediation of the influences of sleep and wakefulness on blood pressure. In addition, several physiologic substances that are knoiwn to induce sleep or arousal are knoiwn to exert actions on blood pressure. Hence, derangements in autonomic nervous system activity, either primitive or secondary to alterations in the circadian rhythm of a variety of neurohumoral factors, are reflected in changes of the circadian blood pressure profile. Important additional influences of sleep on blood pressure may be exerted through respiratory variations, so that sleep-disordered breathing is bound to alter nocturnal blood pressure. Finally, insomnia has to be taken into account as a major cause of sleep-related alteration of the circadian blood pressure profile. The number of medical disorders that can cause insomnia is huge, and includes many if not all of the conditions in which a loss or reversal of the physiologic blood pressure fall at night is found to be prevalent. Unfortunately, objective sleep studies have been performed only in studies of a minority of these disorders, and further studies to assess the pathophysiologic mechanisms actually involved in causing sleep disturbances in each pathologic condition are necessary.
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