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Biomedical subjects

E Lugaresi

Publications and source records attributed to E Lugaresi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Conclusions of the symposium.

On the basis of twenty-one kindreds and three cases from uninformative families, the Symposium has confirmed that fatal familial insomnia (FFI) is genotypically and phenotypically distinct and, likely, the third most common inherited prion disease. The genotype, characterized by the D178N mutation on the prion protein (PrP) gene coupled with the methionine codon at position 129 has been demonstrated in all cases. The immunoblot pattern of the PrPres associated with FFI shows a molecular mass of approximately 19kDa for the core protein and a marked underrepresentation of the unglycosylated form. The histopathology, characterized by marked thalamic and inferior olivary atrophy with a variable degree of cerebral cortical spongiosis has been observed in all but two cases. The disease duration was found to be significantly shorter in the FFI subjects homozygous at codon 129 than in the heterozygous subjects. The FFI sleep disorder is characterized by lack of spindle activity and disruption of the wake-sleep cycle which can only be established , or excluded, by polysomnography. Autonomic, endocrine and cognitive impairments also require careful assessment in each case. A condition lacking the D178N mutation and pathologically identical to FFI has been reported. Presence of sleep, autonomic and endocrine abnormalities needs to be demonstrated to identify this condition as a sporadic form of FFI. The pathophysiology of the sleep disorder, the pathogenic mechanisms, fine and early structural changes, including the role of apoptosis, and disease penetrance are the major unresolved issues in FFI.

Autonomic Nervous System Diseases↗
PubMed1998

Epileptic drop attacks in partial epilepsy: clinical features, evolution, and prognosis.

OBJECTIVES: Sudden falls have been described in patients with partial epilepsy. However, no study has detailed the clinical, EEG, and evolutive features of partial epilepsies with drop attacks. METHODS: In a consecutive series of 222 patients with partial epilepsy admitted for uncontrolled seizures over a 10 year period, 31 patients presented with epileptic drop attacks during evolution of their illness. Twenty two patients had frontal, five temporal, and four multifocal or undefinable lobe epilepsy; 74% of the cases showed an EEG pattern of secondary bilateral synchrony during evolution. A statistical comparison of some clinical and EEG features between the patients with epileptic drop attacks and patients with partial epilepsy without drop attacks (control group of 191 patients) was carried out. RESULTS: Seventy four per cent of patients had a poor prognosis and 45% were mentally retarded; 52% of patients with epileptic drop attacks continued to have epileptic falls associated with partial seizures and mental deterioration at the end of the follow up. These characteristics of patients with epileptic drop attacks were significantly different from the control group. CONCLUSION: Almost all literature reports concur that the physiopathogenetic substrate of epileptic drop attacks is a mechanism of secondary bilateral synchrony. A localised epileptic focus may lead to a process of secondary epileptogenesis involving the whole brain, causing a progressive cerebral disturbance with worsening of the epileptic seizures and higher cerebral functions.

Adult↗
PubMed1998

REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure.

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.

Adult↗
PubMed1998

Fatal familial insomnia in a new Italian kindred.

The authors report a new kindred with fatal familial insomnia (FFI)--an inherited prion disease. The propositus had behavioral, sleep, cognitive, and motor impairment associated with thalamic and olivary atrophy. Spongiosis was confined to the parahippocampal gyrus. Protease-resistant prion protein (PrP(res)) was present with widespread distribution. The propositus fits the histopathology of FFI with similar clinical duration and confirms the role of disease duration in determining histopathology and PrP(res) distribution in FFI.

Age of Onset↗
PubMed1997

Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study in vivo brain and muscle bioenergetics in a male patient with Leber's hereditary optic neuropathy (LHON) and mtDNA mutation at 11,778 bp who developed spastic paraparesis with white matter lesions on brain MR imaging. The study was performed before and during treatment with idebenone (135 mg t.i.d.) and after withdrawal. Clinical amelioration and worsening were associated with parallel changes in brain and skeletal muscle bioenergetics following the administration or withdrawal of idebenone. Reversal of paraparesis by idebenone was paralleled by normalization of 31P-MRS, serum lactate and central motor conduction. Extra-ocular neurological dysfunction in LHON may be amenable to treatment by appropriate quinones.

Adult↗
PubMed1997

Propriospinal myoclonus upon relaxation and drowsiness: a cause of severe insomnia.

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.

Adult↗
PubMed1997

Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome.

We studied the effect of botulinum toxin A (BTA) on painful muscular spasms and rigidity in two bedridden patients with clinical, electrophysiologic, and immunologic evidence of stiff-person syndrome. We injected BTA or saline solution into several limb muscles with both the rater and patient blinded to the order of the injections. A physician, unaware of the treatment order, used an objective rating scale for rigidity and spasm frequency scale and independently assessed the treatment results. BTA administration significantly reduced rigidity and stopped the spasms in all limbs. Following BTA injection on one side, the spasm frequency decreased bilaterally possibly because of the spread of hematogenous toxin.

Botulinum Toxins, Type A↗
PubMed1997

Allelic origin of the abnormal prion protein isoform in familial prion diseases.

The hallmark of prion diseases is the presence of an aberrant isoform of the prion protein (PrP(res)) that is insoluble in nondenaturing detergents and resistant to proteases. We investigated the allelic origin of PrP(res) in brains of subjects heterozygous for the D178N mutation linked to fatal familial insomnia (FFI) and a subtype of Creutzfeldt-Jakob disease (CJD178), as well as for insertional mutations associated with another CJD subtype. We found that in FFI and CJD178 subjects, only mutant PrP was detergent-insoluble and protease-resistant. Therefore, PrP(res) derives exclusively from the mutant allele carrying the D178N mutation. In contrast, in the CJD subtype harboring insertional mutations, wild-type PrP was also detergent-insoluble and likely to be protease-resistant. Our findings indicate that the participation of the wild-type PrP in the formation of PrP(res) depends on the type of mutations, providing an insight into the molecular mechanisms underlying the phenotypic heterogeneity in familial prion diseases.

Alleles↗
PubMed1997

Endozepine stupor in children.

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.

Carrier Proteins↗
PubMed1997

Power spectral analysis of heart rate and diastolic blood pressure variability in migraine with and without aura.

Autonomic function in migraineurs during headache-free periods was studied by means of cardiovascular reflexes and power spectral analysis of heart rate and diastolic blood pressure variability. We examined 56 patients: 37 suffering from migraine without aura and 19 from migraine with aura. Cardiovascular responses to the tilt test and Valsalva manoeuvre showed a normal function of the overall baroreceptor reflex arc. Normal heart rate responses to Valsalva manoeuvre and deep breathing suggested an intact parasympathetic function. Power spectral analysis of both heart rate and diastolic blood pressure variability in basal conditions and during orthostatic test showed similar sympathovagal interactions modulating cardiovascular control in migraine patients and in controls.

Adult↗
PubMed1997

Motor overactivity and loss of motor circadian rhythm in fatal familial insomnia: an actigraphic study.

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.

Body Mass Index↗
PubMed1997

Undiagnosed sleep-disordered breathing among male nondippers with essential hypertension.

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.

Adult↗
PubMed1997

Motor disorders in sleep.

Sleep is normally a time of motor quiescence. Motor disorders may, however, arise during the different phases of sleep. Nocturnal myoclonus or periodic leg movements in sleep usually occur during light sleep and may be considered the motor accompaniment of the cyclic fluctuations in excitability typical of such stages. Nocturnal frontal lobe epilepsy also occurs during NREM sleep and may be misdiagnosed as parasomnia. REM behavior disorders are instead dissociated episodes of REM sleep without atonia, often associated with or even heralding Parkinson's disease or multiple system atrophy.

Basal Ganglia Diseases↗
PubMed1997

Heavy snorer disease: from snoring to the sleep apnea syndrome--an overview.

This short review discusses the clinical, pathophysiological and epidemiological aspects of heavy snorer disease. Snoring and obstructive apneas constitute the end points of the same syndrome, i.e. an enhancement in upper airway resistance during sleep. Obstructive apneas, and possibly snoring, are risk factors of chronic arterial hypertension.

Airway Resistance↗
PubMed1997

REM sleep behavior disorders in multiple system atrophy.

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.

Adult↗