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Biomedical subjects

Pasquale Montagna

Publications and source records attributed to Pasquale Montagna.

At least 19 recordsLinked to original sources
PubMed2007

Augmentation of restless legs syndrome with long-term tramadol treatment.

Restless legs syndrome (RLS) augmentation, defined as a kind of suppression of the circadian rhythm of the disease in which sensory and motor symptoms appear earlier during the day (and over previously unaffected body parts), with a progressive phase advance until, backwards, the symptoms may cover the entire day, has been described only after treatment with dopaminergic drugs. We report clinical and polysomnographic accounts of a patient developing RLS augmentation after long-term treatment with tramadol, an opioid agonist with selectivity for mu-receptor and added norepinephrine and serotonin reuptake inhibition properties. Polysomnographic measures showed an improvement of RLS and a disappearance of diurnal sensory and motor RLS symptoms after tramadol was stopped. Our case confirms a recent retrospective report of augmentation of RLS after treatment with tramadol, and begs the question whether augmentation is truly restricted to dopaminergic drugs.

Aged, 80 and over↗
PubMed2007

Family-based association study of the restless legs syndrome loci 2 and 3 in a European population.

Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family-based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846-D9S171 in a subset of South European trios and with a haplotype at D9S156-D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS.

Chromosomes, Human, Pair 12↗
PubMed2006

Parallel changes in resting muscle sympathetic nerve activity and blood pressure in a hypertensive OSAS patient demonstrate treatment efficacy.

Studies comparing the efficacy of continuous positive airway pressure (CPAP) versus surgery in correcting cardiovascular abnormalities in OSAS are lacking. We describe an OSAS patient with hypertension who responded favorably to CPAP treatment, whereas subsequent uvulopalatopharyngoplasty (UPPP) was less successful. While CPAP markedly lowered daytime muscle sympathetic nerve activity (MSNA) and blood pressure (BP), findings after UPPP were comparable to pre-treatment baseline. Thus, parallel changes in MSNA and BP demonstrated treatment efficacy.

Blood Pressure↗
PubMed2006

A wavelet based method for automatic detection of slow eye movements: a pilot study.

Electro-oculographic (EOG) activity during the wake-sleep transition is characterized by the appearance of slow eye movements (SEM). The present work describes an algorithm for the automatic localisation of SEM events from EOG recordings. The algorithm is based on a wavelet multiresolution analysis of the difference between right and left EOG tracings, and includes three main steps: (i) wavelet decomposition down to 10 detail levels (i.e., 10 scales), using Daubechies order 4 wavelet; (ii) computation of energy in 0.5s time steps at any level of decomposition; (iii) construction of a non-linear discriminant function expressing the relative energy of high-scale details to both high- and low-scale details. The main assumption is that the value of the discriminant function increases above a given threshold during SEM episodes due to energy redistribution toward higher scales. Ten EOG recordings from ten male patients with obstructive sleep apnea syndrome were used. All tracings included a period from pre-sleep wakefulness to stage 2 sleep. Two experts inspected the tracings separately to score SEMs. A reference set of SEM (gold standard) were obtained by joint examination by both experts. Parameters of the discriminant function were assigned on three tracings (design set) to minimize the disagreement between the system classification and classification by the two experts; the algorithm was then tested on the remaining seven tracings (test set). Results show that the agreement between the algorithm and the gold standard was 80.44+/-4.09%, the sensitivity of the algorithm was 67.2+/-7.37% and the selectivity 83.93+/-8.65%. However, most errors were not caused by an inability of the system to detect intervals with SEM activity against NON-SEM intervals, but were due to a different localisation of the beginning and end of some SEM episodes. The proposed method may be a valuable tool for computerized EOG analysis.

Adult↗
PubMed2006

Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies.

Knowing how and when the degenerative process starts is important in neurodegenerative diseases. We have addressed this issue in fatal familial insomnia (FFI) measuring the cerebral metabolic rate of glucose (CMRglc) with 2-[18F]fluoro-2-deoxy-D-glucose PET in parallel with detailed clinical, neuropsychological examinations and polysomnography with EEG spectral analyses. Nine asymptomatic carriers of the D178N mutation, 10 non-carriers belonging to the same family, and 19 age-matched controls were studied over several years. The CMRglc as well as clinical and electrophysiological examinations were normal in all cases at the beginning of the study. Four of the mutation carriers developed typical FFI during the study but CMRglc and the clinical and electrophysiological examinations remained normal 63, 56, 32 and 21 months, respectively before disease onset. The carrier whose tests were normal 32 months before disease onset was re-examined 13 months before the onset. At that time, selective hypometabolism was detected in the thalamus while spectral-EEG analysis disclosed an impaired thalamic sleep spindle formation. Following clinical disease onset, CRMglc was reduced in the thalamus in all 3 patients examined. Our data indicate that the neurodegenerative process associated with FFI begins in the thalamus between 13 and 21 months before the clinical presentation of the disease.

Adult↗
PubMed2006

Polysomnographic and pharmacokinetic findings in levodopa-induced augmentation of restless legs syndrome.

Augmentation, defined as a loss of circadian recurrence with progressively earlier daily onset and increase in the duration, intensity, and anatomy of symptoms, not compatible with the half-life of the drug, is associated with dopaminergic treatment in restless legs syndrome (RLS) patients. The pathogenesis of augmentation is unclear. We describe a patient with idiopathic RLS who developed augmentation after 8 months of levodopa treatment. Videopolysomnographic and pharmacokinetic studies with monitoring of plasma levodopa levels demonstrated marked motor hyperactivity during augmentation, with anarchic discharges of motor unit potentials, tonic grouped discharges and flexor spasms, associated with painful dysesthesia. Symptoms and signs of augmentation were related to low plasma levodopa levels, abating 75 minutes after oral levodopa administration and reappearing after 3 hours, closely mirroring the rapid rise and fall of plasma levodopa concentration. This case is the first report in which RLS augmentation is shown to be characterized by motor hyperkinesias paralleling levodopa plasma pharmacokinetic profile.

Aged↗
PubMed2006

Mitochondrial neurogastrointestinal encephalomyopathy: evidence of mitochondrial DNA depletion in the small intestine.

BACKGROUND & AIMS: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disease clinically defined by gastrointestinal dysmotility, cachexia, ptosis, ophthalmoparesis, peripheral neuropathy, white-matter changes in brain magnetic resonance imaging, and mitochondrial abnormalities. Loss-of-function mutations in thymidine phosphorylase gene induce pathologic accumulations of thymidine and deoxyuridine that in turn cause mitochondrial DNA (mtDNA) defects (depletion, multiple deletions, and point mutations). Our study is aimed to define the molecular basis of gastrointestinal dysmotility in a case of MNGIE. METHODS: By using laser capture microdissection techniques, we correlated histologic features with mtDNA abnormalities in different tissue components of the gastrointestinal wall in a MNGIE patient and ten controls. RESULTS: The patient's small intestine showed marked atrophy and mitochondrial proliferation of the external layer of muscularis propria. Genetic analysis revealed selective depletion of mtDNA in the small intestine compared with esophagus, stomach, and colon, and microdissection analysis revealed that mtDNA depletion was confined to the external layer of muscularis propria. Multiple deletions were detected in the upper esophagus and skeletal muscle. Site-specific somatic point mutations were detected only at low abundance both in the muscle and nervous tissue of the gastrointestinal tract. Analysis of the gastrointestinal tract from 10 controls revealed a non-homogeneous distribution of mtDNA content; the small intestine had the lowest levels of mtDNA. CONCLUSION: Atrophy, mitochondrial proliferation, and mtDNA depletion in the external layer of muscularis propria of small intestine indicate that visceral myopathy is responsible for gastrointestinal dysmotility in this MNGIE patient.

Adult↗
PubMed2006

Nocturnal eating: sleep-related eating disorder or night eating syndrome? A videopolysomnographic study.

STUDY OBJECTIVES: To describe the clinical and videopolysomnographic characteristics of nocturnal eating episodes in sleep-related eating disorder. DESIGN: Descriptive study of outpatients prospectively enrolled in 2 sleep centers. SETTING: Videopolysomnographic recordings done in the sleep laboratory. PATIENTS: Thirty-five consecutive drug-free patients with nocturnal eating. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Clinical interviews disclosed abnormal compulsory nocturnal eating episodes in all patients associated with a clinical report of sleepwalking (in 1), somniloquy (in 5), restless legs syndrome (in 8), and periodic limb movements during sleep (in 4). Videopolysomnography documented 45 episodes of nocturnal eating in 26 patients. Eating always occurred after complete awakenings from non-rapid eye movement sleep and only in 1 patient from REM sleep and was characterized by electroencephalographic alpha activity with no dissociated features of state-dependent sleep variables. Patients interviewed during the eating episodes were fully conscious and remembered the events the next day. Pathological periodic limb movements during sleep index was recorded in 22 and restless legs syndrome dyskinesias in 5 patients. Recurring chewing and swallowing movements during sleep were a feature in 29 patients, associated in about half of the events with electroencephalographic arousals. CONCLUSIONS: In our patients, eating episodes occurred with normal consciousness and recall. Chewing or swallowing movements during sleep occurred frequently, resembling rhythmic masticatory-muscle activity in bruxism patients. The presence of periodic limb movements during sleep and chewing activity, the reported efficacy of dopaminergic medications, and the compulsory food-seeking behavior all argue for a dopaminergic dysfunction underlying the pathogenesis of sleep-related eating disorder.

Adult↗
PubMed2006

Autosomal dominant early-onset cortical myoclonus, photic-induced myoclonus, and epilepsy in a large pedigree.

PURPOSE: Cortical tremor, a form of rhythmic cortical myoclonus (rhythmic CM), and epilepsy have been described in families with autosomal dominant inheritance. Linkage analyses revealed two putative loci on chromosome 2p and 8q. Clinical photosensitivity was not a prominent feature in such families. We describe a large Italian family with rhythmic CM, photosensitivity, and epilepsy. METHODS: Twenty-three individuals of a five-generation family were studied. Linkage analyses for the loci on chromosome 2p11.1 and 8q23.3 were performed. RESULTS: Of the 23 studied family members, 16 were affected. Rhythmic CM of childhood onset was present in all 16 individuals (onset ranging from 3 to 12 years), was associated with photic-induced myoclonic jerks in seven, and with epileptic seizures in six (onset ranging from 23 to 34 years). Five children of the V generation manifested also episodes of arousal with generalized tremor in early infancy ("tremulous arousals"). Jerk-locked back-averaging of rhythmic CM of six affected individuals, documented a premyoclonic EEG correlate. C-reflex at rest was present in two affected adults. Linkage analyses excluded mapping to the 2p11.1 and 8q23.3 loci. CONCLUSIONS: Clinical variability and severity of the phenotypes in this family are in line with those of previously described pedigrees with autosomal dominant cortical myoclonus and epilepsy. In this family, a progression of symptoms was found: rhythmic CM and tremulous arousals occurred in childhood, whereas visually induced manifestations and epileptic seizures occurred during adolescence-adulthood. Exclusion of linkage to the two known loci is consistent with genetic heterogeneity of such familial clustering of symptoms.

Age of Onset↗
PubMed2006

Restless legs syndrome and periodic limb movements.

The history, clinical aspects, and treatment of restless legs syndrome (RLS), a heterogeneous distressing sensorimotor disorder, and periodic limb movements (PLMs) that are the typical motor accompaniment of the syndrome, are described. A positive family history, a positive response to dopaminergic treatment, and the presence of PLM while awake or asleep are supportive criteria for the diagnosis of the disorder. RLS and PLM occur more frequently at the beginning of night and exponentially decline across sleep cycles, suggesting circadian influences. Altered circadian rhythmicity in dopamine metabolism and enhanced circadian variations in dopaminergic functions have been reported in the disorder. Dysfunction or atrophy of A11 cells from the diencephalic-spinal dopamine A11 system has been suggested to explain the efficacy of dopaminergic drugs in relieving RLS symptoms and the circadian rhythmicity of RLS. Studies support the hypothesis that the A11 dopaminergic neurons and spinal pathways may be more involved in the pathophysiology of RLS than the nigrostriatal system. Neurophysiological evidence indicates that the involuntary movements in RLS may be of spinal or propriospinal origin. Despite these findings, however, the pathogenic mechanisms underlying the peculiar sensory and motor manifestations of RLS remain unexplained. Among the current treatment options offered for the treatment of RLS, dopaminergic agents have provided the best evidence for efficacy in symptom relief.

Circadian Rhythm↗
PubMed2005

Endozepines in recurrent stupor.

Stupor is a condition from which the subject can be aroused only by vigorous stimuli. Most patients with stupor have a diffuse organic cerebral dysfunction. Rarely stupor is recurrent and no specific causes can be found. Patients with idiopathic recurrent stupor were awakened by i.v. administration of an antagonist (flumazenil) of the benzodiazepine recognition site located in the GABA(A) receptor. Since no exogenous benzodiazepines were detected in plasma and cerebrospinal fluid by high performance liquid chromatography, an excess of endogenous benzodiazepine-like compounds (endozepines) was proposed as the cause of stupor. The existence of endozepines, their widespread distribution in the CNS and their involvement in hepatic encephalopathy are established. However, the origin of these compounds, how biosynthesis occurs and the mechanisms and causes through which they alter brain functions are poorly understood. The fact that a number of synthetic benzodiazepines are difficult to detect using conventional techniques and the discovery that some cases of recurrent stupor were caused by fraudulent administration of lorazepam question whether the concept of endozepine recurrent stupor can be sustained. This review summarizes the state of endozepine physiology and pharmacology and the clinical syndromes attributed to their involvement. A diagnostic work-up to define endozepine-induced recurrent stupor is suggested.

Coma↗
PubMed2005

NREM sleep alterations in narcolepsy/cataplexy.

OBJECTIVE: NREM sleep patterns of narcoleptic patients with cataplexy were studied, focusing on their sleep 'microstructure', by analyzing the cyclic alternating pattern (CAP). METHODS: Forty-nine HLA DQB1*0602-positive patients with narcolepsy/cataplexy (32 men and 17 women, aged 18-46 years) were included together with 37 age-matched normal controls. Each subject underwent one polysomnographic night recording after an adaptation night. Sleep stages were scored following standard criteria and CAP A phases were detected and classified into 3 subtypes (A1, A2, and A3). Power spectra for frequencies between 0.5 and 25 Hz were obtained for each CAP condition, separately in sleep stage 2 and SWS. RESULTS: Narcoleptic patients displayed reduced total CAP rate. A selective reduction in the number of A1 subtypes/hour and a reduced A3 index were found in narcoleptics who had also a smaller average number of CAP sequences. Narcoleptic patients had higher power spectra for fast frequencies mostly during SWS, while REM sleep power spectra showed significantly higher power density for frequency bins 0.5-1.5, 8.5-9.5, and 17.5-25 Hz. Similarly, CAP A1 subtypes and NCAP epochs during SWS displayed significantly higher power density for fast frequency bins. CONCLUSIONS: The main finding of this study is that the occurrence of the A1 CAP subtypes is impaired during NREM sleep in narcoleptic patients. Thus, narcolepsy seems to be accompanied not only by alterations of REM but also NREM sleep which is subtly but significantly impaired, as reflected by CAP and the corresponding EEG spectral analysis. SIGNIFICANCE: Our findings might indicate that in narcolepsy very-slow oscillation processes less effective than normal might be present, with a subtly impaired capability of grouping the other sleep EEG activities; this aspect deserves further insight in order to obtain a better understanding of its functional meaning.

Adult↗
PubMed2005

Continuous motor unit activity syndromes: a video-polysomnographic study.

OBJECTIVE: To ascertain the presence of abnormalities of sleep in patients with continuous motor unit activity with and without symptoms of central nervous system involvement. METHODS: Five patients with isolated neuromyotonia (Isaacs' syndrome) and 1 patient with Morvan syndrome underwent 24-h videopolysomnographic recording to investigate sleep structure, motor activities and autonomic variables during sleep. RESULTS: Macro- and microstructural organization of sleep and of the attending autonomic variables were substantially normal in patients with Isaacs' syndrome. On the contrary, sleep structure was severely disrupted with subcontinuous dream enactment and hallucinations in the patient with Morvan syndrome. The pattern of the neuromyotonic discharges, however, was not different between the patients with Isaacs' syndrome compared to Morvan syndrome, the EMG discharges persisting throughout the 24 h of recording and affecting wakefulness and sleep equally. CONCLUSIONS: Neuromyotonia is compatible with normal organization of sleep. The severe sleep abnormalities observed in Morvan syndrome cannot be simply attributed to the effects of neuromyotonia of peripheral origin. SIGNIFICANCE: Even though neuromyotonia is common to both Isaacs' and Morvan syndromes, the two conditions differ significantly in regard to CNS involvement with sleep abnormalities and lumping the two conditions together is not justified on clinical and neurophysiological grounds.

Adolescent↗
PubMed2005

Habituation of sympathetic sudomotor and vasomotor skin responses: neural and non-neural components in healthy subjects.

OBJECTIVE: Sympathetic skin response (SSR) and skin vasomotor response (SVR) habituation was thought to be induced by neural mechanisms. Here, we investigate the hypothesis that non-neural mechanisms could also be involved. METHODS: We recorded sympathetic skin nerve activity (SSNA) from median nerve by microneurography and the corresponding SSR and SVR in 16 healthy subjects. Superficial electrical stimulation of the opposite median nerve was used to induce arousal responses. RESULTS: Throughout stimulation, SSNA, SSR and SVR amplitude showed a significant reduction. During the first ten stimuli, SSNA showed a marked decrease highly correlated to SSR and SVR changes. During the subsequent 20 stimuli SSNA did not change whereas SSR and SVR significantly decreased. SVR was significantly influenced by skin temperature changes. CONCLUSIONS: Both neural and non-neural mechanisms are involved in SSR and SVR habituation. The neural mechanisms were predominant during the first part of stimulation whereas non-neural mechanisms prevailed during the last part of stimulation. SIGNIFICANCE: During repeated arousal stimuli SSR and SVR amplitude changes did not reflect the strength of the corresponding sympathetic nerve traffic and must be interpreted with caution.

Adult↗
PubMed2005

Interobserver reliability of ICSD-R minimal diagnostic criteria for the parasomnias.

OBJECTIVE: To estimate the interobserver reliability (IR) of the minimal diagnostic criteria for the parasomnias provided in the International Classification of Sleep Disorders Revised (ICSD-R). METHODS: Fifty consecutive subjects underwent a structured interview by three doctors based on the ICSD-R minimal criteria for the diagnosis of 13 parasomnias at any time in life. IR was calculated by Kappa statistics and interpreted according to conventional categories. RESULTS: In the group of Arousal Disorders, IR was "substantial" (kappa 0.74) for confusional arousals, "slight" (kappa 0.36) for sleepwalking, "fair" (kappa -0.02) for sleep terrors. In the group of Wake-Sleep Transition Disorders, IR was "substantial" to "almost perfect", but "moderate" for sleep starts (kappa 0.41). In the group of Parasomnias usually associated with REM Sleep, IR was "substantial" (kappa 0.69) for sleep paralysis, "moderate" (kappa 0.46) for RBD, "fair" (kappa 0.25) for nightmares. In the group of Other Parasomnias, IR was "substantial" to "almost perfect" (kappa between 0.73 and 0.93). CONCLUSIONS: When the clinical diagnosis of parasomnias is based on the ICSD-R: 1) the majority of Arousal Disorders and REM sleep parasomnias showed only a "fair" to "moderate" IR; 2) all of the other parasomnias showed a "substantial" to "almost perfect" IR. Nosological entities with unsatisfactory IR share complex motor phenomenology associated with a mental state difficult for the patient to define. The source of disagreement probably lies in the difficulty in interpreting patients' reports. For these parasomnias IR must be verified and possibly improved with training.

Adolescent↗
PubMed2005

Novel parkin mutations detected in patients with early-onset Parkinson's disease.

A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.

Adolescent↗
PubMed2005

Propriospinal myoclonus: a motor phenomenon found in restless legs syndrome different from periodic limb movements during sleep.

Three patients presented with a 25-, 15-, and 5-year history of restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS). For 1, 4, and 5 years, they reported additional involuntary trunk and limbs jerks preceding falling asleep and occasionally during intrasleep wakefulness. Videopolysomnography revealed jerks during relaxed wakefulness arising in axial muscles with a caudal and rostral propagation at a slow conduction velocity, characteristic of propriospinal myoclonus (PSM). Jerk-related EEG-EMG back-averaging did not disclose any preceding cortical potential. During relaxed wakefulness preceding falling asleep and during intrasleep wakefulness, PSM coexisted with motor restlessness and sensory discomfort in the limbs. PSM disappeared when spindles and K-complexes appeared on the EEG. At this time, typical PLMS appeared every 20 to 40 seconds, especially during light sleep stages. PLMS EMG activity was limited to leg, especially tibialis anterior muscles, and did not show propriospinal propagation. In one patient, alternating leg muscle activation was also present. Jerks with a PSM pattern represent another motor phenomenon associated with RLS and different from the more usual PLMS.

Adult↗