Biomedical subjects

Pasquale Montagna

Publications and source records attributed to Pasquale Montagna.

At least 37 records · Page 2Linked to original sources

PubMed2005

Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy.

PURPOSE: To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (StratusOCT) in patients with Leber's hereditary optic neuropathy (LHON). DESIGN: Cross-sectional study. PARTICIPANTS AND/OR CONTROLS: Thirty-eight patients with LHON were analyzed and compared with an age-matched control group of 75 patients. Patients with LHON were classified as having early LHON (E-LHON, n = 8) when the duration of the disease was shorter than 6 months and atrophic LHON (A-LHON, n = 30) when the duration was longer than 6 months. METHODS: The fast RNFL thickness (3.4) scan acquisition protocol was used. MAIN OUTCOME MEASURE: Retinal nerve fiber layer thickness as measured by StratusOCT. RESULTS: Compared with the control group, eyes with E-LHON showed a thicker RNFL in the 360 degrees average measurement (P<0.01) and in the superior (P<0.01), nasal (P<0.05), and inferior quadrants (P<0.05); no significant changes were detected in the temporal quadrant. Eyes with A-LHON revealed a thinner RNFL in all measurements (P<0.001); the fibers of the nasal quadrant showed the lowest amount of reduction (38% vs. 42%-49.8% in the other quadrants). In cases with A-LHON and visual recovery, RNFL was significantly thicker in all measurements (P<0.001), except the temporal quadrant, with respect to A-LHON without visual recovery. CONCLUSIONS: On the basis of OCT data, the RNFL is thickened in E-LHON and severely thinned in A-LHON. RNFL is likely to be partially preserved in A-LHON with visual recovery. The temporal fibers (papillomacular bundle) are the first and most severely affected; the nasal fibers seem to be partially spared in the late stage of the disease.

Acute Disease↗

PubMed2005

Retinal nerve fiber layer evaluation by optical coherence tomography in unaffected carriers with Leber's hereditary optic neuropathy mutations.

PURPOSE: To study retinal nerve fiber layer (RNFL) thickness by optical coherence tomography (OCT) in unaffected carriers with Leber's hereditary optic neuropathy (LHON) mutations. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-six unaffected carriers (44 females and 22 males) were analyzed and compared with an age-matched control group of 70 patients (40 females and 30 males). The statistical analysis was performed after grouping both the patients and the control group on the basis of gender and, for unaffected carriers only, mitochondrial DNA mutation. METHODS: The Fast RNFL Thickness (3.4) scan acquisition protocol was used. MAIN OUTCOME MEASURE: Retinal nerve fiber layer thickness as measured by OCT. RESULTS: With respect to the control group, unaffected male carriers showed a thicker RNFL in the temporal and inferior quadrants and in the 360 degrees average measurement (P = 0.025, P = 0.03, and P = 0.018, respectively). These differences reached statistical significance in subjects carrying the 11778 mutation, whereas only a trend was detected in those with the 3460 mutation. Unaffected female carriers had an increased thickness in the temporal quadrant when compared with the control group (P = 0.003) and no differences in the other measurements. The increase in temporal sectors was statistically significant in females with the 11778 mutation, whereas a trend was detected in those with the 3460 mutation. CONCLUSIONS: A thickening of the temporal fibers was detected in all subgroups of unaffected carriers. This is the first evidence indicating the preferential involvement of the papillomacular bundle in subclinical LHON. This notion previously was based on the early loss of fibers from the temporal quadrant in acute LHON and the selective loss of small-caliber fibers at histopathology. Our study also revealed that males have a more diffuse involvement than females.

Adolescent↗

PubMed2005

Fatal familial insomnia: a model disease in sleep physiopathology.

Fatal Familial Insomnia (FFI) is characterized by loss of sleep, oneiric stupor with autonomic/motor hyperactivity and somato-motor abnormalities (pyramidal signs, myoclonus, dysarthria/dysphagia, ataxia). Positon emission tomography (PET) disclosed thalamic hypometabolism and milder involvement of the cortex; neuropathology severe neuronal loss in the thalamic nuclei variably affecting the caudate, gyrus cinguli and fronto-temporal cortices. Genetic analysis disclosed a mutation in the PRNP gene and FFI was transmitted to experimental animals, thus classifying FFI within the prion diseases. Rare Sporadic Fatal Insomnia (SFI) cases occur without PRNP mutation but with features similar to FFI. FFI represents a model disease for the study of sleep-wake regulation: (I) the profound thalamic hypometabolism/atrophy associated with lack of sleep spindles and delta sleep implicate the thalamus in the origin of slow wave sleep (SWS); (II) loss of SWS is associated with marked autonomic and motor hyperactivity; termed 'agrypnia excitata', this association has been proposed as a useful clinical concept representative of thalamo-limbic dysfunction; (III) lack of SWS occurs with substantial preservation of stage 1 NREM sleep, implying that the latter has mechanisms different from SWS and unaffected by thalamic atrophy; accordingly, conflating stage 1 NREM with SWS into NREM sleep is inappropriate.

Adult↗

PubMed2004

Ocular findings in mitochondrial neurogastrointestinal encephalomyopathy: a case report.

PURPOSE: To describe the ocular features of a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) due to a homozygous G1443A mutation in the thymidine-phosphorylase gene. METHODS: A case report with extensive ophthalmological investigation over a 9-year period, until death at age 38 years. Measures used included standard ophthalmological examination, visual field examination and optical coherence tomography (OCT). RESULTS: Ptosis and external ophthalmoplegia progressively worsened during the follow-up, as did the neurological and general status. Corneal and optic disc alterations were also observed at the last visit. Glaucomatous changes of the optic disc were confirmed by the visual field examination and OCT. CONCLUSION: In addition to previously described alterations such as ptosis and external ophthalmoplegia, MNGIE may be associated with glaucomatous-like optic neuropathy.

Adult↗

PubMed2004

Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism.

Two homozygous mutations in the PINK1 gene, encoding a mitochondrial putative protein kinase, recently have been identified in families with PARK6-linked, autosomal recessive early-onset parkinsonism (AREP). Here, we describe a novel homozygous mutation (1573_1574 insTTAG) identified in an AREP patient, which causes a frameshift and truncation at the C-terminus of the PINK1 protein, outside the kinase catalytic domain. The clinical phenotype includes early-onset (28 years) parkinsonism, foot dystonia at onset, good levodopa response, slow progression, early levodopa-induced dyskinesias, and sleep benefit, thereby resembling closely parkin-related disease. These findings confirm that recessive mutations in PINK1 cause early-onset parkinsonism and expand the associated clinical phenotype.

Adult↗

PubMed2004

Status dissociatus after surgery for tegmental ponto-mesencephalic cavernoma: a state-dependent disorder of motor control during sleep.

After surgery for a tegmental ponto-mesencephalic cavernoma, a patient developed sleep-related excessive fragmentary myoclonus, diffuse myoclonic jerks, simple quasipurposeful movements of the limbs, and rapid eye movement (REM) sleep behaviour disorder as motor features of status dissociatus, a condition in which elements of one state of being (wake, NREM and REM sleep) pathologically intrude into another.

Adult↗

PubMed2004

Sleep-related non epileptic motor disorders.

Sleep-related non epileptic motor disorders represent a frequent but often neglected or trivialized source of neurological disability. In recent decades, the widespread adoption of videopolygraphic techniques has better characterized already known nosographic entities and described a bewildering variety of previously unrecognized clinical entities (such as REM sleep behaviour disorder, sleep-related eating disorder, benign neonatal sleep myoclonus, facio-mandibular myoclonus during sleep, fragmentary hypnic myoclonus, propriospinal myoclonus at the wake-sleep transition, rhythmic feet movements during sleep, etc). The scope of the neurophysiological investigations of sleep related disorders has therefore been much expanded. However, advances in the semeiology and clinical description of sleep-related movement disorders has rarely been matched by adequate understanding of the underlying pathophysiological mechanisms, or by major advances in treatment. The main sleep-related motor disorders are described here, following the only classification currently available, e. g. that offered by the International Sleep Disorders Classification of the American Sleep Disorders Association, which is more a classification of diseases of sleep than of movement disorders. The increasing use of functional neuroimaging in vivo and of updated neurophysiological and molecular techniques in man and in the experimental animal will hopefully lead to a better understanding of these disorders in terms of pathophysiology of disordered motor control.

Central Nervous System↗

PubMed2004

Sleep disorders in multiple system atrophy: a correlative video-polysomnographic study.

OBJECTIVE: The reciprocal relation between breathing, heart and motor system abnormalities during sleep was studied in multiple system atrophy (MSA) by means of video-polysomnographic recordings (VPSG). PATIENTS AND METHODS: Nineteen consecutive MSA patients underwent VPSG with scoring for sleep, respiratory abnormalities, heart (HR) and breathing (BR) rates, and abnormal motor activities. A comparative analysis was performed versus 10 patients with obstructive sleep apnoea syndrome (OSAS). RESULTS: All MSA patients displayed snoring, 42% stridor, and 37% OSAS. Mean sleep SaO(2) was 92.7%, and lowest SaO(2) 86%. Patients with stridor had a significant increase in BR from Wake to NREM and REM sleep, and higher HR during sleep. Respiratory muscles and tibialis anterior EMG tonic activity was frequently found, more often in patients with stridor. All patients had REM sleep behaviour disorders (RBD) and 88% periodic limb movements during sleep (PLMS). No OSAS patient had RBD or respiratory muscles and tibialis anterior tonic activity. CONCLUSIONS: MSA patients, especially those with associated stridor, commonly display impaired breathing and abnormal control of respiratory and limb muscles during sleep. Breathing and motor abnormalities are often concomitant in the same patient, indicating a diffuse impairment of sleep homeostatic integration that should be included within the diagnostic features of MSA.

Adult↗

PubMed2003

Investigation of an LDLR gene polymorphism (19p13.2) in susceptibility to migraine without aura.

We performed a genetic association study with the LDL receptor gene (LDLR) on chromosome 19p13.2 in 360 migraine patients, 220 with migraine without aura (MO) and 140 with migraine with aura (MA), and 200 controls, by analysing two polymorphic markers, a G142A transition in exon 10 and a triallelic (TA)n repeat in exon 18. The allelic distribution of the (TA)n polymorphism was significantly different between migraine without aura (MO) and both controls and migraine with aura (MA). We suggest a possible predisposition to MO in the studied population through this polymorphism or another polymorphism in linkage disequilibrium with (TA)n.

Adolescent↗

PubMed2003

Emotional information processing in patients with narcolepsy: a psychophysiologic investigation.

OBJECTIVES: Cataplexy is the key symptom of the narcoleptic syndrome. It is usually triggered by emotions, which play an important role in the manifestation and severity of the disease. Accordingly, we compared the psychophysiologic effects on patients with narcolepsy and healthy subjects of processing visual stimuli that have established emotional valences. METHOD: Eight drug-free patients with narcolepsy with severe cataplexy and 8 controls were studied. Fifty-four color pictures (pleasant, neutral, and unpleasant) selected from the International Affective Picture System were presented on a monitor to the subjects. The effects of exposure to the pictures were assessed in muscular (corrugator, zygomatic and mylohyoid electromyographic activity), autonomic (blood pressure, heart rate, and skin conductance responses) cognitive (scalp-recorded event-related potentials), and subjective (valence, arousal, and dominance by Self-Assessment Manikin) systems. RESULTS: The autonomic, muscular, and cognitive systems showed an attenuated reaction to visual stimuli in patients compared to controls. Furthermore, patients with narcolepsy showed the lowest responses when unpleasant pictures were presented. CONCLUSIONS: Our data suggest that, compared to the group of healthy subjects, patients with narcolepsy suffer from a temporal disadvantage in input processing, in particular, of unpleasant stimuli. The drawback exhibited by these patients suggests reduced reactivity of the aversive motivational system responsible for negative or unpleasant emotions.

Adult↗

PubMed2003

Pelvic movements as rhythmic motor manifestation associated with restless legs syndrome.

Video-polysomnographic monitoring of a patient with a 4-year history of an unpleasant restless sensation originating in his lower abdomen showed stereotyped, repetitive, rhythmic pelvic body movements resembling coital behaviour at the wake-sleep transition. We discuss the association between restless legs syndrome and rhythmic movement disorder as a particular manifestation of a spectrum of rhythmic sleep-related movement disorders.

Abdominal Muscles↗

PubMed2003

Sympathetic skin response: basic mechanisms and clinical applications.

Sympathetic skin response (SSR), defined as the momentary change of the electrical potential of the skin, may be spontaneous or reflexively evoked by a variety of internal or by externally applied arousal stimuli. Although the suprasegmental structures influencing the SSR in humans are not well known, SSR has been proposed as a non-invasive approach to investigate the function of the sympathetic system. SSR is easy to apply but current procedures are not sufficiently reliable for diagnostic purposes, and show imperfect correlations both with clinical features and other measurements of autonomic, in particular, sudomotor dysfunction.

Animals↗

PubMed2003

Familial and sporadic fatal insomnia.

Familial fatal insomnia (FFI)--a hereditary prion disease caused by a mutation at codon 178 of the prion-protein (PrP) gene (PRNP) that leads to a D178N substitution in the protein--and its sporadic form, sporadic fatal insomnia (SFI), have similar disease phenotypes. Both disorders have clinical features of disrupted sleep (loss of sleep spindles and slow-wave sleep and enacted dreams during rapid-eye-movement sleep), autonomic hyperactivation, and motor abnormalities (myoclonus, ataxia, dysarthria, dysphagia, and pyramidal signs). PET shows pronounced thalamic and limbic hypometabolism that becomes more widespread in later stages. Neuropathological assessment reveals severe neuronal loss and astrogliosis of the anterior medial thalamus and inferior olives, with later cerebral cortical and cerebellar involvement. Accumulation of an isoform of protease-resistant PrP fragment in FFI distinct from that found in a familial form of Creutzfeldt-Jakob disease with the same D178N mutation, shows the effect of the polymorphism at codon 129 of PRNP on phenotypic expression and the possibility of distinct prion "strains" with diverse pathological potential. Intriguing clinicopathological correlations in FFI and SFI suggest a role for the thalamolimbic system in the regulation of sleep and other circadian functions.

Amyloid↗

PubMed2003

Novel spastin mutations and their expression analysis in two Italian families.

Mutations in spastin cause the most common form of pure autosomal dominant hereditary spastic paraparesis (SPG4). Here, we report two Italian families affected with SPG4-linked HSP harboring two novel spastin mutations. SSCP/sequencing analysis of the spastin gene showed a single base pair deletion causing a frame-shift in one family (1442delT) and a missense mutation (1726T>C) resulting in a leucine to proline amino-acid change (L534P) in the other family. Total RNA from the mutant and the wild-type spastin allele in muscle biopsies from patients from the two affected families was quantitated. RNA expression was almost absent from the spastin allele harboring the single base pair deletion, while it was nearly normal for the spastin allele harboring the missense mutation. These data suggest that varying spastin RNA levels are found in out-of-frame and missense spastin mutations and imply different mechanisms involved in the molecular pathology of SPG4 linked HSP.

Adenosine Triphosphatases↗

PubMed2002

Biochemical-clinical correlation in patients with different loads of the mitochondrial DNA T8993G mutation.

OBJECTIVE: To investigate the correlation between biochemical and clinical phenotype in 6 patients from 3 unrelated families with different mutation loads (heteroplasmy) of the T8993G mitochondrial DNA mutation associated with neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. METHODS: We studied adenosine triphosphate (ATP) synthase activity (synthesis and hydrolysis) in platelet-derived submitochondrial particles and assessed mutant loads both in platelets used for biochemical analysis and in other available tissues. Biochemical and molecular results were correlated with clinical features. RESULTS: The rate of ATP hydrolysis was normal, but ATP synthesis was severely impaired (30% to 4% of residual activity) in patients harboring 34% to 90% mutant mitochondrial DNA, without any evidence of a threshold for the expression of this defect. There was little variation in heteroplasmy among tissues from each patient, but wider variability was detected in 2 mothers. Correlation of heteroplasmy and clinical and biochemical features suggested that ATP synthesis is defective at mutant loads as low as 34% and is extremely reduced at mutant loads above 80% when the phenotype is neuropathy, ataxia, and retinitis pigmentosa-Leigh syndrome. CONCLUSIONS: This study indicates a close relationship between tissue heteroplasmy, expression of the biochemical defect in platelets, and clinical involvement. The biochemical defect was greater than previously reported, and we found no evidence of a biochemical threshold. The uniform distribution of high mutant loads among our patients' tissues suggests a differential tissue-specific reliance on mitochondrial ATP synthesis.

Adenosine Triphosphate↗

PubMed2002

Localization of autosomal recessive early-onset parkinsonism to chromosome 1p36 (PARK7) in an independent dataset.

Two new loci, PARK6 and PARK7, for autosomal recessive early-onset parkinsonism have recently been identified on chromosome 1p, in single large pedigrees. Among 4 autosomal recessive early-onset families analyzed here, 2 supported linkage to PARK7, 1 with conclusive evidence. These data confirm localization of autosomal recessive early-onset parkinsonism to PARK7, suggesting it to be a frequent locus. Assignment of families to either PARK6 or PARK7 might be difficult because of the proximity of the two loci on chromosome 1p.

Adult↗

PubMed2002

The circadian rhythm of body core temperature (CRT) is normal in patient with congenital generalized anhidrosis.

The temperature of the human body is not constant during the day, and is related to a double modulation of both homeostatic and circadian processes. The circadian rhythm of body core temperature (CRT) is known to depend on the central mechanism involved in thermoregulatory variations. The role of sweating in the nocturnal fall of body core temperature (BcT) is not clear. We evaluated the CRT in a 45-year-old female with a lack of sweating since birth because of congenital generalized anhidrosis. She referred episodes of heat intolerance when ambient temperature was around 35 degrees C. Skin biopsies of both forearms and left axilla revealed atrophy and morphologic changes of eccrine glands. Neurological examination, nerve conduction studies, sympathetic skin response and cardiovascular reflex tests were normal. The study of CRT was performed by monitoring rectal temperature continuously in controlled conditions (ambient temperature 24 +/- 1 degrees C and humidity 40-50% in a light-dark schedule). The rhythmometric analysis showed normal 24-hour fluctuations. This case represents an "experiment of nature"demonstrating that the physiological nocturnal fall of BcT is independent of sweating.

Body Temperature↗

PubMed2002

Does the prion protein gene 129 codon polymorphism influence sleep? Evidence from a fatal familial insomnia kindred.

OBJECTIVE: Experimental and clinical evidence in prion diseases suggests that the prion protein gene (PRNP) plays a role in regulating sleep. METHODS: Seventeen healthy individuals belonging to a single fatal familial insomnia pedigree, 8 carriers and 9 non-carriers of the PRNP codon 178 mutation, underwent polysomnography and spectral electroencephalographic (EEG) analysis. All were also characterized with regard to the codon 129 polymorphism on both PRNP alleles. RESULTS: PRNP codon 129 polymorphism exhibited influences on sleep-EEG activities. In particular, spindle frequency band power and balance between delta and spindle activity were found to correlate with the genotype of PRNP codon 129, irrespective of the mutation at codon 178. CONCLUSIONS: Our data suggest that PRNP codon 129 polymorphism may also affect sleep in the healthy population and warrant further studies in the general population and other sleep disorders.

Adult↗