Multiple sclerosis-like disease in polyglandular autoimmune syndrome.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
P Cortelli
Publications and source records attributed to P Cortelli.
Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a spectral analysis study.
OBJECTIVES: Fatal familial insomnia (FFI) is linked to a mutation at codon 178 (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by selective atrophy of the anteroventral and mediodorsal thalamic nuclei and clinically by loss of sleep, dysautonomia and motor signs. A key early polysomnographic sign of the disease onset is the loss of sleep spindling (sigma activity, SA). In FFI the loss of SA leads to the spectral representation of a sudden slow wave activity (SWA) increase from an awake state, the reaching of a stable plateau without oscillations, followed by abrupt fall down to REM sleep. We evaluated the presence of differences in the spectral sleep EEG pattern in FFI relatives carriers (C178(pos)) or non-carriers (C178(neg)) of the C178 mutation. METHODS: Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI mutation in a preclinical condition and 9 non carriers, underwent two-night polysomnography. The absolute and relative EEG power of the 4 main bands (delta: SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; sigma: SA, 12.5-16 Hz) has been studied for the total sleep time, the period of delta increase after sleep onset, and the period of delta plateau. Multiple regression has been applied to investigate relations between the power of the bands studied and 3 parameters: age, the gender of the subjects and the C178 genotype. RESULTS: Our study could not show evidence of differences in the sleep EEG composition between carriers and non-carriers of the C178 FFI mutation. CONCLUSIONS: The spectral analysis techniques we used were not able to disclose sleep EEG markers linked to the FFI C178(pos) in the preclinical condition. Key sleep EEG alteration become evident only at the clinical onset of the disease.
Adult↗
Ictal bradycardia in partial epileptic seizures: Autonomic investigation in three cases and literature review.
Ictal bradycardia is a rare, probably underestimated, manifestation of epileptic seizures whose pathophysiology is still debated. Autonomic modifications may result either from a sympathetic inhibition or from a parasympathetic activation probably due to the ictal discharge arising from or spreading to the structures of the central autonomic network. We review 60 cases of ictal bradycardia from the available literature and present three additional cases associated with left temporal lobe seizures studied by autonomic polygraphic ictal monitoring. Only 47 of the 63 reported cases were documented by simultaneous EEG and ECG recordings during an attack. About 76% of patients in whom well-localized ictal discharges were recorded had temporal or frontotemporal lobe seizures. Forty-five cases included information allowing confident localization of the side of ictal onset, and a 26 : 19 ratio of the left versus right side was evident. Simultaneous monitoring of ECG and other autonomic parameters during EEG recording in partial seizures should be performed to gain more insight into ictal semiology. Correlation of the symptoms referred to by patients with changes in autonomic parameters could avoid erroneous diagnosis of non-epileptic attacks and disclose a potentially lethal condition. Our cases confirm the preferential role of the left hemisphere in the genesis of ictal bradycardia and shed light on the relationship between suprabulbar control of autonomic function and partial epileptic seizures.
Adult↗
Morvan's syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels.
Morvan's 'fibrillary chorea' or Morvan's syndrome is characterized by neuromyotonia (NMT), pain, hyperhydrosis, weight loss, severe insomnia and hallucinations. We describe a man aged 76 years with NMT, dysautonomia, cardiac arrhythmia, lack of slow-wave sleep and abnormal rapid eye movement sleep. He had raised serum antibodies to voltage-gated K(+) channels (VGKC), oligoclonal bands in his CSF, markedly increased serum norepinephrine, increased serum cortisol and reduced levels and absent circadian rhythms of prolactin and melatonin. The neurohormonal findings and many of the clinical features were very similar to those in fatal familial insomnia, a hereditary prion disease that is associated with thalamic degenerative changes. Strikingly, however, all symptoms in our MFC patient improved with plasma exchange. The patient died unexpectedly 11 months later. At autopsy, there was a pulmonary adenocarcinoma, but brain pathology showed only a microinfarct in the hippocampus and no thalamic changes. The NMT and some of the autonomic features are likely to be directly related to the VGKC antibodies acting in the periphery. The central symptoms might also be due to the direct effects of VGKC antibodies, or perhaps of other autoantibodies still to be defined, on the limbic system with secondary effects on neurohormone levels. Alternatively, changes in secretion of neurohormones in the periphery might contribute to the central disturbance. The relationship between VGKC antibodies, neurohormonal levels, autonomic, limbic and sleep disorders requires further study.
Aged↗
Magnetic resonance spectroscopy of episodic ataxia type 2 and migraine.
Explore the source record for details and available documents.
Ataxia↗
Efficacy and tolerability of sumatriptan in the treatment of multiple migraine attacks.
This cross-over, double blind, randomized, multicentre study evaluated the consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The patients received 50 mg oral sumatriptan or placebo for the treatment of 12 migraine attacks. Within each group of 4 attacks, three were treated with sumatriptan and one with placebo, according to a randomization list. Over all the attacks, the efficacy rate was statistically significant for sumatriptan against placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at relieving the associated symptoms and at reducing clinical disability in most attacks. The incidence of adverse events did not differ between treatment groups. All the events recorded were mild to moderate as intensity and resolved spontaneously.
Adolescent↗
Cardiovascular autonomic function in patients with primary achalasia.
Impaired gastrointestinal function outside the esophagus has been found in achalasic patients. Moreover, achalasia may occur in diseases in which a systemic dysautonomia is evident. These findings raise the question of whether a generalized subclinical alteration of autonomic control is also present in primary achalasia. Cardiovascular reflex tests and power spectral analysis of heart rate variability were studied in patients with primary achalasia to establish whether autonomic nervous system changes are present in districts other than the gastrointestinal tract. Nineteen normotensive patients with untreated primary achalasia and with no history of cardiac, renal, or endocrinological diseases were examined. Cardiovascular reflex tests included: the tilt test (10 min at 65 degrees), Valsalva maneuver (40 mm Hg for 15 sec), deep breathing (6 breaths/min), and sustained handgrip (30% of maximal effort for 5 min). The parameters evaluated were systolic and diastolic blood pressure (continuously recorded), ECG, oronasal and thoracic respiration, tachogram, and plethysmogram. To evaluate the balance between parasympathetic and sympathetic functions, power spectral analysis of the heart rate variability was carried out. Each patient was paired with two sex- and age-matched healthy controls. In achalasic patients the head-up tilt test, Valsalva maneuver, deep breathing test, and sustained handgrip did not show significant differences from the control group. Low-frequency (LF) and high-frequency (HF) spectral powers and the ratio of LF to HF did not differ in both groups. This study failed to disclose impaired cardiovascular autonomic control in achalasic patients. We suggest that in primary achalasia the defect is limited to the gastrointestinal tract.
Adult↗
alpha2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity.
BACKGROUND: Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropeptides and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN: In this study, we investigated the effects of pre-treatment with an alpha2-adrenoceptor agonist, clonidine (2 microg/kg over 10 minutes) and antagonist, yohimbine (0.125 mg/kg bolus, followed by 0. 001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol response to combined CRH (human, 100 microg) plus AVP (0.3 IU) administration, and on noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese women with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and in nonobese controls. RESULTS: During the control CRH + AVP test the ACTH but not the cortisol response was higher (P < 0.05) in obese A-BFD women than in controls, with minor and transient variations of NA levels. Neither the control test nor clonidine or yohimbine influenced basal or post CRH + AVP A concentrations. Clonidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH response to CRH + AVP. Conversely, during yohimbine infusion NA levels steadily and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS: This study shows that alpha2-adrenoceptor regulation of the HPA axis is different in obese and nonobese women, particularly in stressed conditions. We suggest that the abnormal ACTH response to CRH + AVP challenge with increased noradrenergic tone may represent a specific pathophysiological aspect of the abnormal response to stress or to other specific stimulatory factors in obese women, particularly those with abdominal body fat distribution.
Adrenergic alpha-Agonists↗
'Secondary' 4216/ND1 and 13708/ND5 Leber's hereditary optic neuropathy mitochondrial DNA mutations do not further impair in vivo mitochondrial oxidative metabolism when associated with the 11778/ND4 mitochondrial DNA mutation.
The pathogenic role of 'secondary' mitochondrial DNA (mtDNA) point mutations, when occurring in patients with Leber's hereditary optic neuropathy (LHON) in association with 'primary' mutations, is still controversial. We used phosphorus magnetic resonance spectroscopy to establish whether two of these 'secondary' LHON mtDNA mutations, 4216/ND1 and 13708/ND5 (haplogroup J), further affect in vivo mitochondrial oxidative metabolism in subjects with the 'primary' 11778/ND4 mtDNA mutation. Brain and skeletal muscle energy metabolism was assessed in 10 subjects homoplasmic for the 11778/ND4 mtDNA mutation and 10 subjects homoplasmic for the same mutation occurring on the haplogroup J mtDNA background. Brain phosphocreatine concentration and phosphorylation potential were significantly reduced and brain inorganic phosphate concentration was significantly increased compared with controls in both groups of 11778/ND4-positive subjects. The degree of reduction in the phosphocreatine concentration and phosphorylation potential and of increase in the inorganic phosphate concentration was, however, similar in the two groups with the 11778/ND4 mtDNA mutation with or without the haplogroup J. Similarly, the rate of muscle phosphocreatine resynthesis after exercise, a sensitive index of the rate of mitochondrial ATP production, was reduced by the same extent in both groups of LHON subjects. This in vivo study does not support synergism of the 4216/ND1 and 13708/ND5 'secondary' mutations with the 11778/ND4 'primary' mutation in determining the deficit of energy metabolism in LHON.
Adult↗
Phosphorus magnetic resonance spectroscopy in multiple system atrophy and Parkinson's disease.
We performed in vivo phosphorus magnetic resonance spectroscopy on the occipital lobes of 15 patients with multiple system atrophy (MSA; eight with olivopontocerebellar atrophy [OPCA] and seven with the striatonigral degeneration variant [SND]), 13 patients with idiopathic Parkinson's disease (PD), and 16 age-matched healthy subjects. The MSA group showed significantly reduced phosphocreatine (PCr), increased inorganic phosphate (Pi), and unchanged cytosolic free [Mg2+], and pH. We did not find any significant difference between the OPCA and SND variants. However, patients with PD showed significantly increased content of Pi, decreased cytosolic free [Mg2+], and unchanged [PCr] and pH. Comparing the MSA and PD groups, [PCr] was significantly lower in MSA than in PD, whereas cytosolic free [Mg2+] was significantly lower in PD. Despite a certain degree of overlap of [PCr] and [Mg2+] values between the two groups, by considering both variables at the same time it was possible to classify correctly 93% of cases by discriminant analysis. We conclude that phosphorus magnetic resonance spectroscopy discloses abnormal phosphate metabolite and ion contents in both MSA and PD, respectively, and may provide noninvasive diagnostic help to differentiate MSA from PD.
Adult↗
The autonomic nervous system and cluster headache.
Explore the source record for details and available documents.
Autonomic Nervous System↗
Fatal familial insomnia: clinical features and molecular genetics.
Fatal familial insomnia (FFI) is an autosomal dominant prion disease clinically characterized by inattention, sleep loss, dysautonomia, and motor signs and pathologically characterized by a preferential thalamic degeneration. FFI is linked to a missense mutation at codon 178 of the prion protein gene, PRNP, coupled with the presence of the codon methionine at position 129, the locus of a methionine-valine polymorphism. Homozygotes at codon 129, expressing methionine also in the nonmutated allele, have a shorter disease course (often less than 1 year), prominent sleep and autonomic disturbances at disease onset, and pathology restricted to the thalamus. Heterozygotes at codon 129, expressing valine in the nonmutated allele, have a longer disease course (often longer than 1 year), ataxia and dysarthria at disease onset, and lesions widespread to cerebral cortex. Both in the thalamus and in the cortex, the limbic structures are those most consistently and severely involved: the anterior ventral and mediodorsal thalamic nuclei, the cingulate gyrus, and the orbitofrontal cortex. FFI is thus a prion disease selectively damaging the thalamocortical limbic structures. Loss of sleep, sympathetic hyperactivity, and flattening of vegetative and hormonal circadian oscillations characterize FFI and result from a homeostatic imbalance caused by the interruption of the thalamocortical limbic circuits, the phylogenetically most advanced structures involved in the control of the sleep-wake cycle and the body's homeostasis. The selective atrophy of the limbic thalamus that characterizes FFI might be due to the binding of FFI toxic PrP or PrPres to specific receptors on thalamolimbic neurons.
Apoptosis↗
Low brain intracellular free magnesium in mitochondrial cytopathies.
The authors studied, by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS), the occipital lobes of 19 patients with mitochondrial cytopathies to clarify the functional relation between energy metabolism and concentration of cytosolic free magnesium. All patients displayed defective mitochondrial respiration with low phosphocreatine concentration [PCr] and high inorganic phosphate concentration [Pi] and [ADP]. Cytosolic free [Mg2+] and the readily available free energy (defined as the actual free energy released by the exoergonic reaction of ATP hydrolysis, i.e., deltaG(ATPhyd)) were abnormally low in all patients. Nine patients were treated with coenzyme Q10 (CoQ), which improved the efficiency of the respiratory chain, as shown by an increased [PCr], decreased [Pi] and [ADP], and increased availability of free energy (more negative value of deltaG(ATPhyd)). Treatment with CoQ also increased cytosolic free [Mg2+] in all treated patients. The authors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain. Free Mg2+ contributes to the absolute value of deltaG(ATPhyd). The results also are consistent with the view that cytosolic [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part, any changes in rapidly available free energy.
Adolescent↗
A case of cluster headache associated with mitochondrial DNA deletions.
Explore the source record for details and available documents.
Cluster Headache↗
Autonomic and hormonal ictal changes in gelastic seizures from hypothalamic hamartomas.
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.
Adult↗
Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene.
Fatal Familial Insomnia is a hereditary prion disease characterized by a mutation at codon 178 of the prion protein gene cosegregating with the methionine polymorphism at codon 129 of the mutated allele. It is characterized by disturbances of the wake-sleep cycle, dysautonomia and somatomotor manifestations (myoclonus, ataxia, dysarthria, spasticity). PET studies disclose severe thalamic and additionally cortical hypometabolism. Neuropathology shows marked neuronal loss and gliosis in the thalamus, especially the medio-dorsal and anterior-ventral nuclei, olivary hypertrophy and some spongiosis of the cerebral cortex. Detailed analysis of 14 cases from 5 unrelated families showed that patients ran either a short (9.1 +/- 1.1 months) or a prolonged (30.8 +/- 21.3 months) clinical course according to whether they were homozygote met/met or heterozygote met/val at codon 129. Moreover, homozygotes had more prominent oneiric episodes, insomnia and dysautonomia at onset, whereas heterozygotes showed ataxia and dysarthria at onset, earlier sphincter loss and epileptic Grand Mal seizures; they also displayed more extensive cortical involvement on PET and at postmortem examination. Our data suggest that the phenotype expression of Fatal Familial Insomnia is related, at least partly, to the polymorphism at codon 129 of the prion protein-gene.
Adult↗
Molecular pathology of fatal familial insomnia.
Fatal familial insomnia (FFI) is linked to a mutation at codon 178 of the prion protein gene, coupled with the methionine codon at position 129, the site of a methionine/valine polymorphism. The D178N mutation coupled with the 129 valine codon is linked to a subtype of Creutzfeldt-Jakob disease (CJD178) with a different phenotype. Two protease resistant fragments of the pathogenic PrP (PrPres), which differ in molecular mass, are associated with FFI and CJD178, respectively, suggesting that the two PrPres have different conformations and hence they produce different disease phenotypes. FFI transmission experiments, which show that the endogenous PrPres recovered in affected syngenic mice specifically replicates the molecular mass of the FFI PrPres inoculated and is associated with a phenotype distinct from that of the CJD178 inoculated mice, support this idea. The second distinctive feature of the FFI PrPres is the underrepresentation of the unglycosylated PrPres form. Cell models indicate that the underrepresentation of this PrPres form results from the PrP dysmetabolism caused by the D178N mutation and not from the preferential conversion of the glycosylated forms. Codon 129 on the normal allele further modifies the FFI phenotype determining patient subpopulations of 129 homozygotes and heterozygotes: disease duration is generally shorter, insomnia more severe and histopathology more restricted to the thalamus in the homozygotes than in the heterozygotes. The allelic origin of PrPres fails to explain this finding since in both cases FFI PrPres is expressed only by the mutant allele. Despite remarkable advances, many issues remain unsolved precluding full understanding of the FFI pathogenesis.
Brain↗
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↗