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P Avoni

Publications and source records attributed to P Avoni.

At least 19 recordsLinked to original sources
PubMed2006

Anti-ganglioside antibodies in coeliac disease with neurological disorders.

BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. RESULTS: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.

Adult↗
PubMed2004

Idiopathic partial epilepsy with auditory features (IPEAF): a clinical and genetic study of 53 sporadic cases.

The purpose of our study was to describe the clinical characteristics of sporadic (S) cases of partial epilepsy with auditory features (PEAF) and pinpoint clinical, prognostic and genetic differences with respect to previously reported familial (F) cases of autosomal dominant partial epilepsy with auditory features (ADPEAF). We analysed 53 patients (24 females and 29 males) with PEAF diagnosed according to the following criteria: partial epilepsy with auditory symptoms, negative family history for epilepsy and absence of cerebral lesions on NMR study. All patients underwent a full clinical, neuroradiological and neurophysiological examination. Forty patients were screened for mutations in LGI1/epitempin, which is involved in ADPEAF. Age at onset ranged from 6 to 39 years (average 19 years). Secondarily generalized seizures were the most common type of seizures at onset (79%). Auditory auras occurred either in isolation (53%) or associated with visual, psychic or aphasic symptoms. Low seizure frequency at onset and good drug responsiveness were common, with 51% of patients seizure-free. Seizures tended to recur after drug withdrawal. Clinically, no major differences were found between S and F patients with respect to age at onset, seizure frequency and response to therapy. Analysis of LGI1/epitempin exons failed to disclose mutations. Our data support the existence of a peculiar form of non-lesional temporal lobe epilepsy closely related to ADPEAF but without a positive family history. This syndrome, here named IPEAF, has a benign course in the majority of patients and could be diagnosed by the presence of auditory aura. Although LGI1 mutations have been excluded, genetic factors may play an aetiopathogenetic role in at least some of these S cases.

Adolescent↗
PubMed2001

Familial continuous motor unit activity and epilepsy.

A mother and son both had muscle stiffness due to continuous generalized muscle twitching, beginning in childhood and associated with epileptic seizures. Electromyography (EMG) showed continuous motor unit activity (CMUA) at rest, which decreased during ischemia, sleep, and carbamazepine treatment, and was abolished by anesthetic nerve blockade. Genetic analysis disclosed a G724C point mutation in the potassium channel KCNA1 gene. The electrophysiological data suggested pathological impulse generation in both the peripheral and central nervous system, probably related to abnormal ion channel function.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Levodopa therapy monitoring in patients with Parkinson disease: a kinetic-dynamic approach.

The authors assessed differences in both therapeutic and dyskinesia-matched concentrations of levodopa by kinetic-dynamic modeling in a large cohort of patients with Parkinson disease grouped by severity of symptoms. The goal was to provide a kinetic-dynamic approach to levodopa therapy monitoring to assist treating physicians in rationalizing patients' drug schedules in line with disease progression. Eighty-six patients, grouped according to Hoehn & Yahr (H&Y) clinical stage (H&Y I, n = 23; II, n = 25; III; n = 25; IV, n = 13) enrolled in the study. After a 12-hour levodopa washout each patient was examined using a standard oral levodopa test, based on simultaneous serial measurements of plasma levodopa concentrations, finger-tapping motor effects, and dyskinesia ratings. The kinetic-dynamic modeling for both effects was carried out according to the "link" effect compartment model and sigmoidal pharmacodynamic model. Levodopa plasma kinetics did not differ among patient groups. Duration of motor response was significantly (p < 0.001) curtailed in patients in advanced clinical stages whereas dyskinesia duration showed minor changes among the three affected groups (H&Y II, III, and IV). Median effective concentrations (EC 50 ) were increased at the more advanced clinical stage (p < 0.001), from a median 0.2 microg/mL in patients at H&Y stage I to 0.9 microg/mL in patients at H&Y stage IV, whereas the maximum effect showed less consistent changes among the four groups. Intrasubject levodopa therapeutic concentrations were lower than values for dyskinesias in patients at the moderate stage of the disease, equaling dyskinesia-matched drug concentrations in the more affected patients. These findings are in line with previous observations of major changes in levodopa concentration-effects relationship with disease progression and support a stratification of patients with Parkinson disease according to kinetic-dynamic modeling. From a practical point of view, knowledge of individual patients' kinetic-dynamic variables can help the physician assess patients' clinical needs objectively and optimize levodopa dosing according to disease progression.

Adult↗
PubMed2001

Efficacy of lamotrigine add-on therapy in severe partial epilepsy in adults with drop seizures and secondary bilateral synchrony on EEG.

OBJECTIVES: To evaluate the efficacy of lamotrigine (LTG) add-on therapy in drug-resistant, partial epilepsy with epileptic drop attacks (EDA) and secondary bilateral synchrony (SBS) on EEG. METHODS: We carried out a single-center, open-label, prospective study on a restricted group of patients experiencing an EDA frequency of at least one/month during the previous year regardless of multiple antiepileptic drug (AED) trials. Study design consisted of three phases: a 3-month baseline period, a 4-month period in which LTG was titrated and a 9-month maintenance dose observational period. LTG add-on therapy depended on valproate (VPA) association, with a maximum of 200 mg/day with VPA and 600 mg/day in the absence of VPA. Every three months, patients underwent clinical, hematological and EEG evaluation including plasma level of AEDs. To assess the efficacy of LTG add-on therapy, patients were required to keep a detailed seizure diary throughout the study. RESULTS: Fourteen patients (nine men and five women), aged from 21 to 51, were included in the study. All of them had complex partial seizures (CPS), besides EDA, and half of them had secondarily generalized seizures (SGS). Two of the 14 patients had to stop LTG due to side effects, although one of them was seizure-free after LTG. Twelve patients completed the study. The improvement was more than 50% for every type of seizure. SGS disappeared in three cases and improved by more than 50% in another three cases. EDA disappeared in six patients; and improved with more than 50% EDA reduction in five patients. CPS disappeared in two patients and improved by more than 50% in eight. EEG improved in nine cases, with SBS disappearing in six patients. CONCLUSIONS: We have demonstrated a good efficacy of LTG adjunctive therapy on EDA. Results include control of SGS and improvement of EEG tracing.

Adult↗
PubMed2000

Congenital encephalomyopathy with epilepsy, chorioretinitis, basal ganglia involvement, and muscle minicores.

A woman had severe psychomotor retardation, epilepsy, rigidity, and chorioretinitis. Magnetic resonance imaging showed cerebellar and cerebral atrophy and hypointensities in T2-weighted images of the thalami and basal ganglia. Muscle biopsy documented size variations in rounded muscle fibers, fibrosis, and minicores on electron microscopy. Merosin staining was normal. These hitherto unreported features do not permit classification of our patient within the current types of encephalomyopathy and congenital muscular dystrophies.

Adult↗
PubMed2000

Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.

Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system potassium channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage-gated potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug-resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed-rectifier type potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study.

Action Potentials↗
PubMed1998

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↗
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↗
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↗
PubMed1996

Partial epilepsy of long duration: changing semiology with age.

There are few data on changing patterns of localization-related epileptic syndromes with time and particularly on changes in seizure semiology as patients age. We retrospectively reviewed 53 patients aged > 60 years who had had partial epileptic seizures for a mean duration of 44 years. In 29 patients, seizures became progressively less elaborate and briefer with time. In 20 patients, seizures were unchanged. In four patients, seizures worsened, with the appearance of drop attacks, secondarily generalized seizures, increasing drug resistance, and mental deterioration. These latter 4 patients had cerebrovascular disease with multiple strokes.

Adolescent↗
PubMed1996

Fatal familial insomnia: behavioral and cognitive features.

Fatal familial insomnia (FFI) is a familial prion disease linked to a mutation of the prion protein gene. Neuropsychological investigations in seven patients with FFI belonging to two different families showed that the main behavioral and neuropsychological features are (1) early impairment of attention and vigilance, (2) memory deficits, mainly of the working memory, (3) impairment of temporal ordering of events, and (4) a progressive dream-like state with neuropsychological and behavioral features of a confusional state. Neuropathologic examination of six patients showed prominent neuronal loss and gliosis involving the anterior ventral and mediodorsal thalamic nuclei, with additional cerebral cortical involvement in two cases. Clinicopathologic correlations indicate that FFI is associated with a neuropsychological and behavioral syndrome that is distinct from the cortical and subcortical dementias, and Wernicke-Korsakoff syndrome. These findings offer insights into the function of the thalamic nuclei and challenge the notion of thalamic dementia.

Adult↗
PubMed1996

The prognostic value of the electroencephalogram in antiepileptic drug withdrawal in partial epilepsies.

We evaluated the prognostic value of the EEG in 120 seizure-free epileptic patients (49 with complex partial seizures with or without episodic secondarily generalization [CPS], 20 with simple partial seizures with or without episodic secondarily generalization [SPS], 51 with only secondarily generalized seizures [PSG] during and after antiepileptic drug withdrawal. All patients had EEG examination before; during; and 3, 12, 24, and 36 months after drug withdrawal. Relapse rates were 45% in CPS, 100% in SPS, and 65% in PSG. Before reduction, 36 patients had epileptiform EEG and 69% relapsed; in the group with normal EEG, 60% relapsed. EEG worsened in 36 patients, 83% relapsed, whereas only 54% of patients with unchanged EEG relapsed. EEG during but not at the start of drug withdrawal has a prognostic value in partial epilepsy.

Adolescent↗
PubMed1995

Sleep-wake cycle abnormalities in fatal familial insomnia. Evidence of the role of the thalamus in sleep regulation.

Alterations in sleep organization were longitudinally studied in 6 new cases of fatal familial insomnia (FFI) by 24 h polygraphic recording. All patients showed an early reduction in sleep spindles and K complexes, and a drastic reduction in total sleep time and disruption of the cyclic sleep organization. Complete abolition of NREM sleep and persistence of only brief residual periods of REM sleep without atonia were features characteristic of the 3 patients with a short (less than 1 year) clinical course, and lacking in the 3 cases with a longer (more than 2 years) disease course. In the latter, sudden transitions from waking to NREM or REM sleep occurred, sometimes recurring periodically. Our findings confirm that impairment of sleep-wake regulation is a consistent distinctive feature of FFI.

Adult↗