Facioscapulohumeral muscular dystrophy type 1A in northwestern Tuscany: a molecular genetics-based epidemiological and genotype-phenotype study.

Facioscapulohumeral muscular dystrophy type 1A (FSHD1A) is an autosomal dominant inherited disorder characterized by early involvement of facial and scapular muscles with eventual spreading to pelvic and lower limb muscles. A high degree of clinical variability with respect to age at onset, severity, and pattern of muscle involvement, both between and within families, is present. For this reason, diagnosis of FSHD1A can be sometimes difficult and molecular diagnosis is then necessary. A clinical and molecular genetic-based epidemiological investigation has been carried out in the territory of northwestern Tuscany in central Italy to calculate the prevalence rate of FSHD1A as of March, 2004. The molecular diagnosis has been based on the detection of large deletions of variable size of kpnI repeat units on chromosome 4q35. Results have been compared to those of a previous study conducted in the same area in 1981 (in the premolecular diagnosis era). The minimum prevalence rate was 4.60 x 10(-5) inhabitants, a value four times higher compared to our previous study. No significant correlation between fragment size and clinical severity has been observed. This study confirms in an Italian population a prevalence rate of FSHD1A similar to that observed in other populations. Furthermore, it underlines the usefulness of routine adoption of the genetic testing in confirming clinical suspicion of FSHD1A as well as in correctly diagnosing atypical and otherwise misclassified cases.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis.

Randomized Controlled Trials have not let established the best pharmacological management of Acute Disseminated Encephalomyelitis (ADEM). High dose steroids are usually employed with good results, but in a few cases the clinical outcome is poor. In other patients, particularly those affected by the site restricted ADEM variants (myelitis), the disease shows a recurrent course resembling that of Multiple Sclerosis. We present here five patients, 3 of them affected by classic disseminated encephalomyelitis and 2 by a post infectious myelitis, which showed a good response to intravenous immunoglobulin (IVIg) after steroid treatment failure. In our report high dose steroids administration was substantially uneffective in all but one case, who showed a good response only during the first episode. On the contrary IVIg injection (0,4 gr/kg/day) produced a marked functional improvement in all patients starting within the first five days of drug administration and reaching a maximum within three weeks. One patient experienced a good effect nothwithstanding a steady dysability. In all cases, clinical evidence was supported by MRI controls showing improving posttreatment changes.

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits.

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.

The effects of flumazenil on focal, electroinduced after-discharge in rabbits.

1. The anticonvulsive efficacy of flumazenil 10 mg/kg i.v., a BDZ antagonist, was studied in two models of experimental epilepsy electrically induced. 2. The EEG after-discharge, which was induced by the electrical stimulation of selected brain regions [(notably the dorsal hippocampus (Hip) and the amygdala (CAm)] was evaluated in rabbits pre- and post-drug administration. 3. In the animals submitted to electrical stimulation of the amygdala, flumazenil exerted a protective action, thereby inducing an increase in the after-discharge threshold and/or a decrease in after-discharge duration. 4. In the animals submitted to electrical stimulation of the hippocampus, flumazenil did not induced changes statistically significant. 5. Finally, the paper discusses the two possible mechanisms of action of flumazenil (a "per se" partial BDZ activity and/or a BDZ agonistic activity, which displaces the inverse agonist-like ligand) and the differencies in GABA distribution in the hippocampus and the amygdala.

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit.

1. The differential role played by blockade of D-1 or D-2 dopamine receptors in mechanisms underlying seizures was studied in a model of EEG after-discharge induced by electrical stimulation of selective brain regions (dorsal hippocampus and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg) increased significantly after-discharge duration after stimulation of either hippocampus or amygdala and lowered after-discharge threshold in few animals. 3. The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation of amygdala and reduced after-discharge duration when hippocampus was stimulated. 4. Haloperidol exerted a proconvulsant action in this experimental model, having a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas it exerted protection on the hippocampus. 5. The present data suggest that D-1 and D-2 receptors have different roles in generating and spreading the epileptic activity.

Cognitive impairment and cerebral atrophy in "heavy drinkers".

1. Aim of the work was to verify the following three hypotheses in alcoholics: a) right hemisphere; b) diffuse brain deficit; c) anterior brain deficit, by means of a neuropsychological and a neuroradiological assessment. 2. 15 alcoholic right-hand male subjects and 15 matched controls were enrolled in the study. 3. Specifically designed neuropsychological testing was performed to investigate logical abilities, selective attention and memory. 4. Neurological investigation was performed by a standard CT scan to assess the degree and localization of brain damage. 5. Alcoholics performed worse than controls on some neuropsychological tests, i.e. Attention Matrices Test, Verbal Judgement Test, Forward Digit Span, Story Recall and Remote Memory Test. The analysis of variance adjusted by the attentional score showed no significant differences between alcoholics and controls. 6. Neuroradiological data showed a preeminent and a more frequent atrophy of the frontal region. 7. No correlations emerged between neuropsychological and neuroradiological data. 8. In conclusion, the hypothesis of anterior brain deficit seems to be confirmed by our study.

Early effects of GM1 in experimental cerebral focal ischemia in rabbits.

This study aimed to investigate the effects of monosialoganglioside (GM1) when administered early in a model of cerebral focal ischemia, in the rabbit. The statistical evaluation of the electroencephalographic changes (quantified EEG analysis, QEEG) due to the ischemic event showed that the early treatment (1-3-24 h) with GM1 reduced the EEgraphic pattern typical of this model of cerebral ischemia. Considering the observation period, we hypothesized that it was due to the formation of an oedema of a lesser degree compared to the untreated group. Particularly, we did not obtain the increase in delta activity on the contralateral hemisphere, which we thought was expression of the diaschisi phenomenon.

Chronic alcoholism and the frontal lobe: which executive functions are imparied?

OBJECTIVE: Over the last decade, various hypotheses have been advanced concerning the cognitive functions affected by chronic alcoholism. The aim of this study was to identify the pattern of executive function impairment in chronic alcoholism, shedding light on possible differences between specific functions related to the frontal lobe. METHODS: Twenty-two male alcoholics and 22 controls, matched for age, educational level and IQ, were enrolled in the study. MMPI and a battery of neuropsychological tests [i.e. digit symbol, trail making test, Stroop test, digit cancellation test, Wisconsin card sorting test (WCST), simple and choice reaction times] for assessing frontal lobe functioning were administered. RESULTS: The alcoholics were found to be impaired in a wide range of executive domains, with the exception of the Stroop test, which nevertheless showed a trend towards statistically significant differences between patients and controls. CONCLUSION: With the exception of aggression - our subjects did not have high aggression scale scores - the 'frontal lobe hypothesis', according to which alcoholic patients are impaired on function tests related to the frontal lobe, was therefore confirmed in our sample.

Chiropractic complications. Another case report.

We report the case of a 34-year-old man, treated by chiropractic manipulation for tension-type headache. The patient complained of a sharp occipital pain during the first session, followed by vomiting and loss of consciousness, and remained comatose for five days. Neurological examination detected persistence of dysarthria, ataxia, with delayed responses. Neuroradiological findings reveal an ischemic lesion in left PICA region, confirmed by angiography. Clinical and radiological findings suggested complete remission about two months later.

[Electroencephalographic effects of a new triazolobenzodiazepine (Adinazolam) in the rabbit]. / Effetti elettroencefalografici di una nuova triazolobenzodiazepina (Adinazolam) nel coniglio.

In this study we investigated the central effects of adinazolam, a triazolobenzodiazepine, by means of neurophysiological techniques (electroencephalogram, EEG, and quantified analysis of EEG, QEEG). The drug has been administered at the doses of 0.1-1-10 mg/kg i.v. The evaluation of the data obtained by QEEG has demonstrated that this substance acts on the central nervous system. Particularly we observed that the drug at the middle and high doses caused an increase of the "slow waves sleep" EEG pattern. This preclinical study has shown that adinazolam possesses a neuropharmacological profile similar to that of atypical antidepressive and/or anxiolytic drugs.

[Role of the dopaminergic system in experimental models of epilepsy]. / Ruolo del sistema dopaminergico in modelli di epilessia sperimentale.

It has been shown that neuroleptics which interact selectively with either D-1 or D-2 dopamine receptors possess a marked difference in their propensity on seizures. The aim of this work was to investigate whether the D-1 antagonist SCH 23390 differs from haloperidol (D-2 antagonist) in models of experimental epilepsy induced by electrical stimulation of selected brain regions (hippocampus and amygdala), in rabbits. Haloperidol increased and SCH 23390 significantly decreased the susceptibility to seizures in both models investigated. The data suggest that the D-1 and D-2 receptor subtypes have different roles in the mechanisms underlying seizures.

Effects of moderate and high doses of alcohol on carotid atherogenesis.

The role of alcohol consumption on pathophysiology of atherosclerosis is not completely well established. Past studies were conducted with different methodological approaches, sometimes leading to opposing conclusions. The aim of this study was to determine the weight of alcohol intake on carotid atherosclerosis in a group of subjects asymptomatic for cardio-cerebrovascular diseases. They were examined by ultrasonographic assessment during the period 1993 through 1997. Common risk factors of atherosclerosis and drinking habit were assessed by a standardized questionnaire. In this survey we confirm the J-shaped relationship between atherosclerosis and alcohol consumption. The effect of alcohol intake is more evident if we consider the presence of multiple internal carotid stenosis, or those greater than 25%, as outcome variables. These effects are independent from the other risk factors included in logistic regression paradigms (age, arterial hypertension, dyslipidemia, diabetes mellitus, family history of cardio-cerebrovascular disease, smoking and social status). Our study supported that a high level of alcohol intake plays a role as an independent factor in carotid atherogenesis.

A locus for migraine without aura maps on chromosome 14q21.2-q22.3.

Migraine is a common and disabling neurological disease of unknown origin characterized by a remarkable clinical variability. It shows strong familial aggregation, suggesting that genetic factors are involved in its pathogenesis. Different approaches have been used to elucidate this hereditary component, but a unique transmission model and causative gene(s) have not yet been identified. We report clinical and molecular data from a large Italian pedigree in which migraine without aura (MO) segregates as an autosomal dominant trait. After exclusion of any association between MO and the known familial hemiplegic migraine and migraine with aura loci, we performed a genomewide linkage analysis using 482 polymorphic microsatellite markers. We obtained significant evidence of linkage between the MO phenotype and the marker D14S978 on 14q22.1 (maximum two-point LOD score of 3.70, at a recombination fraction of 0.01). Multipoint parametric analysis (maximum LOD score of 5.25 between markers D14S976 and D14S978) and haplotype construction showed strong evidence of linkage in a region of 10 cM flanked by markers D14S1027 and D14S980 on chromosome 14q21.2-q22.3. These results indicate the first evidence of a genetic locus associated with MO on chromosome 14.