The factorial structure of the mini mental state examination (MMSE) in Alzheimer's disease.

Our aim was to evaluate the factorial structure of the mini mental state examination (MMSE) in Alzheimer's disease (AD). Five hundred and twenty-four consecutive outpatients at their first diagnostic work-up (age 78.02+/-6.07 years, education 6.62+/-3.48 years, mean MMSE score 20.23+/-4.89) (+/-S.D.) with probable AD (based on DSM-IV and NINCDS-ADRDA criteria) were enrolled in a multicenter, cross-sectional, regional-based study. For the purpose of the present study, the 11 subtests composing the MMSE and the global MMSE score (ranging from 10 to 29, included) were considered. Factor analysis with Varimax rotation method identified two factors that explained about the 85% of total variance. The first factor explained the 65% of variance and mainly included temporal orientation, delayed recall, attention/concentration, and constructional praxia. The second factor explained the 20% of variance and included reading a sentence, writing a sentence, naming, verbal repetition and immediate memory. The first factor was a reliable index of cognitive deterioration along the MMSE score interval between 29 and 10, whereas the second factor was not a suitable marker in this range. The two-factor structure of the MMSE in AD is shown in a large series of patients. The first factor expresses the ability to use new information and is related with working memory. The second factor is related with a more consolidated knowledge, namely verbal abilities, and is essentially useless in mild to moderate AD.

The prevalence of multiple sclerosis in the north-west Italian province of Genoa.

UNLABELLED: The objective of this study was to assess the prevalence of multiple sclerosis (MS), calculated as point prevalence on 31 December 1997, in the province of Genoa, North-western Italy. METHODS: The province of Genoa is located in North-western Italy, an area of 1,835 km(2). On the point prevalence day the population consisted of 913,218 inhabitants. MS cases were identified by analysing archives of the hospitals with neurological or rehabilitation wards, neurologists serving the community, files of local chapters of the Italian MS society, all requests for oligoclonal bands analysis on CSF in the studied area. Patients included in the study were MS cases diagnosed before 31 December 1997 according to the Poser criteria resident in the province under study. RESULTS: A total of 857 subjects were alive and residing in the province of Genoa on the prevalence day. The overall crude prevalence rate was 94 per 100,000 (95% CI 88-100); 291 were males (34%) with a crude prevalence of 67 per 100,000 (95 % CI 60-76) and 566 were females (66%) with a prevalence of 118 per 100,000 (95% CI 108-128). The female/male ratio was 1.9. When age and sex were adjusted to the Italian standard population of 1991 prevalence was 85 per 100,000. Five hundred and thirty two out of the 857 patients agreed to be interviewed. The interviewed sample was representative of the prevalence sample: sex and gender distributions were identical in the two samples. The overall mean age was 48 (+/-13) years (48 +/-12 years in males; 48+/-14 years in females). Mean disease duration was 15 (+/-10) years for males and 16 (+/-11) years for females. Two hundred and ninety one (55 %) subjects had a relapsing remitting (RR) clinical course, 150 (28%) were secondary progressive (SP) and 91 (17%) were primary progressive (PP). Mean EDSS score was 5 (+/- 2; median 5). The mean age at time of onset was 33 (+/-10) years for males and 32 (+/- 11) years for females. The disease onset was monosymptomatic in 76% (n=407) patients and polysymptomatic in 24% (n=125). The mean length of time between clinical onset and diagnosis was 5 (+/- 6) years. CONCLUSION: We confirmed that the province of Genoa is a very high risk area for MS. We found a high rate of patients with a PP course; also the proportion of patients with high disability scores is greater compared to previous studies.

[Compromise of work capacity and quality of life of epileptic subjects]. / Compromissione della capacità lavorativa e qualità della vita nei soggetti epilettici.

The authors test epileptic subjects as far as their professional ability is concerned. An enquiry into patients admitted to the Epilepsy Centre of San martino Hospital in Genova has been performed through a questionnaire about professional performance and quality of life. As far as work related problems are concerned 44.6 per cent of the subjects show the presence of difficulties, while the quality of life is primarily repressed in men relatively to work and in women relatively to social relationship.

Old and new anti-epileptic drugs in pregnancy.

During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some other promising drugs are in various stages of development. Soon after each drug has found its place in the therapeutic arsenal, pregnancies with exposure occur, with an increased risk of birth defect and developmental disturbances. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinical toxicological studies which are difficult to extrapolate to the human situation, because of the well-known interspecies differences in pharmacokinetics and pharmacodynamics. Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically while these new drugs are prescribed as add-on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the old drugs many questions have still to be defined. The most common and more important are which anti-epileptic drugs or combination of drugs is most safe for a particular woman with epilepsy and if there is an association between single anti-epileptic drugs and specific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to anti-epileptic drug monotherapy during pregnancy. Other questions concern dose-effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the other risk factors, apart from the drugs. All these questions need to be ascertained for both the old and the new anti-epileptic drugs. Owing to these considerations, in 1998 an European Register of anti-epileptic drugs and pregnancy was instituted. The primary objective of the study is to evaluate and determine the degree of safety, with respect to the human foetus, of anti-epileptic drugs with reference to both old and new, and to individual drugs and drugs in combination. Secondary objectives are to establish the pattern of abnormalities, if any, associated with anti-epileptic drugs individually and in combination, to delineate drug-specific syndromes, if any, to evaluate dose-effect relationships. Tertiary objectives are to provide references data for use in pre-pregnancy counselling, and for development of guidelines. The evaluation of other etiological risk factors is also considered.

Old and new anti-epileptic drugs in pregnancy.

During the recent years, a significant number of anti-epileptic drugs have been approved for prescription in different countries. In addition, some other promising drugs are in various stages of development. Soon after each drug has found its place in the therapeutic arsenal, pregnancies with exposure occur, with an increased risk of birth defect and developmental disturbances. As regards the possible teratogenic effect of the new anti-epileptic drugs, apart some individual reports we have only the results of pre-clinical toxicological studies which are difficult to extrapolate to the human situation, because of the well-known interspecies differences in pharmacokinetics and pharmacodynamics. Furthermore, combinations of anti-epileptic drugs are not tested pre-clinically while these new drugs are prescribed as add-on medication. So, metabolic interactions between individual components of such drug combinations may induce unexpected teratogenic effects. Also as for the teratogenic effects of the `old` drugs many questions have still to be defined. The most common and more important are which anti-epileptic drugs or combination of drugs is most safe for a particular woman with epilepsy and if there is an association between single anti-epileptic drugs and specific malformations. The reason is that none of the available reports to date have studied a sufficient number of women with epilepsy exposed to anti-epileptic drug monotherapy during pregnancy. Other questions concern dose-effect relationships, a universally accepted definition of major and minor malformations, and the lack of a thorough, exhaustive evaluation of the other risk factors, apart from the drugs. All these questions need to be ascertained for both the old and the new anti-epileptic drugs. Owing to these considerations, in 1998 an European Register of anti-epileptic drugs and pregnancy was instituted. The primary objective of the study is to evaluate and determine the degree of safety, with respect to the human foetus, of anti-epileptic drugs with reference to both old and new, and to individual drugs and drugs in combination. Secondary objectives are to establish the pattern of abnormalities, if any, associated with anti-epileptic drugs individually and in combination, to delineate drug-specific syndromes, if any, to evaluate dose-effect relationships. Tertiary objectives are to provide references data for use in pre-pregnancy counselling, and for development of guidelines. The evaluation of other etiological risk factors is also considered.

Clinical aspects and biological bases of drug-resistant epilepsies.

The definition of drug-resistant epilepsy (DRE) is elusive and still controversial owing to some unresolved questions such as: how many drugs should be tried before a patient is considered intractable; to which extent side-effects may be acceptable; how many years are necessary before establishing drug resistance. In some cases, the view of epilepsy as a progressive disorder constitutes another important issue. Despite the use of new antiepileptic drugs (AEDs), intractable epilepsy represents about 20-30% of all cases, probably due to the multiple pathogenetic mechanisms underlying refractoriness. Several risk factors for pharmacoresistance are well known, even if the list of clinical features and biological factors currently accepted to be associated with difficult-to-treat epilepsy is presumably incomplete and, perhaps, disputable. For some of these factors, the biological basis may be common, mainly represented by mesial temporal sclerosis or by the presence of focal lesions. In other cases, microdysgenesis or dysplastic cortex, with abnormalities in the morphology and distribution of local-circuit (inhibitory) neurons, may be responsible for the severity of seizures. The possible influence of genes in conditioning inadequate intraparenchimal drug concentration, and the role of some cytokines determining an increase in intracellular calcium levels or an excessive growth of distrophic neurites, constitute other possible mechanisms of resistance. Several hypotheses on the mechanisms involved in the generation of DRE have been indicated: (a) ontogenic abnormalities in brain maturation; (b) epilepsy-induced alterations in network, neuronal, and glial properties in seizure-prone regions such as the hippocampus; (c) kindling phenomenon; (d) reorganization of cortical tissue in response to seizure-induced disturbances in oxygen supply. Such hypotheses need to be confirmed with suitable experimental models of intractable epilepsy that are specifically dedicated, which have until now been lacking.

Vigabatrin vs. carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study.

The clinical efficacy and safety of vigabatrin (VGB) as add-on therapy for pharmaco-resistant focal epilepsies is well established. However, for an objective evaluation, the effects of the drug in the monotherapy of newly diagnosed subjects should be determined. With this aim, VGB was compared, in a randomized, response conditional cross-over study, with carbamazepine (CBZ), the most widely prescribed drug in focal epilepsies. Fifty-one patients with complex partial (CP) seizures were randomly assigned to either the VGB or the CBZ group and evaluated after an initial 4 month period. The cross-over to the alternative drug was carried out, for an analogous period, only in cases with persisting seizures or in the presence of intolerable side effects. Patients who did not respond to either drug were subsequently treated with a combination of VGB and CBZ. No significant difference was revealed in the efficacies of VGB and CBZ; a complete control of seizures was obtained in 17/37 patients (45.9%) treated with VGB and in 20/39 patients (51.3%) treated with CBZ. The side effects were somewhat more frequent (41%) and severe with CBZ than with VGB (21.6%). The power to detect a 20% difference between the two drugs was 75%. The combination of the two drugs suppressed the seizures in 5 out of 14 resistant cases. The preliminary results in this small number of patients are encouraging and suggest that VGB may be considered as a first-line drug for epilepsy with CP seizures and as a valid alternative when other monotherapies are ineffective or poorly tolerated.

Newer antiepileptic drugs as monotherapy: data on vigabatrin.

Studies examining the use of vigabatrin as monotherapy for the treatment of epilepsy are relatively scarce, and of the few that have been reported, only two were of sufficient size to provide definitive data. In both trials, vigabatrin was compared with carbamazepine for efficacy and safety. In one of these studies, carbamasepine was found to be more effective than vigabatrin in reducing seizure frequency, and the two were found to be comparably efficacious in the other study. What differed significantly, however, was vigabatrin's favorable safety profile. Vigabatrin appears to be a reasonable choice for single-drug therapy in the treatment of certain types of seizures. In other patients, it remains useful as an adjunct to other antiepileptic drugs.

Late-onset epilepsy and diffuse cryptogenous cerebral atrophy.

Diffuse cerebral atrophy (CA), a frequent computed tomography (CT) finding in late-onset epilepsy, is sometimes of unknown origin or cryptogenous (CCA). From a series of 228 patients with late-onset epilepsy with diffuse CA, we excluded patients with a presumed etiology. The remaining 73 (36.8%) patients were studied for a mean of 7.2 years; 15.1% had a family history of epilepsy. CCA was cortical in 50.7%, subcortical in 6.8%, and corticosubcortical in 42.5%. Seizures, generalized in 71.2%, and focal in 28.8% were generally of low occurrence with good therapeutic response. Background EEG activity was normal in most patients. During follow-up, the clinical and EEG features remained unchanged. In a control series of 92 nonepileptic subjects with diffuse CA, CCA was noted in only 4 (4.3%). No variation in grade or distribution of CCA was noted in repeated CT scans of the two groups, except in 2 epileptic patients. Psychometric tests demonstrated no cognitive impairment during evolution. The results appear to confirm the hypothesis that late-onset epilepsy associated with CCA constitutes a syndrome that is related to the characteristics of the atrophy.

Epilepsy, pregnancy, and major birth anomalies: an Italian prospective, controlled study.

We followed prospectively 97 women with epilepsy during 138 pregnancies and 88 women without epilepsy, matched for age, during 140 pregnancies. We evaluated seizure frequency, pregnancy outcome, and presence of major congenital malformations, and correlated them with the type of epilepsy, antiepileptic drugs (AEDs) implicated, plasma AED levels during pregnancy, and maternal age. We compared the two groups regarding type and number of pregnancies; complications during gestation, labor, and delivery; prevalence of abortions (spontaneous or induced); perinatal deaths; and type and prevalence of major malformations. No change in seizure frequency during pregnancy was seen in 79.7% of cases. Pregnancy complications and incidence of major congenital malformations were only slightly higher in women with epilepsy than in women without epilepsy. No single AED used as monotherapy correlated with increased risk of malformations, but polypharmacy with phenobarbital and phenytoin seemed to represent a risk factor. Low socioeconomic status, older age at delivery, and family history of malformations were other risk factors for neonatal malformations.

Sleep organization in man during long stays at 30 and 40 bar in a helium-oxygen mixture.

Sleep organization was studied during 5 dives with long holds (from 6 to 15 days) at 30 and 40 bar in a helium-oxygen mixture. In total, 16 professional divers participated in these saturation dives; 337 nights were analyzed. Sleep was disrupted by compression and the stay at pressure, but the disturbances were greater at 40 bar than at 30 bar. There was an increase of awake periods, stages I and II, a decrease of stages III and IV, and instability of rapid eye movement periods. These changes were more intense at the beginning of the stay; some improvements could be found between Days 4 and 6 of the stay but the return to control values was recorded only during the decompression after 20 bar. The disturbances of sleep seem to be related to compression speed and to the pressure itself and appear as another symptom of the high pressure nervous syndrome.

Refractory tonic generalized status epilepticus. Report of a case of exceptionally prolonged duration.

A generalized tonic status epilepticus persisting for 5 months in a young adult previously affected only by tonic-clonic seizures is described. The syndromic classification of the case remains unsettled.

Chloroquine-induced neuromyopathy. Report of a case.

A patient is described in whom a neuromyopathy developed during a long chloroquine treatment for systemic lupus erythematosus (SLE). The presence of a granular deposition within the muscle fibers was observed and led to discontinuation of the drug and to a gradual recovery of muscle strength. The difficult differential diagnosis with polymyositis, steroid-induced myopathy and SLE myositis is discussed.

Carpal tunnel syndrome appearing with prominent skin symptoms.

A case of carpal tunnel syndrome (CTS) occurred in which the skin manifestations predominated over the neurologic symptoms. The skin changes included cyanosis, anhidrosis, alopecia, nail dystrophy, and episodes of acute necrosis. Carpal tunnel syndrome is the most common neuropathy accompanying nerve compression. The results of therapy depend on early diagnosis and the rapid relief from compression. Dermatologists should be well aware of this syndrome, which is almost entirely ignored in the major textbooks of dermatology.

[Cryptogenic cerebral atrophy in late-onset epilepsy]. / L'atrofia cerebrale criptogenetica nell'epilessia ad insorgenza tardiva.

174 subjects suffering from late onset epilepsy were examined. The incidence of cerebral atrophy, defined with objective criteria on CT scans by means of a comparative analysis with a matched for age control group was 37.9%. Head traumas, cerebrovascular disorders and alcoholism were the presumed etiological factors in most of the cases while in 25 subjects (20%) the etiology of cerebral atrophy remained unknown ("cryptogenous atrophy"). Clinical profil, psychometric performance and EEG characteristics of these subjects were investigated and compared with the remainder groups of late-onset epileptics. The results obtained show that the subjects with cryptogenous atrophy behave, as regard the features considered, as the late-onset epileptics with normal CT but present an higher familial prevalence for epilepsy. On the contrary they differs in various ways from late-onset epileptics with atrophy of known origin and from epileptics with focal lesions.

Withdrawal seizures in alcoholics. A transverse and longitudinal investigation.

74 heavy drinkers, divided in two groups by positive or negative history for withdrawal seizures, were evaluated on the history, clinical, biochemical, CT, EEG and psychometric investigations. Some of them have been followed up for 20 months. The results suggest the possible role of a constitutional predisposition for withdrawal seizures.