Onabotulinumtoxin A for prophylaxis in chronic migraine: preliminary data from Headache Regional Centre of Aosta Valley.

Chronic migraine (CM) is a complex neurological disorder associated with substantial disability that affects approximately 2 % of general population. Onabotulinumtoxin A is employed for patients suffering from CM refractory to common therapeutic prophylaxis. Since May 2013, we have selected 22 patients referring to our headache centre with a history of CM which meets the diagnostic criteria of ICHD-3 beta (2013). The patients have been treated with onabotulinumtoxin A injection in 31 sites according to the protocol of the PREEMPT study at the total dosage of 155 U/treatment every 3 months. So far, eight patients have been subjected to three treatment sessions, five patients to two treatments and nine patients to one treatment. Three patients dropped for low compliance, but there were no serious adverse events. The frequency of headache days, the intensity of headache and the headache disability have been measured using headache diary, migraine disability assessment (MIDAS) questionnaire and headache impact test (HIT)-6 score. Data concerning the 13 patients who have been submitted to at least two treatment sessions have already shown a decrease of headache days of 20.64 % after the first treatment; MIDAS and HIT-6 scores have been significantly improved with a reduction of the scores, respectively, of 38.45 % for MIDAS and of 6.95 % for HIT-6. These are preliminary results because the observation time, the number of treatment sessions and the number of patients treated are still few.

Is there a prognostic role for C-reactive protein in ischemic stroke?

OBJECTIVES: We investigated the relationship between C-reactive protein (CRP)-values in the acute phase of stroke and the risk of further fatal and non-fatal ischemic events. MATERIALS AND METHODS: We analysed 462 consecutive incident ischemic strokes. Patients were divided into two subgroups on the basis of a CRP cut-off level of 9 mg/l. Primary end points were any new vascular fatal and non-fatal event recorded during the follow-up period. RESULTS: During a follow-up of 2.27 years, in 132 patients occurred a primary end point. Patients with CRP values > or = 9 mg/l had more frequently primary end point. The hazard ratio (HR) for cardiovascular events was 3.59; 1.93 for cerebrovascular events; 7.43 for vascular deaths and 5.78 for death from any cause. Cox proportional hazard multivariate analysis identified CRP values > or = 9 (HR = 4.19, 95% CI: 1.85-9.50, P = 0.001), the lack of secondary prevention therapy at discharge (HR = 4.35, 95% CI: 1.87-10.1, P = 0.001), age >70 years (HR = 3.09, 95% CI: 1.04-9.24, P = 0.04) as independent predictors of fatal events. CONCLUSIONS: CRP levels > or = 9 mg/l, evaluated in incident ischemic stroke within 24 h, predict a higher risk of further ischemic events and mortality.

Epidemiology of ALS in Italy: a 10-year prospective population-based study.

OBJECTIVE: To describe the temporal patterns of incidence and demographic characteristics of amyotrophic lateral sclerosis (ALS) in Piemonte and Valle d'Aosta, Italy, in the 10-year period 1995 through 2004. METHODS: The Piemonte and Valle d'Aosta Register for ALS (PARALS) is a prospective register collecting all cases of ALS incident in two regions of northwestern Italy (population: 4,332,842) since 1995. The cases are identified using several concurrent sources. ALS diagnosis is based on El Escorial criteria. RESULTS: During the 10-year period of observation, 1,347 residents in the study area were diagnosed with ALS. In 1,260 of these cases, a diagnosis of definite or probable ALS was made at presentation or during the follow-up. The mean annual crude incidence rate was 2.90/100,000 population (95% confidence interval [CI], 2.72 to 3.09). The crude prevalence rate (December 31, 2004) was 7.89 (95% CI, 7.09 to 8.75)/100,000 population. According to the capture-recapture estimation, 27 patients were unobserved, thus increasing the annual observed crude incidence to 2.96/100,000 population. The incidence rate did not show any relevant variation during the 10-year period of the study and was constantly higher among men. The demographics and clinical features did not change between the 1995-1999 and the 2000-2004 cohorts, with the notable exception of the mean time delay from onset to diagnosis, which was significantly decreased in the last 5-year period. CONCLUSIONS: In the examined decade, the incidence of amyotrophic lateral sclerosis in Italy has been stable, and the clinical and demographic characteristics of the patients have shown no relevant modifications.

Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy.

AIM: The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. SUBJECTS AND METHODS: All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d'Aosta (4,334,225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. RESULTS: The crude prevalence rate was 3.58/100,000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting-relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995-2001, the mean annual crude incidence rate was 0.36/100,000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age >60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. CONCLUSION: Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases.

Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities.

OBJECTIVE: To evaluate the effects of tertiary centres for amyotrophic lateral sclerosis (ALS) on ALS outcome and the use of hospital facilities. METHODS: The study was based on the data of an epidemiological, prospective, population-based register on ALS (Piemonte and Valle d'Aosta Register for amyotrophic lateral sclerosis, PARALS). The 221 patients recruited between 1995 and 1996 were prospectively followed up for outcome and use of hospital-based services. RESULTS: In all, 97 patients were followed up by tertiary ALS centres and 124 by general neurological clinics. Patients followed up by tertiary ALS centres were found to be 4 years younger and underwent percutaneous endoscopic gastronomy and non-invasive positive-pressure ventilation more often. Patients followed up by tertiary ALS centres were found to have a considerably longer median survival time (1080 v 775 days), even when stratifying by age, site of onset and respiratory function at diagnosis. In Cox multivariate analysis, attending a tertiary ALS centre was observed to be an independent positive prognostic factor. Moreover, patients attending a tertiary ALS centre were admitted to hospital less often (1.2 v 3.3) and were more frequently admitted for planned interventions. Conversely, patients followed up by general neurological clinics were more frequently admitted for acute events. Also, the hospital stay was considerably shorter for patients attending tertiary ALS centres (5.8 v 12.4 days). CONCLUSIONS: Improved survival was seen in patients with ALS attending tertiary ALS centres, independently from all other known prognostic factors, possibly through a better implementation of supportive treatments. Moreover, because of these centres, the hospitalisation rate was markedly reduced, thus offering a cost-effective service to patients with ALS and to the community as a whole.

Chronic alcohol use and first symptomatic epileptic seizures.

OBJECTIVE: To establish whether chronic alcoholism and alcohol consumption are risk factors for developing a first symptomatic epileptic seizure. METHODS: Multicentre case-control study of 293 patients (160 men, 133 women) with a first seizure symptomatic (either acute or remote) of head trauma, stroke, or brain tumour, matched to 444 hospital controls for centre, sex, age (+/-5 years), and underlying pathology. RESULTS: The risk of first seizure in alcoholics was no higher than in non-alcoholics for men (odds ratio 1.2, 95% confidence interval 0.4 to 3.2) or women (1.5, 0.1 to 54.4). The odds ratio (both sexes) was 1.2 (0.8 to 1.7) for an average intake of absolute alcohol of 1-25 g/day, 0.9 (0.5 to 1.5) for 26-50 g/day, 1.6 (0.8 to 3.0) for 51-100 g/day, and 1.4 (0.5 to 3.5) for >100 g/day. CONCLUSIONS: We found no evidence of an association between alcohol use or alcoholism and a first symptomatic seizure.

Risk factors for a first generalized tonic-clonic seizure in adult life.

To evaluate risk factors for a first generalized tonic-clonic seizure (GTCS) in adults (=15 years), we performed a multicenter, case-control study involving eleven first-referral neurological departments in north-western Italy. The study enrolled 278 patients with a first GTCS, and 556 age- and sex-matched hospital controls. Cases and controls were interviewed through a questionnaire (inter-rater and index-proxy agreement varied between 75% and 100% for the different questions). Risk factors significantly associated with a first GTCS were: severe head trauma (odds ratio 9.9; 95% confidence limits 2.0-67.1), siblings with seizures (5.7; 1.7-21.4), alcohol intake >50 grams/day (4.9; 3.1-7.9), history of stroke (3.8; 1.8-8.0), complications of delivery (2.7; 1.5-5.1), other relatives with seizures (2.4; 1.3-4.6), sleep deprivation (2.4; 1.4-4.1), low gestational age (1.9; 1.1-3.4), mild-moderate head trauma (1.8; 1.2-3.0), and low birth weight (1.6; 1.0-2.7). Genetic and late acquired factors and life habits are major risk factors for a first GTCS in adults, while pre- and perinatal events play only a minor role.

Early symptom progression rate is related to ALS outcome: a prospective population-based study.

OBJECTIVE: To define the factors related to ALS outcome in a population-based, prospective survey. METHODS: The 221 patients (120 men and 101 women) listed in the Piemonte and Valle d'Aosta ALS Register between 1995 and 1996 were enrolled in the study. The patients were prospectively monitored with a standard evaluation form after diagnosis. RESULTS: Mean age at onset was 62.8 (SD = 11.2) years. According to El Escorial diagnostic criteria (EEDC), 112 patients had definite ALS, 85 probable ALS, 18 possible ALS, and six suspected ALS. The median survival time from symptom onset was 915 days (95% CI = 790 to 1065). The median survival time from diagnosis was 580 days (95% CI = 490 to 670). In univariate analysis, outcome was significantly related to age, onset site, EEDC classification, and symptom progression rate (i.e., the rate of decline of muscle strength and bulbar and respiratory function in the 6 months after diagnosis). In the Cox multivariate model, age, progression rate of respiratory, bulbar, and lower limb symptoms, EEDC classification, percutaneous endoscopic gastrostomy, and treatment with riluzole were significantly related to outcome. CONCLUSIONS: The rate of progression of symptoms in early ALS is predictive of disease outcome.

Epidemiology of primary intracranial tumours in NW Italy, a population based study: stable incidence in the last two decades.

Data about the epidemiology of primary intracranial tumours (PIT) are still heterogeneous depending on different methodological approach in collecting data. In Valle d' Aosta, north west side of Italy, we have carried out a prospective consecutive population based study to calculate the incidence of PIT in the last decade (1992-1999) and to compare these rates with the previous period (1986-1991), data reported in a previous paper. The mean annual PIT incidence rate (ri) per 100,000 inhabitants was 25.48. The mean annual incidence rates in the two period of comparison were adjusted to the 1991 Italian population by the direct method. The standardised ratio was 26.43 in the previous period and 23.24 in the second decade. There is no statistically significant difference. The mean annual PIT incidence rates by tumour types were meningiomas 13.27/100,000 (men 9.77; women 16.7), neuroepithelial group 9.3 (men 10.62; women 8.1), adenomas 1.26, neurinomas 0.7. Mean annual incidence rates by tumour class were also stable. The stable incidence rate in the two periods and the similar incidence in England (21.04/100,000 person year), strengthen the evidence for a stable incidence rate of PIT in the last decade. These three papers used similar methodology. The homogeneous methodology allows comparison and further evaluation.

Temporal trends of stroke in Valle d'Aosta, Italy. Incidence and 30-day fatality rates.

The objective of this study was to evaluate temporal changes of stroke in an Italian community by comparing the present incidence rates with those reported in the same area for 1989. The two studies were conducted by the same research group and met almost all the criteria proposed for an "ideal" stroke incidence study. The annual incidence rate per 1000 inhabitants increased (p < 0.01) by 29%, from 2.23 (95% CL, 1.96-2.50) in 1989 to 2.89 (95% CL, 2.58-3.20) in 1997. No statistically significant change was found when these rates were adjusted to the 1991 Italian population. The overall incidence rate was 2.40 (95% CL, 2.14-2.66) in 1989 and 2.65 (95% CL, 2.39-2.91) in 1997. The thirty-day case fatality rate declined dramatically (p < 0.001) from 31% (95% CL, 26-36) to 20% (95% CL, 16-24) between 1989 and 1997. Ageing of the population and better identification of cases could explain the high incidence rate, whereas the decrease of fatality rate may be due to a general improvement in acute care and inclusion of milder cases.

Prevention of cardioembolic stroke: use of oral anticoagulants in patients with atrial fibrillation.

With the aim of quantifying the use of oral anticoagulant (OA) therapy in clinical practice, we surveyed 150 consecutive patients admitted with a diagnosis of atrial fibrillation (AF). Each patient was administered a questionnaire relating to the classic vascular risk factors and to the antithrombotic treatment received at home. The diagnosis of AF was formulated at the time of admission in 45 cases. Of the 105 cases with a previous diagnosis, OA therapy was relatively or absolutely contraindicated in 21 patients (20%), whereas the other 84 (80%) were ideal candidates for the treatment. Of these, 20 (24%) were actually receiving OA, 16 (19%) were on platelet anti-aggregants (PA), and 48 (57%) were receiving no antithrombotic treatment at all. Even lower percentages of OA use were found in the patients with a previous (20%) or recent (16%) history of cerebral ischemia. Upon discharge, of the 115 patients without contraindications to OA (84 with previously known and 31 with newly diagnosed AF), 50% were receiving OA and 20% PA. The results of this survey show that OA therapy is little used in the Valle d'Aosta Region for the prevention of ischemic stroke in AF patients at high risk for cerebral ischemia. The lack of knowledge among the general population, the difficulty of initiating the therapy in patients such as ours with severe comorbidities, and the absence of disorganization of centers for OA monitoring may be the main reasons underlying this low level of use. Population screening or a sensitization campaign could increase the identification of subjects at risk, whereas better organization of coagulation monitoring centers could encourage OA use in subjects at high risk for cerebral ischemia.

Safety and factors related to survival after percutaneous endoscopic gastrostomy in ALS. ALS Percutaneous Endoscopic Gastrostomy Study Group.

Percutaneous endoscopic gastrostomy (PEG) has been proposed as symptomatic treatment of dysphagia in patients with ALS. Safety and factors related to survival after PEG were analyzed in 50 consecutive ALS patients. No major acute or long-term complications were observed. Stabilization or increase in weight were observed after PEG. Median survival after PEG was 185 days, with a worse outcome in patients with weight loss > or =10% healthy body weight and forced vital capacity <65%. PEG may be a useful option in the symptomatic treatment of dysphagia in ALS.

A case-control study on alcohol and seizures: study design, protocol, and data collection. The ALCE (Alcohol and Epilepsy) Study Group.

We designed a multicenter case control study to evaluate whether chronic alcoholism and alcohol are risk factors for developing a first generalized tonic-clonic epileptic seizure. Cases were 278 patients (92 women, 186 men), with a first generalized tonic-clonic seizure (either idiopathic or symptomatic), matched to 556 controls for center, sex, age, and weekday of the seizure. Information on risk factors was obtained through a questionnaire. This paper focuses on the study design (selection of cases and choice of controls), the validity of the instruments for data collection, and the strategies of study conduction (interviews, use of proxy respondents). Inter-rater agreement was excellent for drinking status, patterns of drinking, and broad indicators of consumption (yes/no). Agreement was variable for the number of servings/week, but was excellent (r = 0.91) for a summary of daily alcohol intake.

Alcohol use is a risk factor for a first generalized tonic-clonic seizure. The ALC.E. (Alcohol and Epilepsy) Study Group.

We performed a multicenter case-control study to estimate whether chronic alcoholism and alcohol consumption are risk factors for developing a first generalized tonic-clonic seizure (GTCS). We studied 237 first-seizure patients (158 men, 79 women) matched to 474 hospital controls for center, sex, age (+/-5 years), and weekday of the seizure. The risk of first GTCS in alcoholics was greater than in non-alcoholics for men (odds ratio, 6.8; 95% confidence limits, 3.6-13.0) and women (6.8, 1.6-32.6). The odds ratio (both sexes) was 1.2 (0.8-1.8) for an average daily intake of absolute alcohol of 1 to 25 g/day and rose with the amount of alcohol consumed daily: 1.3 (0.8-2.1) for 26 to 50 g/day, 3.0 (1.7-5.4) for 51 to 100 g/day, 7.9 (2.9-21.9) for 101 to 200 g/day, and 16.6 (1.9-373.4) for >200 g/day. Our study provides evidence of a powerful association between alcohol use, alcoholism, and the first GTCS.

Hereditary ataxias and paraplegias in Valle d'Aosta, Italy: a study of prevalence and disability.

INTRODUCTION: a study was conducted in the Valle d'Aosta Region, Italy, (115270 inhabitants) to determine the prevalence of hereditary ataxias (HA) and hereditary spastic paraplegias (HSP), and the degree of disability they cause. METHODS: we identified all patients with suspected HA or HSP referred from 1981 to 1991 to in- and out-patient departments, EEG, EMG, and CT-scan services, and centres for the handicapped. Harding's criteria were followed for diagnosis and classification. RESULTS: at the prevalence day, 17 patients were alive, with a prevalence ratio of 14.8/100,000 population. There were 2 cases of Friedreich's ataxia (FA), 1 of early onset cerebellar ataxia with retained tendon reflexes (EOCA), 1 of autosomal dominant cerebellar ataxia (ADCA), 8 of sporadic idiopathic late onset cerebellar ataxias, and 5 of HSP. CONCLUSIONS: epidemiological studies on HA and HSP show highly variable prevalence ratios, which could be due in part to the inclusion of sporadic cases. FA, EOCA and ADCA have similar prevalence ratios in most studies.

Epidemiology of primary intracranial tumors in the Valle d'Aosta (Italy) during the 6-year period 1986-1991.

A total of 285 new cases of primary intracranial tumors (PIT: 178 cases, 62%) and secondary forms (107 cases, 38%) were detected by CT scan and MRI during a population-based study of the incidence rates of these neoplasms in the Aosta Valley (N.W. Italy: 114,325 residents in 1988) during the period 1986-1991. The PIT are discussed in this paper. Histological confirmation was obtained in 60%. Age- and sex-adjusted mean annual incidence rate for all PIT was 28.3/100,000 (men 21.7; women 28.1). The incidence rates by types were 9.7 for meningiomas (men 5.3; women 13.9), 9.1 for tumors of the neuroepithelial group (men 10; women 8.1), 3.7 for adenomas (men 2.6; women 4.6), and 1.9 for neurinomas (men 2.9; women 0.9). Incidence rate increased with age. Meningiomas comprised 37% of the PIT, followed by tumors of the neuroepithelial group (35%), adenomas (14%, neurinomas (7.3%) and malignant lymphomas (2.3%). The remaining subtypes were 4.6%. Our data showed a clearly higher incidence rate than in previous population-based surveys. The differences were most marked in the meningioma group. The extensive use of CT scan and the more intensive case-finding could explain the differences.

[Frequency of hereditary neurologic diseases. A clinical study]. / La frequenza delle malattie neurologiche ereditarie. Uno studio clinico.

INTRODUCTION: The nervous system is affected in 30% of hereditary monogenic disorders and as many as 500 single-gene disorders display major neurologic symptoms. We have studied the frequency of hereditary neurological diseases to assess their importance in daily hospital activity. Only single-gene hereditary diseases with central or peripheral nervous system involvement were considered; thus chromosomal diseases and diseases with multifactorial etiology were excluded. METHODS: We surveyed admission to in- and out-patient departments of Neurology, Pediatrics, and Dermatology of the Aosta Regional Hospital for the calendar years 1982-1991, collecting 229 cases, 95 women and 134 men. Out-patient departments held 126 patients, the others came from in-patient departments. Admission to the neurological in-patient department were 1.8% of total neurological admissions in the same period. Each diagnosis was assigned to the code number of the International Classification of Diseases (ICD-IX Revision, 1975). RESULTS: We found 33 different phenotypes. Most frequent diagnoses were: essential tremor (89 patients), hereditary sensory-motor neuropathy (HSMN) type I (28), Huntington's chorea (13), progressive muscular dystrophy limb-girdle type (8), neurofibromatosis type I (9), HSMN type II (9), spinocerebellar ataxia (9), hereditary spastic paraplegia (7), spinal muscular atrophy type IV (5), myotonic dystrophy (5), cerebellar ataxia (4), HSMN type III (4), spinal muscular atrophy type II and III (3), tuberous sclerosis (3). Essential tremor mostly affected persons in the over-50 age groups. On the contrary, the other neurologic monogenic diseases were diagnosed in all ages with the following age-group breakdown: 0-9, 11%; 10-19, 16%; 20-29, 15%; 30-39, 8%; 40-49, 11%; 50-59, 19%; 60-69, 14%, 70+, 7%. Consistently with the general rule, autosomic recessive diseases have the earliest onset and autosomic dominant ones the latest; HSMN, spinal muscular atrophy and Huntington's chorea were the disorders diagnosed in older age group. DISCUSSION: Although the frequency of the single neurologic monogenic disease is low (with the exception of essential tremor), their overall prevalence is higher than the prevalence of multiple sclerosis or the peripheral neuropathies. All age-groups are involved. We separated three groups of diseases: 1) two relatively benign diseases, essential tremor and the HSMN, affecting half of our patients; 2) five severe and more common diseases (Huntington's chorea, progressive muscular dystrophy limb-girdle type, neurofibromatosis type I, spinocerebellar ataxia, hereditary spastic paraplegia), affecting 1/4 of patients; and 3) a group of rare, mostly severe diseases, affecting the remaining 1/4 of patients.

Incidence and prognosis of stroke in the Valle d'Aosta, Italy. First-year results of a community-based study.

BACKGROUND AND PURPOSE: We sought to determine the incidence rate, risk factors, and prognosis of stroke in Valle d'Aosta, Italy, to provide information for planning regional health-care facilities. METHODS: We undertook a prospective study of all new cases of stroke in the geographically defined population of 114,325 residents of Valle d'Aosta in northern Italy. RESULTS: In the first year of the study (January 1-December 31, 1989), 254 cases of first stroke were registered. The crude annual incidence rate was 2.23/1,000, 1.98/1,000 for men and 2.46/1,000 for women. After adjustment to the 1988 Italian population, the incidence rate for first stroke was 2.15/1,000 per year, 2.48/1,000 per year for men and 1.99/1,000 per year for women. The pathological diagnosis was cerebral infarction in 67%, intracranial hemorrhage in 15%, and unknown in 18%. The overall 30-day case-fatality rate was 31%. In survivors, Barthel Index Score recorded at 30 days from stroke onset showed that 100 patients (62%) were dependent in activities of daily living. CONCLUSIONS: Our results do not differ significantly from those reported in Umbria, the only similar study performed in Italy, and support non-Italian data as to risk factors in stroke.

Clinical and neuroradiological findings in a case of pure word deafness.

Pure Word Deafness is a clinical syndrome included among the aphasias and is marked by complete deafness of sudden onset with conserved ability to understand and read the written word and with no speech disorders. We report the case of 61 year old man in whom pure word deafness developed after two episodes of acute cerebral ischemia in quick succession. Neuroimaging procedures, that is: computed tomography scan, single photon emission computed tomography and magnetic resonance imaging, revealed the presence of two ischemic lesions in the temporal cortex bilaterally. Neurophysiological investigations (electroencephalogram, brainstem auditory evoked potentials and stapedial reflex) were also studied. We discuss the outcome of all these investigations in the light of the relevant published work.