Edo Bottacchi

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. ALS = amyotrophic lateral sclerosis; CI = confidence interval; EEC = El Escorial diagnostic criteria; EEC-R = El Escorial revised criteria; MND = motor neuron disease; PARALS = Piemonte and Valle d’Aosta Register for ALS; PCRA = Piemonte Central Regional Archive; VACRA = Valle d’Aosta Central Regional Archive.

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.

Safety and factors related to survival after percutaneous endoscopic gastrostomy in ALS

Article abstract 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 ≥10% healthy body weight and forced vital capacity <65%. PEG may be a useful option in the symptomatic treatment of dysphagia in ALS.

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.

Polyneuropathy in hypothyroidism: clinical, electrophysiological and morphological findings in four cases.

Clinical, neurophysiological and morphological studies of four patients with polyneuropathy and secondary hypothyroidism are reported. Neurophysiological studies revealed signs of muscle denervation and reduction of conduction velocity in all the patients. Sural nerve biopsies showed axonal degeneration in all cases but one. All the patients were treated with replacement therapy and clinical symptomatology and neurophysiological parameters improved in all patients.

Psychosis associated to Parkinson's disease in the early stages: relevance of cognitive decline and depression

Objective To evaluate the prevalence of psychosis associated with Parkinsons disease (PSY-PD) in its early stages, its incidence over a 24 month follow-up period and the association with motor and non-motor clinical features. Methods PRIAMO is a 2 year longitudinal observational study that has enrolled patients with parkinsonism in 55 Italian centres. A cohort of 495 patients with early disease stage PD (baseline Hoehn and Yahr score ≤2, diseases duration (median) 3.4 years) were followed for 2 years. PSY-PD was evaluated by means of a clinician rated questionnaire and defined as the presence of at least one of the following symptoms occurring for at least 1 month: illusions, hallucinations, jealousy ideas and persecutory ideas. Patients with and without PSY-PD were compared on several clinical variables, encompassing motor and non-motor features. Results The prevalence of PSY-PD at baseline was 3%; the incidences at 12 and 24 months were 5.2% and 7.7%, respectively. Longer disease duration and prescription of dopamine agonists at baseline were associated with the development of PSY-PD over the 24 month period. At this follow-up time, worse disease severity, decline in cognitive performances, presence of depressive symptoms and anxiety were more frequently observed in PSY-PD. Conclusions Psychotic type symptoms may occur in the early stages of PD although less frequently than in later stages. Beyond dopaminergic treatment, there are disease related factors, such as disease severity and the occurrence of cognitive and depressive symptoms, which may underlie the onset of psychotic type symptoms from the earliest stages.

Community-Based Study of Stroke Incidence in the Valley of Aosta, Italy

The purpose of our study was to determine the incidence of stroke, case-fatality rate and disability at 1 year in the Valley of Aosta (Italy) in the years 2004 and 2005. All suspected strokes occurring between January 1, 2004, and December 31, 2005, in the resident population of the Valley of Aosta were identified according to the WHO criteria for stroke and included in a stroke registry (Cerebrovascular Aosta Registry, CARe) after revision by a clinical panel. Multiple overlapping sources were used to ascertain the cases. In the study period, 553 incident strokes were registered. A CT scan was performed in 94.2% of cases. The crude annual incidence rate was 223 (95% CI 197–249) per 100,000 inhabitants. After age and sex adjustment to the ‘European’ population, the stroke incidence rate was 126 (95% CI 106–146). In the 1-year follow-up, only a small number of patients with a first-ever stroke in their life time suffered a new event. Compared with the previous study performed in our region (Valley of Aosta) in 1989, a marked decline in the incidence rate was seen after adjustment to the ‘European’ population, and the 28-day case-fatality rate declined dramatically between 1989 and 2004–2005.

Alcohol use is a risk factor for a first generalized tonic-clonic seizure

Article abstract-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. NEUROLOGY 1997;48: 614-620

Risk factors for a first epileptic seizure after stroke: A case control study

INTRODUCTION The risk of seizures increases after stroke, but not all risk factors are known. We aimed to identify factors that increase the risk of a first seizure after a stroke. METHODS Multicenter case-control study of 161 patients with a first seizure after stroke (105 provoked/acute and 56 unprovoked/remote symptomatic) matched to 279 hospital stroke controls by center, gender, age and timing of stroke. RESULTS The risk of first seizure (odds ratio (OR), 95% confidence limits (CL)) was 3.6 (2.4-5.5) for cortical involvement, 2.5 (1.2-5.3) for multiple CT-scan lesions, 2.4 (1.5-3.9) for supratentorial lesions, 2.4 (1.6-3.7) for prior lesions on CT-scan, 2.1 (1.1-4.7) for family history of seizures, 2.0 (1.1-3.6) for use of epileptogenic drugs, 1.7 (1.0-2.9) for large lesions, 1.6 (1.0-2.8) for hemorrhagic lesions, and 1.4 (1.0-2.2) for cortical atrophy. After multivariate analysis, including all the factors significant in univariate analysis, the strongest independent predictor of a first seizure was cortical involvement (OR 3.3; 95% CL=2.1-5.0), followed by prior lesions (2.2; 1.4-3.4) and hemorrhagic stroke (1.8, 1.0-3.2). The multivariate analysis model for remote symptomatic seizures included cortical involvement, large size, and prior lesions; the model for acute seizures included cortical involvement, alcohol consumption >50 g/day, hemorrhagic stroke, and prior lesions on CT-scan. DISCUSSION Cortical involvement, the presence of prior lesions on CT-scan, and hemorrhagic lesion are the most important risk factors for a first-ever seizure after stroke.

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

Abstract. 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.