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.

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.

Skeletal muscle NAD+(P) and NADP+-dependent malic enzyme in Friedreich's ataxia.

Malic enzymes were studied in skeletal muscle from seven patients with Friedreich's ataxia (FA) and nine controls. Muscle contained three different malic enzymes. There were two strictly NADP+-dependent enzymes, one in the cytosol and one in mitochondria. These two enzymes are not allosteric. In FA muscle, activity of the mitochondrial NADP+-linked enzyme was significantly low and the cytosol NADP+-linked enzyme was significantly increased. A third malic enzyme, NAD+(P)-dependent, was found in the mitochondrial fraction. That enzyme had allosteric properties, and its activity was about the same in FA and control muscle.

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.

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.

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.

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.

Parasympathetic assessment in Parkinson's disease.

There is little evidence of autonomic dysfunction in PD, although autonomic disturbance was included in the original description by J. Parkinson. In addition, there are no data for de novo PD patients. We selected 14 de novo parkinsonians (seven men and seven women), aged 62.7 +/- 8.2 years, with mild disease (stage 1 through 2 on the Hoehn and Yahr's scale), without history of diabetes, heart disease, or alcoholism, and without neuropathy or orthostatic hypotension. Fourteen age- and sex-matched normal persons were controls. We found a highly significant difference in the respiratory sinus arrhythmias during deep breathing (p less than 0.01); the basal heart rate, the respiratory sinus arrhythmias during quiet breathing, and the Valsalva ratios did not differ statistically, however. In the absence of neuropathy and orthostatic hypotension and in the presence of normal Valsalva ratios, we believe that the abnormality found by us may apply only to parasympathetic dysfunction, perhaps at a central level. In addition, the abnormality seems to be independent of stage and therapy.

[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.

[The diagnostic course in patients with hereditary ataxias and hereditary spastic paraparesis]. / L'iter diagnostico dei pazienti affetti da atassie e paraparesi spastiche ereditarie.

A postal questionnaire was sent to all patients affected by hereditary ataxias and hereditary spastic paraparesis resident in the province of Turin (Italy) to study their diagnostic process. A 61% response rate was obtained. The mean time interval between onset and diagnosis was 6 years (1 to 32 years). The percentage of late diagnoses dropped from 59% before 1959 to 19% after 1970, mostly because a reduction of the interval between symptom onset and the first contact with the general practitioner. The onset with dysarthria and ataxia led to earlier neurologic consultation, but the whole time requested for the diagnosis was not modified. A reduction of the time needed for the diagnostic process may be important to address the family to an early genetic counselling.

Parasympathetic function in Huntington's disease.

Parasympathetic function in 7 Huntington's chorea patients with a duration of the disease ranging from 1 to 20 years, was evaluated by studying R-R intervals during quiet and deep breathing and Valsalva manoeuvre. All 7 patients were free of neuropathy, orthostatic hypotension, heart or lung disease and had had no medication for at least 15 days prior to hospitalization. Seven normal subjects served as controls. On the whole, the responses of the Huntington's chorea patients were not significantly different from those of the controls. Abnormal responses to all the tests were received in only one patient and a low R-R variability during deep breathing in the youngest patients. Unlike other Central Nervous System degenerative disorders, in Huntington's disease parasympathetic autonomy seems to be sufficiently preserved.

[Acute myopathy and hyperthyroidism]. / Myopathie aiguë et hyperthyroïdie.

A 40 year-old woman with a rapidly progressive proximal muscle deficit of all four limbs had an acute myopathy secondary to hyperthyroidism. Biopsy of the quadriceps femoris revealed signs of non specific muscle impairment with type II fiber atrophy. Treatment with methimazole and correction of the thyroid condition led to rapid disappearance of the disorders. Eighteen months later the clinical status was normal and a second quadriceps femoris biopsy showed that the muscle had normalized.