We have performed a systematic review to summarize current knowledge concerning factors related to survival in ALS and to evaluate the implications of these data for clinical trials design. The median survival time from onset to death ranges from 20 to 48 months, but 10–20% of ALS patients have a survival longer than 10 years. Older age and bulbar onset are consistently reported to have a worse outcome. There are conflicting data on gender, diagnostic delay and El Escorial criteria. The rate of symptom progression was revealed to be an independent prognostic factor. Psychosocial factors, FTD, nutritional status, and respiratory function are also related to ALS outcome. The effect of enteral nutrition on survival is still unclear, while NIPPV has been found to improve survival. There are no well established biological markers of progression, although some are likely to emerge in the near future. These findings have relevant implications for the design of future trials. Randomization, besides the type of onset, should take into account age, respiratory status at entry, and a measure of disease progression pre-entry. Alternative trial designs can include the use of natural history controls, the so-called minimization method for treatment allocation, and the futility approach.

Our objective was to investigate exposure to physical exercise and trauma in patients with amyotrophic lateral sclerosis (ALS) compared to the general population. Previous studies in this area have yielded conflicting results. Using population-based ALS registries from Italy, the UK and Ireland, newly diagnosed patients with definite, probable or possible ALS were enrolled in a case-control study with two age- and sex-matched controls for each patient. Source, intensity and duration of physical activity and history of trauma were recorded. We here present the results of a pilot investigation. We studied 61 patients and 112 controls. Forty-one per cent of cases and 17.0% of controls (p = 0.001) had blue-collar occupations; 13.1% versus 3.6% reported strenuous physical activity at work (p = 0.05). Compared with controls, ALS patients had a longer exposure to work-related (10.7 vs. 7.3 years; p = 0.02) and sport-related physical exercise (9.6 vs. 5.2 years; p = 0.005). Three patients (0 controls) reported professional sports (p < 0.04). Traumatic events were similar. Blue collar occupation (OR 4.27; 95% CI 1.68–10.88) and duration of sport-related physical exercise (OR 1.03; 95% CI 1.00–1.05) were independent variables in multivariate analysis. We concluded that ALS is associated with physical exercise but not with traumatic events.

Effective treatments for amyotrophic lateral sclerosis (ALS) have remained elusive. Only riluzole, a drug thought to affect glutamate metabolism, improves survival albeit to modest extent. Explanations for the negative results of therapeutic trials include a likely heterogeneity, both in disease susceptibility and pathogenic mechanisms, and faulty methodology of clinical trials. Further understanding of these factors will lead to improvements in patient stratification, and in the design of future clinical trials.

Background

Geographical differences in amyotrophic lateral sclerosis (ALS) incidence have been reported in the literature, but comparisons across previous studies are limited by different methods in case ascertainment and by the relatively small size of the studied populations. To address these issues, the authors undertook a pooled-analysis of European population-based ALS registries.

Methods

All new incident ALS cases in subjects 18 years old and older were identified prospectively in six population-based registries in three European countries (Ireland, United Kingdom, Italy) in the two year period 1998-1999 with a reference population of almost 24 million.

Results

Based on 1,028 identified incident cases, the crude annual incidence rate of ALS in the general European population was 2.16 per 100,000 person-years; 95% CI 2.0-2.3), with similar incidence rates across all registries. The incidence was higher among men (3.0 per 100,000 person-years; 95% CI = 2.8 to 3.3) than among women (2.4 per 100,000 person-years; 95% CI=2.2 to 2.6). Spinal onset ALS was more common among men compared to women, particularly in the 70-80 year age group. Disease occurrence decreases rapidly after 80 years of age.

Conclusions

ALS incidence is homogeneous across Europe. Sex differences in incidence may be explained by the higher incidence of spinal onset ALS among males and the age-related disease pattern suggests that ALS occurs within a susceptible group within the population rather than being a disease of aging.

Background

The potential effect of age-related factors on health-related quality of life (HRQOL) of patients with epilepsy has rarely been analyzed in the literature.

Methods

We examined this association in a selected population of 815 adults with epilepsy recruited in the context of a multicentre study for the evaluation of Epi-QoL, one of the first Italian epilepsy-specific measures of HRQOL for adults with epilepsy. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains, which was successfully tested for reproducibility and validity. Ordinary least-squares regression models were used to assess the relationships between age-related factors (patient's age, age at seizure onset, and duration of epilepsy) and overall Epi-QoL score, controlling for the effect of potential confounders. We fitted simple regression models including each age-related factor alone to assess the independent role of each factor on the overall Epi-QoL score. We also fitted multiple regression models including pairs of age-related factors solely, as well as one or two age-related factors together with the same set of confounders.

Results

Simple regression models showed that age and duration of epilepsy were significant negative predictors of the overall Epi-QoL score: the higher was each age-related factor, the lower was the overall Epi-QoL score; age at onset alone was a nonsignificant predictor of the overall Epi-QoL score. Multiple regression models including two age-related factors solely showed that duration of epilepsy was still a significant negative predictor of the overall Epi-QoL score in both pairwise models, whereas age was a significant negative predictor only in the model including age at onset. Age at onset emerged as a significant positive predictor of the overall Epi-QoL score only in the model including age: the higher was age at onset, the higher was the overall Epi-QoL score. Adjusted regression models including either one or two age-related factors and controlling for the selected confounding variables showed that the age-related factors had no significant effect on the overall Epi-QoL score anymore.

Conclusions

If no other known correlates of the overall Epi-QoL score are considered, age and duration of epilepsy can be expected to have a significant negative association with HRQOL in epilepsy (with the effect of duration being stronger and more consistent across models than the one of age), whereas age at onset is a positive predictor of the overall HRQOL of limited significance. However, demographic and clinical factors, such as seizure frequency in the preceding 12 months, may provide a better explanation of HRQOL in epilepsy.

The objective of this paper was to assess prevalence and characteristics of anxiety and depression in migraine without aura and tension-type headache, either isolated or in combination. Although the association between headache and psychiatric disorders is undisputed, patients with migraine and/or tension-type headache have been frequently investigated in different settings and using different tests, which prevents meaningful comparisons. Psychiatric comorbidity was tested through structured interview and the MINI inventory in 158 adults with migraine without aura and in 216 persons with tension-type headache or migraine plus tension-type headache. 49 patients reported psychiatric disorders: migraine 10.9%, tension-type headache 12.8%, and migraine plus tension-type headache 21.4%. The MINI detected a depressive episode in 59.9, 67.0, and 69.6% of cases. Values were 18.4, 19.3, and 18.4% for anxiety, 12.7, 5.5, and 14.2%, for panic disorder and 2.3, 1.1 and 9.4% (p = 0.009) for obsessive–compulsive disorder. Multivariate analysis showed panic disorder prevailing in migraine compared with the other groups (OR 2.9; 95% CI 1.2–7.0). The association was higher (OR 6.3; 95% CI 1.4–28.5) when migraine (with or without tension-type headache) was compared to pure tension-type headache. This also applied to obsessive–compulsive disorder (OR 4.8; 95% CI 1.1–20.9) in migraine plus tension-type headache. Psychopathology of primary headache can reflect shared risk factors, pathophysiologic mechanisms, and disease burden.

Epilepsy is a chronic condition requiring long-term treatment with drugs that have intrinsic limitations. Antiepileptic drugs (AEDs) are effective in suppressing seizures but do not alter the disease process. They have a suboptimal tolerability profile and can be teratogenic. Second-generation compounds may be better tolerated but no more effective than traditional AEDs. In this light, as drug therapy is purely symptomatic, acute symptomatic seizures (i.e. seizures occurring in close temporal relationship with acute CNS insults) may require treatment only until recovery or stabilization of the injury. Treatment of the first unprovoked seizure may be considered in patients with abnormal EEG and imaging findings and in those in whom the relapse has severe social, emotional and personal implications. In these cases and in patients with epilepsy (i.e. repeated unprovoked seizures), drugs for partial seizures supported by class I regulatory trials or pragmatic trials are oxcarbazepine in children, carbamazepine or lamotrigine in adults, and lamotrigine or gabapentin in the elderly. Pragmatic trials support use of valproate for generalized seizures, except for women of childbearing age for whom the drug should be tailored to the individual patient. The lowest maintenance dose should be chosen, based on the efficacy and tolerability of the assigned drug. If the first monotherapy fails, the safety profile of a drug is important when opting for another monotherapy or for an add-on therapy. The epilepsy syndrome and the social, psychological and emotional profile of the patient all contribute to the individualization of treatment discontinuation after long-term seizure remission.

To assess the stroke workload of Italian neurological services and to correlate it with indicators of each hospital’s emergency setting. A semi-structured questionnaire was sent to the 220 neurology units (NU) located in hospitals with an emergency room (ER) (155 responders, 71%). Stroke was the most common discharge diagnosis (29%) (273 patients/year/NU on average) and condition requiring consultation in ER (28%). A stroke unit was available in 28% of NU, bedside monitors in 45%, a 24 hour/day and 7 day/week (24/7) CT scan in 90%, a 24/7-MRI in 32%, a 24/7 on-duty neurologist in 36%. The stroke workload was correlated only with the number of ER consultations per year, and marginally to the presence of stroke units and the number of monitored beds in the univariate, but not in the multivariate analysis. The stroke workload in Italian NU is very high, but is largely unrelated to their structural and functional characteristics, in contrast with the international indications requiring several essential criteria for the best hospital management of all stroke patients.