V. La Bella

Noninvasive positive-pressure ventilation in ALS: Predictors of tolerance and survival

Objective: To identify factors associated with tolerance and survival after noninvasive positive-pressure ventilation (NIPPV) and to investigate the influence of NIPPV on lung function in patients with ALS. Methods: NIPPV was offered to 71 patients with ALS in accordance with currently published guidelines. Effects of NIPPV on lung function and factors influencing tolerance and survival after NIPPV were studied. Results: Forty-four patients (61.9%; 95% CI: 50.6 to 73.2) tolerated NIPPV (NIPPV use ≥4 h/day) and 27 (38.1%; 95% CI: 26.8 to 49.4) were intolerant (NIPPV use <4 h/day). Patients with mild or moderate bulbar symptoms were more likely to tolerate NIPPV than those with severe impairment (odds ratio = 6.09, 95% CI: 1.18 to 31.52, p = 0.031). After NIPPV introduction, a slower decline in forced vital capacity (FVC) was observed in tolerant vs intolerant patients (p = 0.002). The slope of FVC decline after NIPPV initiation (risk ratio [RR]: 0.78, 95% CI: 0.65 to 0.94, p = 0.01) together with NIPPV tolerance (RR: 0.32, 95% CI: 0.13 to 0.78, p = 0.013) were the only independent predictors of survival in the overall group of patients. In multivariate analysis, body mass index was the most powerful predictor of longer survival after NIPPV in tolerant patients (RR: 0.77, 95% CI: 0.61 to 0.96, p = 0.022). Conclusion: Survival after noninvasive ventilation was independently related to ventilatory use (≥4 h/day) and to the modifications of forced vital capacity decline after treatment initiation. The severity of bulbar impairment and the nutritional status of the ALS patients at the introduction of ventilation may predict tolerance and survival.

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Spataro R, Lo Re M, Piccoli T, Piccoli F, La BellaV. Causes and place of death in Italian patients with amyotrophic lateral sclerosis.
Acta Neurol Scand: 122: 217–223.
© 2010 The Authors Journal compilation

Long-term interferon-β treatment for multiple sclerosis

Abstract.The aim of our study was to analyze the dropout rate in patients with relapsing-remitting multiple sclerosis (RRMS) under long-term treatment with the three commercially available interferon beta (IFNβ) preparations. According to the drug taken, we divided 122 RRMS patients into 4 groups: Betaferon group, 56 patients taking INFβ-1b (24 MIU weekly, subcutaneous injections); Avonex group, 38 patients taking IFNβ-1a (6 MIU weekly, intramuscularly); Rebif group, 18 patients taking INFβ-1b (18 MIU subcutaneously). Ten patients who shifted from Betaferon to Avonex were included in a fourth group. Dropouts were registered every trimester with the related cause. Data were evaluated using Kaplan-Meier survival analysis and log-rank test. During the observation period of five years, 48 patients (39.9%) dropped out: 48% of the patients in Betaferon group withdrew at a median of 758 days, 26% of the Avonex group at 356 days; 38% of the Rebif group at 421 days, and 40% of those who shifted from Betaferon to Avonex at 259 days. The differences between groups were not significant on survival analysis. Patients receiving higher dose treatment (Betaferon and Rebif groups) dropped out mainly for clinical adverse events; conversely, patients receiving lower dose therapy (Avonex group) dropped out most often for inefficacy. Patients who shifted to a lower dose treatment (fourth group) had a dropout rate similar to that of the initial treatment. Our data showed that one-third of the patients stopped the therapy, mostly for adverse events and then for inefficacy, while the remaining two-thirds were still on treatment without problems up to 5 years of follow-up. Compliance seems related to the dose of the drug, but further analysis is needed to confirm our data.

Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis

Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti‐apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS).

A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy

Mutations in the Angiogenin gene (ANG) linked to 14q11.2 have been recently discovered to be associated with Amyotrophic Lateral Sclerosis (ALS) in Irish and Scottish populations. In our study we investigated the role of ANG gene in ALS patients from southern Italy. We found a novel mutation in the signal peptide of the ANG gene in a sporadic patient with ALS (SALS). The molecular analysis of the ANG gene also demonstrated an allelic association with the rs11701 single nucleotide polymorphism (SNP) in familial ALS (FALS) but not in SALS patients. Our finding supports the evidence that the ANG gene is involved in ALS.

Elevated cerebrospinal fluid and plasma homocysteine levels in ALS

Background:  High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer’s, Parkinson’s diseases and, recently, amyotrophic lateral sclerosis (ALS).

Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis

Objective: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. Methods: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. Results: We found significantly higher intermediate PolyQ expansions ≥32 for ATXN-1 alleles and ≥28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions. Conclusions: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.

The eye‐tracking computer device for communication in amyotrophic lateral sclerosis

To explore the effectiveness of communication and the variables affecting the eye‐tracking computer system (ETCS) utilization in patients with late‐stage amyotrophic lateral sclerosis (ALS).

Fatigue, sleep, and nocturnal complaints in patients with amyotrophic lateral sclerosis

Background and purpose:  Fatigue is a common symptom in amyotrophic lateral sclerosis (ALS). Although sleep disturbances are a candidate factor that may interfere with fatigue in patients with ALS, the role of sleep‐related abnormalities in determining fatigue in ALS is unknown.

TELEPHONE FOLLOW - UP FOR PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS

The relentless evolution of amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disorder of the upper and lower motoneurons, leads to an increasing level of disability. Most patients, during the course of the disease, become unable to attend the tertiary clinical care center and are thus prevented from enrolling in clinical trials or benefiting from specialized care and management. The main objective of this study was to verify whether the ALS functional rating scale (ALSFRS) could be reliably administered by telephone to patients, when unable to attend the ALS clinic, or to their caregivers. ALSFRS is a validated instrument that assesses the functional status and the disease progression in ALS. We first administered the functional rating scale directly in the clinic to 30 patients, with definite or probable ALS, and to their respective caregivers, and found a very high agreement between the two groups for the total score and the majority of the rating items. Next, we showed, in both patients and caregivers, a high degree of correlation between the total score of the ALSFRS measured by telephone and that reported in the clinic. This indicates that ALSFRS is a reliable instrument for monitoring the disease progression in homebound patients, even when the person contacted by telephone is the caregiver. We also performed a telephone clinic, based on an unstructured interview, with 16 ALS patients at an advanced stage of the disease and unable to attend the ALS clinic. On some occasions, the person interviewed was the caregiver. The symptoms most frequently reported were a worsening of muscle strength, swallowing and breathing problems, constipation, and inability to clear lung secretions. Several patients asked for assistive and adaptive equipment. All patients and caregivers found the telephone clinic very useful and considered it a good complement to the management and care programme.