Paolo Ghiglione

A cross sectional study on determinants of quality of life in ALS

Background: Understanding the determinants of quality of life (QoL) in amyotrophic lateral sclerosis (ALS) has become increasingly important with the recent emphasis on the comprehensive management of patients. Objective: To evaluate the determinants of QoL in ALS using two scales with different theoretical constructs: the Schedule for the Evaluation of QoL-Direct Weighting (SEIQoL-DW), which evaluates subjective aspects of QoL, and the McGill QoL Questionnaire (MQOL), which evaluates both health related and non-health related factors of QoL. Methods: Eighty consecutive patients with ALS underwent a battery of tests evaluating QoL and a series of physical, emotional, psychological, and socioeconomic predictor variables. A stepwise linear regression model was used to compare QoL scores and explicatory variables. Results: SEIQoL-DW score was related to social support, depression, religiosity, and socioeconomic status. Total MQOL score was related to social support, socioeconomic status, and clinical status. MQOL single item score (MQOL-SIS) was related to social support, depression, social withdrawal, and socioeconomic status. SEIQoL-DW score was not related to total MQOL score. Conversely, a significant correlation was found between SEIQoL-DW and MQOL-SIS. Conclusions: With both QoL scales, the most important explicatory variable of QoL was the self perceived quality of social support. Physical status was not relevant in determining QoL. This study indicates that health related QoL measures are not adequate to assess QoL in patients with ALS, because their appreciation of QoL mainly relies on psychological, supportive, and spiritual factors. Therapeutic interventions should consider the psychological needs of patients and pay greater attention to caregivers’ issues.

Caregiver burden and patients’ perception of being a burden in ALS

The determinants of ALS caregiver burden and the feeling of the patients as being a burden were assessed using the Caregiver Burden Inventory and the Self-Perceived Burden Scale in 60 caregiver-patient couples. Caregiver burden was correlated to their level of depression and quality of life and, differently from other chronic disorders, increased with the worsening of patients’ disability. ALS patients have a good objective perception of their impact on caregivers.

Percutaneous radiological gastrostomy: a safe and effective method of nutritional tube placement in advanced ALS

Background: Enteral nutrition may be required in amyotrophic lateral sclerosis (ALS), and is usually achieved by percutaneous endoscopic gastrostomy (PEG). As PEG is not indicated in patients with severe respiratory impairment, an alternative is percutaneous radiological gastrostomy (PRG), involving air insufflation into the stomach under fluoroscopic guidance for tube insertion. Objective: To evaluate the safety of PRG and its effect on survival and respiratory function in ALS patients with respiratory failure. Methods: 25 consecutive ALS patients with severe dysphagia and forced vital capacity (FVC) <50% underwent PRG after October 2000. They were compared with 25 consecutive ALS patients with FVC <50% who underwent PEG before October 2000. Respiratory function was evaluated before and after the procedure. Results: The two groups were similar for all relevant characteristics. PRG was successful in all cases, PEG in 23/25. One patient in each group died after the procedure. The mean survival time after the procedure was 204 days in the PRG group and 85 days in the PEG group (p<0.004). Respiratory function decreased more in the PEG group than in the PRG group (p<0.02). Conclusions: PRG appears to be safer than PEG in ALS patients with moderate or severe respiratory impairment, and is followed by a longer survival.

ALS in Italian professional soccer players: The risk is still present and could be soccer-specific

We previously found an increased risk for ALS in Italian professional soccer players actively engaged between 1970 and 2001 (n =7325). The present study extends previous work with a prospective follow-up of the original cohort to 2006 and investigates the risk of ALS in two other cohorts of professional athletes, basketball players (n =1973) and road cyclists (n =1701). Standardized morbidity ratios (SMRs) were calculated. Among soccer players three new cases of ALS were identified, reaching a total of eight ALS cases (mean age of onset, 41.6 years). The number of expected cases was 1.24, with an SMR of 6.45 (95% CI 2.78–12.70; p<0.00001). The risk of ALS was higher for careers lasting >5 years, for midfielders, and for players engaged after 1980. No basketball player and no cyclist developed ALS. This prospective extension of the Italian soccer players cohort survey confirms the highly significant risk of developing ALS, the young age of onset, the dose-effect risk and a predilection for midfielders. The absence of ALS cases in professional road cyclists and basketball players indicates that ALS is not related to physical activity per se.

Anxiety undermines quality of life in ALS patients and caregivers

Background:  Although depression has been widely studied in amyotrophic lateral sclerosis (ALS), there is little information on anxiety.

ALS patients and caregivers communication preferences and information seeking behaviour.

To evaluate information preferences and information seeking behaviour in ALS patients and caregivers. Sixty ALS patients and caregivers couples were interviewed using a structured questionnaire about the content of diagnosis communication and their information seeking behaviour. The patients (35 men and 25 women) had a mean age of 63.4 years (SD 9.5). The caregivers (21 men and 39 women) had a mean age of 53.3 years (SD 14.9). The overall satisfaction with bad news communication and the impression that the physician had understood their feelings were higher amongst patients. Both parties indicated that the most important aspects to be informed were current researches, disease‐modifying therapies and ALS outcome. Approximately 55% of patients and 83.3% of caregivers searched for information from sources outside the healthcare system. The most frequently checked source was internet, although its reliability was rated low. The caring neurologist should better attune the content of communication to patients’ and caregivers’ preferences, trying to understand what they want to know and encouraging them to make precise questions. Health professionals should be aware that ALS patients and caregivers often use internet to obtain information and should help them to better sort‐out and interpret the news they found.

HFE H63D polymorphism is increased in patients with amyotrophic lateral sclerosis of Italian origin

A role for metal-mediated oxidative stress in the pathogenesis of amyotrophic lateral sclerosis (ALS) was proposed in 1994 in the first studies of familial ALS mutant superoxide dismutase 1, and interference with iron homoeostasis is now postulated.1 The HFE gene on chromosome 6 is a mean corpuscular haemoglobin class I-like molecule related to iron regulation. Mutations in the coding region cause hereditary haemochromatosis, a common autosomal recessive disorder of iron metabolism that leads to iron overload in adulthood. Recent reports on HFE mutations in ALS showed contradictory results. Two studies described a higher prevalence of the HFE mutations in ALS than in the control group, and one study did not find any difference between the patients with ALS and the control group.2–4 We analysed a series of Italian patients with ALS to investigate whether mutations in the HFE gene could represent a risk factor for ALS. A total of 149 sporadic Italian patients with ALS (mean (standard deviation (SD)) age 59.4 (9.7) years) according to El Escorial criteria for clinically definite or probable ALS were consecutively recruited to this study. Control samples were obtained from 168 healthy people, matched by age (difference of 5 years), sex and …

Anaplasia Is Rare and Does Not Influence Prognosis in Adult Medulloblastoma

Histopathologic grading based on increasing anaplasia predicts clinical behavior of pediatric medulloblastomas. The present study was aimed at grading 86 medulloblastomas of adult patients (aged 18 and older) by anaplasia and analyzing the predictive power. Nodularity, desmoplasia, nuclear size, nuclear pleomorphism, necrosis, and endothelial proliferations have been evaluated. Morphometric analysis of nuclear size was performed using the Eclipse Net program. Patients treated with standard postoperative radiotherapy (35 Gy to craniospinal axis and 50 Gy to posterior fossa) were considered for correlation with survival. Pathologic data and total survival were compared by Kaplan-Meier and logrank analysis. No correlation was found between total survival duration and individual pathologic features. Cooccurrence of nuclear pleomorphism, large nuclear diameter, microvascular proliferations, and necroses did not predict outcome. Severe nuclear pleomorphism was found in 4 of 86 cases; the only large-cell medulloblastoma was from an 18-year-old patient. Histopathologic factors have no clinical use for stratification of patients in risk groups. The histologic spectrum of medulloblastoma in adults is different from that in children.

Amyotrophic lateral sclerosis associated with pregnancy: report of four new cases and review of the literature.

Pregnancy in women with ALS is rare and is generally considered a potentially dangerous event. We describe four ALS cases associated with pregnancy, together with a review of the literature. Three of the four women described developed ALS during pregnancy. In three cases a normal delivery was performed, with a healthy child. One patient, with severe respiratory failure, underwent an interruption of pregnancy. Seven other cases are reported in the literature, featuring a total of 11 pregnancies. The association between pregnancy and ALS is quite rare, and a pathogenic relationship cannot be excluded. The pregnancy and the delivery may be normal, but respiratory function should be carefully monitored. Generally, ALS does not have deleterious effects on fetal development. However, pregnancy in a woman with severe respiratory failure may precipitate the disease.

The IVS1 +319 t>a of SOD1 gene is not an ALS causing mutation

Amyotrophic lateral sclerosis (ALS) is caused by mutations in the gene for Cu/Zn superoxide dismutase (SOD1) in 10% of familial and sporadic cases. During the SOD1 analysis of 9 FALS and 121 SALS, in only one sporadic case we found the exonic mutation N19S; in 15 SALS patients we found a 319t>a variation in IVS1 sequence, at 108 bp upstream from exon 2. This variation has an unusually high frequency of 11% and is always in linkage disequilibrium with a described polymorphism in IVS3, +34a>c. The 319t>a variation is classified in two different public databases, HGMD and The ALS Online Database, as a splicing mutation and not as a polymorphism. The unusually high frequency of this mutation in our patients prompted us to determinate its frequency in 130 age- and gender- matched healthy controls and in 54 patients with Alzheimers disease. We found again linkage disequilibrium with the polymorphism in intron 3, and the frequency of 11% and 7.8%, respectively. These results strongly support the idea that the IVS1 +319 t>a alone is not an ALS causing mutation, and that special care must be taken in the interpretation of data from mutations databases for correct genetic counselling.