Correlation between Apolipoprotein E genotype and brain metabolism in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment. METHODS: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates. RESULTS: Brain metabolism was significantly positively correlated with APOE genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme. CONCLUSIONS: We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV.

OBJECTIVE: To assess the effect of neurobehavioral dysfunction on amyotrophic lateral sclerosis (ALS) survival and on the use of life-prolonging therapies in a population-based setting. METHODS: Of the 132 patients diagnosed with ALS in the province of Torino, Italy, between January 1, 2007, and June 30, 2008, 128 participated in the study. Neurobehavioral dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), using the Family Rating forms, administered within 4 months from diagnosis. RESULTS: The 128 patients included 71 men and 57 women, with a mean age at onset of 64.7 (SD 11) years. Forty-one patients (32.0%) had a neurobehavioral dysfunction and 9 (7.0%) an isolated dysexecutive behavior. Enteral nutrition (EN) and noninvasive ventilation (NIV) were performed with similar frequencies in patients with and without neurobehavioral dysfunction. Patients with neurobehavioral dysfunction had a significantly shorter survival than those with a normal FrSBe score (median survival, 3.3 vs 4.3 years; p = 0.02). Patients with isolated dysexecutive behavior had a shorter survival than those without neurobehavioral dysfunction (median survival, 2.5 vs 4.5 years; p = 0.03). Patients with neurobehavioral dysfunction had a shorter survival after EN and NIV, while patients with isolated dysexecutive behavior had a shorter survival after NIV but not after EN. The negative effect of comorbid neurobehavioral dysfunction and of isolated dysexecutive behavior on survival persisted under the Cox multivariate model. CONCLUSIONS: The presence of neurobehavioral dysfunction or of isolate dysexecutive behavior in ALS at diagnosis is a strong predictor of a poor outcome, partially related to a reduced efficacy of life-prolonging therapies.

Pain in amyotrophic lateral sclerosis: a population-based controlled study.

BACKGROUND AND PURPOSE: To assess the prevalence and characteristics of pain in an epidemiological series of patients with amyotrophic lateral sclerosis (ALS) compared to population-based controls. METHODS: Of the 183 patients with ALS resident in the province of Torino, Italy, 160 accepted to be interviewed. Controls were randomly selected from the lists of general practitioners. Pain was assessed using the Brief Pain Inventory. RESULTS: Patients with ALS reported pain more frequently than controls [91 (56.9%) vs. 53 (33.1%); P = 0.001]. Pain frequency and intensity were correlated with a worse functional score and a longer disease duration. In patients with ALS, pain was more frequently located at the extremities (P = 0.006). Pain interfered with all areas of daily function, but patients reported a greater interference than controls in the domains of enjoyment of life and relation with other people. Sixty-four patients (70.3% of those with pain) and 24 controls (45.3% of those with pain) (P = 0.003) were treated for pain, most frequently with non-steroidal anti-inflammatory drugs. ALS cases were also more frequently prescribed non-opioid analgesics and opioids than controls. CONCLUSIONS: Our study indicates that pain is frequent in all stages of ALS, but that it often goes underrecognized and undertreated. It is significantly more frequent in patients with ALS than in population-based controls. Future studies need to clarify the mechanisms of pain in ALS and determine the most effective treatment strategy.

Lower serum lipid levels are related to respiratory impairment in patients with ALS.

BACKGROUND: Recently hyperlipidemia was reported to be related to a significantly better outcome in amyotrophic lateral sclerosis (ALS). To investigate this, we evaluated the status of blood lipids in a large Italian series of patients with ALS, and assessed the effect of hyperlipidemia on patients' survival. METHODS: The study population included 658 patients with ALS consecutively observed in 2 Italian ALS centers between 2000 and 2006. They were compared to a series of 658 healthy subjects, matched by age and gender. RESULTS: The mean levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio were similar in patients with ALS and controls. Total cholesterol, HDL, triglyceride, and LDL/HDL ratio levels showed a significant decrease in patients with forced vital capacity <70% compared to those with FVC >or=90%. For each level of ALS-FRS, poorer respiratory function was related to a lower LDL/HDL ratio. Univariate survival analysis did not find any significant effect of LDL/HDL ratio on survival, either when comparing patients with ratios 2.99 or patients in the first quartile of LDL/HDL ratio (2.79). No dose-response was found for LDL/HDL ratio subdividing patients into 5 quintiles. CONCLUSION: Our findings do not support the observation that patients with amyotrophic lateral sclerosis have hyperlipidemia or that hyperlipidemia in this population is related to longer survival. However, some evidence emerged that respiratory impairment, but not a worse clinical status or a lower body mass index, is related to a decrease in blood lipids and LDL/HDL ratio.

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.

[Traumatic gut perforation (seat-belt syndrome): a case report]. / Perforazione intestinale da trauma addominale chiuso (seat-belt syndrome): descrizione di un caso clinico.

Seat belts have dramatically reduced the severity of traumas in car accidents. On the other hand, specific lesions have appeared, related to seat belt use. These lesions are defined as "seat belt syndrome". The Authors describe an intestinal medio-ileal perforation due to seat belts in a child.

[Epididymal anomalies in cryptorchism and in persistent peritoneo-vaginal duct]. / Anomalie dell'epididimo nel criptorchidismo e nella persistenza del dotto peritoneo-vaginale.

BACKGROUND: Various percentage incidences (36-75%) of the duct system morphologic alterations in cryptorchidism syndrome have been reported in the literature. Etiopathogenic factors, responsible for this syndrome, are yet to be specified, as is their correlation with testicular descent in the scrotum and peritoneal-vaginal duct regression. METHODS: In a prospective multicentric study we have documented seminal duct anatomy in 566 children, undergoing inguinal or scrotal surgical exploration due to acute scrotal syndrome (group A, "control group"), cryptorchidism (group B), and peritoneal-vaginal duct patency syndromes (group C), for a total of 726 testicles. On the basis of anatomical configurations, explored testicles have been subdivided into three groups: normal testicles (type I), suspension anomalies (type II), obstruction anomalies (type III). Prevalence of the above anatomical configurations in the various groups has been statistically evaluated by the chi 2 test. RESULTS: Results have highlighted a significant prevalence (p < or = 0.01) of severe duct system obstructive anomalies (type III) in children with cryptorchidism (group B) and in children with vaginal duct patency (group C). These results can justify the hypothesis of a close correlation between testicle embryologic migration process in the scrotal sac and seminal duct development; this latter seems furthermore correlated with peritoneal duct regression. CONCLUSIONS: The drawn conclusion is that duct system morphologic alterations in cryptorchidism, due to their seriousness and incidence, can condition final fertility capability.