Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues.

Amyotrophic lateral sclerosis (ALS) is a relatively rare disease with a reported population incidence of between 1.5 and 2.5 per 100,000 per year.

Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered.

A genome-wide association study of sporadic ALS in a homogenous Irish population.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive limb or bulbar weakness. Efforts to elucidate the disease-associated loci have to date produced conflicting results. One strategy to improve power in genome-wide studies is to genotype a genetically homogenous population.

Genetics of sporadic amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. There is substantial evidence suggesting that ALS is a heritable disease, and a number of genes have been identified as being causative in familial ALS. In contrast, the genetics of the much commoner sporadic form of the disease is poorly understood and no single gene has been definitively shown to increase the risk of developing ALS.

Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004.

Background: We conducted a prospective, population based study to examine trends in incidence and prevalence of amyotrophic lateral sclerosis (ALS) in Ireland from 1995 to 2004.

Methods: The Irish ALS Register was used to identify Irish residents diagnosed with ALS between the 3 year period from 1 January 1995 to 31 December 1997 and the 3 year period from 1 January 2002 to 31 December 2004.

Results: 465 Irish residents were diagnosed with ALS during the study periods.

Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis.

It has been > 130 years since the first description of the upper and lower motor neuron disease called amyotropic lateral sclerosis (ALS). Sadly, there has been little change in the long interval over which this disease is diagnosed, or in its poor prognosis. Significant gains have been made, however, in understanding its pathophysiology and in symptomatic care.

Ethnic variation in the incidence of ALS: a systematic review.

Background: The findings of recent genetic polymorphism studies in ALS suggest that the influence of genetic risk factors for the disease may vary by ethnicity. It is now widely accepted that the incidence of ALS is uniform across Caucasian populations, but whether racial variation across other ethnicities exists remains unknown.

Method: Systematic review of the known literature on the incidence, prevalence, and mortality of ALS across all ethnicities.

Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes.

Objective: Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD.

Methods: The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS-FTD.

Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data.

Background: The cause of sporadic ALS is currently unknown. Despite evidence for a role for genetics, no common genetic variants have been unequivocally linked to sporadic ALS. We sought to identify genetic variants associated with an increased or decreased risk for developing ALS in a cohort of American sporadic cases.

Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD.

Background: A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p.

Methods: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus.

Results: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2).

Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS.

An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.

A novel candidate region for ALS on chromosome 14q11.2.

Sequence variations with biologic effect in ALS have been identified in the gene for vascular endothelial growth factor (VEGF). The gene for a related protein, angiogenin, lies on chromosome 14q11.2.

Functional outcome measures as clinical trial endpoints in ALS.

The topiramate study was a 12-month randomized placebo-controlled trial in patients with ALS. Follow-up evaluation of the placebo group (n = 97) constituted a well-described cohort of patients with ALS, in whom multiple outcome measures were assessed at 3-month intervals. During the 12-month study period, the decline of forced vital capacity (FVC%) and ALS functional rating scale (ALSFRS) was linear, whereas the decline of maximum voluntary isometric contraction-arm (MVIC-arm) and MVIC-grip Z scores was curvilinear.

Access to health services in Ireland for people with Multiple Sclerosis and Motor Neurone Disease.

We conducted a telephone questionnaire to determine the utilisation of hospital and community based services by patients with Motor Neurone Disease and Multiple Sclerosis in Ireland. 94 MND and 188 MS patients participated in the study. MND patients were more likely to have free medical care than MS patients, despite legislation favouring the converse.

Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000.

Background: In recent years, there has been a paradigm shift in the method of healthcare delivery to amyotrophic lateral sclerosis (ALS) patients with the emergence of multidisciplinary ALS clinics that cater exclusively for patients with this condition. The impact of multidisciplinary management has not been previously evaluated.

Methods: Using data from the Irish ALS Register, we conducted a prospective, population based study of all ALS cases diagnosed in Ireland over a five year period to evaluate the effectiveness of a multidisciplinary clinic on ALS survival.

Models of care for motor neuron disease: setting standards.

Models of care for people with motor neuron disease (MND) must be designed in a patient-centered format, with an in-built flexibility and responsiveness that reflect the evolving nature of the condition. Diagnosis should be made as early as possible. Patients should have early access to centres with specialist knowledge of amyotrophic lateral sclerosis (ALS).

An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996-2000.

Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period.

"True" sporadic ALS associated with a novel SOD-1 mutation.

Mutations in the Cu/Zn superoxide dismutase gene (SOD-1) are reported in 20% of familial amyotrophic lateral sclerosis (ALS) cases, but no definite report of a mutation in a "truly" sporadic case of ALS has been proved. We present the first case of a novel SOD-1 mutation in a patient with genetically proven sporadic ALS. This mutation (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well with the aggressive clinical course and postmortem findings observed in this patient.