Risk factors for respiratory failure of motor neuron disease in a multiracial Asian population.

BACKGROUND: Motor neuron disease (MND) is a devastating degenerative disorder. Amyotrophic Lateral Sclerosis (ALS) is the most common and severe form of MND. Respiratory failure arising from ventilator musculature atrophy is the most common cause of death for ALS patients. Exploring the factors correlated with respiratory failure can contribute to disease management. PURPOSE: To characterize the clinical features of MND and determine the factors that may affect respiratory failure of MND patients. METHODS: The case records of all MND patients seen in Singapore General Hospital (SGH) between January 2004 and December 2014 were examined. Demographic, clinical information were collected by reviewing case records. Mortality data, if not available from records, were obtained via phone call interview of family members. Demographic data and clinical treatments were compared between Respiratory support group and Non-respiratory support group. RESULTS: There were 73 patients included in our study. 49 (67.1%) patients died during follow-up. The mean age of onset was 58±11.1years. With regard to treatment, 63% needed feeding support, and 42.5% required ventilation aid. The median overall survival was 36months from symptom onset. Chi-square tests showed there was significantly higher percentage of respiratory support needed in Chinese than in other races (P=0.016). Compared with non-feeding support patients, patients with feeding support were more likely to require assisted ventilation (P=0.001). CONCLUSIONS: We report for the first time that the need of feeding support is significantly associated with assisted ventilation. Chinese MND patients may be more inclined to require respiratory support.

Ethnic and demographic incidence of amyotrophic lateral sclerosis (ALS) in Brazil: A population based study.

Our objectives were to examine demographic and ethnic factors associated with amyotrophic lateral sclerosis in Brazil. The method used was a retrospective study of death certificates performed in June 2015, identifying the incidence of amyotrophic lateral sclerosis over 10 years, from January 2004 to December 2013, related to gender, age and race. Results revealed 8942 death certificates with 8152 as the underlying cause and 790 as a secondary cause. The average age was 62.7 ± 13.2 years, with a predominance of males (1·3:1). The adjusted mortality rate over 20 years was 0.61 to 0.89/100,000 person-years, and over 45 years was 1.77 to 2.3/100,000 person-years. There was a predominance of amyotrophic lateral sclerosis in Caucasians compared to the general population above 20 years (2010 Census), with an odds ratio (OR) of 2.92 (95% CI 2.78-3.07). The OR in blacks was 0.04 (95% CI: 0.03-0.04), in mestizos was 0.05 (0.04-0.07), and in Indians was 0.02 (0.01-0.04). The mean age was lower than in European populations (48.5 ± 12.3 years) (p < 0.0001). In conclusion, the incidence of amyotrophic lateral sclerosis in Brazil is close to other Latin American populations, with a lower age at death and clear predominance in Caucasians.

Racial differences in motor neuron disease.

Our objective was to compare and contrast clinical features of black and white patients seen in the UAMS ALS/Motor Neuron Disease (MND) clinic from January 2001 to December 2010. Death certificate information was reviewed to determine race of Arkansans who died of ALS/MND between 1999 and 2006. We used a retrospective chart review of patients with ALS/MND seen at least once in our clinic and reviewed state death certificate data. Results showed that from 1999 to 2006, 466 Arkansas deaths were attributed (immediate or contributory) to ALS/MND; 17 (3.6%) were black, four (0.9%) other, and 445 (95.5%) white. During this period, the proportion of black Arkansans was 17%. From 2001 to 2010, we saw 330 patients with ALS/MND: 30 (9.1%) black, six (1.8%) other, 294 (89.1%) white. Average onset age for whites was 58.1 + 12.4 years, for blacks 52.8 + 13.0 (p = 0.038). Gender, onset site, time from symptom onset to first clinic visit and initial vital capacity were similar between the groups. Initial ALSFRS-R was 37.5 + 7.2 for whites and 30.8 + 8.5 (p = 0.004) for blacks. A first or second degree relative with ALS/MND was reported by 8.1% of whites and by none of the black patients (p = 0.15). Riluzole, PEG and non-invasive ventilation use was similar between the groups. Median tracheostomy-free survival was 36 months for white and 40 months for black patients (p = 0.475). In conclusion, although blacks appear relatively spared from ALS/MND, they present at an earlier age and are functionally worse at their first visit. Investigating the genetic make-up of blacks with the disease may help identify genes that modify risk of developing ALS/MND.

Incidence of amyotrophic lateral sclerosis among American Indians and Alaska natives.

IMPORTANCE: More thorough evaluation of amyotrophic lateral sclerosis (ALS) and motor neuron disease in unique populations could provide clues to etiologies for these idiopathic conditions, and educational programs for American Indian and Alaska Native (AI/AN) people and health care professionals on reservations could improve awareness, understanding, diagnosis, and treatment. In the ongoing search for susceptibility genes, studying particular racial groups, such as AI/ANs,might facilitate the identification of new mutations. OBJECTIVE: To provide better understanding of ALS and secondarily of motor neuron disease among AI/AN people by estimating the incidence and prevalence among AI/ANs served by the Indian Health Service health care system. DESIGN AND SETTING: Analysis of electronic records for AI/ANs with ALS and with motor neuron disease separately for the calendar years 2002-2009 using inpatient and outpatient visit data from the Indian Health Service, which provides health care to eligible AI/ANs nationwide. PARTICIPANTS: Cases were defined by at least 2 inpatient or outpatient visits with the diagnosis. MAIN OUTCOME MEASURES: Crude and age-adjusted incidence and prevalence rates were calculated. RESULTS: Seventy-one AI/ANs were diagnosed with ALS, yielding an average annual crude incidence rate of 0.63 cases per 100 000 and an age-adjusted incidence of 0.92. The median age at onset was 56.0 years and was higher among women than men (62.0 vs 55.0 years; P=.06). Age-specific incidence increased to 70 to 74 years. The crude and age-adjusted point prevalence rates were 2.00 and 4.12, respectively. The crude and age-adjusted incidence rates for motor neuron disease were 1.08 and 1.50, respectively. The annual rates were unchanged across the study period. CONCLUSIONS AND RELEVANCE: The incidence of ALS among AI/ANs appears to be lower than that reported for white populations, a finding congruent with reports of other minority populations. Community-based studies are important to confirm these findings and to examine reasons for the low rate of ALS among AI/ANs.

Survival and prognostic factors of motor neuron disease in a multi-ethnic Asian population.

Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival.

Late-onset monomelic amyotrophy in a Caucasian woman.

We describe a 53-year-old Caucasian woman with a 19-year history of an evolving amyotrophy confined to her dominant right arm and hand. Although this atypical case of a late-onset monomelic amyotrophy in some respects mimics Hirayama disease or O'Sullivan-McLeod syndrome, it does not conform precisely with either of those disorders. We compare this individual's difficulties and clinical temporal profile to other disorders considered in the differential diagnoses with regard to her evolving clinical setting.

Temporal and geographic variation in United States motor neuron disease mortality, 1969-1998.

OBJECTIVE: To describe temporal trends of motor neuron disease (MND) mortality in the United States. Variations in MND by demographic variables of sex, age, geography, and race/ethnicity were evaluated to assess the possible explanations for observed trends. METHODS: Multiple-cause mortality files from the National Center for Health Statistics for the years 1969 through 1998 were searched for all United States death records with codes corresponding to MND. Age-adjusted mortality rates were calculated by sex, race/ethnicity, age, birth cohort, and place of death. RESULTS: Overall MND mortality rates increased from 1.25 per 100,000 to 1.82 per 100,000, representing a 46% increase during the 30-year period. Rates among women increased by 60% and continue to rise. Rates among men rose by 35% during this period but have leveled off in the most recent decade evaluated. Mortality rates among African Americans and Hispanics were approximately 50% lower than rates among non-Hispanic whites. A southeast to northwest gradient was observed when rates were grouped by 12 geographic areas. MND mortality rates per 100,000 (and 95% CI) ranged from 2.22 (1.89 to 2.55) in the Northwest to 1.57 (1.44 to 1.71) in the Southeast. CONCLUSIONS: Variations in motor neuron disease (MND) mortality by time, race/ethnicity, sex, and geography were consistent with the hypothesis that environmental exposures, combined with factors of genetic susceptibility, play a role in the development of MND.

Founder effect in spinal and bulbar muscular atrophy (SBMA) in Scandinavia.

We haplotyped 13 Finnish, 10 Swedish, 12 Danish and 2 Norwegian SBMA (spinal and bulbar muscular atrophy, Kennedy disease) families with a total of 45 patients and 7 carriers for 17 microsatellite markers spanning a 25.2 cM region around the androgen receptor gene on chromosome Xq11-q12 in search of a genetic founder effect. In addition, the haplotypes of 50 Finnish, 20 Danish and 22 Swedish control males were examined. All the Scandinavian SBMA families shared the same 18 repeat allele for the intragenic GGC repeat, which was present in only 24% of the controls. Linkage disequilibrium was also seen for the closest microsatellite markers. In addition, extended haplotypes of the Finnish, Swedish and Danish SBMA families revealed country-specific common founder haplotypes, which over time became gradually shortened by recombinations. No common haplotype was found among the controls. The data suggest that the SBMA mutation was introduced into western Finland 20 generations ago. Haplotype analysis implies a common ancestor for the majority of Scandinavian SBMA patients.

Assessment of serum-mediated neurotoxicity in Navajo neuropathy.

Navajo neuropathy is a unique sensorimotor neuropathy which is geographically restricted to Navajo children living on the Navajo Reservation. Affected patients present with weakness, loss of sensation in extremities, corneal ulcerations, and a high incidence of childhood infections. Metabolic complications, such as severe liver disease, may further contribute to peripheral nerve injury in affected patients. In this study, serum-mediated injury to rat peripheral nerve was critically assessed. Serum samples from affected Navajo patients were tested in vivo for effects on peripheral nerve function. Injection of serum from affected Navajo patients into rat sciatic nerve produced a modest slowing of nerve conduction velocity without effecting evoked-compound muscle action potential (CMAP) amplitudes. By comparison, injection of serum from patients with MGUS neuropathy, an immune-mediated disorder, diminished evoked-CMAP amplitudes by approximately 70%. Navajo neuropathy sera had no effect in vitro on the neurite outgrowth of developing dorsal root ganglia neurons. The results argue against serum-mediated toxic injury to peripheral nerves in Navajo neuropathy.

The risk of motor neurone disease and multiple sclerosis is different in Estonians and Russians. Data from South Estonia.

Epidemiological studies were performed in South Estonia to establish the prevalence rate of multiple sclerosis (MS) and motor neurone disease (MND). The case finding method included information from the hospital records of the central hospital in the region-the University Hospital (for MS from 1942 to 1989), from all neurologists in the region, from the Estonian MS Society and Association of Muscular Disorders, and from nursing homes in the region. The prevalence day was 31 December 1989. MND incidence was established for the period of 1986-1995. The results demonstrated high prevalence rates of MS among native Estonians (55.3 per 100 000), somewhat lower prevalence among native-born representatives of other nationalities (43.6 per 100 000) and the lowest prevalence rate of MS among non-Estonian immigrants (26.6 per 100 000). The differences were not statistically significant. The results for MND demonstrated the opposite pattern. The mean annual incidence rate of MND for 10 years was statistically significantly higher among people of other nationalities (2.5 per 100 000) and Russians (2.6 per 100 000), and lower in native-born Estonians (1.1 per 100 000). No differences in health care or clinical picture were established. The reasons for the demonstrated differences in MND incidence remain unclear.