THEME 6 EPIDEMIOLOGY

P136 AMYOTROPHIC LATERAL SCLEROSIS (ALS) ESTIMATES FROM NATIONAL DATABASES IN THE UNITED STATES FROM 2001 TO 2010

Sanchez MS¹

Antao VC¹

Kaye WE²

Muravov O¹

Horton DK¹

^aCDC/ATSRD, Atlanta, GA, USA

^bMcKing Consulting, Atlanta, GA, USA

Email address for correspondence: [email protected]

Keywords: ALS registry, national registry, incidence, prevalence

Background: The uncertainty about the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in the United States, as well as the lack of knowledge about the role of environmental exposures in the etiology of ALS, has created a need for structured data collection through a national ALS registry. In 2008, a law providing for the creation of a national ALS registry was signed. From 2001 to 2005, the Agency for Toxic Substances and Disease Registry (ATSDR) conducted four pilot projects to determine the feasibility of creating a national ALS registry, which showed that approximately 80% of ALS patients can be found through national databases. Nevertheless, several different methodologies would be needed for identifying a large portion of individuals with ALS in the U.S. Therefore, in 2009, ATSDR began implementation of the National ALS Registry using a two-pronged approach to help identify all U.S. cases of ALS. The first approach utilizes existing national administrative databases to identify prevalent cases, based on an algorithm developed through the pilot projects. The second approach, implemented in the fall of 2010, uses a secure web portal to identify cases not included in the national administrative databases. This approach allows patients to self-identify and enrol in the ALS registry and take risk factor surveys.

Objectives: To present preliminary ALS estimates from national databases in the United States.

Methods: We sought to identify U.S. residents with ALS in Medicare, Medicaid, Veterans Health Administration (VHA), and Veterans Benefits Administration (VBA) databases, for the years 2001–2010. Records were searched and identified in Medicare, Medicaid, and VHA for ICD-9 codes of 335.2– 335.29. VBA records were searched and identified for codes of 8005 (Progressive Bulbar Palsy), 8017 (ALS), and 8023 (Progressive Muscular Atrophy).

Results: A total of 147,889 individuals were identified across the four national databases. Medicare contributed the largest number of individuals in all three categories, and contributed the most to identified ALS individuals (95%). The total number of individuals identified as ALS was 36,547, which is 24.7% of the total number of individuals identified with any MND.

Discussion and conclusion: This is the first effort to identify ALS cases for a national registry in the United States. Although the number of individuals identified via the national administrative databases is not a prevalence estimate, it does indicate that a large portion of ALS individuals can be identified for the National ALS Registry by using the national administrative databases selected.

P137 CLINICAL CHARACTERISTICS OF AFRICAN AMERICAN PATIENTS WITH ALS, THE NORTHWESTERN ALS/MDA CLINIC EXPERIENCE

Ajroud-Driss S

Allen J

Sufit R

Heller S

Wolfe L

Siddique T

Northwestern University, Chicago, USA

Email address for correspondence: [email protected]

Keywords: African American, ethnicity, slow progression

Background: Prior whole genome association studies in ALS suggested that the ethnic background may modulate the genetic risk of ALS. There are reports of lower incidence of ALS among African American, Asians or Hispanic compared to those of Caucasian. However, studies that describe the phenotypic characteristics of ALS in these populations are lacking.

Objective: To describe the clinical characteristics of African American patients with ALS/MND.

Methods: Retrospective chart review of ALS/MND patients of African American descent who attended either the ALS or MDA clinic at Northwestern University in Chicago between 2004 and 2013.

Results: We identified 32 African American new patients with ALS/MND among the 900 new patients with ALS/MND seen during that time period. The male to female ratio was 1.90–1.00, the average age of onset was 60.2 years and the average disease duration was 5.25 years. 62.5% of the patients had limb onset disease whereas 28% had bulbar onset disease and about 1% had diaphragmatic onset weakness. Only 34% of the patients had classic ALS. When we looked at the proportion of patients with slow disease progression, we found out that about 31.2% of the patients survived beyond 5 years. 55% of the patients had a lower motor neuron predominant phenotype and 60% of the patients had a spinal ALS phenotype. 15% of patients were lost of follow up and 9% of the patients chose mechanical ventilation.

Discussion: The clinical characteristics of African American patients with ALS seem to be different than Caucasians. Classical ALS was rare. Spinal form of ALS, lower motor neuron predominant disease and slow progression seemed to be the predominant features of this subgroup of patients. The attitude toward care and end-of-life decision with a higher rate of mechanical ventilation and loss of follow-up appear to distinguish this group as well.

Conclusion: African American patients with ALS may constitute a unique subgroup of patients that need to be studied in more detail. Ethnic background ought to be looked at more carefully during the design of clinical trials.

P138 The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004–2007

Caller T^1,2

Andrew A¹

Field N¹

Stommel E^1,2

^cDartmouth-Hitchcock Medical Center, Lebanon, NH, USA

^dGeisel School of Medicine at Dartmouth, Hanover, NH, USA

Email address for correspondence: [email protected]

Keywords: United States, incidence, environmental exposure, occupation

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition with both genetic and environmental risk factors. Epidemiology can provide clues to disease etiology; in the United States (USA), previously published epidemiologic studies of ALS are limited and have been primarily confined to mortality data (1, 2). Previously, we have described a town in New Hampshire (NH) with 25 times the expected incidence rate of ALS (3).This study aims to describe the incidence and mortality trends of ALS in the state of NH, USA, over a four-year period, and to describe the demographics of this ALS population.

Methods: Records from regional ALS centers, clinics, and ALS organizations were retrospectively searched to identify patients diagnosed with ALS in NH from January 2004 to December 2007. Medical records were reviewed when possible to confirm diagnosis and extract details on demographics, tobacco use, and occupational history. Mortality data for 2004–2007 was obtained by reviewing state death certificates to identify those listing the ICD-10 code G12.2 for motor neuron disease as primary or contributing cause of death. Age-standardized incidence and mortality rates were calculated using US census data (4).

Results: We identified 118 NH residents diagnosed with ALS in 2004–2007. The age-standardized incidence rate per 100,000 population, ranged from 1.6 in 2004 to 2.5 in 2006. During the same 4-year period, the standardized mortality rate per 100,000 population varied from 3.5 in 2004 to 2.6 in 2007. Familial ALS was reported in 6%, and five cases were thought to have primary lateral sclerosis (PLS). ALS was more common among men (ratio 1.3:1). Men were more likely than women to have an earlier age of onset (59 ± 13.9 years vs. 65 ± 12.2 years, p = 0.01), and were 1.6 times more likely to have held a high-risk occupations, including medical, factory worker (machinist), carpentry (construction), and chemical production.

Conclusions: While localized areas with high incidence rates in NH have been previously reported, incidence and mortality rates of ALS in NH are overall similar to other industrialized nations (6). A prospective ALS registry will enable us to understand incidence rates and to identify environmental or occupational exposures related to earlier age of onset in males, and clarify the previously reported geographic disparity in ALS incidence.

Acknowledgments:

This work is supported by the ALS Association, the Hitchcock Foundation, and the ALS Center of DHMC.

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P139 INCIDENCE OF AMYOTROPHIC LATERAL SCLEROSIS IN RHINELAND-PALATINATE, GERMANY – THE ALS REGISTRY RHINELAND–PALATINATE

Wolf J¹

Wöhrle J²

Palm F¹

Nix W³

Maschke M⁴

Becher H⁵

Grau A¹

^eDept. of Neurology, Klinikum Ludwigshafen, Ludwigshafen, Germany

^fDept. of Neurology, Katholisches Klinikum, Brüderhaus, Koblenz, Germany

^gDept. of Neurology, Universitätsmedizin, Mainz, Germany

^hDept. of Neurology, Krankenhaus der Barmherzigen Brüder, Trier, Germany

ⁱInstitute of Public Health, Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany

Email address for correspondence: [email protected]

Keywords: epidemiology, population-based register, incidence

Background: In contrast to other Western countries (eg Ireland (1), Scotland (2), and Italy (3–5)) there is a lack of prospective and population-based epidemiological data on amyotrophic lateral sclerosis (ALS) in Germany.

Objectives: We intended to determine the incidence, course and phenotypic variety of ALS in Rhineland–Palatinate, a county in South-West Germany with about 4 million inhabitants.

Methods: During the period 2010–2011, consecutive patients with a first diagnosis of ALS according to the revised El Escorial criteria and were registered using multiple overlapping sources of case ascertainment. To assess the course of the disease patients were followed up in 3–6 months intervals. Death certificates from local health authorities served as an additional registration tool for deceased patients. Age-specific and age-standardised incidence rates were calculated to compare our results with results of other prospective registries.

Results: During the period 2010–2011, 146 incident patients were enrolled. The annual crude incidence for ALS in Rhineland–Palatinate was 1.8/100,000 person years (95% CI: 1.6–2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a peak in the 70–74 age group (10.3/100000 person years, 95% CI: 7.6–13.6) and declined thereafter. Mean age at diagnosis was 66.2 (±10.6) years. About 32% of patients presented with bulbar onset, 34% with symptoms in lower limbs, and 23% with symptom onset in upper limbs. 4% of patients had an initial trunk or respiratory involvement. Mortality rate within the first year of diagnosis was 26%.

Discussion and conclusion: The ALS registry Rhineland–Palatinate is the first population-based prospective ALS register in Germany. Incidence, phenotypic variety and one-year-mortality rate of ALS in Rhineland–Palatinate is within the range of previous prospective population-based registries in Western countries. Gender ratio is nearly balanced, which might reflect a better case ascertainment of female ALS patients.

References:

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P140 CLUSTERING OF ALS IN FRANCE: RESULTS OF THE BMAALS STUDY

Boumediene F^1,2

Bonneterre V³

Camu W⁴

Lagrange E³

Besson G³

Preux PM¹

Couratier P¹

Marin B¹

^jUMR Inserm 1094 NeuroEpidemiologie Tropicale

^kUMR CNRS 6042 Laboratoire de Géographie Environementale; Université de Limoges, Limoges, France

^lEPSP-TIMC (UJF Grenoble/CNRS), Grenoble, France

^mCentre SLA Montpellier, Montpellier, France

Email address for correspondence: [email protected]

Keywords: cluster, L-BMAA, France

Background: The BMAALS study aims to improve scientific knowledge about the possible link between ALS and cyanotoxin L-BMAA. We report here the results of the geoepidemiological step of this survey in identifying all incident cases on the area under consideration and searching for clusters.

Objective: To identify the presence of clusters of ALS among 10 French departments of France (58 254 km²) covering 5.2 million people followed for 9 years.

Methods: Multiple sources of information were used to ensure complete case ascertainment of individuals diagnosed with ALS between 2003 and 2011 according to Airlie House criteria in the following areas of France (i) Limousin region (Corrèze, Creuse, and Haute-Vienne departments); (ii) Rhone–Alpes region (Isere, Savoie, Haute Savoie, Drôme, and Ardèche departments); (iii) Languedoc Roussillon region (Pyrenees Orientales and Herault departments). Multiple sources of case were (i) French national ALS centers; (ii) hospitals and clinics; (iii) health insurance structures; and (iv) private neurologists. Crude incidence per 100,000 inhabitants was assessed using estimates of population from the Insee. Previously applied methods were used for cluster detection (1): Standardized Incidence Ratios (SIR) calculation used the overall incidence in the area as the reference. I Moran and Kulldorf statistics were also performed.

Results: Between 1 January 2003 and 31 December 2011, 1211 patients were diagnosed as having probable, probable laboratory supported or definite ALS in the area under study. The average annual crude incidence rate for those cases was 2.57 (95% CI: 2.43–2.71) per 100,000 person year of follow-up (PYFU). Standardized on 2010 European population the incidence was 2.50 (95% CI: 2.37–2.65) per 100,000 PYFU. Thirteen clusters of ALS were identified within the area. The median SIR value was 3.3 (95% CI: 1.2–7.1).

Discussion and conclusion: We report here the widest study of ALS incidence and clustering ever conducted in France using a thorough methodology. We based our calculation on the incidence assessed in a wide area of France covering 5.2 million inhabitants. The clusters that were identified will be explored for their relation with L-BMAA exposure during the next steps of the BMAALS study.

Acknowledgments: French National Research Agency (ANR) who funded this project: ANR Program CESA 2011 - BMAALS.

BMAALS Group: UMR Inserm 1094 NET, ENSCP, UMR CNRS 6042 GEOLAB, ESPCI, EPSP-TIMC (UJF Grenoble/CNRS), Centre SLA Montpellier.

Reference:

• Boumédiene F, Druet-Cabanac M, Marin B, Preux PM, Allée P, Couratier P. Contribution of geolocalisation to neuroepidemiological studies: incidence of ALS and environmental factors in Limousin, France. J Neurol Sci. 2011;309:115–22.
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P141 RESULTS FROM THE FIRST FRENCH ALS REGISTER: THE LIMOUSIN ALS REGISTER

Marin B¹

Preux PM¹

Boumediene F²

Nicol M^1,3

Leleu JP²

Raymondeau M¹

Hamidou B¹

Lautrette G³

Couratier P^1,3

ⁿUMR Inserm 1094 NeuroEpidemiologie Tropicale

^oUMR CNRS 6042 Laboratoire de Géographie Environementale, Université de Limoges, Limoges, France

^pCentre SLA du Limousin, Service de Neurologie, CHU Limoges, Limoges, France

Email address for correspondence: [email protected]

Keywords: register, incidence, France

Background: In France, until recently, there was no register of ALS cases. Hence description of the disease in France was only hospital based and then exposed to bias.

Objective: To assess the incidence of ALS in the Limousin region of France using multiple sources of cases ascertainment, and to describe the sociodemographical and clinical profile of new ALS cases.

Methods: A register has been settled in the Limousin region of France, 743,000 inhabitants (1). Multiple sources of information were used to ensure complete case ascertainment of individuals diagnosed with ALS according to Airlie House criteria, within the Limousin since 2000. Multiple sources of case were (i) Limousin ALS expert center and other ALS centers of France; (ii) private hospitals and clinics; (iii) health insurance structures (reimbursement of Rilutek^® and long duration affection notification); and (iv) private neurologists. Data were collected in a secured database. Crude incidence per 100,000 inhabitants was assessed using estimates of population from the Insee (2). Direct standardized incidence based on 2010 US population was also calculated (3). Ninety-five percent confidence intervals (95% CI) were calculated assuming a poisson distribution.

Results: Between 1 January 2000 and 31 December 2011 (12 years), 279 patients were diagnosed as having possible, probable, probable laboratory supported, or definite ALS. The median number of sources by patient was 2 (Interquartile range: 2–3). The average annual crude incidence rate was 3.18 per 100,000 person-years (95% CI 2.81–3.56). Standardized incidence on US population was 2.18 (95% CI 1.92–2.45). Mean age at diagnosis was 69.1 ± 11.2 years and the male/female sex-ratio was 1.45. First symptoms were mostly spinal (65.5%) and 6.45% of cases had familial ALS.

Discussion and conclusion: We report here the results of the first ALS register settled in France. The epidemiological profile of ALS incidence in Limousin, France is consistent with those published by other European registers (2). The register will be the base of analytic and geoepidemioloical studies (clustering). We are now extending the register in other region of France: Languedoc Roussillon and some departments of Rhône Alpes.

Acknowledgments: Sources of cases: French National coordination of ALS centers; Health insurance structures: Régime Général, Mutuelle Sociale Agricole, Régime Social des Indépendants, Caisse Nationale Militaire de Sécurité Sociale; Private Neurologists; Hospital and Clinics.

References:

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P142 CLINICAL SPECTRUM AND NATURAL HISTORY OF MOTOR NEURON DISEASE IN KOREAN

Oh K-w¹

Oh S¹

Choi W-J¹

Lim H¹

Shin KJ²

Koh S-H¹

Kim S¹

^qDepartment of Neurology, College of Medicine, Hanyang University, Seoul, Republic of Korea

^rDepartment of Neurology, Haeundae Paik Hospital, Inje University, Busan, Republic of Korea

Email address for correspondence: [email protected]

Keywords: ethnicity, motor neuron disease, survival

Background: The clinical spectrum of motor neuron disease (MND) is wide with a variable course. Recent studies in amyotrophic lateral sclerosis (ALS) suggest that ethnic difference may influence clinical and genetic characteristics of MND.

Objectives: We described the clinical profile and survival of Koreans with MND seen in a tertiary referral center in Seoul, Korea.

Methods: We analyzed clinical features of patients with 792 MND from our ALS Center and verified survival by telephone survey.

Results: ALS was diagnosis in 621 (78.4%) patients, PMA in 106 (13.3%), and Kennedy`s disease in 32 (4%). In ALS, onset of age were more likely to be lower (53.5- vs. 56.4-year-old), and individuals lived longer (39.9 vs. 31.5 months) than progressive muscular atrophy (PMA).

Discussion and conclusions: Although ALS and PMA had similar clinical characteristics, longer survival in ALS is a different finding to previous western studies.

Acknowledgements:

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. (A101712, A120182)

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P143 TRANSITIONAL METAL CONTENTS IN SCALP HAIR AND LIFESTYLE OF ALS PATIENTS AND RESIDENTS IN THE KII PENINSULA, JAPAN: THE SECOND REPORT

Kihira T¹

Sakurai I¹

Yoshida S¹

Wakayama I¹

Takamiya K²

Nakano Y²

Okumura R²

Iinuma Y²

Iwai K³

Kajimoto Y⁴

Hiwatani Y⁴

Kohmoto J⁵

Okamoto K⁶

Kokubo Y⁷

Kuzuhara S⁸

^sKansai University of Health Sciences, Kumatori, Osaka, Japan

^tResearch Reactor Institute, Kyoto University, Kumatori, Osaka, Japan

^uFaculty of Nursing, Kansai University of Health Sciences, Kumatori, Osaka, Japan

^vDepartment of Neurology, Wakayama Medical University, Wakayama, Japan

^wDepartment of Neurology, Wakayama National Hospital, Wakayama, Japan

^xDepartment of Public Health, Aichi Prefectural College of Nursing and Health, Aichi, Japan

^yGraduate School of Regional Innovation Studies, Mie University, Mie, Japan

^zDepartment of Medical Welfare, Suzuka University of Medical Science, Mie, Japan

Email address for correspondence: [email protected]

Keywords: neutron activation analysis, transitional metals, lifestyle

Background: A high incidence of amyotrophic lateral sclerosis (ALS) has continued in the Koza/Kozagawa/Kushimoto (K) area in the Kii Peninsula of Japan. We previously reported an elevation of urinary 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, in patients with ALS in this area (K-ALS). Lifestyle might play a role in increasing oxidative stress.

Objective: The aim of this study is to investigate relationships between the contents of transitional metals in the scalp hair and lifestyle of the residents in this area (K-residents) and patients with K-ALS.

Methods: Hair samples were collected from patients with K-ALS, sporadic ALS, K-residents and controls and approximately 30 mg of each sample was subjected to neutron activation analysis at Kyoto University Research Reactor according to the protocol previously reported (1). As comparative standards, a human hair standard (NIES CRM No.13) and elemental standards were used. K-residents were asked to answer dichotomous questionnaires about lifestyle. The relationship between metal contents in the hair and the questionnaire data was analyzed statistically.

Results: Hair samples from seven patients with K-ALS, 10 patients with sporadic ALS, 86 K-residents and 19 controls were collected between 2010 and 2012 and the contents of Ca, Al, Cu, Mn and V were analyzed. The samples were not treated with chemical procedures including perm. The contents of V (148.3 ± 277.4 ppb, mean ± S.D.) and Mn (0.75 ± 0.66 ppm) of patients with K-ALS were higher than those of the controls (19.2 ± 11.1 and 0.22 ± 0.35, respectively, p < 0.05). Some of the K-residents showed high V in the hair; however, the mean content (28.6 ± 27.9 ppb) was not significantly different from the controls. The contents of V in the hair were positively correlated with the contents of Mn and Al in the hair. No correlation was found between the contents of these metals in the hair and urinary 8-OHdG in K-residents. K-residents who answered that they ate Japanese pickled vegetables daily showed higher hair V and Mn (p < 0.05 and p = 0.056, respectively) and who answered that they worked on a farm almost everyday showed higher Mn and Al in the hair than those who rarely did (p < 0.01, respectively).

Discussion and conclusion: The present results indicate that the contents of V and Mn in the scalp hair of patients with K-ALS were elevated, and it may be related to the lifestyle including eating habits and field labor in this area. These transitional metals may play a role in increasing oxidative stress on patients with K-ALS.

Reference:

• T Kihira et al. Amyotrophic Lateral Sclerosis 2012;13, S1:126–134.
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P144 PRELIMINARY REPORT OF AFRICAN CASES IN THE TROPALS STUDY – A SURVEY OF AMYOTROPHIC LATERAL SCLEROSIS IN TROPICAL AREAS

Marin B¹

Diagana M^2,1

Hamidou B¹

Gouider R³

Basse Faye A⁴

Balogou A⁵

Houinato D^6,1

Boumediene F⁷

Couratier P¹

Preux PM¹

^aaUMR Inserm 1094 NeuroEpidemiologie Tropicale, Université de Limoges, Limoges, France

^abService de Neurologie, Nouakchott, Nouackchott, Mauritania

^acDepartment of Neurology Razi Hospital, Tunis, Tunisia

^adClinique Neurologique CHU Fann, Fann, Senegal

^aeCHU Lome, Lome, Togo

^afCHU Cotonou, Cotonou, Benin

^agUMR CNRS 6042 Laboratoire de Géographie Environementale, Université de Limoges, Limoges, France

Email address for correspondence: [email protected]

Keywords: Africa, ethnic groups, tropics

Background: Epidemiological studies of amyotrophic lateral sclerosis (ALS) in the tropics are rare and their methodologies are heterogeneous (1). Many questions arise as regards the characteristics of this disease in the tropics.

Objective: To describe sociodemographical and clinical characteristics of ALS patients diagnosed in Tropical areas.

Methods: TROPALS (http://www.tropals.unilim.fr/) is a multicentre observational cohort study. A shared methodology and an online database allow centres to collect data in a standardized and homogeneous way. We will here focus on African cases only.

Results: Since May 2012, 40 African patients have been included in five centres (Benin, Mauritania, Senegal, Togo, and Tunisia), other centres are open (Burkina Faso, Gabon, and Mali) and six others are about to open. Mean age at diagnosis was 51.9 ± 13.5 years (two cases less than 25 years), male/female sex ratio was 2.4.

First symptoms were mostly spinal (72.5%) and 80.0% of patients (n = 32/40) had electroneuromyography for diagnosis purpose. At this time mean ALSFRS-R was 32.1 ± 10.5 and 75.0% of patients presented atypical symptoms (mostly dysautonomic or sphincter troubles). After diagnosis, 97.4% of patients were prescribed an occidental treatment: Rilutek^® (n = 12), physiotherapy (n = 17), or symptomatic treatment (n = 12). 21.6% of patients used a traditional treatment based on infusion-decoction for two of them and of unknown type for six patients.

Discussion and conclusion: More inclusions are needed to produce precise estimations. Follow-up data are currently being collected. Our aim is to extend Tropals to other countries in Africa and other Tropical zones. Tropals study will allow us to improve the description of ALS characteristics, prognosis for patients, and comprehension of the disease under the tropics

Acknowledgments

TROPALS Collaboration ([email protected]), Burkina Faso: Athanase Millogo; Bénin: Dismand Houinato, Atoké Mendinatou Agbetou; Cameroun: Callixte Kuate, Alfred Njamnshi; Côte d’Ivoire: Bengré Ernest Kouassi; République du Congo: Bèbène Bandzouzi; Gabon: Philomène Kouna Ndouongo, Yvonne Assegone Zeh, Gertrude Mouangue; France: Benoît Marin, Philippe Couratier, Pierre Marie Preux, Bello Hamidou, Marie Raymondeau, Michel Druet-Cabanac; Guinée: Amara Cisse, Fode Abass Cisse, Lansana Laho Diallo; Mali : Youssoufa Maiga, Sara Diakite; Mauritanie: Mouhamadou Diagana, Abderrahmane Moulaye, Cheikh Ould Hacen; République Centrafricaine: Pascal Mbelesso; Sénégal: Mansour Ndiaye, Amadou Gallo Diop, Anna Basse, Ousmane Cissé; Togo: Agnon Balogou, Damelan Kombate; Tunisie: Riadh Gouider, Imen Kacem, Amina Gargouri.

Reference:

• Marin B, Kacem I, Diagana M, Boulesteix M, Gouider R, Preux PM, Couratier P, TROPALS collaboration. Juvenile and adult-onset ALS/MND among Africans: incidence, phenotype, survival. A review. Amyotroph Lateral Scler. 2012 May;13(3):276–83.
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P145 REAPPRAISAL OF THE NOSOLOGICAL SIGNIFICANCE OF ALS-PDC MIXED CASES ON GUAM

Yoshida S¹

Ueda T²

Uebayashi Y³

Kihira T¹

Yase Y¹

Chen K-M⁴

Garruto RM⁵

^ahResearch Center of Neurological Diseases, Kansai University of Health Sciences, Sennan-Osaka, Japan

^aiUeda Clinic, Wakayama Ciy, Japan

^aj Uebayashi Clinic, Wakayama City, Japan

^akMicronesian Health and Aging Studies, University of Guam, Tammning, Guam, USA

^alLaboratory of Biomedical Anthropology and Neurosciences, Binghamton University, SUNY, USA

Email address for correspondence: [email protected]

Keywords: nosological significance, ALS-PDC mixed case, Guam

Background: The incidence of amyotrophic lateral sclerosis (ALS) on Guam has greatly declined since 1970 and disappeared for these years. However, parkinsonism–dementia complex (PDC) has still retained a relatively high occurrence with a trend changing to late-onset dementia without parkinsonism (Marianas Dementia) (1). Recently, we have observed a similar trend in another ALS/PDC focus in the Kii Peninsula of Japan.

Objective: The purpose of this study is to examine whether these diseases are considered as a single entity with a spectrum of expressions: pure ALS and PDC at each end, and to clarify a nosological significance of the ALS-PDC mixed case.

Methods: Statistical analysis was carried out using the entire NINCDS files for over 25 years from 1958 to 1982 (2), including 540 cases in total; 243 ALS, 286 PDC and 29 mixed cases. Fisher’s exact test was used to examine the independence of occurrence between ALS and PDC, among the groups of year at onset divided by the 5-year study periods and those of age at onset divided by decades. The strength of association between them was evaluated by Odds ratio. We used the population in 1970 as the standard base-population for analysis, at the mid-point of the whole study period.

Results: In the last 5-year period of 1978–1982, the incidence rates of both ALS and PDC cases markedly decreased below one-fifths of that in the first 5-year period of 1958–1962. On the contrary, the incidence rate of ALS–PDC mixed cases kept constant throughout the study period. The independence of occurrence between ALS and PDC cases was significantly denied among any groups of year at onset divided by the 5-year period and those of age at onset divided by the decades (Fisher’s exact test, p < 0.0001). Odds ratios for 20 years from 1958 to 1977 had gradually increased and sharply rose up during the last 5-year period.

Discussion: These results suggested that the ALS-PDC mixed cases might be a core disease rather than a by-chance, combined form between ALS and PDC, and not influenced merely by rapid socioeconomic changes on Guam. We will also discuss a similar trend of ALS/PDC in the Kii Peninsula of Japan.

References:

• Chen, K-M: The History of Guam ALS/PDC: 1900–2010 Annotated chronological bibliography. University of Guam. 2010.
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• Ueda T: Possible linkage between amyotrophic lateral sclerosis (ALS) and parkinsonism- dementia (PD) on Guam: The nosological significance of mixed case (ALS/PD), Wakayama Med. Rep 1993;34:1–5.
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P146 ALSFRS-R DECLINE IN PATIENTS FROM THE EMILIA-ROMAGNA REGISTER FOR ALS (ERRALS)

Mandrioli J¹

Salvi F²

Sette E³

Terlizzi E⁵

Rizzi R⁴

Casmiro M⁶

Liguori R⁷

Pasquinelli M⁸

Pietrini V⁹

Venturini E¹⁰

Biguzzi S¹⁰

Chierici E¹¹

Guidi C¹²

Borghi A¹³

Santangelo M¹⁴

Granieri E¹⁶

Mussuto V¹⁵

Fini N¹

De Pasqua S¹⁷

D’Alessandro R¹⁷

^amDepartment of Neuroscience, St Agostino Estense Hospital, Modena, Italy

^anDepartment of Neurology, Bellaria Hospital, Bologna, Italy

^aoDepartment of Neurology, St Anna Hospital, Ferrara, Italy

^apDepartment of Neuromotor Physiology, Azienda Ospedaliera ASMN, Reggio Emilia, Italy

^aqDepartment of Neurology, G Da Saliceto Hospital, Piacenza, Italy

^arDepartment of Neurology, Faenza and Ravenna Hospital, Ravenna, Italy

^asDepartment of Neurological Sciences, University of Bologna, Bologna, Italy

^atDepartment of Neurology, Infermi Hospital, Rimini, Italy

^auDepartment of Neuroscience, University of Parma, Parma, Italy

^avDepartment of Neurology, Bufalini Hospital, Cesena, Italy

^awDepartment of Neurology, Fidenza Hospital, Parma, Italy

^axDepartment of Neurology, Forlì Hospital, Forlì, Italy

^ayDepartment of Neurology, Maggiore Hospital, Bologna, Italy

^azDepartment of Neurology, Carpi Hospital, Modena, Italy

^baDepartment of Neurology, Imola Hospital, Bologna, Italy

^bbDepartment of Neuroscience, University of Ferrara, Ferrara, Italy

^bcDepartment of Neuroscience, St. Orsola-Malpighi University Hospital, Bologna, Italy

Email address for correspondence: [email protected]

Keywords: ALSFRS-R, population based study, disease progression

Background: The ALSFRS-R is an attractive primary outcome measure in clinical trials of ALS because it is validated, easy to administer, minimizes dropout, reduces cost, and correlates with survival. The ALSFRS-R is also a measure of global function. Few studies, mainly based on ALS centers data, examined the topic of ALSFRS-R decline during the disease course, and the relationship between clinical factors and rate of decline of the scale.

We report the results from a prospective population-based epidemiological study in Emilia Romagna Region, Italy, to describe the rate of decline of ALSFRS-R in relation to the clinical features and phenotypes of ALS patients from 2009.

Methods: This study was performed innine provinces and 11 local health units of Emilia Romagna (population 4.4 million inhabitants), with the involvement of 17 neurological departments. From 2009 onwards, a prospective registry has been collecting all cases of incident ALS among residents in Emilia Romagna region. For each patient, the main demographic and clinical information were collected by the caring physicians. In addition, a case report form has been completed during each patient follow-up.

Results: In the period from 1 January 2009 to 31 December 2011 in Emilia Romagna, 344 patients received a new diagnosis of ALS. Mean time from onset to diagnosis was 12.4 months. The follow-up period ranged from 12 to 48 months. Mean ALSFRS-R score at diagnosis was 39.7 (M = 41.3 and F = 37.8); mean rate of decline in the first year was 0.8 points/month (M 1.03, F 0.55), versus 0.3 points/month during the second year (M = 0.27, F = 0.27). The rate of decline was influenced by age, site of onset and disease phenotype, mainly during the first year after the diagnosis: the rate of decline was 1.08 points/months for patients having > 70 yrs of age at onset, compared to 0.69 for patients having < 71 yrs. Bulbar onset patients lost 1.15 points/month whereas spinal onset patients only 0.60 points/month. Patients with bulbar phenotype lost 1.10 points/months whereas patients with other clinical phenotype (classic, flail, and UMNp) lost 0.7 points/month to ALSFRS-R. Conversely, spinal onset patients had a major decline in FVC than bulbar patients, the latter starting with lower FVC scores at diagnosis.

Discussion and conclusion: Higher rate of decline in ALSFRS-R is present in older age-at-onset and bulbar patients. The first year of the illness after diagnosis shows the most rapid rates of decline, especially for male and bulbar patients. These data can be useful for allocation of patients within clinical trials and for managing the care of ALS patients.

P147 CLINICAL CHARACTERISTICS OF PATIENTS WITH YOUNG-ONSET ALS

Lazo C

Povedano M

Turon G

Montero J

University Hospital of Bellvitge, BARCELONA, Spain

Email address for correspondence: [email protected]

Keywords: clinical, prognosis, young onset ALS

Background: Young-onset amyotrophic lateral sclerosis (ALS) is sporadic ALS typically involving patients less than 45 years. Early onset ALS accounts for approximately 10% of sporadic ALS cases. No one knows the time elapsed since the onset of neurodegeneration and the appearance of symptoms. Phenotypic forms are very variable, being very rare bulbar involvement. Although disease progression is highly variable among all reported cases, there is tendency in slowly progressive symmetric weakness.

Objectives: To describe the clinical characteristics and survival analysis of patients with early onset ALS.

Methods: This is a retrospective study of 43 patients diagnosed with young-onset ALS under the age of 45 years analyzing clinical, prognostic factors and survival, and comparing these data with 180 adult patients with ALS attended in the University Hospital of Bellvitge in the province of Barcelona from the period 1990–2013.

We perform comparative analysis using Chi-square tests. Significant p-values less than 0.05 (significance level 5% alpha). The estimate of survival was performed using Kaplan Meier Test and the Log-Rank Test.

Results: 43 patients were diagnosed with early-onset ALS, 26% of the entire series. Two patients had history of Fronto-temporal Dementia. The male female ratio was 2:1. Spinal onset was observed in 93%. The overall survival was 57 months (older than 45 years, 31 months), 43 months for spinal and 26 months for bulbar onset. The analysis of the different variables that influence survival showed significant differences only in ventilated patients (p = 0.018).

Conclusions: Young patients represent 26% of the entire series. Being young is an independent predictor of increased survival and represents a distinct clinical variant predominantly spinal form, with a higher prevalence in men and increased survival compared to adults. The bulbar form is rare, regardless of gender. Noninvasive ventilation played a significant increase in survival. This study found no benefit in the treatment with riluzole or with the use of enteral nutrition.

P148 RARE ALS VARIANTS IN THE TURKISH POPULATION

Idrisoglu HA^1,2

Idrisoglu FM^1,2

Idrisoglu M^1,2

Polat N^1,2

^bdIstanbul University Medical Faculty of Neurological Department, Istanbul, Turkey

^beKocaeli University Medical Faculty, Istanbul, Turkey

Email address for correspondence: [email protected]

Keywords: SETX gene, VAPB gene, essential tremor

Backround: Mutations in SETX, SOD1, and VAPB genes have been identified in amyotrophıc lateral sclerosis (ALS).

Objectives: Juvenile ALS amyotrophic lateral sclerosis (ALS) is a form of chronic motor neuron disease characterized by combined upper and lower motor neuron symptoms and signs, with onset prior to age 25 years.

ALS4 is an autosomal dominant form of juvenile onset ALS associated with slow progression, severe muscle weakness and pyramidal signs, in the absence of bulbar and sensory abnormalities. We studied two ALS patients with novel mutations. One had juvenile onset of ALS. The second case resembled VAPB (ALS8). The vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) Pro56Ser mutation has been identified in Brazillian families showing various motor neuron syndromes.

Case report:

• Case Study 1, a 25-year-old female presented in December 2010 with an ongoing weakness in her left arm lasting 5–6 months. The patient demonstrated weight loss and respiratory distress and has a family history of consanguinity. Other muscles of extremities were normal. Babinsky sign was positive. Bilaterally Jaw reflex was positive. The patient demonstrated bulbar signs and anterior horn finding were determined by EMG examination. Following neurogenetic examinatıon, SOD1 mutation was negative but the homozygote nonconserved missense variant 682E in SETX gene was positive. Riluzole was started as treatment, dosage is 100mg/per day. FVC is 60% in respiratory test.

• Case Study 2, a 77-year-old male patient with diabetes mellitus disease for 30 years presented to our clinic in August 2008 with a tremor in his hands. The tremor in his right hand had occurred since 1998. The patient has a family history of consanguinity. Two-sided tremor and the proof of cogwheel were determined in the neurological examination and PD was diagnosed. There were no further PD characteristics except minimal tremor, the UPRS was 5 and cranial MR examination was normal. Genetic research was carried out on patients due to intermarriage. Following neurogenetic investigation, the homozygous, non-conserved, missense variant M93T in VAPB gene ALS 8 was identified.

Conclusıons: This study identifies new genetic associations with ALS and provides phenotype correlations with both previously reported and novel mutations. In this study, we wanted to report these very occasional cases which have clinical characteristics and genetic finding.

Reference:

• Hirano M, Quinzii CM et al. Senataxin mutations and amyotrophıc lateral sclerosis ALS 2011 May;12(3):223–7.
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P149 UBQLN2 IN A JUVENILE ALS WITHOUT DEMeNTIA

Idrisoglu HA^1,2

Idrisoglu FM^1,2

Idrisoglu M^1,2

^bfIstanbul University Medical Faculty of Neurological Department, Istanbul, Turkey

^bgKocaeli University Medical Faculty, Istanbul, Turkey

Email address for correspondence: [email protected]

Keywords: juvenile ALS, dementia,UBQLN2

Background: Amyotrophic lateral sclerosis (ALS) is a paralytic and usually fatal disorder caused by motor-neuron degeneration in the brain and spinal cord. Most cases of ALS are sporadic but about 5–10% are familial. Mutations in superoxide dismutase 1(SOD1),TAR DNA-binding protein(TARDBP, also known as TDP43)and fused in sarcoma(FUS, also known as translocated in liposarcoma, TLS) account for approximately 30% of classic familial ALS. Mutations in several other genes have also been reported as rare causes of ALS or ALS-like syndromes.

A case report: A 16-year-old male was examined with a weakness in his right leg which had occurred for 2 years, heel disturbance were determined. The patient demonstrated bilateral atrophy and fasiculation in both distal lower extremities as determined by a neurological examination. Two-sided dropped feet and tibialis anterior weakness were also found. Lumbar and thoracic MR examination was normal. Routine laboratory research was normal. EMG showed anterior horn findings. DNA sequence analyses found no SOD gene mutations however the M329L mutation was identified in 392 position of UBQLN2.

Conclusion: In this study, we report a juvenile-type case with ALS 15 without FTD diagnosis, with a mutation in UBQLN2. This case was discussed.

P150 PHYSICAL ACTIVITY: A RISK FACTOR FOR MOTOR NEURONE DISEASE?

Harwood C¹

Besson H²

Ekelund U²

Finucane F²

Mcdermott C¹

Wareham N²

Shaw PJ¹

^bhUniversity of Sheffield, Sheffield, South Yorkshire, UK

^biMRC Epidemiology Unit, Cambridge, UK

Email address for correspondence: [email protected]

Keywords: physical activity, risk

Background: Reports suggesting a higher incidence of motor neurone disease (MND) in professional sportsmen have motivated research into a potential aetiological association between physical activity (PA) and MND, as part of a gene–environment interaction (1). Unrelated research demonstrates that PA normally augments some known MND pathogenic mechanisms and may also upregulate angiogenic and neurotrophic genes associated with MND (2,3). However, definitive evidence is lacking, with methodological limitations to prior studies.

Objectives: To conduct a case-control study to determine any association of PA with the development of MND, using sound methodology.

Methods: Collaborating with Cambridge MRC Epidemiology Unit, we designed an interview-administered PA questionnaire (HAPAQ), which collects data regarding total adulthood PA (home, work, transport and leisure). Questionnaire validity was determined by comparing HAPAQ-derived data from 100 interviews with historical objective PA energy expenditure (PAEE) measurements from the same individuals. Subsequently, HAPAQ was used to interview incident sporadic MND cases, identified from regional MND services, and age- and gender-matched controls from general practice patient databases. Using the Compendium of Physical Activities (4), individual PAEE scores are determined from questionnaire-derived data. Case and control PAEE will be compared using conditional logistic regression, adjusting for potential confounders.

Results: HAPAQ-derived data correlated with objective total and vigorous PAEE measurements (r = 0.44, p < 0.001; r = 0.40, p < 0.001, respectively) (5). To date, 160 cases (63% male) and 300 controls (63% male) have been recruited (age range: 26–91yrs, mean age 64 years).

Discussion and conclusion: As one of the first questionnaires to be validated against historical objective PAEE measurements, HAPAQ accurately ranks individuals by adulthood PA using a standardised data collection method. Additional strengths of the study include a population-based recruitment approach, El-Escorial defined cases, blinding to the research hypothesis and confounder adjustment. Discussion of results analysis will be submitted as an updated abstract.

Acknowledgements:

This study was funded by a Medical Research Council-MND Association Lady Edith Wolfson Fellowship.

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P151 AMYOTROPHIC LATERAL SCLEROSIS, PHYSICAL ACTIVITY AND SPORT: A LITERATURE REVIEW

Hamidou B¹

Marin B^1,2

Preux PM^1,2

Couratier P^1,2

^bjINSERM U1094, Tropical Neuroepidemiology, Limoges, France

^bkUniversity of Limoges, School of Medicine, Institute of Neuroepidemiology and Tropical Neurology, Limoges, France

^blCHU, Limoges, France

Email address for correspondence: [email protected]

Keywords: physical activity, sport, soccer

Background: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease of unknown aetiology. Occupational and environmental exposures may contribute to the risk of developing ALS. Several hypotheses have been proposed to explain a relationship between the occurrence of ALS and a number of exogenous risk factors such as physical activity (PA), trauma, and exposure to toxic substances alone or in combination with predisposing genetic characteristics.

Objective: To elucidate whether physical activity and sport increase the risk of developing ALS.

Methods: To summarize the available evidence and to conclude on the association between ALS, sport and PA, a systematic review of the epidemiological literature on PA as a potential determinant of ALS was performed according to the MOOSE guidelines. From PubMed (MEDLINE), SCOPUS, Science Direct (Elsevier), Ingenta Connect, Refdoc (the INIST/CNRS), and the Cochrane databases up to January 2013, selected studies were methodologically appraised according to Armon’s classification system for ALS risk factor studies (1). References of previous meta-analyses were also considered and experts were contacted to identify relevant unpublished studies. The search was not limited in time but to articles in French and English languages.

Results: Of 464 potentially relevant studies, only 36 studies were eligible. Of these, 12 were cohort studies (mostly descriptive), 20 case-control studies and four case-series studies. Of all, one study fell into Armon’s level of evidence class I (unpublished): five as class II; eight studies were classified as class III; 16 as class IV and six as class V. Synthesis of data was stratified by definition of PA which strongly varied across studies: (i) sport and PA; (ii) occupational activity (farmers, foresters, fishermen and mason); (iii) soccer; (iv) American football; and (v) proxies. As regards PA and sport, the review achieves a level B of evidence, meaning that it is probably not a risk factor. Nevertheless this result was not stable when the unpublished work was not included.

Conclusion: PA appears to be probably not a risk factor for ALS. However, some data suggest an accelerating effect of PA in predisposed individuals. Further good-quality studies (class I or II) are needed to stabilize and confirm these results.

Acknowledgments: We thank Pr Ettore Beghi chairman of EURALS consortium.

Reference:

• Armon C. An evidence-based medicine approach to the evaluation of the role of exogenous risk factors in sporadic amyotrophic lateral sclerosis. Neuroepidemiology 2003;22(4):217–228.
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P152 THE IMPACT OF PHYSICAL IMPAIRMENT ON EMOTIONAL FUNCTIONING IN ALS SEEN THROUGH THE PATIENT'S EYE

Abdulla S^1,2

Vielhaber S^1,3

Körner S²

Machts J³

Heinze HJ^1,4

Dengler R²

Petri S²

^bmDepartment of Neurology, Otto-von-Guericke University Magdeburg, D-39120 Magdeburg, Germany

^bnDepartment of Neurology, Hannover Medical School, D-30625 Hannover, Germany

^boGerman Center for Neurodegenerative Diseases, D-39120 Magdeburg, Germany

^bpLeibniz Institute for Neurobiology, D-39118 Magdeburg, Germany

Email address for correspondence: [email protected]

Keywords: emotional functioning, physical impairment, patient-reported outcome measure

Background: The diagnosis of amyotrophic lateral sclerosis (ALS) and its relentless progression are a permanent emotional burden for these patients. However, according to the literature emotional functioning does not seem to correlate with physical impairment (1).

Objective: To investigate the impact of physical impairment on emotional functioning when consistently measured by patient-reported health assessment instruments.

Methods: Eighty-five consecutive patients were asked to participate in the study. Emotional functioning was assessed by the ALSAQ-40, a validated patient-reported disease specific tool to assess quality of life. Physical impairment was evaluated by the recently validated extended ALSFRS (ALSFRS-EX) as a patient-reported outcome measure, comprising three additional items to increase sensitivity of the original ALSFRS-R for severe functional impairment (2,3). Pairwise Spearman rank correlation coefficients were used to correlate the ALSFRS-EX with the subscale “emotional functioning” of the ALSAQ-40.

Results: Seventy-six patients participated in the study. We noticed significant negative correlations between emotional functioning and the ALSFRS-EX items ‘facial expression’; ‘dressing’; ‘turning in bed’; ‘walking’;‘getting around at home’ (p < 0.01) and ‘swallowing’; ‘handwriting’; ‘feeding’; ‘finger movement’; ‘climbing stairs’; and ‘breathing on back’ (p < 0.05).

The items of the emotional functioning subscale ‘being bored’; ‘feeling as if I have no freedom’ ; and ‘worried to be a burden’ were significantly correlated with gross and fine motor function impairment (p < 0.01), ‘feeling lonely’ and ‘feeling hopeless’ were correlated with bulbar, gross and fine motor impairment (p < 0.05). Bulbar involvement was significantly correlated with ‘feeling embarrassed in social situations’; ‘feeling worried about future’ (p < 0.01); ‘feeling depressed’; and ‘feeling angry’ (p < 0.05). Fine motor impairment was also correlated with ‘feeling worried about future’ (p < 0.01).

Discussion: Up to now the influence of physical impairment on emotional functioning was found to be only minor or not even present (1). Patient-reported assessment may be more suitable to capture relevant and plausible correlations more sensitively. Our results indicate how multifaceted the impact of physical decline on emotional functioning is when assessed by patient-completed health assessment instruments, thereby directly seen through the patient’s eye.

Conclusion: The impact of physical impairment on emotional functioning should not be underestimated. Timely and comprehensive supportive therapy is crucial to improve emotional functioning as an important domain of quality of life in patients with ALS.

References:

• Salas T, Mora J, Esteban J, Rodríguez F, Díaz-Lobato S, Fajardo M. Spanish adaptation of the Amyotrophic Lateral Sclerosis Questionnaire ALSAQ-40 for ALS patients. ALS 2008;9:168–72.
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• Wicks P, Massagli MP, Wolf C, Heywood J. Measuring function in advanced ALS validation of ALSFRS-EX extension items. Eur J Neurol 2009;16:353–359.
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P153 NECK WEAKNESS IS A POTENT PROGNOSTIC FACTOR IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS PATIENTS

Nakamura R¹

Atsuta N¹

Watanabe H¹

Hirakawa A¹

Watanabe H¹

Izumi Y^2,12

Morita M³

Ogaki K⁴

Taniguchi A⁵

Mizoguchi K⁶

Okamoto K⁷

Hasegawa K⁸

Aoki M⁹

Kawata A¹⁰

Abe K¹¹

Imai T¹³

Tsuji S¹⁴

Kaji R²

Nakano I^3,10

Sobue G¹

^bqNagoya University Graduate School of Medicine, Nagoya, Japan

^brUniversity of Tokushima Graduate School, Tokushima, Japan

^bsJichi Medical University, Tochigi, Japan

^btJuntendo University School of Medicine, Tokyo, Japan

^buMie University Graduate School of Medicine, Tsu, Japan

^bvShizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan

^bwGunma University Graduate School of Medicine, Gunma, Japan

^bxNational Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

^byTohoku University School of Medicine, Sendai, Japan

^bzTokyo Metropolitan Neurological Hospital, Tokyo, Japan

^caOkayama University Graduate School of Medicine, Okayama, Japan

^cbVihara Hananosato Hospital, Miyoshi, Japan

^ccNational Hospital Organization, Miyagi National Hospital, Miyagi, Japan

^cdThe University of Tokyo, Tokyo, Japan

Email address for correspondence: [email protected]

Keywords: neck weakness, prognostic factor, cohort study

Background: Muscle weakness in particular regions of the body affect the prognosis of ALS, although it has not been sufficiently determined which regions are most predictive.

Objectives: To clarify the emergence of muscle weakness in regions of the body that affect survival and deterioration in activities of daily living (ADLs) in ALS patients.

Methods: We conducted a multi-center-based prospective cohort study of ALS patients. We enrolled 401 sporadic ALS patients. Death or the introduction of invasive ventilation was defined as the primary endpoint, and the time to five clinical markers of ADL deterioration associated with bulbar paralysis or limb weakness were defined as ADL milestones. Muscle weakness was assessed in the neck flexor muscles; the bilateral abductors of the shoulders; the bilateral wrist extensor muscles; the bilateral flexor muscles of the hips; and the bilateral ankle dorsiflexion muscles. We performed Cox proportional hazards regression analyses for the primary endpoint and the five ADL milestones, adjusting for known covariate prognostic factors for ALS, and compared survival curves using the Kaplan–Meier method and a log-rank test.

Results: The MRC score for the neck flexors was the most significant prognostic factor for the primary endpoint (HR: 0.74, p < 0.001), loss of speech (HR: 0.66, p < 0.001), and loss of swallowing function (HR: 0.73, p < 0.001), and was one of the significant prognostic factors for loss of upper limb function, difficulty turning in bed, and loss of walking ability (HR: 0.77, p = 0.001; HR: 0.77, p = 0.002; and HR: 0.80, p = 0.008, respectively). The MRC score for the neck flexors was also a significant prognostic factor for covariates of the previously reported prognostic factors. We divided the patients into four categories according to their MRC score for the neck flexors (ie 5, 4, 3, and ≤ 2). All of the differences among the Kaplan–Meier curves for the primary endpoint and each ADL milestone were significant according to a log-rank test (p < 0.001).

Discussion and conclusion: The neck flexor muscles are mainly innervated by motor neurons in the cervical cord (C1–8) and accessory nerve nuclei. Motor neurons for the neck flexion muscles are contiguous or overlapping with those for the respiratory muscles, the bulbar muscles, and the upper limb muscles. It may be speculated that if the contiguous spreading of motor neuron degeneration occurs according to the local spreading hypothesis, neck flexion impairment may eventually affect survival and deterioration in ADLs. In conclusion, neck weakness is an independent prognostic factor for survival and deterioration in ADLs in ALS patients.

P154 OCCUPATIONAL EXPOSURE TO ELECTRIC SHOCKS AND MAGNETIC FIELDS AND MORTALITY DUE TO MOTOR NEURON DISEASE

Vergara X¹

Kheifets L²

Mezei G¹

^ceEPRI, Palo Alto, CA, USA

^cfUCLA - Fielding School of Public Health, Los Angeles, CA, USA

Email address for correspondence: [email protected]

Keywords: occupational exposures, electric shocks, magnetic fields

Background: Motor neuron disease (MND) is consistently linked to electrical occupations, defined as occupations with typically higher exposure to magnetic fields (MF), in epidemiologic studies. However, the association with measured MF levels is weaker (1). Exposure to electric shocks (ES) is proposed as an explanation for the observed association between electrical occupations and MND (2). To date, no epidemiologic study has evaluated the relationship between ES and MND.

Objectives: To examine the association between occupational exposure to ES and MF, and MND, in a case-control study relying on U.S. mortality data between 1991 and 1999.

Methods: For each of the 5886 MND deaths, 10 controls were selected from other deaths and matched on sex, age, year, and region. Occupations obtained from death certificates were linked to job exposure matrices for ES and MF. Mortality odds ratios (MOR) were calculated using conditional logistic regression, adjusting for education level, race, and ethnicity included in models.

Results: For ES, MND MORs were 0.73 (95% confidence intervals (CI): 0.67–0.79) for high exposure and 0.90 (95% CI: 0.84–0.97) for medium exposure compared to low. For MF, MND MORs were 1.09 (95% CI: 1.00–1.19) for high exposure and 1.09 (95% CI: 0.96–1.23) for medium exposure compared to low. For electrical occupations, MND MOR was 1.23 (95% CI: 1.04, 1.47) compared to non-electrical occupations. MND mortality was increased for electric occupations within medium- and low-exposure categories of both ES and MF, but not within high exposure to MF or ES.

Discussion: Among U.S. deaths, we found an inverse association between occupational ES and MND and no consistent association between MF exposure and MND. Similar to others, we observed an increased risk for MND for electrical occupations. However, exposure to ES and MF did not account for this increased risk. We present the first effort to separate the effects of two correlated exposures within electrical occupations in the U.S. population.

Conclusions: Current results are in support of an association between electrical occupations and MND, but provide no evidence that the association is explained by occupational exposure to ES or MF.

References:

• Vergara X et al. Occupational exposure to extremely low-frequency magnetic fields and neurodegenerative disease: a meta-analysis. Journal of occupational and environmental medicine/American College of Occupational and Environmental Medicine 2013;55(2):135–46.
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