Research Article| Volume 276, ISSUE 1-2, P163-169, January 15, 2009

Age at onset influences on wide-ranged clinical features of sporadic amyotrophic lateral sclerosis



      To profile the detailed clinical features of sporadic amyotrophic lateral sclerosis (ALS) on large-scale samples in Japan.


      We assessed the clinical features of sporadic ALS patients in Japan, based on the nationwide registration system of the Ministry of Health, Labor and Welfare of Japan. We described 3428 new cases registered cases between 2003 and 2006 to analyze initial symptoms and related clinical features, 4202 cases registered in the single year of 2005 to describe the cross-sectional overview of the ALS patients, and a total of 2128 cases with tracheostomy positive pressure ventilation (TPPV) from all of the registration data from 2003 to 2006 to describe the features of ALS patients with TPPV.


      The patients with an older age at onset progressed more rapidly to the TPPV stage than those with a younger age at onset. The subpopulation of patients with long-standing TPPV showed ophthalmoplegia, while its appearance rate was less in the patients with an older age at onset than in those with a younger age at onset. Furthermore, age at onset strongly influenced the frequency of initial symptoms: dysarthria, dysphagia, neck weakness and respiratory disturbance were more frequent in patients with an older age at onset, while upper or lower limb weakness was observed more frequently in patients with a younger age at onset. In addition, those initial symptoms were still the most prominent at the follow-up stage, suggesting that the initial symptoms determine the major clinical features even in advanced illness.


      Our present study demonstrated that symptomatic features of ALS are strongly influenced by the age at onset by the large scale of samples.


      ALS (amyotrophic lateral sclerosis), TPPV (tracheostomy positive pressure ventilation)


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        • Millul A.
        • Beghi E.
        • Logroscino G.
        • Micheli A.
        • Vitelli E.
        • Zardi A.
        Survival of patients with amyotrophic lateral sclerosis in a population-based registry.
        Neuroepidemiology. 2005; 25: 114-119
        • del Aguila M.A.
        • Longstreth Jr., W.T.
        • McGuire V.
        • Koepsell T.D.
        • van Belle G.
        Prognosis in amyotrophic lateral sclerosis: a population-based study.
        Neurology. 2003; 60: 813-819
        • Ringel S.P.
        • Murphy J.R.
        • Alderson M.K.
        • Bryan W.
        • England J.D.
        • Miller R.G.
        • et al.
        The natural history of amyotrophic lateral sclerosis.
        Neurology. 1993; 43: 1316-1322
        • Haverkamp L.J.
        • Appel V.
        • Appel S.H.
        Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction.
        Brain. 1995; 118: 707-719
        • Norris F.
        • Shepherd R.
        • Denys E.
        • Mukai E.
        • Elias L.
        • et al.
        Onset, natural history and outcome in idiopathic adult motor neuron disease.
        J Neurol Sci. 1993; 118: 48-55
        • Czaplinski A.
        • Yen A.A.
        • Appel S.H.
        Amyotrophic lateral sclerosis: early predictors of prolonged survival.
        J Neurol. 2006; 253: 1428-1436
        • Traynor B.J.
        • Bruijn L.
        • Conwit R.
        • Beal F.
        • O'Neill G.
        • Fagan S.C.
        • et al.
        Neuroprotective agents for clinical trials in ALS: a systematic assessment.
        Neurology. 2006; 67: 20-27
        • Riviere M.
        • Meininger V.
        • Zeisser P.
        • Munsat T.
        An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole.
        Arch Neurol. 1998; 55: 526-528
        • Bensimon G.
        • Lacomblez L.
        • Meininger V.
        A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group.
        N Engl J Med. 1994; 330: 585-591
        • Lechtzin N.
        • Wiener C.M.
        • Clawson L.
        • Davidson M.C.
        • Anderson F.
        • Gowda N.
        • et al.
        Use of noninvasive ventilation in patients with amyotrophic lateral sclerosis.
        Amyotroph Lateral Scler Other Mot Neuron Disord. 2004; 5: 9-15
        • Moss A.H.
        • Casey P.
        • Stocking C.B.
        • Roos R.P.
        • Brooks B.R.
        • Siegler M.
        Home ventilation for amyotrophic lateral sclerosis patients: outcomes, costs, and patient, family, and physician attitudes.
        Neurology. 1993; 43: 438-443
        • Mizutani T.
        • Aki M.
        • Shiozawa R.
        • Unakami M.
        • Nozawa T.
        • Yajima K.
        • et al.
        Development of ophthalmoplegia in amyotrophic lateral sclerosis during long-term use of respirators.
        J Neurol Sci. 1990; 99: 311-319
        • Hayashi H.
        • Kato S.
        • Kawada A.
        Amyotrophic lateral sclerosis patients living beyond respiratory failure.
        J Neurol Sci. 1991; 105: 73-78
        • Tsuji S.
        • Onodera O.
        • Goto J.
        • Nishizawa M.
        Sporadic ataxias in Japan — a population-based epidemiological study.
        Cerebellum. 2007; : 1-9
        • World Federation of Neurology Research Group on Neuromuscular Diseases Subcommittee on Motor Neuron Disease
        Airlie House guidelines. Therapeutic trials in amyotrophic lateral sclerosis. Airlie House “Therapeutic Trials in ALS” Workshop Contributors.
        J Neurol Sci. 1995; 129 (Suppl): 1-10
        • Ohashi Y.
        • Tashiro K.
        • Itoyama Y.
        • Nakano I.
        • Sobue G.
        • Nakamura S.
        • et al.
        Study of functional rating scale for amyotrophic lateral sclerosis: revised ALSFRS(ALSFRS-R) Japanese version.
        No To Shinkei (in Japanese). 2001; 53: 346-355
        • Smyth A.
        • Riedl M.
        • Kimura R.
        • Olick R.
        • Siegler M.
        End of life decisions in amyotrophic lateral sclerosis: a cross-cultural perspective.
        J Neurol Sci. 1997; 152: S93-96
        • Borasio G.D.
        • Gelinas D.F.
        • Yanagisawa N.
        Mechanical ventilation in amyotrophic lateral sclerosis: a cross-cultural perspective.
        J Neurol. 1998; 245 (discussion S29): S7-12
        • Terao S.
        • Miura N.
        • Osano Y.
        • Adachi K.
        • Sobue G.
        Clinical characteristics of elderly Japanese patients with amyotrophic lateral sclerosis; with special reference to the development of respiratory failure.
        Rinsho Shinkeigaku (in Japanese). 2006; 46: 381-389
        • Traynor B.J.
        • Codd M.B.
        • Corr B.
        • Forde C.
        • Frost E.
        • Hardiman O.M.
        Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: a population-based study.
        Arch Neurol. 2000; 57: 1171-1176
        • Zoccolella S.
        • Beghi E.
        • Palagano G.
        • Fraddosio A.
        • Samarelli V.
        • Lamberti P.
        • et al.
        Signs and symptoms at diagnosis of amyotrophic lateral sclerosis: a population-based study in southern Italy.
        Eur J Neurol. 2006; 13: 789-792
        • Forbes R.B.
        • Colville S.
        • Swingler R.J.
        The epidemiology of amyotrophic lateral sclerosis (ALS/MND) in people aged 80 or over.
        Age Ageing. 2004; 33: 131-134
        • O'Toole O.
        • Traynor B.J.
        • Brennan P.
        • Sheehan C.
        • Frost E.
        • Corr B.
        • et al.
        Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004.
        J Neurol Neurosurg Psychiatry. 2008; 79: 30-32
        • Jagust W.J.
        • Reed B.R.
        • Seab J.P.
        • Budinger T.F.
        Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow.
        Arch Neurol. 1990; 47: 628-633
        • Hamada K.
        • Hirayama M.
        • Watanabe H.
        • Kobayashi R.
        • Ito H.
        • Ieda T.
        • et al.
        Onset age and severity of motor impairment are associated with reduction of myocardial 123I-MIBG uptake in Parkinson's disease.
        J Neurol Neurosurg Psychiatry. 2003; 74: 423-426
        • Muslimovic D.
        • Post B.
        • Speelman J.D.
        • Schmand B.
        Cognitive profile of patients with newly diagnosed Parkinson disease.
        Neurology. 2005; 65: 1239-1245
        • Aarsland D.
        • Tandberg E.
        • Larsen J.P.
        • Cummings J.L.
        Frequency of dementia in Parkinson disease.
        Arch Neurol. 1996; 53: 538-542
        • Kostic V.
        • Przedborski S.
        • Flaster E.
        • Sternic N.
        Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease.
        Neurology. 1991; 41: 202-205
        • Sossi V.
        • de la Fuente-Fernandez R.
        • Schulzer M.
        • Adams J.
        • Stoessl J.
        Age-related differences in levodopa dynamics in Parkinson's: implications for motor complications.
        Brain. 2006; 129: 1050-1058
        • Eisen A.
        • Schulzer M.
        • MacNeil M.
        • Pant B.
        • Mak E.
        Duration of amyotrophic lateral sclerosis is age dependent.
        Muscle Nerve. 1993; 16: 27-32
        • de Carvalho M.
        • Swash M.
        Can selection of rapidly progressing patients shorten clinical trials in amyotrophic lateral sclerosis?.
        Arch Neurol. 2006; 63: 557-560
        • Takeda S.
        • Yamada M.
        • Kawasaki K.
        • Oyanagi K.
        • Ikuta F.
        • Arai M.
        • et al.
        Motor neuron disease with multi-system involvement presenting as tetraparesis, ophthalmoplegia and sensori-autonomic dysfunction.
        Acta Neuropathol (Berl). 1994; 88: 193-200
        • Hayashi H.
        • Oppenheimer E.A.
        ALS patients on TPPV: totally locked-in state, neurologic findings and ethical implications.
        Neurology. 2003; 61: 135-137
        • Mizutani T.
        • Sakamaki S.
        • Tsuchiya N.
        • Kamei S.
        • Kohzu H.
        • Horiuchi R.
        • et al.
        Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators.
        Acta Neuropathol (Berl). 1992; 84: 372-377
        • Sasaki S.
        • Tsutsumi Y.
        • Yamane K.
        • Sakuma H.
        • Maruyama S.
        Sporadic amyotrophic lateral sclerosis with extensive neurological involvement.
        Acta Neuropathol (Berl). 1992; 84: 211-215
        • Takahashi H.
        • Oyanagi K.
        • Ohama E.
        • Ikuta F.
        Clarke's column in sporadic amyotrophic lateral sclerosis.
        Acta Neuropathol (Berl). 1992; 84: 465-470