Portal de Periódicos da CAPES

Pigmentary Retinopathy of ALS/PDC in Kii

2006; Elsevier BV; Volume: 113; Issue: 11 Linguagem: Inglês

10.1016/j.ophtha.2006.07.002

1549-4713

Yasumasa Kokubo, Kunio Ito, T. Fukunaga, Hisashi Matsubara, Shigeki Kuzuhara,

Cholinesterase and Neurodegenerative Diseases

The Kii peninsula of Japan together with Guam has one of the highest incidence rates of the endemic neurodegenerative diseases amyotrophic lateral sclerosis and parkinsonism–dementia complex (ALS/PDC) in the world.1Shiraki H. Yase Y. Amyotrophic lateral sclerosis in Japan.in: Vinken P.J. Bruyn G.W. de Jong J.M. Klawans H.L. Systemic Disorders and Atrophies. North-Holland, Amsterdam1975: 353-419Google Scholar The ALS/PDCs in the Kii peninsula and in Guam are characterized by the clinical features of parkinsonism, dementia, and upper and lower motor symptoms. The cause of ALS/PDC remains unclear.2Kuzuhara S. Kokubo Y. Sasaki R. et al.Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Kii peninsula of Japan: clinical and neuropathological study and tau analysis.Ann Neurol. 2001; 49: 501-511Crossref PubMed Scopus (99) Google Scholar A high prevalence of a peculiar pigmentary retinopathy (PR) resembling ophthalmomyiasis interna posterior (OIP) was reported in ALS/PDC patients and in the healthy Chamorro population in Guam in 1989.3Cox T.A. McDarby J.V. Lavine L. et al.A retinopathy on Guam with high prevalence in Lytico-Bodig.Ophthalmology. 1989; 96: 1731-1735Abstract Full Text PDF PubMed Scopus (35) Google Scholar Ophthalmomyiasis interna posterior–like PR, which was named PR of Guam, shows a linear and crisscrossed pattern of disruption of the retinal pigment epithelium (RPE). We reported PR resembling PR of Guam in one Kii PDC patient in 2003.4Kokubo Y. Ito K. Kuzuhara S. Ophthalmomyiasis-like pigmentary retinopathy in ALS/PDC in the Kii peninsula of Japan.Neurology. 2003; 60: 1725-1726Crossref PubMed Scopus (11) Google Scholar The purpose of our study was to explore the prevalence of PR in the patients and in healthy residents in the ALS/PDC focus on the Kii peninsula. Twelve patients (7 men and 5 women; mean age, 64.3 years), including 5 with Kii ALS and 7 with Kii PDC, and 115 healthy residents (51 men and 64 women; mean age, 64.7 years) underwent ophthalmoscopic examination. The clinical pictures of the patients are summarized in Table 1 (available at http://aaojournal.org). In general, Kii ALS patients showed bulbar palsy, muscle atrophy of the extremities, and pyramidal signs, whereas Kii PDC patients showed dementia, parkinsonism, and ALS features. The healthy residents consisted of 2 people between the ages of 20 and 29, 2 between 30 and 39, 4 between 40 and 49, 22 between 50 and 59, 42 between 60 and 69, 35 between 70 and 79, and 8 between 80 and 89. Institutional ethics committee approval was obtained, and all participants were fully informed and consented to this study.Table 1Summary of Clinical Pictures and the Results of Pigmentary Retinopathy (PR) in the Kii Amyotrophic Lateral Sclerosis and Parkinsonism–Dementia Complex (ALS/PDC) PatientsAge (yrs)GenderDuration of the IllnessMotor Neuron SignsDementiaParkinsonismPRKii ALS No. 166Female5 yrs, 5 mosMA (limbs), PTSsNoneNone− No. 264Male2 yrsBP, MA (upper limbs), PTSsNoneNone+ No. 363Female4 yrsBP, MA, PTSsNoneNone+ No. 462Male2 yrsBP, MA (limbs and respiratory muscle), PTSsMD, disorientationNone− No. 552Male5 yrs, 5 mosMA (limbs), PTSsNoneNone−Kii PDC No. 163Female2 yrs, 7 mosMA (small hand muscles)MD, disorientationRigidity, bradykinesia, GD+ No. 272Female13 yrsMA (limbs), PTSsMD, disorientation, hypobuliaRigidity, bradykinesia, GD− No. 364Female7 yrsMA (limbs), PTSsMD, disorientation, hypobuliaRigidity, bradykinesia− No. 464Male4 yrs, 6 mosMA (small hand muscles), PTSsMDRigidity, bradykinesia, GD− No. 572Male7 yrs, 6 mosMA (upper limbs), PTSsMD, disorientation, hypobuliaRigidity, bradykinesia− No. 652MaleunknownNoneMD, disorientation, psychiatric symptomsRigidity, bradykinesia+ No. 776Male7 yrs, 6 mosMA (limbs)MD, disorientation, hypobuliaRigidity, bradykinesia−AM = akinetic mutism; BP = bulbar palsy; GD = gait disturbance; MA = muscle atrophy; MD = memory disturbance; PTS = pyramidal tract sign. Open table in a new tab AM = akinetic mutism; BP = bulbar palsy; GD = gait disturbance; MA = muscle atrophy; MD = memory disturbance; PTS = pyramidal tract sign. Pigmentary retinopathy was seen in 4 of the 12 Kii ALS/PDC patients (2 of the 5 Kii ALS patients and 2 of the 7 PDC patients), and the frequency was 33.3%. In contrast, PR was seen in only 1 of the 115 healthy residents, and the frequency was 0.9%. The 65-year-old woman, who showed PR without neurological deficits or family history of ALS/PDC, had moved to the ALS/PDC focus from a neighboring village at 20 years. None of those with PR complained of visual symptoms, and their visual acuities were normal. Ophthalmoscopic examination of the fundus after dilatation of pupils revealed PR consisting of linear and crisscrossed defects in the RPE. Any causative substances including other evidence of fly larvae were not detected (Fig 1 [available at http://aaojournal.org]). The characteristic feature of PR is meandering, crisscrossing, hypopigmented tracks of RPE that mimic OIP.5Hanlon S.D. Steele J.C. An unusual retinal pigment epitheliopathy endemic to the island of Guam.Optom Vis Sci. 1993; 70: 854-859Crossref PubMed Scopus (14) Google Scholar In patients with PR or OIP, visual function is usually well preserved, with minimal or no signs or symptoms of inflammation. Although the cause of OIP is subretinal invasion by a fly larva, the cause of PR remains unclear. We believe that PR and OIP are different conditions. An extensive investigation of the epidemiology of PR in the Guam Chamorro population in 1993 revealed that PR was found in 85 of 531 (16%) of the neurologically normal subjects and 38 of 72 (53%) of ALS/PDC patients. In addition, PR was found exclusively in the Chamorro population and never in the other ethnic groups on Guam.5Hanlon S.D. Steele J.C. An unusual retinal pigment epitheliopathy endemic to the island of Guam.Optom Vis Sci. 1993; 70: 854-859Crossref PubMed Scopus (14) Google Scholar Pigmentary retinopathy is thus peculiar to the Chamorro population, and far higher prevalence rates in individuals with ALS/PDC suggest that PR may be related to the pathogenesis of ALS/PDC. In the present study, PR was seen in 33.3% of Kii ALS/PDC patients and in 0.9% of healthy residents. To our knowledge, no patient with PR has ever been reported in other areas of Japan, nor has PR been associated with other diseases in Japanese. These findings suggest that PR occurs almost exclusively in ALS/PDC patients in Japan. The cause of PR is unknown, but the existence of a very rare OIP-like PR in ALS/PDC patients from 2 different isolated ethnic groups on Guam and the Kii peninsula suggests that OIP-like PR is not a coincidental finding, but may be genetically linked to ALS/PDC.