A geographical cluster of progressive supranuclear palsy in northern France

Abstract

Objective: To describe a cluster of progressive supranuclear palsy (PSP) in northern France.PSP has not been reported in geographical, temporal, or occupational clusters. A unit of Neurology and Neurogeriatrics opened in 2005 at the Centre Hospitalier de Wattrelos, serving the population of Wattrelos and Leers (combined population 51,551) and parts of neighboring towns. For most of the 20th century, this area was a center for chromate and phosphate ore processing, textile dyeing, and tanning. Significant industrial waste persists close to residential areas.Methods: From 2005 to 2014, 92 patients with PSP at Centre Hospitalier de Wattrelos were identified and studied. Detailed residential data were available in the medical records. Eighty cases have had magnetic resonance head scanning and 60 have died, of whom 13 have been examined neuropathologically. Results:The ratio of observed to expected PSP incidence over the period 2005 to 2012 was 12.3 (95% confidence interval: 7.4-35.9). Mean onset age was 74.3 years. The Richardson syndrome/PSP-parkinsonism ratio was 43%/42%. Four other phenotypes each occurred in 2% to 5%. Onset was gait/balance difficulty in 52%. None of the 92 affected patients were relatives and 7 were of North African ancestry. MRI was compatible with a clinical diagnostic of PSP in all cases. Histopathologic examination confirmed neurofibrillary degeneration and tufted astrocytes in all autopsied cases. Western blots revealed a typical tau 4R doublet. The tau H1 haplotype occurred in 95.8% of cases' chromosomes. Progressive supranuclear palsy (PSP) is an uncommon sporadic disorder with no reports in the literature of geographical clusters. Its incidence in developed countries is approximately 1.2 per 100,000 per year and the prevalence of investigator-diagnosed cases is 5 to 6 per 100,000. Conclusions: 1-4The cause is unknown but several familial clusters have now been reported. 5,6 Olfaction, affect, and reaction time assessments revealed more frequent dysfunction among relatives of individuals with PSP than among relatives of controls. 7Genetic variations in MAPT locus are a mild risk factor for PSP. 8 An inversion of a 900-kb span of chromosome 17 defines the H1 haplotype.9-11 A subhaplotype of H1 designated H1c is responsible for the association between the H1 haplotype and PSP. 12,13 Studies of nongenetic risk factors have found lesser educational attainment.14-16 Two geographical clusters of illnesses similar to PSP have been described on Guam 17-20 and in Guadeloupe where a case-control survey 21 revealed a strong association (odds ratio 8.3, p , 0.001) of

Environmental and occupational risk factors for progressive supranuclear palsy: Case‐control study

“…However, it is possible that statistical differences were not found because of the overall low frequency of these jobs in our cohort. In fact, a recent report of a cluster of PSP patients in France in a geographical area with severe environmental contamination by industrial metals supports our findings …”

TheMAPTgene is differentially methylated in the progressive supranuclear palsy brain

“…The authors found no significant results because of the low precision of the Matrix‐assisted laser desorption/ionization‐time‐of‐flight mass spectrometry (MALDI‐TOF) technology used. Regarding PSP, the cohorts of postmortem brains described in the literature are relatively small because of the low prevalence of the disease, which is approximately 5 to 6 cases per 100,000 persons . Indeed, larger cohorts are actually clinicopathological descriptions of as many as 100 cases in multicentric studies .…”

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

“…A cluster of PSP cases in an industrial city in France and a multicenter case-control study suggest that environmental risk factors influence PSP incidence. 7,8 …”