Involvement of the spinal posterior horn in Gerstmann–Sträussler–Scheinker disease (PrP P102L)

Yamada, Masahito; Tomimitsu, Hiroyuki; Yokota, Toshifumi; H, Tomi; Sunohara, Nobuhiko; Mukoyama, Masakuni; Itoh, Yoshinori; Suematsu, Naomi; Otomo, E; Okeda, Riki; Matsushita, M.; Mizusawa, Hidehiro

doi:10.1212/wnl.52.2.260

Cited by 35 publications

(33 citation statements)

References 23 publications

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“…Rather, GSS patients with CJD features are more likely to have PSIDDs [3,8,25,[42][43][44]. The EEG features of our patient 2 (IV-3) and patient 3 (V-2) at late disease stages corroborated this point of view.…”

Section: Discussionsupporting

confidence: 77%

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Chi

Lee

et al. 2009

J Neurol

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A P102L point mutation in the prion protein gene (PRNP) usually causes Gerstmann-Sträussler-Scheinker disease (GSS), which is a rare hereditary transmissible spongiform encephalopathy (TSE). The clinical features include ataxia in 50s age group with subsequent dementia, spastic paraparesis and extrapyramidal signs. Many families have been reported from the Caucasian population, but only one from the Chinese. We hereby report a large Chinese family with P102L mutation of PRNP whose clinical manifestations at onset were intriguingly heterogeneous, either rapidly progressive dementia with scanty other neurological features or slowly progressive ataxia followed by cognitive impairment. The four-generation pedigree included eight patients with a mean age at onset of 36.9 +/- 12.9 (mean +/- SD) years. Mean disease duration to death in the four patients was 5.5 +/- 1.7 (mean +/- SD) years. Molecular analysis revealed a P102L mutation and M129 polymorphism in the PRNP gene in all affected individuals. TSE with P102L mutation of PRNP appears to have a remarkably variable phenotypic expressivity that may change with time and does not appear related to the codon 129 polymorphism.

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Section: Discussionsupporting

confidence: 77%

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Chi

Lee

et al. 2009

J Neurol

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“…The brain was 1,150 g in weight, and macroscopically showed mild atrophy of the cerebral cortex and a dural patch over the surface of right lower portion of the cerebellar hemisphere. In histopathological and immunohistochemical examinations with antibodies to PrP [16], marked spongiform changes, neuronal loss, and gliosis with granular PrP accumulation of synaptic type were observed prominently in the cerebral and cerebellar cortices (Fig. 2), and to a less extent in the thalamus, and basal ganglia.…”

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confidence: 98%

Creutzfeldt-Jakob disease after Jannetta's operation with cadaveric dura mater graft: initial manifestations related to the grafted site

Nishida

Yamada

Hara

et al. 2002

Journal of Neurology

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“…These intraocular inoculation studies demonstrate that scrapie is transported along optic nerve axons and that in this model, distribution of scrapie in the brain initially follows the neural circuitry of the visual system. Since the route of prion transport within the spinal cord has not been established and PrP Sc deposits are found in spinal gray matter (19,37,39,40,48,57), the aim of the present study was to investigate the spread of TME from the sciatic nerve to the brain in the Syrian hamster. In addition, we examined the patterns of prion deposition in the spinal cord, brain stem, and cerebrum in order to establish whether prion spread took place by axonal transport in spinal tracts, by cellto-cell spread within the spinal gray matter, or a combination of both pathways.…”

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confidence: 99%

Retrograde Transport of Transmissible Mink Encephalopathy within Descending Motor Tracts

Bartz¹,

Kincaid

Bessen³

2002

J Virol

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The spread of the abnormal conformation of the prion protein, PrP Sc , within the spinal cord is central to the pathogenesis of transmissible prion diseases, but the mechanism of transport has not been determined. For this report, the route of transport of the HY strain of transmissible mink encephalopathy (TME), a prion disease of mink, in the central nervous system following unilateral inoculation into the sciatic nerves of Syrian hamsters was investigated. PrP Sc was detected at 3 weeks postinfection in the lumbar spinal cord and ascended to the brain at a rate of approximately 3.3 mm per day. At 6 weeks postinfection, PrP Sc was detected in the lateral vestibular nucleus and the interposed nucleus of the cerebellum ipsilateral to the site of sciatic nerve inoculation and in the red nucleus contralateral to HY TME inoculation. At 9 weeks postinfection, PrP Sc was detected in the contralateral hind limb motor cortex and reticular thalamic nucleus. These patterns of PrP Sc brain deposition at various times postinfection were consistent with that of HY TME spread from the sciatic nerve to the lumbar spinal cord followed by transsynaptic spread and retrograde transport to the brain and brain stem along descending spinal tracts (i.e., lateral vestibulospinal, rubrospinal, and corticospinal). The absence of PrP Sc from the spleen suggested that the lymphoreticular system does not play a role in neuroinvasion following sciatic nerve infection. The rapid disease onset following sciatic nerve infection demonstrated that HY TME can spread by retrograde transport along specific descending motor pathways of the spinal cord and, as a result, can initially target brain regions that control vestibular and motor functions. The early clinical symptoms of HY TME infection such as head tremor and ataxia were consistent with neuronal damage to these brain areas.The transmissible spongiform encephalopathies, or prion diseases, are progressive neurodegenerative diseases of animals and humans. Prion infection by peripheral routes, such as intraperitoneal infection, results in prion replication in the lymphoreticular system (LRS) prior to neuroinvasion of the peripheral and central nervous system (CNS). In natural prion diseases, oral exposure is the likely route of infection in bovine spongiform encephalopathy, transmissible mink encephalopathy (TME), and kuru of humans. Oral transmission is also a possible route of transmission in scrapie of sheep, chronic wasting disease of deer and elk, and variant Creutzfeldt-Jakob disease in humans.Experimental oral exposure of rodents to scrapie reveals that initial infection is established in the gut-associated lymphoid tissue and autonomic ganglia in the enteric nervous system (5, 37). Spread of the abnormal isoform of the prion protein, PrP Sc , from the gastrointestinal tract proceeds along both the splanchnic nerves to the spinal cord and the vagal nerve to the brainstem (6, 39). Neuroinvasion of the spinal cord from peripheral sites subsequently results in prion transport to the brain (...

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Involvement of the spinal posterior horn in Gerstmann–Sträussler–Scheinker disease (PrP P102L)

Abstract: The PrP abnormalities in synaptic structures of the spinal posterior horn may cause synaptic dysfunction that leads to loss of deep tendon reflexes and painful dysesthesias in patients with GSS102.

Cited by 35 publications

References 23 publications

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan

Creutzfeldt-Jakob disease after Jannetta's operation with cadaveric dura mater graft: initial manifestations related to the grafted site

Retrograde Transport of Transmissible Mink Encephalopathy within Descending Motor Tracts

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