Familiares: Enfermedad de Creutzfeldt – Jacob familiar- Síndrome de Gerstmann – Sträussler – Scheinker- Insomnio familiar fatal- Enfermedades por priones. Gerstmann–Sträussler–Scheinker syndrome (GSS) is an extremely rare, usually familial, fatal De Michele G, Pocchiari M, Petraroli R, et al. (August ). A number sign (#) is used with this entry because of evidence that Gerstmann- Straussler disease (GSD) and a form of cerebral amyloid angiopathy are caused .
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CC HPO: Gerstmann-Straussler disease is a rare inherited prion disease characterized by adult onset of memory loss, dementia, ataxia, and pathologic deposition of amyloid-like plaques in the brain Gerstmann et al. Gerstmann-Straussler disease typically presents with progressive limb and truncal ataxia, dysarthria, and cognitive decline in the thirties and forties, and the average disease duration is 7 years. GSD can be distinguished from CJD by earlier age at onset, longer disease duration, and prominent cerebellar ataxia Masters et al.
On the basis of clinical and pathologic criteria, Hsiao et al. However, these distinctions may only underscore the phenotypic variability in presentation and progression of the disease Panegyres et al. However, PRNP-immunoreactive amyloid deposits within the walls of cerebral vessels have been observed in patients with truncating mutations in the PRNP gene.
Data suggest that C-terminal-truncated PRNP proteins lacking the glycosylphosphatidylinositol GPI anchor required to attach the protein to the plasma membrane may readily form amyloid fibrils that result in cerebrovascular amyloid deposition summary by Revesz et al.
Seitelberger described a kindred with a unique neurologic disorder traced through 5 generations. Gerstmann-straussler-scheinkker deposits were found in the cerebral cortex, basal ganglia, and most extremely all layers of the cerebellum.
Clinically and pathologically the disorder most closely resembled kuru, although the authors noted some differences in the plaque distribution. Peiffer described gerstmsnn-straussler-scheinker family of sheepbreeders in which a father and 2 sons had GSD.
All 3 also had congenital hip dysplasia, as did at least 3 other members of the kindred, all females. The main clinical features included ataxia, dysarthria, and personality changes.
Gerstmann–Sträussler–Scheinker syndrome – Wikipedia
Peiffer noted that GSD was characterized neuropathologically by large gerdtmann-straussler-scheinker distributed throughout the cerebral cortex, basal ganglia, and white matter. The clinical picture included visual loss in 1 patient and sensory loss in another patient.
Dementia only occurred late in the illness in 2 patients. Neuropathologic examination showed multicentric amyloid plaques in the cerebral and cerebellar cortices, basal ganglia, and white matter, as well as degeneration of gerstmann-straussler–scheinker corticospinal tract, spinocerebellar tract, and dorsal columns.
Spongiform changes were limited to the superficial cerebral cortex. The disorder had lasted 8 years.
There were severe spongy changes in the neocortex, extensive and often large amyloid deposits throughout the cerebral hemispheres and cerebellum, and severe astrocytic gliosis throughout all areas of gray and white matter within the brain. The degree of cortical spongy change was much greater than that in relatives who died with a similar clinical eenfermedad. Sixty-four patients showed progressive ataxia, dementia, and parkinsonism with onset in the late thirties to early sixties.
Early features included impaired smooth pursuit eye movements, impaired short-term memory, and clumsiness of the hands. Death occurred 6 months to 2 years after onset. The amyloid core of plaques was immunolabeled with antibodies raised to PrP, but not with antibodies raised to beta-amyloid APP; Spongiform changes were mild.
The disease in the Indiana kindred was traced to the year Farlow et al.
OMIM Entry – # – GERSTMANN-STRAUSSLER DISEASE; GSD
In each of the generations sinceaffected members had been identified by either history or clinical examination. The findings seemed to account for the painful dysesthesias and arreflexia seen in this variant of the disorder.
He had no family history of neurologic disease. At disease onset in his forties, he developed impaired short-term memory function, reduced learning capacity, and personality changes, including emotional immaturity, anxiety, and increasing anger.
Neurologic examination showed apraxia, tremor, rigidity, and hyperreflexia, but no ataxia. Eventually he developed gerstmanh-straussler-scheinker and his dementia progressed. He died at age 51, 9 years after symptom onset. Neuropathologic examination showed mild cerebral and cerebellar atrophy.
There gerstmann-atraussler-scheinker numerous congophilic amyloid plaques throughout the brain that were immunoreactive to PrP. There was no spongiform degeneration; occasional neurofibrillary tangles were seen. Age at onset ranged from 38 to 70 years, with an average of Nine patients verstmann-straussler-scheinker with gait disturbance, 1 with dysarthria, and 1 with dysesthesia of the lower limbs. Common features of the early stage of disease were unsteady gait, truncal ataxia, painful dysesthesias of the lower limbs, weakness of the proximal lower limbs, loss of deep tendon reflexes, and mild dysarthria.
Ten of the 11 patients were initially evaluated gerstmann-strausslr-scheinker orthopedic gerstmann-straussler-schelnker on the suspicion of lumbar spine disease, none of whom diagnosed GSS. Only 1 patient had clear dementia on initial examination. Brain MRIs were normal gerstmann-straussler-scheinekr the initial stages and no patients had cerebellar changes. However, all patients developed cortical and diffuse brain atrophy with disease progression and onset of dementia.
Brain SPECT studies of 5 patients showed hypoperfusion of the occipital lobes and patchy decreased blood flow in the cerebrum, with normal flow in the cerebellum. Diffusion-weighted brain MRI at the initial examination showed enfermedwd signal changes in the frontal, temporal, occipital, and parietal cortical gyri of both hemispheres, although CT scan showed no abnormalities.
His condition deteriorated over the next 8 months, resulting in mutism, akinesia, and spastic tetraplegia.
CT scans performed at 2 and 8 months after the initial examination showed remarkable progression of cortical atrophy in the bilateral frontotemporal lobes and hypodense lesions in frontal subcortical areas. The phenotype was somewhat unusual in that she exhibited supranuclear gaze palsy early in the disease course and had absence of myoclonus, lack of proteins see in the CSF, and no significant EEG or MRI findings. The patient later developed more typical features of the disorder with rapid progression to death 4 months after presentation.
Postmortem examination showed typical diffuse spongiform encephalopathy eenfermedad amyloid-like plaques restricted to the cerebellum. Genetic analysis identified a heterozygous mutation in the PRNP gene Family history was not contributory. Neuropathologic examination showed severe cortical atrophy with amyloid deposits in the parenchymal and leptomeningeal gerstmann-staussler-scheinker vessels and in the perivascular neuropil, as well gerstmann-straussler-scheinkerr marked tau MAPT; -immunoreactive neurofibrillary tangles, similar to those observed in Alzheimer disease.
Amyloid was also present in the surrounding parenchyma. Amyloid was immunoreactive to PrP, and immunoblot analysis detected mainly a 7. Amyloid-laden vessels were also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele was also involved in the pathologic process.
She presented at age 55 years with a month history of increasing cognitive impairment, forgetfulness, and decreased concentration associated enfermedxd hallucinations.
She also had aphasia, but no extrapyramidal signs, ataxia, or myoclonic jerks. EEG showed generalized slowing with a typical pattern of periodic synchronous wave complexes. The disorder progressed, and she developed parkinsonism as a result of neuroleptic treatment, mutism, akinesia, and myoclonic jerks.
She died 27 months after onset. Neuropathologic examination showed enfermerad PRNP-reactive amyloid angiopathy and parenchymal plaques; neurofibrillary gdrstmann-straussler-scheinker were not present, but there were focal tau accumulations.
Her mother was diagnosed with probable CJD on the basis of comparable symptoms and signs. The patient was heterozygous for MV Both YX and QX result in C-terminally truncated proteins lack the GPI anchor and thus cannot localize to the plasma membrane, suggesting that absence of this anchor predisposes to amyloid formation.
The patient was initially diagnosed with Alzheimer disease. Neuropathologic examination showed frontotemporal atrophy, severe tau-immunoreactive neurofibrillary tangles, and amyloid plaques that were immunoreactive gerstmanns-traussler-scheinker PRNP. The prion deposits were immunopositive to residuesbut not toconsistent with C-terminal truncation. Western blot analysis showed a smear of enermedad K-resistant PrP, the most prominent of which was 11 gerstmann-straussler-scheinekr.
PrP-immunoreactive amyloid angiopathy was observed. Spongiform changes were not observed. The patient’s deceased mother had a history of a similar disorder with later onset and accompanied by severe chronic diarrhea.
She was diagnosed with Alzheimer disease, but reexamination of her pathology showed the same abnormalities as observed in her daughter.
The proband was heterozygous for MV, whereas enfremedad mother was homozygous gerstmann-straussler-scheinket M One of these patients was a member of the family reported by Adam et al. They tested for the presence of PrP in brain tissue extracts from 46 cases, including 13 familial cases, of nonspongiform dementias with a variety of associated neurologic signs.
None of the cases transmitted disease to primates, and none had PrP detectable by Western immunoblots. In affected members of 2 unrelated families with autosomal dominant inheritance of Gerstmann-Straussler disease, Hsiao et al.
In a year-old woman who belonged to the original family reported by Gerstmann et al. In affected members of a large Indiana kindred with Gerstmann-Straussler disease reported by Ghetti et al.
In a patient with GSD, Peoc’h enfermedadd al. The patient was homozygous for val Neuropathologic studies showed typical features of GSS, including multicentric amyloid PrP-immunoreactive plaques, spongiform changes, mild gliosis, and neurofibrillary tangles.
Proteinase K-resistant prion protein was found, and immunochemical studies showed accumulation of a C-terminal-truncated PrP fragment roughly covering residues 80 to Biophysical studies showed that the mutant protein had an increased tendency to aggregate, with a different effect on the PrP structural dynamics compared to the EQ mutation In a Japanese woman with PrP-immunoreactive cerebral amyloid angiopathy, Ghetti et al. Clinical data was not provided, but neuropathologic studies showed vascular and parenchymal PRNP-immunoreactive amyloid deposition and extensive neurofibrillary tangle pathology.
They produced a homozygous animal for the mutant transgene array which caused spontaneous disease in a consistently shorter period of time than in the hemizygous animal. The authors concluded that the murine PL mutation is required for CNS degeneration, that the clinical and neuropathic phenotypes of transgenic mice can be dramatically altered by ablation of the wildtype Prnp gene, and that this mouse model recapitulated virtually all features of human GSD.
Expressed MoPrP PL in Drosophila was differentially glycosylated, localized at the synaptic terminals, and mainly present as deposits in adult brains. In addition, type 1 glutamatergic synaptic boutons in larval neuromuscular junctions of MoPrP PL flies showed significantly increased numbers of satellite synaptic boutons.
Brains from scrapie-infected mice showed significantly decreased ELKS ERC1;an active zone matrix marker, compared with control mice. The authors proposed that altered active zone structures at the molecular level may be involved in the pathogenesis of GSD in Drosophila and scrapie-infected mice.
Familial cerebral amyloidosis and spongiform enfermsdad. Real and imagined clinicopathological limits of ‘prion dementia’. Linkage of the Indiana kindred of Gerstmann-Straussler-Scheinker disease to the prion protein gene. Extending the clinical spectrum.