Creutzfeldt-Jakob disease (CJD) is a rare and devastating neurodegenerative disorder. The sporadic form of the disease (sCJD) is the most common, although mutation-associated familial or hereditary cases are also known, as well as iatrogenic forms [1]. CJD is caused by neuronal degeneration due to the neurotoxic properties of the misfolded isoform (PrP Sc ) of cellular or natively folded prion protein

Tolosa-Hunt syndrome (THS) is an idiopathic condition included in the differential diagnosis of painful ophthalmoplegia. Actinomycosis is a treatable, underrecognized condition that mimics neoplasia and other infections and may result in painful ophthalmoplegia with cavernous sinus involvement. Actinomycosis should be included in the differential diagnosis. PATIENT DE SCRIP TI ONA 57-year-old man presented with a 3-week history of refractory pain in the left jaw, which later involved the retroauricular, suboccipital, and retro-ocular areas. Due to the pain, he had several tooth extractions a few days after symptom onset. He had no prior known medical diagnoses.Physical examination disclosed left abducens nerve palsy with horizontal diplopia and decreased sensation to pinprick in the left V3 and V2 territories. Compression of the left trochlear, supraorbital, and infraorbital nerves was painful. There was mild monocytosis and a moderate elevation of C-reactive protein (21 mg/L) and erythrocyte sedimentation rate (48 mm/h). Brain magnetic resonance imaging (3 T) showed enlargement of the left cavernous sinus, occupied by a gadolinium-enhancing tissue with hypointense areas in its interior suggestive of necrosis (Figure 1a). The tissue extended into the extracranial area, following the path of the left V3 trigeminal branch, reaching the parapharyngeal and retroparotid space, where a softtissue lesion of 1.4 cm in diameter was evident (Figure 1b). A whole body computed tomography (CT) scan was normal. A 3-day course of methylprednisolone was ineffective.A lumbar puncture obtained acellular cerebrospinal fluid with normal glucose, protein increase of 60 mg/dl, no oligoclonal banding, normal IgG index, and negative culture. Flow cytometry ruled

Fatal familial insomnia (FFI) is a rare prionopathy with unusually high incidence in the Basque Country. We report detailed data on clinical, diagnostic, histopathological, and biochemical characteristics of a recent FFI case series. The Basque Brain Bank database was screened for patients diagnosed from 2010 to 2021 with standard genetic and/or neuropathological criteria. This series includes 16 patients, 25% without family history, with 12 cases from 9 unrelated (but geographically-linked, Basque country) kindreds, onset ranging from 36 to 70 years, and disease course from 7 to 11.5 months. Insomnia was the initial symptom in most cases, with consistent polysomnography in 92% of the cases. In contrast, 14-3-3 and RT-QuIC from cerebrospinal fluid were negative. Most patients were homozygous for methionine. Gliosis and neuronal loss in basal ganglia and thalamus were the main histopathological findings; Western blotting identified preferentially the protease-resistant prion protein (PrPres) type 2, although detection of the scrapie isoform of the prion protein (PrPSc) identified using brain tissue RT-QuIC was more successful. This is one of the largest current studies on FFI patients performed to provide improvements in diagnostic reliability. Among the analyzed tests, polysomnography and the genetic study show the highest diagnostic value in FFI.

Background Glutaric aciduria type 2 is a rare, lethal disorder that affects metabolism of fatty acids caused by genetic defects in electron transfer (ETF) or in electron transfer flavoprotein dehydrogenase (ETFDH). We aimed to describe the pathological findings of 15 week old foetus, born from a consanguineous couple with 3 previous perinatal deaths. The last son died at 4 days of life and genetic analyses revealed a novel probably pathogenic variant at ETFDH (c.706dupG + c.706dupG) that codifies for a truncated protein (p.Glu236Glyfs*5 + p.Glu236Glyfs*5). Case During the gestation, due to the medical familial history, prenatal echography and a chorial biopsy for ETFDH‐associated glutaric aciduria analysis were carried out. Sanger sequencing confirmed the presence of the homozygous familial variant in the ETFDH gene. The gestation was terminated and the foetal autopsy performed. Autopsy revealed prominent forehead, flat nasal bridge, malformed ears, intrauterine growth retardation, polycystic kidneys and steatosis in the liver, consistent with the diagnosis of glutaric aciduria type II. The comparison of present cases with the previously reported in the literature confirmed the presence of classical criteria, but also revealed the association with urogenital deformities, not previously stated. Conclusions Clinical and foetal findings allowed the characterisation of the novel variant (c.706dupG at ETDFH) as pathogenic. Genotype–phenotype relationship is important when studying rare genetic disorders such as glutaric aciduria type II, as variants are usually family‐specific, leading to a difficulty in the characterisation of their pathogenicity.

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