Co-incidental C9orf72 expansion mutation-related frontotemporal lobar degeneration pathology and sporadic Creutzfeldt-Jakob disease.

BACKGROUND: The C9orf72 hexanucleotide expansion mutation is the most common cause of genetic frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and combined FTD-ALS. Its underlying neuropathology combines TDP-43 pathology and dipeptide repeat protein (DPR) deposits and may also associate with other neurodegeneration-associated protein aggregates. Herein we present a unique combination of C9orf72 mutation with sporadic Creutzfeldt-Jakob disease (CJD) in a 74-year-old patient with rapidly progressive dementia. METHODS: Detailed neuropathological examination including immunohistochemistry for several proteinopathies. Genetic analysis was conducted by repeat primed polymerase chain reaction (PCR). Furthermore, we analyzed additional C9orf72 mutation carriers for prion-protein (PrP) deposits in brain tissue and screened the cerebellar cortex of other CJD cases for p62/DPR neuronal inclusions to assess the frequency of combined pathologies. RESULTS: Postmortem brain examination of a patient with a rapidly progressive neurological deterioration of 8 months' duration confirmed the diagnosis of CJD. She harbored valine homozygosity at PRNP codon 129. In addition, a frontotemporal lobar degeneration (FTLD)-pattern with TDP-43 protein aggregates and p62+/C9RANT+ positive inclusions along with a high degree of Alzheimer-related pathology (A3B3C3) were identified. The suspected C9orf72 expansion mutation was confirmed by repeat-primed PCR. Screening of 13 C9orf72 cases showed no pathological PrP aggregates and screening of 100 CJD cases revealed no other C9orf72 expansion mutation carriers. CONCLUSION: A combination of a C9orf72 expansion mutation-related FTLD with sporadic CJD in the same patient is rare. While the rarity of both diseases makes this concurrence most likely to be coincidental, questions regarding a potential link between these two neurodegenerative pathologies deserve further studies.

Traumatic fatal cerebral hemorrhage in an old patient with a history of multiple sclerosis under dabigatran: a case report and review of the literature.

One disadvantage of direct anticoagulant drug is the lack of an antidote, which may become relevant in patients with traumatic brain injury. A 77-years old man with atrial fibrillation and syncope received dabigatran despite recurrent falls. Due to a ground-level-fall, he suffered from subarachnoidal and intraparenchymal hemorrhages, subdural hematoma and brain edema with a midline shift. Despite osteoclastic trepanation and hematoma-evacuation he remained comatose and died seven days later without regaining consciousness. Most probably, decreased dabigatran clearance due to increased age might have contributed to the fatal course. We suggest withholding anticoagulant therapy in patients with unexplained falls. If anticoagulant therapy is deemed necessary, vitamin-K-antagonists with their potential for laboratory monitoring and reversal of anticoagulant activity should be preferred.

Recovery from acute paraplegia due to spontaneous spinal, epidural hematoma under minimal-dose acetyl-salicylic acid.

OBJECTIVE: Spontaneous spinal epidural hematoma (SEH) has not been reported under anti-thrombotic therapy with acetyl-salicylic acid (ASA) in a dosage of 50 mg/d. METHODS: Spinal MRI, emergency laminectomy. RESULTS: A 77-yo, HIV-negative female under longterm treatment over three years with ASA 50 mg/d for varicositas, prescribed by her general practitioner, experienced sudden onset back pain with radiation towards both knees after getting up in the morning. One-and-a-half hours later she also developed ascending hypesthesia and weakness originating from both distal lower limbs. Three hours after onset, hypesthesia had reached the T10-level bilaterally and she had become paraplegic. There was reduced intestinal motility, stool incontinence, and urinary hesitancy. MRI of the thoraco-lumbar spine demonstrated a SEH T9-L1 indenting the dural sack and compressing the myelon. Immediately after emergency laminectomy T10-12 with micro-surgical evacuation of the clot, 12 h after onset, she could move both legs again and was able to walk with support 7 days after surgery. CONCLUSIONS: This case shows that SEH occurs under a minimal dose of ASA and that such patients rapidly recover upon immediate surgical decompression and evacuation of the hematoma.