P.088 Dysautonomia and Diabetes: A Prodrome to Fatal Familial Insomnia (FFI)

Background: Fatal Familial Insomnia (FFI) is an autosomal dominant multisystem prion disease, with sleep disorders often being the first presentation. Although autonomic dysfunctions are key features, the frequency and timing vary between reports, and may accompany early insomnia. Moreover, endocrine changes are reported, but diabetes rarely is - with unclear timing of onset in relation to the insomnia. Methods: N/A Results: Here we present a 46-year-old previously healthy male, who within 22 months prior to the onset of sleep disturbances, developed hypertension and diabetes. Then within 3-4 months after onset of sleep disturbances development tachycardia and diaphoresis. His sleep continued to deteriorate, and later developed bulbar impairment, ataxia, diplopia, sleep apnea and cognitive decline. He passed away 20 months from onset of insomnia. Polysomnography showed status dissociates and central apnea. He had positive genetic testing, PRNP c.532G>A (p.Asp178Asn) and PRNP c.385A>G (pMet129Val), a pathological confirmation, and a positive family history Conclusions: Here diabetes and hypertension significantly preceded sleep disturbances, and tachycardia and diaphoresis developed shortly after. This illustrates that dysautonomia and endocrine dysfunction may be unrecognized prodromes in some cases of FFI, and could be an early marker of clinical disease onset and therapeutic interventions, especially in genetically confirmed asymptotic patients.

The Fumarprotocetraric Acid Inhibits Tau Covalently, Avoiding Cytotoxicity of Aggregates in Cells

Neurodegenerative disorders, including Tauopathies that involve tau protein, base their pathological mechanism on forming proteinaceous aggregates, which has a deleterious effect on cells triggering an inflammatory response. Moreover, tau inhibitors can exert their mechanism of action through noncovalent and covalent interactions. Thus, Michael’s addition appears as a feasible type of interaction involving an α, β unsaturated carbonyl moiety to avoid pathological confirmation and further cytotoxicity. Moreover, we isolated three compounds from Antarctic lichens Cladonia cariosa and Himantormia lugubris: protolichesterinic acid (1), fumarprotocetraric acid (2), and lichesterinic acid (3). The maleimide cysteine labeling assay showed that compounds 1, 2, and 3 inhibit at 50 µM, but compounds 2 and 3 are statistically significant. Based on its inhibition capacity, we decided to test compound 2 further. Thus, our results suggest that compound 2 remodel soluble oligomers and diminish β sheet content, as demonstrated through ThT experiments. Hence, we added externally treated oligomers with compound 2 to demonstrate that they are harmless in cell culture. First, the morphology of cells in the presence of aggregates does not suffer evident changes compared to the control. Additionally, the externally added aggregates do not provoke a substantial LDH release compared to the control, indicating that treated oligomers do not provoke membrane damage in cell culture compared with aggregates alone. Thus, in the present work, we demonstrated that Michael’s acceptors found in lichens could serve as a scaffold to explore different mechanisms of action to turn tau aggregates into harmless species.

Management of a primary cardiac leiomyosarcoma in a young woman

Cardiac leiomyosarcoma is an extremely rare tumor with a poor prognosis. An 18-year-old female patient was admitted to our clinic with a left atrial leiomyosarcoma extending to the right lower pulmonary veins. We performed complete tumor excision by the right anterolateral mini-thoracotomy approach using minimally invasive techniques. After pathological confirmation of the tumor, right lower lobectomy was performed with the same incision one week later to prevent recurrence. Although no tumor remnant was found in the lobectomy specimen, adjuvant chemotherapy was started. No recurrence was detected during the 12-month follow-up. In conclusion, the right submammarian minithoracotomy approach has the advantages of its less invasive nature and suitability for complete tumor resection with lobectomy.

Extramedullary myeloid sarcoma mimicking tuberculosis of spine: A case report and literature review

Background: A definitive diagnosis of spinal tuberculosis (TB) remains challenging. The “gold standard” is to obtain histopathological confirmation of the lesion. This analysis highlights how to avoid missing the diagnosis of an extramedullary myeloid sarcoma (EMS) versus TB. Case Description: A 25-year-old male presented with paraparesis. Although this was first attributed to TB spondylodiscitis, a PET-CT and reevaluation of the biopsy specimen both confirmed the diagnosis of an EMS. Conclusion: Nontubercular spinal disease should be suspected when a patient deteriorates despite the institution of antitubercular therapy for a reasonable duration. Further, microbiological and/or pathological confirmation is warranted to direct appropriate treatment and differentiate spinal TB from other entities as, in this case, an EMS.