RESUMEN
ABSTRACT: It is recommended that every patient with a new third nerve palsy undergo urgent neuroimaging (computed tomography angiography or magnetic resonance angiography) to exclude a posterior communicating artery aneurysm. Because of the novel coronavirus (COVID-19) pandemic, our institution noted a significant decline in the number of patients with aneurysmal subarachnoid hemorrhage presenting to the hospital. We report one such example of a patient who developed new-onset severe headache and vomiting and did not seek medical attention because of COVID-19. Two months later, she was noted to have ptosis during a routine follow-up and was found to have a complete, pupil-involving third nerve palsy. Computed tomography angiography was performed and revealed an irregular bilobed saccular aneurysm (7 × 9 × 5 mm) of the right posterior communicating (PComm) artery, but no acute hemorrhage was visible on CT. On MRI, immediately adjacent to the aneurysm, there was a small subacute hematoma in the right medial temporal lobe with surrounding vasogenic edema. This case had a fortunate and unique outcome as she had a contained hematoma adjacent to the ruptured PComm aneurysm and did not experience severe morbidity from the subarachnoid hemorrhage nor did she rebleed in the interval in which she did not seek care. This case highlights the importance of providing neuro-ophthalmic care even during a pandemic.
Asunto(s)
Aneurisma Roto/diagnóstico por imagen , COVID-19/complicaciones , Aneurisma Intracraneal/diagnóstico por imagen , Enfermedades del Nervio Oculomotor/diagnóstico por imagen , Anciano , Aneurisma Roto/complicaciones , Angiografía Cerebral , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Angiografía por Resonancia Magnética , Enfermedades del Nervio Oculomotor/complicacionesRESUMEN
Amyotrophic lateral sclerosis (ALS) is predominantly sporadic, but associated with heritable genetic mutations in 5-10% of cases, including those in Cu/Zn superoxide dismutase (SOD1). We previously showed that misfolding of SOD1 can be transmitted to endogenous human wild-type SOD1 (HuWtSOD1) in an intracellular compartment. Using NSC-34 motor neuron-like cells, we now demonstrate that misfolded mutant and HuWtSOD1 can traverse between cells via two nonexclusive mechanisms: protein aggregates released from dying cells and taken up by macropinocytosis, and exosomes secreted from living cells. Furthermore, once HuWtSOD1 propagation has been established, misfolding of HuWtSOD1 can be efficiently and repeatedly propagated between HEK293 cell cultures via conditioned media over multiple passages, and to cultured mouse primary spinal cord cells transgenically expressing HuWtSOD1, but not to cells derived from nontransgenic littermates. Conditioned media transmission of HuWtSOD1 misfolding in HEK293 cells is blocked by HuWtSOD1 siRNA knockdown, consistent with human SOD1 being a substrate for conversion, and attenuated by ultracentrifugation or incubation with SOD1 misfolding-specific antibodies, indicating a relatively massive transmission particle which possesses antibody-accessible SOD1. Finally, misfolded and protease-sensitive HuWtSOD1 comprises up to 4% of total SOD1 in spinal cords of patients with sporadic ALS (SALS). Propagation of HuWtSOD1 misfolding, and its subsequent cell-to-cell transmission, is thus a candidate process for the molecular pathogenesis of SALS, which may provide novel treatment and biomarker targets for this devastating disease.
Asunto(s)
Esclerosis Amiotrófica Lateral/fisiopatología , Exosomas/metabolismo , Pliegue de Proteína , Superóxido Dismutasa/química , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Línea Celular , Electroforesis en Gel de Poliacrilamida , Humanos , Ratones , Microscopía Electrónica , Pinocitosis/fisiología , Interferencia de ARN , ARN Interferente Pequeño/genética , Superóxido Dismutasa/metabolismoRESUMEN
PURPOSE: Both CT myelogram (CTM) and digital-subtraction myelogram (DSM) can be used to evaluate patients for possible cerebrospinal fluid (CSF) leaks. DSM is a relatively new technique. No data exists on the radiation dose associated with this procedure, and how it compares with CTM. MATERIALS AND METHODS: All patients who underwent DSM for spontaneous intracranial hypotension (SIH) refractory to blood patching from Dec 2016 - Sept 2019 were retrospectively assessed. DSM dose factors were then recorded (cumulative fluoroscopy time, total kerma area product (KAP, mGy.cm2), cumulative air kerma (mGy), as well as CTM dose factors (included CTDIvol (mGy) and dose-length product (DLP, mGy.cm). These indices were then used to calculate the effective dose for both procedures using standardized conversion factors. RESULTS: 61 DSMs were performed in 42 patients, 33 of which also underwent CTM. The median effective dose was 6.6 mSv per DSM study (range: 1.2 - 17.7). On a per-patient basis (i.e. those patients who underwent more than one DSM (as the initial one was negative), the median total effective dose was 13 mSv for their total DSM imaging (range: 2.6 -31.7). For the CTM, the median effective dose was 19.7 mSv (range: 3.2 - 82.4 mSv). CONCLUSION: The radiation dose with DSM appears to be significantly lower than that of CTM (p = 0.0005), when looking at CTM doses both from our institution and in the published literature.