Neuropathology, Pathology, USMLE Step 1 - Full Vignette with Extended Explanations скачать в хорошем качестве

Neuropathology, Pathology, USMLE Step 1 - Full Vignette with Extended Explanations

An 82-year-old woman has a year-long history of burning, numbness, and weakness in her feet and hands, with autonomic symptoms like constipation, diarrhea, and orthostatic hypotension. Her examination finds distal sensorimotor loss and atrophy, with abnormal nerve studies and unique biopsy findings. How would you approach identifying the underlying cellular or molecular process in this multifaceted neuropathic case? VIDEO INFO Category: Neuropathology, Pathology, USMLE Step 1 Difficulty: Hard - Advanced level - Challenges experienced practitioners Question Type: Mechanism Case Type: Tricky Findings Explore more ways to learn on this and other topics by going to https://endlessmedical.academy/auth?h... QUESTION An 82-year-old retired construction forewoman is evaluated for one year of progressive burning pain and numbness in the feet ascending to the mid-shins, alternating constipation and watery diarrhea, early satiety, dry mouth, lightheadedness on standing with two recent falls, and hand clumsiness with nocturnal paresthesias. Weight recorded last month is 52 kg and height 160 cm. Remote exposures include exotic reptile breeding decades ago; she has had no pets for 15 years.... OPTIONS A. Extracellular deposition of wild-type transthyretin as beta-pleated sheet amyloid fibrils within endoneurial and perivascular compartments of peripheral nerve, producing length-dependent axonal loss with small-fiber/autonomic involvement; electron microscopy shows nonbranching 8-10 nm fibrils and... B. Extracellular deposition of mutant transthyretin (hereditary ATTR) forming beta-pleated sheet fibrils in endoneurial/perivascular spaces, a mechanism that typically coexists with a pathogenic TTR sequence variant rather than negative TTR sequencing, and may present earlier with prominent neuropat... C. Extracellular deposition of immunoglobulin light chains (AL amyloidosis) injuring peripheral nerves via toxic oligomers and vascular deposition, usually accompanied by a detectable monoclonal gammopathy; cardiac bone scintigraphy lacks specificity for ATTR in the presence of a monoclonal protein. D. Complement-mediated antibody attack on ganglioside-rich nodal axolemma (e.g., anti-GM1) causing acute motor axonal neuropathy with nodal conduction failure and evolving albuminocytologic dissociation rather than chronic sensory-autonomic axonopathy with amyloid fibrils on biopsy. CORRECT ANSWER A. Extracellular deposition of wild-type transthyretin as beta-pleated sheet amyloid fibrils within endoneurial and perivascular compartments of peripheral nerve, producing length-dependent axonal loss with small-fiber/autonomic involvement; electron microscopy shows nonbranching 8-10 nm fibrils and bone scintigraphy demonstrates grade =2 99mTc-pyrophosphate uptake in the absence of a monoclonal protein. EXPLANATION The clinical, electrophysiologic, scintigraphic, and pathologic findings converge on wild-type transthyretin amyloidosis with peripheral nerve involvement. Bone scintigraphy shows grade 3 99mTc-pyrophosphate uptake with an elevated heart-to-contralateral ratio in the absence of a monoclonal protein, which-together with Congo red-positive deposits and 8-10 nm nonbranching fibrils on electron microscopy-strongly supports transthyretin amyloid rather than AL. Negative targeted TTR sequencing, advanced age, carpal tunnel features, autonomic failure, and cardiomyopathy point specifically to wild-type TTR.... Further reading: Links to sources are provided for optional further reading only. The questions and explanations are independently authored and do not reproduce or adapt any specific third-party text or content. --------------------------------------------------- Our cases and questions come from the https://EndlessMedical.Academy quiz engine - multi-model platform. Each question and explanation is forged by consensus between multiple top AI models (i.e. Open AI GPT, Claude, Grok, etc.), with automated web searches for the latest research and verified references. Calculations (e.g. eGFR, dosages) are checked via code execution to eliminate errors, and all references are reviewed by several AIs to minimize hallucinations. Important note: This material is entirely AI-generated and has not been verified by human experts; despite stringent consensus checks, perfect accuracy cannot be guaranteed. Exercise caution - always corroborate the content with trusted references or qualified professionals, and never apply information from this content to patient care or clinical decisions without independent verification. Clinicians already rely on AI and online tools - myself included - so treat this content as an additional focused aid, not a replacement for proper medical education. Visit https://endlessmedical.academy for more AI-supported resources and cases. This material can not be treated as medical advice. May contain errors. ---------------------------------------------------