2/14/2014 CPC: It Can Always Be Syphilis, HIV, May 2003 (Age 45): Cryptogenic Lymphoma, Sarcoid, TB, Obscure Strokes Fungus or a Vascular Problem… normal: TTE/TEE (bubble?) Holter cerebral angio CSF: protein 81 glucose 57 8 rbc, 7 wbc Cheryl A. Jay, MD (94% lymphs) UCSF Department of Neurology IgG index conflicts: none normal SFGH Neurology Service disclosures: none UCSF /SFGH UCSF /SFGH Cryptogenic Strokes in a Ischemic Stroke in the Middle-Aged Man Young Adult unknowns the usual suspects* hypertension, diabetes, hyperlipidemia, smoking vascular risks arterial dissection* trauma, arteriopathy associated systemic features drugs cocaine, methamphetamine <OCPs>… tox screen infection syphilis, HIV, VZV, TB & fungal meningitis, neurocysticercosis, endocarditis… stroke treatment bad blood hypercoagulability: hereditary (factor V Leiden, prothrombin), knowns acquired (APLA, cancer, HIT), both (protein S/C, AT3)… cells: sickle, p vera, essential thrombocytosis… nonsmoker broken heart R � L shunt, myxoma <Chagas> maternal grandmother: busted pipes systemic or primary CNS vasculitides recurrent strokes in her 40s genetic syndromes CADASIL, Fabry’s, mitochondrial (MELAS, POLG1?)… daughter: AML, age 16 other systemic malignant atrophic papulosis, microangiopathic hemolytic anemias, swimming, running marathons, connective tissue disorders, post-radiation… disorders traveling to Spain Ferro JM et al: Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 9:1085 (2010) UCSF /SFGH UCSF /SFGH 1
2/14/2014 January – March 2012 (age 55): Not So Uncommon After All? Left Leg Swelling & Erythema Fabry’s Disease Mitochondrial calf � foot: progressive, with pain Encephalomyopathy Lactic Acidosis & Stroke-Like studies Episodes inheritance X-linked recessive maternal inheritance LE Doppler: no DVT systemic angiokeratomata, eye, short stature, hearing loss, renal, cardiac cardiac, renal, diabetes leukopenic with low ANC neurologic painful neuropathy, migraine, stroke <age 40, seizure, muscle biopsy: focal mild endomysial ischemic stroke (small optic atrophy, generalized vessel) myopathy, neuropathy inflammation in 1 fascicle, with histiocytes mechanism α -galactosidase A mtDNA mutation, infarct vs ox (necrotic fibers or vessel walls?) deficiency phos rx: better with prednisone? diagnosis genetic testing can be challenging treatment enzyme replacement supportive Testai FD, Gorelick PB: Inherited metabolic disorders and stroke part I. Arch UCSF /SFGH UCSF /SFGH Neurol 67:19 (2010) Atraumatic Painful, Swollen May 2012 (Moffitt): Problems Leg: Differential Diagnosis Spanning the Neuroaxis non-neurologic general exam: chronic arterial insufficiency left leg, with erythema, tenderness, pitting edema DVT neurological exam cellulitis diabetics bilateral hemispheric dysfunction (old on the right) left foot drop with painful, swollen posterior muscle infarction compartment muscles pyomyositis • inflammatory +/- ischemic (popliteal artery branches) “focal myositis” muscle dysfunction (compartment syndrome?) local inflammatory • denervation-related muscle abnormalities, in tibial myopathy nerve distribution (microvascular?) neurogenic Ahmed S et al: A case of polyarteritis nodosa limited right ulnar (versus lower plexus) sensory loss to the right calf muscles, fascia, and skin: a case report. J Med Case Rep 5:450 (2011) UCSF /SFGH UCSF /SFGH 2
2/14/2014 FLAIR T1 POST-GAD FLAIR T1 POST-GAD “The Full Moffitt” the usual suspects nonsmoker, normal blood glucose arterial dissection drugs infection negative: HIV, BC x 4 (before antibiotics), RPR; CSF VDRL, VZV PCR, AFB, Whipple PCR, CSF culture likely contaminant bad blood prothrombin G20210A heterozygote normal PT/PTT, anticardiolipin IgM slightly up, protein S slightly down broken heart TTE/TEE neg with bubble, TCD of MCAs quiet x 30” busted pipes current MRA/MRV (& prior angio) negative; arteritis of small & medium vessels? focal, not generalized neuromuscular dysfunction, with systemic genetic syndromes disease largely hematologic (lactate slightly elevated) other systemic pancytopenia, hyperferritinemia, hypofibrinogenemia, ACE slightly up normal: IL-2, NK cell function, kidneys, liver, lungs, SPEP, UPEP, disorders ESR, CRP, ANA, ANCA, C3, C4, CH50 UCSF /SFGH UCSF /SFGH CSF Glucose: How Low Is Completing the Workup Low? the usual suspects Hgb A1C, lipid studies arterial dissection drugs infection CSF VZV antibodies, Bartonella serologies hemolysis studies: LDH, indirect bilirubin, haptoglobin, reticulocyte bad blood count, blood smear (bone marrow biopsy) broken heart busted pipes review muscle biopsy, consider ophthalmology evaluation cerebral angiogram or brain biopsy genetic syndromes Fishman RA: CSF in Diseases of Chow E, Troy S: The differential of other systemic revisit history & exam of skin and joints the Nervous System, 2 nd ed hypoglycorrhachia in adult patients. assessment of other vascular beds (GI?) disorders Am J Med Sci:Dec 10 [Epub ahead (1992) monitor liver & renal function of print] (2013) UCSF /SFGH UCSF /SFGH 3
2/14/2014 HD4 HD16 HD4 HD16 Recurrent Cerebral Ischemia with #2: seizure � PHT � fever & rash #13: ctx #18: IV methylprednisolone + doxy Focal Neuromuscular Disease not typical for cardioembolism (& relevant workup negative) Prothrombin mutation could potentially link the patient & his maternal grandmother but seem unlikely to be sole cause for his illness. Kidney, lung, liver (along with heart) spared, with pancytopenia #2 CSF #5 CSF #14 CSF pro 69 pro 90 pro 96 microangiopathic hemolytic syndrome (DIC or glu 38% glu 48% glu 44% PNH) with multiple thromboses vs sdystemic 1 band vasculitis with central & peripheral nervous system involvement? UCSF /SFGH UCSF /SFGH Paroxysmal Nocturnal Systemic Vasculitis 101 Hemoglobinuria rare hematopoetic stem cell Table 2. Sites and Types of Thrombosis. defect: complement-mediated N O . OF S ITE AND T YPE OF T HROMBOSIS P ATIENTS intravascular hemolysis Intraabdominal Hepatic vein 8 multisystem illness: visceral Inferior vena cava 3 Mesenteric vein 4 (especially abdominal) usually Splenic vein 1 Renal vein 1 venous, neurologic involvement Unspecified 1 Other venous sites typically CNS, not PNS Cerebral vein 4 Pulmonary embolism 9 Deep vein 7 dx: hemoglobinuria, markers of Superficial 3 Arterial intravascular hemolysis, flow Myocardial infarction 6 Cerebrovascular accident 2 cytometry, bone marrow biopsy Hillmen P et al: The natural history of paroxysmal tx: eculizamab + anticoagulation? nocturnal hemoglobinuria. New Engl J Med 333:1253 (1995) Jennette JC et al: 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 65:1 (2013) UCSF /SFGH UCSF /SFGH 4
2/14/2014 Polyarteritis Nodosa, Polyarteritis Nodosa Classified Chapel Hill, 2012: rare necrotizing medium (& small) vessel ACR, 1990 vasculitis “Necrotizing arteritis weight loss > 4kg of medium or small livedo reticularis associated with HBV: epidemiology evolving arteries without testicular pain glomerulonephritis or multisystem illness: constitutional, renal, myalgias vasculitis in arterioles, orchitis, neurologic (PNS>CNS), cutaneous, GI, mononeuritis or capillaries, or venules, cardiovascular (pulmonary & hematologic rare) polyneuritis and not associated hypertension dx: biopsy or angio (stenoses, microaneurysms) with antineutrophil creatinine >1.5mg/dL cytoplasmic tx: corticosteroids + cyclosphosphamide for HBV or HCV antibodies (ANCAs).” severe disease pathologic angio histology UCSF /SFGH UCSF /SFGH Thanks collaborators Mark Burish, MD PhD Andy Bollen, MD DVM co-conspirators Vineeta Singh, MD Alisa Gean, MD UCSF /SFGH 5
Recommend
More recommend
