2/18/2011. Neurological Exam Continued
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1 Recent Advances in Neurology Clinico-pathologic Conference Yana Kriseman MD UCSF Department of Neurology February 18 th, 2011 History of Present Illness 67 year-old man with history of episodic headaches October 2009: Headaches Constant, left parietal Visual Changes a) Right peripheral scotomas b) Scintillations c) Bilateral blurring Cognitive Changes a) Short term memory loss b) Word finding difficulties November 2009: Gait Instability a) Stuck to floor followed by falls b) Shuffling c) Started using walker Initial Imaging MRI brain Sulcal FLAIR hyperintensity and leptomeningeal enhancement over the left parietal, temporal, and occipital regions; mild ventriculomegaly December 2009: Scotomas and scintillations resolved Mild improvement in cognitive deficits BUT Persistent headaches New olfactory hallucinations of stereotyped foul odor Worsening gait: shuffling and bradykinesia Transiently improved after lumbar puncture MRI brain repeated: Progression of left sided leptomeningeal disease; three new foci of reduced diffusion in the left parietal, temporal, and occipital lobes 1
2 Review of Systems: Denied diplopia, painful eye movements, dysarthria, focal weakness or sensory loss, fever/chills/ sweats, weight loss, urinary/bowel changes. Past Medical History: Diabetes Hyperlipidemia Hypertension Head trauma 20 years ago with subsequent headaches GERD Carpal Tunnel Syndrome Medications: Aspirin, Metformin, Glipizide, Lisinopril, Simvastatin, Omeprazole, Omega fish oils, Vicodin. Social History Retired Air Force veteran and wine maker Married 37 pack years of tobacco; quit 5 months prior Rare EtOH; No drug use Family History No neurological diseases Physical Exam General Exam: Vitals: BP 130/75 HR 68 RR 12 HEENT: Neck supple Cardiovascular: RRR; no murmurs Respiratory: Clear to auscultation Skin: No rashes Neurological Exam Mental Status: AAOX3; Naming/repetition intact; Digit span: 7 forwards and 5 backwards; 3 D words and 13 animals in 1 minute. No neglect. MMSE 30/30 Cranial Nerves: PERRL; visual fields full; visual acuity 20/20 bilaterally; optic discs sharp bilaterally; extraoccular movements intact without nystagmus; facial sensation and strength symmetrical and intact; hearing intact to finger rub bilaterally; tongue and palate midline; no dysarthria; shoulder shrug symmetric. 2
3 Neurological Exam Continued Motor: Mild spasticity in bilateral upper extremities; FFM/FFT intact; Right sided finger flexion on pronator drift; no tremor; full power on confrontation throughout Reflexes: Present and symmetric throughout except ankle jerks absent bilaterally; plantar responses flexor Sensory: Intact to all modalities; Negative Romberg Coordination: No dysmetria. No rebound. Mild intention tremor bilaterally Gait: Shuffling with mildly wide based gait; Could not tandem. Two steps back on pull test Differential Diagnosis Dr. S. Andy Josephson Initial Imaging (November) 3
4 December Work-Up CSF Profiles November 2, 2009: 3 WBC (100% lymphocytes); 25 RBC; Glucose 74; Protein 161; IgG index 0.88 Normal Studies November 10, 2009: 2 WBC (100% lymphocytes); 0 RBC; Glucose 94; Protein 95 4
5 Metabolic Serum: Chemistry panel, liver function panel, TSH (0.73), B12 (507), Methylmalonic acid (0.13) Vascular Imaging: CT/CTA Head and Neck No vascular abnormalities Infectious Serum: HIV 1/2, RPR, Treponemal antibody, Hepatitis B/C, Lyme antibodies, Coccidiodes antibodies, Histoplasma antibodies, Crytococcal antigen CSF: HSV 1/2, CMV, and VZV PCRs; West Nile antibodies, Coccidiodes antibodies and complement fixation; Cryptococcal antigen, VDRL, AFB and fungal cultures Inflammatory Serum: ESR (5), ACE (8), lupus anticoagulant, anticardiolipin antibodies, ANA, antimyeloperoxidase, anti-proteinase 3 antibodies, C3, C4, dsdna, rheumatoid factor, Smith antibody, RNP antibody, SSA, SSB PPD: neg 5
6 Neoplastic Serum: LDH (123), SPEP, Serum IFE, UPEP CSF: Cytology x 3; Flow cytometry x 2; ATIII Imaging: CT chest/abdomen/pelvis: 3.2 x 2.2cm calcified, RUL mass most consistent with hamartoma (unchanged from CT chest in 2001 and 2003; No hypermetabolism on PET). Otherwise unremarakable. Further Diagnostic Thoughts Dr. S Andy Josephson Brain Biopsy Dr. Andrew Bollen 6
7 Neuropathologic Findings Andrew Bollen Professor of Neuropathology 7
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13 Primary Angiitis of the CNS Affects small and medium vessels Involves brain and spinal cord Men affected 2x > women Median age 50 1% of all vasculitidies Clinical Presentation Headache (63%) Encephalopathy/Cognitive changes (50%) Seizures (16%) Ischemic stroke (40%) or TIA (28%) or ICH (8%) Hemiparesis (44%) Aphasia (28%) Visual field defects (21%) Ataxia (19%) Diplopia (16%) Dysarthria (15%) Unilateral numbness (13%) Paraparesis or quadraparesis (9%) Systemic symptoms < 9% * Mayo Cohort 13
14 Diagnosis Laboratory Work-up Systemic labs rarely abnormal Elevated ESR <25%; normal ANA, CRP CSF abnormal in 80-90% WBCs (lymphocytic): 5 (0-535); rarely > 250 Protein: Mean 72mg/dl; 73% > 45mg/dl Oligoclonnal bands (20%) when PACNS is the potential diagnosis, the correct diagnosis is usually something else Differential Diagnosis Labs Birnbaum, J. et al. Arch Neurol 2009;66: Infectious: Viral: HIV, HSV, CMV, VZV, Hepatitis B and C Bacterial: Lyme serology, bartonella serology, RPR, PPD, AFB cultures, CSF VDRL Fungal/Parasite: Aspergillus (serum galactomannan), coccidomycosis serology, histoplasma urine antigen, cysticercosis serologies, Inflammatory/Collagen Vascular disorders: ESR, CRP, ANA, dsdna, anti-smith, anti-rnp, C -ANCA, P-ANCA, antiphosphlipid antibodies, SSA, SSB, rheumatoid factor, cryoglobulins, complement, ACE, anti-scl Malignancy: LDH, CSF cytology and flow cytometry Embolic: Blood cultures 14
15 Imaging MRI abnormal in % Infarcts (50%) Mass lesions (15%) ICH (10%) GAD enhancement (1/3) Leptomeningeal enhancement (10-15%) 15%) Diffuse white matter changes MRA 60% with vasculitic changes Beading of vessels Angiography Sensitivity 20 90% Specificity 30% Biopsy Granulomatous vasculitis most common (58%) Lymphocytic vasculitis (28%) and fibrinoid necrosis (14%) can also be seen Sensitivity <50% 7/15 patients with post mortem diagnosis of PACNS had normal biopsies Sensitivity improves with if biopsy samples leptomeninges (58% vs 40%) Still Useful 61 patients went to biopsy for suspected PACNS 36% diagnosed with PACNS 39% with alternate diagnosis 25% biopsy not useful Treatment Steroids Initial course of high dose prednisone (1mg/kg/day) vs solumderol 3-6 week course followed by slow taper Cyclophosphamide 2mg/kg/day 3-6 months course Followed by mycophenolate mofetil, azathioprine, or methotrexate PPX: Bisphosphonates, calcium, vitamin D, Bactrim Serial MRIs 15
16 Outcome 81% good outcome with treatment 25% relapsed Increased mortality with: infarcts, cognitive impairment, large vessel involvement Better prognosis with: Leptomeningeal enhancement or enhancing lesions Back to Our Patient Treatment Initially treated with Cytoxan and prednisone. Tapered off prednisone over 2 months Switched from Cytoxan to Cellcept after 6 months Outcome Headaches resolved Visual and olfactory phenomenon resolved Cognition back to normal Gait almost back to normal no shuffling; no assistive devices Salvarani C, et al. Ann Neurol Nov;62(5): MRI April 2010 Thank You S. Andy Josephson, MD Andrew Bollen, MD John Engstrom, MD Nancy Edwards, MD 16
17 References Alrawi A, et al. Brain biopsy in primary angiitis of the central nervous system. Neurology Sep 11;53(4): Birnbaum J, et al. Primary angiitis of the central nervous system. Arch Neurol Jun;66(6): Miller D, et al. Biopsy findings in primary angiitis of the central nervous system. Am J Surg Pathol Jan;33(1): Hajj-Ali R, et a. Primary angiitis of the central nervous system. Curr Treat Options Neurol May;9(3): Rossi C, et al. The clinical spectrum of the neurological involvement in vasculitides. J Neurol Sci Oct 15;285(1-2): Salvarani C et al. Primary CNS vasculitis with spinal cord involvement. Neurology Jun 10;70(24 Pt 2): Salvarani C, et al Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol Nov;62(5): Salvarani C, et al. Primary central nervous system vasculitis with prominent leptomeningeal enhancement: a subset with a benign outcome. Arthritis Rheum Feb;58(2): Singh S, et al. Primary angiitis of the central nervous system: MRI features and clinical presentation. Australas Radiol Jun;47(2):
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