Patient SPClincopathologic Conference (CPC)

9/17/2015

Neurology Resident: Deepak Soneji

Pathologist: Dr. Ronald Hamilton

CC: cognitive decline, personality changes, hallucinations

HPI: 60 yo F with h/o HTN who presented to the ED per recommendation of her outpt neurologist for ~3 months of cognitive decline. Per husband, sx may have started 8 months prior to admission, with episodes of staring when asked a question or simply not responding when family tried to speak to her. Then 3 months prior to admission, pt and family took trip to rural northern PA where pt was noted to be more withdrawn, exhibited evidence of visual + auditory hallucinations, and made nonsensical statements. Sx acutely worsened in the 4 weeks prior to presentation, where pt was essentially sleeping all day. Her gait was noted to be unsteady, though pt did not have any falls. In the last 2 weeks, pt had become completely dependent on her husband to perform all her IADLs (e.g. pt didn’t know what to do when handed a utensil or a piece of toilet paper). Husband noted some urinary incontinence in the last week. Some family members noted “twitching” of L forearm which lasted ~30s-1 minute each.

Further history: pt had been “stressed” in recent months due to her mother being diagnosed with Alzheimer’s approximately 1 year ago; no h/o depression, anxiety, or substance abuse. No new medications or access to other people’s meds. No recent bug bites, rashes, fevers, chills, sweats, weight loss, headaches, CP, SOB, cough, abd pain, n/v/d

Remainder of ROS: per husband, negative

Histories

PMH/PSH: HTNFam Hx: Mother with unknown thyroid d/o, Alzheimer’s dementia (diagnosed in her 80s)Soc Hx: used to work as telephone operator but currently unemployed, former 0.5ppd smoker for ~5 years, rare EtOH, no illicits; lives in Johnstown, PA with husband; no children

Meds: HCTZ 25mg, no OTCs or herbalsAllergies: None

Physical Exam

T 37.4C, BP 125/82, P 83 and regular, RR 16, O2 97% on RA• GENERAL: NAD, somnolent but easily arousable, oriented to person

only• EYES: no scleral injection, no discharge or icterus• ENT: Oral mucosa dry, pharynx without erythema or exudate• NECK: Supple, non-tender, no LAD, no thyromegaly• LUNGS: Lungs clear to auscultation bilaterally, no crackles or

wheezes appreciated• HEART: normal rate, reg rhythm, no m/g/r, no peripheral edema• ABDOMEN: Non-distended, no stigmata of liver disease, +BS, no

organomegaly, NT, no rebound or guarding• SKIN: warm, dry, without rashes, no jaundice• EXTREMITIES: Without tenderness or deformity, no effusions• PSYCH: flat affect, minimally conversant, poor eye contact

Physical Exam• MS: Somnolent but easily arousable, orientation as above. Language

fluent but makes nonsensical statements. Attention poor. Follows commands inconsistently. Naming intact. Cannot spell "WORLD" backward or perform serial 7s, recalls 0/3 words; +glabellar, +BL grasp

• CN: PERRL. EOMI without nystagmus. +blink to threat. Facial sensation intact to LT. Facial muscles full and symmetric. Hearing intact to conversation. SCMs and shoulder shrug normal. Tongue midline.

• MOTOR: Normal bulk, increased tone and spasticity of UE BL. No pronator drift. Trace low amplitude rhythmic movement of L forearm (only observed this 1x during hospital course)

• UE strength 5/5 deltoids, biceps, triceps, hand grip bilaterally• LE strength 5/5 iliopsoas, gluteals, hamstrings, quadriceps, tibialis

anterior, gastrocnemius• REFLEXES: 3+ at biceps, triceps, brachioradialis, patella, and achilles.

No clonus. Flexor plantar response bilaterally. Hoffman negative.• SENSORY: Withdraws all 4 extremities to noxious stimulation• COORDINATION: Did not participate in FTN or HTS• GAIT: limited exam, required assistance x2 to sit up from bed

Differential Diagnosis

• Infectious vs. autoimmune encephalitis• CJD• Sarcoid• CNS lymphoma• NPH• Neurodegenerative d/o such as DLB• CNS vasculitis

Initial Labs

• CBC: WBC 6.7, Hgb 12.9, Plt 138• BMP: Na 159, K 3.6, Cl 123, CO2 25, BUN 30, Cr 0.9• ALT 107, AST 61, AP 62, Tbili 0.7, Albumin 3.4

Imaging

Imaging

Diagnostic Workup

• ESR 72, Anti-TPO 18 (normal<10), TSH WNL but Free T4 low (0.74)• NH3, copper, ceruloplasmin, Pb, serum ACE, ANA, RF, SSA/SSB,

Lupus ab, B12, anti-thyroglobulin ab, Lyme ab, RPR, HIV ab, Hep A/B/C screen, UA, UDS, serum autoimmune encephalitis panel unremarkable

• SPEP showing elevating 2 and gamma globulins but no monoclonal proteins; UPEP neg

• LP: OP 14 cm H20, 15 WBCs (95% lymphs), glucose 67, protein 105• Cytology neg• VZV, HSV, EBV PCRs neg, bacterial and fungal cx NG; West Nile

ab, Crypto ag, India ink stain, AFB cx neg (OSH)• OCBs and elevated IgG index• Autoimmune encephalitis panel neg

• EEG: mod generalized slowing, no focal slowing, no seizures or epileptiform discharges

• CT C/A/P w/ contrast: incidental BL PEs w/o cardiac strain, 1.2cm R thyroid nodule, no lymphadenopathy, no suspicious masses

• LE venous duplex: BL DVTs

Hospital Course• Pt started on IVF to correct free water deficit• Empiric IV solumedrol 500mg q12 for planned 5d course

• no significant improvement after 3d• Heparin gtt - > therapeutic Lovenox for PE/DVT• WBC rose to 17 on day 5, but we attributed this to steroids

• CXR neg, UA pos -> started pt on cefuroxime• By day 5 of admission, transaminases continued to rise

• RUQ u/s w/ dopplers -> no evidence of cirrhosis, no thrombosis• GI consulted

• On the evening of day 5, pt became tachypneic and hypotensive• Condition C called; by the time CCM arrived, pt was apneic and in

pulseless arrest• CPR, urgent intubation, CCM team noted ?coffee ground emesis in

airway• Stat labs revealed Hgb 4.0, Plt 54, Lactate 26, ABG w/ pH of 6.95• pt transferred to NICU where she continued to deteriorate despite

multiple pressors, bicarb drip, and transfusions; family contacted and eventually made pt CMO

• Autopsy report revealed massive spontaneous LLQ retroperitoneal bleed; no GI bleed; no occult malignancy

Predicted Pathology

Gross specimen -edema in amygdala, temporal lobes, thalami

Microscopic Perivascular inflammation

-lymphocitic infiltration

-viral inclusions?