Geriatric Pearls: Cases from the Fellows Clinic: Malaise, Myoclonus, and Mental Status Changes

Transcription

1 Geriatric Pearls: Cases from the Fellows Clinic: Malaise, Myoclonus, and Mental Status Changes Katie Lowe, M.D. Geriatric Update November 17, MFMER slide-1

2 Case 76 year-old community dwelling and cognitively intact male admitted to the inpatient geriatric service with Generalized malaise Loss of appetite Subjective fevers Lightheadedness Loose stools 2016 MFMER slide-2

3 Case Past medical history Pertinent past medical history: o CLL on current treatment with Ibrutinib o DM2 on oral medications o CKD stage 3 o Atrial fibrillation on Rivaroxaban o Sick sinus syndrome s/p pacemaker placement o Hypertension o Hyperlipidemia o Hypothyroidism o Gout o OSA 2016 MFMER slide-3

4 Case Social history Retired Catholic priest and psychologist Still saying mass on Sundays, including the week before admission 50 pack year smoking history (quit in 1980) One alcoholic drink per night 2016 MFMER slide-4

5 Case Physical Exam General: Well-appearing male in no acute distress. Awake, alert, oriented, pleasant, cooperative, nontoxic. Lymph: No cervical, supraclavicular, or submandibular lymphadenopathy noted. Heart: Irregular rhythm. Normal S1 and S2. Lungs: Clear to auscultation Abdomen: Prominent hyperactive bowel sounds throughout. Abdomen is otherwise soft, nontender, nondistended. No appreciable masses or organomegaly. Neuro: Alert, oriented to person, place, and date. Cranial nerves II through XII were grossly intact. Upper and lower extremity strength is grossly intact and symmetric. No focal deficits MFMER slide-5

6 Case Initial Workup WBC 22 (recent baseline 20) with neutrophilia and lymphocytosis, Hgb 13.6, platelets 186, Na 130, K 4.4, Cr 2.6 (baseline 1.6), lactate 2.2, AST 68, ALT 86, ALP 54, bilirubin 0.8 Chest x-ray, abdominal x-ray, urinalysis, and GI stool pathogen panel unremarkable Blood cultures negative 2016 MFMER slide-6

7 Case Clinical Course Hospital Day 2: Develops high fevers Hospital Day 3: Fevers continue CT chest negative for focal findings; decrease of lymphadenopathy that was noted in prior imaging More confused with fluctuating mental status Hospital Day 4: Development of facial tremors, upper extremity myoclonus, and dysarthric speech. Mental status deteriorates even further CT head obtained and negative for acute intracranial findings ID and Neurology consult obtained Hospital Day 5-7: Fevers ongoing. Unable to follow any commands. Unable to sit up in bed or ambulate. Requiring 1:1 supervision 2016 MFMER slide-7

8 Case Infectious Disease Workup Serum testing EBV PCR CMV PCR Tick borne panel (Anaplasma, Ehrlichia, Lyme disease) Fungal serology (Blastomycoses anbtibody, Cryptococcus antigen, and Histoplasmosis antigen HIV Syphilis St. Louis encephalitis IgG and IgM West Nile Virus IgG and IgM Heavy metal screen QuantiFERON NEGATIVE 2016 MFMER slide-8

9 Case Infectious Disease workup, continued Lumbar puncture Cell count 33 with 68% lymphocytes Glucose 90 Protein 113 Gram stain negative Testing Arbovirus antibody panel Herpes simplex PCR West Nile antibody West Nile PCR VZV PCR CMV PCR EBV PCR Lyme Disease PCR JC virus PCR Tropheryma whipplei PCR Enterovirus PCR Adenovirus PCR HHV-6 PCR Malignant cells VDRL 0.2 AFB stain Fungal smear Cryptococcus antigen. Bacterial culture Powassan virus IgM 2016 MFMER slide-9

10 Case, continued WNV PCR in CSF positive!!!! WNV encephalitis 2016 MFMER slide-10

11 West Nile Virus (WNV) An arbovirus transmitted via mosquito bites Seasonal epidemic in US since % asymptomatic 20% acute febrile illness <1% develop neuroinvasive disease Meningitis Encephalitis Acute flaccid paralysis 2016 MFMER slide-11

12 WNV Infection In the US and MN In the United States, 1352 cases of West Nile virus disease have been reported to CDC this year (as of 10/18/16) 692 (51%) were classified as neuroinvasive In Minnesota, 41 total cases reported this year 17 (41%) classified as neuroinvasive 2016 MFMER slide-12

13 WNV Encephalitis Clinical presentation Fever Encephalopathy Weakness Tremors Myoclonus (typically upper extremities)* Parkinsonian features (rigidity, postural instability, bradykinesia) Headache Cranial neuropathies 2016 MFMER slide-13

14 WNV Encephalitis Risk Factors Elderly Immunocompromised Malignancy Male gender Diabetes Cardiovascular disease Kidney disease Alcohol 2016 MFMER slide-14

15 WNV Encephalitis Diagnosis: What to look for if suspect WNV Serum WNV IgM antibody (MAC-ELISA) and WNV PCR For neuroinvasive disease, obtain CSF and send for WNV IgM antibody and WNV PCR CSF pleocytosis and elevated protein Plaque reduction neutralization test (PRNT): Most specific antibody test and only available through CDC and some state departments. Done to rule out cross-reactions 2016 MFMER slide-15

16 WNV Encephalitis Diagnosis: CDC diagnostic criteria Confirmed case=clinically compatible disease and Isolation of virus from, or demonstration of specific viral antigen or nucleic acid in, tissue, blood, CSF, or other body fluid, OR Fourfold or greater change in virus-specific quantitative antibody titers (PRNT) in paired sera, OR Virus-specific IgM antibodies in serum with confirmatory virus-specific neutralizing antibodies (PRNT) in the same or a later specimen, OR Virus-specific IgM antibodies in the CSF and negative IgM in the CSF for other arboviruses endemic to the region where the exposure occurred Probable case=clinically compatible disease and Virus-specific IgM antibodies are present in CSF or serum but no other testing (i.e., PRNT, PCR) is performed For routine clinical purposes, a diagnosis of probable disease is sufficient for the vast majority of patients 2016 MFMER slide-16

17 WNV Encephalitis Diagnosis: Other supportive evidence EEG with generalized slowing with anterior or temporal prominence Elevated WBC, hyponatremia, and elevated liver enzymes Head imaging is often normal CT nearly always normal MRI can be abnormal (20-70% of cases) with T2-weighted hyperintensities in basal ganglia, thalami, caudate nuclei, brainstem, and cerebellum. If abnormalities are seen, can predict outcome 2016 MFMER slide-17

18 WNV Encephalitis Treatment SUPPORTIVE Several therapeutic agents have been tried (ribavirin, interferon, intravenous immunoglobulin) without promising results Prevention relies on protection from mosquitoes, no vaccines currently available 2016 MFMER slide-18

19 WNV Infection Prognosis Sequelae for many months to years after WNV infection. Physical: muscle weakness, fatigue, myalgia Functional: Trouble performing ADLs Cognitive: Memory loss, depression, difficulty concentrating Disposition: In one series of 221 patients with WNV encephalitis 18% of patients died 46% discharged to rehabilitation or long-term care 15% returned home with assistance 20% returned home independently In another series of 15 patients with WNV neuroinvasive disease at 8 months 73% returned to independence 20% returned home but required assistance 7% remained in rehabilitation In a review article that summarized 14 studies, 45% did not achieve full recovery (did not return home to independence) 2016 MFMER slide-19

20 WNV Infection Prognosis Patients admitted to acute rehabilitation after WNV encephalitis with neuropsychological testing had persistent cognitive deficits and neuropsychiatric symptoms resembling frontal subcortical dementias Language/communication deficits Memory impairments Executive dysfunction Defects in concentration Emotional dysregulation Apathy and agitation 2016 MFMER slide-20

21 Case Resolution Hospitalized for 2 weeks MRI: Suggestion of patchy bilateral T2/FLAIR hyperintensities in the bilateral thalami, basal ganglia, and possibly central brainstem, although significantly degraded by motion artifact Fevers, facial tremor, and myoclonus all resolved Encephalopathy slowly improving but not back to baseline Discharged to inpatient rehabilitation 2016 MFMER slide-21

22 References Arcienagas DB, Anderson CA. Viral encephalitis: neuropsychiatric and neurobehavioral aspects. Curr Psychiatry Rep 2004; 6: Bode AV, Sejvar JJ, Pape WJ, et al. West Nile Virus Disease: A Descriptive Study of 228 Patients Hospitalized in a 4-County Region of Colorado in Clin Infect Dis 2006; 42: Centers for Disease Control and Prevention (CDC). West Nile Virus. Accessed September 26, 2016 Davis LE, DeBiasi R, Goade DE, et al. West Nile virus neuroinvasive disease. Ann Neurol 2006; 60: Hart J, Tillman G, Kraut MA, et al. West Nile neuroinvasive disease: neurological manifestations and prospective longitudinal outcomes. BMC Infectious Diseases 2014; 14:248 Murray KO, Garcia MN, Rahbar MH, et al. Survival analysis, long-term outcomes, and percentage of recovery up to 8 year post-infection among the Houston West Nile virus cohort. PLoS One 2014: 9(7). Patel H, Sander B, Nelder MP. Long-term sequelae of West Nile virus-related illness: a systematic review. Lancet Infect Dis 2015; 15: Petersen LR, Hirsch MS, Mitty, J. Clinical Manifestations and diagnosis of West Nile virus infection. UpToDate Waltham, Mass.: UpToDate; Accessed September 21, MFMER slide-22

23 Questions & Discussion 2016 MFMER slide-23