Case Study: Diagnosis and Progression of Creutzfeldt-Jakob Disease in a Geriatric Patient, Slides of Geriatrics

Download Case Study: Diagnosis and Progression of Creutzfeldt-Jakob Disease in a Geriatric Patient and more Slides Geriatrics in PDF only on Docsity! Geriatrics Rounds Docsity.com • 71 yr RHD male with past Hx of MI, HTN, dyslipidemia, gout, OA, referred to Neurology for incoordination Docsity.com  22 Feb 2011: back to ER  Progressive symptoms:  Lt hand incordination  Gait unsteadiness  Lt facial weakness  Slurred speech  Minor dysphagia of solids  Weight loss 15 lbs over 6 weeks  Chronic cough  Hematuria (occasionally)  Blood on toilet paper since ASA ( x 3 weeks) Docsity.com Vitals normal CVS/Respi/Abdo exam normal Alert & oriented MMI 25/30 (-3 delayed recall, -1 comprehension, -1 Abstract CN exam: EOM, PERLA, VFF Bilateral horizontal hypomatric saccades to lat gaze Lt facial Droop Dysarthric speech Rest of the exam normal Sensory Exam Lt Rt Light Touch Normal Normal Pinprick Normal Normal Vibration ? Lt great toes Ankle normal Normal Motor Exam Normal tone, Bulk, Lt Rt Deltoid 5 5 Biceps 5 5 Triceps 5 5 Wrist ext 5 5 Wrist Flexor 5 5 Lumbricals 5 5 Hip flexors 5 5 Hip extensors 5 5 Quads 5 5 Hamstrings 5 5 Ankle dorsiflex 5 5 Ankle plantflex 5 5 Toe Ext 5 5 Toe Flex 5 5 Docsity.com DTR Lt Rt Biceps 3+ 3+ Triceps 3+ 3+ Brachioradialis 3+ 3+ Knee 3+ 3+ Ankle 3+ 3+ Plantar’s Equivocal Cerebellar Exam Marked dysfunction Lt UE & LE Marked dysdiadochokinesia Lt UE Marked dysrhythmogenesis Lt LE Intention tremor Lt UE Noted Lt UE apraxia (ideomotor/ideational) Gait: Markedly unsteady , leaning to left Docsity.com Docsity.com Course in Hospital: 23 Feb 2011 :MOCA 30/30 24 Feb 2011:Worsening of cerebellar findings bilaterally EEG done Docsity.com rte Na La ah Be Ane Ng Suet rove cmt Me ge at Np ee ete semper etc yA nesta yangent tnd ee tte Apron ryrcadtncannea nr capntiic celta het yoo tabcnrve hr rt ie eR ote YONA Pater ior nano nna ayo sees ayer ntyotn O rowan toe ge wee hay PAPAL ID Arent oP op aii tuple tare atone enna feswee we yeh gander nye pti peneent eettraccosi lt sate Docsity.com PET Docsity.com Pee ed pete feat Dee ees re ry cr * Est a he i r “4 ' “ e 2 » ad Fe Fe Pe DR ol 3 Fa Pr r Ps od _ by % i * z Fy = re -_ PI  a eo <0 Dee Uy a a z Es ca a fi a rs eS a ee 24 2 Docsity.cobm ss 0 co Prion Disease  Prion: small infectious pathogen containing protein but lacking nucleic acid  Non-pathological membrane bound protein in neuronal and non- neuronal cells  Conversion to active, accumulating isomer  Intracellular accumulation of prions = apoptosis, cell death, degenerative neurologic disease  CJD (and variants), kuru, Gerstmann-Straüssler-Scheinker syndrome, familial fatal insomnia Docsity.com Table 1. Classification of human prion diseases. Sporadic Acquired From humans From bovines Genetic Sporadic Creutzfeldt—Jakob disease Sporadic fatal insomnia Protease-sensitive prionopathy Kuru Iatrogenic Creutzfeldt—Jakob disease Variant Creutzfeldt—Jakob disease Familial Creutzfeldt—Jakob disease Gerstmann-Straussler-Scheinker syndrome and variants Fatal familial insomnia Table 2. Prion protein gene polymorphisms in the normal popu- lation and in prion diseases. Prion protein gene codon 129 polymorphisms (%) MM 39 71 MV 50 13 ‘methionine; V, valine; CJD, Creutzfeldt—Jakob disease. Haemophilia (2010), 16 (Suppl. 5,, 775-166 — Journal of Geriatric Psychiatry and Neurology 23(4) 277-298 a single exon on the short arm of chromosome 20 encodes the 253 amino acid PrP. The highest levels of expression are within neurons, Docsity.com Table 2 Distribution of infectivity in the human body” Infectivity Category Tissues, Secretions, and High Infectivity Low Infectivity No Detectable Infectivity Brain Spinal cord Eye CSF Kidney Liver Lung Lymph nodes/spleen Placenta Adipose tissue Adrenal gland Gingival tissue Heart muscle Intestine Peripheral nerve Prostate Skeletal muscle Testis Thyroid gland Blood® WHO/CDS/CSR/APH/2000.3 Kuru • restricted to the Okapa area of the highlands of Papua New Guinea • 36000 population : 2700 documented cases • research by Dr Carleton Gajdusek and colleagues • transmission through endocannibalism • incubation period ranges from 4.5 - >40 yrs (average 12 yrs) • Presents as pure cerebellar syndrome, dementia absent initially • Course of illness: 6-36 months British Medical Bulletin 2003;66 Docsity.com Sporadic CJD  85% of all CJD cases  Hypothesis for occurrence of sCJD:  PrPC  PrPSc spontaneously  age-related somatic mutation of the PrP gene. Docsity.com Table 3. Variant Creutzfeldt-Jakob disease (CJD) cases world- wide (February 2010). No. secondary No. primary cases: transmission Country cases by blood transfusion UK 169 France Spain Ireland USA Netherlands Portugal Italy Canada Japan Saudi Arabia i) a RSPR RPh HM WwW BN Cy Pa Case definition for vCJD (adapted from the revision of the WHO surveillance case definition for variant CJD, 2001) Class I A, Progressive neuropsychiatric disorder B, Duration of illness longer than 6 months C, Routine investigations not suggestive of alternative diagnosis D, No history of iatrogenic exposure E, No history of familial form of transmissible spongiform encephalopathy Class IT A, Early psychiatric symptoms (i.e. depression, anxiety, apathy, with- drawal, delusions) B, Persistent painful sensory symptoms (i.e. including frank pain and/or _ : The possible diagnoses are dysesthesia) Definite, Class Ia and neuropathologic confirmation of variant CJD (i.e. C, Ataxia spongiform change and extensive prion protein deposition with florid D, Myoclonus or chorea or dystonia plaques throughout the cerebrum and cerebellum) E, Dementia Probable, Class I and 4 of 5 of class I and classes [a and IIb or class I and class IVa Class TIT . : . . . Possible, Class I and 4 of 5 of class II and class Ma A, EEG without typical appearance of sporadic CJD (i.e. generalizve triphasic periodic complexes at approximately one per second) or no EEG B, Brain MRI showing bilateral symmetrical pulvinar high signal intensity (relative to the signal intensity of the other deep gray matter nuclei and cortical gray matter; modification of the case definition of the characteristic MRI features [IIb] to brain MRI shows bilateral symmetrical pulvinar hyperintensity relative to the signal intensity of the anterior putamen is recommended to improve the accuracy of the pulvinar sign in variant CJD) Class IV A, Positive findings on tonsil biopsy (biopsy not routinely recommended a commended in cases with EEG appearance typical of sporadic ay be helpful in suspected cases in which the clinical features are with variant CJD without MRI findings of bilateral pulvinar hi nal intensity) Pulvinar Sign in vCJD  hyperintensity of the pulvinar relative to the anterior putamen ( 100% on FLAIR in VCJD) Docsity.com Fatal Insomnia • 2 types: a) Sporadic: sFI b) Familial FI • c/f: Intractable insomnia (early) dysautonomia, ataxiapyramidal/extrapyramidal  cognition impaired(late) • EEG: Slowing • PET/SPECT: Decreased metab thalamus( early) • Onset: 25-61 yr • Duration of illness: 1-2 yrs • Neuropathogy: neuronal loss with astrogliosis within thalamus and inf olives PrPSc detectable in thalamu and temporal lobes Docsity.com EEG findings in CJD Early Late Very late!!! SCJD FIRDA/diffuse slowing PSWC (PPV 95%) Areactive coma - Alpha coma Iatrogenic CJD Regional FIRDA/slowing (inoculation site) PSWC Genetic CJD Slowing PSWC(10%) vCJD Normal or Slowing No PSWC Clinical Neurophysiology 117 (2006) 935–951 PSWC’s in CJD sensitivity, specificity, and positive and negative predictive values were 64%, 91%, 95%, and 49%, respectively Docsity.com Fig. 4. EEG recording of a 73-year-old man with histologically proven sCJD (14-3-3 positive; methionine homozygote at codon 129, no mutation) showing FIRDA-like activity 23 days before death. PSWC were documented 30-16 days before death. Tablei UCSF 2005 and 2010 proposal of MRI criteria for CJD diagnosis Diagnosis UCSF 2005 criteria? UCSF 2011 proposed modifications! additions MRI DWI alo DWI > FLAIR definitely cD @ Subcor Supportive for cortical invol ivement: © Asymmetric involv if ricdli Sparing of the precentral gyrus ADC cortical ribboning hypointensity Cortex only [>3 gyri Diffusion-weighted MRI hyperintensity . Unilateral striatum or corte: Unilateral striatum or cart 3 supportive fa supportive for cortex labo patterns differentiate CJD from other rapid dementias Bilateral striatum or Bilateral striaturn or posteromesial thalamus; posteromesial thalamus sha supportive for subcortical | FLAIR > DW! hyperintensities ee MRI probably not CID DWI hyperintensities dua to artifact (signal distertion) No change from prior criteria Ne change from prier criteria hy prolonged courses of sCJD[—>1 year) brain MRI might show significant with lose of DWI hyperintensity, particularly in areas previously with Docsity.com Figure 4 Frequency of gray matter fluid-attenuated inversion recovery (FLAIR) or diffusion-weightad imaging (DWI) hyperintensities in different disease cohorts 100 5 20 -| 10- o- sCJD fcJD oss npRPD ect with nonprion causes of rapidly progressive dementia (npRPD) had any neocortical hyperintensity, but about 25% had predominantly limbic involvement. Almost half of Gerstmann-Straussler-Scheinker (GSS) cases were believed to have OWI or FLAIR limbic hyperintensity. Predominant limbic hyperintensity is therefore not suggestive of spc ic Creutzfeldt-Jakob disease [sCJD), but possibly of GSS or npRPD. Familial CJD (fCJD) has an overlapping pattern of MRI abnormality with sCJD. Docsity.com Using FLAIR and DWI MRI, MRI sensitivity and specificity for sCJD were 98% and 93%, higher than any other diagnostic test. 4 distinguishing MRI features : •In sCJD, hyperintensity on DWI > FLAIR, •In npRPD, hyperintensity on FLAIR > DWI. •In subjects with sCJD with subcortical DWI hyperintensity assoc with corresponding hypointense ADC (restricted diffusion) which was not seen in npRPD cases •Isolated limbic involvement was not found in sCJD, but often seen in npRPD. •sCJD has characteristic DWI patterns of gray matter involvement. Docsity.com