Creutzfeldt-Jakob DiseaseCreutzfeldt-Jakob DiseaseDiagnosis & ManagementDiagnosis & Management

Creutzfeldt-Jakob DiseaseCreutzfeldt-Jakob DiseaseDiagnosis & ManagementDiagnosis & Management

August 13, 2012August 13, 2012

Florence Kranitz, President, CJD FoundationFlorence Kranitz, President, CJD Foundation

Brian Appleby, M.D., Staff, Lou Ruvo Center for Brain HealthBrian Appleby, M.D., Staff, Lou Ruvo Center for Brain Health

Pierluigi Gambetti, M.D., Director, NPDPSC, Case WesternPierluigi Gambetti, M.D., Director, NPDPSC, Case Western

NO RELEVANT FINANCIAL NO RELEVANT FINANCIAL DISCLOSURESDISCLOSURES

NO RELEVANT FINANCIAL NO RELEVANT FINANCIAL DISCLOSURESDISCLOSURES

ObjectivesObjectivesObjectivesObjectives

I.I. Understand key elements of diagnosing Understand key elements of diagnosing CJDCJD

II.II. Demonstrate strategies for managing Demonstrate strategies for managing patients with CJDpatients with CJD

III.III. Demonstrate knowledge regarding the Demonstrate knowledge regarding the resources of the CJD Foundation & resources of the CJD Foundation & NPDPSCNPDPSC

““Pri-on”Pri-on”““Pri-on”Pri-on”

• proproteinaceous teinaceous and and ininfectiousfectious

• --ionion (infectious, e.g. (infectious, e.g. virionvirion))

• No nucleic acidNo nucleic acid

• Non-degradable by typical Non-degradable by typical sterilizationsterilization

Soto C, Trends Biochem Sci 2006

Age at OnsetAge at OnsetAge at OnsetAge at Onset

vCJDgCJD

sCJD

Adapted from: Appleby BS, J Neuropsychiatry Clin Neurosci 2007

EpidemiologyEpidemiologyEpidemiologyEpidemiology

sCJD=1/1,000,000 people per year1/10,000 deaths per year

Survival TimeSurvival TimeSurvival TimeSurvival Time

Adapted from: Appleby BS, Arch Neurol 2009

Definitive DiagnosisDefinitive DiagnosisDefinitive DiagnosisDefinitive Diagnosis

H & E Immunohistochemistry

Probable sCJDProbable sCJDProbable sCJDProbable sCJD

At least two clinical signs:1.Dementia2.Cerebellar or visual symptoms3.Pyramidal or extrapyramidal symptoms4.Akinetic mutism

At least one of the following:1.PSWC on EEG2.14-3-3 in CSF and disease duration < 2 years3.High signal abnormalities in basal ganglia or at least two cortical regions (temporal, parietal, or occipital) on DWI/FLAIR brain MRI

Zerr I, et al. Brain 2009

Electroencephalogram (EEG)Electroencephalogram (EEG)Electroencephalogram (EEG)Electroencephalogram (EEG)

Periodic sharp wave complexes (PSWC’s)

MRI (DWI/FLAIR)MRI (DWI/FLAIR)MRI (DWI/FLAIR)MRI (DWI/FLAIR)

Acquired Prion DiseaseAcquired Prion DiseaseAcquired Prion DiseaseAcquired Prion Disease

Iatrogenic CJDIatrogenic CJDIatrogenic CJDIatrogenic CJD

Adapted from: Brown P, Neurology 2006

227 total cases

Variant CJDVariant CJDVariant CJDVariant CJD

http://www.cjd.ed.ac.uk/vcjdworld.htm

vCJD CharacteristicsvCJD CharacteristicsvCJD CharacteristicsvCJD Characteristics

Will RG, Lancet 1996

Pulvinar SignPulvinar SignPulvinar SignPulvinar Sign

Zeidler M, Lancet 2000

Creutzfeldt-Jakob Disease in the UK, 18th Annual Report, 2009

MM

MV

BSE1980’s

Care and ManagementCare and ManagementCare and ManagementCare and Management

Education

Communication Implementation

Intervals of CareIntervals of CareIntervals of CareIntervals of Care

I.I. Pre-clinical/Presentation PhasePre-clinical/Presentation Phase

II.II. Diagnostic PhaseDiagnostic Phase

III.III. Caring PhaseCaring Phase

Preclinical/Presentation PhasePreclinical/Presentation PhasePreclinical/Presentation PhasePreclinical/Presentation Phase• Initial interactions with primary Initial interactions with primary

medical doctormedical doctor

• At risk individuals should identify At risk individuals should identify “physician champions”“physician champions”

Kranitz FJ & Simpson DM. CNS Neurol Disord Drug Targets 2009

Diagnosis PhaseDiagnosis PhaseDiagnosis PhaseDiagnosis Phase

• Discuss process with patient and familyDiscuss process with patient and family

• Don’t forget about present needsDon’t forget about present needs

• Refer to organizations and clinicians Refer to organizations and clinicians familiar with the illnessfamiliar with the illness

• Discharge planning (Discharge planning (beforebefore discharge) discharge)

• Must establish a “key worker”Must establish a “key worker”

Douglas M, Patients with nvCJD and their families 1999

Caring PhaseCaring PhaseCaring PhaseCaring Phase

• Frequent reassessment/symptomatic Frequent reassessment/symptomatic treatmenttreatment

• Limit visits to few individuals of short Limit visits to few individuals of short durationsdurations

• Assess caregiver requirementsAssess caregiver requirements

• Hospice/Respite careHospice/Respite care

Symptomatic TreatmentSymptomatic TreatmentSymptomatic TreatmentSymptomatic TreatmentSymptom Suggested Treatment

Psychosis/Agitation Low potency neuroleptics (e.g., quetiapine)

Myoclonus/Hyperstartle Long acting benzodiazepines (e.g., diazepam)Anticonvulsants (e.g., valproic acid)

Seizures Anticonvulsants

Dystonia/Contractures Passive movement Long acting benzodiazepines, Botulinum toxin injections

Constipation Bowel regimen (e.g., dulcolax)

Dysphagia/Rumination Thickener, cueing

Behavioral/Environmental changes first

Start low and go slow

Re-evaluate frequently

AfterwardsAfterwardsAfterwardsAfterwards

• Arrange requested post-mortems prior to Arrange requested post-mortems prior to death death (www.cjdsurveillance.com)(www.cjdsurveillance.com)

• Frequent check-ins with family/caregiversFrequent check-ins with family/caregivers

• If postmortem performed, communicate If postmortem performed, communicate results (in person if possible)results (in person if possible)

• Encourage contact as neededEncourage contact as needed

SummarySummarySummarySummary

• Diagnosing CJD can be difficult and Diagnosing CJD can be difficult and frustratingfrustrating

• Getting a proper diagnosis and managing Getting a proper diagnosis and managing the care of a patient with CJD is stressfulthe care of a patient with CJD is stressful

• Care and management of patients with Care and management of patients with prion disease is supportive and entails prion disease is supportive and entails several disease specific interventionsseveral disease specific interventions