What is the management approach for prion disease?

Management of Prion Disease

Prion disease management is entirely supportive and symptomatic, as no disease-modifying treatments currently exist; the focus must be on quality of life, symptom control, multidisciplinary psychosocial support, and genetic counseling for affected families. 1, 2

Core Management Principles

No Disease-Modifying Therapy Available

• There are currently no treatments that alter disease progression or improve survival in prion disease 1, 2
• All management is directed toward symptomatic relief and optimizing quality of life 2
• The disease is invariably fatal with rapid progression, typically resulting in death within 1-3 years depending on the genetic variant 1

Multidisciplinary Team Approach

A coordinated team including a neurologist, genetic counselor, and social worker should manage all prion disease cases together. 1

• This team structure addresses the complex medical, genetic, and psychosocial needs of patients and families 1
• The CJD Foundation provides patient/family helplines, educational materials, and connects families with support resources 1

Symptomatic Management

Neuropsychiatric Symptoms

The most problematic symptoms for caregivers include mood/behavioral changes, psychotic features, and agitation 3, 4

Pharmacological management should follow this hierarchy: 4

• First-line: Non-pharmacological interventions for all behavioral and psychiatric symptoms 4
• Antipsychotics: Reserved for severe psychosis or agitation only, used judiciously 4
• Benzodiazepines: Particularly effective in late-stage disease for agitation and myoclonus 5, 4
• Antidepressants: For mood disorders when present 4

Important caveat: Many neuropsychiatric symptoms spontaneously improve or resolve as global neurological disability progresses, so avoid overmedication 4

Motor Symptoms

• Benzodiazepines, antipsychotics, and anticonvulsant medications show some efficacy for motor symptoms including myoclonus and coordination problems 5
• Mobility and coordination issues are among the six most problematic symptom domains reported by caregivers 3

Other Symptomatic Domains Requiring Support

The following require active management planning 3:

• Personal care and continence: Anticipate progressive needs
• Eating and swallowing: Monitor for aspiration risk
• Communication: Implement alternative strategies as speech deteriorates
• Cognition and memory: Environmental modifications and caregiver education

Genetic Counseling and Testing

Diagnostic Genetic Counseling

All families with a prion disease case should receive genetic counseling, as 10-15% of cases are genetic. 1

Key counseling points include 1:

• Autosomal dominant inheritance pattern with 50% transmission risk if genetic
• Significant inter- and intra-familial phenotypic variability in presentation, age of onset, and disease duration
• Options for DNA banking or postmortem testing if families are overwhelmed during acute illness
• Reassurance that person-to-person transmission occurs only through extraordinary circumstances (brain-to-brain contact in medical procedures), not through household contact, caregiving, or intimate contact 1

Predictive Testing Protocol

For at-risk individuals considering predictive testing, follow a modified Huntington disease protocol with flexibility based on individual risk factors. 1

High-risk individuals requiring slower, more cautious approach: 1

• Prior history of significant anxiety or depression
• Lack of future planning
• Poor support system
• Poor family communication

Testing session structure: 1

• Strongly advise bringing at least one support person to both counseling and result sessions 1
• Discuss penetrance, phenotypic variation, and age of onset specific to the family variant 1
• Address GINA protections, life/long-term care insurance implications 1
• Explore reproductive options including preimplantation genetic testing 1
• Offer follow-up appointment or phone call within one week of result disclosure 1

Key Resources for Families

Direct families to these organizations 1:

• CJD Foundation (cjdfoundation.org): Patient helpline, educational materials, annual family meetings
• CJD International Support Alliance: Global network connecting families to country-specific resources
• Prion Alliance (prionalliance.org): Research funding and detailed disease information
• Prion Registry (PrionRegistry.org): Connects patients/families to research opportunities and future clinical trials

Emerging Therapeutic Approaches

While no approved treatments exist, the most promising investigational strategies target 6:

• Passive immunization: Antibodies against prion protein
• Antisense oligonucleotides: Gene therapy to lower prion protein expression in asymptomatic mutation carriers

The most realistic therapeutic goal is preventing or delaying symptom onset in asymptomatic carriers of pathogenic mutations, as treatment after symptom onset faces the challenge of existing irreversible brain damage. 6

Critical Pitfalls to Avoid

• Do not delay genetic counseling for families struggling with acute illness—offer DNA banking or postmortem testing as alternatives 1
• Do not introduce the concept of anticipation even to explain it doesn't apply, as this causes unnecessary distress 1
• Do not overprescribe psychotropic medications early in disease course, as many symptoms resolve spontaneously with disease progression 4
• Do not create unnecessary anxiety about transmission risk—prion disease patients pose no hazard to loved ones through normal contact 1
• Do not pressure individuals toward or away from predictive testing—this decision must remain autonomous 1