What is Creutzfeldt-Jakob (CJ) syndrome?

From the Guidelines

Creutzfeldt-Jakob disease (CJD) is a rare, fatal brain disorder caused by abnormally folded proteins called prions, and the most recent and highest quality study suggests that diagnosis involves clinical evaluation, MRI brain imaging, EEG, and cerebrospinal fluid testing for protein markers like 14-3-3 or RT-QuIC 1.

Key Characteristics of CJD

• CJD affects about one person per million annually worldwide
• It typically presents with rapidly progressive dementia, myoclonus (muscle jerks), ataxia (coordination problems), and visual disturbances
• The disease is caused by prions, which are misfolded proteins that trigger normal proteins in the brain to misfold, leading to brain cell death and creating characteristic sponge-like holes in brain tissue

Diagnosis and Management

• Diagnosis involves clinical evaluation, MRI brain imaging showing characteristic changes, EEG showing periodic sharp wave complexes, and cerebrospinal fluid testing for protein markers like 14-3-3 or RT-QuIC 1
• Management focuses on supportive care to alleviate symptoms, including medications like clonazepam or valproate for myoclonus, and palliative care to maintain comfort
• CJD occurs in several forms: sporadic (most common, occurring randomly), genetic (inherited mutations), acquired (from exposure to infected tissue), and variant (linked to bovine spongiform encephalopathy or "mad cow disease") 1

Prognosis

• Unfortunately, there is no cure or effective treatment for CJD, and it is invariably fatal, usually within one year of symptom onset
• The recent development and clinical application of disease-specific protein aggregation and amplification assays such as Real-time Quaking Induced Conversion (RT-QuIC) have constituted major breakthroughs for the confident pre-mortem diagnosis of sCJD 1

From the Research

Definition and Classification of Creutzfeldt-Jakob Disease

• Creutzfeldt-Jakob Disease (CJD) is a rare, degenerative, and fatal brain disease caused by an abnormal form of a protein called a prion 2, 3.
• It is classified into sporadic, hereditary, and acquired forms, with affection linked to different prion varieties and genetic profiles 2.
• There are four types of CJD: Sporadic (sCJD), familial or genetic (gCJD), iatrogenic (iCJD), and variant CJD (vCJD) 4.

Clinical Features and Diagnostic Challenges

• CJD is characterized by rapidly progressive neurodegenerative disease, manifested by psychomotor changes, cognitive dysfunction, motor disorder, and behavioral abnormalities 2.
• Diagnostic strategies have changed, with current methods including imaging, diagnosis through CSF biomarkers, and genetic-based diagnosis 2, 5.
• The gold standard for definitive diagnosis is considered to be histopathological confirmation, but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy 5.

Treatment and Management

• There is no cure for CJD, and management and treatment aim at supporting the patient and alleviating the signs and symptoms of the disease 2, 6.
• Symptomatic treatment follows many of the same principles observed in geriatric and/or hospice care, with some important differences due to disease-specific characteristics 6.
• Education and psychosocial support are also very important in managing patients and families affected by the illness 3, 6.

Neuropathology and Diagnostic Criteria

• The neuropathology of CJD consists of spongiform change, astro- and microgliosis, and poorly defined neuronal loss 4.
• The combination of PrP(Sc) peptide and the status of the codon 129 of the gene (PRNP) encoding for PrP is used to classify sCJD into 6 types 4.
• Current diagnostic criteria are limited, and test sensitivity and specificity vary with the genetics of the disease as well as the clinical stage 5.