Article title: Creutzfeldt- Jakob disease (CJD)
Author: Balqees Jboul
Reviewer: Lobana Mahdawi

Overview

Creutzfeldt-Jakob disease is a rare and fatal transmissible neurodegenerative disorder that the underlying cause of it is misfolded prion proteins (PrPSc). Effective therapeutics for the disease are not available and the accurate diagnosis of the disease can be challenging, but there is a palliative treatment that tries to keep the person as comfortable as possible and reduce the symptoms, The most common form of human prion disease is sCJD with incidence around 1.5 to 2.0 per million person-years. (1)

Pathogenesis 

Different types of CJD may be different with respect to symptoms evolution,  neuropathological characteristics, and biomarker profile, they are related to  Methionine/Valine(M/V) polymorphism and with a molecular mass of (PrPSc). A definitive diagnosis of CJD needs neuropathological confirmation.  There are many types of CJD as Sporadic, iatrogenic, variant, and familial. In the late 1980s to early 1990s, there was high exposure of the UK population to bovine spongiform encephalopathy-contaminated food products, which caused more than  150 deaths from variant type of Creutzfeldt–Jakob disease (vCJD). (1)

Although the pathogenesis is not clearly understood, data from animal models and from patients who have vCJD have shown that oral exposure to BSE is followed by accumulation of (PrPres) in gut-associated lymphoid tissue rapidly, then by hematogenous spread, reaching the lymphoreticular system. Spreading to the central nervous system may not occur for several years, but the blood taken from individuals who were in the pre-clinical phase of their disease appears the ability to transmit the disease. (2)

Clinical presentation and complication

Common clinical manifestations of CJD include a rapid decline in cognitive function, cerebellar dysfunction, behavioral changes, and visual problems. CJD is easily misdiagnosed as another disorder due to unclear early presentation.  Psychiatric symptoms of the disease at the onset, painful sensory symptoms that are persistent, dementia, and development of at least two of the following five neurologic signs: poor coordination, visual signs, chorea, hyperreflexia, or myoclonus after more than 4 months of the onset of the disease should increase the consideration about CJD. Most patients die within 1 year of the onset of the symptoms.  The most common complications of  Creutzfeldt-Jakob disease are overwhelming infections, respiratory failure, and congestive heart failure (5).

Workup and Diagnosis

The neuropathological investigation and immunostaining of PrPSc allow a clear diagnosis of prion diseases also MRI is a very helpful imaging technique for CJD, It usually shows abnormalities of signal in the putamen and head of the caudate (9).

Early presentation of CJD  is characterized by an increased diffusion-weighted imaging (DWI) signal in the cortex or deep gray matte, Figure (1). (3). For definite diagnosis, a brain biopsy is required but it has complications such as infections spreading, the possibility of a false negative result due to sample error in which typical pathology and PrPSc may not be present in all cortical regions, and issues about the quality of the tissue, understanding of all of these considerations and that it is very invasive, brain biopsy is usually only considered when the diagnosis is not clear and in treatable conditions such as encephalitis or lymphoma (6).

A less invasive procedure, tonsillar or even adenoid biopsy, was found helpful in the diagnosis of variant CJD (vCJD) but is not useful for other forms of prion disease. The direct in vivo detection of PrPSc in sCJD employing routinely accessible bio-fluids appears possible but a novel  study using urine showed low sensitivity of 40%, there is also Protein Misfolding Cyclic Amplification (PMCA) test that was  improved  to reproduce and amplify PrPSc in micro-tubes and has an acceptable  sensitivity, especially with vCJD but high sensitivity, could not be found  in sCJD or other prion diseases(6)

Real-time Quaking Induced Conversion (RT-QuIC) test that depends on energizing” the misfolding of prion protein coupled to a fluorescent readout, recently there is (second generation RT-QuIC) to reduce the assay time and to increase the sensitivity. The diagnostic performance of the improved CSF RT-QuIC is better than surrogate marker tests for prion diseases such as 14-3-3 and tau proteins, and together with PRNP gene sequencing, the test promotes the major prion subtypes to be differentiated in vivo(4)

Management 

Until now treatment of prion diseases depends mainly on supportive treatment, and there is no approval-specific therapy that can stop the progression of the disease. Many drugs have been evaluated such as acyclovir, amantadine, antibiotics, antiviral agents, interferon, and steroids but none of these drugs has shown a  consistent benefit. (7)

Prevention

vCJD was acquired by food exposure and transmitted through blood transfusion so to reduce any risk of acquiring vCJD from food, travelers to Europe or other areas with indigenous cases of BSE should avoid beef and beef products to reduce the opportunity of contamination with tissues that may have the BSE agent. Conversely, Milk and milk products from cows are not a common risk for transmission of the BSE agent, however, there is no known way to prevent sporadic Creutzfeldt-Jakob disease (CJD). (8)

Patients with a family history of the neurological disease should talk with a genetics counselor so he can help them sort through the risks associated with their situation, while in the cases of iatrogenic CJD, Properly cleaning and sterilizing the medical equipment can reduce the incidence of transmission and prevent spreading of the disease. Newer regulations that regulate the feeding of cows may also help prevent the spread of prion diseases. (8)

 

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