Introduction 

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal neurodegenerative disorder associated with consuming beef infected with ‘mad cow disease’. It is one of four types of Creutzfeldt-Jakob disease, each caused by prions- small infectious agents. In 1996, vCJD was initially identified in the United Kingdom within humans. Most cases occurred between 1990-2000 and there have been 178 deaths ever since. Although there is no cure for either type, current farming regulations prevent cows from developing the disease. This article dives into the signs and symptoms, causes, epidemiology, and unique clinicopathological features associated with vCJD cases. 

What is variant Creutzfeldt-Jakob disease (vCJD)?

Background 

Initially identified in 1982 by Stanley Prusiner as scrapie in sheep³ - a disease that causes a degenerative disorder of the central nervous system (CNS) usually occurring within sheep and goats.⁴ Slightly later , bovine spongiform encephalopathy (BSE), colloquially known as “mad cow disease” was identified.⁵ “Bovine” implies affecting cows; “spongiform” refers to the spongy-like vacuole-like texture that the tissue takes on upon infection with the prion; “encephalopathy” refers to disease of the brain. There are a few theories on why BSE emerged. One theory states that an older disease affecting sheep called scrapie may have undergone mutations. Meat-and-bone mix of the infected sheep were then fed to cows, which then became infected with this new mutated (prion) disease. 

The first case of vCJD was reported in 1996 in the UK, arising from infected cattle. There are four different subtypes of CJD:

• Sporadic 
• Variant 
• Iatrogenic 
• Familial 

Out of which the variant subtype is the only one that is transmitted via animals to humans. 

Effect on the brain

vCJD is a rare but fatal neurodegenerative disease that is characterised via the reduction of grey matter in the brain. As with other types, vCJD is a prion disease, leading to its shrinkage due to the spread of prions. It affects the frontal and temporal lobes of the brain amongst other regions such as the cerebellum, corpus callosum, thalamus, and motor cortex. 

Figure 1. Labelled parts of an animated sliced brain showing all the important main parts of it.¹³

What are prion diseases?

Proteins are large molecules essential to every cell in our body. Proteins are long chains of amino acids folded into different three-dimensional shapes. ‘Prion’ is derived from the phrase ‘protein infection’. Prion diseases are caused due to issues in the shapes that the proteins adopt. Normal prion proteins begin folding abnormally and aggregate in the brain, encouraging other proteins to do the same. Prion diseases are thus neither initiated by a virus or a bacteria, so cannot be treated by antivirals or antibacterial medications. Different strains of prions cause varying diseases such as scrapie, bovine spongiform encephalopathy (BSE), chronic wasting disease, amongst others. 

Prions are infectious misfolded versions of normal prion proteins that are found in almost all of our cells. 

Figure 1. Brain tissue from a CJD patient under microscopic examination that shows a high concentration of prion proteins that are responsible for progressive neurodegeneration.⁷

Prion diseases are a group of fatal and infectious neurodegenerative diseases affecting humans and diverse animal species.⁶ It shares the characteristics of late-age onset, accumulation of misfolded protein aggregates in the central nervous system, and neurodegeneration with a large group of disorders including Alzheimer’s and Parkinson’s diseases. 

Despite the similarities, prion disease is the only naturally occurring infectious protein misfolding disorder that can be transmitted within and, in rare occasions, between species.¹²

Mode of transmission 

Dietary 

There is a huge body of proof that vCJD has come about due to prions spreading from the BSE-infected cows, causing human contamination.⁸ During infection with prion diseases, the infectious domains of the prions are present within the periphery - spleen and lymph nodes in particular - prior to rising in the brain which ultimately results in the clinical symptoms. 

Consumption of beef contaminated with the abnormal proteins that arise from BSE can lead to cases of vCJD in humans. 

Blood transfusion

There have been five reported cases of such transmission. 

Signs and symptoms of vCJD

In the rare case of infection, vCJD, unlike a few other neurodegenerative diseases, progresses quite quickly. With death after the onset of symptoms typically occurring at around 12-14 months. 

Although most initial symptoms of vCJD are asymptomatic, it is still present with a variety of key signs and symptoms, such as:

• Delusions and paranoia
• Depression and apathy
• Anosognosia 
• Anxiety and withdrawal

Around 6 months and later, the following symptoms appear:

• Myoclonus - muscle twitches and jerks
• Ataxia - loss of muscle coordination
• Onset of dementia
• Blurry vision that eventually leads to blindness
• Sleep disturbances and disorders
• Dysphagia - difficulty swallowing or speaking
• Dysarthria - difficulty in speech
• Loss of weight

Epidemiology and progression

The cases of CJD are quite rare, occurring in about 1-2 people per 100,000. Owing to this, vCJD has a lower fatality rate in general with about 178 people having died due to being afflicted by this disease so far [9]. With a single case of vCJD being reported in the EEA/EU in the year of 2021, the occurrence of vCJD remains extremely rare, with zero deaths between 2017-2020.¹⁰

vCJD tends to affect people of any age depending on when the infected meat is consumed. It can take 10 years or more to begin developing symptoms after coming into contact with the prion. This is termed the incubation period, and it is similar to other prion diseases. 

Diagnosis 

There is no specific tests for vCJD while the infected individual is alive, so many factors will be considered and evaluated, such as:

• Age of the individual
• Symptoms 
• Whether another potential disease could be the reason
• Duration of symptoms (one year or shorter)
• Tests of brain activity before death

Only examination of the brain tissue after an autopsy can confirm the presence of vCJD.

Preventative measures and management

Since there is no exact cure for vCJD, there are only a few palliative care measures that can be carried out in order to lessen the effect of the disease for a temporary period of time. Treatment mostly aims to alleviate symptoms and to make the infected individual feel comfortable during disease progression. 

One of the main ways to prevent the spread of vCJD and avoid its resurgence, is to enforce and follow the ‘feed ban’ against transmissible spongiform encephalopathy and consists of a ban that reduces the consumption of restricted animal materials, also known as processed animal protein (PAP) in livestock. Thereby reducing the spread of prion proteins that can cause neurodegenerative diseases. Farmers also must report suspected cases of BSE in cows to enable a veterinary assessment to take place. Movement of the cow will be restricted if BSE is suspected upon inspection. Cows suspected to have BSE are slaughtered. 

A further European initiative is the classification of countries into risk categories. In July 2000, the European Union Scientific Steering Committee adopted an opinion on the geographic risk of BSE in all Member States and certain third countries. It determined four categories of risk and allocated countries to one of the four categories as shown below:¹¹

• Category I (Highly unlikely to present a BSE risk)
• Category II (Risk of BSE is unlikely but cannot be excluded)
• Category III (Likely to present a BSE risk, even if not confirmed, or presenting a low level of confirmed BSE risk)
• Category IV (Confirmed, at a higher level)

FAQ’s

How does someone get Creutzfeldt-Jakob disease?

Creutzfeldt-Jakob disease (CJD) can express itself in three ways, that can be briefly described as:

1. Sporadically (sCJD): One of the most common forms, that accounts for about 85-90% of sCJD cases. Where it occurs without any known cause or risk factors.

2. Familial (fCJD): Caused and inherited by mutations formed on the PRNP gene, a gene that provides instructions for making the prion protein. Having it account for about 10-15% of the total CJD cases.

3. Acquired (i/vCJD): Although rare, this is caused by exposure to infected brain or nervous system tissue, often through certain medical procedures or contaminated surgical instruments.

What is the life expectancy of someone with CJD?

The life expectancy of an individual affected with CJD is extremely reduced. Most patients succumb to this neurodegenerative disease within a year of its onset. The rapid progression of the disease leads to severe neurological decline, ultimately resulting in the demise of the patient. 

What happens if you get vCJD?

Upon contraction of variant Creutzfeldt-Jakob disease (vCJD), the disease progresses via:

1. Early symptoms: Beginning with the introduction of psychiatric symptoms such as behavioural changes, depression, and anxiety along with sensory disturbances like numbness or tingling.

2. Neurological symptoms: Further as vCJD progresses, certain neurological symptoms become prominent, like cognitive impairment, blindness or blurry vision, involuntary muscle movements, poor coordination, difficulty walking. 

3. Advanced stage: In the final stages, patients tend to often become completely bedridden losing the ability to move or speak - paralysis or dysarthria respectively. They may also experience severe muscle stiffness with myoclonus, dementia, and eventually resulting in the patient falling into a coma.

4. Fatal outcome: Like other forms of CJD, vCJD is invariably fatal, typically within 13 to 14 months after symptoms first appear.

What is a variant form of Creutzfeldt-Jakob disease?

Variant Creutzfeldt-Jakob disease (vCJD) is a rare and fatal neurodegenerative condition that differs from the classic form of CJD in several key ways:

1. Cause: Commonly caused when an individual consumes cow or cattle meat that is afflicted with bovine spongiform encephalopathy (BSE) which is colloquially termed as ‘mad cow disease’. Usually occurring due to the consumption of processed animal produce that result in the formation of prions.

2. Age of onset: vCJD typically affects younger individuals, with an average age of onset in the late 20s, compared to classic CJD, which usually affects older adults.

3. Symptoms: vCJD often presents with psychiatric symptoms such as depression and anxiety in the early stages, followed by severe neurological decline.

4. Disease progression: The progression of vCJD is somewhat longer than that of sporadic CJD, with patients typically living for about 13 to 14 months after symptoms begin.

5. Pathology: Neuropathologically, vCJD is characterised by the presence of numerous amyloid plaques in the brain, surrounded by vacuoles, giving the brain a spongy appearance. This shrinks the brain due to a reduction in grey matter.

Summary 

Variant Creutzfeldt-Jakob disease (vCJD) is one of four types of Creutzfeldt-Jakob disease and is mostly associated with consuming beef from cows infected with BSE. It is a prion disease causing neurodegeneration and death within 10-14 months after the onset of symptoms. Whilst vCJD is very rare, current farming standards in the UK prevent cows from developing BSE. Although incurable, symptoms can be alleviated with different medications.