Variant Creutzfeldt-Jakob Disease

What is variant Creutzfeldt-Jakob disease?

Variant Creutzfeldt-Jakob disease (often shortened to vCJD) is a very rare, progressive and ultimately fatal brain disorder. It belongs to a group of illnesses called prion diseases. A prion is a normal protein found in the body that has folded into an abnormal shape. Once this happens, the misfolded protein can cause nearby normal proteins to change shape too, and the damaged proteins build up in the brain. Over time this destroys nerve cells, leaving the brain tissue with a spongy appearance under a microscope. For this reason prion diseases are also called transmissible spongiform encephalopathies.

Variant Creutzfeldt-Jakob disease is different from the more common form, known as sporadic Creutzfeldt-Jakob disease. The variant form was first recognized in the United Kingdom in the mid-1990s and is strongly linked to eating beef products from cattle infected with bovine spongiform encephalopathy (BSE), sometimes called mad cow disease. Most people who developed vCJD were exposed before strict food-safety controls were introduced, and the number of new cases worldwide has fallen sharply since then.

Unlike sporadic CJD, which mainly affects older adults, variant Creutzfeldt-Jakob disease has most often affected younger people, including teenagers and young adults. The illness also tends to begin with mood and behavior changes rather than obvious memory problems, and it usually lasts longer than the sporadic form. Because it is so rare, most doctors will never see a case, and specialist neurology teams are usually involved in confirming the diagnosis. In hospital groups such as Acibadem, the Neurology department is typically responsible for investigating suspected prion diseases.

Variant Creutzfeldt-Jakob disease symptoms

Variant Creutzfeldt-Jakob disease symptoms develop gradually and worsen over months. They are often described in stages, although the pattern varies from person to person.

Early symptoms are frequently psychiatric, meaning they affect mood, thinking and behavior, and are easily mistaken for depression or anxiety. They may include:

• Low mood, tearfulness or loss of interest in usual activities
• Anxiety, irritability or sudden mood swings
• Withdrawing from friends and family
• Trouble sleeping
• Unusual persistent pain, tingling, burning or unpleasant sensations in the limbs or face (doctors call this dysesthesia)
• Poor concentration and mild forgetfulness

Later symptoms reflect increasing damage to the parts of the brain that control movement, coordination and thinking. These may include:

• Unsteadiness, clumsiness and problems with walking (ataxia)
• Involuntary jerking movements (myoclonus) or writhing movements (chorea)
• Slurred speech and difficulty swallowing
• Worsening memory and confusion progressing to dementia
• Vision problems
• Difficulty controlling the bladder and bowel

Advanced disease leaves the person unable to move or speak and fully dependent on others for care. Awareness of surroundings is usually lost. Death commonly results from complications such as chest infections. The whole course of variant Creutzfeldt-Jakob disease often lasts longer than sporadic CJD, sometimes more than a year, but the exact timeline differs between individuals.

It is important to remember that depression, anxiety and unexplained pain are extremely common and almost never caused by vCJD. The concern arises when psychiatric symptoms in a young person are followed by clear neurological signs such as unsteadiness, involuntary movements and rapidly declining thinking ability.

Causes and risk factors

Variant Creutzfeldt-Jakob disease causes trace back to abnormal prion proteins entering the body from an outside source. This makes it an acquired prion disease, in contrast to sporadic CJD (where the cause is unknown) and inherited forms (caused by a genetic change passed through families).

The main causes and routes of exposure that scientists have identified are:

• Eating contaminated beef products. The BSE epidemic in cattle, mainly during the 1980s and 1990s, is considered the source of most human cases. Products containing brain, spinal cord or certain other tissues were thought to carry the highest risk. Strict controls on animal feed and slaughter practices have since greatly reduced this exposure.
• Blood transfusion. A small number of people developed vCJD after receiving blood from a donor who later developed the disease. This has led many countries to introduce donor screening rules and blood-processing measures.
• Possible transmission through contaminated medical instruments or tissue. Prions are unusually resistant to standard sterilization. Health systems follow special decontamination rules for instruments used on people with suspected prion disease. Documented transmission of vCJD by this route is not established, but it remains a theoretical concern.

Variant Creutzfeldt-Jakob disease is not spread through everyday contact. Living with, caring for, touching, kissing or sharing meals with an affected person does not transmit the disease. It is not spread through the air or by coughing.

Risk factors that influence who develops the disease include:

• Living in, or eating beef products from, regions affected by BSE during the years before controls were introduced
• Younger age at the time of exposure; most cases have occurred in young adults
• A particular genetic make-up. Almost all confirmed cases have occurred in people who inherited two copies of the same version of the prion protein gene (a pattern doctors call methionine homozygous at codon 129). People with other versions may be resistant or may have a much longer incubation period; this is still being studied.
• Receiving a blood transfusion from a donor later diagnosed with vCJD

The incubation period, the time between exposure and the first symptoms, is believed to be very long, often many years and possibly decades. This is one reason why public health authorities continue to monitor for new cases even though the original food exposure has largely ended.

Diagnosis

Variant Creutzfeldt-Jakob disease diagnosis is challenging, especially early on, because the first symptoms look like common psychiatric conditions. Doctors usually become suspicious when a relatively young person develops steadily worsening psychiatric symptoms together with unexplained pain and then neurological signs. There is no single simple blood test that confirms the disease during life, so doctors rely on a combination of the clinical picture, imaging, laboratory tests and, in some cases, tissue samples.

Steps that are commonly used include:

• Detailed medical history and neurological examination. The doctor asks about the timeline of symptoms, past blood transfusions, travel and dietary history, and family history of neurological disease. The examination looks for unsteadiness, involuntary movements and changes in reflexes and thinking.
• Magnetic resonance imaging (MRI) of the brain. MRI uses magnets and radio waves to create detailed pictures of the brain. In vCJD, a characteristic bright signal is often seen in a part of the brain called the pulvinar, at the back of the thalamus. This is known as the pulvinar sign and is an important supportive finding.
• Electroencephalogram (EEG). This test records the brain’s electrical activity through small sensors on the scalp. In sporadic CJD it often shows a typical pattern of repeating waves, but in variant CJD this pattern is usually absent. The EEG therefore helps distinguish between the two forms rather than confirming vCJD.
• Lumbar puncture (spinal tap). A small sample of cerebrospinal fluid, the fluid surrounding the brain and spinal cord, is taken from the lower back with a thin needle. It is tested for proteins released when brain cells are damaged, and it helps rule out infections and inflammation. Newer tests that detect misfolded prion protein are available in specialist laboratories, although they are considered less sensitive in vCJD than in sporadic CJD.
• Tonsil biopsy. Unlike other forms of CJD, variant CJD abnormal prion protein can often be found in lymphoid tissue such as the tonsils. Removing a small piece of tonsil tissue for laboratory examination can support the diagnosis during life. This procedure is done only in specialist centers.
• Blood tests and genetic testing. Routine blood tests are used to exclude other treatable causes of confusion and behavior change, such as thyroid problems, vitamin deficiencies or infections. A blood sample may also be used to check the prion protein gene, which helps interpret the overall picture.
• Brain biopsy or examination after death. A definite diagnosis requires examining brain tissue. Brain biopsy during life is rarely performed because of its risks and because it does not change treatment. In most cases the diagnosis is confirmed by examination of the brain after death.

Because of these limitations, doctors classify a case as possible, probable or definite variant Creutzfeldt-Jakob disease according to internationally agreed criteria. Suspected cases are usually reported to national surveillance units, which also provide expert advice on testing.

Treatment options

At present there is no treatment that can cure variant Creutzfeldt-Jakob disease, slow the underlying process or reverse the brain damage. Several experimental medicines have been studied, but none has been shown to change the course of the disease. Variant Creutzfeldt-Jakob disease treatment therefore focuses on relieving symptoms, maintaining comfort and dignity, and supporting the family. This approach is called supportive or palliative care.

Care is usually coordinated by a neurologist, a doctor who specializes in brain and nerve conditions, working alongside palliative care specialists, nurses, therapists and, where possible, a national prion disease service. Common elements include:

• Medication for psychiatric symptoms. Antidepressant or anti-anxiety medicines may be used for low mood and distress. Low doses of antipsychotic medicines are sometimes given for severe agitation or hallucinations.
• Medication for movement symptoms. Drugs such as clonazepam or sodium valproate are often used to reduce involuntary jerking movements. Muscle relaxants may help stiffness.
• Pain relief. The unusual persistent pain seen in vCJD may respond partly to standard painkillers or to medicines used for nerve pain, such as certain anticonvulsants or antidepressants.
• Physical, occupational and speech therapy. Therapists help maintain mobility for as long as possible, reduce the risk of falls, adapt the home and support safe swallowing. In some cases a feeding tube is discussed when swallowing becomes unsafe; this is a personal decision made with the family.
• Nursing care. Regular repositioning to prevent pressure sores, help with continence, mouth care and prevention of chest infections become increasingly important as the illness advances.
• Psychological and social support. Counseling for the family, help with legal and financial planning, and respite care are often part of the care plan.
• Infection-control precautions. Hospitals follow specific protocols for handling surgical instruments and certain tissues from people with suspected prion disease. These protocols protect others and do not affect the quality of care the patient receives.

Surgery has no role in treating the disease itself. Where appropriate, discussions about the goals of care and the person’s wishes are held early, while the person can still take part in decisions.

Living with variant Creutzfeldt-Jakob disease and outlook

Variant Creutzfeldt-Jakob disease is a life-limiting illness. It progresses steadily, and there is currently no way to stop it. Although the course is often longer than that of sporadic CJD, the outlook is poor in every confirmed case. Doctors are honest about this so that families can plan and make the most of the time available.

Much of the burden falls on families and caregivers. In the early stages, the affected person may still be able to work, socialize and take part in decisions, but they will need increasing help with daily tasks. Practical steps that many families find useful include arranging home adaptations, learning safe lifting and feeding techniques from therapists, and identifying local hospice or palliative care services early. Caregivers are encouraged to accept help and to look after their own physical and mental health.

Emotional reactions such as shock, anger, guilt and grief are normal for the person and for loved ones. Counseling services, patient-support organizations for prion disease and national surveillance units can provide information and emotional support tailored to this rare condition. Some families also choose to participate in research studies, which may help future patients even though they do not offer direct benefit.

It is worth noting that new cases of vCJD have become extremely rare since the food-safety controls of the 1990s. Ongoing surveillance, blood-donor policies and instrument decontamination rules exist to keep it that way.

Frequently asked questions

Is variant Creutzfeldt-Jakob disease the same as mad cow disease?

Not exactly. Mad cow disease is the informal name for bovine spongiform encephalopathy (BSE), a prion disease of cattle. Variant Creutzfeldt-Jakob disease is the human illness that is believed to result from exposure to BSE prions, mostly through eating contaminated beef products before food-safety controls were introduced. The two conditions are caused by closely related abnormal prions but affect different species.

What are the first variant Creutzfeldt-Jakob disease symptoms?

The earliest symptoms are usually psychiatric, such as depression, anxiety, social withdrawal and personality change, sometimes accompanied by persistent unpleasant pain or tingling in the limbs. Because these are common complaints with many other causes, they are rarely due to vCJD. Neurological signs such as unsteadiness, involuntary movements and declining memory typically appear later and prompt further investigation.

What are the main variant Creutzfeldt-Jakob disease causes?

The disease is acquired from an external source of abnormal prion protein. The main cause is thought to be eating beef products from cattle with BSE during the years before controls were in place. A small number of cases have been linked to blood transfusions from donors who later developed the disease. It is not caused by stress, diet in general or everyday contact with an affected person.

How is variant Creutzfeldt-Jakob disease diagnosis confirmed?

Doctors combine the clinical picture with brain MRI, EEG, cerebrospinal fluid tests, blood tests and sometimes a tonsil biopsy to reach a diagnosis of probable vCJD. A definite diagnosis requires examining brain tissue, which in most cases happens after death. Suspected cases are usually reviewed by a national surveillance unit that has experience with this rare disease.

Is there any effective variant Creutzfeldt-Jakob disease treatment?

No treatment is currently known to cure the disease or slow its progression. Treatment aims to control symptoms, for example medicines for mood changes, involuntary movements and pain, together with nursing, therapy and palliative care to keep the person as comfortable as possible. Research into potential therapies continues, but no proven disease-modifying treatment is available.

Can I catch vCJD from a family member who has it?

No. Variant Creutzfeldt-Jakob disease is not spread through ordinary contact, including touching, hugging, sharing utensils or breathing the same air. Special precautions apply only to certain medical procedures involving tissues such as the brain, spinal cord, eye and lymphoid tissue, and these are managed by healthcare staff.

Is it still possible to get variant Creutzfeldt-Jakob disease from eating beef today?

The risk is considered extremely low because of strict controls on animal feed, the removal of high-risk tissues from the food chain and ongoing testing of cattle in many countries. Most cases seen today are thought to reflect exposure many years ago because the incubation period is very long.

When to see a doctor

Variant Creutzfeldt-Jakob disease is extremely rare, and the symptoms described on this page are far more likely to have another cause. However, any rapidly worsening change in thinking, mood or movement should be assessed by a doctor. Urgent medical attention is advisable if you or someone you know develops:

• Rapidly progressive confusion, memory loss or personality change over weeks or months
• New unsteadiness, frequent falls or difficulty walking without an obvious explanation
• Sudden jerking or writhing movements that cannot be controlled
• Persistent unexplained pain, burning or tingling in the limbs together with mood or behavior changes
• Difficulty speaking or swallowing that is getting worse
• Vision changes combined with any of the above
• Depression or anxiety in a young person that does not respond to treatment and is accompanied by new neurological symptoms

Anyone who has been informed that they received blood from a donor later diagnosed with vCJD, or who has been contacted by a public health authority about possible exposure, should follow the advice they are given and discuss any new symptoms with their doctor promptly.