Creutzfeldt-Jakob disease

This is an extremely rare brain disease: worldwide it is diagnosed in roughly one or two people per million each year. What made it famous was not how often it occurs but what causes it. The culprit is neither a virus nor a bacterium but one of the body's own proteins that has taken the wrong shape — a prion. There is still no cure, and the illness moves fast. But this text has a second and far more practical purpose: rapidly worsening cognitive decline turns out to be something else far more often, and a good share of those something elses can be treated. So a discussion of Creutzfeldt-Jakob disease is above all a discussion of why, in that situation, waiting is the wrong choice.

What a prion is and why it is dangerous

Every one of us carries prion protein, and the brain holds the most of it. What lets the protein work is its three-dimensional shape: the chain of amino acids folds in a particular way, rather like origami. Occasionally the fold goes wrong. The body usually dismantles such proteins, but a faulty molecule can survive, and that is where the trouble begins: it forces neighbouring normal molecules to refold in its own image, each spoiled one produces more, and the process snowballs. Nerve cells die, deposits of the protein build up in the brain, and the tissue takes on a porous, sponge-like appearance — the origin of the old name for this whole family of diseases.

A prion does not behave like an ordinary infectious agent. It carries no genetic material, so antibiotics and antivirals have no effect on it whatsoever. It is also exceptionally tough: the routine sterilisation of surgical instruments, dependable against bacteria and viruses, does not inactivate prions, which is why separate decontamination protocols exist for them.

How the illness announces itself

Its defining feature is pace. In the commonest form, the distance from the first oddities to a severe state is not years, as in Alzheimer's disease, but weeks and months. It is that speed, rather than any particular symptom, that raises the suspicion of a prion disease. Neurological signs usually come first:

• unsteadiness when walking, clumsy hands, loss of coordination;
• slurred, hard-to-follow speech;
• sudden involuntary muscle jerks, especially in response to a sound or a touch;
• visual disturbance — double vision, loss of visual field, distorted shapes and colours, sometimes progressing to blindness with healthy eyes;
• dizziness, numbness or pins and needles in various parts of the body;
• fast-deepening memory gaps, confusion, and difficulty with long-familiar tasks.

Less often the illness starts in the mind: low mood, anxiety, irritability, withdrawal from family, insomnia, unusual suspicions — with neurological problems joining only some months later. That opening pattern belongs to the form acquired from outside the body and usually affects noticeably younger people.

After that the problems compound: the person loses the ability to walk, swallow and speak, stops recognising their surroundings and needs round-the-clock care. Most people with the commonest form die within a year of the first symptoms, usually from a chest infection or respiratory failure. The inherited form often unfolds more slowly, over a year or two.

Where it comes from

Prions accumulate for several different reasons, and those determine both the age of onset and the course.

• Spontaneous. The commonest, around eight or nine cases in ten. The protein misfolds for no visible reason and the process starts on its own. Lifestyle, diet and past illnesses play no part. It usually affects older adults, most often in their sixties.
• Inherited. A mutation in the prion protein gene, dominant in its behaviour: inheriting the altered gene from one parent is enough, and the chance of passing it on to a child is one in two. Symptoms arrive in middle age, long after the children have been born, so a family may go years without knowing the risk exists. The same group includes several related inherited prion diseases, among them the one that shows itself mainly by destroying sleep.
• Acquired through meat. The form linked to bovine spongiform encephalopathy, so-called mad cow disease. Cattle were infected through bone meal in feed, and the prion reached people in meat products. Once such feed was banned and slaughter rules tightened, this form all but vanished and new cases are barely recorded. Its incubation period, though, is very long — years and decades — so writing it off entirely would be premature.
• Introduced during treatment. Growth hormone used to be extracted from the pituitary glands of deceased donors, and some of the children treated that way until the mid-1980s were infected; the switch to synthetic hormone closed that route. Isolated cases have been traced to dura mater grafts, corneal grafts and neurosurgical instruments. Today this is exceptionally rare.

Can it be caught from a patient?

The short answer is no, not in everyday life. Prions are not passed on through the air, through talking, hugging or kissing, through shared crockery, through nursing care or through sex. Feeding a relative, changing their bedding and sitting with them are all safe.

Transmission is possible only when infected nerve tissue enters another person's body: through a tissue graft, through poorly decontaminated instruments that have been inside a brain, and — for the meat-associated form — through a blood transfusion. That is why many countries refuse blood and organs from people with risk factors, remove white cells from donated blood, and either process neurosurgical instruments under special protocols or retire them when a prion disease is suspected.

Why the work-up is urgent and what is looked for first

This is the section worth reading the article for. A decline in thinking, memory and walking that deepens over weeks or months is not a diagnosis but an alarming pattern with a long list of possible causes. A fair number of them are treatable, sometimes completely, if time is not lost. Among the things a doctor will rule out:

• autoimmune inflammation of the brain, which responds to treatment that dampens the immune response, and responds better the earlier it starts;
• deficiency of vitamin B12 and other B vitamins;
• severe disorders of thyroid function;
• infections affecting the nervous system;
• brain tumours and lymphomas, and also the remote effect a tumour elsewhere can have on the nervous system;
• normal pressure hydrocephalus, where a shunt helps;
• inflammation of the brain's blood vessels;
• poisoning, drug side effects, and severe depression, which can convincingly mimic dementia.

A neurologist leads the work-up: magnetic resonance imaging with particular sequences, which in prion disease produces a fairly recognisable picture; an electroencephalogram; and examination of the cerebrospinal fluid. The fluid is now tested with a method that detects the prion's own ability to reshape normal protein, and its accuracy comfortably exceeds the older protein markers. Where an inherited form is suspected, a blood test looks for the gene mutation, always preceded by genetic counselling, since the result concerns not only the patient but their children too. Only examination of brain tissue confirms the diagnosis outright, and biopsy is rarely done during life — chiefly when there is hope of finding something treatable instead of a prion disease.

What can be done for the person

No medicine halts the disease, and online offers to "cure prions" are always a fraud. Care is aimed at keeping the person calm and free of pain, and on that front a great deal can be achieved.

Anxiety and low mood are eased with antidepressants and sedative medicines; muscle jerks and spasms usually settle with antiepileptic drugs; pain is treated where needed up to and including strong opioid painkillers. Swallowing and nutrition specialists, physiotherapy, skin care and pressure sore prevention all come into play. Relatives almost always need support of their own, both practical and emotional.

One conversation is best had early, while the person can still take part in it — about their own wishes: where they want to be in the late stage, at home or in a hospice; whether they accept tube feeding if swallowing fails; how they feel about mechanical ventilation; whether they wish to donate tissue for research after death. Wishes set down in advance spare the family from guessing at the hardest moment. The form such a document takes and the legal weight it carries differ from country to country, so it is worth checking locally.

Online consultation

Three things are well suited to a remote appointment. First, how fast the situation is actually changing: the doctor will help build a timeline from your observations, and it is precisely that pace which decides whether a routine neurology referral will do or whether an appointment must be pressed for immediately. Second, which investigations are worth having in hand and in what order, so that weeks are not lost going round in circles. Third, the practicalities of care at home: feeding when swallowing is difficult, safety when moving about, managing anxiety and agitation. Families in which a prion disease has already occurred can also discuss whether genetic testing is advisable and what it does and does not tell them. This diagnosis cannot be made or excluded remotely — it requires an in-person neurological assessment.

This material is for information only and does not replace medical advice.