Symptoms of prion disease: more detail

Onset phenotypes

The opening picture differs by form, and recognising which one you are looking at shortens the path to diagnosis.

Sporadic CJD usually opens with a rapidly progressive dementia accompanied by neurological signs. The NHS account lists gait difficulty from impaired balance and coordination, dysarthria, vertigo, visual disturbance such as diplopia, hallucinations, and paraesthesia, worsening within a few months. Myoclonus commonly appears early.

Variant CJD characteristically opens with psychiatric or sensory features. The NHS lists severe depression, social withdrawal, anxiety, irritability and insomnia, with neurological symptoms following around four months later. CDC describes prominent painful dysaesthesia and delayed neurological signs, with dementia and ataxia appearing later than in the classic form, and a median age at death of 28 years against 68 for classic CJD. Median duration of illness is 13 to 14 months for variant CJD and 4 to 5 months for classic CJD.

Genetic forms broadly follow the sporadic pattern with a slower course, usually around two years. Iatrogenic disease has no fixed pattern, since the presentation depends on the route and site of exposure, and a progressive cerebellar syndrome after cadaveric pituitary hormone is the classic example.

The domains affected

Cognition and behaviour. Severe memory loss, impaired concentration, confusion, agitation, aggression, paranoia and unusual emotional responses all occur as the illness advances.

Motor. Ataxia, myoclonus, muscle twitching and spasm, and progressive loss of voluntary movement, ending in akinetic mutism in many people.

Visual. Diplopia, cortical visual disturbance and eventual blindness are described across the forms.

Sensory. Paraesthesia in sporadic disease, and persistent painful dysaesthesia as a defining early feature of variant CJD.

Bulbar and autonomic. Dysphagia, loss of speech, and bladder and bowel incontinence.

Nutrition and weight. Loss of appetite with weight loss is common and interacts with swallowing difficulty.

Myoclonus

Treat myoclonus that interferes with daily functioning or care or causes distress. Infrequent jerks that trouble no one need no treatment, and that threshold is worth stating explicitly to families who ask why nothing has been started.

Levetiracetam is suggested first line, being generally well tolerated, straightforward to titrate and available in multiple formulations, which helps once swallowing becomes unreliable. Clonazepam is reserved for the more advanced stages, when a person is no longer ambulant, because of sedation and fall risk earlier on.

Neuropsychiatric symptoms

The guiding principle in the recommendations is that so-called challenging behaviour should generally be seen as the communication of an unmet need. The first moves are therefore to look for a cause, including pain, constipation, urinary retention, infection, fear, overstimulation and unfamiliar surroundings, and to adjust the environment and the approach to care.

Because symptoms in prion disease can emerge and resolve quickly, the authors state that a watch-and-wait approach to troubling symptoms such as delusional ideas is often justified. Medication is kept for distress or safety risk that has not responded to non-drug approaches. They also note that delirium appears less common in prion disease than in other dementias, which is a reason to look harder for a specific unmet need before reaching for an antipsychotic.

Pain

Pain is generally not found to be a problematic symptom in sporadic CJD, and that statement should not be used to dismiss a particular person’s pain. Variant CJD is different, since painful sensory symptoms are intrinsic to it.

Assessment depends on caregiver history and observational tools once self-report is unreliable. Treat identifiable causes. A stepped pharmacological approach with regular paracetamol first line is suggested, and opioids should be used with caution under the guidance of palliative care specialists.

Sleep

Sleep problems are managed with non-pharmacological strategies where possible. Where those are insufficient, sedating antidepressants, hypnotics or melatonin may be considered, weighed against fall risk and daytime sedation. Fatal familial insomnia is a separate situation, in which sleep disruption is the presenting feature of the illness itself.

Swallowing and nutrition

Swallowing typically deteriorates, and oral feeding can become harmful through aspiration. Whether clinically assisted nutrition and hydration is in the best interests of a person in a state of akinetic mutism is a decision to be made on an individual basis. National guidance advises against routine clinically assisted nutrition and hydration in severe dementia unless there is a potentially reversible comorbidity, and where it is used it should be reviewed at every care review. Speech and language therapy input early, while a person can still take part in decisions, is worth arranging before it is needed.

Communication and prognosis

The recommendations are direct about the conversation itself. Clear and compassionate communication is described as particularly paramount in this disease, and communicating prognostic information with sensitivity as essential. In practice that means finding out what the person and the family already understand, asking what they want to know, and returning to the conversation as the situation changes.

Early involvement of palliative care is encouraged to help guide these conversations, including advance care planning while the person can still take part. In the United Kingdom, all individuals with suspected prion disease should be referred to the National Prion Clinic.

Support for the people caring

Caring for someone dying of prion disease is described in the recommendations as often a profoundly emotional experience. The components listed are disease-specific information about what to expect, training in practical care, respite, financial support, mental health support and peer networks such as the CJD Support Network. Offering these before a crisis is more useful than offering them after one.

Practical, stage-by-stage guidance for families is on what to expect. The plain version of this page is symptoms of prion disease.