Volume 8: Variant CJD
6. Diagnosis, treatment and care of vCJD patients
Diagnosis of vCJD by the medical profession
General practitioners
Psychiatrists
Neurologists

6.5 In his written evidence to the Inquiry, Dr Will observed that the clinical diagnosis of CJD (as with many other neurological disorders) was not dependent on the application of standardised research diagnostic criteria but was a matter of clinical training and experience. ¹ Thus, the identification of patients with vCJD was largely dependent on the diagnostic expertise of the medical professional.

General practitioners

6.6 In most cases, following the manifestation of vCJD symptoms, the patient's first contact with the medical profession was with the family general practitioner (GP). In evidence to the Inquiry, the families of vCJD victims described some of the symptoms they observed that influenced their decision to consult a GP. These included depression, ² coordination problems, ³ memory loss and mood swings, ⁴ pins and needles and pains in the limbs, ⁵ bad headaches, ⁶ cold extremities, ⁷ pain in the feet, ⁸ rashes ⁹ and short-term memory loss. ¹⁰ In all cases, the symptoms worsened over a relatively short space of time and the GP referred the patient on to a psychiatrist or neurologist. In all cases, the patients were ultimately referred to a neurologist.

Psychiatrists

6.7 The part played by the psychiatrists in the diagnosis and management of cases of vCJD is summarised in a large study by the CJDSU of the psychiatric features of 33 cases in the Psychiatric Bulletin. ¹¹ The article noted that the majority of vCJD cases had seen a psychiatrist, often as the first specialist referral, but that the non-specific characteristics of the psychiatric symptoms of vCJD made early recognition difficult or impossible.

6.8 The cases took an average of 8 months to be referred to a psychiatrist - where this was the first specialist referral - after onset of illness (ranging from 2 weeks to 16 months). ¹² Seventeen of the cases were initially referred to a psychiatrist, and eight cases involved psychiatrists after referral to a neurologist. The average time between consultation with a psychiatrist and referral to a neurologist was 9 weeks (ranging from one day to 32 weeks). Similarly, where the initial referral was to a neurologist, the average time before referral to a psychiatrist was 10 weeks (ranging from 2 to 38 weeks).

6.9 All but one of the 33 cases exhibited psychiatric symptoms at an early stage and for most cases these symptoms were the first manifestation of the disease. The main symptoms were depression, anxiety, withdrawal, aggression, hallucinations and delusions. In addition, loss of memory was an early symptom in four cases. Two patients had suicidal thoughts. Neurological symptoms were often also present during the early 'psychiatric' phase. Persistent and severe sensory complaints were noted as a symptom in 17 cases, including pain and abnormal sensations in hands, feet, face, mouth and lumbar region. ¹³ These are discussed more fully in the section on neurologists below.

6.10 Despite these neurological symptoms, many of the patients were initially thought to be suffering from a psychiatric, as opposed to neurological, disorder. The predominantly psychiatric symptomatology meant some patients were referred for psychological testing even after being seen by a neurologist. In most cases the diagnosis given was depression, and 19 cases were prescribed antidepressants, often initially by their GP. Organic disease ¹⁴ was suspected in a minority of cases with early cognitive impairment, ¹⁵ and with those displaying forgetfulness. In a small number of cases a psychotic illness ¹⁶ was suspected. Neuropsychological assessments carried out in ten cases recorded clear evidence of cognitive impairment, but the majority of these examinations were performed after the development of earlier neurological signs. Two cases had already demonstrated cognitive impairment, with one case showing forgetfulness as an initial symptom. ¹⁷

6.11 The Psychiatric Bulletin article noted that tests carried out during the psychiatric phase were invariably normal and thus 'almost always unhelpful' because they did not point to a neurological disease. ¹⁸ These tests included EEG and magnetic resonance imaging (MRI). The tests that had been performed before neurological referral detected no abnormalities. (These tests are discussed more fully at paragraphs 6.22-6.39.)

6.12 In conclusion, the article noted that the diagnosis of vCJD might not be possible in the early stages of the illness, because of the difficulty of distinguishing between psychiatrically determined neurological features and those symptoms due to an underlying organic disease. This was compounded by the fact that some patients showed transient improvement following treatment with antidepressants. The diagnosis of vCJD was often considered not possible until the occurrence of overt neurological signs. However, the article identified some symptoms that might aid the diagnosis of vCJD during the 'psychiatric' phase:

The identification of cognitive impairment in addition to the psychiatric symptoms may raise the possibility of an underlying organic disorder in some cases. Persistent painful limb or joint pain, dysaesthesia ¹⁹ or paraesthesia ²⁰ in combination with the psychiatric symptoms is unusual and may raise the suspicion of new variant CJD. Such symptoms include painful sensory disturbance in the hands and feet, in the face or mouth, or in discrete areas of the trunk. Some patients describe dysaesthesia in a similar distribution and some limb or joint pain. The persistence of these symptoms and their severity is distinct from the transient paraesthesia that may accompany anxiety and hyperventilation. Other suggestive neurological symptoms during the psychiatric phase include gait imbalance, visual disturbance, dysarthria, ²¹ dysgeusia ²² and involuntary movements, although it is understandable that these symptoms have in some cases been attributed to side effects of medication. ²³

6.13 The article noted that any delay in diagnosis was distressing to the relatives of patients but that the evidence suggested that the psychiatric community was referring cases of vCJD promptly to neurologists. ²⁴

Neurologists

6.14 In 1997, the CJDSU published an article describing the neurological features of the first 14 cases of vCJD and the tests used to provide a diagnosis. ²⁵ The description of the diagnostic tests is covered at paragraphs 6.22-6.39. Here, the clinical neurological features of vCJD of the first 14 cases are explored.

6.15 The article noted that although a minority of cases suffered from mild unsteadiness of gait from an early stage, clear neurological symptoms were not apparent before an average of 6¼ months after onset of illness, ranging from 4 to 24½ months. The first neurological symptom was generally ataxia, ²⁶ including cerebellar, limb or gait ataxia. The ataxias occurred in isolation and in combination with involuntary movements, pyramidal signs, ²⁷ limited reflexes or sensory signs. The remaining cases first developed either pyramidal signs (with or without problems with language) or involuntary movements, with unsteadiness of gait apparent within weeks. ²⁸

6.16 Usually, the symptoms progressed quite rapidly to include global cognitive impairment, involuntary movement, progressive immobility, unresponsiveness, mutism and urinary incontinence. In the days before death, the patients were akinetic mutes and three developed cortical blindness. On average, there was 6 months' lapse between developing unsteadiness and becoming bedridden (range 2½-12½ months). On average there was 1½ months between becoming bedridden and death (ranging from 1 week to 6 months). Two patients remained alive 6½ and 18 months respectively after becoming bedridden. ²⁹

6.17 For those with a long delay in the onset of neurological symptoms, these initial symptoms were prolonged with personality change or forgetfulness followed by sensory disturbance. ³⁰ Most cases developed primitive reflexes, cerebellar and pyramidal signs: all had persistent involuntary movements. Seven cases were noted to have upgaze paralysis, a condition which prevents a patient from looking upwards and which is an uncommon feature of CJD.

6.18 In oral evidence, Professor Martin Rossor of the National Hospital of Neurology and Neurosurgery, London, described the difficulties faced by clinicians when diagnosing vCJD. ³¹ Professor Rossor had established an inpatient and outpatient service specialising in early onset and unusual dementias. He also led the Dementia Research Group and held an MRC Special Project Grant specifically to study vCJD.

6.19 Professor Rossor commented upon the problems encountered in the diagnosis of CJD in young patients. He began by defining what is meant by 'early onset dementia':

Classically, early onset is below the age of 65, which has more to do with the common retirement age than any biological distinction. In general we would see people with dementia starting sometimes as young as their 20s, through to people in their 50s. We do, of course, see older people as well but that is the special area of interest. ³²

6.20 Professor Rossor then commented upon the problems of obtaining a clear diagnosis in cases of early onset dementia:

. . . We always try to give a name. And often, because we have to work with the tools that we have, one always tends to try to fit something into a category. In this area it is very difficult. I think two points. One is that I would think that approximately, and this is my first thought, perhaps 30 per cent of cases I see I may not be able to arrive at a clinical diagnosis. So one leaves it in very broad terms. Even when one can examine the brain by cerebral biopsy, which we do sometimes have to do, or can examine the brain after death at autopsy, one is sometimes still left without being able to make a diagnosis.

. . . If we take the group below the age of 65 taking the orthodox view of early onset. Approximately 50 - if you just allow me to think through this. Probably about 40 per cent are Alzheimer's disease . . .

Another large group are those we loosely refer to as the frontotemporal dementias. Those are characterised by the fact they have early behavioural change followed often by changes with language. That can create considerable diagnostic difficulties. That group consists of four different diseases that we tend to recognise, and they include a disorder called frontal lobe degeneration of the non-Alzheimer type. The second is Pick's disease. The third is referred to as the frontotemporal degeneration and motoneurone disease complex, and another type that we increasingly identify is that of frontotemporal degeneration with what are referred to as ubiquitin inclusions. There are other diseases that are very rare. Our ability to make a specific diagnosis is very limited unless we carry out a brain biopsy. That probably accounts for about 80 per cent of cases of early onset, although these figures are very broad. The remainder are a variety of disorders which will include CJD, will include vascular disease where there are multiple strokes due to a variety of causes, alcoholism and some other rare disorders. ³³

6.21 Professor Rossor also referred to problems in the early diagnosis of CJD in the young due to the initial presentation of cognitive impairment:

Cognitive impairment or dementia which just refers to a generality of cognitive impairment, not just memory lack, visuoperceptual problems, thinking, planning, is of course seen with many, many different causes and the list runs into hundreds of potential diseases. And many are relatively easily excluded right at the beginning, but the path to a differential diagnosis of an early onset unusual dementia can be a very long one. ³⁴