Volume 8: Variant CJD
3. Establishment of the CJD Surveillance Unit
Review of the CJDSU by the Allen Committee
4 April 1991
1 July 1991
22 February 1993
19 July 1995

3.11 The work of the CJDSU was reviewed by the MRC Allen Committee, chaired by Professor Ingrid Allen, which met four times between 1991 and 1995. This Committee was established on the basis of concerns raised by Professor Allen at a meeting of the MRC Coordinating Committee for Research on Spongiform Encephalopathies in Man (The Murray Committee; see vol. 2: Science) in October 1990. She considered that the design of Dr Will's study could mean that atypical features of dementia, like those exhibited by patients developing CJD as a result of treatment with human growth hormone, might fall outside the study. A Clinical Subcommittee was therefore established to coordinate and facilitate studies relating to the epidemiological monitoring and neuropathological definition of human SEs, to monitor patients at risk of iatrogenic infection and to apply new methodologies and technologies to refine the definition and improve diagnosis of SEs. ¹ The Allen Committee had powers to co-opt relevant experts when necessary. Dr Will was a co-opted member of the group.

4 April 1991

3.12 At their first meeting on 4 April 1991, Dr Will presented a paper on the CJD surveillance project at the CJDSU. This covered the objectives and the criteria for referral of 'suspected CJD' cases. It was agreed that the clinical criteria for referral should be sufficiently broad-based so that atypical cases would not be missed. ² Classification would be based on the neuropathological findings obtained post-mortem. The criteria adopted by Dr Will were:

• Definite CJD - neuropathologically confirmed spongiform encephalopathy in a case of progressive dementia with at least one of the following features:
  
  
  1. myoclonus; ³
  2. cortical blindness;
  3. pyramidal, cerebellar or extrapyramidal signs;
  4. akinetic mutism; ⁴ or
  5. characteristic EEG. ⁵
• Probable CJD - neuropathologically unconfirmed cases with at least two of the features mentioned above and the characteristic EEG.
• Possible CJD - progressive dementia plus three of the above clinical features but either an uncharacteristic EEG or no EEG recording.

All 'possible CJD' cases were excluded from analysis (but not from surveillance) in Dr Will's study and in the studies that Professor Matthews had carried out between 1970 and 1985. ⁶

3.13 The Subcommittee did not identify any compelling clinical reason to modify the clinical criteria for referral, which were essentially the same as in the Matthews study. ⁷ Indeed, it was considered advantageous to be able to use the Matthews study as a baseline for the current study. However, it was recognised that the criteria might need to change as scientific developments dictated.

3.14 The biochemical aspects of CJD were also discussed, including the prion protein gene mutations that had been linked with familial CJD. The CJDSU were collaborating with The Prion Disease Group, St Mary's Hospital, London, who undertook the screening of patients for familial mutations. ⁸

3.15 It was also agreed that the biochemical methods for detecting abnormal forms or distributions of prion protein were not yet sufficiently well developed to be used in the diagnosis or classification of CJD by the CJDSU. ⁹ The Committee members agreed that they should review the methods for the 'potential molecular or histochemical definition of CJD' annually. ¹⁰

1 July 1991

3.16 The second meeting of the Allen Committee took place on 1 July 1991 as a joint meeting with the MRC Murray Committee. ¹¹ Dr Will updated the members on the progress made in the surveillance of CJD. Presentations were also given by Dr John , Dr John Collinge and Dr Mark Palmer (St Mary's Hospital, London) on the genetics of human TSEs, and by Dr Gareth Roberts (St Mary's Hospital, London) on biochemical diagnosis. Although much progress had been made in the area of molecular genetics and immunocytochemical techniques, those present at the meeting 'reaffirmed their view that clinical neuropathology remained the best anchor point for diagnosis'. ¹²

22 February 1993

3.17 The third meeting of the Committee took place on 22 February 1993. ¹³ It had been called in response to Dr Will's concerns about the ethical problems arising from the identification of genetic mutations in individuals with sporadic CJD. ¹⁴ Standard procedures were agreed. Prior consent from the GP/clinician of the patient and the patient's closest relative should be obtained before the genetic analysis of blood samples. The relative should also be asked whether they would like to know the results of the test and any feedback requested should be given by the clinician/GP.

3.18 By the time of this meeting, even more progress had been made in the biochemical detection of prion protein (PrP) and so the Allen Committee decided to organise a workshop to achieve a consensus on the techniques used, in an attempt to coordinate the work in this area, including that of the CJDSU. ¹⁵ The workshop took place on 23 April 1993 during which all the techniques were discussed and it was then agreed that the next step was to run a multi-centre study to compare and optimise the methods for detection of PrP. ¹⁶

19 July 1995

3.19 A report of the multi-centre study was presented to the Allen Committee on 19 July 1995, ¹⁷ and although final results had not been published, it was felt that the study had been extremely successful. ¹⁸ The results from the second and third CJDSU reports, along with the preliminary data from the draft of the fourth report, were discussed. The questionnaire used to ascertain putative risk factors for CJD in the case-control study was also discussed. The introduction of a supplementary questionnaire aimed at investigating more fully possible links to diet or occupational exposure was suggested. The Allen Committee supported a proposal that the CJDSU undertake genetic analysis of CJD cases in-house rather than having to rely on their London colleagues, and recommended that the Health Departments ensured that the CJDSU was 'appropriately' resourced.