Elizabeth has a genetic form of Creutzfeldt-Jakob disease (CJD) and Colin’s wife was diagnosed with sporadic CJD in 2006. They explain how it affects their lives
Service de Psychiatrie, BP 27, Centre Hospitalier Général, F-91401 Orsay.
The new variant of Creutzfeldt-Jakob disease (nvCJD) was first described in the UK in 1996 (16). The nvCJD differs from sporadic, genetic and iatrogenic CJD. Creutzfeldt-Jakob disease is closely associated with an abnormal isoform PrPSc of a cell-surface glycoprotein, prion protein (14). Molecular analysis suggests that nvCJD is caused by the same prion strain as bovine spongiform encephalopathy (BSE) (4, 10). To the end of September 2000, there have been 82 cases of nvCJD in the UK. We report the second French case of nvCJD to our knowledge (5, 13).
This 36 year old woman was referred by a local general practitioner with a 6 month history of psychiatric symptoms of major depressive disorder. According to her family, the patient had suffered from personality change for several months before the onset of depression including apathy, emotional lability, infantile affect. There was no history of health problems. As she was admitted to the psychiatric department of our hospital in Paris suburbs, she presented a major depressive disorder. There were no specific psychiatric features allowing distinction from common depressive disorders, except a marked emotional lability. The patient’s condition progressed rapidly within the following days. She presented memory impairment and disorientation. Drug treatments, clomipramine (125 mg/day) and venlafaxine (200 mg/day), were used with no benefit. She presented subsequently transient delusions and auditory hallucinations, fleeting for some hours. The predominant delusional themes were somatic type and pregnancy. The delusions were concomitant with delusions of the onset of cognitive impairment. The patient tested negative for the P 14.3.3 protein in the CSF. Computed tomography scan of the brain did not show any relevant abnormality. The electroencephalogram showed non specific slow wave activity. The neurological symptoms developed 7 months after the onset of depressive symptoms including ataxia, myoclonus, excessive daytime drowsiness, headache. After the onset of neurological symptoms, the illness progressed rapidly over the next 2 months with cognitive impairment, particularly memory impairment, myoclonus, ataxia, incontinence of urine and progressive immobility leading to dependency. CSF tests were negative. She was referred to a neurology department where the diagnosis was confirmed by brain biopsy (detailed elsewhere). The patient died in a state of akinetic mutism.
The clinical features of our patient were consistent with previous descriptions of nvCJD, mainly those of the National CJD Surveillance Unit studies (17): early psychiatric symptoms, prolonged duration of illness (median: 14 months), earlier age at death, compared with sporadic CJD. Psychiatric symptoms occur in the clinical course in about a third of cases of sporadic CJD (3). In contrast, of the 35 cases that have died of nvCJD identified in the study by Will et al. (17), 34 suffered from early and prominent psychiatric symptoms, mainly depression and anxiety. In most of the patients, the first symptoms were psychiatric. Drug treatment was used in most cases, some patients had a transient improvement (18). The patient without psychiatric symptoms reported by the NCJDSU (17) was emotionally labile. Infantile affect and emotional lability, found in our patient, are frequently reported in other studies (1, 18). Schizophreniform disorders have been described during the clinical course, with auditory and visual hallucinations and paranoid delusions (17, 18). The insomnia and excessive daytime drowsiness our patient presented have been described in similar cases (18). Investigations are important to rule out alternative diagnoses. EEG records do not show periodic triphasic complexes as in sporadic CJD. The P 14.3.3 protein in the CSF is positive in half the cases of nvCJD (17). First neurological symptoms developed 6 months after the onset of psychiatric symptoms including ataxia, myoclonus and persistent painful sensory symptoms (17, 18). In most of the cases, MRI brain scans show bilateral pulvinar high signal (17), found subsequently in our patient and detailed elsewhere (13). The terminal stages are progressive cognitive impairment, helplessness and akinetic mutism.
The first symptoms of this patient were purely psychiatric and difficult to distinguish from common psychiatric disorders. Clinical surveillance of human prion disease is crucial in France, as in UK. The link with BSE has dramatically highlighted the need for neurological and neuropsychological precise investigations.