Jakob-Creutzfeldt disease.

Accessible online at: www.karger.com/ene Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. It is characterised pathologically by neuronal loss, spongy changes in the grey matter and an astrocytosis, and clinically by rapidly progressing dementia, pyramidal and extrapyramidal disease with myoclonus and triphasic discharges in the electroencephalogram. This dreaded fatal illness remained mysterious in its cause until Pruisner’s exciting discovery of proteinaceous infectious particles, which could replicate themselves, though they had no nucleic acid [1]. They became known as prion proteins. Pruisner justly received the Nobel Prize in 1997. Historically, Westphal [2] had introduced the term ‘spastic pseudosclerosis’ in 1883, in patients with disseminated sclerosis. It was for a time thought to be a variety of Wilson’s disease, but Wilson rightly objected. It was then confused with CJD when in 1921, Alfons Jakob described 4 cases of: ‘spastic pseudo-sclerosis, disseminated encephalomyelopathy’ [3]. He acknowledged earlier work, including Creutzfeldt’s case [4]. Jakob published a fourth case in the same year, ‘resembling pseudosclerosis.’ His fifth case appears in his 1923 book The Extrapyramidal Diseases [5]. He classed them all as ‘spastic pseudosclerosis’. Creutzfeldt confirmed that Jakob’s 3 cases were identical, and included them [4, 6]. In 1913, while working at Alzheimer’s clinic, Creutzfeldt studied a ‘new and unusual type of neurological disease’ in a 22-year-old woman who had developed an ataxic gait at the age of 16. Her mother died of unknown cause at the age of 56, and 2 siblings were mentally defective. She had spastic pyramidal signs, tremors and became ataxic and demented. She developed a symmetrical rash affecting her face, later also both hands, groin and both feet. While on a dermatology ward, she had a ‘hysterical seizure’ with arc de cercle. All of her symptoms, including the gait disorder improved. One year later, her gait deteriorated. She refused to eat or wash, and showed agitated paranoid behaviour and inappropriate laughter. Temperature was 38.9°C; she was disorientated with staccato speech. She had myoclonic limb jerks, intention tremor, nystagmus, increased tone, brisk reflexes, hyperaesthesia and hyperalgesia. Over 3 months, she deteriorated and died in status epilepticus with tonic seizures, some with Jacksonian march, and myoclonus. Creutzfeldt’s detailed pathology does not mention spongiform change or plaques (a hallmark of variant CJD). The brain showed moderate atrophy, patchy neuronal loss, gliosis and degeneration of both corticospinal tracts. The pathology, familial mental retardation, her remitting course and rash make improbable either ‘variant’ or sporadic CJD. Jakob’s third patient was a 42-year-old man with vertigo, and later weakness of his legs, dysarthria, diplopia, ataxia and dementia. He became stuporose 9 months after the onset and died. Like Creutzfeldt, Jakob found microscopical diffuse abnormalities but no record was made of neuronal vacuolation or spongiform change. Creutzfeldt’s slides unfortunately disappeared during World War II [7, 8]. Jakob was to examine 2 further cases. The first in the 44-year-old man Paul Bacher. His maternal grandmother and 8 of her siblings had died of unexplained cerebral disease, as eventually did his sister. Paul Bacher’s autopsy, and that of the sister, and 2 of his children showed the spongiform changes, typical of CJD. These observations