NR AMHF
AU Weber,T.; Tumani,H.; Holdorff,B.; Collinge,J.; Palmer,M.; Kretzschmar,H.A.; Felgenhauer,K.
TI Transmission of Creutzfeldt-Jakob disease by handling of dura mater
QU Lancet 1993 Jan 9; 341(8837): 123-4
KI Lancet. 1993 Mar 6;341(8845):641-2. PMID: 8094877
PT letter
VT
Sir,- Creutzfeldt-Jakob disease (CJD) can be transmitted iatrogenically by human pituitary growth hormone, corneal transplants, and dura mater grafts (1). Possible accidental transmission has been reported in only four people - a neurosurgeon (2), a pathologist (3), and two laboratory technicians (4,5). We have encountered an unusually rapid case of CJD probably acquired through handling of sheep and human dura mater. In May, 1992, a 55-year-old orthopaedic surgeon developed paraesthesia of the left arm. A few days later he had spatial disorientation, apraxia, and gait ataxia. In June he was admitted and a neurologist suspected CJD on the basis of the clinical signs, typical electroencephalogram (EEG) pattern, and history. An EEG in June revealed a typical pattern of periodic biphasic and triphasic sharp wave complexes. We saw the patient in July, 1992. He was awake and oriented, with dyscalculia, dysgraphia, disturbed vision, apraxia mainly of the left side, rigidity of wrists, spasticity of all muscles, myoclonus of the left arm, increased tendon reflexes, ataxia of limbs and trunk, and incoordination of left arm. Within 3 weeks he had impaired consciousness and attention, mildly impaired memory, and threatening visual hallucinations with restless turning. He had periodic states with movements of his head and eye-bulbs resembling tonic adversive seizures. During sleep these motor disturbances stopped. 2 1/2 months later the patient died.
This patient had worked with sheep and human dura mater from 1968 to 1972. He handled about 150 specimens of ovine origin and at least a dozen human preparations for research. Handling involved opening skulls with a band saw, removing dura, and testing them either fresh (usually), preserved, or lyophilised for mechanical qualities. These specimens were sent to a company that has sold dura mater preparations by which CJD was transmitted in six instances. No information was available from the company about a possible connection with this patient's disease and the earlier cases of transmitted CJD. Brain biopsy was consistent with diagnosis of CJD. Cerebrospinal fluid obtained in July showed neuron-specific enolase (NSE) at 82.0 ng/mL, compared with 16.7 ng/mL in serum of other cases (6). Proton magnetic resonance spectroscopy of parieto-occipital and temporal grey matter, parietal white matter, and thalamus revealed a 20-30% reduction of N-acetylaspartate, as described (7). DNA was genotyped with allele-specific oligonucleotides (8) and was homozygous for methionine at the polymorphic codon 129. Subsequent direct DNA sequencing for the PrP gene open-reading frame demonstrated normal sequence on both alleles, excluding known or novel pathogenic PrP mutations.
It is tempting to speculate that prions were transmitted to this patient from sheep or human dura mater through small lacerations of his skin, but the patient and his wife did not remember any significant injury during his four years of working with these samples. It cannot be excluded that this was a case of sporadic CJD although this assumption is unlikely in view of the clinical course which was similar to iatrogenic CJD transmitted by peripheral inoculation, such as with human pituitary growth hormone or gonadotropin or to kuru (1). Iatrogenic cases resulting from intracerebral inoculation with the transmissible agent, for instance following dura mater grafts (2-5), present with a dementing picture, as is usual in sporadic CJD, rather than with ataxia as in this case.
We thank Tracy Campbell and Sukhvir Mahal, Prion Disease Group, St Mary's Hospital, for technical assistance.
REFERENCES
1. Brown P, Preece MA, Will RG. "Friendly fire" in medicine: hormones, homografts, and Creutzfeldt-Jakob disease. Lancet 1992; 340: 24-27.
2. Schoene WC, Masters CL, Gibbs CJ Jr, et al. Transmissible spongiform encephalopathy (Creutzfeldt-Jakob Disease): atypical clinical and pathological findings. Arch Neurol 1981; 38: 473-77.
3. Gorman DG, Benson DF, Vogel DG, Vinters HV. Creutzfeldt-Jakob disease in a pathologist. Neurology 1992; 42: 463.
4. Miller DC. Creutzfeldt-Jakob disease in histopathology technicians. N Engl J Med 1988; 318: 853-54.
5. Sitwell L, Lach B, Atack E, Atack D, Izukawa D. Creutzfeldt-Jakob disease in histopathology technicians. N Engl J Med 1988; 318: 854.
6. Wakayama Y, Shibuya S, Kawase J, Sagawa F, Hashizume Y. High neuron-specific enolase level of cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease. Klin Wochenschr 1987; 65: 798-801.
7. Bruhn H, Weber T, Thorwirth V, Frahm J. In-vivo monitoring of neuronal loss in Creutzfeldt-Jakob disease by proton magnetic resonance spectroscopy. Lancet 1991; 337: 1610-11.
8. Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 1991; 337: 1444-42.
IN
Im Mai 1992 entwickelte ein 55 Jahre alter orthopädischer Chirurg eine Erschlaffungslähmung im linken Arm. Wenige Tage später bekam er Probleme mit der räumlichen Orientierung, eine Apraxie und Gangstörungen. Im Juni 1992 wurde er ins Krankenhaus aufgenommen und ein Neurologe diagnostizierte aufgrund der Symptome und eines typischen EEG-Musters mit scharfen periodischen bi- und triphasischen Wellenkomplexen die Creutzfeldt-Jakob-Krankheit. Die Autoren sahen den Patienten im Juli 1992. Er war wach und orientiert, litt aber unter Sehstörungen, Apraxie vorwiegend auf der linken Körperhälfte, Ataxie (Störung der Koordination von Bewegungen) in Rumpf und Gliedern, unbeweglichen Handgelenken, Spasmen in allen Muskeln, einem Myoklonus und Koordinationsproblemen im linken Arm, sowie verstärkten Sehnenreflexen. Binnen 3 Wochen reduzierten sich Bewustsein, Aufmerksamkeit und Gedächtnis und er bekam Halluzinationen. Sein Kopf und seine Augen bewegten sich periodisch und 2,5 Monate danach starb der Mann. Die Diagnose Creutzfeldt-Jakob-Krankheit wurde histoathologisch bestätigt. Die Rückenmarksflüssigkeit enthielt im Juli 1992 82 ng/ml neuronenspezifische Enolase. Eine Protonenmagnetresonanzspektroskopie der grauen Substanz in Hinterkopfgroßhirnrinde (parieto-occipital) und Schläfenlappen, der äußeren weißen Substanz und des Thalamus zeigte eine um 20-30% reduzierte N-Acetylaspartat-Konzentration. Der Patient hatte am Codon 129 Methionin in beiden Allelen und keine Mutation in der kodierenden Region.
Von 1968 bis 1972 hatte der Patient etwa 150 Schafen und mindestens einem Dutzend Menschen die dura mater entnommen und diese frisch, konserviert oder lyophylisiert getestet. Diese dura mater Präparationen sollen Forschungszwecken gedient haben, zumindest einige gingen aber an Braun Melsungen.
MH Case Report; Creutzfeldt-Jakob Syndrome/genetics/*transmission; Dura Mater/*microbiology; Human; *Iatrogenic Disease; Male; Middle Age
SP englisch
PO England
OR Prion-Krankheiten 8