Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK.

Between 1970 and 2003, seven cases of human dura mater-associated Creutzfeldt-Jakob disease (CJD) were identified in the UK. Furthermore, we identified a case of CJD in a porcine dura graft recipient. The mean incubation period of the human dura mater cases was 93 (range 45-177) months. The clinico-pathological features of the cases are described and compared with cases previously reported in the world literature.

A case-control study of sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of clustering.

BACKGROUND: The authors investigated whether cases of sporadic Creutzfeldt-Jakob disease (CJD) had lived closer to one another at some time in life than individuals without sporadic CJD. Such a phenomenon would be compatible with some cases resulting from transmission. METHODS: UK sporadic CJD cases occurring from 1990 to 1998 were identified. Age-, sex- and hospital-matched controls were recruited. Lifetime residential histories were obtained by interview, usually with a proxy respondent. With use of Monte Carlo simulation, the residential proximity of cases during various time periods was compared with that expected in the absence of any clustering, using the information collected on the controls. RESULTS: Two hundred twenty sporadic CJD disease cases and 220 controls were included. Cases lived closer together than might be expected in the absence of any disease-clustering mechanism. This evidence became stronger as the critical period during which residential proximity was required to have occurred extended further into the past. CONCLUSIONS: These findings are consistent with some sporadic Creutzfeldt-Jakob disease (CJD) cases resulting from exposure to a common external factor. The rarity of sporadic CJD suggests that repeated point-source outbreaks of infection are more likely to explain our observations than direct case-to-case transmission. Identifying sources of such outbreaks many years after the event will be extremely difficult.

Profile of cognitive progression in early Huntington's disease.

OBJECTIVE: To examine the pattern of cognitive decline in early Huntington's disease (HD). METHODS: The authors studied 61 patients with mild to moderate HD who had at least three annual neuropsychological assessments using the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease short battery. A subset of 34 patients had additional neuropsychological tests, and another subset of 21 patients was assessed annually on the Cambridge Neuropsychological Test Automated Battery. Neuropsychological measures that changed significantly over time were submitted to a multiple analysis of covariance to explore associations with demographic and neurologic indices. RESULTS: Patients showed a progressive impairment in attention, executive function, and immediate memory, with timed tests of psychomotor skill being particularly sensitive to decline. In contrast, general cognition, semantic memory, and delayed recall memory were relatively unaffected. CONCLUSION: The profile of cognitive performance shows selective and progressive dysfunction of attention and executive function in patients with mild to moderate HD, consistent with frontostriatal pathology at this stage of disease.

Shunting for normal pressure hydrocephalus (NPH).

BACKGROUND: Since the condition was first described in 1965, the syndrome of normal pressure hydrocephalus (NPH) has conventionally been managed by placement of a cerebrospinal fluid (CSF) shunt. OBJECTIVES: To determine the effectiveness of shunting procedures in promoting stability or improvement in the neurological symptoms and signs of NPH. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 June 2001 using the terms 'shunt*' and 'normal pressure hydrocephalus'. SELECTION CRITERIA: Studies included for analysis were those involving the placement of a CSF shunt for the treatment of NPH as part of a randomized controlled trial. DATA COLLECTION AND ANALYSIS: No data matching the selection criteria were found. MAIN RESULTS: No randomized controlled trials of shunt placement versus no shunt were found. REVIEWER'S CONCLUSIONS: There is no evidence to indicate whether placement of a shunt is effective in the management of NPH.

A neurological evaluation of adult phenylketonuria in Northern Ireland.

To investigate the extent of neurological disease in adults with phenylketonuria and also their requirement for specialist medical services, we assessed 27 such patients in Northern Ireland. Most had been diagnosed early and with one exception had dietary relaxation by early adolescence. Abnormal neurological features were elicited in 21/27 cases with significant delay of visual evoked potentials and somatosensory evoked potentials occurring in 63.6 and 13.6% of cases respectively. Periventricular white matter abnormalities were observed in 5/12 patients undergoing magnetic resonance imaging, whilst phenylalanine levels were high (mean 1,226 micromol/l). These data accord with the observation that even early treated patients with phenylketonuria can have significant neurological morbidity in adulthood, although the correlation with current or recent dietary control is unclear and requires further study.

Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96.

OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN: Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING: England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS: During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.

Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene.

Creutzfeldt-Jakob disease (CJD) is a transmissible neurodegenerative disorder characterized by the accumulation of aggregates of a cellular protein, PrP, in the brain. In both human and animals, genetic alterations to the gene encoding PrP (PRNP in human) modulate susceptibility to CJD. The recent epidemic of bovine spongi-form encephalopathy in the UK has raised the possibility of transmission from animal produce to humans. To provide a baseline against which to assess possible risk factors, we have determined the frequencies of predisposing mutations and allelic variants in PRNP and their relative contributions to disease. Systematic PRNP genotype analysis was performed on suspected CJD cases referred to the National Surveillance Unit in the UK over the period 1990-1993. Inspection of 120 candidate cases revealed 67 patients with definite and probable CJD, based on clinical and neuropathological criteria. No PRNP mutations were detected in any of the remaining 53 patients assessed as "non-CJD". A disease-associated mutation in the PRNP gene was identified in nine (13.4%) definite and probable cases of CJD, a reliable estimate of the incidence of PRNP-related inherited CJD based on a prospective epidemiological series. Within the group of sporadic CJD patients (lacking PRNP mutations), we confirmed that the genotype distribution with respect to the common methionine/valine (Met/Val) polymorphism at codon 129 within PRNP was significantly different from the normal Caucasian population. The incidence of Met homozygosity at this site was more than doubled and correlated with increased susceptibility to the development of sporadic CJD. Unlike other recent studies, Val homozygosity was also confirmed to be a significant risk factor in sporadic CJD, with the relative risks for the three genotypes Met/Met: Val/Val:Met/Val being 11:4:1.

Neuropsychological performance, disease severity, and depression in progressive supranuclear palsy.

To investigate the relationship between disease severity, cognitive impairment and depression in progressive supranuclear palsy (PSP) we studied a group of 25 patients who fulfilled strict research criteria and 25 matched controls. Disease severity was judged from the duration of symptoms, level of physical disability using the Columbia Rating Scale (CRS), and the degree of eye movement abnormality. The neuropsychological battery was designed to assess attention and executive function, visual and auditory perception, semantic memory and language production. Although the PSP group were significantly impaired on almost all of these measures, the most profound deficits were on tests of sustained and divided attention. There was no correlation between cognitive impairment and either disease duration or scores on the CRS, but performance on tests of attention correlated significantly with the degree of ocular motor impairment. Depression was found to be common in PSP but did not correlate with any other parameters. It is concluded that the cognitive deficit in PSP is widespread and independent of depression. The association between the severity of eye movement disorder and deficits in sustained and divided attention leads us to postulate that pathology involving the midbrain periaqueductal region may be critical for breakdown in these fundamental processes.

Progressive supranuclear palsy presenting with dynamic aphasia.

BACKGROUND: Progressive supranuclear palsy (PSP) is an akinetic-rigid syndrome of unknown aetiology which usually presents with a combination of unsteadiness, bradykinesia, and disordered eye movement. Speech often becomes dysarthric but language disorders are not well recognised. METHODS: Three patients with PSP (pathologically confirmed in two) are reported in which the presenting symptoms were those of difficulty with language output. RESULTS: Neuropsychological testing showed considerable impairment on a range of single word tasks which require active initiation and search strategies (letter and category fluency, sentence completion), and on tests of narrative language production. By contrast, naming from pictures and from verbal descriptions, and word and sentence comprehension were largely intact. The degree of semantic memory impairment was also slight. CONCLUSIONS: Relatively selective involvement of cognitive processes critical for planning and initiating language output may occur in some patients with PSP. This presentation resembles the phenomenon of "verbal adynamia" or "dynamic aphasia" seen in patients with frontal lobe damage. Although definite cortical changes were present at postmortem examination, it is likely that the neuropsychological deficits reflect functional frontal deafferentation secondary to interruption of frontostriatal feedback loops.

Neuralgic amyotrophy and infectious mononucleosis: a case report.

A 27 year old man developed neuralgic amyotrophy of the right upper limb 5 weeks after an acute febrile illness which was proven serologically to be caused by Ebstein-Barr virus. The weakness developed in a limb that had been used to perform heavy manual labour. A parallel with a similar phenomenon described in association with paralytic poliomyelitis is noted.-

Neuropathological phenotype and 'prion protein' genotype correlation in sporadic Creutzfeldt-Jakob disease.

A systematic study of 'prion protein' genotype in cases of sporadic Creutzfeldt-Jakob disease showing amyloid plaques staining with anti-prion protein antibody has been performed. This revealed a relative excess of cases with valine at position 129 of the gene's open reading frame. The observation emphasises the importance of this site of common polymorphism in influencing the neuropathological phenotype in human spongiform encephalopathy.

Creutzfeldt-Jakob disease and lyophilised dura mater grafts: report of two cases.

Two further cases of Creutzfeldt-Jakob disease (CJD) in association with cadaveric dura mater grafts are described. The clinical features of all such reported cases resemble more closely those of sporadic CJD, in contrast with kuru and the cases of CJD which have arisen after therapy with human pituitary-derived growth hormone. This observation may reflect the route of inoculation of the agent.