A prospective radiologic and neurologic follow-up study of 61 HIV-1 -infected subjects: early beginning and slow progression of brain atrophy

The course of the organic brain disease caused by human immunodeficency virus (HIV-1) was evaluated in a follow-up study. The primary material included 200 consecutive HIV-1 infected persons. Sixty-one subjects, in whom other brain-affecting factors were excluded, consented to the follow-up. They underwent 278 radiologic examinations: computed tomography, magnetic resonance imaging, or a combination of both (mean 4.6 examinations/subject). Clinical neurologic status and, in 40 subjects, cognitive performance were repeatedly evaluated. Sixteen subjects were followed up until death and 11 of them were autopsied. Median follow-up time was 27 mo (range 2.5–66 mo). The most common radiologic finding was atrophy, found in 19 subjects at study entry and developing in 10 subjects during the study. Twenty-four subjects (39%) showed the development and/or progression of atrophy. Atrophic changes progressed most rapidly in acquired immunodeficiency syndrome (AIDS), but mild developing/progressive atrophy was found even in 33% of asymptomatic or neurologically intact subjects. Cognitive and radiologic worsening were simultaneous in 6/7 subjects with declining neuropsychologic test performance. Signal intensity changes including HIV-1 leukoencephalopathy appeared in AIDS patients with clear cognitive decline.     

Comparative typing of Campylobacter jejuni by heat-stable serotyping and PCR-based restriction fragment length polymorphism analysis

Campylobacter jejuni has become the most common bacterial cause of human gastroenteritis worldwide. Rapid, discriminatory typing methods are required to identify potential clusters of infections. The major disadvantage of the well-evaluated and widely used Penner heat-stable serotyping method is the high level of nontypeability. The correlation of the types determined by the Penner heat-stable serotyping method and PCR-based restriction fragment length polymorphism (RFLP) analysis of the lipooligosaccharide (LOS) biosynthesis genes of C. jejuni was studied with 149 C. jejuni strains. Of these strains, 79 were patient strains belonging to 25 Penner serotypes, 60 were nontypeable patient strains, and 10 were reference strains. A 9.6-kb DNA fragment of the LOS gene cluster was amplified and digested with the restriction enzymes HhaI and DdeI. Altogether, 39 different RFLP types (including 30 HhaI profiles and 32 DdeI profiles) were identified. Type Hh1Dd1 was the most common type, with 36% of the strains and strains of 12 serotypes being of this type. A high level of discrimination was obtained, and a correlation between the Penner serotypes and the PCR-RFLP types could be seen. Also, variation in the LOS biosynthesis genes within a single Penner serotype was found. Although the PCR-RFLP method may not be sufficient to compensate for Penner serotyping, it can give valuable information about nontypeable strains and further characterize strains of common serotypes.     

Erythropoietin and renin substrate in cerebellar haemangioblastoma

We examined eight cerebellar haemangioblastoma tumours from eight patients, aged 16-63 years, 5 females and 3 males. Preoperative haemoglobin values exceeded 180 g/l in four patients, and 150 g/l in four. All high Hb values were normalized upon surgical removal of the tumours. All tumours contained scattered cells which stained positively with antisera against pure human urinary erythropoietin and plasma renin substrate. We conclude that cerebellar haemangioblastomas produce immunoreactive erythropoietin, which shares common antigenic determinants with renin substrate.     

Neuropathological Diagnostic Criteria for Creutzfeldt-Jakob Disease (CJD) and Other Human Spongiform Encephalopathies (Prion Diseases)

Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: CJD - sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (PrP) immuno-reactivity (plaque and/or diffuse synaptic and/or patchy/perivacuolar types). Gerstmann-Sträussler-Scheinker disease (GSS) (in family with dominantly inherited progressive ataxia and/or dementia): encephalo(myelo)pathy with multicentric PrP plaques. Familial fatal insomnia (FFI) (in member of a family with PRNP178 mutation): thalamic degeneration, variable spongiform change in cerebrum. Kuru (in the Fore population). Without PrP data, the crucial feature is the spongiform change accompanied by neuronal loss and gliosis. This spongiform change is characterised by diffuse or focally clustered small round or oval vacuoles in the neuropil of the deep cortical layers, cerebellar cortex or subcortical grey matter, which might become confluent. Spongiform change should not be confused with non-specific spon-giosis. This includes status spongiosus (“spongiform state”), comprising irregular cavities in gliotic neuropil following extensive neuronal loss (including also lesions of “burnt-out” CJD), “spongy” changes in brain oedema and metabolic encephalopathies, and artefacts such as superficial cortical, perineuronal, or perivascular vacuolation; focal changes indistinguishable from spongiform change may occur in some cases of Alzheimer's and diffuse Lewy body diseases. Very rare cases might not be diagnosed by these criteria. Then confirmation must be sought by additional techniques such as PrP immunoblotting, preparations for electron microscopic examination of scrapie associated fibrils (SAF), molecular biologic studies, or experimental transmission.     

Variant Alzheimer's disease with spastic paraparesis: clinical characterization

OBJECTIVE: To present the clinical, neuroimaging, and electrophysiologic characteristics of a variant AD phenotype. BACKGROUND: The authors have identified a large Finnish kindred with presenile dementia and spastic paraparesis due to deletion of exon 9 of presenilin 1. Neuropathologic analysis showed unusual cortical "cotton wool" plaques, immunoreactive for the beta-amyloid peptide but lacking congophilic cores. PATIENTS AND METHODS: Twenty-two affected individuals (16 men and 6 women) were identified in four successive generations. All surviving five patients were examined and subjected to molecular genetic analysis. In addition, the neurologic records of nine deceased patients were evaluated. Electrophysiologic investigations were available in eight cases. CT or MRI of the head had been performed on 11 patients and PET was performed on three patients. RESULT: The mean age at onset (+/-SD) was 50.9 +/- 5.2 years (range 40 to 61 years). Memory impairment was present in all patients. Memory impairment appeared simultaneously with or was preceded by walking difficulty due to spasticity of the lower extremities (10/14). Impaired fine coordination of hands (9/14) and dysarthria (6/14) in some patients suggested cerebellar involvement. EEG showed intermittent generalized delta-theta activity. Head MRI showed temporal and hippocampal atrophy; PET showed bilateral temporo-parietal hypometabolism. CONCLUSION: Spastic paraparesis or brisk stretch reflexes of lower extremities or clumsiness of hands combined with dementia suggests this variant of AD.     

Diagnostic tools in respiratory tract infections: use and comparison with Finnish guidelines

The objectives of this prospective epidemiological study were to describe the diagnosis and treatment of respiratory tract infections by Finnish general practitioners and to compare current practice with national evidence-based guidelines. All patients (n = 4386) seeking primary care for a respiratory tract infection for the first time in 30 health centres during 1 week in November 1998 participated in the study. The main outcome measures were the amounts and types of diagnostic tests used and antimicrobials prescribed. Tympanometry was used in 1% of patients with acute otitis media. Ultrasonography, sinus radiography or both were used in 80% of cases of sinusitis and antigen detection or culture for Streptococci in 57% of throat infections. In acute bronchitis, a chest radiograph was taken in 5% of cases and the CRP level determined in 8%. The corresponding figures for pneumonia were 49% and 39%. In pneumonia and throat infection, diagnostic testing was statistically significantly associated with the use of antimicrobials, but not in otitis, sinusitis or acute bronchitis. Diagnostic tests were underused in respiratory tract infections compared to evidence-based recommendations.     

Fatal measles encephalopathy with retinopathy during cytotoxic chemotherapy

A 14-year-old boy receiving post-operative cytotoxic chemotherapy for a testicular rhabdomyosarcoma developed a fatal encephalopathy associated with retinal changes 2 months after an episode of acute measles. Post-mortem histological examination showed intranuclear inclusion bodies in the neurons and glial cells, but inflammatory cell infiltrations were absent. Electron-microscopic and immunofluorescent studies revealed intracellular masses of paramyxovirus nucleocapsid-like structures, which had the morphological and antigenic properties of measles virus. Recent reports have emphasized the possibility of occurrence of a similar encephalopathy in treated childhood leukaemia. It is evident, however, that this potentially fatal complication must be borne in mind when measles is contracted during any form of cytotoxic treatment or immunosuppression. Retinal changes may be of value for the diagnosis during life. We propose the designation “measles encephalopathy during immunosuppression” (MEI) for this condition.