William C. Halliday

Beware of connective tissue proteins: assignment and implications of collagen absorptions in infrared spectra of human tissues

Infrared spectra of human central nervous system tissue and human breast carcinoma are presented. The spectra are discussed in terms of the composition of the tissues. It is shown that differences between spectra of white and grey matter can be rationalised on the basis of differences in lipid content. Spectra of the choroid plexus and arachnoid villus of the meninges show a series of absorptions not observed in other CNS tissue. These absorptions are discussed in terms of the connective tissue content of the samples. We demonstrate that the presence of collagen results in the appearance of a series of characteristic absorptions which may be mis-assigned as DNA phosphate absorptions. The implications of the presence of collagen in tissues for the diagnosis of disease states by IR spectroscopic methods, with particular reference to cancer, is discussed.

AIDS- and non-AIDS-related PML association with distinct p53 polymorphism.

Article abstract A population-based analysis of progressive multifocal leukoencephalopathy (PML) showed PML frequencies of 5.1% among patients with AIDS and 0.07% among patients with hematologic malignancies, but similar clinical features of PML in both groups. Sequencing of the p53 gene, exon 4, showed heterozygosity (Arg-Pro) at codon 72 in five of six PML patients. These findings indicate that frequencies of non–AIDS- and AIDS-related PML differ markedly but p53 polymorphisms may influence the occurrence of PML in both groups.

Infrared Spectroscopic Characterization of Alzheimer Plaques

Neuritic plaques in the brains of victims of Alzheimers disease are primarily composed of a 42 amino acid polypeptide, the β-amyloid peptide (βA4), the neurotoxicity of which is related to its aggregation. Fourier transform infrared spectroscopy has been used to study the conformational properties of two synthetic analogues of βA4 peptides known to be involved in the formation of the neuritic plaques formed in patients with Alzheimers disease and the influence of a single, naturally occurring point mutation upon the tendency of the peptide to aggregate. Peptides from both “normal” Alzheimers and the more severe Dutch variant of the disease were found to form aggregated antiparallel strands. However, the replacement of a single, negatively charged amino acid (glutamic acid) with an uncharged amino acid (glutamine) in the Dutch-type peptide results in significant differences in the strength and stability of these aggregates and the microenvironment of a number of amino acids. The differences in the strength and the stability of the aggregates are attributed to the presence of varying (small) proportions of the classical secondary structures and differences in net charge. Environmental (solvent) effects were shown to significantly affect the strength of the inter-molecular hydrogen bonding in the aggregates, solvent systems mimicking the membrane/water interface resulting in more strongly hydrogen bonded aggregates. Infrared spectra of material from autopsied human Alzheimers brains show spectral features indicative of the formation of similar aggregates, which may be related to plaque formation. This observation suggests that IR spectroscopic methods may in the future be useful in the diagnosis and monitoring of Alzheimers disease.

Neuropathological changes in chronic adult hydrocephalus: cortical biopsies and autopsy findings.

BACKGROUNDnThe cortical changes resulting from chronic hydrocephalus in adults are not well defined.nnnMETHODSnRetrospective analysis of twenty-one patients (age 64-88 years) with a clinical diagnosis of normal pressure hydrocephalus who underwent cortical biopsy at the time of intracranial pressure monitoring or shunt insertion, and eight patients who were biopsied but not shunted. Eleven brains (age 26-92 years), seven from patients who could be considered to have normal pressure hydrocephalus, were also examined following autopsy. Age- and sex-matched control brains with small ventricles and no history of dementia were compared to the hydrocephalic brains. Senile plaques and neurofibrillary tangles were assessed semiquantitatively and a non-parametric statistical analysis was employed.nnnRESULTSnFive biopsies exhibited both senile plaques and rare neurofibrillary tangles, while two had only neurofibrillary tangles. Neurofibrillary tangles were more prevalent in hydrocephalic brains than in controls. There was no difference in the prevalence of senile plaques between the two groups. Grumose bodies in the substantia nigra were identified in five autopsy brains, a prevalence higher than in control brains.nnnCONCLUSIONSnThese pathological features are not specific for hydrocephalus; however, they suggest that long-standing ventriculomegaly is associated with degenerative brain changes in sites beyond the periventricular white matter. The presence of senile plaques in cortical biopsies from hydrocephalic patients does not appear to be a contraindication to shunting; however a prospective study in patients undergoing intracranial pressure monitoring would better address the issue.

Infrared spectroscopic characterisation of multiple sclerosis plaques in the human central nervous system

Fourier transform infrared spectroscopy has been used for the characterisation of white matter, grey matter and multiple sclerosis plaques from human central nervous system tissue. We demonstrate significant differences in the infrared spectra of the three types of tissue, which show that an infrared spectroscopic discrimination of multiple sclerosis plaques from healthy brain tissue is possible in principle. The spectral changes reveal pronounced lipid loss in plaques, consistent with the demyelinating nature of the disease. The chronic plaques studied here can also be distinguished from other non-myelinated areas of the brain, based on differences in water content.

Neurological manifestations of West Nile virus infection.

BACKGROUNDnOver the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada.nnnMETHODSnPatients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented.nnnRESULTSnIn August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised.nnnCONCLUSIONSnThe most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.

Neural network classification of infrared spectra of control and Alzheimer's diseased tissue.

Artificial neural network classification methods were applied to infrared spectra of histopathologically confirmed Alzheimers diseased and control brain tissue. Principal component analysis was used as a preprocessing technique for some of these artificial neural networks while others were trained using the original spectra. The leave-one-out method was used for cross-validation and linear discriminant analysis was used as a performance benchmark. In the cases where principal components were used, the artificial neural networks consistently outperformed their linear discriminant counterparts; 100% versus 98% correct classifications, respectively, for the two class problem, and 90% versus 81% for a more complex five class problem. Using the original spectra, only one of the three selected artificial neural network architectures (a variation of the back-propagation algorithm using fuzzy encoding) produced results comparable to the best corresponding principal component cases: 98% and 85% correct classifications for the two and five class problems, respectively.

The fetal cerebellar vermis: assessment for abnormal development by ultrasonography and magnetic resonance imaging.

Fetal magnetic resonance provides a new tool in the imaging of the posterior fossa and is proving useful in cases that are difficult to assess sonographically by allowing further assessment of the fourth ventricle, cisterna magna, and vermian growth and development. We describe various criteria with which to evaluate vermian growth, including vermian biometry and the relationship between the superior and inferior lobes. We demonstrate 2 markers of normal vermian development: the primary fissure and fastigial point. We illustrate the tegmento-vermian angle, closure of the fourth ventricle, and communication of the fourth ventricle with the basal cisterns during development and in several disorders. We correlate those features with the expected embryological course of development and illustrate identification of these features and associated abnormalities of the posterior fossa, brain stem, and central nervous system in mid-trimester scans of fetuses with abnormal development. Correlation with contemporaneous ultrasound examinations is demonstrated.

MR diffusion-weighted imaging in a case of West Nile virus encephalitis

We report the first case of West Nile virus (WNV) encephalitis in which the only MRI abnormality during the initial phase of the infection was restriction in water mobility observed on diffusion-weighted imaging (DWI). The potential impact of hyperacute DWI in WNV encephalitis is discussed.nnA 58-year-old woman, 2 years after liver transplantation and taking 1.5 g mycophenolate mofetil and 200 mg cyclosporine daily, was admitted with fever and myoclonic jerks. Admission CSF revealed 58 cells (18 neutrophils and 17 lymphocytes), glucose 80 mg/100 mL, and protein 60 mg/100 mL. Serum virology shell vial assay for cytomegalovirus, varicella zoster, and herpes simplex, and viral tube culture were negative. Serum hemagglutinin inhibition for WNV antibodies (immunoglobulin [Ig] G and IgM) was negative on admission and days 7, 12, and 19 (titers <1:10 at the Ontario Ministry of Health Laboratory), becoming positive on day 36 with titers ≥1:2,560. Serum plaque reduction neutralization was also positive at 1:160 (Zoonotic Diseases and Special Pathogens Section, National Microbiologic Laboratory, Winnipeg, Canada). Noncontrast CT on day 4 was normal. MR examinations at 1.5 T on days 5 and 13 included T1- (pregadolinium and postgadolinium) and T2-weighted sequences, fluid-attenuated inversion recovery (FLAIR), and …

Periodontoid Synovial Cyst Causing Cervico-medullary Compression

BACKGROUNDnPeriodontoid synovial cysts are rare lesions which may produce symptomatic cervico-medullary compression.nnnMETHODnWe report such a patient, whose progressive neurological deterioration required surgical treatment by transoral odontoidectomy and decompression.nnnRESULTSnThe diagnostic and theraputic interventions are described, including a lumbar puncture which precipitated a transient loss of consciousness and respiratory arrest. Surgery achieved clinical improvement, without complications or need for operative stablization. Detailed neuropathology is presented, as well as a literature review.nnnCONCLUSIONnAppropriate neuroradiological assessment is required in patients with suspected cervico-medullary compression, and symptomatic periodontoid synovial cysts may respond well to transoral surgical decompression.