Brain injuries are a serious burden of illness to Canada and the US. Advances in managing head trauma have allowed more patients to emerge from decreased levels of consciousness and helped them cope with neurocognitive, neurobehavioural, and neuropsychiatric deficits. In this article, we review the current (1986-2002) evidence surrounding the pharmacological management of arousal states and the aforementioned neurological sequelae of head injury in either acute or chronic conditions. This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson’s medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury. The review did not include all anticonvulsants, neuroleptics, beta-blockers, benzodiazepines, azospirones or cognitive enhancers. Unfortunately, the quality of the evidence is generally poor, and sometimes conflicting, which in turn results in indecisive guidelines for treating patients. Accepting the inherent flaws in the evidence we feel that this paper may serve as a stepping-stone for future researchers to improve data gathering that targets neurocognitive, neurobehavioural and neuropsychiatric symptoms following a head injury.

The management of low-grade gliomas represents one of the most challenging and controversial areas in neuro-oncology. Many aspects of the treatment of low-grade gliomas are debated, including the optimal timing of surgery and radiotherapy, the benefit of extensive surgery, and the impact of these variables on the natural history of these indolent and generally incurable tumours. The recently published results of several large multicentre trials addressing the timing and dose of radiotherapy have provided solid evidence for delayed and reduced dose irradiation. These studies have also confirmed prognostic variables that can be used to guide management of individual patients. Among these variables is the observation that tumours with oligodendroglial features have a better natural history and response profile. The recognition that as many as two thirds of low-grade gliomas have oligodendroglial features, advances in molecular diagnostics making accurate pathologic diagnosis of oligodendroglial tumours possible, and the established chemosensitivity of malignant oligodendrogliomas, have raised new issues surrounding the potential value of chemotherapy for low-grade gliomas. This review will be restricted to low-grade diffuse astrocytomas, oligodendrogliomas, and low-grade mixed oligoastrocytomas in adults, and provide evidence-based guidelines for the management of these tumours, including the emerging role of chemotherapy as initial treatment.

The objective of this review is to summarize the literature on Alzheimer's disease progression utilizing cognitive batteries to track change over time. Studies published in English and obtained through PubMed searches (1983-2004) were included i) if they had a longitudinal design and followed probable Alzheimer's patients diagnosed by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association or Diagnostic and Statistical Manual III/IV criteria, and ii) if the techniques used for serial assessment were well-established in terms of validity and reliability. Longitudinal studies examining Alzheimer's disease progression report highly variable annual rates of change in decline rate. It remains unclear if this reflects disease subgroups or stage-related rate of decline. In conclusion a combination of stage-appropriate cognitive tests such as the Mattis Dementia Rating Scale and the Severe Impairment Battery, along with appropriate statistical methods to account for individual variability in decline rates, can capture the progression of Alzheimer disease and may be useful in further investigation.

Neurons and synapses in the central nervous system are plastic, undergoing long-term changes throughout life. Studies of molecular and cellular mechanisms of such changes not only provide important insight into how we learn and store new knowledge in our brains, but they also reveal the mechanisms of pathological changes that occur following injury. The author proposes that during induction, neuronal mechanisms underlying physiological functions, such as learning and memory, may share some common signaling molecules with abnormal or injury-related changes in the brain. Distinct synaptic and neuronal network mechanisms are involved in pathological pain as compared to cognitive learning and memory. Nociceptive information is transmitted and regulated at different levels of the brain, from the spinal cord to the forebrain. Furthermore, N-methyl-D-aspartate receptor-dependent and calcium-calmodulin activated adenylyl cyclases (AC1 and AC8) in the anterior cingulate cortex play important roles in the induction and expression of persistent inflammatory and neuropathic pain. Neuronal activity in the anterior cingulate cortex can also influence nociceptive transmission in the dorsal horn of the spinal cord by activating the endogenous facilitatory system. Our results provide important synaptic and molecular insights into physiological responses to injury.

Muscle biopsy provides the best tissue to confirm a mitochondrial cytopathy. Histochemical features often correlate with specific syndromes and facilitate the selection of biochemical and genetic studies. Ragged-red fibres nearly always indicate a combination defect of respiratory complexes I and IV. Increased punctate lipid within myofibers is a regular feature of Kearns-Sayre and PEO, but not of MELAS and MERRF. Total deficiency of succinate dehydrogenase indicates a severe defect in Complex II; total absence of cytochrome-c-oxidase activity in all myofibres correlates with a severe deficiency of Complex IV or of coenzyme-Q10. The selective loss of cytochrome-c-oxidase activity in scattered myofibers, particularly if accompanied by strong succinate dehydrogenase staining in these same fibres, is good evidence of mitochondrial cytopathy and often of a significant mtDNA mutation, though not specific for Complex IV disorders. Glycogen may be excessive in ragged-red zones. Ultrastructure provides morphological evidence of mitochondrial cytopathy, in axons and endothelial cells as well as myocytes. Abnormal axonal mitochondria may contribute to neurogenic atrophy of muscle, a secondary chronic feature. Quantitative determinations of respiratory chain enzyme complexes, with citrate synthase as an internal control, confirm the histochemical impressions or may be the only evidence of mitochondrial disease. Biological and technical artifacts may yield falsely low enzymatic activities. Genetic studies screen common point mutations in mtDNA. The brain exhibits characteristic histopathological alterations in mitochondrial diseases. Skin biopsy is useful for mitochondrial ultrastructure in smooth erector pili muscles and axons; skin fibroblasts may be grown in culture. Mitochondrial alterations occur in many nonmitochondrial diseases and also may be induced by drugs and toxins.

There are numerous concerns related to treatment choices involving early dopaminergic therapy in Parkinson's disease. These include the effect on the underlying progression of the neurodegenerative process as well as the development of motor complications such as fluctuations and dyskinesias. A number of recent basic and clinical studies have provided new insights but have also added confusion and controversy. This report summarizes presentations and discussion dealing with these issues from a one-day symposium involving Canadian Movement Disorders neurologists.