Measurement of functional ability following traumatic brain injury using the Clinical Outcomes Variable Scale: A reliability study

This study determined the inter-tester and intra-tester reliability of physiotherapists measuring functional motor ability of traumatic brain injury clients using the Clinical Outcomes Variable Scale (COVS). To test inter-tester reliability, 14 physiotherapists scored the ability of 16 videotaped patients to execute the items that comprise the COVS. Intra-tester reliability was determined by four physiotherapists repeating their assessments after one week, and three months later. The intra-class correlation coefficients (ICC) were very high for both inter-tester reliability (ICC > 0.97 for total COVS scores, ICC > 0.93 for individual COVS items) and intra-tester reliability (ICC > 0.97). This study demonstrates that physiotherapists are reliable in the administration of the COVS.

Morphosyntactic and syntactic priming: an investigation of underlying processing mechanisms and the effects of Parkinson’s disease

There is now considerable evidence to suggest that non-demented people with Parkinson's disease (PD) experience difficulties using the morphosyntactic aspects of language. It remains unclear, however, at precisely which point in the processing of morphosyntax, these difficulties emerge. The major objective of the present study was to examine the impact of PD on the processes involved in accessing morphosyntactic information in the lexicon. Nineteen people with PD and 19 matched control subjects participated in the study which employed on-line word recognition tasks to examine morphosyntactic priming for local grammatical dependencies that occur both within (e.g. is going) and across (e.g. she gives) phrasal boundaries (Experiments 1 and 2, respectively). The control group evidenced robust morphosyntactic priming effects that were consistent with the involvement of both pre- (Experiment 1) and post-lexical (Experiment 2) processing routines. Whilst the participants with PD also recorded priming for dependencies within phrasal boundaries (Experiment 1), priming effects were observed over an abnormally brief time course. Further, in contrast to the controls, the PD group failed to record morphosyntactic priming for constructions that crossed phrasal boundaries (Experiment 2). The results demonstrate that attentionally mediated mechanisms operating at both the pre- and post-lexical stages of processing are able to contribute to morphosyntactic priming effects. In addition, the findings support the notion that, whilst people with PD are able to access morphosyntactic information in a normal manner, the time frame in which this information remains available for processing is altered. Deficits may also be experienced at the post-lexical integrational stage of processing.

Allelic Variation Investigation of the Estrogen Receptor Within an Australian Multiple Sclerosis Population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

No Association Between MTHFR A1298C and MTRR A66G Polymorphisms, and MS in an Australian Cohort

Multiple sclerosis (MS) is a complex neurological disease that affects the central nervous system (CNS) resulting in debilitating neuropathology. Pathogenesis is primarily defined by CNS inflammation and demyelination of nerve axons. Methionine synthase reductase (MTRR) is an enzyme that catalyzes the remethylation of homocysteine (Hcy) to methionine via cobalamin and folate dependant reactions. Cobalamin acts as an intermediate methyl carrier between methylenetetrahydrofolate reductase (MTHFR) and Hcy. MTRR plays a critical role in maintaining cobalamin in an active form and is consequently an important determinant of total plasma Hcy (pHcy) concentrations. Elevated intracellular pHcy levels have been suggested to play a role in CNS dysfunction, neurodegenerative, and cerebrovascular diseases. Our investigation entailed the genotyping of a cohort of 140 cases and matched controls for MTRR and MTHFR, by restriction length polymorphism (RFLP) techniques. Two polymorphisms: MTRR A66G and MTHFR A1298C were investigated in an Australian age and gender matched case-control study. No significant allelic frequency difference was observed between cases and controls at the α = 0.05 level (MTRR χ^2 = 0.005, P = 0.95, MTHFR χ^2 = 1.15, P = 0.28). Our preliminary findings suggest no association between the MTRR A66G and MTHFR A1298C polymorphisms and MS.

Test–retest repeatability of self-reported environmental exposures in Parkinson’s disease cases and healthy controls

There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson’s disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test–retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age-and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for ‘lifestyle’ exposures, such as smoking and coffee/tea consumption (kappas 0.70–1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39–0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.

Excitability changes in human forearm corticospinal projections and spinal reflex pathways during rhythmic voluntary movement of the opposite limb

Rhythmic movements brought about by the contraction of muscles on one side of the body give rise to phase-locked changes in the excitability of the homologous motor pathways of the opposite limb. Such crossed facilitation should favour patterns of bimanual coordination in which homologous muscles are engaged simultaneously, and disrupt those in which the muscles are activated in an alternating fashion. In order to examine these issues, we obtained responses to transcranial magnetic stimulation (TMS), to stimulation of the cervicomedullary junction (cervicomedullary-evoked potentials, CMEPs), to peripheral nerve stimulation (H-reflexes and f-waves), and elicited stretch reflexes in the relaxed right flexor carpi radialis (FCR) muscle during rhythmic (2 Hz) flexion and extension movements of the opposite (left) wrist. The potentials evoked by TMS in right FCR were potentiated during the phases of movement in which the left FCR was most strongly engaged. In contrast, CMEPs were unaffected by the movements of the opposite limb. These results suggest that there was systematic variation of the excitability of the motor cortex ipsilateral to the moving limb. H-reflexes and stretch reflexes recorded in right FCR were modulated in phase with the activation of left FCR. As the f-waves did not vary in corresponding fashion, it appears that the phasic modulation of the H-reflex was mediated by presynaptic inhibition of Ia afferents. The observation that both H-reflexes and f-waves were depressed markedly during movements of the opposite indicates that there may also have been postsynaptic inhibition or disfacilitation of the largest motor units. Our findings indicate that the patterned modulation of excitability in motor pathways that occurs during rhythmic movements of the opposite limb is mediated primarily by interhemispheric interactions between cortical motor areas.

Governing coordination: Behavioural principles and neural correlates

The coordination of movement is governed by a coalition of constraints. The expression of these constraints ranges from the concrete—the restricted range of motion offered by the mechanical configuration of our muscles and joints; to the abstract—the difficulty that we experience in combining simple movements into complex rhythms. We seek to illustrate that the various constraints on coordination are complementary and inclusive, and the means by which their expression and interaction are mediated systematically by the integrative action of the central nervous system (CNS). Beyond identifying the general principles at the behavioural level that govern the mutual interplay of constraints, we attempt to demonstrate that these principles have as their foundation specific functional properties of the cortical motor systems. We propose that regions of the brain upstream of the motor cortex may play a significant role in mediating interactions between the functional representations of muscles engaged in sensorimotor coordination tasks. We also argue that activity in these ldquosupramotorrdquo regions may mediate the stabilising role of augmented sensory feedback.

Entanglement between a qubit and the environment in the spin-boson model

The quantitative description of the quantum entanglement between a qubit and its environment is considered. Specifically, for the ground state of the spin-boson model, the entropy of entanglement of the spin is calculated as a function of α, the strength of the ohmic coupling to the environment, and ɛ, the level asymmetry. This is done by a numerical renormalization group treatment of the related anisotropic Kondo model. For ɛ=0, the entanglement increases monotonically with α, until it becomes maximal for α→1-. For fixed ɛ>0, the entanglement is a maximum as a function of α for a value, α=αM

Multiple Sclerosis with Idiopathic Dilated Cardiomyopathy: A Case Report

Multiple sclerosis and idiopathic dilated cardiomyopathy are two conditions in which an autoimmune process is implicated in the pathogenesis. There is evidence to support clustering of autoimmune diseases in patients with multiple sclerosis and their families. To our knowledge, this is the first report of idiopathic dilated cardiomyopathy occurring in a patient with multiple sclerosis.

Increased apoptosis of T lymphocytes and macrophages in the central and peripheral nervous systems of Lewis rats with experimental autoimmune encephalomyelitis treated with dexamethasone

Using light and electron microscopic histological and immunocytochemical techniques, we investigated the effects of the glucocorticoid dexamethasone on T cell and macrophage apoptosis in the central nervous system (CNS) and peripheral nervous system (PNS) of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP). A single subcutaneous injection of dexamethasone markedly augmented T cell and macrophage apoptosis in the CNS and PNS and microglial apoptosis in the CNS within 6 hours (h). Pre-embedding immunolabeling revealed that dexamethasone increased the number of apoptotic CD5+ cells (T cells or activated B cells), αβ T cells, and CD11b+ cells (macrophages/microglia) in the meninges, perivascular spaces, and CNS parenchyma. The induction of increased apoptosis was dose-dependent. Daily dexamethasone treatment suppressed the neurological signs of EAE. However, the daily injection of a dose of dexamethasone (0.25 mg/kg). which, after a single dose, did not induce increased apoptosis in the CNS or PNS, was as effective in inhibiting the neurological signs of EAE as the high dose (4 mg/kg), which induced a marked increase in apoptosis. This indicates that the beneficial clinical effect of glucocorticoid therapy in EAE does not depend on the induction of increased apoptosis. The daily administration of dexamethasone for 5 days induced a relapse that commenced 5 days after cessation of treatment, with the severity of the relapse tending to increase with dexamethasone dosage.

Autoimmune Neurological Disease

This book provides a comprehensive and critical overview of the immunological aspects of autoimmune neurological disease. These diseases include common conditions such as multiple sclerosis, the Guillain–Barré syndrome and myasthenia gravis. The introductory chapters on antigen recognition and self–non-self discrimination, and on neuroimmunology, are followed by chapters on specific diseases. These are presented in a standardized format with sections on clinical features, genetics, neuropathology, pathophysiology, immunology and therapy. Each chapter has a concluding section which summarizes key points and suggests directions for future research. Animal models of autoimmune neurological disease are also covered in detail because of their importance in understanding the human diseases. The book is suitable for clinicians and neurologists managing patients with these diseases, and for immunologists, neuroscientists and neurologists investigating the pathogenesis and pathophysiology of these disorders.

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers.

Immunopathology and Pathophysiology of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system (CNS), and is widely studied as an animal model of the human CNS demyelinating diseases, including multiple sclerosis (Raine, 1984). EAE can be induced by inoculation with whole CNS tissue, purified myelin basic protein (MBP) or myelin proteolipid protein (PLP), together with adjuvants. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens. EAE may have either an acute or a chronic relapsing course. Acute EAE closely resembles the human disease acute disseminated encephalomyelitis, while chronic relapsing EAE resembles multiple sclerosis. EAE is also the prototype for T-cell-mediated autoimmune disease in general. This chapter will focus on the immunopathology and pathophysiology of EAE, which are the subjects of investigation in my laboratory.