CLINICAL NEUROLOGICAL SCIENCES
| DEPARTMENT OF CLINICAL NEUROLOGICAL SCIENCES |
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The Department of CNS has many strong research groups, some of which are described below. A special story has
been written about Dr. George Ebers of the Multiple Sclerosis Research Group and Dr. Michael Strong of the Neuromuscular
group.
The Neuromuscular Group includes Drs. A. Hahn, M. Nicolle and M. Strong
In the area of Neuroimmunology/Neuromuscular Research, our research attempts to tie together clinical observations,
basic science and eventually clinical trials. The primary areas of interest are: The acquired immune-mediated neuropathies
such as the Guillain Barré Syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathies (CIDP), and
multi-focal motor neuropathies with conduction block, amyotrophic lateral sclerosis, myasthenia gravis, the neurophysiology
of respiratory changes in some of these disorders and channelopathies such as hypokalemic periodic paralysis.
Drs. Hahn and Nicolle have established a laboratory research program to study the immunopathology and immunoregulation
of experimental allergic neuritis (EAN), the animal model of GBS, as well as chronic experimental allergic neuritis
(CEAN), the animal model for CIDP. The goals are to further define the immunopathological processes involved in
these diseases, including a better definition of the target antigen, and in the experimental models to attempt
therapies looking at immune deviation through immunosuppressive cytokines (EAN), or at the induction of antigen-specific
tolerance (CEAN).
Dr. Hahn is engaged in clinical trials to critically evaluate the current treatment modalities for GBS, CIDP, and
multi-focal motor neuropathy with conduction block, as well as the periodic paralyses. She is also involved in
molecular genetic studies in such disorders as hereditary hyperexplexia, hereditary episodic cerebellar ataxia,
hereditary vitamin E deficiency and hypokalemic periodic paralysis. Correlations between genotype and phenotype
are being carried out for some forms of hereditary motor and sensory neuropathy (Charcot-Marie Tooth disease) to
further characterize the mechanisms of identified mutations. Dr. Nicolle is involved in the study of the cellular
immunology of myasthenia gravis, specifically the anti-acetylcholine receptor antibody producing B lymphocytes
found within the hyperplastic thymus. He is also looking at the utility of electrophysiological investigation of
the respiratory system in the management of myasthenia gravis.
Dr. M. Strong is involved in basic science research studying amyotrophic lateral sclerosis (ALS) in which he is
looking at the effects of aluminum and endogenous nitration of neurofilaments, as well as modifications of neurofilaments
and their role in motor neuron diseases.
In the area of Neurophysiology / Critical Care, Drs. C.F. Bolton and
G.B. Young carry out investigations in collaboration with colleagues in CNS and in Critical Care Medicine. They
have utilized electrical recordings of both the central and peripheral nervous systems for more accurate diagnoses
and thus have improved treatment and management.
Dr. Bryan Young has developed and utilized the technique of continuous recording of electrical activity from the
brain in order to manage patients who arrive in an unconscious state; the cause of which is uncertain. Continuous
recording has disclosed continuous seizures which while not obvious on simple examination, can be effectively treated.
This technique has also proved valuable in arriving at a more precise reason for the unconscious state, resulting
in improved treatment and the ability to render a prognosis.
In patients who experience a severe heart attack, varying degrees of brain damage may arise from the sudden reduction
in blood flow. A variety of treatment modalities are applied in the critical care unit, but it is equally important
to make some assessment of the long term prognosis. The group has shown that the technique of somatosensory evoked
potential recording can increase our ability to make an accurate prognosis.
Patients may experience difficulty in breathing, not only due to disturbances in the heart and lungs, but due to
a disturbance of the central and peripheral nervous systems' control of breathing. Until now, assessment of this
was based almost entirely on simple clinical observations, but these proved relatively inaccurate. Thus, a number
of techniques have been developed which record electrical activity from the brain, spinal cord, and nerves and
muscles of breathing. Details of these techniques have been published, and have been applied to investigate several
conditions: critical illness; myotonic dystrophy (a form of muscular dystrophy); patients who have a periodic fluctuation
in muscle weakness, myasthenia gravis. It is now possible to manage such patients more successfully. These techniques,
developed at LHSC-VC, are now being utilized in a number of centres in North America and Europe.
A number of years ago, Drs. C. Bolton, A. Hahn, J. Gilbert and W. Sibbald described for the first time a degeneration
of the nerves in patients who were critically ill and injured. The disorder was named critical illness polyneuropathy.
There was initial skepticism, but recently, these observations have been confirmed in two major centres in Europe,
and, in a third centre, basic investigations have disclosed the toxic substance causing the nerve degeneration.
As a result, a specific method of treatment may soon become available. The importance of this work and the collaborative
efforts in the hospital and in the Faculty of Medicine were recently cited in an editorial in the journal, Critical
Care Medicine.
Investigations here, and in other centres, have been brought together in three published books: Paediatric Clinical
Electromyography, Ed - Jones, Bolton and Harper (1996); Clinical Neurology, Critical Care, Ed - Bolton and Young
(1996); and Coma, Ed - Young, Ropper and Bolton (1997).
The importance of collaborators in these investigations are obvious, but it is important to emphasize the role
of research Fellows and Residents. This was recognized at the Canadian Congress of Neurological Sciences meeting
in London, Ontario in 1996, when Dr. Robert Chen, a Resident in Neurology, and Dr. Udo Zifko, a Research Fellow,
received the Francis McNaughton Memorial Prize and the Herbert Jasper Prize respectively. These were presented
for excellence in clinical research.
The Multiple Sclerosis Group, Drs. D. Bulman, G. Ebers, and G. Rice
focus on advancing our knowledge of the molecular genetics of neuromuscular diseases and multiple sclerosis. In
addition the laboratory group, (Drs. Ebers and Bulman) has been successful in identifying the first linkages for
Thomsen's disease (a disease of muscle with myotonia), and paroxysmal ataxia. Other studies focus on the genetics
of obesity and on human behaviour. A busy program of clinical trials which encompasses and derives from definitive
studies of the natural history of MS is being carried out by Drs. Rice and Ebers.
A third area concerns the genetic epidemiology of multiple sclerosis and this is part of a Canada-wide study aimed
at identifying noninheritable factors involved in the pathogenesis of this disorder. Dr. Ebers and Dr. D. Sadovnick
(University of British Columbia) have been funded by the MS Research Foundation. London is the centre for the basic
research using molecular techniques for these studies which involve some 800 families having more than one person
affected with MS.
Stroke Prevention Research involves Drs. D.F. Cechetto, (Physiology), M. Eliasziw, (Epidemiology and Biostatiscs
at Robarts Research Institute), V. Hachinski, C. Munoz, and D. Spence.
The brain mechanisms of sudden death are being investigated by neurophysiological and biochemical mapping of the
pathways involved in mediating brain effects on the heart. The group has previously shown that lesions of the insula
in the brain are crucial in affecting the heart. Currently, the effect of a combination of a brain lesion and stress,
and identifying the critical period for cardiac complication after stroke is being studied. The neuroprotective
mechanisms are being actively investigated in stroke as related to imidazoline and neuropeptide receptors. Imidazoline
may have particular promise in prevention since it is an antihypertensive agent that may minimize ischemic damage
should it occur in high risk patients.
Dr. David Spence, the primary investigator in the Stroke Prevention & Atherosclerosis Research Centre (SPARC)
is located at the Siebens-Drake Building. Atherosclerosis is the commonest cause of stroke. Regression modelling,
using the known risk factors for atherosclerosis, with carotid plaque as the dependent variable, has demonstrated
the effect on atherosclerosis of hemodynamic re: responses to mental stress. This work, in collaboration with the
Advanced Imaging Group (jointly with the Robarts Research Institute), has led to measurement of atherosclerosis
progression by 3-D ultrasound, and a new regression model, eliminating the effect of aging, will be the best method
available for making explicit the effect of new risk factors such as postprandial hyperlipidemia. The regression
modelling with 3-D ultrasound measurement of progression not explained by the usual risk factors will be used to
find new genes for atherosclerosis, and in turn the discovery of new genetic causes will lead to new treatments
for atherosclerosis. The 3-D measurement of atherosclerosis progression is now the best method available in the
world for demonstrating efficacy of anti-atherosclerotic drugs. This will be particularly important for new drugs
that do not have other efficacy endpoints such as the lowering of cholesterol. 3-D ultrasound is currently being
evaluated in a prospective study comparing it to 2-D ultrasound, magnetic resonance angiography and conventional
contrast cerebral angiography.
The Search For Treatable Causes Of Dementia
About 25% of patients with symptomatic and asymptomatic cerebrovascular disease have some degree of cognitive
impairment. Drs. Spence, Hachinski and others are trying to delineate to what extent the risk factors for frank
stroke are the same for vascular cognitive impairment, and to seek new risk and protective factors. Several projects
include;
Stroke Prevention - Clinical Trials:
Through several international clinical trials, training of vascular neurologists, neuroradiologists, and neurosurgeons
and the personal contacts of members of the research group interested in stroke, there is an extensive international
network of collaborators.
Drs. H.J.M. Barnett, M. Eliasziw, G.G. Ferguson, A.J. Fox, V. Hachinski, S. Lownie, R. Rankin, D. Spence,
W. Taylor are investigators in currently active clinical trials which include, North American Symptomatic Carotid
Endarterectomy Trial. This is an international trial involving over 100 centres evaluating the role of carotid
endarterectomy in symptomatic patients with stenoses from 30% to 69% in one carotid artery directed from London,
Ontario and primarily through the Robarts Research Institute.
To prevent Atherosclerosis and thus lessen the incidence of stroke, Dr. David Spence is conducting clinical trials
involving lipid lowering agents, antihypertensives, vitamins, endothelin antagonists and postmenopausal hormone
replacement.
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