Neurology

EPILEPSY

Director	Contact
Peter Carlen	University Health Network Toronto Western Hospital Ec 8-005 399 Bathurst Street Toronto, ON M5T 2S8

Brief Description

The Epilepsy Program represents a multidisciplinary approach to diagnosis, medical management, and surgical treatment of epilepsy. The goal of exemplary patient care is fostered through implementation of state-of-the-art techniques and technologies and by a collaborative team of specialists who bring complementary skills and perspectives to bear in each case.  Patient care is integrated with strong clinical and basic science research.

Principal Investigators

Recent Original Research Publications

Hodaie M, Wennberg RA, Dostrovsky JO, Lozano AM. Chronic anterior thalamus stimulation for intractable epilepsy. Epilepsia 43:603-608, 2002.

Billingsley RL, McAndrews MP, Crawley AP, Mikulis DJ. Functional MRI of phonological and semantic processing in temporal lobe epilepsy. Brain 124:1218-27, 2001.

Sarkissian S, Politzer N, Zahn C, Irvine D . Implementation of a change process to improve outcomes of patients admitted to epilepsy monitoring unit. Outcomes Management for Nursing Practice 5:11-17, 2001.

Perez Velazquez JL, Carlen PL. Gap junctions, neural synchrony, and seizures. TINS 23:68-74, 2000.

Francis J, Jung B, Zhang G, Cheng J, Ho W, Burnham WM, Eubanks JH. Kindling induces the mRNA expression of methyl DNA-binding factors in the adult rat hippocampus. Neuroscience 113:79-87, 2002.

Future Directions

We are currently focusing on further recruitment and integration of epileptologists and basic scientists. We are also the focus for development of a transCanada epilepsy research initiative under the aegis of the Canadian League against Epilepsy. Functional MRI coupled with neuropsychological studies are expanding in the field of preoperative evaluation of epilepsy surgery patients. We are expanding our neurosurgical capabilities to include a strong intraoperative research capability including cortical recordings. We plan to acquire and launch a major research and clinical program using MEG (magnetoencephalography). Nursing research is an important focus for quality of life studies and the implementation of clinical trials of new anticonvulsant drugs.

At the basic scientific level, we are examining novel cellular and molecular targets for anticonvulsants, and the development of new theoretical and biological models for the study of epileptogenesis. Studies are underway, combining neural modeling with neurostimulation techniques, for the anticipation and possible prevention of seizure activity in in vitro and in vivo models of epilepsy.

MULTIPLE SCLEROSIS

Brief Description

This program involves basic science, epidemiological, and clinical research, directed to the causes and treatment of multiple sclerosis. The work is multidisciplinary and inter-institutional, and encompasses the Canadian Network of MS Clinics.

Principal Investigators

Recent Original Research Publications

Chamczuk AJ, Ursell M, O’Connor P, Jackowski G and Moscarello MA. A rapid Elisa-based serum assay for myelin basic protein. J Immunol Meth 21-27, 2002.

Panitch H, Goodin D, Coyle PK, O’Connor P, Weinshenker B for the Evidence Study Group. A randomized comparative study of interferon-beta dose in MS: the EVIDENCE trial. Neurology 59:1496-1506, 2002.

Dyment DA, Steckley JL, Willer C, Sadovnick AD, Risch N, Ebers GC and the Canadian Collaborative Study Group. No evidence to support CTLA-4 as susceptibility gene in Canadian MS families. J Neuroimmunol 123:193-8, 2002.

Miller DH, Khan OA, Sheremata WS, Blumhardt LD, Rice G, Dalton C, Miszkiel K, Hulme A, Libonati MA, O’Connor P, and the International Natalizumab (Antegren) MS Trial Group. A Double-Blind Randomized Placebo-Controlled Phase-2 Trial of Natalizumab in Patients with Relapsing Multiple Sclerosis. N Engl J Med 348:15-23, 2003.

Feinstein A, Feinstein K, O’Connor PW. Multiple sclerosis, interferon beta-1b and depression. a prospective investigation. J Neurol 249:815-820, 2002.

Future Directions

• Enhance our clinical research program, especially in clinical trials through greater trial leadership.
• Increase our research in MRI aspects of MS.
• Increase our local basic science research into the neuroimmunology of MS.
• Strengthen our contribution to ongoing molecular genetic and genetic epidemiology studies looking at the cause of MS.
• Explore the role of novel putative etiologic factors in MS, such as vitamin D3.
• Continue to maintain our national and international reputation for leadership in MS education.

NEURO-OPHTHALMOLOGY AND NEURO-OTOLOGY

Brief Description

This program is directed towards understanding the physiology of vision, eye movements of vestibular function, and abnormal mechanisms in neurological diseases that cause blindness, double vision, imbalance, dizziness, and falling. This understanding is applied to helping patients afflicted with many disorders of the brain. Additional goals are understanding vision in the workplace, aviation and space. The program has been based in systems physiology, which is required to translate advances in cellular biology to the understanding of functions of normal humans and patients.

Principal Investigators

Recent Original Research Publications

Priesol AJ, Jones GEG, Tomlinson RD, Broussard DM. The frequency-dependent effects of glutamate antagonists on the vestibulo-ocular reflex. Brain Res 857:252-264, 2000.

Broussard DM, Hong JA. The response of vestibulo-ocular reflex pathways to electrical stimulation after canal plugging. Exp Brain Res (In press). online, DOI 10.1007/s00221-002-1345-9.

Kim JS, Sharpe JA. The vertical vestibulo-ocular reflex, and its interaction with vision during active head motion: effects of aging. J Vestibular Res 11:3-12, 2001.

Sharpe JA, Kim JS. Midbrain disorders of vertical gaze: a quantitative re-evaluation. Ann N Y Acad Sci 956:143-154, 2002.

Wong AMF, Tweed D, Sharpe JA. Adaptive neural mechanisms for Listing’s law revealed in patients with sixth nerve palsy. Invest Ophthalmol Visual Science. 43:112-119, 2002.

Future Directions

Humans are highly visual animals. Visual and vestibular disorders are extremely common. The capacities of the brain for plasticity and repair, and for prevention by rehabilitation and pharmacological intervention are burgeoning areas of neuroscience. Precise methods for analyzing abnormalities of vision, vestibular, and ocular motor function are unsurpassed in other areas of the neurosciences. Future plans include studies in cerebral cortical control of eye movements and visual perception; investigation of plasticity of visual or ocular motor processing in tissue slices; and integrative studies of brainstem mechanisms of plasticity and repair in humans.

NEURODEGENERATIVE DISEASE

Director	Contact
Anthony Lang	University Health Network Toronto Western Hospital Main Pavilion 11-306 399 Bathurst Street Toronto, ON M5T 2S8

Brief Description

The Neurodegenerative Disease program at the University of Toronto is a broadly based basic and clinical research program. Areas of interest encompass all aspects of neurodegenerative disease including: etiology (basic genetic disturbances, genetic predisposing factors, epidemiological studies of genetic and environmental risk factors); cellular biology (mechanisms of neurodegenerative cell death, transgenic animal models); mechanisms of brain dysfunction using functional imaging (MRI volumetry, fMRI, MRS, SPECT, PET), electrophysiological studies (transcranial magnetic stimulation, and the evaluation of intracranial electrodes in patients with deep brain stimulators); neurobehavioural-neuropsychological techniques); clinical-pathological correlation; and experimental therapeutics (neuroprotective, neuro-regenerative, novel symptomatic therapies). Studies in the fields listed above are applied to numerous different neurodegenerative diseases including Alzheimer’s disease and other degenerative dementias, Parkinson’s disease and other parkinsonian disorders, other neurodegenerative movement disorders, amyotrophic lateral sclerosis, prion disease, and ataxia telangiectasia.

Principal Investigators

Recent Original Research Publications

Staines WR, Black SE, Graham SJ, McIlroy WE.  Somatosensory gating and recovery from stroke involving the thalamus. Stroke 33:2642‑51, 2002.

Cunic D, Roshan L, Khan F, Lozano AM, Lang AE, Chen R. Effects of subthalamic nucleus stimulation on motor cortex excitability in Parkinson's disease. Neurology 58:1665-1672, 2002.

Rozmahel R, Mount HTJ, Chen F, Nguyen V, Huang J, Erdebil S, Liauw J, Yu G, Hasegawa H, Gu Y, Song YQ, Schmidt SD, Nixon RA, Mathews PM, Bergeron C, Fraser P, Westaway D, St.George‑Hyslop P. Alleles at the Nicastrinlocus modify presenilin 1‑deficiencyphenotype. Proc Natl Acad Sci USA 99:14452‑7, 2002.

Levine B, Cabeza R, McIntosh AR, Black SE, Grady CL, Stuss DT. Functional reorganisation of memory after traumatic brain injury: a study with H(2)(15)0 positron emission tomography. J Neurol Neurosurg Psychiatry 73:173‑181, 2002.

Liotti M, Mayberg HS, McGinnis S, Brannan SL, Jerabek P. Unmasking disease‑specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression. Am J Psych 159:1830‑40, 2002.

Grimes DA, Han F, Lang AE, St. George-Hyslop P, Racacho L, Bulman DE. A novel locus for inherited myoclonus-dystonia on 18p11. Neurology 59:1183-1186, 2002.

Future Directions

During the next five years members of the program will continue to work toward defining the causes, the basic cellular mechanisms, and the consequent brain systems dysfunctions that underlie various neurodegenerative disorders. Discoveries in these fields will fuel integrative studies that will establish more effective methods of diagnosing and defining neurodegenerative diseases, including the evaluation of at risk individuals. In addition, progress in understanding the basic biology of neurodegenerative diseases will be applied to the field of experimental therapeutics with the development and testing of new treatment modalities designed to improve symptoms and particularly to ameliorate the progressive degenerative process.