The Neurotrophic Effects of Lithium Carbonate Following Stroke: A Feasibility Study

• Cognitive tasks of the Neurological Disorders and Stroke - Canadian Stroke Network's (NINDS-CSN) 30 min. battery [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
• Serum brain-derived neurotrophic factor (BDNF) levels [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
• Serum lithium and creatinine levels [ Time Frame: 1-week, 4-weeks, 8-weeks ] [ Designated as safety issue: Yes ]

• Cognitive tasks of the NINDS-CSN 30 min. battery [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
• Serum BDNF levels [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
• Serum lithium and creatinine levels [ Time Frame: 1-week, 4-weeks, 8-weeks ] [ Designated as safety issue: Yes ]

Stroke is the leading cause of adult disability and the third leading cause of death in Canada. Most stroke survivors live with residual impairments that diminish independence and quality of life. This may include vascular cognitive impairment (loss of ability to plan, think and reason) which can lead to dementia and loss of mental and functional independence.

The current treatment to reduce stroke induced brain tissue injury is limited to thrombolytics (clot busters), a therapy useful only if given in the first hours following stroke. One major new approach aims to reduce cell death after stroke by targeting the ongoing tissue loss initiated by the stroke. The tissue can be maintained by interfering with later neurochemical processes that are activated by stroke, potentially through activating natural substances in the brain that help survival and growth of nerve cells ("neurotrophic" factors).

The recent recognition of lithium as a neurotrophic agent has generated the first studies of lithium treatment for managing brain diseases. Clinically, lithium has now been shown to increase brain gray matter volume in bipolar patients. This effect is potentially important in stroke because gray matter loss has been implicated in the development of cognitive impairment after stroke, a result of the series of brain processes that are activated by lack of oxygen due to stroke. Our primary objective is to examine the effects of lithium on total brain gray matter volume in the post-stroke population, as measured by volumetric magnetic resonance imaging (MRI) with the hope that lithium may increase gray matter volume in post-stroke patients and lead to greater cognitive and functional rehabilitation. This study will provide valuable information on the tolerability of lithium, and its effects on clinical outcomes relevant to stroke, providing the information needed for designing a large-scale clinical trial.

Inclusion Criteria:

• age >40 years
• male or female
• speaks and understands English
• within 12 months post-stroke

Exclusion Criteria:

• subarachnoid or intracranial hemorrhage
• severe aphasia or dysphasia
• impaired level of consciousness that would preclude neuropsychiatric testing
• significant acute medical illness that may contraindicate lithium treatment(including renal dysfunction; >106 umol/L creatinine level) affect neuropsychiatric assessments or serum BDNF results or put subject at risk from MRI procedure
• other psychiatric (exception of post-stroke depression) or neurological illnesses
• initiation of diuretic treatment
• use of antidepressant medications or initiation of antidepressant medications during the study