Traumatic brain injury (TBI) remains a significant public health issue with an incidence
of 55-70 million individuals worldwide. In Canada, TBI leads to 23,000 hospitalizations
per year with 8% of individuals succumbing to their injuries. In addition to neurologic
deficits, TBI may lead to a spectrum of long-term impairments, including cognitive
difficulties (e.g., attention, memory), neurologic symptoms (e.g., headaches, dizziness)
and neuropsychiatric sequalae (e.g. anxiety, post-traumatic stress disorder). TBI has
also been associated with neurodegenerative disorders, such as chronic traumatic
encephalopathy and the development of Alzheimer's-type pathology.
Cognitive rehabilitation programs are important tools for clinical recovery of TBI
patients, improving functional outcomes and the quality of life. Some of these strategies
are based on the development of compensatory strategies and neuroplasticity. Due to the
short liver nature of some of the associated improvements and neuroplastic phenomena,
stimulating specific neuronal circuits has been proposed.
To date, class I evidence suggests that cognitive improvement following rehabilitation is
more effective than sham treatment. In general, however, cognitive rehabilitation therapy
is effective in 80-90% of patients. This means that 10-20% of patients remain severely
disabled despite treatment.
Deep Brain Stimulation is a neurosurgical tool that has been widely used for over twenty
years. Most of the experience with DBS comes from the movement disorder literature where
significant success has been had with the management of disabling Parkinson's Disease
(PD) and dystonia. Owing to similar underlying circuitry, and the frequent co-occurrence
of psychiatric and neurologic conditions, DBS has been suggested for the management of
treatment resistant neuropsychiatric conditions, with some promising results.
To date, clinical studies using DBS following TBI are largely comprised of case reports
and small case series. The most common application of invasive neurostimulation has been
for the treatment of post-TBI dystonic symptoms and tremor. In addition to motor
improvement, Miller et al reported a series of 4 patients who presented an improvement in
visuospatial memory following fornix burst stimulation. Zhou et al reported that DBS
delivered to the anterior limb of internal capsule and the region of the nucleus
accumbens improved post-TBI auditory hallucinations, mood changes, and insomnia in a
single female patient. Kuhn et al. reported a patient who had a substantial reduction in
post- TBI self-mutilating behavior following posterior hypothalamus stimulation. An
improvement in emotional adjustment and functional independence was reported in 4 TBI
patients treated with nucleus accumbens DBS.Aside from the cognitive, psychiatric and
mood improvements described above, DBS has also been investigated for the recovery of
consciousness in patients in minimally conscious states. Out of 10 patients reported in
the literature, an improvement was observed in 8 individuals using coma scales and
related metrics.
Patients with memory and cognitive deficits following TBI that do not respond to
conventional treatments experience a decrease in quality of life. Despite advances in
neuroimaging, genetics, pharmacology and psychosocial interventions in the last half
century, little progress has been made in altering the natural history of the condition
or its outcome.
This study would explore whether a surgical therapy is safe and potentially effective in
patients who develop refractory memory and cognitive deficits following TBI. Preclinical
studies suggest that DBS may improve memory deficits in TBI models. Moreover, DBS
delivered to the fornix has shown promising clinical results in patients with Alzheimer's
disease. The main mechanism for the improvements induced by DBS in memory tests is the
development of multiple forms of plasticity.