Langston T. Holly, Yun Dong, Richard Albistegui-Dubois, Jonathan Marehbian and Bruce Dobkin
Recent investigations have demonstrated that the cerebral cortex can reorganize as a result of spinal cord injury and may play a role in preserving neurological function. Reorganization of cortical representational maps in patients with cervical spondylotic myelopathy (CSM) has not been previously described. The authors sought to determine the feasibility of using functional magnetic resonance (fMR) imaging in patients with CSM to investigate changes in the cortical representation of the wrist and ankle before and after surgical intervention.
Four patients with clinical and imaging evidence of CSM were prospectively enrolled in this study. The patients underwent preoperative neurological examination, functional assessment, cervical imaging, and brain fMR imaging. The fMR imaging activation task undertaken was either wrist extension or ankle dorsiflexion, depending on whether the patient's primary impairment was hand dysfunction or gait difficulty. The cohort then underwent further evaluations at 6 weeks and 3 and 6 months postoperatively. In addition, five healthy volunteers underwent fMR imaging at two different time points and served as controls.
In the healthy volunteers fMR imaging demonstrated areas of focal cortical activation limited to the contralateral primary motor area for the assigned motor tasks; the activation patterns were stable throughout repeated imaging. In comparison, in patients with CSM fMR imaging demonstrated expansion of the cortical representation of the affected extremity. Surgical decompression resulted in improvements in neurological function and reorganization of the representational map.
The findings of this preliminary study demonstrate the potential of fMR imaging to assess changes in cortical representation before and after surgical intervention in patients with CSM. A future study involving a larger cohort of patients as well as the stratification of patients with CSM, based on the aforementioned factors that influence cortical adaptation, will allow a more detailed quantitative analysis.
Yun Dong, Langston T. Holly, Richard Albistegui-Dubois, Xiaohong Yan, Jonathan Marehbian, Jennifer M. Newton and Bruce H. Dobkin
The goal of this study was to compare cortical sensorimotor adaptations associated with neurological deterioration and then recovery following surgical decompression for cervical spondylotic myelopathy (CSM).
Eight patients with CSM underwent functional MR (fMR) imaging during wrist extension and the 3-finger pinch task, along with behavioral assessments before and 3 and 6 months after surgery. Six healthy control volunteers were scanned twice.
Cervical spine MR imaging demonstrated successful cord decompression. The patients improved after surgery on the modified Japanese Orthopaedic Association score for the upper extremity, which correlated with the changes in task-associated activation in specific sensorimotor regions of interest. Pinch-related activation in sensorimotor cortex contralateral to the movement paradigm was reduced before surgery then increased toward the extent of healthy controls after surgery. Before surgery, patients showed broader activation in ipsilateral sensorimotor cortex during wrist extension than during pinch, but activations became similar to those of healthy controls after surgery. Pinch-related activation volume in the ipsilateral sensorimotor cortex and the magnitude of activation in the contralateral dorsal premotor cortex evolved linearly across time after surgery, along with wrist extension–related activation magnitude in the contralateral supplementary motor area.
Serial fMR imaging studies in CSM can capture the adaptations in specific sensorimotor cortices that accompany clinical deterioration and postsurgical improvement in sensorimotor function associated with damage and partial recovery of conduction in corticospinal pathways. These adaptive regions can be monitored by serial fMR imaging to detect a critical loss of supraspinal reserve in compensatory plasticity, which might augment clinical information about the need for surgical decompression.
Randy S. D’Amico, Justin A. Neira, Jonathan Yun, Nikita G. Alexiades, Matei Banu, Zachary K. Englander, Benjamin C. Kennedy, Timothy H. Ung, Robert J. Rothrock, Alexander Romanov, Xiaotao Guo, Binsheng Zhao, Adam M. Sonabend, Peter Canoll and Jeffrey N. Bruce
Intracerebral convection-enhanced delivery (CED) has been limited to short durations due to a reliance on externalized catheters. Preclinical studies investigating topotecan (TPT) CED for glioma have suggested that prolonged infusion improves survival. Internalized pump-catheter systems may facilitate chronic infusion. The authors describe the safety and utility of long-term TPT CED in a porcine model and correlation of drug distribution through coinfusion of gadolinium.
Fully internalized CED pump-catheter systems were implanted in 12 pigs. Infusion algorithms featuring variable infusion schedules, flow rates, and concentrations of a mixture of TPT and gadolinium were characterized over increasing intervals from 4 to 32 days. Therapy distribution was measured using gadolinium signal on MRI as a surrogate. A 9-point neurobehavioral scale (NBS) was used to identify side effects.
All animals tolerated infusion without serious adverse events. The average NBS score was 8.99. The average maximum volume of distribution (Vdmax) in chronically infused animals was 11.30 mL and represented 32.73% of the ipsilateral cerebral hemispheric volume. Vdmax was achieved early during infusions and remained relatively stable despite a slight decline as the infusion reached steady state. Novel tissue TPT concentrations measured by liquid chromatography mass spectroscopy correlated with gadolinium signal intensity on MRI (p = 0.0078).
Prolonged TPT-gadolinium CED via an internalized system is safe and well tolerated and can achieve a large Vdmax, as well as maintain a stable Vd for up to 32 days. Gadolinium provides an identifiable surrogate for measuring drug distribution. Extended CED is potentially a broadly applicable and safe therapeutic option in select patients.
2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010