Pathophysiology of primary spinal syringomyelia.

OBJECT: The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. METHODS: To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. RESULTS: In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 ± 1.2 vs 1.6 ± 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the thecal sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. CONCLUSIONS: These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245.

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

CONTEXT: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. OBJECTIVE: To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. DESIGN: A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. SETTING: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). INTERVENTIONS: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. MAIN OUTCOME MEASURES: Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. RESULTS: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. CONCLUSION: In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.

Intraoperative infrared functional imaging of human brain.

We hypothesized that it would be possible to detect the distribution of cortical activation by using a sensitive, rapid, high-resolution infrared imaging technique to monitor changes in local cerebral blood flow induced by changes in focal cortical metabolism. In a prospective study, we recorded in 21 patients the emission of infrared radiation from the exposed human cerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02 degrees C). The language and sensorimotor cortex was identified by standard mapping methods (cortical stimulation, median nerve somatosensory-evoked potential, functional magnetic resonance imaging), which were compared with infrared functional localization. The temperature gradients measured during surgery are dominated by changes in local cerebral blood flow associated with evoked functional activation. The distribution of the evoked temperature changes overlaps with, but extends beyond, functional regions identified by standard mapping techniques. The distribution observed via infrared mapping is consistent with distributed and complex functional representation of the cerebral cortex, rather than the traditional concept of discrete functional loci demonstrated by brief cortical stimulation during surgery and by noninvasive functional imaging techniques. By providing information on the spatial and temporal patterns of sensory-motor and language representation, infrared imaging may prove to be a useful approach to study brain function.