Zach Pennington, Bowen Jiang, Erick M. Westbroek, Ethan Cottrill, Benjamin Greenberg, Philippe Gailloud, Jean-Paul Wolinsky, Ying Wei Lum, and Nicholas Theodore
Myelopathy selectively involving the lower extremities can occur secondary to spondylotic changes, tumor, vascular malformations, or thoracolumbar cord ischemia. Vascular causes of myelopathy are rarely described. An uncommon etiology within this category is diaphragmatic crus syndrome, in which compression of an intersegmental artery supplying the cord leads to myelopathy. The authors present the operative technique for treating this syndrome, describing their experience with 3 patients treated for acute-onset lower-extremity myelopathy secondary to hypoperfusion of the anterior spinal artery.
All patients had compression of a lumbar intersegmental artery supplying the cord; the compression was caused by the diaphragmatic crus. Compression of the intersegmental artery was probably producing the patients’ symptoms by decreasing blood flow through the artery of Adamkiewicz, causing lumbosacral ischemia.
All patients underwent surgery to transect the offending diaphragmatic crus. Each patient experienced substantial symptom improvement, and 2 patients made a full neurological recovery before discharge.
Diaphragmatic crus syndrome is a rare or under-recognized cause of ischemic myelopathy. Patients present with episodic acute-on-chronic lower-extremity paraparesis, gait instability, and numbness. Angiography confirms compression of an intersegmental artery that gives rise to a dominant radiculomedullary artery. Transecting the offending diaphragmatic crus can produce complete resolution of neurological symptoms.
Darin D. Dougherty, Tina Chou, Andrew K. Corse, Amanda R. Arulpragasam, Alik S. Widge, Cristina Cusin, Karleyton C. Evans, Benjamin D. Greenberg, Suzanne N. Haber, and Thilo Deckersbach
Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS.
Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity.
Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = −0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact.
DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.
Scott L. Rauch, Darin D. Dougherty, Donald Malone, Ali Rezai, Gerhard Friehs, Alan J. Fischman, Nathaniel M. Alpert, Suzanne N. Haber, Paul H. Stypulkowski, Mark T. Rise, Steven A. Rasmussen, and Benjamin D. Greenberg
Deep brain stimulation (DBS) of the ventral [anterior internal] capsule/ventral striatum (VC/VS) is under investigation as an alternative to anterior capsulotomy for severe obsessive–compulsive disorder (OCD). In neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and anterior cingulate cortex, striatum, and thalamus has been identified; and modulation of activity in this circuit has been observed following successful nonsurgical treatment. The purpose of the current study was to test hypotheses regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the VC/VS target in patients with OCD who were participating in a clinical DBS trial.
Six patients enrolled in a DBS trial for OCD underwent positron emission tomography to measure rCBF; the rCBF measured during acute DBS at high frequency was then compared with those measured during DBS at low frequency and off (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS and neuroimaging data on OCD, the authors predicted that acute DBS at this target would result in modulation of activity within the implicated frontal–basal ganglia–thalamic circuit. Data were analyzed using statistical parametric mapping.
In a comparison of acute high-frequency DBS with control conditions, the authors found significant activation of the orbitofrontal cortex, anterior cingulate cortex, striatum, globus pallidus, and thalamus.
Acute DBS at the VC/VS target is associated with activation of the circuitry implicated in OCD. Further studies will be necessary to replicate these findings and to determine the neural effects associated with chronic VC/VS DBS. Moreover, additional data are needed to investigate whether pretreatment imaging profiles can be used to predict a patient’s subsequent clinical response to chronic DBS.
Andre F. Gentil, Antonio C. Lopes, Darin D. Dougherty, Christian Rück, David Mataix-Cols, Teagan L. Lukacs, Miguel M. Canteras, Emad N. Eskandar, K. Johan Larsson, Marcelo Q. Hoexter, Marcelo C. Batistuzzo, Benjamin D. Greenberg, and Euripedes C. Miguel
Recent findings have suggested a correlation between obsessive-compulsive disorder (OCD) symptom dimensions and clinical outcome after limbic system surgery for treatment-refractory patients. Based on previous evidence that the hoarding dimension is associated with worse outcome in conventional treatments, and may have a neural substrate distinct from OCD, the authors examined a large sample of patients undergoing limbic surgery (40 with capsulotomy, 37 with cingulotomy) and investigated if symptom dimensions, in particular hoarding, could influence treatment outcome.
Data from 77 patients from 3 different research centers at São Paulo (n = 17), Boston (n = 37), and Stockholm (n = 23) were analyzed. Dimensional Yale-Brown Obsessive Compulsive Scale (Y-BOCS; São Paulo) or Y-BOCS Symptom Checklist scores (Boston and Stockholm) were used to code the presence of 4 well-established symptom dimensions: forbidden thoughts, contamination/cleaning, symmetry/order, and hoarding. Reductions in YBOCS scores determined clinical outcome.
Mean Y-BOCS scores decreased 34.2% after surgery (95% CI 27.2%–41.3%), with a mean follow-up of 68.1 months. Patients with hoarding symptoms had a worse response to treatment (mean Y-BOCS decrease of 22.7% ± 25.9% vs 41.6% ± 32.2%, respectively; p = 0.006), with no significant effect of surgical modality (capsulotomy vs cingulotomy). Patients with forbidden thoughts apparently also had a worse response to treatment, but this effect was dependent upon the co-occurrence of the hoarding dimension. Only the negative influence of the hoarding dimension remained when an ANOVA model was performed, which also controlled for preoperative symptom severity.
The presence of hoarding symptoms prior to surgery was associated with worse clinical outcome after the interventions. Patients with OCD under consideration for ablative surgery should be carefully screened for hoarding symptoms or comorbid hoarding disorder. For these patients, the potentially reduced benefits of surgery need to be carefully considered against potential risks.