Shannon W. Clark

Trigeminal Pain Molecules, Allodynia, and Photosensitivity Are Pharmacologically and Genetically Modulated in a Model of Traumatic Brain Injury

The pain-signaling molecules, nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic headache (PTH) as they are for migraine. This study assessed the changes of inducible NOS (iNOS) and its cellular source in the trigeminal pain circuit, as well as the relationship between iNOS and CGRP after controlled cortical impact (CCI) injury in mice. The effects of a CGRP antagonist (MK8825) and sumatriptan on iNOS messenger RNA (mRNA) and protein were compared to vehicle at 2 weeks postinjury. Changes in CGRP levels in the trigeminal nucleus caudalis (TNC) in iNOS knockouts with CCI were compared to wild-type (WT) mice at 3 days and 2 weeks post injury. Trigeminal allodynia and photosensitivity were measured. MK8825 and sumatriptan increased allodynic thresholds in CCI groups compared to vehicle (p < 0.01), whereas iNOS knockouts were not different from WT. Photosensitivity was attenuated in MK8825 mice and iNOS knockouts compared to WT (p < 0.05). MK8825 and sumatriptan reduced levels of iNOS mRNA and iNOS immunoreactivity in the TNC and ganglia (p < 0.01). Differences in iNOS cellular localization were found between the trigeminal ganglia and TNC. Although the knockout of iNOS attenuated CGRP at 3 days (p < 0.05), it did not reduce CGRP at 2 weeks. CGRP immunoreactivity was found in the meningeal layers post-CCI, while negligible in controls. Findings support the importance of interactions between CGRP and iNOS in mediating allodynia, as well as the individual roles in photosensitivity. Mitigating prolonged increases in CGRP may be a promising intervention for treating acute PTH.

Comparison of non–stent retriever and stent retriever mechanical thrombectomy devices for the endovascular treatment of acute ischemic stroke

OBJECTIVE Mechanical thrombectomy is standard of care for the treatment of acute ischemic stroke. However, limited data are available from assessment of outcomes of FDA-approved devices. The objective of this study is to compare clinical outcomes, efficacy, and safety of non-stent retriever and stent retriever thrombectomy devices. METHODS Between January 2008 and June 2014, 166 patients treated at Jefferson Hospital for Neuroscience for acute ischemic stroke with mechanical thrombectomy using Merci, Penumbra, Solitaire, or Trevo devices were retrospectively reviewed. Primary outcomes included 90-day modified Rankin Scale (mRS) score, recanalization rate (thrombolysis in cerebral infarction [TICI score]), and incidence of symptomatic intracranial hemorrhages (ICHs). Univariate analysis and multivariate logistic regression determined predictors of mRS Score 3-6, mortality, and TICI Score 3. RESULTS A total of 99 patients were treated with non-stent retriever devices (Merci and Penumbra) and 67 with stent retrievers (Solitaire and Trevo). Stent retrievers yielded lower 90-day NIH Stroke Scale scores and higher rates of 90-day mRS scores ≤ 2 (22.54% [non-stent retriever] vs 61.67% [stent retriever]; p < 0.001), TICI Score 2b-3 recanalization rates (79.80% [non-stent retriever] vs 97.01% [stent retriever]; p < 0.001), percentage of parenchyma salvaged, and discharge rates to home/rehabilitation. The overall incidence of ICH was also significantly lower (40.40% [non-stent retriever] vs 13.43% [stent retriever]; p = 0.002), with a trend toward lower 90-day mortality. Use of non-stent retriever devices was an independent predictor of mRS Scores 3-6 (p = 0.002), while use of stent retrievers was an independent predictor of TICI Score 3 (p < 0.001). CONCLUSIONS Stent retriever mechanical thrombectomy devices achieve higher recanalization rates than non-stent retriever devices in acute ischemic stroke with improved clinical and radiographic outcomes and safety.

Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine.

Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied.

189 Comparison of Efficacy of Tonic and Burst Occipital Nerve Stimulation in Treating Trigeminal Allodynia: Chronic Result.

INTRODUCTION Burst stimulation is a new paradigm that eliminates paresthesias typically observed with traditional tonic stimulation. We used a rodent model of episodic migraine to compare the efficacy of tonic and burst stimulation in treating trigeminal allodynia. METHODS Twelve Sprague-Dawley rats with spontaneous trigeminal allodynia1 were implanted with miniaturized paddle leads over the occipital nerves, and the leads connected to a pulse generator located dorsally. Rats were randomly assigned to receive 4 frequencies: tonic 60 Hz, tonic 500 Hz, burst 40 Hz, and burst 50 Hz. Tonic 500 Hz and burst 50 Hz were the most effective parameters on short-term trials conducted previously. Tonic 60 Hz and burst 40 Hz are the most common parameters in clinical use. After establishing baseline hypersensitivity, the stimulation was turned ON for 10 days, followed by OFF for 10 days. Daily periorbital sensitivity was assessed using von Frey filaments (VFF). Rats were characterized as hypersensitive or as responders when VFF thresholds were 4 g or 6 g, respectively. Analysis of variance tests were used for analysis. RESULTS Overall, both tonic and burst ONS significantly improved VFF thresholds compared with baseline (P < .005). Tonic stimulations had a superior response (P = .022) on day 1, but the burst stimulations produced superior efficacy from day 3. On 3, 4, 6, and 9 of ON days, there were statistically superior reduction of allodynia observed for burst stimulations. After the stimulation was turned OFF on day 10, tonic stimulations lost efficacy sooner, whereas burst stimulations had a trend in maintaining superior efficacy for an additional day (day 11, P = .053). CONCLUSION Tonic stimulation had superior take-off efficacy, but there was a latent positive response associated with burst stimulation that made it superior to tonic stimulation. In addition, burst stimulations exhibited a better therapeutic carryover effect that lasted for a day after stimulation was OFF. Human trials of burst stimulation for headache disorders are warranted to clinically validate our results.