Xiaosong He, Dorian Pustina, Michael R Sperling, Ashwini Sharan, and Joseph I Tracy
Developing a quantitative algorithm for predicting seizure outcome following anterior temporal lobectomy (ATL) in temporal lobe epilepsy (TLE) patient would constitute a significant advance for presurgical decision making. In this project, we tested the ability of topographic properties extracted from presurgical resting-state (rsfMRI) data to predict surgical outcome, using two separate maching learning classification methods (support vector machine, SVM, and random forest RF).
The (R)- isomer of isometheptene decreases trigeminal sensitivity in a rat model of primary headache
Jessica Perino, MS; Nathan T. Fried, PhD; Michael L. Oshinsky, PhD; Bruce Daugherty, PhD, MBA; Seth Lederman, MD; and Melanie B Elliott, PhD
Isometheptene is thought to be the active ingredient of the commonly known headache medication, Midrin. Previously, we found only the (R) enantiomer to be effective in alleviating headache behavior in two models of headache compared to the (S) enantiomer.
Experiments using electrical and mechanical stimulation of the dura in animals with no history of head pain have been used to elucidate the mechanisms of the trigeminovascular system at the level of the trigeminal ganglion, trigeminal nucleus caudalis, periaqueductal gray, and the thalamus. The limitation of these acute models is that electrical and mechanical stimulation of the dural blood vessels does not cause long lasting pain similar to recurrent headache pain in humans. Two animal models for the investigation of headache pathophysiology that include aspects of the chronic nature of headache were included in this study. These models provide a new approach to study the pathophysiology of recurrent headache and support validation of novel treatments.
Using behavior methods of monitoring trigeminal allodynia in rats, our group discovered a rat with spontaneous episodic trigeminal allodynia (STA) (Oshinsky et al, 2012). The model was established through 18 generations of inbreeding for testing analgesics and the further understanding of mechanisms of migraine. STA rats experience similar symptoms to human migraine patients, such as episodic trigeminal sensitivity, phonophobia, responsiveness to abortive and prophylactic headache treatments, and sensitivity to migraine triggers. A second well-characterized model of repeated dural inflammatory stimulation (IS), in which an inflammatory stimulant is infused over the dura, also results in persistent headache behavior that has been accepted as a valid model for drug testing. Although the pathological mechanisms between the two models are different, one being considered idiopathic or a spontaneous model and the other inflammatory in nature, the precise mechanism(s) remain elusive.
The aim of this study is to determine the dose response of the (R)-isomer of isometheptene on trigeminal sensitivity in the STA and IS rat models and study the mechanism of action of isometheptene.
Poster presented at: American Headache Society 58th Annual Scientific Meeting in San Diego CA.
Anitha Somasundaram, MD; Kevin D. Judy, MD; and Kevin Furlong, DO
Metastatic involvement of the pituitary gland is extremely rare. We present a case of metastatic pituitary disease with panhypopituitarism and diabetes insipidus.
Anitha Somasundaram, MD and Edward B. Ruby, MD
Giant hemangiomas of the adrenal gland are very rare. We present a case of giant adrenal hemangioma presenting as adrenal incidentaloma.
Cannabinoid receptor type-2 modulates nociceptive signaling molecules in a model of post-concussion headache
Jarred M. Stratton, Lan Cheng, Ashley L. Tyburski, Jessica Perino, and Melanie B Elliott
The goal of this study was to investigate the role of the cannabinoid receptor type-2 (CB2R) in the trigeminal pain pathway in a model of post-concussion headache. Sprague Dawley rats were randomized to receive either a repeated mild closed head injury (CHI) or served as incision controls. Changes in CGRP, nNOS, and IBA-1 were assessed in the trigeminal nucleus caudalis (TNC) and trigeminal ganglia via IHC. A subset of CHI rats received either a cannabinoid receptor type 2 (CB2R) anti-inflammatory agonist (JWH133), an NSAID (Ketorolac), or vehicle and underwent von Frey testing for trigeminal allodynia. An in vitro brain slice study was performed on TNC and cerebrum slices incubated with capsaicin, capsaicin plus a or media control solutions for 24hrs; CGRP and PGE2 were assessed via ELISA. Repeated CHI showed increases in CGRP and PGE2, and altered nNOS and IBA-1 immunoreactivity in the trigeminal ganglia and TNC, respectively. JWH-133 blocked capsaicin-induced increases in CGRP and PGE2 in the TNC and cerebrum slices. Findings show the CB2R modulates trigeminal pain in a model of concussion, although the mechanisms eliciting analgesia warrant a more in depth investigation.
Poster presented at: American Headache Society in San Diego California.
Non-psychotropic cannabinoid based therapy modulates nociceptive signaling molecules, microglia, and pain behavior in a model of post-concussion headache
Jarred M. Stratton, Lan Cheng, Ashley L. Tyburski, Jessica Perino, and Melanie B. Elliott
Background & Objectives
Headache is a common symptom of post-concussion syndrome which may persist in a substantial portion of patients contributing to a poor quality of life and disability. There is a pressing need to develop novel treatments for post-traumatic headache as current treatments have a number of side effects, are contraindicated or lack efficacy. The Elliott laboratory first established models of post-traumatic headache demonstrating sensitization of trigeminal neurons in rodent models of post-traumatic headache using well-known nociceptive and behavioral markers in the pain and migraine fields1-3. Traumatic brain injury in mice increases expression of calcitonin gene related peptide (CGRP) and inducible nitric oxide synthase (iNOS) in the trigeminal pathway, changes that are accompanied by persistent headache behavior, trigeminal allodynia1-3.
The endogenous cannabinoid (eCB) system is a potential therapeutic target for post-traumatic headache. In a series of studies, our laboratory showed CB2R-mediated anti-inflammatory actions in a model of TBI, whereby the reduction of iNOS mRNA and protein and substance P immunoreactivity have implications for headache4-6. The cannabinoid receptor type-2 (CB2R) is an ideal analgesic target as it is devoid of psychoactive properties, shows anti-nociceptive actions upon stimulation, and regulates immune function. What is unclear, is precisely how anti-nociceptive actions are elicited by the CB2R, and if CB2R stimulation will be effective at alleviating trigeminal hypersensitivity in model of post-traumatic concussion or closed head injury. The objective of this study was to determine the role of the CB2R in the trigeminal pain pathway in a model of post-concussion headache, while identifying mechanisms underlying trigeminal pain after mild TBI.
Functional Integrity of Resting-state Networks predicts Seizure Outcome after Anterior Temporal Lobectomy
Gaelle Doucet, Xiaosong He, Michael R. Sperling, Ashwini Sharan MD, and Joseph I. Tracy
Predicting seizure outcome (SO) after anterior temporal lobectomy (ATL) is a major clinical goal. With clear evidence that even focal epilepsies disrupt large scale brain networks, resting-state functional connectivity (FC) methods have been increasingly used on a pre-surgical basis to characterize the impact of seizures on brain activity. In this project, we sought to determine whether the functional integrity of resting-state networks (RSNs) prior to surgery can discriminate between patients who obtain good versus poor seizure control after ATL.