Induction of calcitonin gene-related peptide expression in rats by cortical spreading depression.

OBJECTIVE: The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. METHODS: CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. RESULTS: The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased CGRP was observed in the ipsilateral frontal, motor, somatosensory, and visual cortices, but not the cingulate cortex, or contralateral cortices. CSD also induced CGRP peptide expression in the ipsilateral, but not contralateral, cortex. CONCLUSIONS: Repeated CSD provides a mechanism for prolonged elevation of CGRP in the cerebral cortex, which may contribute to migraine and post-traumatic headache.

Neuropathologic changes associated with stereoelectroencephalography depth electrode placement.

BACKGROUND: The aim of this study was to detail the neuropathologic changes resulting from the surgical placement of stereoelectroencephalography (SEEG) leads in an initial small group of epilepsy cases and to raise awareness of this iatrogenic pathology, especially to those medical providers who specialize in the care of epilepsy patients. METHODS: Five consecutive patients who underwent epilepsy resection surgery following SEEG monitoring at OSF Saint Francis Medical Center were included in our report. Resection specimens were examined grossly and entirely submitted for microscopic evaluation by a neuropathologist. Seizure-related pathologies, as well as histologic changes related to SEEG electrode placement, were documented. RESULTS: The patient cohort included two females and three males, with an age range of 9 to 47 years. Neuropathologic examination revealed one or more seizure-related pathologies in each patient's resection specimen. In addition, all brain resection specimens showed multiple microinfarcts, which appeared to correlate with the placement and size of SEEG electrodes. Patchy leptomeningeal chronic inflammation was also seen in most cases. CONCLUSIONS: SEEG electrode placement is an effective procedure for determining epileptogenic regions and guiding subsequent resection surgeries in medically refractory epilepsy. Multiple microinfarcts and chronic inflammation are commonly seen in brain resection specimens following SEEG electrode insertion, but studies detailing these iatrogenic histopathologic changes are lacking. The clinical significance and long-term implications of multiple small foci of electrode-induced injury that remain in the patient's brain after resection of the epileptogenic focus are unknown and may provide a welcome area for future study.

Neural activity in trigeminal neuralgia patients with sensory and motor stimulations: A pilot functional MRI study.

OBJECTIVE: Trigeminal neuralgia (TN) is a neuropathic pain syndrome that typically exhibits paroxysmal pain. However, the true mechanism of pain processing is unclear. We aim to evaluate the neural activity changes, before and after radiofrequency rhizotomy, in TN patients using functional MRI (fMRI) with sensory and motor stimulations. METHODS: Six patients with classical TN participated in the study. Each patient underwent two boxcar paradigms of fMRI tasks: air-sensation and jaw-clenching around 1-3 weeks before and after the surgical intervention. McGill Pain Questionnaire (MPQ) was used to evaluate the pain intensity prior to fMRI study. RESULTS: Before rhizotomy, the jaw-clenching stimulation yielded reduced brain activation in primary motor (M1) and primary (SI) and secondary somatosensory (SII) cortices. Following intervention, activation in those regions returned to near normal levels observed in healthy subjects. For air-sensation stimulation, several pain and pain modulation regions such as right thalamus, right putamen, insula, and brainstem, were activated before the intervention, but subsided after the intervention. This correlated well with the change of MPQ scores (p < 0.01). CONCLUSIONS: In our study, we observed significant pain reduction accompanied by increased motor activities after rhizotomy in patients with TN. We hypothesize that the reduced motor activities identified in fMRI may be reversed after the treatment with radiofrequency rhizotomy. More research is warranted.