Epidural Posterior Insular Stimulation Alleviates Neuropathic Pain Manifestations in Rats With Spared Nerve Injury Through Endogenous Opioid System.

OBJECTIVES: Neuropathic pain (NP) is defined as constant disabling pain secondary to a lesion or disease of the somatosensory nervous system. This condition is particularly difficult to treat because it often remains resistant to most treatment strategies. Despite the recent diversification of neurostimulation methods, some patients still suffer from refractory pain syndromes. The central role of the posterior insular cortex (PI) in the modulation of pain signaling and perception has been repeatedly suggested. The objective of this study is to assess whether epidural insular stimulation (IS) could reverse NP behavior. MATERIALS AND METHODS: A total of 53 adult Sprague-Dawley rats received left-sided spared nerve injury (SNI) or Sham-SNI to induce NP symptoms. Afterward, epidural electrodes were implanted over the right PI. After two weeks of postoperative recovery, three groups of SNI-operated rats each received a different stimulation modality: Sham-IS, low-frequency-IS (LF-IS), or high-frequency-IS (HF-IS). Behavioral and functional tests were conducted before and after IS. They comprised the acetone test, pinprick test, von Frey test, and sciatic functional index. An additional LF-IS group received a dose of opioid antagonist naloxone before IS. Intergroup means were compared through independent-samples t-tests, and pre- and post-IS means in the same group were compared through paired t-tests. RESULTS: We found a significant reduction of cold allodynia (p = 0.019), mechanical hyperalgesia (p = 0.040), and functional disability (p = 0.005) after LF-IS but not HF-IS. Mechanical allodynia only showed a tendency to decrease after LF-IS. The observed analgesic effects were reversed by opioid antagonist administration. CONCLUSION: These results suggest a significant reversal of NP symptoms after LF-IS and offer additional evidence that IS might be beneficial in the treatment of resistant NP syndromes through endogenous opioid secretion. Relying on our novel epidural IS model, further fine tuning of stimulation parameters might be necessary to achieve optimal therapeutic effects.

Pentoxifylline significantly reduces radicular pain secondary to lumbar disc hernia: A prospective, randomized crossover, single-blind controlled pilot study.

BACKGROUND AND OBJECTIVES: Optimal medical treatment for low back pain, sometimes associated to radicular pain, has yet to be established. Herniated nucleus pulposus has been found to release TNFα, a pro-inflammatory cytokine involved in radiculopathy. Interestingly, Pentoxifylline (PTX), a phosphodiesterase inhibitor, blocks the activity of TNFα. The aim of this study is to assess the effectiveness of PTX when added to the treatment protocol of radiculopathy in lumbar disc herniation. METHODS: Fifty-eight patients with radicular pain secondary to a lumbar disc hernia were included in this prospective, randomized crossover, single-blind controlled study. PTX was added randomly to the same treatment protocol (ibuprofen + paracetamol + pregabalin) either during the first or the second 15 days of treatment. Patients' pain was assessed at day 15 via the Numeric Rating Scale (NRS) and the Patient's Global Impression of Change score (PGIC). D15 NRS value was considered as the primary outcome measure. RESULTS: Mean D15 NRS score was 3.2 ± 0.84 during the 15-days treatment with PTX, and 5,1 ± 0.97 during the 15-days treatment without PTX (p < 0.0001). During the 15 days treatment period with/without PTX, PGIC score was (7) in 19/3 patients, (6) in 30/10 patients, (5) in 7/27 patients and (4) in 2/18 patients respectively, difference being highly significant (p < 0.0000). CONCLUSION: Adjunction of PTX to the standard medical treatment of radicular pain associated with lumbar disc hernia seems to significantly decrease patients' pain intensity in addition to improving their global satisfaction with treatment.

Infratentorial ganglioglioma mimicking a cerebellar metastasis.

We report a case of an infratentorial ganglioglioma in a 56-year-old male, who underwent magnetic resonance imaging (MRI) during the diagnostic workup for a suspected lung cancer. The MRI scan revealed a space-occupying lesion of the left lobulus semilunaris superior cerebelli, which was assumed being a metastasis. The asymptomatic lesion was resected to establish the diagnosis. Histologic and immunohistochemical studies showed a ganglioglioma with World Health Organization grade I characteristics. Although ganglioglioma typically exhibits a supratentorial predilection, it should be included in the differential diagnosis of lesions occurring in the cerebellum.

False-positive results in transcranial motor evoked potentials for outcome prognostication during surgery for supratentorial lesions.

During monitoring of motor evoked potentials (MEP) elicited by transcranial electrical stimulation (TES) for prognostication of postoperative motor deficit, significant MEP changes without postoperative deterioration of motor function represent false-positive results. We aimed to investigate this phenomenon in a large series of patients who underwent resection of supratentorial lesions. TES was applied in 264 patients during resection of motor-eloquent supratentorial lesions. MEP were recorded bilaterally from arm, leg, and/ or facial muscles. The threshold criterion was applied assessing percentage increase in threshold level, which was considered significant if being > 20% higher on affected side than on the unaffected side. Subcortical stimulation was additionally applied to estimate the distance to corticospinal tract. Motor function was evaluated at 24 h after surgery and at 3-month follow-up. Patients with false-positive results were analyzed regarding tumor location, tumor volume, and characteristics of the monitoring. MEP were recorded from 399 muscles (264 arm muscles, 75 leg muscles, and 60 facial muscles). Motor function was unchanged postoperatively in 359 muscles in 228 patients. Among these cases, the threshold level did not change significantly in 354 muscles in 224 patients, while it increased significantly in the remaining 5 muscles in 4 patients (abductor pollicis brevis in all four patients and orbicularis oris in one patient), leading to a false-positive rate of 1.1%. Tumor volume, opening the ventricle, and negative subcortical stimulation did not significantly correlate with false-positive results, while the tumor location in the parietal lobe dorsal to the postcentral gyrus correlated significantly (p = 0.012, odds ratio 11.2, 95% CI 1.8 to 69.8). False-negative results took place in 1.1% of cases in a large series of TES-MEP monitoring using the threshold criterion. Tumor location in the parietal lobe dorsal to the postcentral gyrus was the only predictor of false-positive results.

Somatosensory Thalamic Activity Modulation by Posterior Insular Stimulation: Cues to Clinical Application Based on Comparison of Frequencies in a Cat Model.

BACKGROUND: The posterior insula (PI) has been proposed as a potential neurostimulation target for neuropathic pain relief as it represents a key-structure in pain processing. However, currently available data remain inconclusive as to efficient stimulation parameters. OBJECTIVE: As frequency was shown to be the most correlated parameter to pain relief, this study aims to evaluate the potential modulatory effects of low frequency (LF-IS, 50 Hz) and high-frequency (HF-IS, 150 Hz) posterior insular stimulation on the activity of somatosensory thalamic nuclei. MATERIALS AND METHODS: Epidural bipolar electrodes were placed over the PI of healthy adult cats, and extracellular single-unit activities of nociceptive (NS), nonnociceptive (NN), and wide dynamic range (WDR) thalamic cells were recorded within the ventral posterolateral nucleus and the medial division of the thalamic posterior complex. Mean discharge frequency and burst firing mode were analyzed before and after either LF-IS or HF-IS. RESULTS: LF-IS showed a significant thalamic modulatory effects increasing the firing rate of NN cells (p ≤ 0.03) and decreasing the burst firing of NS cells (p ≤ 0.03), independently of the thalamic nucleus. Conversely, HF-IS did not induce any change in firing properties of the three recorded cell types. CONCLUSION: These data indicate that 50 Hz IS could be a better candidate to control neuropathic pain.