Nimodipine improves vocal fold and facial motion recovery after injury: A systematic review and meta-analysis.

INTRODUCTION: Nimodipine is a calcium channel blocker that has been used to treat hypertension and vasospasm. Emerging evidence in the literature suggests that it is neuroprotective by reducing cellular apoptosis after neuronal injury and promoting axonal sprouting at the nodes of Ranvier. OBJECTIVES: To conduct a systematic review of the usage of nimodipine in cranial nerve injury and to perform a meta-analysis to estimate the efficacy of nimodipine on functional recovery of the injured cranial nerves. METHODS: Literature search was performed in eight databases using preferred reporting items for systematic reviews and meta analyses (PRISMA) guidelines. Human studies that used nimodipine as a monotherapy for treating cranial nerve injury were included for review. Cranial nerve function recovery was the primary outcome measure. RESULTS: 672 records were screened and 58 full texts in English were assessed. Nine studies were included in the final review. 5 of these, including 110 participants who received nimodipine for either recurrent laryngeal nerve or facial nerve injury and 556 controls, were used for meta-analysis. Nimodipine significantly increased the odds of vocal fold motion recovery (odds ratio [OR] 13.73, 95% confidence interval [CI] 6.21, 30.38, P < .01), and the odds of facial motion recovery (OR 2.78, 95% CI 1.20, 6.44, P = .02). Overall, nimodipine-treated patients had significantly higher odds of recovering vocal fold or facial motion compared with controls (OR 6.09, 95% CI 3.41, 10.87, P < .01). CONCLUSION: Existing evidence supports the positive effect of nimodipine on vocal fold and facial motion recovery after injury. Future research should focus on randomized clinical trials comparing recovery rates between nimodipine- and placebo-treated groups. Laryngoscope, 129:943-951, 2019.

Multiple cranial nerve injuries and neck abscesses caused by a transorally penetrating organic stick.

Foreign bodies cause a remarkable number of otolaryngological emergency visits and occasionally result in life-threatening conditions and later-emerging complications. Patient recovery depends on the detection and proper extraction of all foreign materials. Despite various obtainable diagnostic tools, adequate anamnesis forms the basis of clinical reasoning and should direct later examinations and radiological imaging. This case report describes a challenging patient with a unique trauma mechanism: many pieces of a fragmented organic foreign body emerged within 1 year of the initial injury, leading to repeated operations, a long period in an intensive care unit and a long-term swallowing and speech dysfunction.

Collapsin Response Mediator Protein-2 Ameliorates Sevoflurane-Mediated Neurocyte Injury by Targeting PI3K-mTOR-S6K Pathway.

BACKGROUND Collapsin response mediator protein-2 (CRMP-2) is the first member of the CRMP family that has been identified in primary neuronal cells; it was originally found and identified in the regulation of microtubule dimerization into microtubules. MATERIAL AND METHODS In the present study, we aimed to investigate the roles and mechanisms of CRMP-2 in sevoflurane-induced neurocyte injury. Cell viability, proliferation, and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Colorimetry was performed to measure the activity of caspase-3. Western blot and quantitative real-time reverse transcription assays were used to evaluate the related mRNAs and proteins expression. RESULTS We found that CRMP-2 reversed the inhibitory effect of sevoflurane on the viability of nerve cells. Moreover, CRMP-2 accelerated the proliferation and suppressed the apoptosis of sevoflurane-induced nerve cells. CRMP-2 modulated the expression levels of apoptosis-associated protein in sevoflurane-induced nerve cells. Furthermore, it was demonstrated that CRMP-2 impacted the PI3K-mTOR-S6K pathway. CONCLUSIONS CRMP2 ameliorated sevoflurane-mediated neurocyte injury by targeting the PI3K-mTOR-S6K pathway. Thus, CRMP2 might be an effective target for sevoflurane-induced neurocyte injury therapies.

Complement component C3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis.

Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

Pharmacologic management of trigeminal nerve injury pain after dental implant surgery.

PURPOSE: Injuries to the trigeminal nerve are a common postoperative complication of dental implant surgery. Usually, the altered sensation and neuropathic pain caused by the nerve injury is temporary, but a permanent neurosensory disorder can sometimes occur. Surgery is commonly used to treat this condition, but the treatment is associated with some complications and a relatively low success rate. This study analyzed the characteristics of pharmacologic management of trigeminal nerve injury pain after dental implant surgery. MATERIALS AND METHODS: Eighty-five patients who visited a temporomandibular joint and orofacial pain clinic with a history of trigeminal nerve injury pain after dental implant surgery were enrolled in this study. The pharmacologic management for trigeminal nerve injury pain was evaluated by prescribing a variety of medications for 12 weeks according to the prescription protocol of the study. The patients' pain characteristics, average percentage of pain reduction, and pain relieving factors were investigated prospectively. RESULTS: Patients who took anticonvulsants and antidepressants for at least 12 weeks reported a mean reduction in pain of 24.8%. Interestingly, patients who experienced an altered sensation and neuropathic pain for more than 1 year also reported a reduction in pain and discomfort, with an average decrease of 17.1%. In addition, it was found that early treatment using medications had a significant effect on reducing the level of pain and discomfort. CONCLUSION: These results suggest that pharmacologic management can be used for treating trigeminal nerve injury pain after dental implant surgery.

Use of botulinum toxin type A injection for neuropathic pain after trigeminal nerve injury.

OBJECTIVE: To present a case that neuropathic pain following traumatic injury of the inferior alveolar nerve, which was relieved by the injection of BTX-A. DESIGN: Case report. SETTING: Tertiary care University hospital. SUBJECT: A 62-year-old female was referred by her general dentist to our clinic due to numbness and pain over the left side of her lower lip and chin region. INTERVENTION: Botulinum toxin type A injected into the middle of chin area subcutaneously. RESULTS: At 1 month after BTX-A injection, the affected area had decreased in size. And at 2 months, the patient reported a slight decreased in pain, and CPT differences being sustained at a reduced level. CONCLUSIONS: This case report suggests an effective new modality for treating neuropathic pain after trigeminal nerve injury. A further randomized controlled study involving a large number of patients is needed.

Effect of SB-750364, a specific TRPV1 receptor antagonist, on injury-induced ectopic discharge in the lingual nerve.

Abnormal neural activity generated at a site of nerve injury is thought to contribute to the development of dysaesthesia. Vanilloid receptor 1 (TRPV1), a transducer of noxious stimuli, may be involved in the initiation of this abnormal activity and could provide a useful therapeutic target. We investigated the effect of a specific TRPV1 antagonist (SB-750364) on injury-induced discharge in the lingual nerve. In 12 anaesthetised adult ferrets the left lingual nerve was sectioned and animals were allowed to recover for 3-7 days. In terminal experiments under general anaesthesia, the nerve was re-exposed and electrophysiological recordings made from spontaneously active axons in fine filaments dissected from the nerve central to both the injury site and the junction with the chorda tympani. SB-750364 was infused via the cephalic vein in order to achieve three increasing but stable systemic blood levels of the compound (0.3, 1.0 and 3.0 microM). Twenty-eight spontaneously active units were studied, with discharge frequencies ranging from 0.02 to 4.9 Hz. There was a significant reduction in spontaneous activity in 17 units (61%) at 1.0 microM or less of SB-750364 (p<0.01; Friedman test with Dunn's multiple comparisons). A further 4 units (14%) showed a significant reduction in activity at 3.0 microM (p<0.01). In the remaining 7 units (25%) the discharge was unaffected (p>0.05). These data show that the TRPV1 antagonist SB-750364 can reduce the level of spontaneous activity initiated in some axons following lingual nerve injury.

Curative-like analgesia in a neuropathic pain model: parametric analysis of the dose and the duration of treatment with a high-efficacy 5-HT(1A) receptor agonist.

High-efficacy activation of central 5-HT(1A) receptors by means of the recently discovered, selective 5-HT(1A) receptor ligand, F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]methyl}piperidin-1-yl]methanone, fumaric acid salt] causes an unprecedented, broad-spectrum analgesia in rat models of acute and chronic pain of nociceptive and neuropathic origin; it also is effective in conditions where opioids either are ineffective, induce analgesic tolerance, or elicit persistent hyperalgesia/allodynia. Inversely mirroring morphine's actions, F 13640's ("curative-like") analgesic effects persist after the discontinuation of treatment. Here, we examined the relationships, if any, between the dose and the duration of F 13640 treatment on the one hand, and the duration of persistent analgesia on the other. Rats received unilateral infraorbital nerve injury and developed allodynia - as assessed by an increased response to von Frey filament stimulation - within 24 days; thereafter, using osmotic pumps, rats were subcutaneously infused with F 13640 in two experiments. In one, a one-week infusion was instituted at 0.04-10-mg/day doses; in a second experiment, a 0.63-mg/day dose was implemented for a duration ranging from 1 to 56 days. These 250- and 56-fold variations of the dose and duration of treatment caused post-treatment, persistent analgesia for about 10 and 40 days, respectively. At least as much as dose, the duration of F 13640 treatment determines F 13640-induced persistent analgesia. Neuroadaptive modulations at pre- and postsynaptic, brain and spinal cord 5-HT(1A) receptors may be involved in the dynamical, dose- and time-dependent, pre-treatment rise and post-treatment decay of the analgesia induced by high-efficacy 5-HT(1A) receptor activation.

The effect of carbamazepine on injury-induced ectopic discharge in the lingual nerve.

Previous studies have shown that the development of ectopic activity from damaged axons following nerve injury may contribute to the aetiology of sensory disturbances, including dysaesthesia. Pharmacological manipulation of this activity could provide a method of treatment for this intractable condition. In this study we have investigated the effect of carbamazepine, an anti-convulsant, as it is known to have membrane stabilising properties. In eight anaesthetised adult ferrets the left lingual nerve was sectioned and the animals allowed to recover for 3 days. Then, in terminal experiments under general anaesthesia, the nerve was re-exposed and electrophysiological recordings were made from spontaneously active units in fine filaments dissected from the nerve proximal to the injury site. Carbamazepine in a modified cyclodextrin (hydroxypropyl-beta-cyclodextrin) was administered intravenously in increments, in order to achieve a progressively increasing systemic concentration, and serum levels were determined at the point that activity ceased. Twenty-one spontaneously active units were studied, with conduction velocities of 2.1-28.9 m s(-1) and discharge frequencies of 0.25-15.3 Hz. Spontaneous activity ceased in 13 units with a serum concentration of carbamazepine ranging from 3.5 to 8.4 mg/l, which was within the normal therapeutic range (4-12 mg/l). Four units ceased activity with carbamazepine levels above the therapeutic range (15.4-17.2 mg/ml), but the remaining four continued to discharge throughout the recording period. These data suggest that systemic carbamazepine can reduce the level of spontaneous activity initiated in some axons following lingual nerve injury.

The effect of substance P on the spontaneous discharge from injured inferior alveolar nerve fibres in the ferret.

Previous studies in our laboratory have shown that, at a site of inferior alveolar nerve (IAN) injury, there is a close association between the development of spontaneous neural activity and the accumulation of neuropeptides in the damaged axons. As this ectopic activity may contribute to the development of sensory disturbances after injury, we have examined further this relationship by determining the potential role of one neuropeptide, substance P (SP), in the initiation or modulation of the spontaneous discharge. Thirty-six adult ferrets were anaesthetised, the IAN sectioned, and the animals allowed to recover for 3-4 days. In terminal experiments under general anaesthesia, electrophysiological recordings were made from axons in fine filaments dissected from the nerve, central to the injury site. The effect of SP (2 x 10(-12), 10(-6) and 10(-4) M) and SP-antagonist (10(-4) M) applied either close-arterially or topically to the injury site was determined. Of the 101 units studied, 59% were spontaneously active. Close-arterial administration of SP increased the level of spontaneous discharge in a dose-dependent manner, with higher concentrations affecting more units (2 x 10(-12) M, 14%; 10(-6) M, 58%; 10(-4) M, 85%). SP also initiated spontaneous discharge in some previously silent units. Activity in 46% of units also increased in response to the SP-antagonist. None of the units responded to topical application of either SP or SP-antagonist. This study shows that SP can both initiate and modulate the spontaneous discharge from damaged axons, and this mechanism may be a potential therapeutic target in the management of sensory disturbances after nerve injury.

Efficacy of steroid treatment for sensory impairment after orthognathic surgery.

PURPOSE: Steroid hormones are therapeutic for motor and/or sensory dysfunctions caused by nerve injury. However, the timing for giving such medicine is unclear. This study aimed to estimate the efficacy of steroid treatment and determine an appropriate start time after sensory impairment. PATIENTS AND METHODS: Twenty-seven patients with sensory impairment who received orthognathic surgery were classified into groups called 1W (n = 6), 3W (n = 6), or 6W (n = 8) group on the basis of start time for steroid treatment, being 1 week, 3 weeks, or 6 weeks after surgery, respectively, and a no steroid treatment (NST) group (a control group) (n = 6) that did not receive treatment for 10 to 12 weeks after surgery. Sensory impairment was diagnosed if postoperative first week mechanical-touch threshold was over 4.0 as measured by Semmes aesthesiometer. Prednisolone treatment was administered orally to patients at 30 mg for 7 days, 15 mg for 4 days, and 5 mg for 3 days. Mechanical-touch threshold and thermal perceptions were compared before and after treatment. RESULTS: At 1 week postoperatively, there were no significant differences in mechanical-touch threshold among the 4 groups (analysis of variance, P >.05). Changes in mechanical-touch threshold in the 1W group showed no significant improvement (analysis of variance, P >.05), but in the 3W and 6W groups, there were significant differences compared with the NST group (Dunns methods, P <.05). CONCLUSIONS: Steroid treatment for sensory impairment after orthognathic surgery has the potential to accelerate recovery and it appears desirable to start treatment later than 1 week postoperatively.