The association between orofacial neurotoxicity and chemotherapy treatment is still unclear. In this context, the purpose of this study is to relate the orofacial alterations that manifest during antineoplastic pharmacological treatment, highlighting the drugs commonly related to orofacial neuropathy and the adequate instrument to verify the alterations at clinical levels.
This prospective cohort study, addressed patients who would start therapy with taxanes, platinum, or related therapy. The collection of signs and symptoms was divided into 3 different times (baseline, second or third cycle of antineoplastic chemotherapy treatment, and sixth cycle). A total of 40 patients were submitted to the application of the Short McGill pain questionnaire and Neutoxicity Induced by Antineoplastics questionnaire (QNIA). To verify sensory alterations in the face, a clinical evaluation was performed with the help of Semmes-Weinstein monofilaments.
Taxanes show greater orofacial neurotoxic potential, being associated with sensory alterations assessed by monofilaments (P = .003) and the presence of orofacial pain analyzed by the Short McGill pain questionnaire (P = .001). These medications related to neuropathy in the orofacial region measured through the QNIA, demonstrating a predominantly acute nature (P < .001).
It is suggested that chemotherapy may induce neurotoxicity in the orofacial region.

We determined the efficacy and safety of 0.1% RGN-259 ophthalmic solution (containing the regenerative protein thymosin ß4) in promoting the healing of persistent epithelial defects in patients with Stages 2 and 3 neurotrophic keratopathy. Complete healing occurred after 4 weeks in 6 of the 10 RGN-259-treated subjects and in 1 of the 8 placebo-treated subjects (p = 0.0656), indicating a strong efficacy trend. Additional efficacy was seen in the significant healing (p = 0.0359) with no recurrent defects observed at day 43, two weeks after cessation of treatment, while the one healed placebo-treated subject at day 28 suffered a recurrence at day 43. The Mackie classification disease stage improved in the RGN-259-treated group at Days 29, 36, and 43 (p = 0.0818, 0.0625, and 0.0467, respectively). Time to complete healing also showed a trend towards efficacy (p = 0.0829, Kaplan-Meier) with 0.1% RGN-259. RGN-259-treated subjects had significant improvements at multiple time points in ocular discomfort, foreign body sensation, and dryness which were not seen in the placebo group. No significant adverse effects were observed. In summary, the use of 0.1% RGN-259 promotes rapid healing of epithelial defects in neurotrophic keratopathy, improves ocular comfort, and is safe for treating this challenging population of patients.

UNASSIGNED: Data on the outcomes of microsurgical resection (SR) and stereotactic gamma knife radiosurgery (GKRS) in patients with trigeminal neuralgia associated with small petrous apex meningiomas are scarce.
UNASSIGNED: We conducted this study to evaluate the pain relief, tumor control, and procedure costs following SR and GKRS for small petroclival meningiomas (less than 3 cm in maximal diameter) using real-world data from our center in Egypt.
UNASSIGNED: We conducted a retrospective cohort study of 47 patients with small petrous apex meningiomas presenting with intractable trigeminal nerve pain (SR: n = 22 and GKRS: n = 25). Data regarding pain relief on Barrow Neurological Institute (BNI), procedure cost, and tumor control were retrieved and analyzed using appropriate statistical tests.
UNASSIGNED: Patients who underwent SR had lower median BNI pain intensity scores compared to those patients who underwent GKRS, and a significantly higher proportion of patients in the SR group had good BNI scores compared to those in GKRS group (P < 0.05); however, the total costs of SR were significantly less than GKRS (30,519$ vs. 92,372$, respectively).
UNASSIGNED: Both SR and GKRS provide pain relief and tumor control in patients with trigeminal neuralgia associated with petrous apex meningioma. However, in the present study, SR achieved better pain control and was more affordable than GKRS.

OBJECTIVE: To investigate the effect of multiple sclerosis (MS) on corneal and retinal nerve fiber by quantifying corneal subbasal nerve fibers and retinal ganglion cells.
METHODS: A total of 46 eyes of 23 patients with MS and 42 eyes of 21 healthy subjects were included in the study. All patients and healthy subjects underwent a comprehensive ocular examination. In vivo confocal microscopy with Heidelberg Retina Tomograph in association with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany) and a swept-source optical coherence tomography (Topcon Corporation) were performed in all patients and healthy subjects. The number of subbasal nerve fibers and the nerve fiber density were calculated. Student t test was used to compare eyes with MS with control eyes. The normal distribution was first confirmed with the Shapiro-Wilk test.
RESULTS: A statistically significant (P < 0.05) decrease was found for nerve fiber number, ganglion cell-inner plexiform layer, and retinal nerve fiber layer in patients with MS compared with those of healthy subjects. Moreover, an inverse correlation was found between retinal nerve fiber layer (r = -0.32), nerve fiber number (r = -0.47), and ganglion cell-inner plexiform layer (r = -0.51) and Expanded Disability Status Scale. A direct correlation between Expanded Disability Status Scale and optic neuritis frequency was found (r = 0.322).
CONCLUSIONS: In vivo confocal microscopy showed a difference in corneal morphological parameters and retinal damage; moreover, these changes seemed to be related to the degree of neurological disability. Both retinal ganglion and trigeminal cell atrophy measurements could become affordable and accessible biomarkers for clinical trials in progressive disease.

UNASSIGNED: Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies.
UNASSIGNED: This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis.
UNASSIGNED: Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients.
UNASSIGNED: Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.

To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes.
Seventy individuals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve; TNS ≥ 2; T1D, n = 19; T2D, n = 16) and without DPN (DPN-ve; TNS ≤ 1; T1D, n = 19; T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN.
In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced (P < .010) in DPN+ve. Also, for the nerve excitability measures, mean peak response, percentage of threshold electrotonus at peak and after 90-100 ms, superexcitability and subexcitability were significantly reduced (P < .050) in DPN+ve. In T2D, except for inferior whorl length (P = .190), all other corneal confocal microscopy measures were significantly reduced (P < .010) in DPN+ve, but there was no difference in substance P concentration. For the diagnosis of DPN in T1D, the AUC for inferior whorl length (0.910), mean peak response (0.800) and concentration of substance P (0.770) were high and in T2D, the AUC for corneal nerve fiber length (0.809) and nerve fractal dimension (0.777) were high.
Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.

To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy.
Multicenter, randomized, double-masked, vehicle-controlled trial.
Patients with neurotrophic persistent epithelial defect with or without stromal thinning.
The NGF0214 trial, conducted among 11 sites in the United States, randomized 48 patients 1:1 to cenegermin 20 μg/ml or vehicle eye drops, 6 drops daily for 8 weeks of masked treatment. Follow-up was 24 weeks. Safety was assessed in all patients who received study drug. Efficacy was assessed by intention to treat.
The primary end point was healing of the neurotrophic lesion (persistent epithelial defect or corneal ulcer) after 8 weeks of masked treatment. Masked central readers measured neurotrophic lesions in randomized clinical pictures, then assessed healing status conventionally (<0.5 mm of fluorescein staining in the greatest dimension of the lesion area) and conservatively (0-mm lesion staining and no other residual staining). Secondary variables included corneal healing at 4 weeks of masked treatment (key secondary end point), overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity from baseline to week 8.
Conventional assessment of corneal healing showed statistically significant differences at week 8: compared to 7 of 24 vehicle-treated patients (29.2%), 16 of 23 cenegermin-treated patients (69.6%) achieved less than 0.5 mm of lesion staining (+40.4%; 95% confidence interval [CI], 14.2%-66.6%; P = 0.006). Conservative assessment of corneal healing also reached statistical significance at week 8: compared to 4 of 24 vehicle-treated patients (16.7%), 15 of 23 cenegermin-treated patients (65.2%) achieved 0 mm of lesion staining and no other residual staining (+48.6%; 95% CI, 24.0%-73.1%; P < 0.001). Moreover, the conservative measure of corneal healing showed statistical significance at week 4 (key secondary end point). Compared to vehicle, cenegermin-treated patients showed statistically significant reductions in lesion size and disease progression rates during masked treatment. Cenegermin was well tolerated; adverse effects were mostly local, mild, and transient.
Cenegermin treatment showed higher rates of corneal healing than vehicle in neurotrophic keratopathy associated with nonhealing corneal defects.

Purpose: This study aimed to characterize the sensory profile of patients with post-implant trigeminal neuropathy and identify the association between subjective symptoms and objective signs including psychophysical testing and radiographic imaging. This study further evaluated to the association between quantitative sensory testing (QST)/qualitative sensory testing (QualST) and the severity of nerve injury graded by radiographic imaging. Materials and methods: This retrospective study included 34 patients diagnosed with post-implant trigeminal neuropathy. Data on the neuropathic pain symptom inventory (NPSI), thermal and electric QST, bedside QualST, and cone beam computed tomography (CBCT) was collected and the association between these variables were analysed. Results: Numbness was the most common subjective symptom and evoked pain was the most frequent neuropathic pain. There was no significant correlation between negative and positive symptoms. Spearman\'s rank correlation analyses indicated that objective findings including QST/QualST correlated with a sensory loss profile rather than a gain of function profile. Moderate positive correlations between some positive symptoms and the score of QualST were observed. The Mann-Whitney U test showed that subjective symptoms did not differ according to the severity of nerve damage according to CBCT, but the electric QST and QualST was discriminative. Conclusions: This study suggests that QST/QualST associated with the severity of nerve damage according to CBCT might be useful in assessing numbness in patients with negative and positive symptoms after implant surgery, but may be of marginal utility in the evaluation of neuropathic pain within the limitation of this cross-sectional study with small sample size.

暂无摘要。

Transient receptor potential ankyrin type-1 (TRPA1) channels are known to actively participate in different pain conditions, including trigeminal neuropathic pain, whose clinical treatment is still unsatisfactory. The aim of this study was to evaluate the involvement of TRPA1 channels by means of the antagonist ADM_12 in trigeminal neuropathic pain, in order to identify possible therapeutic targets. A single treatment of ADM_12 in rats 4 weeks after the chronic constriction injury of the infraorbital nerve (IoN-CCI) significantly reduced the mechanical allodynia induced in the IoN-CCI rats. Additionally, ADM_12 was able to abolish the increased levels of TRPA1, calcitonin gene-related peptide (CGRP), substance P (SP), and cytokines gene expression in trigeminal ganglia, cervical spinal cord, and medulla induced in the IoN-CCI rats. By contrast, no significant differences between groups were seen as regards CGRP and SP protein expression in the pars caudalis of the spinal nucleus of the trigeminal nerve. ADM_12 also reduced TRP vanilloid type-1 (TRPV1) gene expression in the same areas after IoN-CCI. Our findings show the involvement of both TRPA1 and TRPV1 channels in trigeminal neuropathic pain, and in particular, in trigeminal mechanical allodynia. Furthermore, they provide grounds for the use of ADM_12 in the treatment of trigeminal neuropathic pain.