Evaluating Persistent Neurosensory Disturbances After Trigeminal Nerve Injury

Motor Neurons (Multipolar) with many Processes
Motor Neurons (Multipolar) with many Processes (mostly Dendrites), Spinal Cord–50X. Shows: 4 multipolar neurons, processes (mostly dendrites), cell bodies, nuclei and neuroglial cells. These motor neurons are located in the anterior (ventral) horn of the spinal cord (gray matter).
Researchers sought to identify risk factors for neurosensory disturbances persistence in patients with posttraumatic trigeminal neuropathies.

Persistent neurosensory disturbances (NSDs) are common after trigeminal nerve injury, with numerous patient- and surgery-related factors contributing to neurosensory recovery, according to authors of a study published in Pain.

The investigators believe their study is the first to investigate a large population of patients with posttraumatic trigeminal neuropathies (PTTNs) and posttraumatic trigeminal neuropathic pain.

To identify risk factors for NSD persistence in patients with PTTNs, researchers analyzed retrospective, longitudinal data from a patient cohort in Belgium, then developed a prognostic prediction model. They also sought to determine ways in which symptoms might evolve over time in patients with persistent NSDs.

Data were collected from the TrigNerVeBeUK (TNVBUK) Registry (ClinicalTrials.gov Identifier: NCT04612855). Patients were screened between 2010 and 2018 for posttraumatic trigeminal nerve injury and a clinical diagnosis of a neurosensory deficit.

Neuroassessment protocols employed included qualitative sensory testing. Patients were categorized into painful and nonpainful PTTN groups based on recent ICOP (International Classification of Orofacial Pain) criteria.

In total, 384 patients (66% women; mean age, 50.1±16.6 years) were included in the study. The mean follow-up period was 322±302 weeks. Sixty percent of patients presented with a persistent trigeminal nerve injury; the most frequently damaged nerve was the inferior alveolar nerve (45%), followed by the maxillary nerve and its terminal branches (35%). In 34% of cases, third molar surgery was the causative event, followed by tooth extraction (29%) and dental implant placement (19%). Most patients experienced sensory loss and pain—40% and 24%, respectively—with a mean visual analogue scale (VAS) pain score of 2.3 out of 10.

Treatments included over-the-counter analgesics (65% of patients), antidepressants (45%), and opioids (14%); 18% had topical treatment and 8% required surgical intervention. Among those who received surgical intervention, improvement was noted in 42%.

Several patient- and surgery-related predictors were significantly associated with persistent NSDs. Results of a bivariate analysis showed that women were more likely to experience persistent NSDs (odds ratio [OR], 2.23; 95% CI, 1.39-3.58), as were older patients (OR, 1.03; 95% CI, 1.02-1.05).

Lingual nerve injuries were associated with significantly lower rates of persistent NSDs (OR, 0.48; 95% CI, 0.27-0.85), while maxillary nerve lesions were more associated with persistent rather than temporary NSDs (OR, 3.05; 95% CI, 1.80-5.18).

Persistent NSDs were also associated with the presence of pain (OR, 3.39; 95% CI, 1.82-6.30) and with higher pain VAS scores (OR, 1.35; 95% CI, 1.19-1.53). Thermal hyperesthesia was also more frequent among patients with persistent NSDs (OR, 5.10; 95% CI, 1.97-13.25).

More pain diagnoses were associated with persistent NSDs (OR, 26.20; 95% CI, 1.58-434.99), and the condition was generally associated with a lower quality of life as indicated by a lower VAS score (OR, 0.94; 95% CI, 0.92-0.97). Those with persistent NSDs rated their current health at 65±1.9 of 100, vs a score of 80±1.4 of 100 by those with temporary NSDs.

Fifteen variables were entered into a statistically significant logistic regression model. The model explained 46% of variance found in persistent trigeminal nerve injuries, and correctly classified 76.9% of cases with a sensitivity of 81.8%, a specificity of 70%, a positive predictive value of 79.4%, and a negative predictive value of 73.1%.

Six of the 15 variables were statistically significant: sex, pain caused by local anesthesia, extraction, third molar surgery or endodontic treatment, and the presence of thermal hyperesthesia. According to researchers, the discrimination of the model was “excellent” (overall AUC, 0.84; 95% CI, 0.79-0.90).

After pain was dichotomized into low and moderate to high intensity groups, a significant correlation was observed between age, sex, injured nerve, and initiating event. Odds of moderate to severe pain increased with the presence of neurosensory disturbances and thermal or mechanical hyperesthesia.

Results of bivariate analyses also showed that age, sex, injured nerve, third molar surgery initiation, persistence of NSDs, sensory loss phenotype, and the number of other pain diagnoses was associated significantly with patient quality of life, which was particularly adversely impacted when patients had maxillary nerve lesions, NSDs, or multiple pain diagnoses.

Pairwise Kaplan-Meier distributions showed a statistically significant difference in NSD frequency over time between sex, age, painful and nonpainful PTTNs, initiating event, injured nerve, and sensory profile. Older age, female sex, and diagnosis of painful PTTN were all negatively associated with time to symptom resolution; painful diagnoses demonstrated less tendency towards recovery of neurosensory disturbances—86.2% of patients still reported these disturbances after 2 years.

Those with lingual nerve injuries had the best long-term outcomes; only 44% experienced disturbances after 2 years. Comparatively, patients with maxillary nerve lesions reported “almost no improvement” of disturbances over time (with 92% still experiencing NSDs after 2 years).

Study limitations include those inherent to retrospective analyses, potential selection bias associated with the tertiary setting, and qualitative sensory testing.

“The proposed multivariable prediction model may aid in predicting an individualized estimate of neurosensory recovery, but further prospective validation is needed,” the researchers concluded.


Van der Cruyssen F, Peeters F, De Laat A, Jacobs R, Politis C, Renton T. Prognostic factors, symptom evaluation, and quality of life of posttraumatic trigeminal neuropathy. Pain. Published online July 13, 2021. doi:10.1097/j.pain.0000000000002408