A New Clinical Syndrome: Trigeminal Neuralgia Associated with a Brain Lesion

Post by Kasey Hemington

What's the science?

Trigeminal Neuralgia (TN) is an excruciatingly painful condition. Patients experience severe pain attacks in areas associated with the trigeminal nerve, which innervates the face. In some cases, TN is associated with demyelination (damage to myelin – a protective covering for the nerve) either due to compression of the trigeminal nerve itself or secondary to Multiple Sclerosis (MS-TN), which can cause demyelinating plaques in the brainstem. A few case studies have noted that some TN patients have lesions of the brainstem, but do not have Multiple Sclerosis. However, this unique patient sub-group has not been extensively studied. This week in PAIN, Tohyama and colleagues used magnetic resonance imaging (MRI) and clinical evidence to define a new syndrome: TN associated with solitary pontine lesion (SPL-TN; ‘pontine’ refers to the pons, a region of the brainstem)

How did they do it?

The authors examined clinical records and MRI brain scans for 481 TN patients who underwent neurosurgical TN treatment (commonly gamma knife surgery, a non-invasive type of surgery that uses beams of radiation). All patients underwent an anatomical MRI (T1-weighted), and a subset of patients also underwent a diffusion-weighted MRI. SPL-TN was defined based on an idiopathic TN diagnosis (e.g. TN not secondary to Multiple Sclerosis), a single lesion along the trigeminal nerve pathway, and no other brain lesions. To characterize the lesions, the authors used an anatomical MRI and mapped the lesion by hand in each patient before comparing lesion distribution and area across subjects. The authors hypothesized SPL-TN patients to be surgical treatment non-responders, and defined treatment non-response as having undergone three or more surgical procedures, or having undergone one surgical procedure without experiencing substantial pain relief. Lack of relief was defined as <75% pain reduction using an 11-point pain Numerical Rating Scale and a score of 4 or higher on the Barrow Neurological Institute Scale, which measures the frequency of medication use for pain control.

From diffusion-weighted MRI scans of the lesions, the authors calculated metrics including fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, which reflect the brain’s white matter microstructure, neuroinflammation, myelination, and axonal integrity, respectively. To act as a healthy control group, the authors recruited healthy individuals, age- and sex-matched to SPL-TN patients for whom anatomical and diffusion-weighted MRI brain scans were available. The healthy control group underwent these same brain scans.

What did they find?

Upon reviewing the 481 TN patient records, the authors found 24 cases of SPL-TN. Eighteen of those patients had clinical follow-up information available post-surgery and it was determined that 17/18 of those patients did not respond to surgical treatment, suggesting non-response to surgical treatment is characteristic of SPL-TN. For these 17 patients (6 men, 11 women), lesions were mapped and found to be along the trigeminal pathway in the pons on the affected side of the brain in all cases. Overlap amongst patients was maximal in the trigeminal brainstem sensory nuclear complex. Diffusion-weighted MRI scans were available for 11 of the 17 patients, and were used to compare the lesions on the affected side of the brain in SPL-TN patients versus a) the same region on the non-affected side and b) the brains of 11 healthy controls. No differences in fractional anisotropy, mean diffusivity, axial diffusivity, or radial diffusivity were found between the non-affected side in patients and healthy controls, while lower fractional anisotropy and higher mean diffusivity and radial diffusivity were found on the affected side versus the non-affected sides and healthy controls. Additionally, axial diffusivity was higher on the affected side versus the non-affected side. These findings indicate abnormal white matter properties in SPL-TN lesions.

FA = Fractional Anisotropy, MD = Mean Diffusivity, RD = Radial Diffusivity, AD = Axial Diffusivity

SPL-TN patient lesions were also compared to lesions in a group of 17 MS-TN patients, age-matched for the age of TN onset. In MS-TN patients, between 1-5 lesions could be found along the trigeminal nerve pathway. No differences between groups were found in diffusivity metrics when comparing whole lesions. However, when the analysis was restricted precisely to the trigeminal brainstem tract within a lesion, lower fractional anisotropy, and higher axial diffusivity, mean diffusivity, and radial diffusivity were found in SPL-TN lesions versus MS-TN lesions.

What's the impact?

This study is the first to define SPL-TN, a subtype of TN characterized by non-response to surgical treatment and a single brainstem lesion commonly in the trigeminal nucleus. These lesions have changes in diffusivity metrics that characterize abnormal white matter microstructure. The identification of SPL-TN will guide specialized treatment plans for these patients.

Tohyama et al. Trigeminal neuralgia associated with a solitary pontine lesion. PAIN (2020). Access the original scientific publication here.