Altered perivascular-aligned diffusivity in postherpetic neuralgia assessed by the DTI-ALPS index

The glymphatic system has been proposed as a key pathway for interstitial fluid clearance in the brain, but its role in chronic neuropathic pain conditions such as postherpetic neuralgia (PHN) remains unclear. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has been suggested as a noninvasive proxy of perivascular-aligned diffusivity related to glymphatic-associated processes.

A total of 83 participants were recruited, comprising 42 patients with PHN and 41 age- and sex-matched healthy controls. All participants underwent DTI, and the DTI-ALPS index was calculated using DSI Studio. The primary group comparison was performed using analysis of covariance adjusted for age and white matter hypointensity volume. In the PHN group, neuropathic symptom severity was assessed using the Douleur Neuropathique en 4 questionnaire (DN4).

In the primary adjusted analysis, the DTI-ALPS index remained lower in patients with PHN than in healthy controls (estimated marginal means: 1.247 vs. 1.348; mean difference = -0.100, 95% CI: -0.172 to -0.029, p = 0.006). In an exploratory subgroup analysis, participants with higher DN4 scores (≥ 4) had a higher DTI-ALPS index than those with lower DN4 scores (<4) (1.270 vs. 1.108, p = 0.023). In patients with PHN, the DTI-ALPS index was negatively correlated with age (r = -0.397, p = 0.009) and positively correlated with DN4 score (r = 0.441, p = 0.003).

Patients with PHN demonstrate altered perivascular-aligned water diffusivity as reflected by the DTI-ALPS index. These findings may reflect alterations in perivascular-aligned diffusivity, an indirect proxy related to glymphatic-associated processes. Further studies are warranted to clarify the relationship between neuropathic pain and glymphatic-related processes.