Hippocampal and trigeminal nerve volume predict outcome of surgical treatment for trigeminal neuralgia

Abstract

Background Many medically-refractory trigeminal neuralgia patients are non-responders to surgical treatment. Few studies have explored how trigeminal nerve characteristics relate to surgical outcome, and none have investigated the relationship between subcortical brain structure and treatment outcomes. Methods We retrospectively studied trigeminal neuralgia patients undergoing surgical treatment with microvascular decompression. Preoperative magnetic resonance imaging was used for manual tracing of trigeminal nerves and automated segmentation of hippocampus, amygdala, and thalamus. Nerve and subcortical structure volumes were compared between responders and non-responders and assessed for ability to predict postoperative pain outcome. Results In all, 359 trigeminal neuralgia patients treated surgically from 2005–2018 were identified. A total of 34 patients met the inclusion criteria (32 with classic and two with idiopathic trigeminal neuralgia). Across all patients, thalamus volume was reduced ipsilateral compared to contralateral to the side of pain. Between responders and non-responders, non-responders exhibited larger contralateral trigeminal nerve volume, and larger ipsilateral and contralateral hippocampus volume. Through receiver-operator characteristic curve analyses, contralateral hippocampus volume correctly classified treatment outcome in 82% of cases (91% sensitive, 78% specific, p = 0.008), and contralateral nerve volume correctly classified 81% of cases (91% sensitive, 75% specific, p < 0.001). Binomial logistic regression analysis showed that contralateral hippocampus and contralateral nerve volumes together classified outcome with 84% accuracy (Nagelkerke R2 = 65.1). Conclusion Preoperative hippocampal and trigeminal nerve volume, measured on standard clinical magnetic resonance images, may predict early non-response to surgical treatment for trigeminal neuralgia. Treatment resistance in medically refractory trigeminal neuralgia may depend on the structural features of both the trigeminal nerve and structures involved in limbic components of chronic pain.

Pre-operative limbic system functional connectivity distinguishes responders from non-responders to surgical treatment for trigeminal neuralgia

“…Our patients were suitably representative of medically refractory TN sufferers who are offered surgery, and overall demonstrated a 73% surgical response rate at one year, in agreement with our previous work and the existing literature, notwithstanding differences in the categorization of surgical outcome across studies (4,9). In line with previous reports, non-responders showed a female preponderance and on average suffered from TN for more than twice as long as responders at the time of surgery (20).…”

“…These ndings are in line with recent reports of thalamic hyperactivity compared to HCs both in TN(8), and in other pain conditions affecting the trigeminal system, such as migraine (27). We have previously reported that thalamus volume is enlarged in TN contralateral to the side-of-pain, which may re ect a structural consequence of sustained hyperactivity (9). Overall, our ndings add support to the notion that abnormalities in sensory-relay architecture are indeed a robust feature in patients with TN.…”

“…However, a nerve-centric conceptualization of TN inadequately explains many key features of the disease, notably the development of medicationrefractoriness and variability in response to treatment (4). Several structural and functional brain abnormalities have been identi ed in TN patients, particularly within the limbic system and closely connected paralimbic or sensory-salience structures (e.g., anterior cingulate cortex (ACC), insula, thalamus, and hippocampus (7)(8)(9)(10)(11)). Brain abnormalities in TN show overlap with those observed in other chronic pain and headache conditions: in particular, altered resting-state functional connectivity and atrophy of limbic system structures are recurrent observations (7,8,10,(12)(13)(14)(15), as are alterations in functional connectivity of the right insula, exempli ed in migraine (16) and temporomandibular joint pain (17).…”

“…How structural and functional brain alterations relate speci cally to treatment-resistance in TN, however, has been relatively understudied. We recently showed that structural variability in the limbic systemspeci cally in hippocampal volume-may predict durability of pain relief following surgical treatment in TN (9). However, to date, functional MRI (fMRI) studies explicitly comparing functional connectivity between responders and non-responders to surgery are lacking.…”

The Thalamus in Trigeminal Neuralgia: Structural and Metabolic Abnormalities, and Influence on Surgical Response

“…11 Despite the well-known structural and functional alterations of the thalamus in chronic pain 17 , and its role in the trigeminal sensory system, very few TN studies have directly examined the thalamus or its relationship to treatment outcome. [18][19][20][21] Recently, we retrospectively identi ed pre-operative enlargement of the thalamus contralateral to the painful side of the face in patients with TN 22 , though, whether thalamic volume is related to surgical outcome per se remains uncertain. Accordingly, the motivation for this study was to further elucidate the role of the thalamus in TN.…”