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Surgical Interventions Targeting the Nucleus Caudalis for Craniofacial Pain: A Systematic and Historical Review

Open AccessPublished:September 30, 2022DOI:https://doi.org/10.1016/j.neurom.2022.08.454

      Abstract

      Introduction

      Craniofacial pain is a prevalent group of conditions, and when refractory to conventional treatments, it poses a significant burden. The last decade has seen a renewed interest in the multimodal management of pain. Interventions targeting the nucleus caudalis (NC) of the trigeminocervical complex have been available as a treatment option since the 1930s, yet evidence for efficacy remains limited.

      Materials and Methods

      We present a systematic review of the literature providing a historical perspective on interventions targeting the NC leading up to the present. We examine the various intervention techniques, clinical indications, and procedural efficacy. A novel outcome-reporting scheme was devised to enable comparison among studies owing to historically variable reporting methods.

      Results

      A review of the literature revealed 33 retrospective studies published over the last 80 years, reporting on 827 patients. The most common technique was the open NC dorsal root entry zone nucleotomy/tractotomy; however, there has been an emergence of novel approaches such as endoscopic and spinal cord stimulation in the last ten years. Regardless of intervention technique or preoperative diagnosis, 87% of patients showed improvement with treatment.

      Conclusions

      The literature surrounding NC intervention techniques is reviewed. Recent advancements and the wide range of craniofacial pain syndromes for which these interventions show potential efficacy are discussed. New and less invasive techniques continue to emerge as putative therapeutic options. However, prospective studies are lacking. Furthermore, the evidence supporting even well-established techniques remains of poor quality. Future work should be prospective, use standard outcome reporting, and address efficacy comparisons between intervention type and preoperative diagnosis.

      Keywords

      Introduction

      Refractory craniofacial pain is a heterogeneous group of disorders with multiple classification systems depending on clinical features that include anatomical distribution, anatomical origin, pathology, and symptomatology.
      • Zakrzewska J.M.
      Facial pain: neurological and non-neurological.
      The prevalence of craniofacial pain is estimated to be 26%.
      • Macfarlane T.V.
      • Blinkhorn A.S.
      • Davies R.M.
      • Kincey J.
      • Worthington H.V.
      Oro-facial pain in the community: prevalence and associated impact.
      Epidemiologic studies have yet to define the social and economic burden of this complex and debilitating group of diseases; however, estimates may be made from the literature on trigeminal neuralgia (TN), the best studied of the chronic craniofacial pain syndromes outside the realm of headache. TN has been reported to affect multiple health status domains, including activity, mood, ambulation, work, relationships, sleep, and life enjoyment.
      • Tölle T.
      • Dukes E.
      • Sadosky A.
      Patient burden of trigeminal neuralgia: results from a cross-sectional survey of health state impairment and treatment patterns in six European countries.
      More than one-third of patients with TN had employment affected through work-hour reduction, disability, or unemployment.
      • Tölle T.
      • Dukes E.
      • Sadosky A.
      Patient burden of trigeminal neuralgia: results from a cross-sectional survey of health state impairment and treatment patterns in six European countries.
      Despite advancements over the past two decades, many patients with TN remain refractory to medical and conventional surgical options.
      • Cruccu G.
      • Aziz T.Z.
      • Garcia-Larrea L.
      • et al.
      EFNS guidelines on neurostimulation therapy for neuropathic pain.
      Conventional surgical approaches to treat TN have targeted the nerve root and ganglion with demonstrated efficacy in treating typical paroxysmal TN type 1 pain but are relatively ineffective at treating the background pain characteristic of TN type 2.
      • Tyler-Kabara E.C.
      • Kassam A.B.
      • Horowitz M.H.
      • et al.
      Predictors of outcome in surgically managed patients with typical and atypical trigeminal neuralgia: comparison of results following microvascular decompression.
      Worsening of constant background pain and the development of neuropathic pain can be seen with repeated treatments targeting the anterior system (distal to the nerve root).
      • Broggi G.
      • Ferroli P.
      • Franzini A.
      • Galosi L.
      The role of surgery in the treatment of typical and atypical facial pain.
      Therefore, an investigation into alternative surgical approaches and treatment options for these syndromes remains crucial to improving pain management.
      Nociceptive craniofacial sensation, temperature, and crude touch are carried by general somatic afferent first-order neurons of the fifth, seventh, ninth, and tenth cranial nerves to the trigeminocervical nuclear complex, where they synapse to second-order neurons within the nucleus caudalis (NC).
      • Bullard D.E.
      • Nashold Jr., B.S.
      The caudalis DREZ for facial pain.
      The trigeminal nucleus forms ascending connections to structures involved in processing nociceptive stimuli, such as the thalamus, hypothalamus, locus coeruleus, and periaqueductal gray. Here, nociceptive stimuli are modulated, and pain is perceived.
      • Goadsby P.J.
      • Holland P.R.
      • Martins-Oliveira M.
      • Hoffmann J.
      • Schankin C.
      • Akerman S.
      Pathophysiology of migraine: a disorder of sensory processing.
      There is partial functional overlap between the C2 and C3 substantia gelatinosa and the NC, and it is this close anatomical relationship that inspired the use of dorsal root entry zone (DREZ) lesioning techniques to treat craniofacial pain.
      • Goadsby P.J.
      • Holland P.R.
      • Martins-Oliveira M.
      • Hoffmann J.
      • Schankin C.
      • Akerman S.
      Pathophysiology of migraine: a disorder of sensory processing.
      Interruption of the trigeminocervical complex at the level of the brainstem was first reported in humans in 1938.
      • Sjoqvist O.
      Studies of pain conduction in the trigeminal nerve.
      Introduced in 1968, DREZ procedures for chronic pain have progressed to include various methods of lesioning or modulating the DREZ at the spinal level of the pain, attempting to eliminate hyperactivity and spontaneous discharges that result in central perception of pain.
      • Loeser J.D.
      • Ward A.A.
      • White L.E.
      Chronic deafferentation of human spinal cord neurons.
      • Guenot M.
      • Bullier J.
      • Rospars J.P.
      • Lansky P.
      • Mertens P.
      • Sindou M.
      Single-unit analysis of the spinal dorsal horn in patients with neuropathic pain.
      • Sindou M.
      Drez lesions for brachial plexus injury.
      • Drake C.G.
      • Stavraky G.W.
      An extension of the law of denervation to afferent neurones.
      Favorable outcomes in DREZ operations for other pain syndromes and advancements in techniques for open and percutaneous trigeminal tractotomy helped provide motivation for NC DREZ procedures for craniofacial pain.
      • Mckenzie K.G.
      Trigeminal tractotomy.
      • Hitchock E.R.
      • Schvarcz J.R.
      Stereotaxic trigeminal tractotomy for post-herpetic facial pain.
      • Schvarcz J.R.
      Spinal cord stereotactic techniques re trigeminal nucleotomy and extralemniscal myelotomy.
      • Gorecki J.P.
      • Nashold Jr., B.S.
      • Rubin L.
      • Ovelmen-Levitt J.
      The Duke experience with nucleus caudalis DREZ coagulation.
      Similarly to standard spinal DREZ procedures that target the dorsal horn of the spine, NC DREZ operations target the spinal trigeminal nucleus pars caudalis at the cervicomedullary junction, relieving pain through destruction of the second-order neurons.
      • Loeser J.D.
      • Ward A.A.
      • White L.E.
      Chronic deafferentation of human spinal cord neurons.
      ,
      • Gorecki J.P.
      • Nashold Jr., B.S.
      • Rubin L.
      • Ovelmen-Levitt J.
      The Duke experience with nucleus caudalis DREZ coagulation.
      • Anderson L.S.
      • Black R.G.
      • Abraham J.
      • Ward A.A.
      Neuronal hyperactivity in experimental trigeminal deafferentation.
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      • Moossy J.J.
      Nucleus caudalis DREZ lesions for facial pain.
      Although the first application of lesioning of the trigeminocervical complex dates to the 1930s, prospective studies assessing its efficacy and indications remain lacking. Evidence supporting the use of surgical techniques targeting the NC is limited to small retrospective case reports and case series. A comprehensive summary of the efficacy, indications, and variations in intervention technique has yet to be reported. In this study, we performed a systematic review of the literature published regarding the surgical intervention of the NC, providing an historical perspective for the development of NC-related interventions to the present day.

      Materials and Methods

      Literature Search and Inclusion Criteria

      On May 31, 2021, we conducted a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase, MEDLINE, and Cochrane CENTRAL data bases were queried using the search strategy indicated in Supplementary Data Supplementary Material 1. The search comprised the search terms (combination of subject headings and keywords) “caudalis,” “trigeminal nucleus,” “trigeminal tractotomy,” “trigeminal nucleotractotomy,” “trigeminal nucleotomy,” “dorsal root entry zone,” “ablation,” “lesion,” “stimulation,” and various combinations of the above.
      The search strategies were modified for each data base to include data base-specific thesaurus terms, syntax, and field names. Only original peer-reviewed clinical studies in humans published in the English language were included. Studies were not restricted on the basis of diagnosis or the lesioning/stimulation method. Additional relevant studies that met our inclusion criteria were identified through examination of bibliographies of relevant articles and selected reviews. Conference abstracts and unpublished studies were excluded. Anatomical studies, descriptions of technique, studies reporting on the same patient population, and reviews were excluded. Full-text analysis excluded studies with fewer than five patients as a method to reduce bias from case reports or small case series. The Population, Intervention, Comparison, Outcomes, and Study Design format was used to depict study eligibility with prespecified inclusion and exclusion criteria (Table 1).
      Table 1Inclusion and Exclusion Criteria Used for Article Screening Presented in Population, Intervention, Comparison, Outcomes, and Study Design Format.
      Framework itemInclusion criteriaExclusion criteriaData extracted
      PopulationPatients who underwent NC intervention for craniofacial pain.

      Adults (18 y of age or older).
      Patients who underwent intervention at anatomical site other than NC.

      Children, adolescents, or nonhuman subjects.
      Total number of patients (n)

      Preoperative diagnosis
      InterventionNC lesioning or modulation for craniofacial pain.Anatomic studies or studies focused on description of technique or technologic advancement.Intervention technique used.
      ComparatorSingle-arm studies reporting outcome data.Studies published on the same patient population.Intervention technique utilized.
      OutcomePain-related outcomes.

      Procedure-related complications.
      None.Pre- and postoperative pain rating.

      Mean follow-up duration.

      Total number of perioperative complications, in addition to postoperative facial dysfunction, corneal anesthesia, oropharyngeal dysfunction, ataxia, limb dysfunction, transient neurological dysfunction, reoperation rate, general medical complication, and mortality.
      Study designAny clinical study design: randomized control trial, observational (case-control; retrospective or prospective cohort), case series.Nonclinical study.

      Conference abstract, review, editorial, letter, or commentary.

      Study cohort of < 5 patients.
      Study design.

      Year of publication.

      Quality Assessment

      Two reviewers (Brendan Santyr, Mohamad Abbass) independently screened each article title and abstract for relevance. Disagreements were resolved by discussion and consensus in the presence of a third reviewer (Alan Chalil). All authors reviewed the preliminary results and the final analysis.

      Data Collection and Outcome Measures

      Of the included studies, information regarding study type, study size, mean follow-up duration, interventional technique, preoperative diagnosis, and pre- and postoperative pain rating was collected (Table 2). Postoperative pain rating was considered a primary outcome. Mean follow-up duration was collected in years after intervention. All reported preoperative diagnoses were collected and classified on the basis of available information. Diagnostic classification included TN or trigeminal neuropathic pain, oncologic craniofacial pain, postherpetic pain, anesthesia dolorosa, traumatic craniofacial pain, glossopharyngeal neuralgia, poststroke craniofacial pain, headache or migraine, multiple sclerosis-related craniofacial pain, and geniculate neuralgia. Most of the literature failed to distinguish between different classifications or causes of craniofacial pain, thereby necessitating the combination of these pathophysiological entities. Intervention techniques were classified into all procedural variations of open procedures targeting the NC or trigeminocervical complex, including nucleotomy, nucleotomy/tractotomy, and DREZ lesioning procedures; computed tomography (CT)-guided and free-hand percutaneous nucleotomy/tractotomy; endoscopic DREZ nucleotomy/tractotomy; cervical spinal cord stimulation (SCS); and ultrasonic nucleotomy (Fig. 1). Information regarding total perioperative complications was collected. These were further subdivided into postoperative facial dysfunction (pain, numbness, weakness), corneal anesthesia, oropharyngeal dysfunction (dysarthria, dysphagia, vocal cord paralysis), ataxia, limb dysfunction (pain, numbness, weakness, dysmetria), transient dysfunction (pain, numbness, weakness, ataxia), reoperation rate, general medical complication, and mortality.
      Table 2Summary of Articles Reporting Interventions Targeting the Nucleus Caudalis for Craniofacial Pain.
      Author (y)Patients, no.Diagnoses (n)Intervention techniquePercent of patients improved
      Grant et al (1940)
      • Grant F.C.
      • Groff R.
      • Lewy F.H.
      Section of the descending spinal root of the fifth cranial nerve.
      12TN (4)

      Oncologic (8)
      Open DREZ nucleotomy/tractotomy100%
      Grant (1941)
      • Grant F.C.
      Experiences with intramedullary tractotomy.
      17TN (6)

      Oncologic (11)
      Open DREZ nucleotomy/tractotomy88%
      Olivecrona (1942)
      • Olivecrona H.
      Tractotomy for relief of trigeminal neuralgia.
      34TN (34)Open DREZ nucleotomy/tractotomy91%
      Hamby et al (1948)
      • Hamby W.B.
      • Shinners B.
      • Marsh I.
      Trigeminal tractotomy: observations on forty-eight cases.
      48TN (35)

      Oncologic (13)
      Open DREZ nucleotomy/tractotomy67%
      Falconer (1949)
      • Falconer M.A.
      Intramedullary trigeminal tractotomy and its place in the treatment of facial pain.
      20TN (13)

      Postherpetic (4)

      Anesthesia dolorosa (2)

      Not specified (1)
      Open DREZ nucleotomy/tractotomy84%
      Guidetti (1950)
      • Guidetti B.
      Tractotomy for the relief of trigeminal neuralgia; observations in 124 cases.
      97TN (97)Open DREZ nucleotomy/tractotomyNot reported
      Raney et al (1950)
      • Raney R.
      • Raney A.A.
      • Hunter C.R.
      Treatment of major trigeminal neuralgia through section of the trigeminospinal tract in the medulla.
      59TN (59)Open DREZ nucleotomy/tractotomy62%
      Kunc (1965)
      • Kunc Z.
      Treatment of essential neuralgia of the 9th nerve by selective tractotomy.
      6Glossopharyngeal neuralgia (6)Open DREZ nucleotomy/tractotomy100%
      Fox (1971)
      • Fox J.L.
      Intractable facial pain relieved by percutaneous trigeminal tractotomy.
      12TN (1)

      Oncologic (7)

      Postherpetic (2)

      Anesthesia dolorosa (2)
      Percutaneous nucleotomy/tractotomy67%
      Hosobuchi and Rutkin (1971)
      • Hosobuchi Y.
      • Rutkin B.
      Descending trigeminal tractotomy. Neurophysiological approach.
      6TN (1)

      Oncologic (3)

      Anesthesia dolorosa (1)

      Not specified (1)
      Open DREZ nucleotomy/tractotomy100%
      Crue et al (1972)
      • Crue B.L.
      • Carregal E.J.A.
      • Felsoory A.
      Percutaneous stereotactic radiofrequency trigeminal tractotomy with neurophysiological Recordings1.
      12TN (4)

      Oncologic (8)
      Percutaneous nucleotomy/tractotomy100%
      Fox (1973)
      • Fox J.L.
      Percutaneous trigeminal tractotomy for facial pain.
      18Oncologic (14)

      Postherpetic (2)

      Anesthesia dolorosa (1)

      Not specified (1)
      Percutaneous nucleotomy/tractotomy61%
      Schvarcz (1978)
      • Schvarcz J.R.
      Spinal cord stereotactic techniques re trigeminal nucleotomy and extralemniscal myelotomy.
      100TN (19)

      Oncologic (31)

      Trauma (25)

      Anesthesia dolorosa (14)

      Postherpetic (8)

      Glossopharyngeal neuralgia (2)

      MS (1)
      Percutaneous nucleotomy/tractotomy77%
      Plangger et al (1987)
      • Plangger C.A.
      • Fischer J.
      • Grunert V.
      • Mohsenipour I.
      Tractotomy and partial vertical nucleotomy--for treatment of special forms of trigeminal neuralgia and cancer pain of face and neck.
      20TN (12)

      Oncologic (6)

      Postherpetic (1)

      Anesthesia dolorosa (1)
      Open DREZ nucleotomy/tractotomy100%
      Bernard et al (1988)
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      27Not specified (27)Open DREZ nucleotomy/tractotomy95%
      Rossitch et al (1989)
      • Rossitch Jr., E.
      • Zeidman S.M.
      • Nashold Jr., B.S.
      Nucleus caudalis DREZ for facial pain due to cancer.
      5Oncologic (5)Open DREZ nucleotomy/tractotomy100%
      Young et al (1989)
      • Young J.N.
      • Nashold Jr., B.S.
      • Cosman E.R.
      A new insulated caudalis nucleus DREZ electrode. Technical note.
      9Not specified (9)Open DREZ nucleotomy/tractotomyNot reported
      Morita and Hosobuchi (1992)
      • Morita M.
      • Hosobuchi Y.
      Descending trigeminal tractotomy for trigeminal neuralgia after surgical failure.
      7TN (7)Open DREZ nucleotomy/tractotomy100%
      Grigoryan (1994)
      • Grigoryan YuA.
      • Slavin K.V.
      • Ogleznev K.Ya
      Ultrasonic lesion of the trigeminal nucleus caudalis for deafferentation facial pain.
      14Oncologic (10)

      Postherpetic (4)
      Ultrasonic nucleotomy93%
      Nashold et al (1994)
      • Nashold B.S.
      • El-Naggar A.O.
      • Ovelmen-Levitt J.
      • Abdul-Hak M.
      A new design of radiofrequency lesion electrodes for use in the caudalis nucleus DREZ operation. Technical note.
      21TN (8)

      Postherpetic (5)

      Anesthesia dolorosa (2)

      Traumatic (1)

      Poststroke (3)

      MS (1)

      Headache (1)
      Open DREZ nucleotomy/tractotomy57%
      Gorecki et al (1995)
      • Gorecki J.P.
      • Nashold Jr., B.S.
      • Rubin L.
      • Ovelmen-Levitt J.
      The Duke experience with nucleus caudalis DREZ coagulation.
      46Oncologic (1)

      Postherpetic (8)

      Anesthesia dolorosa (15)

      Poststroke (5)

      MS (1)

      Headache (4)

      Not specified (12)
      Open DREZ nucleotomy/tractotomy83%
      Kanpolat and Cosman (1996)
      • Kanpolat Y.
      • Cosman E.R.
      Special radiofrequency electrode system for computed tomography-guided pain-relieving procedures.
      19TN (14)

      Oncologic (5)
      Percutaneous nucleotomy/tractotomyNot reported
      Bullard and Nashold (1997)
      • Bullard D.E.
      • Nashold Jr., B.S.
      The caudalis DREZ for facial pain.
      25TN (8)

      Oncologic (1)

      Postherpetic (1)

      Anesthesia dolorosa (3)

      Traumatic (4)

      Poststroke (1)

      MS (3)

      Not specified (4)
      Open DREZ nucleotomy/tractotomy100%
      Husain et al (2002)
      • Husain A.M.
      • Elliott S.L.
      • Gorecki J.P.
      Neurophysiological monitoring for the nucleus caudalis dorsal root entry zone operation.
      5Postherpetic (1)

      Traumatic (2)

      Headache (1)

      Not specified (1)
      Open DREZ nucleotomy/tractotomy80%
      Delgado-Lopez (2003)
      • Delgado-López P.
      • García-Salazar F.
      • Mateo-Sierra O.
      • Carrillo-Yagüe R.
      • Llauradó G.
      • López E.
      Trigeminal nucleus caudalis dorsal root entry zone radiofrequency thermocoagulation for invalidating facial pain.
      6Anesthesia dolorosa (6)Open DREZ nucleotomy/tractotomy83%
      Teixeira et al (2003)
      • Teixeira M.J.
      • Lepski G.
      • Aguiar P.H.P.
      • Cescato V.A.S.
      • Rogano L.
      • Alaminos A.B.
      Bulbar trigeminal stereotactic nucleotractotomy for treatment of facial pain.
      58TN (2)

      Postherpetic (28)

      Oncologic (14)

      Poststroke (7)

      Not specified (7)
      Percutaneous nucleotomy/tractotomy90%
      Kanpolat (2008)
      • Kanpolat Y.
      • Kahilogullari G.
      • Ugur H.C.
      • Elhan A.H.
      Computed tomography-guided percutaneous trigeminal tractotomy-nucleotomy.
      65TN (5)

      Oncologic (13)

      Postherpetic (3)

      Anesthesia dolorosa (1)

      Glossopharyngeal neuralgia (17)

      Geniculate neuralgia (4)

      Headache (1)

      Not specified (21)
      Percutaneous nucleotomy/tractotomy95%
      Kanpolat (2008)
      • Kanpolat Y.
      • Tuna H.
      • Bozkurt M.
      • Elhan A.H.
      Spinal and nucleus caudalis dorsal root entry zone operations for chronic pain.
      11TN (5)

      Oncologic (3)

      Glossopharyngeal neuralgia (2)

      Geniculate neuralgia (1)
      Open DREZ nucleotomy/tractotomy73%
      Raslan (2008)
      • Raslan A.M.
      Percutaneous computed tomography-guided radiofrequency ablation of upper spinal cord pain pathways for cancer-related pain.
      10Oncologic (10)Percutaneous nucleotomy/tractotomy80%
      Chivukula et al (2015)
      • Chivukula S.
      • Tempel Z.J.
      • Chen C.J.
      • Shin S.S.
      • Gande A.V.
      • Moossy J.J.
      Spinal and nucleus caudalis dorsal root entry zone lesioning for chronic pain: efficacy and outcomes.
      16TN (9)

      Postherpetic (3)

      Glossopharyngeal neuralgia (3)

      Traumatic (1)
      Open DREZ nucleotomy/tractotomy100%
      Rahimpour and Patel (2015)
      • Rahimpour S.
      • Patel V.
      Endoscopic trigeminal nucleus caudalis doral root entry zone lesioning for atypical facial pain.
      5Not specified (5)Endoscopic DREZ nucleotomy/tractotomy80%
      VPatel and Lohani (2018)
      • Patel K v
      • Lohani M.
      Paresthesia-free relief: higher frequency stimulation of high cervical leads for patients with chronic facial pain.
      5Not specified (5)Cervical SCS100%
      Velásquez et al (2018)
      • Velásquez C.
      • Tambirajoo K.
      • Franceschini P.
      • Eldridge P.R.
      • Farah J.O.
      Upper cervical SCS as an alternative treatment in trigeminal neuropathy.
      12Traumatic (12)Cervical SCS75%
      MS, multiple sclerosis.
      Figure thumbnail gr1
      Figure 1Illustration of the dorsal aspect of the cervicomedullary junction, depicting the lesion site for nucleus caudalis interventions including DREZ nucleotomy/tractotomy, percutaneous nucleotomy/tractotomy, and cervical SCS. PICA, posterior inferior cerebellar artery.
      Owing to the historical nature of this review dating back to the first descriptions of interventional procedures involving the NC, we observed a wide variability of methods for reporting pain in the literature. Most commonly, qualitative and nonstandardized methods were used to report pain outcomes, with only five studies reporting using the standardized Visual Analog Scale (VAS). To accommodate this and facilitate the comparison of modern and classic studies, a composite rating scale was employed in this review (Table 3). A composite pain score of 1 includes patients who are pain free, VAS 0, or who have had a 100% pain reduction. A pain score of 2 includes those with a “good” response, VAS 1 to 3, or a > 50% pain reduction. A pain score of 3 includes those with a “satisfactory” or “fair” response, VAS 4 to 6, or a < 50% pain reduction. Finally, a pain score of 4 includes those who experienced no improvement, pain worsening, or VAS 7 to 10.
      Table 3Composite Pain Reporting Scale.
      Composite pain scoreDescription
      1Pain free, VAS 0, 100% pain reduction
      2“Good” response, VAS 1–3, > 50% pain reduction
      3“Satisfactory” or “fair” response, VAS 4–6, < 50% pain reduction
      4No improvement, pain worsening, VAS 7–10
      The fraction of patients showing any symptomatic improvement after a procedure (pain score of 1–3) was calculated as a percentage of the total number of subjects included in the study (Table 2). Patients with mortality before follow-up or if the outcome was not reported were deemed outcome unknown. To determine the relative surgical success between techniques, they were divided as follows: open focal lesioning techniques (nucleotomy/tractotomy), DREZ (multipoint lesioning technique), percutaneous nucleotomy/tractotomy, and neuromodulation (cervical SCS). Pain outcome distribution was compared between each using a chi-squared test. The fraction of patients with postprocedural improvement was assessed with respect to publication date to determine the influence of procedural modification over time (Supplementary Data Supplementary Material 3). This analysis used a linear model for all intervention types in addition to individually for those with an inadequate number of studies. Linear models were implemented using the R statistical language and environment.
      • R Core Team
      R Core Team (2022). R: A language and environment for statistical computing.
      Event rates for composite scores and complications were pooled across studies, and logit transformed with 95% CIs calculated assuming a binomial distribution. This was calculated using MATLAB R2019b.
      • Lau J.C.
      • Kosteniuk S.E.
      • Walker T.
      • Iansavichene A.
      • Macdonald D.R.
      • Megyesi J.F.
      Operative complications with and without image guidance: a systematic review and meta-analysis of the Ommaya reservoir literature.

      Results

      A total of 782 articles were identified through the literature search and underwent title and abstract review (Fig. 2). Two separate reviewers (Brendan Santyr and Mohamad Abbass) screened each article to meet inclusion/exclusion criteria. After removal of duplicates, review of bibliographies from relevant articles, and exclusion of studies with n < 5 patients (Supplementary Data Supplementary Material 2), 33 studies encompassing 827 patients were included for analysis, as summarized in Table 2. Disagreement was resolved by a third reviewer (Alan Chalil). All identified studies for inclusion were case series published between 1940 and 2020. No randomized or prospective trials were identified. The results of the data extraction for included studies are summarized in Table 2. The publications included in this work represent an 80-year history of techniques targeting the NC for treatment of craniofacial pain (Fig. 3). The rate of publications continues to increase over time, and there are emerging techniques including endoscopic approaches and spinal cord stimulation (SCS) seen in the last ten years (Fig. 3)
      Figure thumbnail gr2
      Figure 2Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart outlining article selection. ∗Articles with fewer than 5 patients ( ).
      Figure thumbnail gr3
      Figure 3Cumulative number of studies examining nucleus caudalis targeting interventions in the treatment of craniofacial pain. Over the last 80 years, 33 articles have been published investigating techniques targeting the NC for treatment of craniofacial pain. The 1940s and 1970s saw the development of open (blue) and percutaneous approaches (orange), respectively. The rate of publication continues to increase, and novel techniques continue to emerge, including endoscopic approaches (light blue) and SCS (green) seen in the last ten years and ultrasonic (gray) previously.

      Preoperative Diagnosis

      Treatments targeting the NC have been used to ameliorate craniofacial pain in a wide range of patient populations. Of the 827 patients included in this review, 41.5% (n = 343) had a diagnosis of TN or trigeminal neuropathic pain (Fig. 4). Oncologic craniofacial pain comprised 19.7% (n = 163); 8.5% (n = 70) had postherpetic pain; 5.7% (n = 47) had anesthesia dolorosa; 5.6% (n = 46) had traumatic craniofacial pain; 3.6% (n = 30) had glossopharyngeal neuralgia; 1.9% (n = 16) had poststroke craniofacial pain; 0.8% (n = 7) had headache or migraine; 0.7% (n = 6) had multiple sclerosis-related craniofacial pain; 0.6% (n = 5) had geniculate neuralgia; and 11.4% (n = 94) had multiple diagnoses or unspecified craniofacial pain (Fig. 4).
      Figure thumbnail gr4
      Figure 4Distribution of preoperative diagnoses. Thirty-three articles reporting on 827 patients show a wide range of sources of craniofacial pain treated with NC interventions, the most common being trigeminal neuralgia/trigeminal neuropathic pain (n = 343, 41.5%), oncologic pain (n = 163, 19.7%), and postherpetic pain (n = 70, 8.5%). Rarer causes of craniofacial pain are also represented, such as headache (n = 7, 0.8%), MS (n = 6, 0.7%), and geniculate neuralgia (n = 5, 0.6%). MS, multiple sclerosis.

      Intervention Technique

      Review of the included articles revealed five intervention techniques targeting the NC for craniofacial pain (Figs. 1 and 5). The most common approach was open NC DREZ nucleotomy/tractotomy, reported in 21 studies and comprising 60.1% of patients (n = 497). CT-guided and free-hand percutaneous nucleotomy/tractotomy are reported in eight studies and 35.6% of patients (n = 294). Cervical SCS is reported in two studies and 2.1% of patients (n = 17). Ultrasonic nucleotomy is reported in one study and 1.7% of patients (n = 14). Endoscopic DREZ nucleotomy/tractotomy is reported in one study and 0.6% of patients (n = 5). Although not included in the analysis, Gamma Knife radiosurgery was reported in a single case series of 2 patients.
      • Chang J.W.
      • Choi J.Y.
      • Yoon Y.
      • Park Y.G.
      • Chung S.S.
      Unusual causes of trigeminal neuralgia treated by gamma knife radiosurgery. Report of two cases.
      Figure thumbnail gr5
      Figure 5Distribution of intervention technique. The included studies encompass five main intervention techniques targeting the NC. In order of decreasing prevalence: open NC DREZ nucleotomy/tractotomy (n = 497, 60.1%), percutaneous nucleotomy/tractotomy (n = 294, 35.6%), cervical SCS (n = 17, 2.1%), ultrasonic nucleotomy (n = 14, 1.7%), and endoscopic DREZ nucleotomy/tractotomy (n = 5, 0.6).

      Treatment Outcomes

      As mentioned previously, various pain reporting methods are used in the studies reviewed. To facilitate comparison of treatment outcomes between studies, a composite pain rating scale was developed and outlined in Table 3. Preoperative pain is even less consistently reported. Of the 827 included patients, 142 (17.2%) have preoperative VAS reported, with a mean of 8.6. Using the implemented composite score developed to facilitate comparison between modern and historical studies, interventions targeting the NC resulted in a pain score of 1 (ie, pain freedom, VAS 0, or 100% pain reduction) in 237 patients (28.7%), pain score of 2 (ie, “good” response, VAS 1–3, or a > 50% pain reduction) in 215 patients (26.0%), pain score of 3 (ie, “satisfactory” or “fair” response, VAS 4–6, or a < 50% pain reduction) in 35 patients (4.2%), pain score of 4 (ie, no improvement, pain worsening, or VAS 7–10) in 49 patients (5.7%) (Fig. 6). The treatment outcome was unknown in 291 patients (35.2%). This includes patients lost to follow-up or who died or were inadequately reported.
      Figure thumbnail gr6
      Figure 6Postintervention craniofacial pain outcome. Intervention efficacy was reported for 536 patients. A composite pain score was created to facilitate comparison between modern and historical studies. Of those with reported outcome, 44.2% (n = 237) were pain free, 40.1% (n = 215) had a “good” response, 6.5% (n = 35) had a “satisfactory” response, and 9.1% (n = 49) had no improvement or worsening pain.
      Focusing on subjects with clearly reported outcome values, the intervention types were reclassified as open focal lesioning techniques (nucleotomy/tractotomy) (n patients = 154), open DREZ (multipoint lesioning technique) (n patients = 141), percutaneous nucleotomy/tractotomy (n patients = 224), and cervical SCS (n patients = 17), and outcome distribution were compared between the types (Fig. 7). Chi-squared shows a significant difference in the outcome distribution between the intervention types (χ 2 = 57.5322, p < 0.001) (Supplementary Data Supplemental Material 3). Of the 22 studies (66.7%) that reported follow-up duration, the mean duration was 2.44 years. When stratified by intervention type, the mean follow-up duration for open focal lesioning techniques (nucleotomy/tractotomy) was 1.66 years; for open DREZ (multipoint lesioning technique), 2.46 years; for percutaneous nucleotomy/tractotomy, 2.10 years; and for cervical SCS, 3.55 years.
      Figure thumbnail gr7
      Figure 7Distribution of pain outcomes by intervention technique. The intervention types were reclassified as open focal lesioning techniques (nucleotomy/tractotomy) (n patients = 154), open DREZ (multipoint lesioning technique) (n patients = 141), percutaneous nucleotomy/tractotomy (n patients = 224), and cervical SCS (n patients = 17). Proportion of patients with a given outcome was reported with error bars representing 95% CIs. Chi-squared shows a significant difference in the outcome distribution between the intervention types (χ 2 = 57.5322, p < 0.001). Perc, percutaneous.
      Linear regression failed to show a trend toward improving postoperative outcomes in interventions over the 80-year history (Supplementary Data Supplemental Material 4). A nonsignificant trend toward improved outcomes is seen in open focal lesioning and percutaneous nucleotomy/tractotomy when separated by intervention type. The correlation coefficients are 0.45 and 0.44; the covariances are 1.05 and 1.12; and p values are 0.19 and 0.33, respectively (Supplementary Data Supplemental Material 4).

      Complications

      A total of 251 complications are reported. The proportion of individual complications per intervention type is presented in Figure 8. All complications except corneal anesthesia (n = 5), oropharyngeal dysfunction (n = 11), and limb dysfunction (n = 14) indicate a statistically significant difference in distribution between intervention types (focal lesioning techniques, DREZ, percutaneous, and neuromodulation) (p < 0.001) (Supplementary Data Supplemental Material 5).
      Figure thumbnail gr8
      Figure 8Proportion of patients with a given complication arranged by intervention technique. All complications except corneal anesthesia (n = 5), oropharyngeal dysfunction (n = 11), and limb dysfunction (n = 14) show a statistically significant difference in distribution between intervention types. Proportion of patients with a given complication is reported with error bars representing 95% CIs. shows data and statistical results.

      Discussion

      In this study, we performed a systematic review of the published literature regarding the surgical interventions of the NC and investigated the efficacy and indications for these procedures. Some improvement from NC-targeted treatment was shown in 87% of subjects. Furthermore, 44.2% reported complete pain freedom postoperatively. We show percutaneous lesioning has a relatively lower complication rate than do other intervention types. Despite the increase in described surgical options for craniofacial pain, up to 27% of patients who undergo surgical treatment have insufficiently managed pain at five years.
      • Macfarlane T.V.
      • Blinkhorn A.S.
      • Davies R.M.
      • Kincey J.
      • Worthington H.V.
      Oro-facial pain in the community: prevalence and associated impact.
      ,
      • Al-Quliti K.W.
      Update on neuropathic pain treatment for trigeminal neuralgia. The pharmacological and surgical options.
      This study shows that there has been a recent increase in publication rate over the 80 years since the original descriptions of NC interventions. Contributing to this are not only the advancements in open and percutaneous techniques but also the emergence of new approaches such as ultrasonic lesioning, radiosurgery, and SCS.
      The studies included in this review report on diverse diagnoses resulting in chronic craniofacial pain, including postherpetic pain, TN or trigeminal neuropathic pain, oncologic pain, migraine, multiple sclerosis-related craniofacial pain, and geniculate neuralgia. A detailed description regarding the pathophysiology of pain associated with each of these conditions is outside the scope of this review; however, common to each of these diseases is injury (compression, denervation/deafferentation, demyelination) of the general somatic afferent fibers of the fifth, seventh, ninth, or tenth cranial nerves. These fibers synapse onto second-order neurons within the descending trigeminocervical complex, which extends from the pons to the upper cervical spinal cord on the dorsal surface of the brainstem.
      • Teixeira M.J.
      • Fonoff E.T.
      Technique of trigeminal nucleotractotomy.
      On the basis of anatomic and clinical data, the NC was identified as the most important locus for modulation, integration, and conduction of nociception from craniofacial structures to higher-order intracranial structures for pain perception.
      • Sjoqvist O.
      Studies of pain conduction in the trigeminal nerve.
      ,
      • Hosobuchi Y.
      • Rutkin B.
      Descending trigeminal tractotomy. Neurophysiological approach.
      ,
      • Hu J.W.
      • Sessle B.J.
      Trigeminal nociceptive and non-nociceptive neurones: brain stem intranuclear projections and modulation by orofacial, periaqueductal gray and nucleus raphe magnus stimuli.
      • Wall P.D.
      • Taub A.
      Four aspects of trigeminal nucleus and a paradox.
      • Broton J.G.
      • Rosenfeld J.P.
      Rostral trigeminal projections signal perioral facial pain.
      This provides a logical target for treatment of pain associated with injury to cranial nerves V, VII, IX, and X. Intervention techniques such as the NC DREZ nucleotomy/tractotomy use a small suboccipital craniectomy and C1–C2 laminectomy to elevate the cerebellar tonsils and visualize the obex. The NC occupies the triangular area between the dorsolateral sulcus and the emerging points of the accessory nerve. It tapers caudally before joining the spinal DREZ of C2. During NC DREZ nucleotomy/tractotomy, multiple rostrocaudal and mediolateral lesions are made at a depth of 3 to 4 mm covering 5 mm below the obex to the upper dorsal rootlets of C2.
      • Teixeira M.J.
      • Fonoff E.T.
      Technique of trigeminal nucleotractotomy.
      The identified articles reveal progressive adaptation of intervention techniques targeting the NC. Most studies (21 studies comprising 60.1% of patients) report on the open NC DREZ nucleotomytractotomy. Open procedures in this region date back to the 1930s, when Sjoqvist demonstrated that sectioning of the trigeminocervical complex at the level of the medulla above the obex resulted in ipsilateral thermoanalgesia of the face.
      • Sjoqvist O.
      Studies of pain conduction in the trigeminal nerve.
      Although this procedure was initially plagued by complications, a near century of surgical advancement has considerably improved its safety and efficacy, including the development of the more selective vertical trigeminal partial nucleotomy in 1965.
      • Kunc Z.
      Treatment of essential neuralgia of the 9th nerve by selective tractotomy.
      The 1970s saw the emergence of stereotactic and percutaneous targeting techniques, improving pain outcomes through patient cooperation and intraoperative monitoring of lesion-induced analgesia under local anesthetic.
      • Hitchock E.R.
      • Schvarcz J.R.
      Stereotaxic trigeminal tractotomy for post-herpetic facial pain.
      Surgical refinement and improved anatomical understanding of the region in the 1970s and 80s resulted in specific open NC DREZ lesioning procedures gaining popularity, with higher immediate success rates.
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      In recent decades, a trend toward less invasive techniques is apparent because morbidity related to injury of nearby structures of the spinal cord and medulla from open procedures remains high; historically, 5% encounter ataxia, 25%, paresthesias, and 8% to 24%, lesioning of the tenth nerve.
      • Teixeira M.J.
      • Fonoff E.T.
      Technique of trigeminal nucleotractotomy.
      Endoscopic NC DREZ nucleotomy/tractotomy procedures have been developed to minimize the morbidity associated with large incisions and craniotomies.
      • Rahimpour S.
      • Patel V.
      Endoscopic trigeminal nucleus caudalis doral root entry zone lesioning for atypical facial pain.
      ,
      • Teixeira M.J.
      • de Almeida F.F.
      • de Oliveira Y.S.
      • Fonoff E.T.
      Microendoscopic stereotactic-guided percutaneous radiofrequency trigeminal nucleotractotomy.
      Noninvasive techniques using ultrasound
      • Grigoryan YuA.
      • Slavin K.V.
      • Ogleznev K.Ya
      Ultrasonic lesion of the trigeminal nucleus caudalis for deafferentation facial pain.
      and Gamma Knife radiosurgery
      • Chang J.W.
      • Choi J.Y.
      • Yoon Y.
      • Park Y.G.
      • Chung S.S.
      Unusual causes of trigeminal neuralgia treated by gamma knife radiosurgery. Report of two cases.
      have similarly been developed. Finally, the most recent adaptation of techniques targeting the NC is in the form of SCS as a titratable and reversible form of neuromodulation of the region.
      • Patel K v
      • Lohani M.
      Paresthesia-free relief: higher frequency stimulation of high cervical leads for patients with chronic facial pain.
      ,
      • Velásquez C.
      • Tambirajoo K.
      • Franceschini P.
      • Eldridge P.R.
      • Farah J.O.
      Upper cervical SCS as an alternative treatment in trigeminal neuropathy.
      ,
      • Yearwood T.L.
      • Venkatesan L.
      • Harrell C.C.
      Resolution of primary cervicogenic headache with sub-perception active recharge spinal cord stimulation (10721).
      • Richter B.
      • Tomycz N.D.
      • Patterson M.
      C1 retrograde spinal cord stimulation for trigeminal deafferentation pain. Case study with long-term follow-up.
      • Jones M.R.
      • Rosenow J.M.
      Importance of laterality in cervical spinal cord stimulation for facial pain: case report and anatomic review.
      Clearly, the techniques targeting the NC for ablation or neuromodulation represent an additional option for the treatment of intractable craniofacial pain of diverse pathophysiological origins. Despite the variations in intervention technique and preoperative diagnosis, 87% of subjects showed some improvement from treatment. Furthermore, 44.2% reported complete pain freedom postoperatively, suggesting remarkable efficacy for a group of treatments typically reserved for complex and otherwise surgically and medically refractory craniofacial pain. Although this might be an overestimation of the overall effectiveness of these procedures due to publication bias, it is nevertheless encouraging for continued prospective study of these procedures. Also shown here are significant differences in outcome distributions between different procedural techniques. However, owing to the inconsistencies in outcome reporting from the inclusion of studies before standardization of reporting pain metrics, efficacy comparisons between intervention type or preoperative diagnosis could not be reliably made. There have been efforts in the literature to standardize pain-outcome reporting, with multiple well-validated pain-rating scales available.
      • Younger J.
      • McCue R.
      • Mackey S.
      Pain outcomes: a brief review of instruments and techniques.
      Here, we present added evidence for the need to continually report outcomes in a way that allows robust comparisons. It is imperative that future prospective studies address these lingering questions.
      Analysis of reported complication rates shows significant differences in complications between the different intervention techniques. The data support percutaneous interventions having a relatively lower rate of complications than do others (Fig. 8). These results should be interpreted cautiously because they are certainly confounded by publication bias, inadequate reporting of complications, limited duration of follow-up (2.44 years), and lack of longitudinal outcome reporting. However, encouragingly, a treatment response durability of at least a year is shown for each intervention type. Further investigation should be the subject of future prospective trials.
      Open trigeminal tractotomy (focal lesioning technique) as a procedure has become largely historical owing to frequent partial/patchy craniofacial analgesia,
      • Falconer M.A.
      Intramedullary trigeminal tractotomy and its place in the treatment of facial pain.
      high recurrence rates,
      • Moffie D.
      Late results of bulbar trigeminal tractotomy. Some remarks on recovery of sensibility.
      and frequency of morbidity and mortality.
      • Teixeira M.J.
      • Fonoff E.T.
      Technique of trigeminal nucleotractotomy.
      Advancements in technology and understanding in the 1970s paved the way for the more common adaptation of procedures seen today, caudalis DREZ lesioning (multipoint lesioning technique) and percutaneous lesioning. Determining when to pursue each technique and for whom remains a difficult question to answer when prospective trials and comparison studies are lacking. The literature reviewed here suggests that with caudalis DREZ lesioning, pain improvement may be achieved in 70% of patients. Bernard et al surmise that patient description of pain may help predict postoperative outcome,
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      with patients with sharp/burning pain finding better relief than those with dull pain, 55% and 24%, respectively.
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      Better results were also achieved when pain is restricted to the trigeminal territory and with fewer trigeminal distributions involved.
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      Good outcome is observed in 75% of patients with pain involving one trigeminal distribution, 50% of patients with two, and 38% of patients in whom all three territories are involved.
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      Similarly, percutaneous procedures demonstrate pain improvement in 71% of patients. However, these procedures as described in the literature tend to target afferent fiber tracts, second-order neurons, and internuncial neurons and tracts in the spinal trigeminal complex, eliminating abnormal discharging of deafferented neurons and thereby providing better pain relief in patients with central or deafferentation pain than does caudalis DREZ lesioning.
      • Anderson L.S.
      • Black R.G.
      • Abraham J.
      • Ward A.A.
      Neuronal hyperactivity in experimental trigeminal deafferentation.
      ,
      • Bernard Jr., E.J.
      • Nashold Jr., B.S.
      • Caputi F.
      Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain.
      ,
      • Grigoryan YuA.
      • Slavin K.V.
      • Ogleznev K.Ya
      Ultrasonic lesion of the trigeminal nucleus caudalis for deafferentation facial pain.
      ,
      • Hitchcock E.R.
      • Tsukamoto Y.
      Physiological correlates in stereotactic spinal surgery.
      ,
      • Westrum L.E.
      • Black R.G.
      Changes in the synapses of the spinal trigeminal nucleus after ipsilateral rhizotomy.
      Furthermore, we show a lower total complication rate in percutaneous techniques, with only a slightly higher reoperation/revision rate than that of caudalis DREZ lesions. Historical literature and the results from this work support the use of percutaneous procedures in providing an equivalent degree of craniofacial pain reduction to caudalis DREZ lesioning, with better efficacy in deafferentation pain and fewer complications. Caudalis DREZ lesioning may be reserved for uncooperative patients or those with pain refractory to other treatments, and those with sharp/burning pain in a limited distribution.
      Newer techniques such as endoscopy, ultrasound, gamma knife, and SCS report on too few patients to draw meaningful conclusions regarding their indications and relative efficacy; however, neuromodulation with cervical SCS is showing a recent rise in publication rate.
      • Patel K v
      • Lohani M.
      Paresthesia-free relief: higher frequency stimulation of high cervical leads for patients with chronic facial pain.
      ,
      • Velásquez C.
      • Tambirajoo K.
      • Franceschini P.
      • Eldridge P.R.
      • Farah J.O.
      Upper cervical SCS as an alternative treatment in trigeminal neuropathy.
      ,
      • Yearwood T.L.
      • Venkatesan L.
      • Harrell C.C.
      Resolution of primary cervicogenic headache with sub-perception active recharge spinal cord stimulation (10721).
      • Richter B.
      • Tomycz N.D.
      • Patterson M.
      C1 retrograde spinal cord stimulation for trigeminal deafferentation pain. Case study with long-term follow-up.
      • Jones M.R.
      • Rosenow J.M.
      Importance of laterality in cervical spinal cord stimulation for facial pain: case report and anatomic review.
      The efficacy and safety of SCS in the treatment of chronic pain are well accepted and supported in the literature.
      • Deer T.R.
      • Mekhail N.
      • Provenzano D.
      • et al.
      The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the neuromodulation appropriateness consensus committee.
      Likewise, this efficacy is replicated in this review, in which 88% of patients receiving cervical SCS experience some degree of pain reduction. Velásquez et al report a mean pain reduction of 57.1%, making it comparable with ablative procedures on a patient level.
      • Velásquez C.
      • Tambirajoo K.
      • Franceschini P.
      • Eldridge P.R.
      • Farah J.O.
      Upper cervical SCS as an alternative treatment in trigeminal neuropathy.
      ,
      • Chivukula S.
      • Tempel Z.J.
      • Chen C.J.
      • Shin S.S.
      • Gande A.V.
      • Moossy J.J.
      Spinal and nucleus caudalis dorsal root entry zone lesioning for chronic pain: efficacy and outcomes.
      ,
      • Kanpolat Y.
      • Tuna H.
      • Bozkurt M.
      • Elhan A.H.
      Spinal and nucleus caudalis dorsal root entry zone operations for chronic pain.
      However, large prospective studies are lacking, and indication recommendations are limited. We show a lower overall complication rate relative to caudalis DREZ lesioning, with no reported mortality or permanent neurologic deficit such as ataxia, weakness, or paresthesia. There was a slightly higher total complication rate than with percutaneous techniques, likely secondary to a higher reoperation/revision rate from infection, loss of efficacy, and lead malpositioning, rather than neurologic deficit.
      • Velásquez C.
      • Tambirajoo K.
      • Franceschini P.
      • Eldridge P.R.
      • Farah J.O.
      Upper cervical SCS as an alternative treatment in trigeminal neuropathy.
      With a body of literature that is continually growing, cervical SCS is presenting itself as a potential early, titratable, and reversible therapy with a lower complication risk and comparable outcomes.
      The need for ongoing innovation in chronic pain management is apparent, and less invasive methods are emerging. Of particular interest, recent reports have described both intraventricular and intrathecal analgesia administration in cases of refractory craniofacial pain.
      • Dupoiron D.
      Targeted drug delivery (intrathecal and intracranial) for treatment of facial pain.
      ,
      • Lee D.J.
      • Gurkoff G.G.
      • Goodarzi A.
      • Muizelaar J.P.
      • Boggan J.E.
      • Shahlaie K.
      Intracerebroventricular opiate infusion for refractory head and facial pain.
      As the evidence continues to evolve, these procedures may become viable options for patients for whom other strategies have failed or whose pain is bilateral.
      • Dupoiron D.
      Targeted drug delivery (intrathecal and intracranial) for treatment of facial pain.
      ,
      • Lee D.J.
      • Gurkoff G.G.
      • Goodarzi A.
      • Muizelaar J.P.
      • Boggan J.E.
      • Shahlaie K.
      Intracerebroventricular opiate infusion for refractory head and facial pain.
      The first application of lesioning of the trigeminocervical complex dates to the 1930s
      • Sjoqvist O.
      Studies of pain conduction in the trigeminal nerve.
      ; however, evidence supporting its use is limited to small retrospective case series and case reports. These study designs are particularly at risk of several biases potentially confounding the results presented here, including selection bias, recording bias, misclassification bias, and uncontrolled confounding bias. Furthermore, as previously mentioned, the limitations encountered are a lack of prospective studies and inadequate outcome reporting to strengthen comparisons between intervention types and diagnosis. These limitations have restricted the critical appraisal of the sources of evidence for risk of bias assessment. Historical studies, as encountered in this work, particularly suffer from a lack of access to more recently devised outcome-reporting schemes and classification systems. For example, the contemporary classification of TN, and as such differentiating trigeminal neuropathic pain from TN, could not be performed. Furthermore, the heterogeneity of included studies with respect to intervention, diagnosis, and outcome-reporting measures necessitated grouping all these factors together and creating a custom postprocedural pain-reporting scale. This may limit the strength of efficacy conclusions; however, it does contribute greatly to the generalizability of the included results and allowed comparison with historical studies. In addition, information regarding follow-up and treatment outcome durability is almost universally lacking in the literature, and only 64.8% of patients have reported outcome data. Combining preoperative diagnoses further limits the conclusions able to be drawn because life expectancy for some conditions, that is, those with oncologic facial pain, may be shorter than the time it may take to achieve full benefit from the procedure.

      Conclusions

      This review summarizes 80 years of literature regarding interventions targeting the NC for chronic refractory craniofacial pain. Recent advancements in intervention techniques are highlighted, but shortcomings in the literature also impede widespread adoption. Only 64.8% of included subjects have outcomes reported, and owing to the inclusion of studies before the standardization of pain reporting metrics, there are inconsistencies in the way these outcomes are reported. New and less invasive techniques continue to emerge; however, prospective studies remain absent in the literature. More studies addressing efficacy comparisons between intervention type or preoperative diagnosis would help solidify these techniques in the armamentarium of craniofacial pain treatments.

      Authorship Statements

      Brendan Santyr, Mohamad Abbass, Alan Chalil, and Jonathan C. Lau designed the study. Data collection was performed by Amirti Vivekanandan and Margaret Tindale. Data analysis and statistical support were provided by Brendan Santyr and Mohamad Abbass. Brendan Santyr prepared the manuscript draft with important intellectual input from Mohamad Abbass, Alan Chalil, Nicholas M. Boulis, and Jonathan C. Lau. All authors approved the final version of the manuscript.

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