Tr i g e m i n a l neuralgia is a form of facial pain that. Trigeminal neuralgia in young adults. Clinical article

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1 J Neurosurg 114: , 2011 Trigeminal neuralgia in young adults Clinical article Di a a Ba h g a t, M.D., Di b y e n d u K. Ray, M.B.B.S., M.S., M.Ch., Ahm e d M. Ra s l a n, M.D., Sh i r l e y McCa r t n e y, Ph.D., a n d Kim J. Bu r c h i e l, M.D. Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon Object. Trigeminal neuralgia (TN) is a form of facial pain that can be debilitating if left untreated. It typically affects elderly adults and is thought to be related to neurovascular compression. It is uncommon in people younger than 30 years of age, with only 1% of cases reportedly occurring in those younger than 20 years of age. The most common cause of compression in young adults is thought to be venous nerve compression either alone or in association with arterial nerve compression. The objective of this study was to review data in cases of TN in which patients were 25 years of age or younger and to identify TN disease characteristics, demographics, clinical features, operative findings, and outcome. Methods. The authors retrospectively reviewed the clinical records, surgical treatment, and long-term outcome in patients 25 years of age or younger with TN who underwent surgery performed by the senior author (K.J.B.) at Oregon Health & Science University between 1995 and Results. Seven patients (2 males and 5 females) met the inclusion criteria. The average age at symptom onset was 19.6 ± 3.4 years (± SD) and the average age at surgery was 22.9 ± 1.7 years. Six patients had right-sided symptoms and 1 had left-sided symptoms. Pain distribution was the V2 in 3 cases, V2 3 in 3 cases, and V3 in 1 case, with no cases of V1 affliction. A total of 11 procedures were performed in 7 patients, and 4 patients underwent a second procedure. Surgery and imaging revealed venous compression in all cases. The average follow-up period was 35.5 ± 39.9 months (median 12 months). Three patients reported a good outcome (no pain with or without medications) and 4 reported a poor outcome (either no pain relief or mild pain relief after surgery). Conclusions. Trigeminal neuralgia is uncommon in young adults. Patients tend to present with symptoms similar to those in adults: long periods of pain and venous compression, but outcome unfortunately is not as good as that reported in the older population. (DOI: / JNS10781) Ke y Wo r d s trigeminal neuralgia young adult venous compression Tr i g e m i n a l neuralgia is a form of facial pain that can be debilitating if left untreated. It typically affects elderly adults (1 in 25,000 of the population) and is thought to be related to neurovascular compression. 15 It is uncommon in those younger than 30 years of age, with only 1% of cases occurring in those younger than 20 years of age. 10,17 The mean age at presentation in childhood varies but has been reported to be 13.6 years; 26 however, patients presenting as young as 13 months have also been noted. 23 Reports on children and young adults are few. One large study has detailed 23 patients in whom TN developed at an age younger than 18 years and who underwent surgery at a mean age of 29.1 years. 26 The most common cause of compression in young Abbreviations used in this paper: GKS = Gamma Knife surgery; MVD = microvascular decompression; TN = trigeminal neuralgia. adults is thought to be venous either alone or associated with arterial nerve compression. 26,28 Other reports have pointed to secondary causes such as lipoma, arachnoid cysts, Chiari malformation, and carcinoma. 9,14,22,25 There is controversy regarding medical therapy outcome, with some investigators reporting a good response and others reporting no response. 5,20,25 Surgical outcome in children, compared with adults, is not encouraging: 43% of children are reportedly pain free after 1 year 26 compared with 70% of adults reportedly being pain free at 10 years. 2 Despite being recognized as early as 1921 as a cause of facial pain in children, 1 the characteristics of TN in younger adults and children have not been adequately reported and the natural history and outcome not fully understood. The aim of this study was to review the clinical, operative, and outcome characteristics of TN in younger adults in the hope of reaching a better understanding of the disease process J Neurosurg / Volume 114 / May 2011

2 Trigeminal neuralgia in young adults Patient Population Methods The Oregon Health & Science University Institutional Review Board approved this study. Patient selection criteria included the following: a diagnosis of TN, a history of TN and initial medical therapy improvement without surgery, or a diagnosis of TN in a patient (aged years) who underwent a surgical procedure to treat TN, and a treatment period between January 1995 and December Data Collection Patient charts were reviewed retrospectively. Demographic data (age and sex) and details of prior surgery and history, location, character, and duration of the pain complaint were recorded, as was response to prior pain treatment(s). Operative findings were noted and postoperative outcome was determined. The patients were mailed an invitation to participate in a follow-up telephone questionnaire (Table 1). Patients were asked over the telephone to grade their current pain compared with that before the surgery. Final outcome was grouped as follows: A, no pain and no medications; B, no pain with medications; C, pain reduced to a tolerable level with or without medications; D, insufficient pain reduction; and E, pain same or worse. Groups A and B were considered to reflect a good outcome and Groups C E to reflect a poor outcome. Mean results are presented ± SD. Results Ten patients were identified who fit the selection criteria. Two patients were lost to follow-up. One patient with a brainstem venous malformation did not undergo surgery and was managed conservatively. Of the remain- TABLE 1: Follow-up telephone questionnaire 1. Can you grade your pain now compared to that before the surgery as (select one) a. No pain w/ no medication YES NO b. No pain w/ medication YES NO c. Mild tolerable pain w/ or w/o medication YES NO d. Pain reduction w/ medication but to unsatisfactory or intolerable levels YES NO e. No change in pain YES NO 2. Did your symptoms improve initially & then got worse afterward? YES NO 3. And if so how good did it get? (select one) a. No pain w/ no medication YES NO b. No pain w/ medication YES NO c. Mild tolerable pain w/ or w/o medication YES NO d. Pain reduction w/ medication but to unsatisfactory or intolerable levels YES NO e. No change in pain YES NO 4. If you have had recurrence of pain (if yes) YES NO a. How long was it until the pain recurred again? b. Has the character or intensity of pain changed? YES NO (what was it THEN and what is it now ) c. How frequently do you get the pain attacks? All of the time Most of the time Some of the time A little of the time None of the time d. Is the pain affecting your daily living quality? All of the time Most of the time Some of the time A little of the time None of the time 5. Regarding your medication a. Was there a time when you stopped medication? YES NO b. Have you needed to change the medication dose (whether by increasing or decreasing dosage) YES NO c. Have you changed the medication itself by adding or substituting a different drug? YES NO 6. Have you had multiple procedures for your trigeminal neuralgia? (if yes) YES NO a. How many? b. What were they? c. What was the outcome of each? d. What was the average duration of improvement if any? e. Have you had any procedures done outside OHSU after your last one at OHSU and what was its YES NO outcome? J Neurosurg / Volume 114 / May

3 D. Bahgat et al. ing 7 patients, 2 were male and 5 female. The average age of the patients at symptom onset was 19.6 ± 3.4 years and the average age at surgery was 22.9 ± 1.7 years (Table 2). All patients had undergone a trial of medical therapy before presentation; medications included one or more of the following: carbamazepine, gabapentin, Lyrica, and/or baclofen. Five patients had tried more than one form of medication; 2 had stopped carbamazepine due to side effects and intolerance, 6 reported some benefit from medication but were still in pain with frequent attacks, and 2 others reported limited benefit. One patient had undergone previous procedures (MVD, which provided pain relief for 2 months, and GKS, which yielded no benefit) before presenting to our institution. Six patients presented with right-sided symptoms and 1 with left-sided symptoms. Distribution of symptoms was the V2 in 3 cases, V2 3 in 3 cases, and V3 in 1 case. There were no cases of V1 affliction. Four patients presented with sharp, shooting, episodic pain, representative of TN Type 1; 3 patients described a more constant pain (either dull aching pain or deep burning pain, with sharp painful episodes, representative of TN Type 2). 8 Symptom duration ranged from 6 months to 6 years (mean 34 ± 28.9 months, median 24 months) (Table 3). Before surgery, 5 patients underwent MR imaging and MR angiography performed in a 3-T unit with 1-mm slices to evaluate the trigeminal nerve (1 patient had previously undergone MVD, and MR imaging revealed the trigeminal nerve with a mass of Teflon around it and no significant compression). Two patients had undergone MR imaging prior to the year 2000 when imaging criteria were different. Nevertheless, imaging confirmed venous compression and no arterial compression in all cases (Fig. 1). A total of 11 procedures were undertaken in 7 patients; 4 patients underwent a second procedure (2 of which were performed at an another institution after the patient underwent MVD at our institution). Of the procedures performed at our institution, 8 were MVDs, 1 was a redo MVD necessary when the patient s pain recurred after a 2-year pain-free interval, and 1 was a radiofrequency procedure, performed as a second procedure for pain recurrence after a 6-month pain-free interval following MVD. Two patients underwent procedures at an outside TABLE 3: Symptom-related data Case No. Duration of Symptoms (yrs) TN Symptom Side Distribution TN Diagnosis 1 5 burning, sharp, shoot- rt V3 Type 1 ing, episodic 2 2 ache, dull constant & rt V2 Type 2 sharp spells stabbing lt V2 Type constant burning & rt V2 3 Type 2 sharp attacks 5 6 episodic, sharp, aching, rt V2 3 Type 1 burning 6 5 constant deep burn rt V2 3 Type sharp, episodic, triggerable rt V2 Type 1 institution after MVD at our institution. One patient who had a 2-month pain-free period following MVD experienced recurrent pain and underwent GKS. The Gamma Knife procedure provided pain relief for 5 months after which pain again recurred and medication was resumed. A second patient, who had undergone 2 previous surgeries (MVD [provided 2 months of pain relief] and GKS [provided no benefit]) before presenting to our institution for an MVD procedure and internal neurolysis, experienced no benefit and 1 year later underwent motor cortex stimulation (Table 4). In all operative cases, venous compression and not arterial compression was observed (Table 4). One patient had no evident compression, but had undergone a previous MVD and an internal neurolysis (performed during TABLE 2: Summary of demographic data in patients who underwent surgery for TN Case No. Sex Age (yrs) at Symptom Onset at Surgery Previous Therapy* 1 male medication, MVD, GKS 2 female medication 3 female medication 4 female medication 5 male medication 6 female medication 7 female medication * Medication includes both antiepileptic and pain. Fig. 1. Axial T2-weighted MR image with 1-mm cuts showing the left trigeminal nerve and venous compression J Neurosurg / Volume 114 / May 2011

4 Trigeminal neuralgia in young adults TABLE 4: Operative procedures and outcome* Case No. OHSU Op Compression Early Outcome Grade Second Op Follow-Up* (mos) Final Outcome Grade 1 MVD & internal neurolysis none E MCS (outside) 12 E 2 MVD venous B 72 B 3 MVD venous A GKS (outside) 36 D 4 MVD venous D 6 E 5 MVD venous D 9 C 6 MVD large venous A RFL (OHSU) 6 A 7 MVD large venous A MVD (OHSU) 108 A * See Data Collection section for definition of outcome grades. Abbreviations: RFL = radiofrequency lesion; MCS = motor cortex stimulation; OHSU = Oregon Health & Science University. Follow-up from date of last procedure, if performed at Oregon Health & Science University. a second procedure at our institution). In most cases the compressing vein was coagulated, except in one case in which an abnormally close cranial nerve VII VIII complex where the vein was filling the intervening position and thus could not be coagulated; in this instance, Teflon was placed around the vein and the trigeminal nerve. In 1 patient undergoing a second MVD, a large vein was found to be obscured by the petrous ridge, and the vein was coagulated after drilling the bone. There was 1 postoperative complication of wound discharge, which later cleared with no sequela. The average follow-up period was 35.5 ± 39.9 months (median 12 months, range 6 months 9 years). Three patients had what was considered a good outcome (complete pain relief without medication [Grade A] in 2 patients and no pain while taking medication [Grade B] in 1 patient). Of note, however, of the 2 patients with a Grade A outcome, the initial post-mvd improvement was followed by pain recurrence at 6 months in one case and at 2 years in the other. An additional procedure was performed in each case (radiofrequency lesioning in one case and MVD in the other), and at 6-month and 9-year follow-up neither patient had pain or was receiving analgesic medication. The other 4 patients reported a poor outcome with either no pain relief or mild pain relief after surgery (Grades D and E, respectively). Only 1 of the 4 patients with TN Type 1 reported a good outcome, whereas 2 of the 3 patients with TN Type 2 had a good outcome. Of note, the nonsurgical candidate who did not undergo surgery due to a venous brainstem malformation was followed up for 7 years and had tolerable pain relief with medication (Grade C). In most cases the patients described the character of recurrent pain as similar to that of initial pain, although 2 patients who initially described sharp pain later developed pressurelike constant pain with episodes of sharp pain. Three patients with only V2 pain had recurrence in the V2 3 area distribution, whereas 1 patient with V2 3 pain had recurrence only in the V2 area. Discussion Trigeminal neuralgia is considered primarily an adult disease with an average age of onset ranging from 57 to 61 years; 2,30 less than 15% of these patients are younger J Neurosurg / Volume 114 / May 2011 than 50 years of age, 31 and pediatric cases comprise less than 1.5% of all TN cases. 26 The pathophysiology behind TN is related to vascular compression of the trigeminal nerve, and it is thought that with age, atherosclerosis and arterial elongation lead to repositioning of the arterial vessel into proximity to and contact with the nerve. 15 This compression leads to nerve damage like demyelination and axonopathy, and this reduces the threshold of nerve firing in such a way that minor stimulation induces a burst of spontaneous firing, perceived as intense pain, which lasts for seconds or minutes; this has been referred to as the ignition hypothesis. 6,7 Not all cases present with vascular compression, however, and there is no clear explanation why TN develops in these cases when no clear pathology, such as multiple sclerosis, can be identified. Ishikawa and colleagues 13 provided a hypothesis, based on their observation in such cases, that arachnoid thickening and granulomatous adhesions between the nerve root and surrounding structures cause root angulation and torsion leading to an abnormal root stretching force, which might promote hyperexcitability of the nerve. Compared with TN in adults, there are few reports addressing TN in young adults. 5,12,20,22,23,25,26,28 In our series of 7 patients presenting with TN, the average age at presentation was 19 years and the average age at time of surgery was 22.9 years. The mean symptom duration was 4 years, compared with a mean of 15.5 ± 13.2 years reported by Resnick et al. 26 in a similar population. Symptom duration in adults is also variable, with an average of 6 years (range 1 44 years). 2,3,30 Debate surrounds whether symptom duration has a predictive impact on surgical outcome, with some groups reporting that it does play a role 2,3 and others stating that it does not. 24,29 In our series, the most common distribution of symptoms was the V2 division in 3 cases and V2 3 in 3 cases. This is in agreement with previous results in young adults, which indicate V2 is the most involved division of the trigeminal nerve. 2,26,29 Intraoperatively, we observed no case of arterial compression only venous compression and 1 case in which compression was absent. In a previous pediatric TN study, Resnick et al. 26 reported that 86% of the patients had compression, with venous compression being the sole source of compression in 18% of the cases. This differs from the 1309

5 D. Bahgat et al. studies in adults with TN by Sindou and associates, 29,30 who reported venous compression in 26.5% of their cases, most being associated with arterial compression; only in 3.3% of the cases was the compressing vessel a vein. Barker et al. 2 reported that a vein contributed to the compression in 68% of patients and was the only compressing vessel in 12%. Venous compression has been correlated with outcome failure and has been recognized as a negative prognosticator. 2,4,11,15,18,19,29,33 A previous study by the senior author (K.J.B.) found that 57% of patients with venous compression suffered from recurrent pain. 4 Sindou et al. 29 reported that venous compression was a negative prognosticator if found alone without any arterial component. Barker et al., 2 Kolluri and Heros, 19 and others 11,18,33 reported similar findings. Presently, there is no explanation for the lack of arterial compression in our series or why there are reports of increased venous compression in young patients with TN. 26,28 However, it is possible that a lack of atherosclerosis and a crowded posterior fossa may play a role in the genesis of TN, either by placing the vessel in close proximity to, or putting traction and distortion on, the nerves. 16 The incidence of cases in which there is no arterial compression ranges from 1.4% to 28.5%. 19,34 Ishikawa et al. 13 reported that 17% of their cases had no compression and that the patients in such cases tended to experience a delayed improvement of symptoms. They suggested that arachnoid thickening leads to nerve angulation and torsion, which may be a factor in the genesis of TN. Outcome in a younger population differs from that in adults. In our series, within 2 months of surgery, 4 patients reported a good outcome (Grade A or B), whereas 3 reported a poor outcome (Grades C E). At long-term follow-up (mean 35.5 ± 39.9 months, median 12 months), 3 of 7 cases reported no pain with or without the use of medication, and 4 reported either mild or no pain improvement. Of these 4 patients, 2 reported that their pain was actually worse. This was also reported by Resnick et al.; 26 87% of their patients had a good initial response immediately after surgery, indicating either no pain or significant pain reduction, but after 1 year of follow-up 43% reported complete pain relief and 14% reported more than 75% pain relief. These results contradict those obtained after MVD in adults, which has a reported half-life of 10 years. 4 There are several reports on the long-term outcome of TN in adults. Bederson and Wilson 3 noted that by 5 years 75% of their patients experienced an excellent outcome and reported a 2% annual recurrence rate. Sindou et al. 30 reported a successful outcome in 81.2% at 1 year that decreased to 75% at 15 years. Barker et al. 2 reported the 1-year outcome was excellent in 79.7% and the 10-year outcome was excellent in 69.6%. In a recent literature review, the initial pain-free rate following MVD was 91%, the follow-up (average 6.7 ± 1.9 years) pain-free rate was 76%, and the recurrence rate was 18%. 35 There are a few questions that have to be addressed for future management of TN in younger and older adults. For instance, how do we manage cases in which preoperative MR images demonstrate no compression, the prevalence of which has been reported to range from 3.1% to 17% of cases? 13,32 Several reports indicate the use of partial rhizotomy, nerve combing, or nerve manipulation as treatment options, 3,13,21,27 but these therapies were used in an older age group and there was a major recurrence rate of 50%. 4 Revuelta-Gutiérrez et al. 27 reported an initial good outcome with a 43.2% failure rate at 48 months. Ma and Li 21 reported on 10 patients who underwent nerve combing in which the trigeminal nerve was longitudinally split into fascicles along its length; the 3-year follow-up outcome was excellent in 70% of their patients. Bederson and Wilson 3 reviewed 252 cases and performed MVD in patients with vascular contact that caused nerve root distortion, whereas 30 patients without vascular contact underwent partial rhizotomy. Fifty-six patients with vascular contact but no nerve root distortion underwent both MVD and rhizotomy. There was a trend toward a better outcome following MVD and rhizotomy, and toward a worse outcome following partial rhizotomy alone. It is difficult to reach a definitive conclusion from such a small series, but in a young age group venous compression, as in adults, 24,29 is an indicator of poor outcome, and in this younger age group a neuropsychological evaluation may be indicated as part of the evaluation. Given these results, cases without vascular compression, as evidenced on preoperative MR imaging, should be approached with caution. The potential limitations of our study include the small patient cohort. One also could argue that there is limited value in asking patients to recall their pre- and postoperative pain retrospectively. These limitations should be addressed in future studies. For example, a larger prospective study that compared symptomatology and outcome before and after surgery would be prudent for future consideration. Conclusions Trigeminal neuralgia is uncommon in the young adult and pediatric populations; symptoms, such as long periods of sharp lancinating pain, tend to be similar to those in adults. The offending vessel is usually venous and unfortunately the outcome after surgery is not as good as that achieved in adults. Treatment of young adults and pediatric patients can be challenging because of the poor prognosis and young age; one must wonder how the individuals will continue to live with their pain and what alternatives they have. Careful preoperative discussion should emphasize that the surgical objective of long-term pain relief may not be met in all cases. Long-term followup and a better understanding of the pathophysiology of TN may help to provide a solution in the future. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Burchiel, Bahgat, Ray, McCartney. Acquisition of data: Bahgat, Ray. Analysis and interpretation of data: Bahgat, Ray, Raslan. Drafting the article: Bahgat, McCartney. Critically revising the article: all authors. Reviewed final version and approved it for submission: all authors. Administrative/technical/material support: McCartney J Neurosurg / Volume 114 / May 2011

6 Trigeminal neuralgia in young adults Acknowledgment The authors express their appreciation and thanks to Andy Rekito, M.S., for illustrative assistance. References 1. Barclay JH: A case of trigeminal neuralgia in a boy, age 10 years, treated by intracranial division of the second and third divisions of the nerve. Br J Surg 9: , Barker FG II, Jannetta PJ, Bissonette DJ, Larkins MV, Jho HD: The long-term outcome of microvascular decompression for trigeminal neuralgia. N Engl J Med 334: , Bederson JB, Wilson CB: Evaluation of microvascular decompression and partial sensory rhizotomy in 252 cases of trigeminal neuralgia. J Neurosurg 71: , Burchiel KJ, Clarke H, Haglund M, Loeser JD: Long-term efficacy of microvascular decompression in trigeminal neuralgia. J Neurosurg 69:35 38, Childs AM, Meaney JF, Ferrie CD, Holland PC: Neurovascular compression of the trigeminal and glossopharyngeal nerve: three case reports. 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Acta Neurochir (Wien) 150: , 2008 Manuscript submitted May 21, Accepted October 24, Please include this information when citing this paper: published online December 3, 2010; DOI: / JNS Address correspondence to: Kim J. Burchiel, M.D., Department of Neurological Surgery (CH8N), Oregon Health & Science University, 3303 SW Bond Avenue, Portland, Oregon burchiek@ ohsu.edu. J Neurosurg / Volume 114 / May