- Email: [email protected]
Microvascular Decompression for Trigeminal Neuralgia: The Role of Mechanical Allodynia
Accepted Manuscript Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia Chenlong Liao, M.D., Ph.D., Wenchuan Zhang, M.D., Ph.D, Min Yang, M.D., Wenxiang Zhong, M.D., Pengfei Liu, M.D., Shiting Li, M.D PII:
S1878-8750(16)30221-2
DOI:
10.1016/j.wneu.2016.04.092
Reference:
WNEU 4021
To appear in:
World Neurosurgery
Received Date: 20 February 2016 Revised Date:
21 April 2016
Accepted Date: 25 April 2016
Please cite this article as: Liao C, Zhang W, Yang M, Zhong W, Liu P, Li S, Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.04.092. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page Title: Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia Authors and Affiliations Wenxiang Zhong, M.D., Pengfei Liu, M.D., Shiting Li, M.D.
RI PT
Chenlong Liao, M.D., Ph.D., Wenchuan Zhang, M.D., Ph.D., Min Yang, M.D.,
Department of Neurosurgery, XinHua Hospital, affiliated to Shanghai JiaoTong
SC
University School of Medicine, Shanghai, P. R. China Corresponding author:
M AN U
Name: Wenchuan Zhang,
Address: NO.1665 Shanghai Kongjiang Road, Yangpu District, Shanghai, China. Phone: +8613901853383
TE D
E-mail: [email protected]
Key words: trigeminal neuralgia, microvascular decompression, mechanical allodynia, neurovascular compression, pathological mechanism Abbreviations list
EP
CI: Confidence interval
MA: Mechanical allodynia
AC C
MVD: Microvascular decompression NVC: Neurovascular compression OR: Odds ratio
TN: Trigeminal neuralgia T1TN: Type 1 trigeminal neuralgia T2TN: Type 2 trigeminal neuralgia
ACCEPTED MANUSCRIPT
Abstract Objective: This study was conducted to determine whether mechanical allodynia (MA) acts as a predictor of outcome after microvascular decompression (MVD) for trigeminal neuralgia (TN) and discuss the potential pathological mechanisms
RI PT
involved. Methods: A series of 246 patients who underwent MVD for TN were involved in the study. The classifications were based on the characteristic of pain (shock-like or constant), and the presence of MA was defined from the chart review, retrospectively.
SC
The surgical outcome is defined as excellent, good, and poor. Immediate and long-term outcomes were compared to provide the information on recurrence and
M AN U
delayed relief. The relationship among the groups was investigated, and the strength was determined.
Results: Both presence of MA and type of TN pain are significant predictors of surgical outcome (P < 0.05). MA was proven to be an independent predictor of surgical outcome and also a significant predictor of existence of neurovascular
TE D
compression (P < 0.05) and lower rate of recurrence (P < 0.05). No statistically significant predictors of delayed relief were detected in this study. Conclusions: The presence of MA is a reliable predictor of immediate and long-term
EP
outcome after MVD for TN. Compared to the patients without MA, the incidence rate of intraoperative neurovascular compression (NVC) was higher in MA-positive
AC C
patients, who were more likely to achieve a better outcome and lower rate of recurrence after MVD for TN. Application of the information in this study will be helpful in patient selection of MVD for TN.
Introduction
Since Dandy first proposed the vascular compression of the trigeminal nerve as the cause of trigeminal neuralgia (TN) [1] and Jannetta successfully developed and popularized microvascular decompression (MVD) to manage the pain [2], the theory of neurovascular compression (NVC) has been generally accepted to date. Although there are other treatments for TN, for example, medications, such as carbamazepine or
ACCEPTED MANUSCRIPT Botox,
gamma
knife
radiosurgery,
and
percutaneous
therapies,
including
radiofrequency thermocoagulation, balloon compression, and glycerol rhizotomy, MVD is ranked as the most effective remedy for TN [3]. Nevertheless, not all patients can be completely cured by MVD, and recurrence or delayed relief may occur in a
RI PT
small proportion of patients [3-5]. Some patients with refractory pain go through a series of medical treatments mentioned above and eventually fail to achieve any pain relief. This dilemma reflects the lack of thorough understanding TN mechanisms, which are now considered a unique form of neuropathic pain [6] and the most
SC
common type of neuralgia [7].
TN is a facial pain syndrome characterized by paroxysmal, shock-like pain
M AN U
attacks located in the somatosensory distribution of the trigeminal nerve [8]. It has been traditionally divided into “typical” and “atypical” forms according to the presence of episodic pain attacks, trigger points, long pain-free intervals, and so forth. Better outcomes are more likely to be achieved in patients with “typical” TN [9, 10]. Recently, a new classification [11], in which the type of pain (shock-like pain vs.
TE D
constant pain) is isolated as the base of categorization, had been proposed and later reported to act as a predictor of long-term outcome after MVD [12]. In this study, we allowed for the fact that there are too many factors to be taken into account in the
EP
traditional classification, and the underlying mechanisms had become too equivocal to be explored because of this. Therefore, we extracted one of the characteristics of typical TN descriptions, mechanical allodynia (MA), which is a hallmark of
AC C
neuropathic pain, as the base of classification to evaluate its effect in predicting the outcome after MVD.
In this retrospective study, we evaluated the effect of MA in predicting the
outcome after MVD and compared it to that of the TN pain type. The underlying mechanism was also discussed.
Material and methods We retrospectively reviewed a series of 254 patients who had undergone MVD for TN performed by the senior author (Zhang WC) from January, 2010 to June, 2013.
ACCEPTED MANUSCRIPT The classifications, based on the type of pain (shock-like or constant) and the presence of trigger point (MA), could be defined from the medical history charts. Intraoperative findings, including the presence of NVC were obtained from the operation videos. Every patient was contacted via telephone by an interviewer who
RI PT
was blinded to the classifications and immediate outcome of patients. Interviewers inquired about the patients’ long-term outcomes, including pain relief, the characteristic of residual pain, the presence of trigger point (MA), and unusual sensations. The combination of immediate and long-term outcomes could provide
SC
information on recurrence and delayed relief.
Patients with TN in our institution might undergo more than one operation to
M AN U
achieve satisfactory outcome. Rigorous exploration and decompression of the trigeminal nerve was performed in every operation. Those who still experienced pain after MVD were advised to accept a second MVD, in which we would perform the internal neurolysis after reviewing the operation videos and ensured no vascular compression. Internal neurolysis would be performed in the first MVD when there
TE D
were no signs of NVC. Radiofrequency lesioning is another frequent choice for patients with refractory pain following a second MVD or the first MVD, during which no NVC was observed. Only those who underwent MVD(s) but not radiofrequency
EP
lesioning were included in this study.
Three groups were defined based on the outcome: 1) excellent, totally pain relief without medication; 2) good, pain controlled with low-dose medication; and 3) poor,
AC C
persistent pain remained nearly unchanged [12]. Statistical analyses were performed employing SPSS 18.0 for Windows. The
chi-square test was applied for contingency tables with a P value of < 0.05 considered significant. Odds ratio (OR) and its 95% confidence interval (CI) were used to detect the strength of relation. This study is approved by the Xinhua Hospital Medical Ethics Committee.
Results We lost contact with 8 patients lost contact during the follow up period. A total of
ACCEPTED MANUSCRIPT 246 patients (74 males and 172 females, with a mean age of 63 years) were involved in this study. Demographic and clinical characteristics of patients are summarized in Table 1. There was a predominance of female and right side in TN. MA is present in the majority of patients, most of which is classified as type 1 TN (T1TN) (86.2%),
RI PT
and also with NVC (79.8%). Patients with MA are more likely to be detected with the presence of NVC involved (P =0.001< 0.05, OR 2.79, 95% CI 1.48-5.24), while there is no statistically significant relationship between the presence of MA and T1TN (P =0.21> 0.05, OR 1.63, 95% CI 0.76-3.47).
SC
Overall, the immediate outcome after MVD according to the chart review is as follows: 130 (53%) patients with excellent outcome, 60 (24%) patients with good
M AN U
outcome, and 56 (23%) patients with poor outcome. (Table 2) The long-term outcome was evaluated through the telephone interview, and with combination of immediate and long-term outcome, the recurrence was defined as “from good to poor” or “from excellent to good or poor”, while the delayed relief was defined as “from good to excellent” or “from poor to good or excellent”. The overall rate of recurrence and
TE D
delayed relief is 13% and 8%, respectively.
The results of long-term outcome after MVD, as well as the numbers of patients with recurrence and delayed relief, are shown in Table 3. Patients with MA had a
EP
greater likelihood of immediate (P < 0.05, OR 3.84, 95% CI 2.01-7.33) and long-term (P < 0.05, OR 5.39, 95% CI 2.86-10.13) pain relief (excellent and good), but less likelihood (P =0.001< 0.05, OR 0.30, 95% CI 0.14-0.65) of recurrence than those
AC C
without MA. Meanwhile, patients with T1TN pain had a greater likelihood of immediate (P =0.002< 0.05, OR 3.06, 95% CI 1.47-6.34) and long-term (P =0.005< 0.05, OR 2.70, 95% CI 1.33-5.49) pain relief, but no less likelihood (P =0.325> 0.05, OR 0.63, 95% CI 0.25-1.58) of recurrence than those with type 2 TN (T2TN) pain. In addition, there is no significant difference regarding the rate of delayed relief between patients with MA and those without MA (P =0.480> 0.05), nor between those with T1TN and T2TN pain (P =0.217> 0.05). Immediate and long-term results based on the presence of MA and TN type are shown in Figure 1. Figure 2 further specified the distribution of patients with recurrence and delayed relief, providing a direct view on
ACCEPTED MANUSCRIPT the effect of MA. Furthermore, the type of pain was controlled in order to assess whether MA may represent an independent predictor of surgical outcome. In patients with T1TN pain, those with MA had greater likelihood of immediate (P < 0.05, OR 2.65, 95% CI
RI PT
1.25-5.61) and long-term (P < 0.05, OR 5.22, 95% CI 2.57-10.59) pain relief than those without MA. Likewise, in T2TN pain group, patients with MA also had greater likelihood of immediate (P < 0.05, OR 16.67, 95% CI 2.84-97.97) and long-term (P < 0.05, OR 5.67, 95% CI 1.22-26.33) pain relief than those without MA.
SC
Discussion
The findings in this study confirm the role of MA in predicting the immediate
M AN U
and long-term outcome after MVD for TN. Patients with MA are more than 3 to 5 times as likely as those without MA to achieve immediate and long-term pain relief following MVD, respectively. The strength of relation is higher than that between better outcome and type of TN. The rate of recurrence is lower in patients with MA, indicating that the absence of MA is a predictor of recurrence. In addition, a higher
TE D
rate of delayed relief is also observed to occur in patients with MA, although the effect was fairly small and did not reach a statistically significance. As Hutchinson eloquently put forward, a classification system of facial pain
EP
should be based on an understanding of the underlying pathophysiology of the neuralgia [13]. Trigger point in TN is a particular form of MA, which is mainly
AC C
mediated by peripheral low-threshold large myelinated Aβ-fibers under pathological conditions, such as nerve injury and inflammation. Several changes within the peripheral and central nervous system that could underlie MA have been proposed and reviewed [14]. They consist of alterations in properties of low-threshold mechanoreceptive Aβ afferents [15, 16], development of long-term potentiation (LTP, generally defined as the long-lasting but not necessarily irreversible increase in synaptic strength) [17], reduction of GABAergic and/or glycinergic inhibitory neurotransmission (disinhibition) [18], and changes in intrinsic plasticity (long-lasting changes in membrane excitability) of neurons and descending modulation from the
ACCEPTED MANUSCRIPT upper center [19]. However, concrete analysis should be made in specified diseases. TN has been generally related to the NVC at the root entry zone, which is supported by the intraoperative observations and the high rate of pain relief by MVD [20-23]. Due to the different sensitivities of different nerve fibers [24, 25], the
RI PT
demyelination and injury of nerves following NVC would first impair large myelinated Aβ fibers and lead to so-called “ectopic excitation” and “ephaptic connections”, which act as explanations of existence of trigger point [6, 26]. In this phase, TN is characterized by the MA. The shock-like pain evoked by innocuous
SC
tactile stimulation and the pain caused by NVC could be well relieved by MVD as revealed in this study.
M AN U
Otherwise, as the compression continues to exist or aggravate, the small unmyelinated C fibers may be stimulated by inflammatory stimuli following nerve compression or be directly impaired by further compression. The pain of TN may thus become constant and diffuse, or incorporate a variety of sensory disorders, representing a mix of chronic pain (mediated by slow-conduction C fibers), episodic
TE D
pain attacks, burning pain, hypesthesia, numbness, and so on. All of these make up the so-called “atypical TN”. In patients with the presence of MA, which may indicate that retention of the conduction of Aβ fibers and the following remyelination is possible,
EP
MVD should be performed with the hope for pain relief or delayed relief. However, if the sensory disturbance existed preoperatively, it would most likely remain unchanged or even worsen after the operation [27].
AC C
The sensory conduction pathway of different levels may continue to be impaired
without elimination of NVC, and there are a series of reversible and irreversible events, such as early-phase and late-phase LTP involved in the progression [28, 29]. The former is independent of de novo protein synthesis and lasts for up to 3 hours, while the latter involves protein synthesis and lasts longer than 3 hours, up to the whole life span [14]. However, the precise delimitation between the time course of reversible and irreversible changes could not be defined largely due to the individual difference. The effect of MVD for TN may decrease after the occurrence of irreversible events because the pain or other uncomfortable sensations are not purely
ACCEPTED MANUSCRIPT caused by peripheral NVC anymore. Similarly, the response to conservative treatment, such as carbamazepine, usually wanes with the development of the disease. The absence of MA indicates that the pattern of pain has changed, and even if pain relief is temporarily achieved, the etiological factors could not be eliminated solely by MVD.
RI PT
As demonstrated in this study, recurrence is not uncommon. In these situations, however, invasive interventions such as rhizotomy [30] and stereotactic radiosurgery [31] would be beneficial for pain relief.
Findings in this study and the discussion about sequential impairment of
SC
different types of nerve fibers and different levels of the sensory conduction pathway (Figure 3) support the theory that different phenotypes of TN represent a continuous
M AN U
spectrum of degree of injury to the nerve rather than discrete diagnoses [6]. Nevertheless, there are some patients without any evidence of NVC during the operation, and most of them represent atypical symptoms, which may be attributed to the unrevealed pathological states, for example, alteration in intrinsic plasticity and descending modulation within the trigeminal nuclei or other areas of sensory
TE D
conduction system. Surgical intervention for partly or completely blocking conduction of peripheral afferents, such as internal neurolysis [32], and trigeminal root compression [33, 34] in these cases might help with pain relief; however, the
EP
long-term efficacy and relative complication are still under controversy. Accordingly, although NVC is the dominating causation, it is neither sufficient nor necessary for the development of TN. The exploration for more efficient treatment of TN in
AC C
different situations and individuals will mainly rest on understanding of the pathological mechanisms involved.
Conclusions
The presence of MA is a reliable predictor of the immediate and long-term outcome after MVD for TN. Compared to patients without MA, the incidence rate of intraoperative NVC is higher in those with MA, which are more likely to achieve a lower rate of recurrence after MVD for TN. Application of the information in this study will be helpful in patient selection of MVD for TN.
ACCEPTED MANUSCRIPT
References [1]
Dandy WE. Concerning the cause of trigeminal neuralgia. Am J Surg 1934;24:447-455.
[2]
Jannetta PJ,
Robbins LJ. Trigeminal neuropathy--new observations. Neurosurgery
1980;7(4):347-51. [3]
Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM, American Academy of Neurology S, European Federation of Neurological S. AAN-EFNS
RI PT
guidelines on trigeminal neuralgia management. European journal of neurology : the official journal of the European Federation of Neurological Societies 2008;15(10):1013-28. [4]
Bakker NA, Van Dijk JM, Immenga S, Wagemakers M, Metzemaekers JD. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia. Journal of neurosurgery 2014;121(4):936-9.
[5]
Gu W,
Zhao W. Microvascular decompression for recurrent trigeminal neuralgia. Journal of
SC
clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2014;21(9):1549-53. Burchiel KJ,
Slavin KV. On the natural history of trigeminal neuralgia. Neurosurgery
2000;46(1):152-4; discussion 4-5. [7]
M AN U
[6]
Kumar S, Rastogi S, Kumar S, Mahendra P, Bansal M, Chandra L. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review. Journal of medicine and life 2013;6(4):383-8.
[8]
Montano N, Conforti G, Di Bonaventura R, Meglio M, Fernandez E, Papacci F. Advances in diagnosis and treatment of trigeminal neuralgia. Therapeutics and clinical risk management 2015;11:289-99.
Li ST, Pan Q, Liu N, Shen F, Liu Z, Guan Y. Trigeminal neuralgia: what are the important factors
TE D
[9]
for good operative outcomes with microvascular decompression. Surgical neurology 2004;62(5):400-4; discussion 4-5. [10]
Tyler-Kabara EC, Kassam AB, Horowitz MH, Urgo L, Hadjipanayis C, Levy EI, Chang YF. Predictors of outcome in surgically managed patients with typical and atypical trigeminal
EP
neuralgia: comparison of results following microvascular decompression. Journal of neurosurgery 2002;96(3):527-31. [11]
Burchiel KJ. A new classification for facial pain. Neurosurgery 2003;53(5):1164-6; discussion
AC C
6-7. [12]
Miller JP, Magill ST, Acar F, Burchiel KJ. Predictors of long-term success after microvascular
decompression for trigeminal neuralgia. Journal of neurosurgery 2009;110(4):620-6.
[13]
Hutchinson J. The Surgical Treatment of Facial Neuralgia. Vol. p 1. New York: Wm. Wood &
Co.,, 1905.
[14]
Sandkuhler J. Models and mechanisms of hyperalgesia and allodynia. Physiological reviews
2009;89(2):707-58. [15]
Campbell JN, Raja SN, Meyer RA, Mackinnon SE. Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 1988;32(1):89-94.
[16]
Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992;51(2):175-94.
[17]
Sandkuhler J. Understanding LTP in pain pathways. Molecular pain 2007;3:9.
[18]
Torsney C,
MacDermott AB. Disinhibition opens the gate to pathological pain signaling in
ACCEPTED MANUSCRIPT superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26(6):1833-43. [19]
Todd AJ. Neuronal circuitry for pain processing in the dorsal horn. Nature reviews. Neuroscience 2010;11(12):823-36.
[20]
Sandel T,
Eide PK. Long-term results of microvascular decompression for trigeminal
neuralgia and hemifacial spasms according to preoperative symptomatology. Acta neurochirurgica 2013;155(9):1681-92; discussion 92. Ibrahim S. Trigeminal neuralgia: diagnostic criteria, clinical aspects and treatment outcomes. A retrospective study. Gerodontology 2014;31(2):89-94. [22]
RI PT
[21]
McLaughlin MR, Jannetta PJ, Clyde BL, Subach BR, Comey CH, Resnick DK. Microvascular decompression of cranial nerves: lessons learned after 4400 operations. Journal of neurosurgery 1999;90(1):1-8.
[23]
Sekula RF, Jr., Frederickson AM, Jannetta PJ, Quigley MR, Aziz KM, Arnone GD. Microvascular
SC
decompression for elderly patients with trigeminal neuralgia: a prospective study and systematic review with meta-analysis. Journal of neurosurgery 2011;114(1):172-9. [24]
Battista AF,
Alban E. Effect of graded ligature compression on nerve conduction.
[25]
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139(2):267-84.
[26]
M AN U
Experimental neurology 1983;80(1):186-94.
Sabalys G, Juodzbalys G, Wang HL. Aetiology and pathogenesis of trigeminal neuralgia: a comprehensive review. Journal of oral & maxillofacial research 2013;3(4):e2.
[27]
Sekula RF, Jr., Frederickson AM, Jannetta PJ, Bhatia S, Quigley MR. Microvascular decompression after failed Gamma Knife surgery for trigeminal neuralgia: a safe and effective
[28]
TE D
rescue therapy? Journal of neurosurgery 2010;113(1):45-52.
Ikeda H, Heinke B, Ruscheweyh R, Sandkuhler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 2003;299(5610):1237-40.
[29]
Ikeda H, Stark J, Fischer H, Wagner M, Drdla R, Jager T, Sandkuhler J. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 2006;312(5780):1659-62. Bender M, Pradilla G, Batra S, See A, Bhutiani N, James C, Carson BS, Lim M. Effectiveness of
EP
[30]
repeat glycerol rhizotomy in treating recurrent trigeminal neuralgia. Neurosurgery 2012;70(5):1125-33; discussion 33-4. Daugherty E, Bhavsar S, Hahn SS, Bassano D, Hall W. A successful case of multiple stereotactic
AC C
[31]
radiosurgeries for ipsilateral recurrent trigeminal neuralgia. Journal of neurosurgery 2015;122(6):1324-9.
[32]
Ko AL, Ozpinar A, Lee A, Raslan AM, McCartney S, Burchiel KJ. Long-term efficacy and safety
of internal neurolysis for trigeminal neuralgia without neurovascular compression. Journal of
neurosurgery 2015;122(5):1048-57.
[33]
Cheng J, Lei D, Zhang H, Mao K. Trigeminal root compression for trigeminal neuralgia in patients with no vascular compression. Acta neurochirurgica 2015;157(2):323-7.
[34]
Revuelta-Gutierrez R, Martinez-Anda JJ, Coll JB, Campos-Romo A, Perez-Pena N. Efficacy and safety of root compression of trigeminal nerve for trigeminal neuralgia without evidence of vascular compression. World neurosurgery 2013;80(3-4):385-9.
ACCEPTED MANUSCRIPT
Figures legends Figure 1: Graphs of results of immediate (upper) and long-term (lower) outcomes based on the presence of MA, as well as the type of TN pain. (NMA, non-MA, absence of mechanical allodynia.)
RI PT
Figure 2: Graphs of results of recurrence (upper) and delayed relief (lower) based on the presence of MA, as well as the type of TN pain. (NMA, non-MA, absence of mechanical allodynia.)
Figure 3: The schema illustrates the sequential impairment of different types of nerve
SC
fibers and different levels of the sensory conduction pathway in the development of TN. Pathological mechanisms accounting for different symptoms were listed and
AC C
EP
TE D
M AN U
correlated for a better understanding of this process.
ACCEPTED MANUSCRIPT Table 1 Demographic and clinical characteristics of 246 patients* MA (n=188)
NMA (n=58)
Mean age (yr)
62.7
63.9
Female (%)
132 (70.0)
40 (69.0)
Mean duration (mo)
64.5
80.9
Right side (%)
110 (58.5)
30 (51.7)
History of hypertension
86
22
History of DM
24
T1TN (%)
162 (86.2)
46 (79.3)
NVC (%)
150 (79.8)
34 (58.6)
Mean postop follow up (mo)
43.1
42.4
SC
RI PT
Characteristics
M AN U
0
AC C
EP
TE D
*Values represent numbers of patients (%) unless otherwise indicated. NMA, non-MA, absence of mechanical allodynia; DM, diabetes mellitus.
ACCEPTED MANUSCRIPT Table 2 The results of immediate outcome after MVD* Excellent
Good
Poor
MA (%)
115 (61)
42 (22)
31 (17)
NMA (%)
15 (26)
18 (31)
25 (43)
T1TN (%)
120 (58)
48 (23)
40 (19)
T2TN (%)
10 (26)
12 (32)
16 (42)
AC C
EP
TE D
SC
M AN U
*Values represent numbers of patients (%) NMA, non-MA, absence of mechanical allodynia.
RI PT
Classification
ACCEPTED MANUSCRIPT Table 3 The results of long-term outcome after MVD* Excellent
Good
Poor
Recurrence
Delayed relief
MA (%)
116 (61)
35 (19)
37 (20)
18 (10)
14 (7)
NMA (%)
12 (21)
13 (22)
33 (57)
15 (26)
6 (10)
T1TN (%)
118 (57)
38 (18)
52 (25)
26 (13)
15 (7)
T2TN (%)
10 (26)
10 (26)
18 (48)
7 (18)
5 (13)
RI PT
Classification#
AC C
EP
TE D
M AN U
SC
*Values represent numbers of patients (%) #The classification is based on the initial review of medical history chart. NMA, non-MA, absence of mechanical allodynia.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights 1. Mechanical allodynia predicted both the immediate and long-term outcome after
AC C
EP
TE D
M AN U
SC
RI PT
MVD for TN. 2. Higher rate of neurovascular compression is found in patients with MA. 3. Lower rate of recurrence is found in patients with MA. 4. Sequential impairment of the sensory conduction pathway may be involved in TN
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Conflicts of interest: none
S1878-8750(16)30221-2
DOI:
10.1016/j.wneu.2016.04.092
Reference:
WNEU 4021
To appear in:
World Neurosurgery
Received Date: 20 February 2016 Revised Date:
21 April 2016
Accepted Date: 25 April 2016
Please cite this article as: Liao C, Zhang W, Yang M, Zhong W, Liu P, Li S, Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.04.092. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title page Title: Microvascular decompression for trigeminal neuralgia: the role of mechanical allodynia Authors and Affiliations Wenxiang Zhong, M.D., Pengfei Liu, M.D., Shiting Li, M.D.
RI PT
Chenlong Liao, M.D., Ph.D., Wenchuan Zhang, M.D., Ph.D., Min Yang, M.D.,
Department of Neurosurgery, XinHua Hospital, affiliated to Shanghai JiaoTong
SC
University School of Medicine, Shanghai, P. R. China Corresponding author:
M AN U
Name: Wenchuan Zhang,
Address: NO.1665 Shanghai Kongjiang Road, Yangpu District, Shanghai, China. Phone: +8613901853383
TE D
E-mail: [email protected]
Key words: trigeminal neuralgia, microvascular decompression, mechanical allodynia, neurovascular compression, pathological mechanism Abbreviations list
EP
CI: Confidence interval
MA: Mechanical allodynia
AC C
MVD: Microvascular decompression NVC: Neurovascular compression OR: Odds ratio
TN: Trigeminal neuralgia T1TN: Type 1 trigeminal neuralgia T2TN: Type 2 trigeminal neuralgia
ACCEPTED MANUSCRIPT
Abstract Objective: This study was conducted to determine whether mechanical allodynia (MA) acts as a predictor of outcome after microvascular decompression (MVD) for trigeminal neuralgia (TN) and discuss the potential pathological mechanisms
RI PT
involved. Methods: A series of 246 patients who underwent MVD for TN were involved in the study. The classifications were based on the characteristic of pain (shock-like or constant), and the presence of MA was defined from the chart review, retrospectively.
SC
The surgical outcome is defined as excellent, good, and poor. Immediate and long-term outcomes were compared to provide the information on recurrence and
M AN U
delayed relief. The relationship among the groups was investigated, and the strength was determined.
Results: Both presence of MA and type of TN pain are significant predictors of surgical outcome (P < 0.05). MA was proven to be an independent predictor of surgical outcome and also a significant predictor of existence of neurovascular
TE D
compression (P < 0.05) and lower rate of recurrence (P < 0.05). No statistically significant predictors of delayed relief were detected in this study. Conclusions: The presence of MA is a reliable predictor of immediate and long-term
EP
outcome after MVD for TN. Compared to the patients without MA, the incidence rate of intraoperative neurovascular compression (NVC) was higher in MA-positive
AC C
patients, who were more likely to achieve a better outcome and lower rate of recurrence after MVD for TN. Application of the information in this study will be helpful in patient selection of MVD for TN.
Introduction
Since Dandy first proposed the vascular compression of the trigeminal nerve as the cause of trigeminal neuralgia (TN) [1] and Jannetta successfully developed and popularized microvascular decompression (MVD) to manage the pain [2], the theory of neurovascular compression (NVC) has been generally accepted to date. Although there are other treatments for TN, for example, medications, such as carbamazepine or
ACCEPTED MANUSCRIPT Botox,
gamma
knife
radiosurgery,
and
percutaneous
therapies,
including
radiofrequency thermocoagulation, balloon compression, and glycerol rhizotomy, MVD is ranked as the most effective remedy for TN [3]. Nevertheless, not all patients can be completely cured by MVD, and recurrence or delayed relief may occur in a
RI PT
small proportion of patients [3-5]. Some patients with refractory pain go through a series of medical treatments mentioned above and eventually fail to achieve any pain relief. This dilemma reflects the lack of thorough understanding TN mechanisms, which are now considered a unique form of neuropathic pain [6] and the most
SC
common type of neuralgia [7].
TN is a facial pain syndrome characterized by paroxysmal, shock-like pain
M AN U
attacks located in the somatosensory distribution of the trigeminal nerve [8]. It has been traditionally divided into “typical” and “atypical” forms according to the presence of episodic pain attacks, trigger points, long pain-free intervals, and so forth. Better outcomes are more likely to be achieved in patients with “typical” TN [9, 10]. Recently, a new classification [11], in which the type of pain (shock-like pain vs.
TE D
constant pain) is isolated as the base of categorization, had been proposed and later reported to act as a predictor of long-term outcome after MVD [12]. In this study, we allowed for the fact that there are too many factors to be taken into account in the
EP
traditional classification, and the underlying mechanisms had become too equivocal to be explored because of this. Therefore, we extracted one of the characteristics of typical TN descriptions, mechanical allodynia (MA), which is a hallmark of
AC C
neuropathic pain, as the base of classification to evaluate its effect in predicting the outcome after MVD.
In this retrospective study, we evaluated the effect of MA in predicting the
outcome after MVD and compared it to that of the TN pain type. The underlying mechanism was also discussed.
Material and methods We retrospectively reviewed a series of 254 patients who had undergone MVD for TN performed by the senior author (Zhang WC) from January, 2010 to June, 2013.
ACCEPTED MANUSCRIPT The classifications, based on the type of pain (shock-like or constant) and the presence of trigger point (MA), could be defined from the medical history charts. Intraoperative findings, including the presence of NVC were obtained from the operation videos. Every patient was contacted via telephone by an interviewer who
RI PT
was blinded to the classifications and immediate outcome of patients. Interviewers inquired about the patients’ long-term outcomes, including pain relief, the characteristic of residual pain, the presence of trigger point (MA), and unusual sensations. The combination of immediate and long-term outcomes could provide
SC
information on recurrence and delayed relief.
Patients with TN in our institution might undergo more than one operation to
M AN U
achieve satisfactory outcome. Rigorous exploration and decompression of the trigeminal nerve was performed in every operation. Those who still experienced pain after MVD were advised to accept a second MVD, in which we would perform the internal neurolysis after reviewing the operation videos and ensured no vascular compression. Internal neurolysis would be performed in the first MVD when there
TE D
were no signs of NVC. Radiofrequency lesioning is another frequent choice for patients with refractory pain following a second MVD or the first MVD, during which no NVC was observed. Only those who underwent MVD(s) but not radiofrequency
EP
lesioning were included in this study.
Three groups were defined based on the outcome: 1) excellent, totally pain relief without medication; 2) good, pain controlled with low-dose medication; and 3) poor,
AC C
persistent pain remained nearly unchanged [12]. Statistical analyses were performed employing SPSS 18.0 for Windows. The
chi-square test was applied for contingency tables with a P value of < 0.05 considered significant. Odds ratio (OR) and its 95% confidence interval (CI) were used to detect the strength of relation. This study is approved by the Xinhua Hospital Medical Ethics Committee.
Results We lost contact with 8 patients lost contact during the follow up period. A total of
ACCEPTED MANUSCRIPT 246 patients (74 males and 172 females, with a mean age of 63 years) were involved in this study. Demographic and clinical characteristics of patients are summarized in Table 1. There was a predominance of female and right side in TN. MA is present in the majority of patients, most of which is classified as type 1 TN (T1TN) (86.2%),
RI PT
and also with NVC (79.8%). Patients with MA are more likely to be detected with the presence of NVC involved (P =0.001< 0.05, OR 2.79, 95% CI 1.48-5.24), while there is no statistically significant relationship between the presence of MA and T1TN (P =0.21> 0.05, OR 1.63, 95% CI 0.76-3.47).
SC
Overall, the immediate outcome after MVD according to the chart review is as follows: 130 (53%) patients with excellent outcome, 60 (24%) patients with good
M AN U
outcome, and 56 (23%) patients with poor outcome. (Table 2) The long-term outcome was evaluated through the telephone interview, and with combination of immediate and long-term outcome, the recurrence was defined as “from good to poor” or “from excellent to good or poor”, while the delayed relief was defined as “from good to excellent” or “from poor to good or excellent”. The overall rate of recurrence and
TE D
delayed relief is 13% and 8%, respectively.
The results of long-term outcome after MVD, as well as the numbers of patients with recurrence and delayed relief, are shown in Table 3. Patients with MA had a
EP
greater likelihood of immediate (P < 0.05, OR 3.84, 95% CI 2.01-7.33) and long-term (P < 0.05, OR 5.39, 95% CI 2.86-10.13) pain relief (excellent and good), but less likelihood (P =0.001< 0.05, OR 0.30, 95% CI 0.14-0.65) of recurrence than those
AC C
without MA. Meanwhile, patients with T1TN pain had a greater likelihood of immediate (P =0.002< 0.05, OR 3.06, 95% CI 1.47-6.34) and long-term (P =0.005< 0.05, OR 2.70, 95% CI 1.33-5.49) pain relief, but no less likelihood (P =0.325> 0.05, OR 0.63, 95% CI 0.25-1.58) of recurrence than those with type 2 TN (T2TN) pain. In addition, there is no significant difference regarding the rate of delayed relief between patients with MA and those without MA (P =0.480> 0.05), nor between those with T1TN and T2TN pain (P =0.217> 0.05). Immediate and long-term results based on the presence of MA and TN type are shown in Figure 1. Figure 2 further specified the distribution of patients with recurrence and delayed relief, providing a direct view on
ACCEPTED MANUSCRIPT the effect of MA. Furthermore, the type of pain was controlled in order to assess whether MA may represent an independent predictor of surgical outcome. In patients with T1TN pain, those with MA had greater likelihood of immediate (P < 0.05, OR 2.65, 95% CI
RI PT
1.25-5.61) and long-term (P < 0.05, OR 5.22, 95% CI 2.57-10.59) pain relief than those without MA. Likewise, in T2TN pain group, patients with MA also had greater likelihood of immediate (P < 0.05, OR 16.67, 95% CI 2.84-97.97) and long-term (P < 0.05, OR 5.67, 95% CI 1.22-26.33) pain relief than those without MA.
SC
Discussion
The findings in this study confirm the role of MA in predicting the immediate
M AN U
and long-term outcome after MVD for TN. Patients with MA are more than 3 to 5 times as likely as those without MA to achieve immediate and long-term pain relief following MVD, respectively. The strength of relation is higher than that between better outcome and type of TN. The rate of recurrence is lower in patients with MA, indicating that the absence of MA is a predictor of recurrence. In addition, a higher
TE D
rate of delayed relief is also observed to occur in patients with MA, although the effect was fairly small and did not reach a statistically significance. As Hutchinson eloquently put forward, a classification system of facial pain
EP
should be based on an understanding of the underlying pathophysiology of the neuralgia [13]. Trigger point in TN is a particular form of MA, which is mainly
AC C
mediated by peripheral low-threshold large myelinated Aβ-fibers under pathological conditions, such as nerve injury and inflammation. Several changes within the peripheral and central nervous system that could underlie MA have been proposed and reviewed [14]. They consist of alterations in properties of low-threshold mechanoreceptive Aβ afferents [15, 16], development of long-term potentiation (LTP, generally defined as the long-lasting but not necessarily irreversible increase in synaptic strength) [17], reduction of GABAergic and/or glycinergic inhibitory neurotransmission (disinhibition) [18], and changes in intrinsic plasticity (long-lasting changes in membrane excitability) of neurons and descending modulation from the
ACCEPTED MANUSCRIPT upper center [19]. However, concrete analysis should be made in specified diseases. TN has been generally related to the NVC at the root entry zone, which is supported by the intraoperative observations and the high rate of pain relief by MVD [20-23]. Due to the different sensitivities of different nerve fibers [24, 25], the
RI PT
demyelination and injury of nerves following NVC would first impair large myelinated Aβ fibers and lead to so-called “ectopic excitation” and “ephaptic connections”, which act as explanations of existence of trigger point [6, 26]. In this phase, TN is characterized by the MA. The shock-like pain evoked by innocuous
SC
tactile stimulation and the pain caused by NVC could be well relieved by MVD as revealed in this study.
M AN U
Otherwise, as the compression continues to exist or aggravate, the small unmyelinated C fibers may be stimulated by inflammatory stimuli following nerve compression or be directly impaired by further compression. The pain of TN may thus become constant and diffuse, or incorporate a variety of sensory disorders, representing a mix of chronic pain (mediated by slow-conduction C fibers), episodic
TE D
pain attacks, burning pain, hypesthesia, numbness, and so on. All of these make up the so-called “atypical TN”. In patients with the presence of MA, which may indicate that retention of the conduction of Aβ fibers and the following remyelination is possible,
EP
MVD should be performed with the hope for pain relief or delayed relief. However, if the sensory disturbance existed preoperatively, it would most likely remain unchanged or even worsen after the operation [27].
AC C
The sensory conduction pathway of different levels may continue to be impaired
without elimination of NVC, and there are a series of reversible and irreversible events, such as early-phase and late-phase LTP involved in the progression [28, 29]. The former is independent of de novo protein synthesis and lasts for up to 3 hours, while the latter involves protein synthesis and lasts longer than 3 hours, up to the whole life span [14]. However, the precise delimitation between the time course of reversible and irreversible changes could not be defined largely due to the individual difference. The effect of MVD for TN may decrease after the occurrence of irreversible events because the pain or other uncomfortable sensations are not purely
ACCEPTED MANUSCRIPT caused by peripheral NVC anymore. Similarly, the response to conservative treatment, such as carbamazepine, usually wanes with the development of the disease. The absence of MA indicates that the pattern of pain has changed, and even if pain relief is temporarily achieved, the etiological factors could not be eliminated solely by MVD.
RI PT
As demonstrated in this study, recurrence is not uncommon. In these situations, however, invasive interventions such as rhizotomy [30] and stereotactic radiosurgery [31] would be beneficial for pain relief.
Findings in this study and the discussion about sequential impairment of
SC
different types of nerve fibers and different levels of the sensory conduction pathway (Figure 3) support the theory that different phenotypes of TN represent a continuous
M AN U
spectrum of degree of injury to the nerve rather than discrete diagnoses [6]. Nevertheless, there are some patients without any evidence of NVC during the operation, and most of them represent atypical symptoms, which may be attributed to the unrevealed pathological states, for example, alteration in intrinsic plasticity and descending modulation within the trigeminal nuclei or other areas of sensory
TE D
conduction system. Surgical intervention for partly or completely blocking conduction of peripheral afferents, such as internal neurolysis [32], and trigeminal root compression [33, 34] in these cases might help with pain relief; however, the
EP
long-term efficacy and relative complication are still under controversy. Accordingly, although NVC is the dominating causation, it is neither sufficient nor necessary for the development of TN. The exploration for more efficient treatment of TN in
AC C
different situations and individuals will mainly rest on understanding of the pathological mechanisms involved.
Conclusions
The presence of MA is a reliable predictor of the immediate and long-term outcome after MVD for TN. Compared to patients without MA, the incidence rate of intraoperative NVC is higher in those with MA, which are more likely to achieve a lower rate of recurrence after MVD for TN. Application of the information in this study will be helpful in patient selection of MVD for TN.
ACCEPTED MANUSCRIPT
References [1]
Dandy WE. Concerning the cause of trigeminal neuralgia. Am J Surg 1934;24:447-455.
[2]
Jannetta PJ,
Robbins LJ. Trigeminal neuropathy--new observations. Neurosurgery
1980;7(4):347-51. [3]
Cruccu G, Gronseth G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM, American Academy of Neurology S, European Federation of Neurological S. AAN-EFNS
RI PT
guidelines on trigeminal neuralgia management. European journal of neurology : the official journal of the European Federation of Neurological Societies 2008;15(10):1013-28. [4]
Bakker NA, Van Dijk JM, Immenga S, Wagemakers M, Metzemaekers JD. Repeat microvascular decompression for recurrent idiopathic trigeminal neuralgia. Journal of neurosurgery 2014;121(4):936-9.
[5]
Gu W,
Zhao W. Microvascular decompression for recurrent trigeminal neuralgia. Journal of
SC
clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2014;21(9):1549-53. Burchiel KJ,
Slavin KV. On the natural history of trigeminal neuralgia. Neurosurgery
2000;46(1):152-4; discussion 4-5. [7]
M AN U
[6]
Kumar S, Rastogi S, Kumar S, Mahendra P, Bansal M, Chandra L. Pain in trigeminal neuralgia: neurophysiology and measurement: a comprehensive review. Journal of medicine and life 2013;6(4):383-8.
[8]
Montano N, Conforti G, Di Bonaventura R, Meglio M, Fernandez E, Papacci F. Advances in diagnosis and treatment of trigeminal neuralgia. Therapeutics and clinical risk management 2015;11:289-99.
Li ST, Pan Q, Liu N, Shen F, Liu Z, Guan Y. Trigeminal neuralgia: what are the important factors
TE D
[9]
for good operative outcomes with microvascular decompression. Surgical neurology 2004;62(5):400-4; discussion 4-5. [10]
Tyler-Kabara EC, Kassam AB, Horowitz MH, Urgo L, Hadjipanayis C, Levy EI, Chang YF. Predictors of outcome in surgically managed patients with typical and atypical trigeminal
EP
neuralgia: comparison of results following microvascular decompression. Journal of neurosurgery 2002;96(3):527-31. [11]
Burchiel KJ. A new classification for facial pain. Neurosurgery 2003;53(5):1164-6; discussion
AC C
6-7. [12]
Miller JP, Magill ST, Acar F, Burchiel KJ. Predictors of long-term success after microvascular
decompression for trigeminal neuralgia. Journal of neurosurgery 2009;110(4):620-6.
[13]
Hutchinson J. The Surgical Treatment of Facial Neuralgia. Vol. p 1. New York: Wm. Wood &
Co.,, 1905.
[14]
Sandkuhler J. Models and mechanisms of hyperalgesia and allodynia. Physiological reviews
2009;89(2):707-58. [15]
Campbell JN, Raja SN, Meyer RA, Mackinnon SE. Myelinated afferents signal the hyperalgesia associated with nerve injury. Pain 1988;32(1):89-94.
[16]
Gracely RH, Lynch SA, Bennett GJ. Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992;51(2):175-94.
[17]
Sandkuhler J. Understanding LTP in pain pathways. Molecular pain 2007;3:9.
[18]
Torsney C,
MacDermott AB. Disinhibition opens the gate to pathological pain signaling in
ACCEPTED MANUSCRIPT superficial neurokinin 1 receptor-expressing neurons in rat spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26(6):1833-43. [19]
Todd AJ. Neuronal circuitry for pain processing in the dorsal horn. Nature reviews. Neuroscience 2010;11(12):823-36.
[20]
Sandel T,
Eide PK. Long-term results of microvascular decompression for trigeminal
neuralgia and hemifacial spasms according to preoperative symptomatology. Acta neurochirurgica 2013;155(9):1681-92; discussion 92. Ibrahim S. Trigeminal neuralgia: diagnostic criteria, clinical aspects and treatment outcomes. A retrospective study. Gerodontology 2014;31(2):89-94. [22]
RI PT
[21]
McLaughlin MR, Jannetta PJ, Clyde BL, Subach BR, Comey CH, Resnick DK. Microvascular decompression of cranial nerves: lessons learned after 4400 operations. Journal of neurosurgery 1999;90(1):1-8.
[23]
Sekula RF, Jr., Frederickson AM, Jannetta PJ, Quigley MR, Aziz KM, Arnone GD. Microvascular
SC
decompression for elderly patients with trigeminal neuralgia: a prospective study and systematic review with meta-analysis. Journal of neurosurgery 2011;114(1):172-9. [24]
Battista AF,
Alban E. Effect of graded ligature compression on nerve conduction.
[25]
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139(2):267-84.
[26]
M AN U
Experimental neurology 1983;80(1):186-94.
Sabalys G, Juodzbalys G, Wang HL. Aetiology and pathogenesis of trigeminal neuralgia: a comprehensive review. Journal of oral & maxillofacial research 2013;3(4):e2.
[27]
Sekula RF, Jr., Frederickson AM, Jannetta PJ, Bhatia S, Quigley MR. Microvascular decompression after failed Gamma Knife surgery for trigeminal neuralgia: a safe and effective
[28]
TE D
rescue therapy? Journal of neurosurgery 2010;113(1):45-52.
Ikeda H, Heinke B, Ruscheweyh R, Sandkuhler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 2003;299(5610):1237-40.
[29]
Ikeda H, Stark J, Fischer H, Wagner M, Drdla R, Jager T, Sandkuhler J. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 2006;312(5780):1659-62. Bender M, Pradilla G, Batra S, See A, Bhutiani N, James C, Carson BS, Lim M. Effectiveness of
EP
[30]
repeat glycerol rhizotomy in treating recurrent trigeminal neuralgia. Neurosurgery 2012;70(5):1125-33; discussion 33-4. Daugherty E, Bhavsar S, Hahn SS, Bassano D, Hall W. A successful case of multiple stereotactic
AC C
[31]
radiosurgeries for ipsilateral recurrent trigeminal neuralgia. Journal of neurosurgery 2015;122(6):1324-9.
[32]
Ko AL, Ozpinar A, Lee A, Raslan AM, McCartney S, Burchiel KJ. Long-term efficacy and safety
of internal neurolysis for trigeminal neuralgia without neurovascular compression. Journal of
neurosurgery 2015;122(5):1048-57.
[33]
Cheng J, Lei D, Zhang H, Mao K. Trigeminal root compression for trigeminal neuralgia in patients with no vascular compression. Acta neurochirurgica 2015;157(2):323-7.
[34]
Revuelta-Gutierrez R, Martinez-Anda JJ, Coll JB, Campos-Romo A, Perez-Pena N. Efficacy and safety of root compression of trigeminal nerve for trigeminal neuralgia without evidence of vascular compression. World neurosurgery 2013;80(3-4):385-9.
ACCEPTED MANUSCRIPT
Figures legends Figure 1: Graphs of results of immediate (upper) and long-term (lower) outcomes based on the presence of MA, as well as the type of TN pain. (NMA, non-MA, absence of mechanical allodynia.)
RI PT
Figure 2: Graphs of results of recurrence (upper) and delayed relief (lower) based on the presence of MA, as well as the type of TN pain. (NMA, non-MA, absence of mechanical allodynia.)
Figure 3: The schema illustrates the sequential impairment of different types of nerve
SC
fibers and different levels of the sensory conduction pathway in the development of TN. Pathological mechanisms accounting for different symptoms were listed and
AC C
EP
TE D
M AN U
correlated for a better understanding of this process.
ACCEPTED MANUSCRIPT Table 1 Demographic and clinical characteristics of 246 patients* MA (n=188)
NMA (n=58)
Mean age (yr)
62.7
63.9
Female (%)
132 (70.0)
40 (69.0)
Mean duration (mo)
64.5
80.9
Right side (%)
110 (58.5)
30 (51.7)
History of hypertension
86
22
History of DM
24
T1TN (%)
162 (86.2)
46 (79.3)
NVC (%)
150 (79.8)
34 (58.6)
Mean postop follow up (mo)
43.1
42.4
SC
RI PT
Characteristics
M AN U
0
AC C
EP
TE D
*Values represent numbers of patients (%) unless otherwise indicated. NMA, non-MA, absence of mechanical allodynia; DM, diabetes mellitus.
ACCEPTED MANUSCRIPT Table 2 The results of immediate outcome after MVD* Excellent
Good
Poor
MA (%)
115 (61)
42 (22)
31 (17)
NMA (%)
15 (26)
18 (31)
25 (43)
T1TN (%)
120 (58)
48 (23)
40 (19)
T2TN (%)
10 (26)
12 (32)
16 (42)
AC C
EP
TE D
SC
M AN U
*Values represent numbers of patients (%) NMA, non-MA, absence of mechanical allodynia.
RI PT
Classification
ACCEPTED MANUSCRIPT Table 3 The results of long-term outcome after MVD* Excellent
Good
Poor
Recurrence
Delayed relief
MA (%)
116 (61)
35 (19)
37 (20)
18 (10)
14 (7)
NMA (%)
12 (21)
13 (22)
33 (57)
15 (26)
6 (10)
T1TN (%)
118 (57)
38 (18)
52 (25)
26 (13)
15 (7)
T2TN (%)
10 (26)
10 (26)
18 (48)
7 (18)
5 (13)
RI PT
Classification#
AC C
EP
TE D
M AN U
SC
*Values represent numbers of patients (%) #The classification is based on the initial review of medical history chart. NMA, non-MA, absence of mechanical allodynia.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights 1. Mechanical allodynia predicted both the immediate and long-term outcome after
AC C
EP
TE D
M AN U
SC
RI PT
MVD for TN. 2. Higher rate of neurovascular compression is found in patients with MA. 3. Lower rate of recurrence is found in patients with MA. 4. Sequential impairment of the sensory conduction pathway may be involved in TN
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
Conflicts of interest: none