Is There a Safe and Effective Way to Treat Trigeminal Neuralgia Associated with Vertebrobasilar Dolichoectasia? Presentation of 8 Cases and Literature Review

Accepted Manuscript Is there a Safe and Effective Way to Treat Trigeminal Neuralgia Associated with Vertebrobasilar Dolichoectasia? Presentation of Eight Cases and Literature Review Vicente Vanaclocha, MD PhD, Juan Manuel Herrera, MD, Deborah Martínez-Gómez, Marlon Rivera-Paz, MD, Cristina Calabuig-Bayo, MD, Leyre Vanaclocha, (Medical Student) PII:

S1878-8750(16)30768-9

DOI:

10.1016/j.wneu.2016.08.085

Reference:

WNEU 4496

To appear in:

World Neurosurgery

Received Date: 12 June 2016 Revised Date:

19 August 2016

Accepted Date: 20 August 2016

Please cite this article as: Vanaclocha V, Herrera JM, Martínez-Gómez D, Rivera-Paz M, CalabuigBayo C, Vanaclocha L, Is there a Safe and Effective Way to Treat Trigeminal Neuralgia Associated with Vertebrobasilar Dolichoectasia? Presentation of Eight Cases and Literature Review, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.08.085. 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

IS THERE A SAFE AND EFFECTIVE WAY TO TREAT TRIGEMINAL NEURALGIA ASSOCIATED WITH VERTEBROBASILAR DOLICHOECTASIA? PRESENTATION OF EIGHT CASES AND LITERATURE REVIEW

Article Title

Vanaclocha MD PhD, Juan Manuel Herrera MD, Deborah Martínez-Gómez, Marlon Rivera-Paz MD, Cristina Calabuig-Bayo MD, Leyre Vanaclocha (Medical Student)

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Authors Vicente

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I certify that there is no actual or potential conflict of interest in relation to this article. We had no funding at all and no help from any commercial firm.

12th June 2016

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Vicente Vanaclocha MD PhD

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IS THERE A SAFE AND EFFECTIVE WAY TO TREAT TRIGEMINAL

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NEURALGIA ASSOCIATED WITH VERTEBROBASILAR

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DOLICHOECTASIA? PRESENTATION OF EIGHT CASES AND

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LITERATURE REVIEW. ABSTRACT

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Background: surgical treatment of trigeminal neuralgia (TN) associated with vertebro-

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basilar dolichoectasia (VBD) is challenging.

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Aim: to analyze the treatments for this disease discussing its advantages and drawbacks,

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presenting our own technique and series.

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Methods: retrospective study January 2006-January 2016. On pre and postop MRI

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images VBD deviation from midline, BA and VA diameter, and BA apex distance

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above posterior clinoid process were measured. BA repositioned and kept in place

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coagulating the clivus dura, Teflon pledgets and fibrin glue. Also a thorough Pubmed

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search done.

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Results: 5 males/3 females, mean age 64.88±10.32SD years (range 48- 81 years). 7

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cases TN and 1 PTC. 6 cases pain in left side, right in 2. All cases affected V2 and/or V3

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divisions. V2 and V3 affected in 4 cases, V3 in 3 and V2 in 1. Hypertension in 5 cases.

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Postop TN disappeared in all cases. One patient took Clonazepam 2mg/24h for 3

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months due to facial dysesthesia. 1 postop hearing loss. 1 postop facial paresis plus

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diplopia, that resolved in 3 months. Postop arterial hypertension improved in all

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affected patients, only 2 discontinued the anti-hypertensive medication. Mean follow-up

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56.50±40.08 months (range 14 months to 9 years and 9 months). No patient showed

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pain recurrence.

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Conclusion: TN associated with VBD can be treated surgically with minimal

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morbidity. Basilar artery repositioning has the highest success rate. Our technique

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inducing a dural scar to fix the basilar artery it in its new position away from the

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trigeminal nerve is simple, not technically demanding and highly effective.

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ACCEPTED MANUSCRIPT 1

IS THERE A SAFE AND EFFECTIVE WAY TO TREAT TRIGEMINAL

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NEURALGIA

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DOLICHOECTASIA?

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LITERATURE REVIEW.

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INTRODUCTION

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Dolichoectasia (DC) (from the Greek “dolicho”, elongated, and “ectasia”, dilated) is a

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vasculopathy consisting in an increase in the diameter and length of the affected

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artery1,2. The wall is thin, and sometimes harbors an intraluminal thrombus and/or

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atherosclerotic plaques2. It involves mostly the basilar (BA) and vertebral (VA) arteries,

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but other arteries, intracranial3–5 and extracranial6–10, can also be affected.

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The prevalence of intracranial DC ranges from 0.05% to 0.611,12. It is more frequent in

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elderly people1,7 but it has also been reported among youngsters and even in children13–

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fact, on microscopic examination the media shows degeneration of the internal elastic

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lamina of unknown origin2,5,7,16,17.

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On CT images the diagnostic criteria for vertebro-basilar dolichoectasia (VBD) are18:

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BA diameter >4.5mm, vertical elongation over the posterior clinoid process or the

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suprasellar cistern, or lateral deviation outside of the clivus or dorsum sellae. On MRI

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the criteria are19,20: BA >29.5mm in length or with a midline deviation >10mm; VA

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>23.5mm in length, or if it reaches a height >10mm above its entry point in the

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intracranial cavity, and if any portion the VA or the origin of the BA lie above the

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pontomedullary junction20.

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Although sometimes asymptomatic, VBD can be associated with posterior circulation

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transient ischemic attacks and strokes1,7,17,20, intracranial bleeding11,12,21 brainstem

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compression22, hemifacial spasm (HFS)23–26,26,27, trigeminal neuralgia (TN)28–34,

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compression of other cranial nerves1,20,35 or even hydrocephalus7,36. The VIIth is the

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most commonly affected cranial nerve, followed by the Vth1, while the VIth is rarely

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involved37. The incidence of TN associated with VBD ranges from 0.9% to 5.8%5,20,38–

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where patients suffer from both TN and HFS.

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The publications on TN or PTC associated with VBD are mostly isolated case

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reports23,26,26,28,29,32,34,45,45,47–54

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. This makes it unlikely that hypertension and atherosclerosis are the only causes1. In

, 0.7% for HFS43 and a 0.37% to 0.66% for paroxysmal tic convulsive (PTC) 25,27,43–46,

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series24,25,30,44,45,55–59

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ACCEPTED MANUSCRIPT exceptions27,33,40,55,60. Treatments are varied depending on the inventiveness of each

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surgeon.

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The purpose of this article is to review all the reported data on TN or PTC associated

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with VBD adding 8 cases of our own, analyzing the advantages, disadvantages and

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results of each treatment modality. Cases with HFS alone or with brainstem

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compression with no facial pain have been excluded. The reasoning behind this is that

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the methods and directions of decompression are slightly different in TN, HFS and

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brain stem compression.

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MATERIALS AND METHODS

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We analyzed retrospectively the medical records of our patients with TN with or

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without HFS from 1st January 2006 to 1st January 2016. Patients suffering only from

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HFS and no TN were excluded. In this 10-year period, out of 137 patients harboring TN

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we identified 8 patients suffering from TN with or without HFS associated with VBD.

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All patients had received previously medical treatment for years until the treating

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physician felt that surgical treatment was indicated, as the facial pain could not be

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controlled in spite of high doses of medication with some occasionally unpleasant side

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effects.

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Patients demographics were recorded (age, sex) as well as diagnosis, side, affected

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trigeminal divisions, hypertension, pre-operative neurological deficits, BA diameter,

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lateral displacement (most lateral position of BA), vertical elongation of the BA (plane

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of BA bifurcation), grade of compression of the Vth nerve, previous surgical treatments,

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time until recurrence of TN pain since prior surgical treatments, current method of TN

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treatment, materials used for Microvascular Decompression (MVD), offending vessel/s,

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degree of pain improvement after MVD, complications seen, follow-up time and

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recurrence.

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MRI studies were performed before the surgical procedure and in the follow-up with a

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General Electric 1.5 Tesla (GE Signa) superconducting magnet.

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MRI images were reviewed and VBD deviation from midline, BA and VA diameter,

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and BA apex distance above posterior clinoid process measured with the electronic

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medical recording system of our own hospital. The diagnosis of VBD was established

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according to the MRI criteria of Giang et al.19 and Ubogu and Zaidat20. We attempted to

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ACCEPTED MANUSCRIPT classify the lateral displacement and vertical elongation of the BA according to Szapiro

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et al.61 (Table 1), but we found it easier and more reliable to measure directly the

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distance from the midline (Figure 1). The grade of compression of the trigeminal nerve

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was classified according to Sindou et al.62 (Table 2).

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For the surgical procedure, patients were placed in the supine position with their head

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supported on a Mayfield head clamp, rotated towards the contralateral side. A bolster

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was placed under the ipsilateral shoulder. A generous retromastoid suboccipital

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craniotomy was performed, bigger than the ones done for regular TN cases involving

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small vessels. The cerebellum was approached through its tentorial aspect until the

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trigeminal cistern was visualized. On opening the arachnoid of this cistern as much CSF

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as possible was drained. The area was inspected to evaluate the offending vessels

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(Figure 2). The superior petrosal vein was coagulated and sectioned. The trigeminal

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nerve and the BA were dissected free of any arachnoid adhesions (Figure 3). Any

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additional vessel compressing the Vth nerve was also freed and moved out of place.

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Veins compressing the trigeminal nerve were coagulated and sectioned. The dura of the

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clivus medial to the VIth nerve, where the BA will lie after repositioning, was

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thoroughly coagulated with the bipolar forceps (Figure 4). To minimize the chance of

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VIth nerve damage we coagulated under low power, with a bipolar forceps with a tip

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0.3mm in diameter, and we irrigated with mannitol. Irrigation with saline during this

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coagulation was avoided to reduce the spreading of the electric current and thus the

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chance of incidental VIth nerve injury.

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Once completely free of any arachnoid adhesions and having evaluated the perforating

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vessels and its length, the VBD complex was moved medially and supported in place

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with Teflon pledgets. Human fibrin glue had to be added in some but not all cases to

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prevent the VBD to return to its earlier position where it compressed the trigeminal and,

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at times, facial nerves. The SCA was also thoroughly freed of any adhesions and

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arachnoid bands, displaced cranially until it lied at the tentorial incisura in the crural

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cistern and supported in its new position with a Teflon pledget (Figure 5). In one case a

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pontine artery, branch of the AICA, had to be displaced and held in place with another

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Teflon pledget. The whole surgical procedure can be seen in the two supplemental

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videos provided.

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Patients were examined at 1 and 6-month post-op and then at yearly intervals. An MRI

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examination was performed at 1 and 6-month post-op and at yearly intervals to see the

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ACCEPTED MANUSCRIPT degree of medial displacement of the VBD and to rule out any recurrence of the Vth

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nerve vascular compression (Figure 6). Patients were inquired for any facial

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hypoesthesia, facial paresis, masseteric weakness, hearing loss, diplopia, hypertension

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or any other additional symptoms. For the study, patients underwent a new follow-up

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visit to confirm their actual status or were contacted through the phone. That was

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particularly important with the very elderly patients, as they could have died of

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unrelated causes.

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We reviewed the data of all the publications available in PubMed dealing with TN or

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PTC. All reports of patients on HFS with no concomitant TN were excluded.

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Statistical analysis. Statistical analysis was performed using both Excel (Microsoft

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Corporation, Redmond, WA, USA) and R sofware63,64, conducting a basic descriptive

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analysis based on the calculation of the mean, median, standard deviation and range.

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RESULTS

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The data of our patients is summarized in Table 3. Our series included 8 patients, 5

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males and 3 females, with a mean age of 64.88±10.32SD years, range 48 to 81 years

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old. We had 7 cases of TN and 1 case of PTC. The pain was localized in the left side in

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6 cases and in the right in 2. All cases affected the V2 and/or V3 branches. V2 and V3

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were affected in 4 cases, V3 in 3 and V2 in 1. Hypertension was present in 5 out of 8

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cases. Mild facial hypoesthesia was present in 2 cases that had previously undergone

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three percutaneous radiofrequency thermocoagulation (RFTC) of the Vth nerve in an

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attempt to avoid a major surgical procedure in elderly and frail patients. Recurrence of

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TN after RFTC happened with a mean of 8.33±6.37SD months, range 1 to 19 months.

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On MRI examination the mean BA diameter was 5.73±0.81SDmm, range 4.6 to 6.9mm.

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The mean VBD complex lateral deviation was 13.92±1.47mm, range 11.7 to 16.1mm.

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Mean vertical BA elongation above the posterior clinoid process was 9.75±5.57mm,

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range 2 to 20mm. The degree of trigeminal nerve compression, classified according to

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the Sindou et al62 scale, was grade II in 2 cases and grade III in 6 cases. The offending

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vessel was the BA in 4 cases, the BA + VA in 2 cases and the BA + the SCA in 2 more

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cases, one of which also had a pontine artery, branch of the AICA, compressing the

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trigeminal nerve at its root entry zone.

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All the patients were treated with MVD, repositioning the VBD and holding it in its

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new position with Teflon pledgets. In three cases human fibrin glue was added to hold

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ACCEPTED MANUSCRIPT the VBD in its new position until the scarring held it in place. TN pain disappeared after

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MVD in all cases but in 4 out of 8 there was some mild ipsilateral facial hypoesthesia.

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Two of those 4 aforementioned patients had undergone previous RFTC. One of these

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patients had to take daily 1 Clonazepam 2mg tablet at night time for 3 months to control

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facial dysesthesia. Subsequently he slowly discontinued it and he has not required any

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further medication to control his TN since. The hemifacial spasm disappeared in the

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only patient that suffered from it. She had a mild case, and underwent the MVD because

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of her TN pain. We also had a case with mild post MVD hearing loss which did not

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improve over time. It was an 81-year old patient in whom three previous RFTC had

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been attempted. The patient is pleased to be finally rid of the pain. Another case that

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involved the VIth nerve ended with a post-operative facial paresis and a diplopia, both of

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which took 2 and 3 months respectively to resolve. Arterial hypertension improved in

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all five patients but only 2 could discontinue the anti-hypertensive medication. The

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mean follow-up of our patients was 56.50±40.08 months, range 14 months to 9 years

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and 9 months. Up to now no patient has shown recurrence of the pain.

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Literature research

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In PubMed we found 31 publications dealing with VBD associated TN or PTC with a

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total amount of 174 cases. Seven publications report 9 or more cases (4560, 3140, 2033,

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1130, 1065 and 927 cases, respectively). These series represent 126 of the 174 cases

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(72%). Six reports24,31,56–58,66 dealt with 3 cases, two25,59 with 2 cases and 16 with 1

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single case26,28,29,32,34,37,45,48–54. The first report is from 197934 and the last from 201525.

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The diagnosis was TN alone in 21 reports24,28–34,37,40,47–49,51,54,56–60,65, PTC in 823,25–

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27,45,50,52,53

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(87%) suffered only from TN and 22 cases (13%) from PTC. Sex was male in 102

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(62%) and female in 72 (42%). The mean age for the whole group was 64.61 years,

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range 44 to 95 years. The oldest subgroup of patients were those submitted to Gamma

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Knife Surgery (GKS)33, as over 75 years old co-morbidities often make a craniotomy

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unadvisable. The left side of the face was involved in 99 (57%) cases and the right in 75

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(43%). The affected divisions were V2 + V3 in 84 cases (48%), V2 in 36 cases (20%), V3

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in 21 cases (12%), V1 and V2 in 11 cases (6%), V1 + V2 + V3 in 7 cases (4%) and V1 in

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4 cases (2%). In 11 cases (6%) there was no report on the affected trigeminal division/s.

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If we add all the cases affecting V2 and or V3 and exclude those affecting V1 we have

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141 cases (86%) out of the 163 in whom the affected trigeminal division/s were

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and a mixture of patients with either TN or PTC in 2 cases55,66. 152 patients

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ACCEPTED MANUSCRIPT reported. So, V1 is less commonly affected and when it does this is mostly due to

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PTC26,45,52. All these data are summarized in Table 5.

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Arterial hypertension: it has been reported in 74 patients (42.5%), excluded in 26

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patients (15%), and not specified if they were hypertensive or not in another 74

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(42.5%). So, arterial hypertension is common but due to the absent data from 74

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patients no firm conclusions can be drawn. These data are summarized in Table 6.

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Neurological deficits BEFORE MVD/GKS were present in 49 cases (28%): facial

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hypoesthesia 30 cases30,40,50,52,55,58; burning or persistent lingering facial pain 5 cases33;

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weak corneal reflex 4 cases26,52,55; hyperesthesia over V1 + V2 + V3 2 cases50,56;

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persistent hemifacial spasm 2 cases30; slight dysarthria + spastic gait 1 case34; epileptic

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seizures 1 case51, chronic headache 1 case57, facial weakness 1 case55; downbeat

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nystagmus 1 case55; ipsilateral hearing loss 1 case30. Most of these deficits were related

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with initial neurolitic treatments, like peripheral neurectomies, alcohol injections and

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RTFC.

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Surgical treatments BEFORE MVD/GKS had been applied in 40 cases (23%): RFTC

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11 cases29–31,40,50,55,58,59, previous GKS 9 cases33, MVD 3 cases (1 with Ivalon)31,40,53,

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peripheral nerve alcohol injections 3 cases40,50,58, peripheral neurectomy 2 cases40,

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glycerol rhizotomy 1 case40, and previous non-specified surgical treatments 11 cases33.

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In those cases in which it is reported, the TN pain recurred in a period spanning from a

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few days (alcohol injections58) to a maximum of 4 years after RFTC29, the majority

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happening around 2 years30,31,53,59. These treatments showed a limited pain control and

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for a short period of time, so they are not to be recommended except in case a

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craniotomy is deemed unadvisable.

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Last reported treatment method: MVD in 84 cases24–27,29–32,37,47–50,52–60,65, GKS in 21

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cases23,33, MVD +

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cases23,33,40,45,66, open posterior trigeminal rhizotomy (PPTR) in 4 cases34,66, RFTC in 2

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cases58, inferior alveolar nerve neurectomy in 1 case51 and open bipolar coagulation of

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the posterior root of the trigeminal nerve in 1 case28. GKS has a very high recurrence

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rate as 15 of the 21 cases (71.42%) treated with GKS required further surgical

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treatments, not detailed in the publications23,33.

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Material used for MVD (91 out of 174 cases, 52.29%): simple decompression with

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autologous muscle patch50,58, Teflon25,27,29,30,40,45,49,55,56,65, Ivalon40 or a vascular graft47

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open posterior partial trigeminal rhyzotomy (PPTR) in 5

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ACCEPTED MANUSCRIPT in 80 cases (87.91%); different types of tapes fixed to dura with sutures32,37, hemoclips53

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or aneurysm clips 6 cases (6.5%)24,40, titanium plates 3 cases (3.2%)48,59, fenestrated

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aneurysm clip around Vth nerve 1 case (1.0%)26, silicone tubing around trigeminal nerve

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1 case (1.0%)54. The use of muscle patch or Ivalon are not reported in TN associated

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with VBD since 199440. The conclusion is that the immense majority of cases have been

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treated with simple MVD with no VBD repositioning. In 5 additional cases some

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surgeons have associated an open partial posterior trigeminal rhizotomy (PPTR) to the

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MVD with excellent pain control but with significant facial hypoesthesia34,45,66.

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Offending vessel/s: out of the 145 cases in which the vessel was identified (83.33%),

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the BA + VA + SCA + AICA were the offending vessels in 44 cases40,60, BA in 38

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cases25,26,28,33,34,45,48,49,51,53–55,58,60, VA in 32 cases24,26,27,33,40,50,55,65,66, VA + other vessels

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in 20 cases24,40,55,65, BA + SCA in 9 cases37,55,65, BA +VA in 3 cases25,32,66, BA + AICA

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in 1 case65, pontine artery in 1 case66. In 26 cases (16,77%)

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offending vessel was not specified. Hence, multiple vessels are involved in 78 cases

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(53.79%), followed by the BA in 38 cases (26.2%) and the VA in 32 cases (20.01%).

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TN pain control: residual facial post MVD pain was reported by Linskey et al. in 10%

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of 31 patients40 and by García de Sola et al.56 in 1 out of 3 patients. So, almost all

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patients that underwent some form of MVD with or without VBD repositioning

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achieved an excellent pain control. Meanwhile, with GKS Park et al.33 reported that

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pain relief was maintained in 53% at 1 year, 38% at 2 years, and 10% at 5 years and

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Lakhan reported a pain relief lasting some months (quantity not specified)23. Although

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GKS was associated with mediocre results we have to consider that those patients had

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already undergone other surgical procedures that proved to be unsuccessful to control

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the pain. PPTR34,45,66, as mentioned above, had an excellent control of the pain but at

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the price of a severe facial hypoesthesia. Percutaneous procedures like neurectomy of

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the inferior alveolar nerve51 and RFTC31,58 had unsatisfactory and short lasting results.

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HFS control: in those patients with PTC the TN was well controlled in all 28 cases23,25–

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27,32,40,45,50,52,55,66

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Complications associated with the last treatment method: hemifacial hypoesthesia

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was the most common unwanted side effect (20% of patients). It was reported in all 7

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cases of PPTR30,34,45,66, in the case of neurectomy of the inferior alveolar nerve51, in the

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2 cases in which RTFC was applied31 and in 25 cases of MVD24,30,40,55,56,65. Other

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complications were facial hyperesthesia in 25 cases of MVD26,50,60 (14%); facial paresis

23,27,29–31,47,52,56–59

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and the HFS in all but two55.

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ACCEPTED MANUSCRIPT after MVD with or without PPTR in 12 cases26,30,55,66 (6%); diplopia in 6 cases28,55,60

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(3%); permanent neurological deficits in 6 cases of MVD60 (3%); 1 case of masseter

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muscle weakness after MVD40; 1 case mild disequilibrium after MVD29, hearing

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impairment in 1 case after MVD31 and 1 post-op death a week after a MVD58. Some

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authors did not describe their complications in detail30,40,60.

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Follow-up: in the 129 cases (75%) in which it was reported, the mean follow-up was

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35.39 months, range 1 month to 9 years. In 45 cases (25%) there is no follow-up

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reported. The problem with drawing any conclusions is that the follow-up is short in

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most series. Only a few report a follow-up of five or more years37,47,48,54,55 and all

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together they only amount to 12 cases. Lindskey et al.40 report an average follow-up of

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5 years in 31 patients but the range is 1 month to 15 years, and it is not reported how

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many of these patients had a follow-up over 5 years.

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TN pain recurrence: in RTFC reported in 2 out of 2 cases at 1 year by Lye et al.58 and

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in 2 out of 2 cases by Noma et al.31. In MVD it is reported by Miyazaki et al.60 in 2 out

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of 45 cases, Linskey et al.40 in 3 out of 31 cases at 1, 2 and 5-years follow-up and

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Alcalá-Cerra et al.47 in 1 case at 9-year follow-up. After GKS Park et al.33 reported it in

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14 out of 20 cases and in another case after a few months by Lakham23. No recurrence is

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reported in 60 cases of MVD25,27,28,30,32,37,48,49,53–55,65,66, and not specified if there was

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recurrence or not in 19 additional cases (PPTR in 4 cases34,66, MVD in 11

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cases26,29,50,56,57,59, MVD + PPTR in 1 case45). Again it is difficult to draw conclusions

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from such incomplete data, but it seems that MVD with or without VBD replacement

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has the lowest rate of TN recurrence.

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DISCUSSION

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VBD is an unusual cause of TN but when happens it represents is a formidable

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challenge5,20,38–42. Conservative treatment with drugs can help many patients for some

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time67, but when pain gets out of control other forms of treatment are required. The pain

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can become so severe that patients commit suicide68.

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Treatment modalities in refractory TN associated with VBD

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When TN is not controlled by medical treatment, other options have been considered,

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such as botulinum toxin injection23, peripheral neurectomies51, peripheral nerve alcohol

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ACCEPTED MANUSCRIPT injections40,50,58, GKS33, RFTC29–31,40,50,55,58,59 and MVD with or without VBD

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repositioning and with or without PPTR.

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Botulinum toxin injection

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It has been used in some cases of PTC23,69 or TN70,71 but relief is temporary69. It is

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recommended only for desperate cases in which the patient’s general condition makes a

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surgical procedure unadvisable or when other therapeutic attempts have already

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failed70,72.

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Peripheral neurectomies and alcohol injections

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They have been used in the past and abandoned as the results were short lived and

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patients ended up requiring other treatment modalities40,51,58. The same applies to

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alcohol injections40,50,58.

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RFTC

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It has been attempted in some cases to attain pain relief with a reduced surgical

272

aggressivity29–31,33,40,50,58,59. The results in all cases have been unsatisfactory with early

273

recurrences that required a repeat procedure58 or applying other treatment modalities,

274

mostly MVD26,29–31,40,50,55,58,59. There is also the added problem of an induced hemi-

275

facial hypoesthesia that makes the result of a MVD less likely to be successful23,33. Two

276

of our cases were previously treated 3 times each with RFTC with an unsatisfactory

277

control of the pain and early recurrence that were finally treated with MVD.

278

GKS

279

It has been applied both in recurrent and in primary cases, finding that pain control rates

280

were inferior and with shorter duration than those observed in patients with TN not

281

associated with VBD23,33. Some degree of facial sensory dysfunction happened in 10%,

282

and in 70% an additional procedure including repeat GKS, RFTC or MVD had to be

283

performed33. It does not seem to compare favorably with MVD for primary cases, but it

284

is an interesting option for failures or recurrences after MVD33.

285

Surgical techniques to decompress the trigeminal nerve

286

According to Lin et al.24 the open surgical techniques used for TN associated with VBD

287

can be classified into 3 groups: shielding (MVD), VBD repositioning, and partial

288

resection of the vertebral artery to shorten it. In addition, PPTR has been used to

289

supplement both MVD and VBD repositioning30,34,45,66.

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ACCEPTED MANUSCRIPT There is only one reported case of unilateral VA resection in a 30-year old man with

291

brainstem compression but with no trigeminal neuralgia73. The procedure is risky and

292

the result was so unsatisfactory that nobody else has ever reported performing it again

293

since 1993.

294

MVD

295

Simple MVD with no attempt of VBD repositioning by inserting autologous muscle

296

pieces40,50,58, Ivalon40,53, a vascular graft piece47 or Teflon25,27,29,30,40,45,49,54–56,65 between

297

the offending artery and the compressed nerve has become commonplace, not only in

298

isolated TN25,29,49,55,56 but also in PTC25,27,45. The autologous muscle pieces have been

299

abandoned as pain recurrence is frequent40. Ivalon prosthesis in TN associated with

300

VBD has also been abandoned due to higher recurrence rates when compared to

301

Teflon40,53. Although some have used simple pieces of Teflon25,45,49,55,56,65, shredded

302

pieces

303

complications25,27,29,45,49,55,65. Only Miyazaki et al.60 reported 6 permanent neurological

304

deficits in a series of 45 cases. In any case the results of MVD in TN associated with

305

VBD have been worse than in those cases where the offending vessel is a small one40,60.

306

The surgical maneuvers required to insert a prosthesis between the offending vessel and

307

the offended nerve might further aggravate the compression of the Vth nerve28,32 and at

308

times

309

hypoesthesia30,40,45,55,56,60,65, hearing loss24,31,40,60, facial paresis30,45,55, diplopia55,60 or

310

temporary disequilibrium29.

311

Although not common, some recurrences have been reported40,44,47,60, particularly with

312

Ivalon sponges40,53. Suzuki et al. in 199053 reported a case that recurred after MVD with

313

Ivalon sponges successfully re-operated and VBD repositioned with a vascular tape

314

fixed to the dura with a Weck Hemoclip®. The pain did not recur but the reported

315

follow-up was only 30 months53. Recurrence was also reported in 3 cases out of 31 in

316

the series of Linskey et al40. These cases were treated with GKS but with limited

317

success33. Miyazaki et al. reported 2 recurrences in 45 cases60.

318

In an attempt to protect the trigeminal nerve but without repositioning the VBD, this

319

nerve has been encircled with a silicone rubber supplemented with shredded Teflon54.

320

This is not devoid of risks as handling the trigeminal nerve can damage it and this nerve

321

has to keep bearing the pulsatile pressure of the VBD. The experience with this

often

used27,29,30,40.

cranial

nerve

deficits

The

such

results

as

a

are

new

or

good

with

worsened

few

facial

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10

ACCEPTED MANUSCRIPT technique is very limited as it has only been used in one patient54. It also raises some

323

concern as the silicone piece might migrate inducing recurrence of the pain.

324

VBD repositioning

325

Repositioning with a sling has been reported as more successful than interposing a pad

326

between the offending vessel and the Vth nerve62 but repositioning the VBD vessels is

327

technically much more demanding. In fact, the VA and BA not only are dilated and

328

tortuous but also rigid and firm2,3. Several surgical procedures have been proposed to

329

pull the VBD vessels towards the dura: use of a silicone sling37 or Gore-Tex® graft32

330

sutured with stitches to the dura of the petrous pyramid, a vascular tape fixed to the dura

331

with a Weck Hemoclip®53, a Gore-Tex® tape fixed to the dura with an aneurysm clip24

332

and even a titanium plate48,59. Using some sort of sling allows to move the VBD away

333

from the nerves, and the vessels can be repositioned without kinking24,32. The sutures32

334

or the aneurism clip24 fixed to the dura should guarantee that the VBD will not return to

335

its previous location with cranial nerve compression. The reported techniques for VBD

336

repositioning have rendered the patients pain-free but the series are small24,48,53,59.

337

Moreover, extensive neurovascular manipulation is necessary to achieve effective

338

decompression, besides the fact that the suturing technique is not easy in this area29,59.

339

Among all the approaches, the one described by Lin et al.24 entailing VBD repositioning

340

with a Gore-Tex sling fixed to the dura with an aneurysm clip seems the easiest and

341

safest. The advantage of the titanium plate techniques is that they can be performed

342

though a much smaller suboccipital craniotomy than the sling-techniques, but it seems

343

risky for general use. Only 3 cases have been reported48,59.

344

To keep the VBD in its new position but in a much less technically demanding way,

345

some used glue (cyanoacrylate)74. It induces a severe local inflammatory reaction that in

346

one case was related to a posterior cerebral artery occlusion with a subsequent infarct74.

347

In any case this material is not available since 2003. The alternative is to use fibrin glue

348

but it is not as strong as cyanoacrylate. It can be helpful to support the VBD in its new

349

position for a while, but something else is needed long-term.

350

In an attempt to hold the VBD in its new location we have coagulated the clivus dura to

351

induce the creation of a fibrous scar that might hold the VBD in its new position. We

352

have sparingly used shredded Teflon pledgets to hold the VBD in place and

353

complemented it in selected cases with fibrin glue. All this maneuvers are easier to

354

perform, require less handling of the posterior fossa structures and can be performed

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11

ACCEPTED MANUSCRIPT through a smaller craniotomy than the “sling” techniques. Less handling of posterior

356

fossa structures should induce less post-operative problems. The scar is thick and we

357

have not seen any recurrence of the TN pain.

358

Instead of moving the VBD away from the trigeminal nerve, Takamiya26 moved the

359

trigeminal nerve away from the VBD with a Sugita’s fenestrated clip fixed to the

360

tentorium in a case of PTC while the facial and acoustic nerves were wrapped with a

361

Dacron patch. Postoperatively, the TN pain disappeared but the patient had a mild facial

362

paresis and hyperesthesia on the left side of her face. The fact that it is a single case

363

report with no follow-up reported decreases its validity. Moreover, it does not seem

364

advisable, as the VBD may continue its expansion47 and compress the trigeminal nerve

365

again in its new position.

366

PPTR

367

It has been performed in cases when no MVD, with or without VBD repositioning, is

368

possible30,34,40,45,66. It entails sectioning the two caudal thirds of the trigeminal root,

369

being aware that V1 has to be spared to avoid corneal problems. Some have gone even

370

further, recommending to associate it regularly to the MVD in VBD to ensure pain

371

relief30. This helps to control the pain but at the price of a facial numbness30,34,45,66 and

372

the risk of anesthesia dolorosa30. The reported data are small series with short or no

373

follow-up at all, making it impossible to draw any firm conclusions30,34,40,45,66.

374

Ishii et al.28 modified the technique and in 1 single case performed a partial posterior

375

trigeminal sensory root thermocoagulation with the regular bipolar forceps28. The pain

376

was controlled but at the price of postoperative facial hypoesthesia and temporary

377

diplopia due to abducens nerve palsy28. Compared to the classical PPTR, the main

378

disadvantage of this technique is that there are no defined parameters for the bipolar

379

coagulation and no objective way to effectively control intra-operatively the results

380

achieved with the intensity, frequency and time in which this specific bipolar

381

coagulation was made. That makes it difficult to replicate and reduces the interest in the

382

technique. The reported follow-up is only one and a half years.

383

Results of surgical treatments of TN associated with VBD

384

Immediate post-operative pain control is habitual in the immense majority of cases.

385

Only El-Ghandour55 reported residual pain in 2 out of 10 cases. Recurrence of the pain

386

has been described by Mizayaki et al.60 in 2 out of 45 cases and by Linskey et al.40 in 3

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ACCEPTED MANUSCRIPT out of 31 cases. Those are the biggest series and with the longest reported follow-up

388

(mean follow-up of 19-month for the first and 5-year for the second). We have not seen

389

any recurrence in our cases with a mean follow-up of 56.50±40.08 months.

390

Improvement of pre-operative arterial hypertension has happened in the great majority

391

of cases22,24,25,30,30,32. We have confirmed this in our series. This is an added bonus for

392

patients who request the operation for the intolerable pain, but not the main reason to

393

undertake it.

394

Complications of surgical treatment of TN associated with VBD

395

These are more frequent than in TN cases for smaller vessels. The incidence seems to

396

increase in proportion with the handling of structures in the posterior fossa. Most of the

397

post-operative deficits are temporary and resolve in less than 3 months (diplopia28,55,60,

398

facial paresis26,30,55,66 or masseteric weakness40). One of our patients developed a post-

399

operative facial paresis with diplopia due to VIth nerve palsy that had resolved 3 months

400

later. Other complications, like the facial hypoesthesia, are common but tolerable for the

401

patients as an acceptable price to get rid of such an unpleasant pain24,30,40,45,55,56,60,65.

402

Hearing loss deserves special attention. It is often permanent and more often in cases of

403

PTC, as the facial and cochlear nerves have to be handled27. One of our patients

404

suffered this complication.

405

The highest reported complication rate is from Miyazaki et al. in 198760. This is an old

406

series without the technical advances available today and is to be commended by their

407

honesty. Their complication rate was 51% with MVD, although the majority of the

408

complications were temporary and resolved in less than 3 months. The most frequent

409

unpleasant side-effects were facial hyperesthesia and diplopia (due to IVth or VIth

410

cranial nerve deficit). Permanent neurological deficits happened in 6 out of 45 patients,

411

but there is no thorough description on their nature. Pain initially disappeared in all

412

patients but recurred in 2 in less than 2 months. Linskey et al. in 1994 reported new or

413

mildly worsened post-operative hypoesthesia/hypoalgesia in 41.9% of 31 cases.

414

Only one death in the first postoperative week has been reported58. It was due to a heart

415

attack in a case of MVD with a muscle patch in a patient with a suboptimal pre-

416

operative general condition. Conversely, no death has ever been reported due to

417

intraoperative rupture of the VBD. This is striking if we consider that the wall of these

418

vessels is thin and weak7,16,17.

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13

ACCEPTED MANUSCRIPT Follow-up

420

Long term follow-up over five years is provided only in a few cases38,41,49,50. In one of

421

them, 9 year later, there was recurrence of the TN accompanied with signs of brain stem

422

compression47, attesting that this is a serious condition that is not stopped by our

423

treatments. The dolichoectasia had progressed, also affecting both internal carotid

424

arteries. In our series the mean follow-up of our patients was 56.50±40.08 months,

425

range 14 months to 9 years and 9 months.

426

Limitations of the study

427

The main limitation of our study is the small simple size, making any conclusions

428

difficult to extrapolate. Unfortunately, this is the case for the great majority of the

429

series. We have tried to analyze all the available data to be able to draw some

430

conclusions but often they are incomplete in many of the series. Too many reports are

431

single case reports.

432

CONCLUSIONS

433

TN associated with VBD can be surgically treated with minimal morbidity.

434

Repositioning the BA has the highest success rate. Our technique entailing coagulation

435

the clivus dura to induce a scar that may fix the basilar artery it in its new position away

436

from the trigeminal nerve is simple, not technically demanding and highly effective.

437

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588 589

56.

García De Sola R, Escosa Bagé M. [Microvascular decompression of trigeminal neuralgia caused by vertebrobasilar dolichoectasia]. Rev Neurol. 2001;32(8):742-745.

590 591 592

57.

Kirsch E, Hausmann O, Kaim A, Gratzl O, Steinbrich W, Radü EW. Magnetic resonance imaging of vertebrobasilar ectasia in trigeminal neuralgia. Acta Neurochir (Wien). 1996;138(11):1295-1298; discussion 1299.

593 594

58.

Lye RH. Basilar artery ectasia: an unusual cause of trigeminal neuralgia. J Neurol Neurosurg Psychiatry. 1986;49(1):22-28.

595 596 597

59.

Taki W, Matsushima S, Hori K, Mouri G, Ishida F. Repositioning of the vertebral artery with titanium bone fixation plate for trigeminal neuralgia. Acta Neurochir (Wien). 2003;145(1):55-61. doi:10.1007/s00701-002-1033-3.

598 599 600

60.

601 602

61.

Szapiro J, Sindou M, Szapiro J. Prognostic factors in microvascular decompression for trigeminal neuralgia. Neurosurgery. 1985;17(6):920-929.

603 604 605

62.

Sindou M, Amrani F, Mertens P. [Microsurgical vascular decompression in trigeminal neuralgia. Comparison of 2 technical modalities and physiopathologic deductions. A study of 120 cases]. Neurochirurgie. 1990;36(1):16-25-26.

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568 569 570

Miyazaki S, Fukushima T, Tamagawa T, Morita A. [Trigeminal neuralgia due to compression of the trigeminal root by a basilar artery trunk. Report of 45 cases]. Neurol Med Chir (Tokyo). 1987;27(8):742-748.

18

ACCEPTED MANUSCRIPT 63.

Kirby KN, Gerlanc D. BootES: an R package for bootstrap confidence intervals on effect sizes. Behav Res Methods. 2013;45(4):905-927. doi:10.3758/s13428-013-0330-5.

608 609

64.

R: The R Project for Statistical Computing. https://www.r-project.org/. Accessed April 1, 2016.

610 611 612

65.

Yang X-S, Li S-T, Zhong J, et al. Microvascular decompression on patients with trigeminal neuralgia caused by ectatic vertebrobasilar artery complex: technique notes. Acta Neurochir (Wien). 2012;154(5):793-797; discussion 797. doi:10.1007/s00701-012-1320-6.

613 614 615

66.

Love S, Hilton DA, Coakham HB. Central demyelination of the Vth nerve root in trigeminal neuralgia associated with vascular compression. Brain Pathol Zurich Switz. 1998;8(1):111-12.

616 617

67.

Yoshida M, Asano M. Direct compression by megadolichobasilar anomaly as a cause of trigeminal neuralgia; a case diagnosed by MRI. Tohoku J Exp Med. 1994;172(4):327-332.

618 619 620

68.

Peñarrocha M, Peñarrocha MA, Soler F, Bagán JV. Trigeminal neuralgia associated to basilar artery dolichoectasia. Med Oral Órgano Of Soc Esp Med Oral Acad Iberoam Patol Med Bucal. 2001;6(1):36-39.

621 622 623

69.

Felicio AC, Godeiro C de O, Borges V, Silva SM de A, Ferraz HB. Bilateral hemifacial spasm and trigeminal neuralgia: a unique form of painful tic convulsif. Mov Disord Off J Mov Disord Soc. 2007;22(2):285-286. doi:10.1002/mds.21202.

624 625 626

70.

Wang S, Yue J, Xu Y, Xue L, Xiao W, Zhang C. [Preliminary report of botulinum toxin type A injection at trigger point for treatment of trigeminal neuralgia: experiences of 16 cases]. Shanghai Kou Qiang Yi Xue Shanghai J Stomatol. 2014;23(1):117-119.

627 628

71.

Xia J-H, He C-H, Zhang H-F, et al. Botulinum toxin A in the treatment of trigeminal neuralgia. Int J Neurosci. 2016;126(4):348-353. doi:10.3109/00207454.2015.1019624.

629 630 631

72.

Xia L, Zhong J, Zhu J, et al. Effectiveness and safety of microvascular decompression surgery for treatment of trigeminal neuralgia: a systematic review. J Craniofac Surg. 2014;25(4):1413-1417. doi:10.1097/SCS.0000000000000984.

632 633 634

73.

Hongo K, Kobayashi S, Hokama M, Sugita K. Vertebral artery section for treating arterial compression of the medulla oblongata. Case report. J Neurosurg. 1993;79(1):116-118. doi:10.3171/jns.1993.79.1.0116.

635 636

74.

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Hanakita J, Kondo A. Serious complications of microvascular decompression operations for trigeminal neuralgia and hemifacial spasm. Neurosurgery. 1988;22(2):348-352.

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ACCEPTED MANUSCRIPT 638

FIGURE LEGEND

639

Figure 1: Measurement of the lateral displacement of the VBD.

641

Figure 2: The area was inspected to evaluate the offending vessels (BA: basilar artery;

642

Vth: trigeminal nerve; VIth: abducens nerve; VIIth: facial nerve; SCA: superior

643

cerebellar artery).

RI PT

640

Figure 3: The trigeminal nerve and the BA were dissected free of any arachnoid

645

adhesions (BA: basilar artery; PPA: perforating pontine artery; Vth: trigeminal

646

nerve; VIth: abducens nerve; VIIth: facial nerve; SCA: superior cerebellar

647

artery).

SC

644

Figure 4: The dura of the clivus medial to the VIth nerve, where the BA will lie after

649

repositioning, is coagulated with the bipolar forceps (BA: basilar artery; Vth:

650

trigeminal nerve; VIth: abducens nerve; VIIth: facial nerve; SCA: superior

651

cerebellar artery).

M AN U

648

Figure 5: The basilar artery is displaced with a Teflon pledget (TA: Teflon pledget; Vth:

653

trigeminal nerve; CD: clivus dura; SCA: superior cerebellar artery).

654 655

Figure 6: Pre and post-operative MRI showing the repositioning of the VBD with Vth nerve decompression.

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652

20

ACCEPTED MANUSCRIPT 656

TABLES

657

Table 1: Scoring system to grade lateral displacement and vertical elongation of basilar

658

artery (taken from Szapiro JJ, Sindou M, Szapiro J. Prognostic factors in

659

microvascular decompression for trigeminal neuralgia. Neurosurgery 1985;

660

17:920-929). Table 2: Grade of compression of the trigeminal nerve (taken from Sindou M, Howeidy

662

T,

G.

Anatomical

observations

during

microvascular

663

decompression for idiopathic trigeminal neuralgia (with correlations

664

between topography of pain and site of the neurovascular conflict).

665

Prospective study in a series of 576 patients. Acta Neurochirurgica (Wien)

666

2002; 144(1):1-13).

SC

Acevedo

RI PT

661

Table 3: Demographics, pre-operative clinical status and VBD size of our patients (TN:

668

Trigeminal Neuralgia; PTC: Painful Tic Convulsive; RFTC: percutaneous

669

radiofrequency thermocoagulation).

M AN U

667

Table 4: Definitive treatment, offending vessels and results in our patients (TN:

671

trigeminal neuralgia; HFS: hemifacial spasm; MVD: Microvascular

672

Decompression; BA: basilar artery; VA: vertebral artery; SCA: superior

673

cerebellar artery).

TE D

670

Table 5: Demographics, side and affected divisions in the published series (TN:

675

Trigeminal Neuralgia; PTC: Painful Tic Convulsive; L: left side; R: right

676

side).

EP

674

Table 6: pre-operative status and definitive method of TN treatment (TN: Trigeminal

678

Neuralgia; PTC: Painful Tic Convulsive; HFS: hemifacial spasm; CR:

679 680 681

AC C

677

corneal reflex; AI: alcohol injection; FH: facial hypoesthesia; NT: peripheral neurectomy; GL: glycerol rhizotomy; VBD: Vertebro-Basilar Dolichoectasia; RFTC: percutaneous radiofrequency thermocoagulation;

682

PPTR: open posterior partial trigeminal rhyzotomy; VBD R: vertebro-

683

basilar complex repositioning; BA: basilar artery; VA: vertebral artery;

684

GKS: Gamma Knife Surgery; MVD: Microvascular Decompression without

685

VBD repositioning; N/A: Not available).

686

Table 7: pre-operative status and definitive method of TN treatment (TN: Trigeminal

687

Neuralgia; PTC: Painful Tic Convulsive; HFS: hemifacial spasm; CR: 21

ACCEPTED MANUSCRIPT corneal reflex; AI: alcohol injection; FH: facial hypoesthesia; FHs: facial

689

hyperesthesia; FP: facial paresis; NT: peripheral neurectomy; GL: glycerol

690

rhizotomy; VBD: Vertebro-Basilar Dolichoectasia; RFTC: percutaneous

691

radiofrequency thermocoagulation; PPTR: open posterior partial trigeminal

692

rhyzotomy; VBD R: vertebro-basilar complex repositioning; BA: basilar

693

artery; VA: vertebral artery; PA: Pontine artery; GKS: Gamma Knife

694

Surgery; MVD: Microvascular Decompression without VBD repositioning;

695

BT: botulinum toxin N/A: Not available).

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688

22

ACCEPTED MANUSCRIPT

0 1 2 3

Lateral displacement (most lateral position of BA) Midline throughout Medial to lateral margin of clivus or dorsum sellae Lateral to lateral margin of clivus or dorsum sellae Within cerebellopontine angle cistern

0 1

Vertical elongation (plane of BA bifurcation) At or below dorsum sellae Within Suprasellar cistern

2

At the level of third ventricle floor

3

Indenting and elevating floor of third ventricle

RI PT

Score

AC C

EP

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SC

Table 1: Scoring system to grade lateral displacement and vertical elongation of basilar artery (taken from Szapiro JJ, Sindou M, Szapiro J. Prognostic factors in microvascular decompression for trigeminal neuralgia. Neurosurgery 1985; 17:920-929).

ACCEPTED MANUSCRIPT Score Grade I Grade II Grade III

Grade of compression of the trigeminal nerve The vessel is simply in contact with the nerve but without any visible deformity of the root There is displacement or distortion of the root A clear-cut and marked indentation on the root is present

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Table 2: Grade of compression of the trigeminal nerve (taken from Sindou M, Howeidy T, Acevedo G. Anatomical observations during microvascular decompression for idiopatic trigeminal neuralgia (with correlations between topography of pain and site of the neurovascular conflict). Prospective study in a series of 576 patients. Acta Neurochirurgica (Wien) 2002; 144(1):1-13).

ACCEPTED MANUSCRIPT

Age

Diagn ose

Side

Affected divisions

Hypertension

Case 1

M

70

TN

L

V2 + V3

Yes

Case 2 Case 3

M

48

TN

R

V3

No

M

81

TN

L

V2 + V3

Yes

F

75

TN

L

V2 + V3

F

63

PTC

R

F

59

TN

M

64

M

59

BA artery diameter

5.2mm

6.6mm

No

Mild facial hypoesthesia V2 + V3 None

V3

Yes

None

5.9mm

L

V2

Yes

TN

L

V3

No

TN

L

V2 + V3

Yes

TE D

M AN U

4.9mm

6.9mm

None

6.2mm

None

5.6mm

None

4.6mm

EP

Degree most lateral position BA

Vertical length BA above post clinoid

Grade Vth nerve compress ion

Previous surgical treat.

Time TN recurrence from previous treatments

11.7m m

2mm

Grade III

RFTC x 3

18,6 and1 months

12.3m m 13.7m m

9mm

Grade II

None

-

6mm

Grade II

RFTC x 3

13, 9 and 3 months

15.3m m 14.2m m 16.1m m 13.4m m 14.7m m

20mm

Grade III

None

-

14mm

Grade III

None

-

9mm

Grade III

None

-

12mm

Grade III

None

-

6mm

Grade III

None

-

SC

Mild facial hypoesthesia V2 + V3 None

AC C

Case 4 Case 5 Case 6 Case 7 Case 8

Pre-op neurological deficits

RI PT

Sex

Table 3: Demographics, pre-operative clinical status and VBD size of our patients (TN: Trigeminal Neuralgia; PTC: Painful Tic Convulsive; RFTC: percutaneous radiofrequency thermocoagulation).

ACCEPTED MANUSCRIPT

Material

Offending Pain control vessel/s Shredded BA 100% Teflon

HFS control -

BA+ VA

100%

Yes

Residual symptoms Mild facial hypoesthesia V2 + V3 Mild facial dysesthesia. Clonazepam 2mg at night time 3 months Mild facial hypoesthesia V2 + V3 No

-

BA + VA

100%

-

No

None

BA

100%

-

No

None

-

No

Facial paresis, VIth nerve diplopia

19 months

No

-

No

None

14 months

No

Case 1

MVD

Case 2

MVD

Shredded BA Teflon

Case 3

MVD

Shredded BA + SCA 100% Teflon

-

Case 4 Case 5 Case 6 Case 7

MVD

Shredded Teflon Shredded Teflon Shredded Teflon Shredded Teflon

Recurrence

None

9 years and 9 months

No

None

8 years and 4 months

No

Mild hearing loss left side

6 years and 11 months

No

None

5 years and 4 months 2 years and 8 months 23 months

No No

MVD

BA + SCA 100% + small pontine artery Shredded BA 100% Teflon

TE D

MVD

EP

MVD

AC C

Case 8

MVD

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90%

Complications Follow-up

RI PT

Last TN treatment

No

Table 4: definitive treatment, offending vessels and results in our patients (TN: trigeminal neuralgia; HFS: hemifacial spasm; MVD: Microvascular Decompression; BA: basilar artery; VA: vertebral artery; SCA: superior cerebellar artery).

ACCEPTED MANUSCRIPT

Age (years) 54 44 65 72 67, 82, 71 Mean 65.4 65 54 77 53 47 Mean 62±6.7 65 Mean 55.3 53, 50, 74 70, 70, 55 71, 63 63 78, 59, 61 54 72 Mean 60 77, 76, 75 Mean74,range48-95

Side L R L L R=1, L=2 L=23, R=22 L L R L L L=20,R=11 L L=2, R=1 L=1, R=2 L=3 R=2 L R=3 L=6, R=4 L L=6, R=3 L=3 L=12, R=8 L=5, R=5 R R R=8, L=3 L L L=1, R=1

Mean 63.9range 47-86

63 64 Mean62.5,range52-73

77 65 64 + 75

Affected divisions V3 V3 V1 + V2 V1 V3=1, V2=1, V1+V2=1

RI PT

Female 1 1 2 27 1 10 1 1 1 1 1 4 4 2 6 5 3 1

SC

Male 1 1 1 18 1 1 1 1 21 2 2 2 2 1 2 6 1 5 1 14 5 1 1 8 1 1 1

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Diagnosis TN TN PTC PTC TN TN PTC PTC PTC TN TN TN TN TN TN=2,PTC=1 TN TN TN TN TN=6,PTC=4 TN PTC TN TN TN TN PTC TN TN TN PTC

TE D

Cases 1 1 1 1 3 45 1 1 1 1 1 31 1 3 3 3 2 1 3 10 1 9 3 20 10 1 1 11 1 1 2

EP

Year 1979 1980 1985 1986 1986 1987 1990 1991 1991 1992 1993 1994 1995 1996 1998 1998 2003 2006 2009 2010 2011 2011 2012 2012 2012 2012 2013 2013 2013 2014 2015

AC C

Author Waga et al. Miner et al. Takamiya et al. Miyagi et al. Lye Miyazaki et al. Suzuki et al. Harsh et al. Grigoryan et al. Ogawa et al. Stone et al. Linskey et al. Yoshimoto et al. Kirsch et al. Love et al. García-Sola et al. Taki et al. Kraemer et al. Noma et al. El-Ghandour Alcalá-Cerra Zhong et al. Lin et al. Park et al. Yang et al. Campos et al. Lakham Ma et al. Ishii et al. Banczerowski et al. Revuelta-Gutiérrez et al.

V2+V3=20, V2=11,V3=5, V1 + V2+V3=5, V1+V2 =3,V1=1

Not reported V1 V3 V1 + V2 V2 V2 ± V3 in 31/31 V1 V2 + V3=2 V3=3 V1 + V2=1, V2=1, V3=1 V2 = 1 case, V2 + V3=1 case V2 + V3 V3=2, 1 V2=1 V2 + V3 V2 + V3=8, V2=1, V3=1 Not reported V2 + V3 V2 + V3=10,V2=4,V3=3,V1 + V2=2,V1 + V2 + V3=2 V2 + V3=4, V2=3, V3=1, V1 + V2=2 V2 + V3 No reported V2=11, V3=5 V2 V2 + V3 V3=1, V2 + V3=1

Table 5: Demographics, side and affected roots in the published series (TN: Trigeminal Neuralgia; PTC: Painful Tic Convulsive; L: left side; R: right side).

ACCEPTED MANUSCRIPT

SC

RI PT

Actual method of TN Material for MVD treatment PPTR NT x 2 MVD Aneurysm clip pulls Vth to tent + Dacron VIIth&VIIIth MVD N/A RFTC=2, MVD=1 Autologous muscle pieces MVD N/A MVD + VBD R Vascular tape fixed to dura with hemoclip MVD + PPTR 2 Teflon pieces MVD Autologous muscle pieces MVD + VBD R Gore-Tex around VA + sutured to dura MVD + VBD R Silicone tape sutured to dura MVD Teflon, Ivalon, muscle or silicone; 1aneur clip sutured to tent + PPTR, 1 PPTR MVD Silicone tube surrounding Vth + Teflon 2 MVD, 1 VP shunt N/A PPTR None MVD Teflon pieces MVD + VBD R Titanium bone fixation plate MVD Shredded Teflon pieces MVD 1 case N/A MVD Teflon coated felt + Teflon pieces MVD + VBD R Vascular graft piece MVD Shredded Teflon MVD + VBD R Gore-Tex sling + aneurysm clip GKS None MVD Teflon pieces MVD Teflon pieces GKS + Botulinum Toxin for HFS None MVD, 2 PPTR added Shredded Teflon Bipolar coagulation Vth None MVD Titanium microplate MVD Teflon pieces

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Yoshimoto et al Kirsch et al. Love et al. García-Sola et al. Taki et al. Kraemer et al. Noma et al. El-Ghandour Alcalá-Cerra Zhong et al. Lin et al. Park et al. Yang et al. Campos et al. Lakham Ma et al. Ishii et al. Banczerowski et al. Revuelta-Gutiérrez et al.

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Waga et al. Miner et al. Takamiya et al. Miyagi et al. Lye Miyazaki et al. Suzuki et al. Harsh et al. Grigoryan et al. Ogawa et al. Stone et al. Linskey et al.

HyperPrevious Pre-op deficits Time to tension treatments recurrence 1/1 None Dysarthria + spastic gait N/A None Epileptic seizures 1/1 None ⇓ CR 1/1 None FH + ⇓ CR 1/3 RFTC=1 +1AI infraor n. FA RFTC=1yr, AI=days N/A None N/A N/A MVD Ivalon N/A 2 years 1/1 None N/A N/A AI inf.alv.n.&RFTC ⇓CR+⇓V1+V2+V3 3 years 1/1 None None N/A None None 20/31 NT 2 AI 1 GL 1 FH 51.6% N/A RFTC2, MVD1 N/A None None 3/3 None 1 headache 2/3 None None 1/3 None 1 FH No RFTC x 3 N/A 2 years N/A RFTC N/A 4 years 3/3 2RFTC,1MVD None RFTC6mo&2yrs 6/10 2 RFTC N/A 4 ⇓ V2+V3, 1 FP+CR +nystagmus 1/1 None None N/A None None No None No 15/20 11 MVD, 9 GKS 5/20 persistent pain N/A N/A None None 1/1 None None N/A None N/A A few months 10/11 RFTC 7FH,2HFS,1hear loss 5mo - 2yrs, N/A None 1 None None 2/2 None -

AC C

Author

ACCEPTED MANUSCRIPT

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Table 6: pre-operative status and definitive method of TN treatment (TN: Trigeminal Neuralgia; PTC: Painful Tic Convulsive; HFS: hemifacial spasm; CR: corneal reflex; AI: alcohol injection; FH: facial hypoesthesia; NT: peripheral neurectomy; GL: glycerol rhizotomy; VBD: Vertebro-Basilar Dolichoectasia; RFTC: percutaneous radiofrequency thermocoagulation; PPTR: open posterior partial trigeminal rhyzotomy; VBD R: vertebro-basilar complex repositioning; BA: basilar artery; VA: vertebral artery; GKS: Gamma Knife Surgery; MVD: Microvascular Decompression without VBD repositioning; N/A: Not available).

ACCEPTED MANUSCRIPT

Residual pain

Complications

Follow-up

Recurrence

SC

RI PT

No FH 1 month N/A No FH 18 months N/A FHs FP + FHs N/A N/A No None N/A N/A No Death 1-week post op MVD 14mo 2RFTC 2RFTC 1yr,repeated 2 & 3 times No FH 51%,diplopia3,neurol deficits6 Mean 19mo range6-50mo 2/45 cases No No 30 months No No 3 months N/A ⇓V1,⇓CR, FP No V3 hyperesthesia N/A N/A No None 18 months No No No 5 years No 10% patients FH42%,⇓masseter 1 Mean5yrs (1mo-15yrs) 3 at 1,2&5-year post-op No No 9 months No No None N/A N/A No N/A N/A 3⇓V2 + V3, FP 1 No No 2yrs + 2mo 1,1yr + 5mo 1 N/A 1/3 6-mo-2 yrs N/A 1 ⇓ V2 + V3 No Imbalance 3mo N/A N/A Yes, 2/2 RFTC=FH, MVD=hear loss N/A In both cases of RFTC 2/10 FH2, temp diplopia1,FP1 Mean 7.8-yrs No No None 9 years Recurrence TN + brain stem compres 1/9 None Range 3-30mo No No FH 1/3 66.3wks, range16-92wks No 12/20 FH 10% Mean 29mo range 8-123mo 14 new surgical procedures 2/10 FH 1 30 months No No None 24months No 1/1 N/A N/A Yes, after a few months No FH, PF&HFS N/A how many Mean 22mo,range3-37mo No 0/1 Transient diplopia 1 + ½ yrs No No None 9 years No 0/5 None 1 year No

M AN U

No HFS Waga et al. BA 1/1 Miner et al. BA 1/1 Takamiya et al. BA 1/1 1/1 Miyagi et al. N/A 1/1 1/1 Lye BA 1, 2 N/A 3/3 Miyazaki et al. BA4,BA+SCA,AICAorVA41 45/45 Suzuki et al. BA 1/1 Harsh et al. BA 1/1 1/1 Grigoryan et al. VA 1/1 1/1 Ogawa et al. VA + BA 1/1 Stone et al. BA + SCA 1/1 Linskey et al. BA4+ vessels8,VA4+ vessels15 Ø pain 90% 5/5 Yoshimoto et al. BA 1/1 Kirsch et al. N/A (VBD) 3/3 Love et al. PA=1,VA=1, VA-BA junction 1 3/3 1/1 García-Sola et al. N/A 2/2 Taki et al. N/A 2/3 Kraemer et al. N/A 1/1 Noma et al. N/A 3/3 El-Ghandour BA4+SCA2,VA2+AICA 1+vein1 10/10 4/6 Alcalá-Cerra N/A 1/1 Zhong et al. VA 8, 1N/A 8/9 9/9 Lin et al. VA 2,VA + SCA 1 3/3 Park et al. BA=13,VA=7 Pain relief 53% 1 yr,38% 2 yrs,10% 5yrs Yang et al. VA 3,+SCA2,+AICA1,BA+SCA3,+AICA1 10/10 Campos et al. BA 1/1 Lakham N/A 1/1 1/1 Ma et al. N/A 11/11 Ishii et al. BA 1/1 Banczerowski et al. BA 1/1 Revuelta-Gutiérrez et al. BA + VA 1, BA 1 2/2 2/2

TE D

No pain

EP

Offending vessel/s

AC C

Author

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

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Table 7: pre-operative status and definitive method of TN treatment (TN: Trigeminal Neuralgia; PTC: Painful Tic Convulsive; HFS: hemifacial spasm; CR: corneal reflex; AI: alcohol injection; FH: facial hypoesthesia; FHs: facial hyperesthesia; FP: facial paresis; NT: peripheral neurectomy; GL: glycerol rhizotomy; VBD: Vertebro-Basilar Dolichoectasia; RFTC: percutaneous radiofrequency thermocoagulation; PPTR: open posterior partial trigeminal rhyzotomy; VBD R: vertebro-basilar complex repositioning; BA: basilar artery; VA: vertebral artery; PA: Pontine artery; GKS: Gamma Knife Surgery; MVD: Microvascular Decompression without VBD repositioning; BT: botulinum toxin; N/A: Not available).

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

AC C

EP

TE D

M AN U

SC

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ACCEPTED MANUSCRIPT

AC C

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TE D

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ACCEPTED MANUSCRIPT

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT IS THERE A SAFE AND EFFECTIVE WAY TO TREAT TRIGEMINAL NEURALGIA ASSOCIATED WITH VERTEBROBASILAR DOLICHOECTASIA? PRESENTATION OF EIGHT CASES AND LITERATURE REVIEW. Abbreviations

RI PT

VBD: vertebro-basilar dolichoectasia BA: basilar artery VA: vertebral artery TN: Trigeminal Neuralgia

PTC: Paroxysmal Tic Convulsive

SC

HFS: hemifacial spasm

RFTC: percutaneous radiofrequency thermocoagulation

SCA: superior cerebellar artery CR: corneal reflex AI: alcohol injection FH: facial hypoesthesia

GL: glycerol rhizotomy

TE D

NT: peripheral neurectomy

M AN U

MVD: Microvascular Decompression

PPTR: open posterior partial trigeminal rhyzotomy VBD R: vertebro-basilar complex repositioning

EP

GKS: Gamma Knife Surgery FH: facial hypoesthesia

FHs: facial hyperesthesia

AC C

FP: facial paresis

NT: peripheral neurectomy PA: Pontine artery

BT: botulinum toxin N/A: Not available