“Sacral radiculopathies” by “Pelvic Compartment Syndrome” - a unknown cause for unexplained intractable “neuropathic chronic pelvic pain” Univ.-Prof. Prof. Dr. med. Marc Possover, MD, PhD

Introduction Chronic pelvic pain (CPP) is a commonly encountered problem in many medical offices and is defined as pain that has been present for 6 months or more. Usual investigation involves a thorough gynaecological and/or urological work-up, imaging and, in most cases, laparoscopy. When CPP produce genital (vulvodynia), coccygeal (coccygodynia), gluteal/pudendal pain or sciatica, diagnosis is becoming confusing for most physicians especially when clinical examination and laparoscopy are inconspicuous. Numerous hypotheses have been then proposed as to the origin of such syndromes, including pain from the pelvic soft tissues, pelvic congestion syndrome, spasm of the muscles of the pelvic floor, referred pain from lumbar pathology, arachnoiditis of the lower sacral nerve roots, local posttraumatic lesions, somatization, etc. Thus far, there has been no sound confirmation of any of these. Recently we reported about the sacral radiculopathy as a possible explanation since irritation or lesion of the sacral nerves roots (SNR) may induce such pudendal pain (SNR#2-4), vulvo- or coccygodynies (SNR#3-4) or even sciatica (L#5,SNR#1-2) 1. Most common etiologies reported in the literature are then metabolic diseases like diabetes and autoimmune diseases progressing with vasculitis 2,3,4,5. Lesions by external traumas are rare as the plexus is situated within the relative protection of the pelvic wall. Less well known but much more frequent, are the lesions of the SNR by deeply infiltrating endometriosis 6 and by damages during or secondary to pelvic surgeries 7,8,9,10. In a more recent publication we reported about a new potential etiology we called “sacral radiculopathy by vascular entrapment”

11

. Indeed, in some of our patients with clinical evidence for a sacral radiculopathy of pelvic origin,

laparoscopic exploration did not permit confirmation of any etiology (fibrosis entrapment, endometriosis…), but just showed veins in direct contact to the SNR. Referring to the well-known vascular entrapment syndrome

12

, we

hypothesized that the sacral radiculopathy may correspond in this situation to a nerve irritation as a result of the vulnerability of the nerve as it passes in close relationship with vessels. We started 2006 to resect such vessels, collected all data prospectively and observed significant pain improvements in such patients suffering sometime since years from intractable CPP. The purpose of this manuscript is to report about our experience in 57 consecutive 1

patients with this pathology and to draw the medical community´s attention to this unrecognized pathology responsible for much different kind of “unclear chronic pelvic pains”.

Methods We report here on all consecutive patients presented in our department since 2006 for treatment for intractable “CPP” in whom we just performed a laparoscopic exposure of the sacral nerves roots with resection of all vessels showing direct contact to the SNR. Patients with associated nerves pathologies or damages (endometriosis, postsurgical damages, meshoma…) were excluded from this series. Previous consultations by neurosurgeons, psychiatrists and MRI had excluded any pathologies of the CNS. Preoperative assessment not only focused on gynecological aspects, but also included neurologic symptoms for pelvic nerves pathologies. Patients were asked preoperatively a set of questions regarding potential causes (previous obstetrical/pelvic interventions inclusive orthopedic and vascular surgeries, thrombosis risk factors...), time of apparition, duration, and severity of pain using a graduated scale (Visual Analog Scale – VAS) from 0 “no pain” to 10 ”worst imaginable pain” for standardized quantification of pain. This included also detailed information’s of pain involving the buttock, the pudendal and genital areas and the lower extremities. Information’s were also obtained on possible motor deficits of hip adduction (L#3/Obturator Nerve) and flexion (L#5,S#1), knee extensors (L#14/Femoral Nerve) and flexors (L#5,S#1), ankle dorsiflexion (foot drop – L#5) and ankle plantar flexion (S#1). Patients were requested to keep a record of their consumption of analgesics. Patients who reported about pollakisuria, nykturia or any other troubles of micturition underwent urodynamic testing. Beside gynecologic palpation, clinical examination included exploration of all lumbosacral dermatomes and vaginal palpation (with eventual local anesthetic infiltrations) of pudendal nerves and lower sacral nerves roots. Vaginal sonography with Doppler exploration focused on gynecologic aspects and visualization of pelvic/parametric varicosities. Besides a systematic pelvic MRI imaging for exclusion pathologies (myelomeningocele, sacrococcygeal teratoma…), all local citizens - for organization reasons - underwent a MRI performed in our institution for visualization of pelvic veins and relationships with sacral nerves roots. Laparoscopic explorations were indicated in all patients by strong clinical suspicion of a neuropathic nonneurogenic sacral radiculopathy unknown etiology. The therapeutic principle of all procedures was based on the exploration with decompression of the sacral nerves roots by laparoscopic transperitoneal approach. This included systematic transection of the sacral hypogastric fascia, exposure the sacral nerves roots below the hypogastric vessels followed by a selective dissection, coagulation and resection of all perineural vessels. All procedures were performed under general anesthesia, using simple instruments such as bipolar forceps, scissors, grasping forceps and 2

a laparoscopic nerve stimulator. The technique for exposure the sacral nerves roots has been reported largely in previous publications

13

. In difficulties for identification or differentiation of the SNR, intraoperative electrical

stimulation of nerves with harmless currents (250 s / 35 Hz / 0 to 12 V) was used: while S#4 stimulation does not produce any motoric reaction in the lower extremities, stimulation of S#3 nerves is confirmed visually by a deepening and flattening of the buttock groove as well as a plantar flexion of the large toe and to a lesser extent of the smaller toes. Stimulation of S#2 produces an outward rotation of the leg and plantar flexion of the foot as well as a clamp-like squeeze of the anal sphincter from anterior/posterior. To avoid postoperative urinary and fecal dysfunctions, exposures of the sacral nerve roots #3 and #4 were limited to their dissection laterally to the pelvic fascia. If a more ventral dissection was required, selective exposure of the pelvic splanchnic nerves was performed in order to avoid their damages. All patients were clinically evaluated at the time of discharge, and on a two-month basis for the first 6 months following surgery, then yearly. Patients living abroad were followed up by telephone or by mail. Pelvic organs dysfunctions were systematically controlled by urodynamic testing at one-year follow up in our institution or in institution of origin. All data were collected prospectively in an Excel database (Microsoft Corporation). This series was designed as a prospective “Before-After Study” since surgeries were always considered as the last therapeutic option. Every patient provided written informed consent for the procedure and for collection of the data.

Results Fifty-seven consecutive patients were included in this study, thirty-nine women and eighteen men. Mean age of patients was 56 years (31-87) and mean BMI 30,1 (23-33). Findings by preoperative anamnesis Most common diagnosis for referral were “chronic pelvic pain unknown genesis”, “pelvic congestion syndrome” and “intractable piriformis syndrome” while most common characters for pain description by referring physicians were “intractable pain”, “non cyclical” and “neuropathic pain”. Table 1 shows the repartition of symptoms collected during preoperative consultation in our department. Fourteen patients had reported on a previous hysterectomy before apparition of the pain, nine about radical prostatectomy and twenty seven (male and female together) about surgical treatment for varicose veins of the lower extremities. All patients reported on failure to respond to diverse medical treatments and/or no longer accepted the side effects of the various medications. Table 2 shows all interventional procedures being performed previously by the patients of this series for tentative pain cure. Some characters in pain descriptions were constant in all patients: pains were systematically described as “not 3

cyclical”, with apparition or deterioration before or during the menstrual cycle, during or after sexual intercourse, after prolonged standing and sitting position while lying may improve considerably the pain. Findings by preoperative examination Thirty-nine patients (males and females together) presented leg varicose veins, twelve females a vulvar and/or bottom varicose veins and seven males a varicocele. Transvaginal sonography had demonstrated in most female pelvic sidewall or parametric varicose veins with in Doppler reverse flow. Transvaginal/transrectal palpation had objective in all patients asymmetric pain by triggering the lower sacral nerves roots (S#3-4) while palpation of pudendal nerve at Alcock´s canal was normal or minimal painfully. Neurologic examination was normal in fiftyfour patients; three presented minor hyperesthesia in sacral dermatomes. Pain topography was never uniform and involved only part of the sacral dermatomes. Urodynamic testing showed bladder hypersensitivity in forty-two patients and bladder hyperactivity in six patients. Eleven patients were scanned by MRI: enlarged pudendal, gluteal and sacral veins could be visualized but radiologists were not able to make a clear lesion diagnosis in term of “which veins induce a compression or irritation of which sacral nerve root”. Surgical data & pain evolutions All procedures were performed by laparoscopy without any conversion to laparotomy and no any major intra- or post-operative complication occurred. Mean surgical time was 67 minutes (34- 190 minutes). We have a loss follow up in three patients. A mean reduction in Visual Analog Score (VAS) from 8.7 (±1.64; 5-10) preoperatively to 1.6 (± 2.4; 0-5) at one year follow-up was obtained in patients after laparoscopic nerve decompression (n=54; p< 0,001). Success, defined as a reduction in VAS score of greater than 50%, was obtained in 91% of patients. Most patients reported on a period of “post-decompression syndrome” occurring after a few days of postoperative pain relief, characterized by the appearance of severe sacral allodynia and paresthesia which disappeared again after an average period of 6 months (3-23 months). With a mean follow up varying of 29 months (12-63 months), actual overall VAS is 1.2.

Discussion Chronic pelvic pain is a common condition in daily medical practice and reports in literature indicate that more than 30% of women complain about pain the lower abdomen sometimes in their life time. Although CPP can be produced by many gynecologic or urologic conditions, some causes are frequently overlooked and underdiagnosed, resulting in an inappropriate management. The conditions most often unrecognized are endometriosis, pelvic congestion, and less common congenital and acquired abnormalities. Pathologies of the sacral nerves roots are generally not even mentioned. The lack of awareness that pelvic nerves pathologies may exist is not 4

least due to diagnostic difficulties in etiologies. In CPP for gynecologic conditions, location of pain is usually similar to corresponding pathology, while in neuropathic CPP, pains are felt at afferent nerves endings (dermatomes). Therefore the etiology is usually more proximal in the pelvis or even in the CNS. The first and most important step in the diagnosis work-up is the recognition of the characters “somatic” and “neuropathic” of the symptoms. While the visceral nerves are like a spider´s web within organs, the somatic nerves are very specific in their location so that the symptomatology is generally precise, clearly described with mostly irradiations to corresponding dermatomes. Neuropathic pain descriptions are numerous varying from allodynias, paresthesias, sensations of electrical discharges to phantom sensations that are even more confusing when no morphologic correlates are found. The second most important step is the exclusion of a “neurogenic” pathology of the peripheral nervous system (polyneuropathies…), of the SNC (multiple sclerosis…) or pathologies of the spinal cord. Once the diagnosis of a neuropathic non-neurogenic sacral radiculopathy of pelvic origin is established, a laparoscopic exploration is indicated. The description of a “sacral radiculopathy by vascular entrapment” remind strongly to a other pathology, the Pelvic Congestion Syndrome (PCS). In this pathology, the presence of varicoses surrounding the uterus and ovaries, has been shown to be the underlying etiology in a significant proportion of patients with chronic pelvic pain. In normally functioning veins, blood flows in only one direction, and is prevented from flowing backwards by periodically occurring valves in the veins that route the blood and close after blood passes through. In patients with PCS, these valves do not work properly: they either open at the wrong time or never close completely, allowing blood to pool where it does not belong. This pooling causes the veins to stretch, putting unhealthy amounts of stress on veins and vein walls, and with painful results. This explanation appears logical, but do not correspond with real pain situations in PCS: congestion of pelvic organs may induce “visceral pain”, while classical PCS symptoms reported in the literature are of somatic origin and correspond exactly with those observed in sacral radiculopathies. This led us to believe that PCS are not painfully because of pelvic organs venous stasis but because of irritation of the sacral nerves roots by pelvic varicosis. Characters extrinsic of nerves irritation explain incomplete repartition of pain in the different sacral dermatomes while bladder hypersensitivity may due to irritation of sacral nerves roots #3 and #4. This hypothesis might explain why all situations that induce an increase in pelvic venous pressure (prolonged standing and sitting position…), or any marked pulsation of the pelvic veins (tricuspid insufficient, close anatomic relationship with arteries…) increase the pain. Because pelvic and lower limb veins are similarly in constitution, patients with varicose in the legs should present a higher risk for pelvic varicose veins. Also pelvic interventions and pelvic vein thrombosis may promote changes in pelvic veins circulation: if simple tubal sterilization may induce uterine congestion, uterovaginal and ovarian varicosities and pelvic venous stasis 14, there is 5

no doubts that more invasive interventions such as hysterectomies or radical prostatectomies are all the more risk situations for development pelvic varicose veins. Different treatments for PCS have been reported in the literature (transvenous catheter embolization, surgical ligation, hysterectomy, or hormonal suppression) but current treatment studies reporting ordinal outcomes found improvement from 24% to 100% significant long term efficacy

16

15

. Surgical treatment based on ligature ovarian veins have not show

and available evidence is also not sufficient to determine whether embolization of

the ovarian and internal iliac veins is effective as a treatment of pelvic congestion syndrome. There is a lack of data in the published literature concerning diagnostic criteria for pelvic congestion syndrome, so patient selection criteria for these procedures are uncertain. Long-term safety and effectiveness are uncertain as there is a lack of reliable data on treatment outcomes related to embolization therapy. There are no prospective, randomized trials comparing embolization to other therapies for PCS. The literature regarding the clinical outcomes of embolization therapy consists entirely of case series

17-25

. Because a venous stasis upstream after embolization might induce formation of

collateral veins responsible for recurrence, the laparoscopic resection of sacral varicose veins might show less risk for recurrence because veins resections are done distal to the nerves and because postoperative fibrosis reduce risk for collateral development in proximity to the nerves. However, the hypothesis of the PCS does not explain pain situations in all patients of our series. Indeed some patients reported about a significant improvement in pain after the procedure although laparoscopic exploration just showed small and normal veins in proximity to the SNR. For this reason we strongly believe that the problem of this pathology is not just a vascular entrapment or a nerves irritation by enlarged veins, but more a kind of “compartment syndrome” defined as the compression of the sacral nerves roots inside the closed space lateral to the pelvic fascia within the pelvis. Indeed, the SNR are passing in a very small anatomical space limited ventrally by the hypogastric vessels, dorsally by the sacrum, medially by the pelvic fascia (which is very strong) and laterally by the piriformis muscle. Therefore all conditions that might reduce this space (hematoma after sacral traumas, endometriosis, fibrosis…) or might increase the pressure in this space (pelvic varicosis, hypertrophie piriformis muscle  piriform syndrome) might produce a sacral radiculopathy by irritation or compression of the SNR. According with this hypothesis, not only resection of the veins is important but also the transection of the sacral hypogastric fascia (sacral fasciotomy) that decompresses probably at best the nerves.

Conclusion In consideration of the dramatic of the situation of patients suffering from such neuropathic pains and the amount of inadequate and invasive treatments that are still proposed to these patients - table 2! -,”sacral 6

radiculopathies” must be considered as a potential etiology for all intractable neuropathic CPP. The most important step in diagnosis workup is the recognition of the characters “neuropathic non-neurogenic” and the character “of pelvic origin” of the symptoms. The laparoscopic exploration is then indicated even when no any clear etiology has been demonstrated in preoperative assessment, since a “Pelvic Compartment Syndrome” can only be confirmed and treated efficiently by laparoscopy.

References 1. Possover M. New surgical evolutions in management of sacral radiculopathies. Surg Technol Int 2010;19: 123-128 2. Awerbuch GI, Nigro MA, Sandyk R, Levin JR. Relapsing lumbosacral plexus neuropathy. Eur neuronl 1991; 31: 348-351 3. Dyck PJB, Windebank AJ. Diabetic and non-diabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. Muscle Nevre 2002; 25: 477-491 4. van Alfen N, van Engelen BG. Lumbosacral plexus neuropathy: a case report and review of the literature. Clin Neurol Neurosurg 1997; 99: 138-141 5. Yee T. Recurrent idiopathic lumbosacral plexopathy. Muscle Nevre 2000; 23: 1439-1442 6. Possover M, Baekelandt J, Flaskamp C, Li D, Chiantera V. Laparoscopic neurolysis of the sacral plexus and the sciatic nerve for extensive endometriosis of the pelvic wall. Minim Invasive Neurosurg 2007;50(1):33-36 7. Alsever DJ. Lumbosacral plexopathy after gynecologic surgery: case report and review of the literature. Am J Obstet Gynecol 1996; 174: 1769-77 8. Possover M. Laparoscopic management of neural pelvic pain in women secondary to pelvic surgery. Fertil Steril 2009;91(6):2720-2725 9. Possover M. Laparoscopic management of endopelvic etiologies of pudendal pain in 134 consecutive patients. J Urol 2009;181(4):1732-1736 10. Possover M, Lemos N. Risks, symptoms, and management of pelvic nerve damage secondary to surgery for pelvic organ prolapse: a report of 95 cases. Int Urogynecol J 2011; 22(12):1485-1490 11. Possover M, Schneider T, Henle KP. Laparoscopic therapy of endometriosis and vascular entrapment of sacral plexus. Fert Steril 2011; 95(2):756-758.

7

12. Zhong H, Gan J, Zhao Y, Xu Z, Liu C, Shao G et al. Role of CT Angiography in the Diagnosis and Treatment of popliteal Vascular Entrapment Syndrome. AJR Am J Roentgenol. 2011;197(6):W1147-1154 13. Possover M, Chiantera V, Baekelandt J. Anatomy of the sacral roots and the pelvic splanchnic nerves in women using the LANN technique. Surg Laparosc Endosc Percutan Tech 2007;17(6):508-510. 14. El-Minawi MF, Mashhor N, Reda MS. Pelvic venous changes after tubal sterilization. J Reprod Med 1983; 28(10):641-648. 15. Tu FF, Hahn D, Steege JF. Pelvic congestion syndrome-associated pelvic pain: a systematic review of diagnosis and management. Obstet Gynecol Surv 2010; 65(5): 332-340. 16. Gargiulo T, Mais V, Brokaj L, Cossu E, Melis GB. Bilateral laparoscopic transperitoneal ligation of ovarian veins for treatment of pelvic congestion syndrome. J Am Assoc Gynecol Laparosc 2003;10(4):501504. 17. Maleux G, Stockx L, Wilms G, Marchal G. Ovarian vein embolization for the treatment of pelvic congestion syndrome: long-term technical and clinical results. J Vasc Interv Radiol 2000;11(7):859-864. 18. Sichlau MJ, Yao JS, Vogelzang RL. Transcatheter embolotherapy for the treatment of pelvic congestion syndrome. Obstet Gynecol 1994;83:892-896. 19. Venbrux AC, Lambert DL. Embolization of the ovarian veins as a treatment for patients with chronic pelvic pain caused by pelvic venous incompetence (pelvic congestion syndrome). Curr Opin Obstet Gynecol 1999; 11(4):395-399 20. Tarazov PG, Prozorovskij KV, Ryzhkov VK. Pelvic pain syndrome caused by ovarian varices. Treatment by transcatheter embolization. Acta Radiol 1997;38(6):1023-1025. 21. Kim HS, Malhotra AD, Rowe PC, Lee JM, Venbrux AC. Embolotherapy for pelvic congestion syndrome: long-term results. J Vasc Interv Radiol 2006;17(2 Pt 1):289-297. 22. Kwon SH, Oh JH, Ko KR, Park HC, Huh JY. Transcatheter ovarian vein embolization using coils for the treatment of pelvic congestion syndrome. Cardiovasc Intervent Radiol 2007;30(4):655-661. 23. Creton D, Hennequin, L Kohler, F, Allaert FA. Embolisation of symptomatic pelvic veins in women presenting with non-saphenous varicose veins of pelvic origin - three-year follow-up. Eur J Vasc Endovasc Surg 2007;34(1):112-117. 24. Gandini R, Chiocchi M, Konda D, Pampana E, Fabiano S, Simonetti G. Transcatheter foam sclerotherapy of symptomatic female varicocele with sodium-tetradecyl-sulfate foam. Cardiovasc Intervent Radiol 2008;31(4):778-784.

8

25. Tropeano G, Di Stasi C, Amoroso S, Cina A, Scambia G. Ovarian vein incompetence: a potential cause of chronic pelvic pain in women. Eur J Obstet Gynecol Reprod Biol 2008;139(2):215-221.

Symptoms

n

Lower abdomen pain

46

Dysmenorrhea

11

Vaginodynia / Dys-Apareunia

13

Pudendal Pain

7

Coccygodynia

32

L#5-sciatica

3

S#1-sciatica

7

S#2-sciatica

8

Dyschezia

19

Tenesmus

8

Bladder hypersensitivity*

42

Bladder Overactivity*

6

* Confirmed by urodynamic testing

Table 1: Repartition of symptoms collected during preoperative consultation

9

Previous procedures

n

Hysterectomy ± colporrhaphy

6

Coccygectomy

7

Vulvectomy

3

Radiation of the vulva

1

Laser vaporization of the vulva

4

Vaginoplasty

2

Transgluteal/transperineal neurolysis pudendal nerve

4

Laparoscopic exploration/adhesiolysis

25

Laparoscopic uterine nerve ablation (LUNA)

6

Sacrouterine ligaments destruction (methanol injections)

1

Laparoscopic salpingo-oophorectomy

5

Laparoscopic ovarian vessels clipping

1

Ovarian and internal iliac vein embolization

7

Ganglia impar destruction

9

Sacral nerve stimulation / spinal cord stimulation

5

Retrorectal omentum interposition (laparotomy)

1

Inguinal herrniorrhaphy

4

Inguinal triple neurectomy

1

Stapled haemorrhoidopexy/haemorrhoidectomy

3

Prostate resection (TUR)

5

Varicocelectomy

2

Bladder / perineal botulinum toxin A injections

13

Table 2: Previous interventional procedures performed by the patients for tentative of pain control

10