Treatment Algorithm of Pudendal Neuropathy - A Cross-sectional Study with Questionnaire on 119 Patients

A Cross-sectional Study with Questionnaire on 119 Patients
Zur Erlangung des akademischen Grades
Doktorin der gesamten Heilkunde
Universitätsklinik für Chirurgie des AKH Wien
Unter der Anleitung von
Dr. Johannes Mayer
2.2 Variations of the Pudendal Nerve and its Branches ........................................................ 3
2.2.1 Inferior Rectal Nerves ................................................................................................. 3
2.2.2 Perineal Nerves ............................................................................................................ 4
III. Background ..................................................................................................................... 5
VI. Pudendal Nerve Entrapment ............................................................................................ 9
VII. Diagnosis ....................................................................................................................... 11
7.4 X-ray .............................................................................................................................. 14
7.5 Ultrasound ..................................................................................................................... 14
VIII. Differential Diagnosis ................................................................................................ 17
9.1 Medication ..................................................................................................................... 18
10.2 Sonographic Infiltration ................................................................................................ 22
10.3 CT-guided Cryoablation ................................................................................................ 22
10.4.2 Sacral Nerve Stimulation ........................................................................................... 23
10.5 Operative Treatments .................................................................................................... 24
10.5.1 Anterior Approach ..................................................................................................... 24
10.5.2 Transperineal Approach ............................................................................................ 25
10.5.3 Transgluteal Approach .............................................................................................. 25
10.5.4 Transischial Approach ............................................................................................... 26
10.5.5 Laparoscopic Approach ............................................................................................. 26
11.1 Study Population ........................................................................................................... 28
11.2 The Study ...................................................................................................................... 28
11.3 Statistical Analysis ........................................................................................................ 29
12.4.1 Medication ................................................................................................................. 38
Abstract
Purpose: The aim of this study was to delineate a treatment algorithm pertaining to both
conservative and operative treatments for patients with irritation of the pudendal nerve and
evaluate patients’ quality of life in the course of treatment.
Methods: This clinical study included 119 patients presenting with irritation of their pudendal
nerve due to different causes. Treatments conducted between the years of 2010 and 2016 ranged
inter alia from conservative treatment with medication intake, electro-modulated or
sonographic infiltration to distal, as well as proximal neurolysis of the pudendal nerve. The
level of pain, the concomitant symptoms and the influence on patients’ quality of life were
amongst others assessed via questionnaire prior to examination and thereafter.
Results: The Wilcoxon signed rank test showed a significant decrease in pain intensity
(p<0.001; α=0.05) in both treatment groups. Additionally, we were able to show a significant
reduction in medication intake post treatment in the operatively treated cohort.
Conclusion: Pudendal neuropathies are principally treated in a multidisciplinary approach. If
clinical symptoms and radiography are indicative of a local nerve compression, we suggest
electro-modulated infiltration and if successful, a pudendal nerve decompression. If infiltrations
do not succeed, we additionally recommend physiotherapy, long-term medication and lifestyle
modification.
Zusammenfassung
Zielsetzung: Das Ziel dieser Studie war die Beschreibung, sowohl der konservativen, als auch
operativen Therapiemöglichkeiten bei Irritationen des Nervus pudendus, sowie die Evaluierung
der Lebensqualität der Patienten_innen im Verlauf der Behandlung.
Material & Methodik: Diese klinische Studie umfasste 119 Patient_innen, welche sich mit
unterschiedlichen Formen einer Irritation des Nervus pudendus im Zeitraum zwischen 2010
und 2016 präsentierten und fortlaufend bis in das Jahr 2016 behandelt worden sind. Hierbei
schloss die konservative Behandlung unter anderem Medikamenteneinnahme und
elektromodulierte und ultraschallgeführte Infiltrationen ein. Die operative Therapie umfasste
eine distale und/oder proximale Neurolyse des Nervus pudendus. Im Rahmen der
Voruntersuchung und nach der jeweilig indizierten Behandlung wurde von den Patienten_innen
eine genaue Beschreibung und Bewertung der Schmerzen, sowie begleitende Umstände und die
Beeinträchtigung der Lebensqualität mittels Fragebögen ermittelt.
Resultate: In dieser Studie konnten wir die positiven Effekte unserer Therapieansätze durch
eine signifikante Schmerzminderung (p<0,001; α=0,05) in beiden Behandlungsgruppen
nachweisen. Außerdem, konnten wir in der operativ behandelten Gruppe eine signifikante
Reduktion der Anzahl an Medikamenten nach Therapieverlauf zeigen.
Conclusio: Sofern die angewandte Infiltration einen kurzzeitigen Erfolg brachte, wurde eine
Dekompression des N. pudendus angestrebt. Bei folglichen Restbeschwerden haben wir die
Medikation angepasst und Physiotherapie und Lebensstilländerung empfohlen.
1
Although the most significant advances on peripheral nerves and their pathologies have been
made over the last few decades, peripheral nerves were first described in Hippocrates’s writings
and therefore date back to the fourth century B.C. (1) However, entrapment of these nerves
were delineated much later, namely in the 1820s by Sir A. Cooper and 1850s by Sir J. Paget. A
century later, starting from the 1920s, surgical interventions were performed by James R.
Learmonth, who supposedly was the first surgeon to focus on decompression, reconstruction
and denervation of peripheral nerves. (2, 3)
In 1915, G. Zuelzer first described pudendal neuralgia and delineated the prevailing problem of
misconception and therefore misdiagnosis in his publication. He mainly pointed out the
associated urinary symptoms and suggested a dissection of the pudendal nerve for pain relief;
thus leading to other issues due to deafferentation. (4)
Later in 1987, G. Amarenco et al. delineated PNE, which is the main cause of pudendal nerve
irritation. They described prolonged compression and repetitive micro-trauma as the reason for
irritation. (5) This publication was followed by a detailed report on the characteristics of
pudendal neuropathy by Robert et al. one year later. Two entrapment sites were described then:
Posteriorly, between the STL and SSL and anteriorly the falciform edge of the STL. (6) Up
until now six possible entrapment sites have been defined, which will be described in the
following chapters. (7)
2.1 The Pudendal Nerve
As a mixed nerve, the PN has up to 50% sensory, 30% autonomic and 20% motor functions
and predominantly originates from the ventral branches of the second to fourth sacral spinal
nerves. (8) Innervation may additionally be provided by the contiguous sacral roots S1 and S5.
(9) Through the major sciatic foramen right underneath the piriformis muscle the PN nerve exits
the pelvis and reaches the backside of the coccygeus muscle, which forms a muscle tendon
connection with the SSL. Here, the PN is ventrally surrounded by the back of the SSL and
dorsally by the backside of the STL. Medially from the STL the PN circuits the ischial spine
and enters the perineum through the lesser sciatic foramen, being superiorly accompanied by
the pudendal vessels. The nerve vessel bundle enters the canal, which is named after Benjamin
Alcock: The Alcock’s canal, often simply referred to as the pudendal canal, which reaches from
the ischial spine to the dorsum of the urogenital diaphragm. (8-13)
Figure 2.1-1. The Pudendal Nerve. The PN is illustrated from its most common origin from the first to forth sacral root and
pathway through the pudendal canal formed by the fascia of the obturator internus muscle. © Aron Cserveny.
3
This sheath is formed by the fascia of the obturator internus muscle and ranges from 2.0 to 3.2
cm. (12) After circling the ischial spine, the PN typically gives off the inferior rectal nerves,
that may also branch out at the height of the superior margin of the SSL or the sacral plexus
itself. By going through the ischioanal fossa inferior-medially, the inferior rectal nerves reach
and supply the external anal sphincter, the anal canal and the perianal and anal skin. These
branches connect to the perineal branch of the posterior femoral cutaneous nerve and may
additionally innervate the levator ani muscle. Within Alcock’s canal the PN is divided into
further sub-branches, namely the perineal and the dorsal nerves. Throughout its course, the
dorsal nerves stay caudally to the perineal membrane, sending out perforating branches to
various muscles to ensure their functions. These dorsal nerves also remain caudally to the
ventral part of the perineal membrane when exiting the pudendal canal. They innervate erectile
tissue of the corpora cavernosa, the crura and the skin over the dorsal and lateral aspect of penis
or clitoris. Commonly, the perineal division splits up into two sections, the superficial and deep
branches. The latter ones innervate the transversus perinei superficialis and profundus muscle,
the ischiocavernosus muscle, the urethral sphincters, the external anal sphincter anteriorly, parts
of the levator ani muscle and the bulbospongiosus muscle. (14) The branches reaching the
bulbospongiosus muscle pierce through the corpus spongiosum and supply the urethral bulb
and urethral mucosa. The superficial perineal branches supply the posterior section of the
scrotum or labia majora after perforating the inferior fascia of the urogenital diaphragm. (9-12)
2.2 Variations of the Pudendal Nerve and its Branches
As opposed to prior beliefs, that the PN would be one individual trunk coming from the sacral
roots, studies have shown that multiple trunks exist. (7, 12, 14, 15)
2.2.1 Inferior Rectal Nerves
In various studies, a common pudendal trunk giving off the inferior rectal nerve after passing
the pudendal canal has only been seen in around half of the examined specimen. The inferior
rectal branch predominantly originates from the third sacral spinal nerve. In cases of a rectal-
dorsal trunk, nerve fibres from the third and fourth sacral roots form the nerve-bundle, which
persists for a short distance, before the dorsal nerve and inferior rectal nerve separate from one
another. The rectal branch then courses behind the SSL before joining nerve fibres coming from
4
the second and third sacral roots, thus forming a common perineal-rectal trunk. If all three
pudendal divisions branched separately, the inferior rectal part would course proximally to the
superior SSL margin originating either solely from the fourth or from both the third and fourth
sacral roots. (7, 12, 14)
2.2.2 Perineal Nerves
The perineal nerve with its posterior scrotal or labial as well as muscular nerve divisions, mostly
forms a trunk with the rectal nerve. The perineal nerve can also form a dorsal-perineal trunk
primarily originating from the second sacral nerve roots with the rectal nerve branching off in
two possible ways or alternatively arising independently from the sacral plexus. This trunk then
passes beneath the SSL and forms its subdivisions of the dorsal nerve and perineal branches at
the inferior margin of the SSL, having the perineal branches give off superficial, as well as deep
ramifications after 2 cm. In this case, perineal fibres were found to originate from the second
and third sacral nerve roots and have connections to the dorsal nerve to the clitoris and the
inferior rectal branch. If all three pudendal divisions branch separately, the perineal part
branches off distally to the inferior margin of the SSL. (7, 12)
2.2.3 Dorsal Nerve to the Penis or Clitoris
According to Furtmueller et al., the dorsal nerve mainly originates as an individual ramification
from the sacral plexus, slightly more than one centimetre proximal to the ischial spine,
determining its location more anteriorly along the inferior pubic ramus in comparison to the
perineal branch. Furthermore, a high course was delineated of not only the pudendal, but
particularly of the dorsal nerve, which courses from the ischial spine to the parasymphyseal
area in a horizontal matter and therefore lies superior to the perineal branches within Alcock’s
canal and is surrounded by fatty tissues of the ischiorectal fossa. As soon as the dorsal nerve
reaches the inferior pubic ramus, it perforates the superior fascia of the urogenital diaphragm
to course through the inferior pubic ramus canal and either perforate the inferior fascia of the
urogenital diaphragm or the inferior transverse pubic ligament. Subsequently, the dorsal nerve
of the penis or clitoris lies within its own osteofibrotic canal, which has been delineated by Sedý
et al. and Hruby et al. The canal is formed by the inferior pubic ramus and a ligament derived
by the corpora cavernosa and leads to the supplying area. (7, 16-18)
5
Neuropathies resulting from compression usually occur at specific sites of peripheral nerves,
with tunnel syndromes being the most common presentation site. These entrapments arise from
increase in pressure, leading to a compression of the neural microvasculature and an alteration
in hemodynamic. While high pressure may lead to epineural arterial ischemia, low pressure
results in a compromised venous outflow leading to venous stasis, which can amount to
capillary leakage, intraneural and extraneural oedema and therefore increased pressure.
Persistence of any form of pressure may result in inflammation, fibrosis, demyelination and
finally axonal loss. Mild nerve compressions mainly cause degeneration of small diameter
myelinated axons, whereas axons myelinated by large diameter do not undergo any change in
structure. Unmyelinated nerve fibres are also affected by compression. In case of chronic
compression, Wallerian degeneration occurs. The ongoing impairment of intraneural
microcirculation results in epineural and intrafascicular oedema, which lead to a higher pressure
in endoneural fluid, therefore developing a base for fibroblast invasion formed by the oedema
itself. A compressing epineural scar may emerge. (19-21)
Nerve damage has been classified into different degrees by Seddon and Sunderland. Mackinnon
added one further degree. The first three degrees may result of closed, the fourth degree of open
injuries and influence the microanatomy within and surrounding the affected nerve, while the
fifth degree is only present if the damage on the nerve results in transection. Sixth degree
damage basically represents a mixture of the other injuries. (22)
The mildest form is neuropraxia or block in conduction through demyelination. Depending on
the intensity of injury recovery can occur within minutes up to a couple of months after damage.
As no Wallerian degeneration and no regeneration is present, no Tinel’s sign will be found.
This sign will be present with second degree damage due to regeneration after Wallerian
degeneration of axons mainly because of axonotmesis. In this case, the endoneural as well as
perineurial and epineural layers of tissue around the axons rest unimpaired. Therefore, no
discontinuity and no obstacles in terms of scar tissue along the axonal pathway will be present,
resulting in a complete recovery. As scarring within the nerve is detectable with third degree
injuries, full recovery might occur. Scarring is more severe with fourth degree injuries and
6
cannot be penetrated by axons that are regenerating. Hence, excision of the scar to restore
previous functionality is required. Tinel’s sign will not be progressed as regenerating axons
cannot pierce through the scar. A recovery of distal function will not be possible without
intervention. This type of injury can be caused by motor vehicle accidents with crush
phenomena. Fifth degree injuries can also be caused by such accidents and by laceration
induced by knives, glass, fractures or sports injuries and result in neurotmesis. In these cases, a
direct nerve transection injury and non-progressive Tinel’s sign are characteristic. A compound
of all aforementioned degrees is defined as the sixth and most severe degree. While the first
three degree damages are usually managed without any surgical intervention, fourth and fifth
degree injuries are an indication for surgery. With sixth degree injury, the choice of treatment
depends on what functions are preserved and to what extent recovery is possible. (22, 23)
Nerve compression injury may be caused by space occupying lesions such as enhanced muscles,
tumours or cysts. Diseases that are associated with extracellular matrix in soft tissues, such as
muscle compartment syndromes or pregnancy, may trigger compressions. Patients suffering
from diabetes mellitus are susceptible to nerve compressions through an inflammatory reaction
resulting in gliding impairment of the affected nerve. (24)
Patients suffering from compression neuropathies typically present with a combination of
neurological symptoms depending on the affected nerve. They are in pain and have sensory and
motor complaints. Therefore, history taking and physical examination are followed by imaging
methods and or electro-diagnostic studies. Conservative treatment is usually carried out for at
least three months and includes anti-inflammatory and pain medication, splinting, resting and
circumventing any positions or movements that worsen the pain. Additionally, physical therapy
and local steroid injections are prescribed. If findings are advanced, severe symptoms arise and
make operative treatment recommendable. The surgical intervention primarily consists of nerve
decompression and may include a relocation of the original pathway of the affected nerve to
prevent further entrapments or even nerve transfer. (19, 22)
7
IV. Predictors of Pudendal Nerve Irritation
There are certain risk factors that make some people more prone to developing PN irritation.
These factors can be of anatomical origin, influenced by gender, age, other medical conditions,
regularly performed exercises or surgical interventions. The common age of onset lies between
50 and 70 years. Younger patient groups present because of anatomical varieties or damage due
to trauma or sports injuries. As for the anatomical predominance, an enlarged ischial spine or
variations of the pudendal pathway can be the source of entrapment. Women are more likely to
having pudendal neuropathy. Repetitive abdominal pressure and sexual intercourse aggravate
perineal descent, which distend the PN. Over time, this can lead to a denervation provoking
perineal amyotrophy which incites further perineal descent leading to more denervation, thus
creating a vicious circle, that lastly causes pudendal neuropathy. (25) The exercises, that may
result in pudendal neuralgia, are cycling and strength training. Frequent cycling causes a
repetitive micro trauma on the PN and its vessels resulting in repeated mechanical and vascular
compression applicable to both men and women. If dysesthesia and or numbness are
experienced shortly after biking, a change in saddle should be taken into consideration. A saddle
distributing the cyclist’ weight on the saddle with comparably more weight on the ischial
tuberosities may help prevent a compression. Training with weights may cause muscle
hypertrophy, resulting in a compression as well. (25, 26) Chronic constipation may also be the
origin of pudendal neuropathy due to repetitive abdominal pressing that leads to perineal
descent and thus distends the PN. (25, 27) Patients diagnosed with diabetic polyneuropathy tend
to suffer from peripheral entrapment neuropathies. In these cases, an early detection of pudendal
neuropathy is essential to intervene operatively to avoid further progression and complications.
The neuropathy affects the distal branches of the PN. (16, 25, 26) Spinal, pelvic,
gynaecological, urologic and proctologic surgeries can affect the neurophysiology of the PN.
Sacro-spinofixation can directly have a traumatizing effect on the PN or indirectly via retractor
or postoperatively due to hematoma. Excision of Bartholin’s glands can result in injury of the
perineal branches distally with formation of a neuroma or fibrous reaction. (24, 25)
8
V. Irritation of the Pudendal Nerve
Restrictions during the pathway of the PN can cause compression while moving. Pain resulting
from its compression or irritation becomes apparent as perineal, scrotal, testicular and penile or
vulvar, vaginal and clitoral pain. It is a subtly developing ache that may be accompanied by
paraesthesia in the same regions, gradually becoming more apparent as a unilateral or bilateral
pain sensation, with possible emphasis on one side. The quality of pain is not paroxysmal or
pruritic. Patients describe it being a burning, aching, constricting sensation in the perineal area,
occasionally accompanied by a stabbing perception and foreign body sensation. Finally, this
cluster manifests as a continuous discomfort. While this discomfort is known to decrease while
standing or walking, it increases through the pressure resulting from sitting. Nevertheless,
patients are not complaining about any ache while sitting on toilet seats since pressure is then
distributed differently. As pain is seldom provoked in a lying position, people affected by
pudendal irritation are not disturbed by pain worsening during their sleep and are free of pain
when waking up. The discomfort starts after a while and reaches its peak by evening in most
cases. (7, 8, 10, 25)
This pain may also extend to areas which are not supplied by the PN per se, but lie adjoining to
it. As described by Labat et al., the area innervated by the obturator nerve can therefore evoke
an obturator internus syndrome because of its proximity to the PN resulting in medial posterior
thigh pain. Another associated pain described in this context is sciatica triggered by injury of
either the sciatic trunk or posterior femoral cutaneous nerve, as well as perineal neuralgia
combined with buttock pain affected by the lesion of the latter nerve or the inferior gluteal
nerve. (27)
In terms of patients’ sexual life reduced sexual activity due to pudendal neuralgia has been
outlined by Labat et al. Not only effects of the PN itself are held accountable for that, but also
the decrescendo in libido resulting from the long-lasting pain condition. While women are
described to often experience an increase in pain after intercourse, men are prone to decreases
in sexual sensation and rigidity with possible numbness of their genitals. (25, 27)
Although urinary symptoms not necessarily correlate with pudendal neuralgia, they may appear
9
owing to relaxation difficulties resulting in dysuria. It…