1 but research in and sexologists 20 5,22 Feigenbaum and Komisaruk ting identified anatomically 14 www.painreportsonline.com 7,8,17,19,22–24,26 a,c Some cases are attributed to brain effects ith sacral neuropathy—70% had urologic 2,11 Veterans Administration and other investigators ov cysts were most common (in 4), then sensory 4 1,20 , Bruce H. Price c 90% of patients, diagnostic tes Here, we begin neurological investigation of persistent genital egan between ages 11 to 70 years. Two patterns emerged: ed or significantly improved PGAD symptoms in 4/5 patients, mostly conducted inpatients. spinal cord–injured or multiple sclerosis have studied effects of myelopathies,thies, and radiculopathies, various neuropa- medications on male arousal, arousal disorder (PGAD), a largelyout-of-context female-reported sexual syndrome arousal of and/ormostly orgasm. PGAD investigated hasneuroscientists been by largely unaware psychologists. ofbeen it, systematically With investigated. medical causality physicians has not and of serotonergic and dopaminergic drugs, established the firmestcysts. association to These date, formganglia with and exclusively roots. sacral Tarlov on and can damage sensory have hypothesized thatassociated, other mentioning neurologicalgenital restless problems sensory may leg hyperesthesia, be neuropathy, syndrome, neuropathic but pain, fibromyalgia, and wefocused investigations. sensory are unaware of previous neurologically female patients isinappropriate nearly arousal nonexistent. are Women’s typicallymale complaints attributed of evaluators) (by predominantly beneficial. to psychopathology or misinterpreted as qualifying participants’ records and recontacted some for rug-withdrawal effect as apparently causal; lumbosacral disc 30/day) that usually included orgasm and 40% reported lesser, # this retrospective university-hospital study. We extracted and analyzed *, Katie Kessler c, als. Most also had symptoms consistent w Department of Neurology, McLean c l neurological lesions. Sacral dorsal-root Tarl , Saurabh Sharma a,b Department of Pathology (Neuropathology), Massa- b Although limited by small size and referral bias to neurologists, this series strengthens associations with Tarlov cysts Persistent genital arousal (PGAD) is a syndrome of unprovoked sexual arousal/orgasm of uncertain cause primarily Studies mapping human arousal are rare and Neuropathic pain, Pelvic pain, Tarlov cysts, Peripheral neuropathy, Spinal cord, C-fibers The IRB waived consent requirements for All 10 participants were female; their PGAD symptoms b Brief Report Neuropathic 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf

15,16,27 ©

80% reported daily out-of-context sexual arousal episodes ( complaints and 60% hadappropriate neuropathic and perineal plausibly or causa buttockpolyneuropathy pain. (2). In One had spina bifida occulta and another d neurological symptoms, test, anddetails. treatment results fromResults: all often longer-lasting, nonorgasmic arous herniation was suspected in another. Neurological treatments cur Abstract Introduction: reported in female patients.neurological Most symptoms patients and are conditions, referred thereMethods: is for need mental-health to treatment, analyze but cases as comprehensively evaluated research by suggests neurologists. associations with including 2 cures. Conclusions: and sensory polyneuropathy and suggests new ones.C-fibers We in hypothesize the that many regional cases special of sensory PGADmechanisms neurons are that with caused subserve by neuropathic sexual unprovoked pain firing arousal. of Some and PGAD itch. symptoms may share pathophysiologic Keywords: Department of Neurology, Massachusetts General Hospital, Harvard Medical of The International Association for thedistributed Study under of the Pain. terms This of the isNo Creative an Derivatives Commons open License Attribution-Non access 4.0 Commercial- (CCBY-NC-ND), article where itshare is the permissible work to provided download it and is properlyor cited. used The commercially work cannot without be permission changed from in any thePR9 way journal. 5 (2020) e801 http://dx.doi.org/10.1097/PR9.0000000000000801 School, Boston, MA, USA, 5 (2020) e801 a Sponsorships or competing interests that mayat be the relevant end to of content this are article. disclosed The anatomy andsexual arousal physiology—and are thusexclusively dimorphic, the but in it innervation—of pathways male has patients, been studiedrodents. and and almost the neurotransmitters peripheral and mapped spinal primarily in 1. Introduction

sense neuropathy Anne Louise Oaklander Persistent genital arousal disorder: a special chusetts General Hospital, Boston, MA, USA, Hospital, Harvard Medical School, Belmont, MA, USA *Corresponding author. Address: 99 Beauvoir522-2829; Ave, fax: Summit, 214-702-0473. NJ E-mail 07901. address: Tel:(S. [email protected] 908- Sharma). Copyright

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2. Methods Psychiatric treatment was universally ineffective, including 7 psychiatric hospitalizations and 17 electroconvulsive therapy A lack of standardized nomenclature (synonyms include persis- sessions for patient 10. Gynecological and urological treatments, tent sexual arousal syndrome and restless genital syndrome) and including medications, injections, and electrotherapies, were also billing codes precluded systematic case ascertainment, so we ineffective. Local anesthetics and/or corticosteroid injections reviewed records from our university–hospital neurology practi- never had lasting benefit, but a few gave temporary relief, ces for PGAD mentions and solicited additional referrals regard- suggesting the potential for diagnostic localization of hyperexcit- less of whether neurological symptoms were present. The review able sensory nerves as with neuropathic pain conditions. board waived consent, although we obtained verbal consent Genitofemoral nerve blocks gave transient relief to 2/3, but to anonymous publication. All genders and ages were eligible; pudendal nerve blocks were ineffective or worsened symptoms in inclusion required neurological evaluation of diagnosed or 5/5. All epidural corticosteroid injections worsened symptoms. suspected PGAD, and some patients were reinterviewed. One intravaginal botulinum toxin administration was ineffective. We analyzed demographics, medical histories and exami- By contrast, neurological treatment was effective in 80% of nations, results about localization, etiology, and treatment. patients. Gradual duloxetine taper (patient 5) and Tarlov-cyst resection (patient 2; Fig. 1) were curative. Immunoglobulins (2 grams/kg/4 weeks) improved patient 8’s PGAD and motor 3. Results symptoms dramatically. Another Tarlov-cyst patient found in- All participants were female, and on average 53.4 years old on trathecal pressure reduction helpful, whereas surgical resection December 31, 2018 (Table 1). Ages at PGAD onset ranged from was ineffective for another. puberty to postmenopausal. We identified 2 patterns of arousal—episodic and sustained. Eighty percent of patients 4. Discussion reported daily transient sexual arousals (minutes/few hours) with 40% reporting longer, lesser near-continuous arousals for days- This report associates PGAD with disorders and lesions of the years (2 had both). All PGAD illnesses began as anorgasmic but lower spinal cord, roots, and nerves that control sexual arousal almost always progressed to include spontaneous orgasms. and orgasm. Genital sensory innervation is mostly through the Patient 4, with #30 arousals daily, had 2 unprovoked orgasms in dorsal nerve of the clitoris/penis, a branch of the pudendal nerve front of a hospital teaching-conference audience. Almost all that enters the cord through S4 dorsal roots to excite T12-S1 patients tried masturbation to terminate arousals, and this helped dorsal-horn interneurons (lamina VI and X27)1,16 and send axons 20%.13 Patient 10 masturbated 4 to 5 times daily despite the lack up the dorsal columns and gracile fasciculus to affect the brain of pleasure, to obtain a few hours relief. Patient 3 induced several widely.3,12 In female rats, electrophysiological recordings link orgasms each afternoon to quell symptoms until the next pelvic contractions to rhythmic pudendal nerve firing, with L4 morning. Five reported no postorgasm refractory relief, and spinal cord injury increasing this firing.1 Autonomic mapping in patient 6 avoided all vulvar contact because of allodynia. mice identifies hypogastric sympathetic afferents entering at Chronic PGAD always terminated sexual relations. All 6 partnered L2,16 with efferents exiting the T12-L2 ventral roots and white patients initially sought sex during their arousals, but all of their rami to synapse paravertebrally then send postganglionic fibers partners came to perceive their approaches as too frequent and/or through gray rami to the hypogastric nerve. Parasympathetic “mechanical,” and terminated sexual relations, although all mar- efferents arise from S2-5, exit as splanchnic nerves through the riages continued. Among the 3 patients who were virgins at PGAD inferior hypogastric plexus to synapse in ganglia in pelvic organ onset, 2 remained abstinent and 1 tried intercourse only once, an walls, and increase pelvic blood flow and other arousal encounter abrogated by vulvodynia. Every patient reported that responses. PGAD caused new or worse depression and anxiety. Onset in Given our patients’ lesion localizations, etiologies, and colocalizing childhood was bewildering, causing confusion, shame, and fear. All neurological signs and symptoms, we propose that at least some patients considered themselves disabled from PGAD and associ- PGAD cases arise from lesions affecting the sacral sensory networks ated symptoms, and most had curtailed daily activities. At pre- that transmit sexual arousal—that it is a disorder of special sensation sentation, only 20% of patients’ physicians recognized their akin to neuropathic pain and itch. To reflect this, we propose symptoms as PGAD, so most self-diagnosed online. Before onset, congruent Greek-derived neurophysiologic nomenclature. For all were functioning well and none had major psychiatric diagnoses, sexual arousal after nonsexual stimulation, we suggest “allodieger- yet several reported psychiatric attribution and treatment—for sis” (allo/άllo) for “other” plus diegersis/diέgersh§ (sexual arousal), example, with sex therapy and electroconvulsive treatments. analogous to “allodynia” for pain and “alloknesis” for itch. For Eighty percent of patients first sought care for their other pelvic spontaneous sexual arousal or orgasm without physical or mental symptoms and only mentioned PGAD after establishing trust. stimulation, we propose “aftodiegersis” from aftomato/aytomato Among medical consultations, neurological evaluations were the (unprovoked) and diegersis/diέgersh§ (sexual arousal). A genito- most productive. They documented colocalizing somatosensory pelvic nosology has been developed,19 but adding conventional symptoms in 90%, including perineal, buttock, or leg pain and/or neurological nomenclature could improve general medical aware- sensory loss. Neurological testing was also productive, with 78% ness, care, and research. (6/8) of sacral magnetic resonance imaging studies revealing Our findings will have clinical implications if confirmed because radiculopathy, 2/2 nerve-conduction studies diagnostic for sen- most PGAD patients now linger medically undiagnosed and sory polyneuropathy along with 2/5 lower-leg, PGP9.5- untreated. Patient-initiated internet sites document thousands of immunolabeled skin biopsies. Among 2 composite autonomic (usually female) questioners. Therefore, this small series, although function tests, 1 was abnormal, the other borderline. Abnormal among the largest of examined patients, cannot fully represent urodynamic and anorectal manometry testing confirmed myelop- PGAD nor provide accurate prevalences, causes, or treatment athy in the spina bifida patient. Four electroencephalograms in 2 outcomes because of referral bias. However, it offers an interim patients were unremarkable, including one capturing 4 spontane- clinical framework. It independently identifies sacral dorsal root ous orgasms.9 Tarlov cysts as causal2,11 and strengthens associations with 22)e801 (2020) 5 Table 1 Patient characteristics. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Demographics Caucasian female Arabic female age Caucasian female Caucasian female Caucasian female Caucasian female Caucasian female Caucasian female Caucasian female Caucasian female age 29.3 years 35.9 years age 36.8 years age 42.1 years age 50.0 years age 58.4 years age 59.0 years age 60.9 years age 71.8 years age 79.8 years Onset At menarche (age At 32, developed At 11, near At 30, developed At 46, developed At 50, developed At 58, developed At 53, developed At 69, developed At 70, developed 12), developed unprovoked arousals menarche, unprovoked arousals unprovoked arousals unprovoked arousals continuous strong continuous low-level unprovoked clitoral unprovoked arousals unprovoked arousals without orgasm developed without orgasm without orgasm for 2 without orgasm anorgasmic arousals arousal without tingling and without orgasm without orgasm unprovoked arousals days, then with for 2–3 months, orgasm arousals, then without orgasm orgasm then with orgasm orgasms early on Temporal Multiple (#10) daily Multiple (#5) daily Multiple (#6) daily Multiple (#30) daily Multiple 2 hours Near-continuous 40% 1–2 hours of Near-continuous Initially once every Near constant characteristics episodes of arousal episodes that never episodes often brief episodes of episodes daily arousal without strong arousal per waxing and waning few weeks, then arousal worse as day of PGAD for 5–40 minutes, caused orgasm including orgasm, almost immediate subsided after orgasms, severe day, 60% 1–2/day arousal, 1 month- more frequent until progresses, one 3–4 episodes 20% include worse in afternoon. orgasm even during duloxetine was mechanical episodes of long remission, only near-daily episodes week remission after orgasms that gave Gradual lessening sleep resumed at 60 mg vulvodynia continuous mild or 3 spontaneous clozapine stopped a few hours relief after adolescence then tapered; PGAD strong arousal, orgasms ended after 3-week 1 spontaneous taper, no known orgasm/mo while recurrence sleeping Precipitants Sitting, vibration Standing, lying flat, Premenses and None Sitting, squeezing Sitting, vulvar Sitting, travel Orgasms and genital Daily onset at 4–5 Valsalva, defecation travel (sitting menses menses legs together contact including (vibration 1 sitting) herpes outbreaks, AM, standing, 1 vibration) clothing gives lying flat, twisting, sudden walking sensation of vaginal stress, sleeping discontinuation of distention sertraline Ameliorants Avoiding Normal aging None Restarting Wearing panty liners Avoiding some None Sitting, lying down Showering precipitants duloxetine, cooling to prevent brushing positions vulva, drinking wine against vulva, avoiding pants with seams Effects of Tried, not helpful Tried, not helpful Tried, used daily Tried, not helpful Tried, not helpful Tried, only brief Tried, only brief Tried, only brief Tried, not helpful Tried, anhedonic masturbation afternoon refractory period, so refractory period, so refractory period, so masturbation masturbation with not helpful not helpful not helpful and 4–53 daily gave 1 several orgasms to premature orgasms hour of relief dampen baseline were unpleasant arousal until next day

Urologic Neurogenic bladder Frequency, urgency, Hesitancy, some None Strong urgency Urgency, frequency, None Frequency None Frequency www.painreportsonline.com symptoms since infancy, self- mild hesitancy, incontinence during and between urinary incontinence (153 daily), catheterizes sense of incomplete episodes occasional bladder voiding pain labeled interstitial cystitis Other Sacral dimple at Age 23 neuropathic Tachycardia, None Restless leg Perineal and right Low back, right leg Neuropathic pain, Pelvic pain soon Bilateral neurologic birth, neurogenic pain in left vulva, gastrointestinal movements at night buttock burning, pain and numbness, numbness, itch in after onset at right paresthesias in signs and bladder, bowel since rectum, upper thigh, dysmotility with and while sleeping itching, pain, severe occasional clitoral hands and feet, T11-T12, mons- thighs and legs, symptoms birth, uses bilateral low back nausea, vomiting, pain with vaginal pain, allodynia postorgasm buzzing, poking right leg cramps cecostomy tube to and leg pain, 50 lb weight loss, insertion headache attributed feelings. Pin void bowels, radicular sensory neurogenic to CSF leak from examination of right perineal sensory loss left vulva, constipation since cervical TC, chronic labium majus felt as loss, pain radiating buttock, thigh, childhood fatigue, exertional not sharp, tingling, to upper inner chronic occipital intolerance, “sexy” thighs, rarely to toes headaches syncope, abnormal 3 GI motility (continued on next page) 4 Table 1 (continued) Patient characteristics.

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 al. et Oaklander A.L. Obstetric- Nulliparous, severe Nulliparous, bilateral Nulliparous, Nulliparous, Three One pregnancy Two pregnancies, One pregnancy; Tubal ligation, Two uncomplicated gynecology pelvic pain worse on ovarian cysts extrauterine menorrhagia- uncomplicated terminated, one preterm, one Cesarian delivery; breast biopsy, vaginal childbirths history right, severe vaginal endometriomas and treated hormonally vaginal childbirths; premenopausal twin endometriosis abdominal surgery insertional pain, adhesions, and surgically; no gynecological menorrhagia treated with lysis of for ovarian cyst and polycystic ovarian managed previously concerns adhesions; uterine appendectomy syndrome hormonally, anorgasmic despite fibroid; genital

surgically attempts with herpes since youth · stimulator e801 (2020) 5 Sexual No sexual No sexual No sexual Sexual relations with Remained abstinent Sexual relations with Sexual relations with New Clitoral stimulation Sexual relations with sequelae experience at PGAD experience at PGAD experience at PGAD fianc´e ended within until PGAD husband ended; husband ended; near-immediate painful, sexual husband ended; onset, one failed onset, remained onset, remained a year, then resolution then abstinent then abstinent orgasm during sex, relations with then abstinent intercourse attempt, abstinent abstinent abstinent sexual relations with husband ended; then abstinent husband ended; then abstinent then abstinent Psychiatric Depression, anxiety Depression Depression, anxiety Depression Depression, anxiety Depression, anxiety Pre-existing Depression Depression Depression, anxiety symptoms depression tardive dyskinesia, benzodiazepine dependence Initial PGAD Attributed to STD Depression, stress, Uncertain Hypersexuality, Sudden duloxetine Sexologist- Prolonged sitting No explanation Pudendal “Psychosexual attribution despite no previous myofascial leg pain seizures, endocrine discontinuation diagnosed PGAD, position during offered by neuropathy mania” prompting partners plus occipital dysfunction uncertain of cause medical procedure gynecologist 7 psychiatric neuralgia hospitalizations Lumbosacral Malfusion of S1 Sacral TC, 6.3 cm at No full sacral MRI, L5-S1 HNP with Not performed Sacral TC; small Noncontributory, Lumbar TC, bilateral Sacral TC; 5-mm Sacral TC; large MRI (Fig. 1) arch, L4-S1 facet S1, into pelvis lumbar moderate foraminal right S1, large sacral MRI with only L5 1 cm on right, right S3, L4-L5, L5- bilateral S3, S4 arthropathy, L5-S1 compressing noncontributory, stenosis, right L5 bilateral S2, S3 mild sacroiliac DJD two 0.4-cm cysts on S1 DJD, disc bulges, HNP with mild left iliopsoas, bilateral mild lumbar DJD. root contact small S4 lumbar mild DJD, left bilateral root compression S2 cysts with L45, L5-S1 facet mild–moderate foraminal erosion; arthropathy, foraminal stenosis mild lumbar DJD Peripheral Urodynamics with Not performed Abnormal lower leg Normal lower leg Not performed NCS with right-only Normal lower leg In 2015 had 28 ENF/ Normal distal leg Not performed nerve testing outlet obstruction, skin biopsy (103 skin biopsy (398 slow pudendal nerve skin biopsy (278 mm2 skin surface skin biopsy (235 postvoid residual, ENF/mm2 skin ENF/mm2 of skin motor latency, EMG ENF/mm2 skin area; ,1st centile of ENF/mm2 skin anorectal surface area, at surface area, at 84th normal surface area, at 86th predicted, EMG/NCS surface area, at 88th manometry with ,1st centile of centile of predicted) centile of predicted), with demyelinating centile of predicted) high resting anal predicted), EEG noncontributory 1 axonal motor pressure with outlet borderline sensory changes, obstruction, low composite normal AFT. 2018 squeeze pressure, autonomic function skin biopsies poor rectal sensation testing diagnostic for SFN at distal leg and thigh, reduced sweat- gland innervation at distal leg, AFT diagnostic for SFN Reports PAIN (continued on next page) ® 22)e801 (2020) 5 Table 1 (continued) Patient characteristics. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Other Thoracic MRI with None performed Cervical MRI with 3 normal EEGs Brain MRI None None performed Cervical MRI with None performed Brain MRI, CTA neurologic T11-12 HNP and mild DJD, 56-panel including 1 during 4 noncontributory C6, C8 Tarlov cysts, normal; thoracic and testing mild cord signal whole exome spontaneous multilevel DJD Brain lumbar MRI with changes sequencing with no orgasms, brain MRI MRI, PET mild DJD pathogenic variants noncontributory noncontributory Current PGAD Symptomatic sacral Sacral radiculopathy Small-fiber L5S1 HNP with L5 Sudden duloxetine Sacral radiculopathy Unknown, sacral Atypical CIDP with Sacral radiculopathy Sacral radiculopathy attribution spina bifida occulta from multiple Tarlov neuropathy, possible radiculopathy discontinuation from multiple Tarlov MRI recommended small-fiber from right S3 Tarlov from multiple Tarlov cysts plexus irritation by cysts involvement plus cyst cysts endometriomas lumbar Tarlov cysts Ineffective Pudendal nerve None offered Nortriptyline offered Sex therapy, Unknown Pudendal nerve Pudendal nerve Unknown Bilateral pudendal, Pudendal nerve symptom block, empiric anti- but declined levetiracetam blocks, caudal blocks, epidural genitofemoral, blocks, TENS, treatments infectives for STDs, epidural steroids, steroids, trigger ilioinguinal, nerve electroconvulsive vaginal Botox testosterone, pelvic point injections, blocks, gabapentin, therapy 317, injections to bladder PT, TENS, tibial gabapentin, topical pregabalin, citalopram neck, clitoris, pelvic nerve stimulator amitriptyline, sertraline, leuprolide, floor, topical baclofen, local acupuncture, topical escitalopram, lidocaine anesthetics lidocaine, amitriptyline, amitriptyline/ ovarian vein gabapentin/baclofen embolization Effective Bilateral Mild improvement Gradual Mild improvement None None Mild help from None None None symptom genitofemoral nerve with duloxetine, improvement with with risperidone gabapentin cream, treatments block gave 80% acetazolamide aging genitofemoral nerve relief for 3 days only blocks gave few weeks of 85% relief Definitive None tried Complete remission None tried; trial of None tried; surgical 5 year total Resection of left and None recommended IVIg reduced PGAD None tried; None tried; Tarlov- neurologic after surgical Tarlov- IVIg recommended consultation for HNP remission after right S2 and right S3 or tried days from maximum acetazolamide trial cyst resection treatments cyst resection 1.5 but declined decompression duloxetine 60 mg Tarlov cysts was of 30 days/month to recommended recommended but years ago recommended resumed on day ineffective 4 days/month and declined 3; tapered over 3 greatly improved weeks other neuropathy symptoms eg, weakness AFT, autonomic function testing; CIDP, chronic inflammatory demyelinating polyneuropathy; CSF, cerebrospinal fluid; DJD, degenerative disk disease; ECT, electroconvulsive therapy; EEG, electroencephalogram; EMG, electromyography; ENF, epidermal nerve fibers; GI, gastrointestinal; HNP, herniated nucleus pulposus; LS, lumbosacral; MRI, magnetic resonance imaging; NCS, nerve conduction study; PGAD, persistent genital arousal disorder; PT, physical therapy; TC, tarlov cyst; TENS, transcutaneous electrical nerve stimulation. www.painreportsonline.com 5 6 A.L. Oaklander et al.·5 (2020) e801 PAIN Reports®

herniations, her PGAD may be unrelated, but the associations of PGAD with sacral radiculopathy from Tarlov cysts convey plausibility. Female over-representation of published PGAD is high—we know of only 5 to 6 unique male cases (including 1 with L5-S1 disc herniation and 2 with small-fiber polyneuropathy).8,10,21,24 Conceivably, male patients merely seek treatment less often, but we propose 3 biological contributors. A total of 90% to 95% of symptomatic Tarlov-cyst patients are women, because of their thinner meninges and tilted pelvis containing more-vertical nerve roots more exposed to CSF pressure waves. In addition, female patients represent 3/4 of many small-fiber neuropathy cohorts,13 and 2/3 of US antidepressant users.18 Female patients thus have a higher risk of associated neurologic conditions. For lesion localization, 3-mm-cut sacral MRI and tests for neuropathy were highly useful. Pudendal nerve conduction should be measured more often, particularly with glove electro- des now standard. Brain MRI and EEG were futile.23 Regarding treatment, skilled neurosurgeons report good outcomes for Tarlov-cyst resection.2 Medical management of PGAD symptom should include gradual tapering of causal medications, and perhaps considering libido-dampening drugs. For nerve and nerve-root lesions, tricyclics, ion-channel blockers, and anti- epileptics—effective for neuropathic pain and itch—deserve consideration. Neurological evaluation and treatment should precede psychotherapy, electroconvulsive therapy, or clitoridectomy.25

Disclosures The authors have no conflict of interest to declare. Supported in part by NIH R01NS093653 and K24NS059892 (to A.L.O.) and Sydney R. Baer Jr. Foundation (to B.H.P.). Presented in abstract form to the 2018 meeting of the International Association for the Study of Pain.

Figure 1. Magnetic resonance imaging identifying sacral Tarlov cysts (patient 1). (A) Sagittal view. Green arrows depict trilobed, multiseptate T2 hyperintense, T1 hypointense nonenhancing Tarlov perineurial cysts in the left L5-S1, left S1-S2, Acknowledgements and left S2-S3 neural foramina (right S1-S2 cysts were also present and seen on other images). (B) Coronal view. Green arrows depict multiseptated T2 The authors appreciate the referral of two patients by neuro- hyperintense, T1 hypointense perineurial cysts in the same patient. The largest urologist Dr. Elise De and the assistance of Dr. Marinos Dalakas cyst, at left L5-S1, tracks along the course of the L5 nerve root and measures 6 with Greek terminology. cm in greatest dimension. Article history: Received 7 June 2019 sensory polyneuropathy. It adds another case associated with Received in revised form 13 September 2019 lumbosacral disc herniation and proposes cauda equina malfor- Accepted 6 November 2019 mation and sensory CIDP as potential new causes. It associates Available online 6 January 2020 PGAD with abrupt duloxetine withdrawal, given that duloxetine resumption was curative, extending reported associations beyond initiation of libido-promoting drugs (eg, dopaminergics) References and abrupt discontinuation of libido-inhibitors (eg, serotonergic 5,6,8,22 [1] Alexander MS, Marson L. The neurologic control of arousal and orgasm antidepressants). It is unknown whether the synapses with specific attention to spinal cord lesions: integrating preclinical and involved in drug-associated PGAD are central or peripheral. In clinical sciences. Auton Neurosci 2018;209:90–9. patient 8, the fact that immunoglobulin treatment resolved not [2] Feigenbaum F, Boone K. Persistent genital arousal disorder caused by only motor CIDP symptoms but also reduced PGAD- spinal meningeal cysts in the sacrum: successful neurosurgical symptomatic days from 30 to 4/month and stopped spontaneous treatment. Obstet Gynecol 2015;126:839–43. [3] Georgiadis JR, Kortekaas R, Kuipers R, Nieuwenburg A, Pruim J, orgasms suggests potentially broader associations between Reinders AATS, Holstege G. Regional cerebral blood flow changes PGAD and sensory polyneuropathy, and potential effectiveness associated with clitorally induced orgasm in healthy women. Eur J of standard neuropathy treatment for PGAD. Patient 4 developed Neurosci 2006;24:3305–16. isolated PGAD with only L5-S1 disc herniation identified. Given [4] Giraldi A, Rellini AH, Pfaus J, Laan E. Female sexual arousal disorders. J Sex Med 2013;10:58–73. her L5 foraminal but not central stenosis, if this contributed, [5] Healy D, Le Noury J, Mangin D. Enduring sexual dysfunction after impingement of entering clitoral afferents was a more likely source treatment with antidepressants, alpha-reductase inhibitors and than the conus medullaris.16 Given the high prevalence of disc isotretinoin: 300 cases. Int J Risk Saf Med 2018;29:125–34. 5 (2020) e801 www.painreportsonline.com 7

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