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3. Hart SR, Weiser EB. Abdominal sacral colpopexy mesh erosion resulting in a sinus tract formation and sacral abscess. Obstet Gynecol 2004;103:1037– 40. 4. Unger JB. A persistent sinus tract from the vagina to the sacrum after treatment of mesh erosion by partial removal of a GORETEX soft tissue patch. Am J Obstet Gynecol 1999;181:762– 63. 5. Muffly TM, Diwadkar GB, Paraiso MF. Lumbosacral osteomyelitis after robot-assisted total laparoscopic hysterectomy and sacral colpopexy. Int Urogynecol J Pelvic Floor Dysfunct 2010;21:1569 –71.

Stiff Person Syndrome and Pregnancy Jennifer Goldkamp, MD, Robert Blaskiewicz, and Thomas Myles, MD

MD,

BACKGROUND: Stiff person syndrome, also known as Moersche-Woltman syndrome, is a debilitating disorder that is rarely seen in the pregnant patient. It is characterized by muscle spasms triggered by startle, voluntary movement, or tactile or emotional stimuli, occurring predominantly in the axial musculature. CASE: A woman diagnosed with stiff person syndrome became pregnant 2 months after her diagnosis. Her medication regimen was adjusted because of pregnancy, and anesthesia was initiated early in labor to control her pain. She was able to have a full-term pregnancy with few complications. CONCLUSION: Stiff person syndrome may be successfully managed in pregnancy. Patients can deliver vaginally with adequate pain control to avoid muscle spasms. (Obstet Gynecol 2011;118:454–7) DOI: 10.1097/AOG.0b013e318216196b

S

tiff person syndrome, also known as MoerscheWoltman syndrome or stiff man syndrome, is a progressive disorder of symmetric muscle spasms triggered by startle, voluntary movement, or tactile or emotional stimuli occurring predominantly in the axial musculature. Approximately two-thirds of these patients have an autoantibody against glutamic acid From St. Louis University School of Medicine, St. Louis, Missouri; and the Department of Obstetrics and Gynecology and Women’s Health Division of Maternal-Fetal Medicine, St. Mary’s Health Center, St. Louis, Missouri. Corresponding author: Jennifer Goldkamp, MD, St. Mary’s Health Center, 6420 Clayton Road, Richmond Heights, MO 63117; e-mail: jgoldka2@slu.edu. Financial Disclosure The authors did not report any potential conflicts of interest. © 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/11

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6. Nesseir SB, Kim YH, Lind LR, Winkler HA. Sacral osteomyelitis after robotically assisted laparoscopic sacral colpopexy. Obstet Gynecol 2010;116:513–5. 7. Cundiff GW, Varner E, Visco AG, Zyczynski HM, Nager CW, Norton PA, et al. Risk factors for mesh/suture erosion following sacral colpopexy. Am J Obstet Gynecol 2008;199: 668.e1–5. 8. Rardin CR, Washington BB. New considerations in the use of vaginal mesh for prolapse repair. J Minim Invasive Gynecol 2009;16:360 – 64.

decarboxylase, which is the rate limiting enzyme in the synthesis of ␥ aminobutyric acid, the brain’s main inhibitory neurotranslator (Box 1). This leads to an imbalance of inhibition and excitation of motor neurons. This disease is suspected to be autoimmune in nature, and these patients often have other autoimmune diseases, including type one diabetes mellitus, thyroiditis, pernicious anemia, and vitiligo. The other one-third of patients have an idiopathic form of the disease or rarely a paraneoplastic syndrome with antibodies to synaptic proteins amphiphysin and gephyrin Ropper.1,2 A literature search was conducted using the search engine PubMed. A search using the key words “stiff person” and “pregnancy” were done separately and then combined. This search was also repeated

Box 1. Stiff Person Syndrome8 Seven diagnostic criteria Prodrome of stiffness and rigidity in axial muscles Slow progression of stiffness to include proximal limb muscles, making volitional movement and ambulation difficult Fixed deformity of the spine (most commonly lordosis) Presence of superimposed episodic spasm precipitated by sudden movement, jarring, noise, and emotional upsets Normal motor and sensory nerve examination Normal intellect Typical electromyographic findings of continuous motor activity abolished by the administration of diazepam Incidence True incidence unknown, rare 2:1 female:male ratio Risk factors None known Treatment1 Diazepam, clonazepam, baclofen, plasma exchange, gabapentin, valproate, or intravenous gamma globulin. Dosage highly variable among individuals depending on severity of disease.

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combining “stiff man” and “pregnancy” and “Moersche Woltman” and “pregnancy.” There were no additional limits used such as time, language, or type of article. Of the articles returned in these searches, only two discussed pregnancy in patients diagnosed with stiff person syndrome. The first case was of a 41-year-old woman who had stiff limb syndrome, a variant of stiff person syndrome. She was diagnosed before pregnancy; she was negative for antiglutamic acid decarboxylase, but her electromyogram showed persistent motor unit firing. During her pregnancy, the patient was able to decrease her need for baclofen and diazepam in the second trimester. She had a full-term pregnancy and delivered by forcepsassisted vaginal delivery for fetal indications. During the delivery, the patient had a generalized spasm in response to her episiotomy, although she had an epidural. She noted increasing symptoms postpartum.2 The second case depicted a 36-year-old primigravida who was admitted in the third trimester for back pain and muscle spasms, which prohibited her from walking. The patient underwent a diagnostic work-up, which revealed an elevated glutamic acid decarboxylase immunoglobulin G and electromyography showed continuous motor unit activity. The patient was diagnosed with stiff person syndrome and treated with diazepam for the rest of her pregnancy. She delivered a healthy neonate by scheduled cesarean delivery under general anesthesia. In this case, the patient reported remission of her symptoms by 2 weeks postpartum.3

CASE A 27-year-old woman, G2A2, with no significant medical history presented to the emergency department at an outside facility with respiratory failure. She was intubated and transferred to the intensive care unit; her diagnosis at the time of admission was diaphragmatic spasms. During her hospitalization, the patient had a muscle biopsy that showed evidence of type 1 fiber atrophy and her laboratory results were positive for antiglutamic acid decarboxylase antibodies. She was diagnosed with stiff person syndrome, treated with intravenous immunoglobulin, and her symptoms improved. She was hospitalized in the intensive care unit for almost 20 days before being discharged home on 900 mg gabapentin three times daily, 10 mg diazepam three times daily, and a prednisone taper. Two months later, the patient reported a positive urine pregnancy test to her primary obstetrician; she was referred to the Maternal-Fetal Medicine Department of St Louis University to continue prenatal care. The patient’s prednisone and gabapentin were continued, but her diazepam was discontinued. Her muscle spasms increased without the diazepam, and she was started on 10 mg baclofen three times daily. Her prenatal course was characterized by rare episodes of muscle spasms.

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At 39 weeks 6 days, the patient presented with leaking of fluid and painful contractions every 3 minutes. She was admitted to labor and delivery and received an epidural shortly thereafter in an effort to attain early pain control. At 7– 8 cm dilation, the fetus had repetitive late decelerations and the patient underwent an urgent low transverse cesarean delivery for nonreassuring fetal heart tones. She delivered a female neonate with Apgar scores of 5 at 1 minute and 8 at 5 minutes; birth weight was 3,230 g, arterial cord gas pH was 7.229, PCO2 was 53.8, PO2 was not recorded, and base excess was ⫺6.2. On postpartum day 1, the patient’s neurologist restarted her on diazepam three times daily. The patient and neonate were discharged in stable condition on postpartum day 4. The patient followed up for a 6-week postpartum visit, at which time she received an Implanon (Merck) for birth control. Currently she is taking prednisone and diazepam, with moderate control of her disease; she continues to work part-time. The infant never was tested for antibodies and is doing well.

COMMENT Stiff person syndrome is a rare, progressively debilitating disorder that requires patients to rely on medication to perform activities of daily living. Most patients have paraspinal muscle spasms, which lead to lumbar lordosis. Treatment options include diazepam, clonazepam, vigabatrin or baclofen, plasma exchange, high-dose corticosteroids, or intravenous gamma globulin.1 Our patient was on diazepam, gabapentin, and prednisone at conception. She was changed from diazepam to baclofen in early pregnancy and then allowed to return to diazepam in her second trimester. Diazepam is a category D medication, with the potential for the neonate to develop withdrawal after birth if taken near the time of delivery. Congenital malformations have also been linked with use of diazepam during pregnancy; however, this information is now being reinvestigated.4 Two case reports of three children born to mothers with stiff person syndrome revealed that the neonates had elevated levels of antiglutamic acid decarboxylase 65 at birth, but none of the children were symptomatic and their titers dropped over the subsequent year. This suggests transplacental spread of the antibody and that this disease is likely multifactorial because the antibodies did not affect the children. Additionally, one mother breastfed without complications.4 Although these children were found to be asymptomatic at birth and had decreasing serum levels of antiglutamic acid decarboxylase, it is uncertain what lies ahead because this disease likely has a genetic component. Burns et al5,6 report a father– daughter pair with different forms of stiff per-

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son syndrome. The father had stiff limb syndrome, and the daughter had an intermittent axial form. In this study, the father, daughter, and nine other family members were tested for antibodies and underwent DNA analysis. Antibodies to glutamic acid decarboxylase 65 were detected in six family members, including the father and daughter; however, the other family members had much lower antibody titers than the affected individuals. Thyroid antibodies were detected in five family members, and three of these people had subclinical disease. Antinuclear antibody was detected in three of the family members, and smooth muscle antibodies were detected in one person. Neither the father nor the daughter had the haplotype DRB1*1303-DQB1*0301, which is thought to be associated with stiff person syndrome. There are several cases of stiff person syndrome in reference to anesthesia management. Some cases of prolonged hypotonia are reported after using nondepolarizing muscle relaxants, whereas other case reports use nondepolarizing muscle relaxants without any additional difficulties. Elkassanbany et al reports using a somatic paravertebral block supplement with conscious sedation on a patient undergoing a right indirect inguinal hernia repair to avoid enhancing the ␥ aminobutyric acid agonistic effects of muscle relaxers with some of the general anesthetics.7 Because of concern for our patient, anesthesia services consult was sought while the patient was in her third trimester and their preference was for regional anesthesia, ie, epidural, early in the patient’s labor. They too were concerned about prolonged hypotonia. Although our patient had a cesarean delivery, it was secondary to her disease. Weatherby et al reported a mother who had a successful forceps-assisted delivery; the forceps were applied secondary to fetal distress. However, Cerimagic et al concluded that cesarean delivery is the appropriate method of delivery for patients with stiff person syndrome. We believe that with adequate pain control, these patients should be able to deliver vaginally. In addition, the increased pain and prolonged recovery period associated with cesarean delivery may result in increased exposure to muscle spasm triggers associated with stiff person syndrome. Although our patient and the other patient who delivered by forceps-assisted vaginal delivery experienced fetal distress, there is no reason to believe the nonreassuring fetal heart tones were secondary to the maternal disease unless possibly the uterus was having tetanic contractions. However, that was not the case in our patient and is not mentioned

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in the other case report by Weatherby et al. Although the antibodies have been reported to pass through the placenta, there does not appear to be any sequelae for the neonate and thus no fetal contraindication to vaginal delivery. Both our patient and the patient with stiff limb syndrome were able to wean down their medications during pregnancy. The patient with stiff limb syndrome had a relapse after delivery. In the second case by Cerimagic et al, the patient did not develop the disease until pregnancy and then had spontaneous remission afterward. All of these things suggest an autoimmune disease process, and thus, with the limited number of case reports in pregnancy, it is impossible to predict the course of the disease in pregnancy or even a trend in pregnancy. In conclusion, there are a few case reports of stiff person syndrome. Our patient had life-threatening diaphragmatic spasms 2 months before becoming pregnant. She had a relatively uneventful pregnancy and was able to wean down her medications in the second and third trimesters. Other authors feel that these patients would benefit from a cesarean delivery; we, however, believe that these patients can deliver vaginally with adequate pain control. Adequate pain control should be a priority to avoid a pain trigger for muscle spasms. Regional anesthesia can be used successfully, and general anesthesia may increase the risk of complications with this group of patients. Finally, medications need to be addressed for pregnancy. Diazepam may have potential to cause birth defects, which would require medication adjustment in the first trimester. Therefore, it is important that a patient be switched to a drug such as baclofen as early in the pregnancy as possible. The patient can be transitioned back to diazepam later in the pregnancy, but the dose should be monitored because diazepam may cause respiratory depression in the neonate and he may develop withdrawal. The anesthesiologist needs to be aware of the patient’s medical condition because of possible complications of prolonged hypotonia, and pain control should be achieved early in labor to prevent episodes of spasm. REFERENCES 1. Ropper AH, Samuels MA. Disorders of muscle characterized by cramp, spasm, pain, and localized masses. Adams and Victor’s principles of neurology. 9th ed. Available at: www. accessmedicine.com/content.aspx?aID⫽3643105. Retrieved March 20, 2010. 2. Weatherby SJ, Woolner P, Clarke CE. Pregnancy in stiff-limb syndrome. Mov Disord 2004;19:852– 4.

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3. Cerimagic C, Bilic E. Stiff-person syndrome first manifesting in pregnancy. Gynecol Obstet Invest 2009;67:134 – 6. 4. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol 1994;8: 461–75. 5. Burns TM, Phillips LH, Jones HR, Nemni R, Caniatti LM, Gironi M, et al. Stiff person syndrome does not always occur with maternal passive transfer of GAD65 antibodies. Neurology 2005;64:399 – 400.

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Diabetic Papillopathy in Pregnancy A Marker for Progression to Proliferative Retinopathy Alexandra Bargiota, MD, PhD, Maria Kotoula, MD, Evangelia Tsironi, and Georgios Koukoulis, MD, PhD

6. Burns TM, Jones HR, Phillips LH 2nd, Bugawan T, Erlich H, Lennon VA. Clinically disperate stiff-person syndrome with GAD65 autoantibody in a father and daughter. Neurology 2003;61:1291–3. 7. Elkassabany N, Tefzlaff JE, Argalious M. Anesthetic management of a patient with stiff person syndrome. J Clin Anesth 2006;18:218 –20. 8. Lorish TR, Thorsteinsson G, Howard FM Jr. Stiff-man syndrome updated. Mayo Clin Proc 1989; 64:629 –36.

MD, PhD,

BACKGROUND: Diabetic papillopathy is an uncommon cause of transient acute optic disc edema, and during pregnancy it may be easily confused with other more serious disorders that may result in acute visual loss. CASE: We present a case of acute bilateral optic disc edema attributable to diabetic papillopathy in a young woman with an unplanned pregnancy and childhoodonset type 1 diabetes mellitus. The patient presented 16 months after fetal death of unknown etiology at 26 weeks of gestation with acute visual impairment in both eyes; severe proliferative retinopathy was diagnosed. Despite immediate therapeutic intervention with panretinal laser photocoagulation, the patient is legally blind. CONCLUSION: Early recognition of diabetic papillopathy in pregnancy is important to prevent unnecessary testing, invasive procedures, and inappropriate treatment. Patients with diabetic papillopathy should be monitored closely even after delivery because this condition may be associated with rapid progression to proliferative retinopathy. (Obstet Gynecol 2011;118:457–60) DOI: 10.1097/AOG.0b013e318216ecd7

cute optic disc edema during pregnancy can occur because of several conditions of different clinical importance, can indicate a high-risk pregnancy, and poses additional diagnostic and therapeutic challenges.1 Accurate and prompt determination of its cause is essential for the management, which can have implications for both mother and fetus. Diabetic papillopathy is an uncommon optic nerve condition described in patients with type 1 and type 2 diabetes mellitus and is characterized by transient unilateral or bilateral optic disc edema, which generally resolves after a few months without permanent severe visual loss and requires no treatment.2– 4 In rare instances, it can precede the development of anterior ischemic optic neuropathy, which usually presents in older patients with atherosclerosis, has acute onset and permanent visual loss, and diabetic papillopathy may be a mild and reversible form of it.8 Diabetic papillopathy can be easily misdiagnosed and thus may lead to unnecessary and inappropriate investigations and management. Here, we present a case of diabetic papillopathy in pregnancy, discuss its clinical importance and its relation to diabetic retinopathy, and review the literature. We performed a literature search in PubMed from 1970 to November 2010 in English and French and, to our knowledge, only six previous cases occurring during pregnancy have been reported.2,3,5–7

CASE

© 2011 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/11

A young primigravid woman who had had type 1 diabetes mellitus since the age of 7 was referred at 8 weeks of gestation to our combined antenatal clinic. Her pregnancy was not planned, and she had received no prepregnancy counseling. She was not known to have any diabetic complications, and her medical history was unremarkable. She did not drink alcohol, smoke, or use illicit drugs. There was no family history of note. She was using folic acid 400 micrograms per day. At examination her HbA1c level was 9.6% and blood pressure was 110/60 mm Hg. There were no pathologic findings on clinical examination, dilated fundoscopy, and laboratory tests. Fetal growth was within the normal range for gestational age, with no other patho-

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From the Departments of Endocrinology and Metabolic Diseases and Ophthalmology, University Hospital of Larissa, Larissa Greece. Corresponding author: Alexandra Bargiota, Department of Endocrinology and Metabolic Diseases, University Hospital of Larissa, Biopolis, 41110 Larissa, Greece; e-mail: abargio@yahoo.gr. Financial Disclosure The authors did not report any potential conflicts of interest.

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