Obstentrics_Williams

Obstentrics_Williams. Madazli R, Yuksel MA, Oncul M, et al: Obstetric outcomes and prognostic factors of lupus pregnancies. Arch Gynecol Obstet 289:49, 2014 Makol A, Wright K, Amin S: Rheumatoid arthritis and pregnancy: safety considerations in pharmacological management. Drugs 71(1t5):1973,t20t11 McInnes IB, Scherr G: The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205,t2011 Meier FM, Frommer W, Dinser R, et al: Update on the proile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 71(8):1355,t2012


Obstentrics_Williams

Obstentrics_Williams. Meier FM, Frommer W, Dinser R, et al: Update on the proile of the EUSTAR cohort: an analysis of the EULAR Scleroderma Trials and Research group database. Ann Rheum Dis 71(8):1355,t2012 Mekinian A, Bourrienne Me, Carbillon L, et al: Non-conventional antiphos pholipid antibodies in patients with clinical obstetrical APS: prevalence and treatment eicacy in pregnancies. Semin Arthritis Rheum 46(2):232, 2016 Mekinian A, Lazzaroni MG, Kuzenko A, et al: The eicacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 14(6):498, 2015 Meroni PL, Borghi MO, Raschi E, et al: Pathogenesis of anti phospholipid syn drome: understanding the antibodies. Nat Rev Rheumatol 7(6):330, 201t1 Missumi LS, Souza FH, Andrade JQ, et al: Pregnancy outcomes in dermatomyositis and polymyositis patients. Rev Bras Reumatol 55(2):95, 2015


Obstentrics_Williams

Obstentrics_Williams. Miyakis S, Lockshin MD, Atsumi T, et al: International consensus statement on an update of the classiication criteria for deinite antiphospholipid syndrome (APS). J hromb Haemost 4:295, 2006 Mohamed MA, Goldman C, EI-Dib M, et al: Maternal juvenile rheumatoid arthritis may be associated with preterm birth but not poor fetal growth. J Perinatol 36(4):268, 2016 Moroni G, Doria A, Giglio E, et al: Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st centuly. A prospective multicenter study. J Autoimmun 74:6, 2016a Moroni G, Doria A, Giglio E, et al: Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study. J Autoimmun 74:194,t2016b Moroni G, Ponticelli e Pregnancy after lupus nephritis. Lupus 14:89,t2005 Moroni G, Quaglini S, Bani G, et al: Pregnancy in lupus nephritis. Am J Kidney Dis 40:713,t2002


Obstentrics_Williams

Obstentrics_Williams. Moroni G, Ponticelli e Pregnancy after lupus nephritis. Lupus 14:89,t2005 Moroni G, Quaglini S, Bani G, et al: Pregnancy in lupus nephritis. Am J Kidney Dis 40:713,t2002 Moroni G, Ventura D, Riva P, et al: Antiphospholipid antibodies are associated with an increased risk for chronic renal insuiciency in patients with lupus nephritis. Am J Kidney Dis 43:28, 2004 Morra M, Bofa MC, Tincani A, et al: Follow-up of babies born to mothers with anti phospholipid syndrome: preliminary data from the European neonatal registry. Lupus 21(7):761, 2012 Moutsopoulos HM, Vlachoyiannopoulos PG: Antiphospholipid syndrome In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hili, 2015


Obstentrics_Williams

Obstentrics_Williams. Moutsopoulos HM, Vlachoyiannopoulos PG: Antiphospholipid syndrome In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hili, 2015 Munoz-Suano A, Kallikourdis M, Sarris M, e al: Regulatory T cells protect from autoimmune arthritis during pregnancy. J Autoimmun 38(2-3):J103, 2012 Musiej-Nowakowska E, Ploski R: Pregnancy and early onset pauciarticular juvenile chronic arthritis. Ann Rheum Dis 58:475, 1999 Nalli e, Iodice A, Andreoli L, et al: Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome. Lupus 26:552,t2017 Nelson JL, Hughes A, Smith AG, et al: Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis. N Engl J Med 329:466, 1993 Nelson JL, 0stensen M: Pregnancy and rheumatoid arthritis. Rheum Dis C1in North Am 23:195,t1997


Obstentrics_Williams

Obstentrics_Williams. Nelson JL, 0stensen M: Pregnancy and rheumatoid arthritis. Rheum Dis C1in North Am 23:195,t1997 Nodler J, Moolamalla SR, Ledger EM, et al: Elevated antiphospholipid antibody titers and adverse pregnancy outcomes: analysis of a population-based hospital dataset. BMC Pregnancy Childbirth 9(1):11, 2009 Ojeda-Uribe M, AfifN, Dahan E, et al: Exposure to abatacept or rituximab in the irst trimester of pregnancy in three women with autoimmune diseases. Clin Rheumatol 32(5):695, 2013 Oshiro BT, Silver M, Scorr JR, et al: Antiphospholipid antibodies and fetal death. Obstet Gynecol 87:489, 1996 0stensen M: Pregnancy in patients with a history of juvenile rheumatoid arthritis. Arthritis Rheum 34:881, 1991 0stensen M, Villiger PM: he remission of rheumatoid arthritis during pregnancy. Semin Immunopathol 29:185, 2007 Owen J, Hauth Je Polyarteritis nodosa in pregnancy: a case report and brief literature review. Am J Obstet Gynecol 160:606, 1989


Obstentrics_Williams

Obstentrics_Williams. Pagnoux e Updates in ANCA-associated vasculitis. Eur J Rheumatol 3(3): 122, 2016 Pagnoux C, Le Guern V, Goinet F, et al: Pregnancies in systemic necrotizing vasculitides: report on 12 women and their 20 pregnancies. Rheumatology (Oxford) 50(5):953,t2011 Papadopoulos NG, A1amanos Y, Voulgari PV, et al: Does cigarerre smoking influence disease expression, activity and severity in early rheumatoid arthritis patients? Clin Exp Rheumatol 23(6):861, 2005 Parderr R, Roussou E: he treatment of rheumatoid arthritis during pregnancy. Rheumatol Int 31(4):445,t2011 Patrono e Cardiovascular efects of nonsteroidal anti-inlammatory drugs. Curr Cardiol Rep 18(3):25,t2016 Peart E, Clowse ME: Systemic lupus erythematosus and pregnancy outcomes: an update and review of the literature. Curr Opin Rheumatol 26(2): 118,2014 Pepin M, Schwarze U, Superti-Furga A, et al: Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 342:673, 2000


Obstentrics_Williams

Obstentrics_Williams. Pepin M, Schwarze U, Superti-Furga A, et al: Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med 342:673, 2000 Petri M: Pregnancy in SLE. Baillieres Clin Rheumatol 12:449, 1998 Petri M, Kim MY, Kalunian Ke, et al: Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 353:2550, 2005 Petri M, he Hopkins Lupus Pregnancy Center: Ten key issues in manage ment. Rheum Dis Clin North Am 33:227, 2007 Phansenee S, Sekararithi R, Jatavan P, et al: Pregnancy outcomes among women with systemic lupus erythematosus: a retrospective cohort study from Thailand. Lupus January 1, 2017 [Epub ahead of print] Pierro E, Cirino G, Bucci MR, et al: Antiphospholipid antibodies inhibit prostaglandin release by decidual cells of early pregnancy: possible involvement of extracellular secretory phospholipase 2. Fertil Steril 71 :342, 1999


Obstentrics_Williams

Obstentrics_Williams. Pikwer M, Bergstrom U, Nilsson JA, et al: Breast feeding, but not use of oral contraceptives, is associated with a reduced risk of rheumatoid arthritis. Ann Rheum Dis 68(4):526, 2009 Pinal-Fernandez I, Selva-O'Callaghan A, Fernandez-Codina A, et al: Pregnancy in adult-onset idiopathic inlammatory myopathy: report from a cohort of myositis patients from a single center. Semin Arthritis Rheum 44(2):234, 2014 Prockop OJ, Bateman JF: Heritable disorders of connective tissue. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hili, 2015 Putterman C, Wu A, Reiner-Benaim A, et al: SLE-key rule-out serologic test for excluding the diagnosis of systemic lupus erythematosus: developing the ImmunArray iCHIP. J Immunol Methods 429:1,t2016 Rai RS, Cliford K, Cohen H, et al: High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and anti phospholipid antibodies. Hum Reprod 10:3301,t1995


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Obstentrics_Williams. Rai RS, Cliford K, Cohen H, et al: High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and anti phospholipid antibodies. Hum Reprod 10:3301,t1995 Rak JM, Maesrroni L, Balandraud C, et al: Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. Arthritis Rheum 60(1):73, 2009a RakJM, Pagni PP, Tiev K, et al: Male microchimerism and HLA compatibility in French women with scleroderma: a diferent proile in limited and difuse subset. Rheumatology 48(4):363, 2009b Ramaeus K, Johansson K, Askling J, et al: Juvenile onset arthritis and pregnancy outcome: a population-based cohort study. Ann Rheum Dis 76: 1809, 2017 Rand JH, Wu X, Andree HA, et al: Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a "lupus procoagulant" phenomenon. Blood 92:1652, 1998


Obstentrics_Williams

Obstentrics_Williams. Rand JH, Wu X, Andree HA, et al: Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: a "lupus procoagulant" phenomenon. Blood 92:1652, 1998 Rand JH, Wu X, Andree HA, et al: Pregnancy loss in the anti phospholipid antibody syndrome-a possible thrombogenic mechanism. N Engl J Med 337: 154, 1997 Ritchie J, Smyth A, Tower C, et al: Maternal deaths in women with lupus nephritis: a review of published evidence. Lupus 21 (5):534, 2012 Robertson B, Greaves M: Antiphospholipid syndrome: an evolving stoty. Blood Reviews 20:201, 2006 Robinson DP, Klein SL: Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm Behav 62(3):263, 2012 Rom AL, Wu CS, Olsen J, et al: Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis. A nationwide cohort study. Arthritis Rheumatol 66:3265, 2014


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Obstentrics_Williams. Rom AL, Wu CS, Olsen J, et al: Fetal growth and preterm birth in children exposed to maternal or paternal rheumatoid arthritis. A nationwide cohort study. Arthritis Rheumatol 66:3265, 2014 Roman MJ, Pugh NL, Hendershot TP, et al: Aortic complications associated with pregnancy in Marfan syndrome: the NHLBI National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). J m Heart Assoc 5(8), 2016 Roque H, Paidas M, Funai E, et al: Maternal thrombophilias are not associated with early pregnancy loss. hromb Haemost 91t(2):290,t2004 Rosenzweig BA, Rotmensch S, Binette SP, et al: Primary idiopathic polymyositis and dermatomyositis complicating pregnancy: diagnosis and manageme1t. Obstet Gynecol Surv 44: 162, 1989 Rudd NL, Nimrod C, Holbrook A, et al: Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet 1(8314-5):50,t1983


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Obstentrics_Williams. Rudd NL, Nimrod C, Holbrook A, et al: Pregnancy complications in type IV Ehlers-Danlos syndrome. Lancet 1(8314-5):50,t1983 Rufatti A, Tonello M, Visentin MS, et al: Risk factors for pregnancy failure in patients with anti-phospholipid syndrome treated with conventional therapies: a multicentre, case-control study. Rheumatology 50(9):1684, 2011 Ruiter-Ligeti J, Czuzoj-Shulman N, Spence AR, et al: Pregnancy outcomes in women with osteogenesis imperfecta: a retrospective cohort study. J PerinatoIt36(10):828,t2016 Saccone G, Maruotti GM, Berghella V, et al: Obstetric outcomes in pregnant women with primary anti phospholipid syndrome according to the antibody proile: the PREGNANTS study. Abstract No. 62, Am J Obstet Gynecol 21t6:S45,t20t17 Sammaritano LR: Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 23(12):1242, 2014


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Obstentrics_Williams. Sammaritano LR: Contraception in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 23(12):1242, 2014 Sanchez-Guerrero J, Uribe AG, Jimenez-Santana L, et al: A trial of cotraceptive methods in women with systemic lupus erythematosus. N Engl J Med 353:2539, 2005 SchoenhofF, Schmidli J, Czerny M, et al: Management of aortic aneurysms in patients with connective tissue disease. J Cardiovasc Surg 54(1 suppl 1): 125, 2013 Schreiber K, Hunt BJ: Pregnancy and antiphospholipid syndrome. Semin Thromb Hemost 42(7):780,t2016 Sciascia S, Hunt BJ, Talavera-Garcia E, et al: The impact of hydroxychloroquine treatment on pregnancy outcome in women with anti phospholipid antibodies. Am J Obstet GynecoI214(2):273.e1, 2016 Shah A, St. Clair EW: Rheumatoid arthritis. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hill, 2015


Obstentrics_Williams

Obstentrics_Williams. Shah A, St. Clair EW: Rheumatoid arthritis. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hill, 2015 Sharma BK, Jain S, Vasishta K: Outcome of pregnancy in Takayasu arteritis. Int J Cardiol 75:S159, 2000 Sherer Y, Gorstein A, Fritzler MJ, et al: Autoantibody explosion in systemic lupus erythematosus: more than 100 diferent antibodies found in SLE patients. Semin Arthritis Rheum 34(2):501,t2004 Shinohara K, Miyagawa S, Fujita T, et al: Neonatal lupus erythematosus: results of maternal corticosteroid therapy. Obstet Gynecol 93:952, 1999 Silman A, Kay A, Brennan P: Timing of pregnancy in relation to the onset of rheumatoid arthritis. Arthritis Rheum 35: 152, 1992 Silver M, Parker CB, Reddy UM, et al: Antiphospholipid antibodies in stillbirth. Obstet Gynecol 122(3):641,2013 Silverman E, Jaeggi E: Non-cardiac manifestations of neonatal lupus erythematosus. Scand J Immunol 72:223, 2010


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Obstentrics_Williams. Silverman E, Jaeggi E: Non-cardiac manifestations of neonatal lupus erythematosus. Scand J Immunol 72:223, 2010 Simchen MJ, Goldstein G, Lubetsky A, et al: Factor V Leiden and anti ph ospholipid antibodies in either mothers or infants increase the risk for perinatal arterial ischemic stroke. Stroke 40(1):65, 2009 Simpson JL: Cell-free fetal DNA and maternal serum analytes for monitoring embryonic and fetal status. Fertil Steril 99(4):1124, 2013 Singh JA, Saag KG, Bridges SL] r, et aI: 2015 American College of Rheumatology Guideline for the management of rheumatoid arthritis. Arthritis Care Res (Hoboken) 68(1):1, 2016 Singh N, Tyagi S, Tripathi R, et al: Maternal and fetal outcomes in pregnant women with Takayasu aortoarteritis: does optimally timed intervention in women with renal artery involvement improve pregnancy outcome? Taiwan ] Obstet Gynecol 54(5):597, 2015


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Obstentrics_Williams. Sitar G, Brambati B, Baldi M, et al: he use of non-physiological conditions to isolate fetal cells from maternal blood. Exp Cell Res 302: 153, 2005 Smok DA: Aortopathy in pregnancy. Semin Perinatol 38(5):295, 2014 Sneller MC: Wegener's granulomatosis.]AMA 273:1288, 1995 Sobanski V, Launay D, Depret S, et al: Special considerations in pregnant systemic sclerosis patients. Expert Rev Clin Immunol 12(11):1161, 2016 Solomons ], Coucke P, Symoens S, et al: Dermatosparaxis (Ehlers-Danlos type VIIC): prenatal diagnosis following a previous pregnancy with unexpected skull fractures at delivery. Am ] Med Genet A 161 (5): 1122, 2013 Spinillo A, Beneventi F, Epis OM, et al: he efect of newly diagnosed undif ferentiated connective tissue disease on pregnancy outcome. Am ] Obstet GynecoIt199(6):632.e1,t2008


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Obstentrics_Williams. Spinillo A, Beneventi F, Epis OM, et al: he efect of newly diagnosed undif ferentiated connective tissue disease on pregnancy outcome. Am ] Obstet GynecoIt199(6):632.e1,t2008 Spinillo A, Beneventi F, Locatelli E, et al: The impact of unrecognized autoimmune rheumatic diseases on the incidence of preeclampsia and fetal growth restriction: a longitudinal cohort study. BMC Pregnancy Childbirth 16(1):313,t2016 Srivatsa B, Srivatsa S, Johnson K, et al: Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet 358:2034,t2001 Steen VD: Pregnancy in women with systemic sclerosis. Obstet Gynecol 94: 15, 1999 Steen VD, Conte C, Day N, et al: Pregnancy in women with systemic sclerosis. Arthritis Rheum 32: 15t1, 1989 Stevens M. Maternal microchimerism in health and disease. Best Pract Res Clin Obstet GynecoIt31:121, 2016


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Obstentrics_Williams. Arthritis Rheum 32: 15t1, 1989 Stevens M. Maternal microchimerism in health and disease. Best Pract Res Clin Obstet GynecoIt31:121, 2016 Stojan G, Baer AN: Flares of systemic lupus erythematosus during pregnancy and the puerperium: prevention, diagnosis and management. Expert Rev Clin Immunol 8(5):439, 2012 Sukara G, Baresic M, Sen tic M, et al: Catastrophic antiphospholipid syndrome associated with systemic lupus erythematosus treated with rituximab: case report and a review of the literature. Acta Reumatol Port 40(2):169,t2015 Sundelin HE, Stephansson 0, Johansson K, et al: Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome. Acta Obstet Gynecol Scand 96(1):1t14, 2017 Sykes B, Ogilvie D, Wordsworth P, et al: Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COLIAI and COUA2. Am] Hum Genet 46(2):293, 1990


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Obstentrics_Williams. Sykes B, Ogilvie D, Wordsworth P, et al: Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COLIAI and COUA2. Am] Hum Genet 46(2):293, 1990 T araborelli M, Ramoni V, Brucato A, et al: Brief report: successful pregnancies but a higher risk of preterm births in patients with systemic sclerosis: an Italian multicenter study. Arthritis Rheum 64(6):1970, 2012 Tayabali S, Andersen K, Yoong W: Diagnosis and management of HenochSch6nlein purpura in pregnancy: a review of the literature. Arch Gynecol Obstet 286(4):825,t2012 Tenti S, Cheleschi S, Guidelli GM, et al: Intravenous immunoglobulins and antiphospholipid syndrome: how, when and why? A review of the literature. Autoimmun Rev 15(3):226,t2016 Tincani A, Rebaioli CB, Andreoli L, et al: Neonatal efects of maternal anti phospholipid syndrome. Curr Rheumatol Rep 11 (1):70, 2009 Toglia MR, Weg ]G: Venous thromboembolism during pregnancy. N Englt] Med 335:108, 1996


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Obstentrics_Williams. Toglia MR, Weg ]G: Venous thromboembolism during pregnancy. N Englt] Med 335:108, 1996 Tower C, Mathen S, Crocker I, et al: Regulatory T cells in systemic lupus ery thematosus and pregnancy. Am J Reprod Immunol 69(6):588, 2013 Tsokos GC: Systemic lupus erythematosus. N Engl] Med 365(22):21t10, 2011 Unger A, Kay A, Griin A], et al: Disease activity and pregnancy associated beta2-glycoprotein in rheumatoid arthritis. BM] 286:750, 1983 Van Dijk FS, Pals G, Van Rijn RR, et al: Classification of osteogenesis imperfecta revisited. Eur] Med Genet 53(1):1, 2010 Varga]: Systemic sclerosis (scleroderma) and related disorders. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternal Medicine, 19th ed. New York, McGraw-Hill, 2015 Varner MW, Meehan RT, Syrop CH, et al: Pregnancy in patients with systemic lupus erythematosus. Amt] Obstet Gynecol 145:1025, 1983


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Obstentrics_Williams. Varner MW, Meehan RT, Syrop CH, et al: Pregnancy in patients with systemic lupus erythematosus. Amt] Obstet Gynecol 145:1025, 1983 Volkov N, Nisenblat V, Ohel G, et al: Ehlers-Danlos syndrome: insight on obstetric aspects. Obstet Gynecol Surv 62:51, 2006 Wagner S, Craici I, Reed 0, et al: Maternal and foetal outcomes in pregnant patients with active lupus nephritis. Lupus 18(4)342, 2009 Waldorf M, Nelson ]L: Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. Immunol Invest 37:63t1,t2008 Wallenius M, Salvesen A, Daltveit AK, et al: Rheumatoid arthritis and outcomes in first and subsequent births based on data from a national birth registry. Acta Obstet Gynecol Scand 93(3):302, 2014 Wei S, Lai K, Yang Z, et al: Systemic lupus erythematosus and risk of preterm birth: a systematic review and meta-analysis of observational studies. Lupus 26: 563, 2017 Wong LF, Porter TF, Scott ]R: Immunotherapy for recurrent miscarriage.


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Obstentrics_Williams. Wong LF, Porter TF, Scott ]R: Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 1 O:CDOOO 112, 2014 Wu H, Birmingham OJ, Rovin B, et al: D-dimer level and the risk for thrombosis in systemic lupus erythematosus. Clint] Am Soc Nephrol 3:1628, 2008 Yang H, Liu H, Xu D, et al: Pregnancy-related systemic lupus erythematosus: clinical features, outcome and risk factors of disease flares-a case control study. PLoS One 9(8):el04375, 2014 Yang W, Tang H, Zhang Y, et al: Meta-analysis followed by replication identiies loci in or near CDKNIB, TET3, CD80, DRAMl, and ARID5B as associated with systemic lupus erythematosus in Asians. Am ] Hum Genet 92(1):41,t2013 Yasuda M, Takakuwa K, Tokunaga A, et al: Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet Gynecol 86:555, 1995


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Obstentrics_Williams. Yasuda M, Takakuwa K, Tokunaga A, et al: Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet Gynecol 86:555, 1995 Ye Y, van Zyl B, Varsani H, et al: Maternal microchimerism in muscle biopsies from children with juvenile dermatomyositis. Rheumatology (Oxford) 51(6):987,t2012 Zangari M, Lockwood CJ, Scher J, et al: Prothrombin activation fragment (F1.2) is increased in pregnant patients with antiphospholipid antibodies. Thromb Res 85:177, 1997 Zhao C, Zhao J, Huang Y, et al: New-onset systemic lupus erythematosus during pregnancy. Clin Rheumatol 32(6):815, 2013 Zuppa A, Riccardi R, Frezza A, et al: Neonatal lupus: follow-up in infants with anti SSA/Ro antibodies and review of the literature. Autoimmun Rev ,2017 CENTRAL NERVOUS SYSTEM IMAGING.. . . . . . . . . . .. 1156 HEADACHE ................................... 1157


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Obstentrics_Williams. CENTRAL NERVOUS SYSTEM IMAGING.. . . . . . . . . . .. 1156 HEADACHE ................................... 1157 SEIZURE DISORDERS.. . . . . . . . . . . . . . . . . . . . . . . . . .. 1158 CEREBROVASCULAR DISEASES . . . . . . . . . . . . . . . . .. 1160 DEMYELINATING OR DEGENERATIVE DISEASES ..... 1164 NEUROPATHIES ............................... 1166 SPINAL CORD INJURY.. . . . . . . . . . . . . . . . . . . . . . . . .. 1167 IDIOPATHIC INTRACRANIAL HYPERTENSION ....... 1168 MATERNAL VENTRICULAR SHUNTS ............... 1168 MATERNAL BRAIN DEATH ....................... 1168 Epilepsy appears to have no fect on pregnancy, though at the time of labour it may be mistaken or eclampsia by inexperienced observers. f the attacks are requent the patient should be put upon large doses of potassium bromide and treated just as at other times. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) Although several neurological diseases are relatively common in women of childbearing age, less than two pages were devoted to Diseases of the Nervous System in this textbook's first edition. In the past, some may have precluded pregnancy, however, few do so now. Most encountered during pregnancy are the same as for nonpregnant women, however a few neurological disorders may be seen more frequently in pregnant women. Examples are Bell palsy, specific types of strokes, and benign intracranial hypertension or pseudotumor cerebri. Neurovascular disorders are an important cause of maternal mortality and accounted for nearly 7 percent of maternal deaths in the United States from 2011 through 2013 (Creanga, 2017).


Obstentrics_Williams

Obstentrics_Williams. Many neurological disorders frequently precede pregnancy. fost women with chronic neurological disease who become pregnant will have successful outcomes, but some disorders have speciic risks. Conversely, other women will have newonset neurological symptoms during pregnancy, and these often must be distinguished from pregnancy complications. Psychiatric disorders can also manifest with cognitive and neuromuscular abnormalities and should be considered in the evaluation.


Obstentrics_Williams

Obstentrics_Williams. Computed tomography (CT) and magnetic resonance (MR) imaging assist in the diagnosis, classification, and management of many neurological and psychiatric disorders. As discussed in Chapter 46 (p. 907), these imaging methods can be used safely during pregnancy. CT scanning is often used when rapid diagnosis is necessary and is excellent for detecting recent hemorrhage. Because it does not use radiation, MR imaging is oten preferred and is particularly helpful to diagnose demyelinating diseases, arteriovenous malformations, congenital and developmental nervous system abnormalities, posterior fossa lesions, and spinal cord diseases. Whenever either test is done, the woman with advanced pregnancy should be positioned in a left lateral tilt with a wedge under one hip to prevent hypotension and to diminish aortic pulsations, which may degrade the image.


Obstentrics_Williams

Obstentrics_Williams. Cerebral angiography with contrast injection, usually via the femoral artery, is a valuable adjunct to the diagnosis and treatment of some cerebrovascular diseases. Fluoroscopy delivers more radiation but can be performed with abdominal shielding. Positron emission tomography (PET) and functional MR imaging (fMI) have not been evaluated for use in pregnant patients (Chiapparini, 2010).


Obstentrics_Williams

Obstentrics_Williams. In one national survey in the United States in 2012, 17 percent ofthose aged 18 to 44 years reported a severe headache or migraine within the past 3 months (Blackwell, 2014). Burch and coworkers (2015) reported that 24 percent ofnonpregnant women in this age group were similarly afected. Of pregnant women presenting with headache who received a neurological consultation, two thirds were due to primary disorders, with over 90 percent due to migraine. Of the other third due to secondary conditions, over half were due to hypertensive disorders (Robbins, 2015). Interestingly, Aegidius and associates (2009) reported a decline in the rate of all headache types during pregnancy in nulliparas, especially during the third trimester. The classification by the International Headache Society (20l3) is shown in Table


Obstentrics_Williams

Obstentrics_Williams. The classification by the International Headache Society (20l3) is shown in Table In pregnant women, primary headaches are more common than those stemming from secondary causes (Digre, 2013; Sperling, 2015). Migraine headaches are those most likely to be afected by the hormonal changes of pregnancy (Pavlovic, 2017). The incidences ofsevere headache causes in pregnancy are shown in Figure 60-1 . These are the most frequent cause of all headaches. Characteristic features include muscle tightness and mild-to-moderate pain in the back ofthe neck and head that can persist for hours. Neurological disturbances or nausea are typically absent. The pain usually responds to rest, massage, application of heat or ice, antiinlammatory medications, or mild tranquilizers. Hospital admission is seldom necessary.


Obstentrics_Williams

Obstentrics_Williams. The term migraine describes a periodic, sometimes incapacitating neurological disorder with episodic attacks ofsevere headache and autonomic nervous system dysfunction (Goadsby, 2015). The International Headache Society (20l3) classifies TABLE 60-1. Headache Classification Disorders of homeostasis Data from International Headache Society, 2013. Pituitary, 3.6% Infection, 2.1% Stroke, 2.8% Other headache, 6% (tension 3%) Migraine, 59% With aura, 37% Without aura, 24••• Chronic, 6% FIGURE 60-1 Incidences of headache causes in 140 consecutive pregnant women for whom in-hospital neurology consultation was requested. (Data from Robbins, 201o5.) three migraine types based on chronicity and on the presence or absence ofan aura. 1. Migrainewithoutaura-formerlytermedcommon migraineis characterized by a unilateral throbbing headache, nausea and vomiting, or photophobia. 2.


Obstentrics_Williams

Obstentrics_Williams. 1. Migrainewithoutaura-formerlytermedcommon migraineis characterized by a unilateral throbbing headache, nausea and vomiting, or photophobia. 2. Migraine with aura-formerly termed classic migraine-has similar symptoms preceded by premonitory neurological phenomena such as visual scotoma or hallucinations. A third of patients have this type of migraine, which sometimes can be averted ifmedication is taken at the first premonitory sign. 3. Chronic migraine is defined by a migraine headache occurring at least 15 days each month for more than 3 months.


Obstentrics_Williams

Obstentrics_Williams. 3. Chronic migraine is defined by a migraine headache occurring at least 15 days each month for more than 3 months. These are the most common reason for admission for headache evaluation and management. Migraines may begin in childhood, peak in adolescence, and tend to diminish in both frequency and severity with advancing years. According to Lipton and associates (2007), their annual prevalence is 17 percent in women and 6 percent in men. Another 5 percent ofwomen have probable migraine, that is, they have all criteria but one (Silberstein, 2007). Speciic polymorphisms have been identified that modulate the risk of migraines (Chen, 2015; Schiirks, 2010). hese headaches are especially common in young women and have been linked to hormone levels (Charles, 2017; Pavlovic, 2017). They are frequently encountered during pregnancy.


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Obstentrics_Williams. Sensory sensitivity with migraines is likely caused by monoaminergic sensory control systems in the brainstem and hypothalamus (Goadsby, 2015). his exact pathophysiology is uncertain, but they occur when neuronal dysfunction leads to decreased cortical blood How, activation ofvascular and meningeal nociceptors, and stimulation oftrigeminal sensory neurons (Brandes, 2007; D'Andrea, 2010). A predilection for the posterior circulation has been described (Kruit, 2004). Migrainesespecially those with aura in young women-are associated with increased risk for ischemic strokes. The risk is greater in those who smoke or use combination oral contraceptives.


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Obstentrics_Williams. The prevalence of migraine headaches in the first trimester is 2 percent (Chen, 1994). Most migraineurs have improvement during pregnancy (Kvisvik, 2011). Still, migraines-usually those with an aura-occasionally appear for the first time during pregnancy. Pregnant women with preexisting migraine symptoms may have other symptoms suggestive of a more serious disorder, and new neurological symptoms should prompt a complete evaluation (Detsky, 2006; Heaney, 2010).


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Obstentrics_Williams. Although conventional thinking has been that migraine headaches do not pose increased maternal or fetal risks, several recent studies have refuted this (Allais, 2010). In these, rates of preeclampsia, gestational hypertension, preterm birth, and other cardiovascular morbidities, including ischemic stroke, were increased (Grossman, 2017; Wabnitz, 2015). Bushnell and coworkers (2009) identiied an incidence of migraines during pregnancy of 185 per 100,000 deliveries. Of diagnoses associated in these gravid migraineurs, risks were signiicantly higher for stroke, 16-fold; myocardial infarction, ivefold; heart disease, twofold; venous thromboembolism, twofold; and preeclampsia/gestational hypertension, twofold.


Obstentrics_Williams

Obstentrics_Williams. Data are limited regarding non pharmacological management in pregnancy such as biofeedback techniques, acupuncture, and transcranial magnetic stimulation (Airola, 2010; Dodick, 2010). Efective medications include nonsteroidal antiinlammatory drugs (NSAIDs), and most migraine headaches respond to simple analgesics such as ibuprofen, acetaminophen, or Midrin, especially if given early. Severe migraines are vexing for the patient and her caregivers. Multitargeted drug therapy is necessary in most cases for migraine relief (Gonzalez-Hernandez, 2014). Headaches are treated aggressively with intravenous hydration and parenteral antiemetics and opioids for immediate pain relie. Although a 2-g infusion of magnesium sulfate has gained favor in the past few years, a metaanalysis reported no beneits (Choi, 2014). Ergotamine derivatives are potent vasoconstrictors and are avoided in pregnancy because of their uterotonic efects (Briggs, 2015).


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Obstentrics_Williams. Triptans are serotonin 5-HT I Bl20-receptor agonists that efectively relieve headaches by causing intracranial vasoconstriction (Contag, 2010). They also relieve nausea and vomiting and greatly reduce the need for analgesics. Triptans can be given as an oral tablet, injection, rectal suppository, or intranasal spray. hey are best used in combination with NSAIDs (Goadsby, 2015). The greatest experience is with sumatriptan (Imitrex), and although not studied extensively in pregnancy, it appears to be safe (Briggs, 2015; Nezvalova-Henriksen, 2010). However, in one follow-up study at 36 months of children exposed to triptans in pregnancy, Wood and colleagues (2016) found neurodevelopment diferences, including emotionality and activity problems.


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Obstentrics_Williams. Some women will beneit from peripheral nerve blocks, and Govindappagari and coworkers (2014) described their experiences with 13 pregnant women. For women with frequent migraine headaches, oral prophylactic therapy is warranted. Amitriptyline (Elavil), 10 to 175 mg daily; propranolol (Inderal), 40 to 120 mg daily; or metoprolol (Lopressor, Toprol), 25 to 100 mg daily, have been used with success (Contag, 2010; Goadsby, 2015; Lucas, 2009). This rare primary headache disorder is characterized by severe unilateral lancinating pain radiating to the face and orbit, lasting 15 to 180 minutes, and occurring with autonomic symptoms and agitation. Pregnancy does not afect symptom severity. Afected women should avoid tobacco and lcohol. Acute mnagement includes 100-percent oxygen therapy and sumatriptan given as a 6-mg dose subcutaneously (VanderPluym, 2016). If recurrent, prophylaxis is administered using a calcium-channel blocking agent.


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Obstentrics_Williams. The Centers for Disease Control and Prevention reported that the prevalence of epilepsy in adults in 2005 was 1.65 percentthus over 1 million American women of childbearing age are afected (Kobau, 2008). After headaches, seizures are the next most prevalent neurological condition encountered in pregnancy, and they complicate 1 in 200 births (Brodie, 1996; Yerby, 1994). Importantly, epilepsy accounted for 5 percent of maternal deaths in the United Kingdom for the 2011 to 2013 triennium (Knight, 2015).


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Obstentrics_Williams. A seizure is deined as a paroxysmal disorder of the central nervous system characterized by an abnormal neuronal discharge with or without loss of consciousness. Some identiiable causes of convulsive disorders in young adults include head trauma, alcohol-and other drug-induced withdrawals, cerebral infections, brain tumors, biochemical abnormalities, and arteriovenous malformations. A search for these is prudent with a new-onset seizure disorder in a pregnant woman. he diagnosis of idiopathic epilepsy is one of exclusion. Epilepsy encompasses diferent syndromes whose cardinal feature is a predisposition to recurrent unprovoked seizures. he International League Against Epilepsy Commission on Classiication and Terminology recently updated the following deinitions (Fisher, 2014).


Obstentrics_Williams

Obstentrics_Williams. These originate in one localized brain area and afect a correspondingly localized area of neurological unction. They are believed to result from trauma, abscess, tumor, or perinatal factors, although a speciic lesion is rarely demonstrated. Focal seizures without dyscognitive eatures start in one region of the body and progress toward other ipsilateral areas of the body, producing tonic and then clonic movements. Simple seizures can afect sensory unction or produce autonomic dysfunction or psychological changes. Cognitive function is not impaired, and recovery is rapid. Focal seizures with dyscognitive eatures are oten preceded by an aura and followed by impaired awareness manifested by sudden behavioral arrest or motionless stare. Involuntary movements such as picking motions or lip smacking are common.


Obstentrics_Williams

Obstentrics_Williams. These involve both brain hemispheres and may be preceded by an aura before an abrupt loss of consciousness. There is a strong hereditary component. In generalized tonic-clonic seizures, loss of consciousness is followed by tonic contraction of the muscles and rigid posturing, and then by clonic contractions of all extremities while the muscles gradually relax. Return to consciousness is gradual, and the patient may remain confused and disoriented for several hours. Absence seizures-also called petit mal seizures-are a form of generalized epilepsy that involve a brief loss of consciousness without muscle activity and are characterized by immediate recovery of consciousness and orientation.


Obstentrics_Williams

Obstentrics_Williams. Women with epilepsy ideally are counseled before pregnancy and relevant points are presented also in Chapter 8 (p. 148). Folic acid supplementation with 0.4 mg per day is begun at least 1 month before conception. The dose is increased to 4 mg when the woman taking antiepileptic medication becomes pregnant. hese medications are assessed and adjusted with a goal of mono therapy using the least teratogenic medication. If this is not feasible, then attempts are made to reduce the number of medications used and to use them at the lowest efective dose (Patel, 2016). Medication withdrawal should be considered if a woman is seizure free for 2 years or more.


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Obstentrics_Williams. The major pregnancy-related risks to women with epilepsy are fetal malformations and increased seizure rates. Seizure control is the main priority to avoid its attendant morbidity and mortality risks. Early studies described worsening seizure activity during pregnancy, however, this is less so now because of more efective drugs. Contemporary studies cite higher rates of seizure activity in only 20 to 30 percent of pregnant women (Mawer, 2010; Vajda, 2008). Women who are seizure free for at least 9 months before conception will likely remain so during pregnancy (Harden, 2009b).


Obstentrics_Williams

Obstentrics_Williams. Greater seizure frequency is often associated with decreased and thus subtherapeutic anticonvulsant serum levels, a lower seizure threshold, or both. An impressive number of pregnancyassociated alterations can result in sub therapeutic serum levels. These include nausea and vomiting, slower gastrointestinal motility, antacid use that diminishes drug absorption, pregnancy hypervolemia ofset by protein binding, induction of hepatic enzymes such as cytochrome oxidases, placental enzymes that metabolize drugs, and increased glomerular iltration that hastens drug clearance. Importantly, some women discontinue medication because of teratogenicity concerns. Finally, the seizure threshold can be afected by pregnancyrelated sleep deprivation and by hyperventilation and pain during labor.


Obstentrics_Williams

Obstentrics_Williams. Women with epilepsy have a small increased risk of pregnancy complications that include spontaneous abortion, hemorrhage, hypertensive disorders, preterm birth, fetal-growth restriction, and cesarean delivery (Harden, 2009b; Viale, 2015). Importantly, MacDonald (2015) also reports a tenfold higher maternal death rate, and, as mentioned earlier, epilepsy accounted for 5 percent of maternal deaths in the United Kingdom. Postpartum depression rates are also reportedly higher in epileptic women (Turner, 2009). Finally, children of epileptic mothers have a 10-percent risk of developing a seizure disorder. For years, it was diicult to separate efects of epilepsy from those of its therapy as the primary cause of fetal malforma tions. As discussed in Chapter 8 (p. 148), it is now believed that untreated epilepsy is not associated with an elevated fetal malformation rate (Thomas, 2008). That said, the fetus of an has an indisputably greater risk for congenital malformations.


Obstentrics_Williams

Obstentrics_Williams. Moreover, mono therapy is associated with a lower birth defect rate compared with multiagent therapy. hus, if necessary, increasing monotherapy dosage is at least initially preferable to adding another agent (Buhimschi, 2009). Specific drugs, when given alone, increase the malformation rate (Chap. 12, p. 240). Some of these are listed in Table 60-2. Phenytoin and phenobarbital increase the major malformation rate two-to threefold above baseline (Perucca, 2005; Thomas, 2008). Valproate is a particularly potent teratogen, which has a dose-dependent efect and raises the malformation risk four-to eightfold (Eadie, 2008; lein, 2014; Wyszynski, 2005). Val proate is also associated with lower cognitive performance (Kas radze, 2017). In general, with poly therapy, the risk rises with each drug added. A metaanalysis of 31 studies found lamotrig ine and levetiracetam to carry the lowest risk of malformations (Weston, 2016).


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Obstentrics_Williams. The American Academy of Neurology and the American Epilepsy Society have guidelines regarding treatment in pregnant women (Harden, 2009a-c). The major goal is seizure prevention. To accomplish this, treatment for nausea and vomiting is provided, seizure-provoking stimuli are avoided, and medication compliance is emphasized. The fewest necessary anticonvulsants are given at the lowest dosage efective for seizure control. Although some providers routinely monitor serum drug levels, these concentrations may be unreliable because of altered protein binding. Free or unbound drug levels, although perhaps more accurate, are not widely available. Importantly, there is no evidence that such monitoring improves seizure control (Adab, 2006). For these reasons, drug levels may be most informative if measured following seizures or if noncompliance is suspected.


Obstentrics_Williams

Obstentrics_Williams. For women taking anticonvulsant drugs, a targeted so nographic examination at midpregnancy is recommended by some to search for anomalies. Testing to assess fetal well-being is generally not indicated for women with uncomplicated epilepsy. For women desiring to breastfeed, data regarding the safety of the various anticonvulsant medications are limited. That said, no obvious deleterious efects, such as long-term cognitive issues, have been reported (Briggs, 2015; Harden, 2009c). Of birth control methods, oral contraceptive pill failure rates are higher with some of the anticonvulsant agents, especially lamotrigine. Thus, other more reliable methods should be considered (Chap. 38, p. 680). TABLE 60-2. Teratogenic Effects of Common Anticonvulsant Medications Neural-tube defects, clefts, cardiac anomalies; associated developmental delay Fetal hydantoin syndrome-craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac anomalies, clefts


Obstentrics_Williams

Obstentrics_Williams. Fetal hydantoin syndrome-craniofacial anomalies, fingernail hypoplasia, growth deficiency, developmental delay, cardiac anomalies, clefts Fetal hydantoin syndrome, as above; spina bifida Clefts, cardiac anomalies, urinary tract malformations aRisk categories from Briggs, 2015; Food and Drug Administration, 2011; Harden, 2009b; Holmes, 2008; Hunt, 2008.


Obstentrics_Williams

Obstentrics_Williams. Clefts, cardiac anomalies, urinary tract malformations aRisk categories from Briggs, 2015; Food and Drug Administration, 2011; Harden, 2009b; Holmes, 2008; Hunt, 2008. Abnormalities of the cerebrovascular circulation include strokes-both ischemic and hemorrhagic, as well as anatomical anomalies, such as arteriovenous malformations and aneurysms. Cerebral ischemia is caused by reduction in blood low that lasts longer than several seconds. Early, neurological symptoms may manifest. Ater a few minutes, however, infarction often follows. Hemorrhagic stroke is caused by bleeding directly into or around the brain. It produces symptoms by its mass efect, by toxic efects of blood, or by increasing intracranial pressure. Of strokes in pregnant women, roughly half are ischemic and the other half hemorrhagic (Zofkie, 2018).


Obstentrics_Williams

Obstentrics_Williams. he current obesity endemic in this country, along with concomitant increases in rates of heart disease, hypertension, and diabetes, has increased the prevalence of strokes (Centers for Disease Control and Prevention, 2012). Women have higher lifetime risk of stroke than men and greater associated mortality rates (Martinez-Sanchez, 2011; Roger, 2012). Moreover, pregnancy increases the immediate and lifetime risk of both ischemic and hemorrhagic stroke (Jamieson, 2010; lung, 2010).


Obstentrics_Williams

Obstentrics_Williams. Stroke is relatively uncommon in pregnant women, occurring in 10 to 40 per 100,000 births, but it contributes disparately to maternal mortality rates (Lefert, 2016; Miller, 20 16; Yoshida, 2017). he incidence is rising as measured by pregnancy-related hospitalizations for stroke (Callaghan, 2008; Kukiina, 2011). Importantly, most are associated with hypertensive disorders or heart disease. Of the pregnancy-related mortality rate in the United States, 6.6 percent is due to cerebrovascular accidents, and 7.4 percent is associated with preeclampsia (Creanga, 2017). Of maternal deaths after 42 days postpartum, 9.8 percent were attributable to cerebrovascular accidents.


Obstentrics_Williams

Obstentrics_Williams. Most strokes in pregnancy manifest either during labor and delivery or in the puerperium. In a study of 2850 pregnancyrelated strokes, approximately 10 percent developed antepartum, 40 percent intrapartum, and almost 50 percent postpartum (James, 2005). In contrast, Lefert (2016) reports a timing of 45 percent antepartum, 3 percent intrapartum, and 53 percent postpartum in 145 women. Several risk factorsunrelated and related to pregnancy-have been reported from studies that included more than 10 million pregnancies. These include age; migraines, hypertension, obesity, and diabetes; cardiac disorders such as endocarditis, valvular prostheses, and patent foramen ovale; and smoking. hose related to pregnancy include hypertensive disorders, gestational diabetes, obstetrical hemorrhage, and cesarean delivery. By ar, the most common risk actors are pregnancy-associated hypertensive disorders. A third of strokes are associated with gestational hypertension, and hypertensive women compared


Obstentrics_Williams

Obstentrics_Williams. cesarean delivery. By ar, the most common risk actors are pregnancy-associated hypertensive disorders. A third of strokes are associated with gestational hypertension, and hypertensive women compared with normotensive counterparts have a three-to eightfold greater risk of stroke (Scott, 2012; Wang, 2011). Women with preeclampsia undergoing general anesthesia may be at higher risk of stroke compared with those given neuraxial anesthesia (Huang, 2010). Another risk factor for peripartum stroke is cesarean delivery, which raises the risk 1.5-fold compared with vaginal delivery (Lin, 2008).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy-induced efects on cerebrovascular hemodynamics include enhanced autoregulation that maintains blood low despite changes in systemic blood pressure (van Teen, 2016). Although cerebral blood low decreases by 20 percent from midpregnancy until term, it increases signiicantly with gestational hypertension (Zeeman, 2003, 2004b). Such hyperperfusion at least intuitively would be dangerous for women with certain vascular anomalies. FIGURE 60-2 Illustrations of a brain showing various types of strokes seen in pregnancy: (1) subcortical infarction (preeclampsia), (2) hypertensive hemorrhage/ (3) aneurysm, (4) embolism or thrombosis in middle cerebral artery, (5) arteriovenous malformation, and (6) cortical vein thrombosis. Cocaine, amphetamines From Smith, 2015; Yager, 2012. Neurological Disorders 1161


Obstentrics_Williams

Obstentrics_Williams. Cocaine, amphetamines From Smith, 2015; Yager, 2012. Neurological Disorders 1161 Acute occlusion or embolization of an intracranial blood vessel causes cerebral ischemia, which may result in death of brain tissue (Fig. 60-2). he more common associated conditions and etiologies of ischemic stroke are shown in Table 60-3. A transient ischemic attack (TIA) is caused by reversible ischemia, and symptoms usually last less than 24 hours. Approximately 10 percent of these patients have a stroke by 1 year (Amarenco, 2016). Patients with a stroke usually have a sudden onset of severe headache, hemiplegia or other neurological deicits, or occasionally seizures. In contrast, focal neurological symptoms accompanied by an aura usually signiy a irst-episode migraine (Liberman, 2008).


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Obstentrics_Williams. Evaluation of an ischemic stroke includes echocardiography and cranial imaging with CT, MR, or angiography. Serum lipids are measured with the caveat that their values are distorted by normal pregnancy (Appendix, p. 1259). Tests to detect antiphospholipid antibodies and lupus anticoagulant are performed. These underlie up to a third of ischemic strokes in otherwise healthy young women (Chap. 59, p. 1143). Also, sickle-cell syndromes are evaluated when indicated (Buonanno, 2016). With a thorough evaluation, most causes of embolism can be identified, although treatment is not always available. Some of these include cardiacassociated embolism, vasculitis, or vasculopathy such as Moyamoya disease (Ishimori, 2006; Miyakoshi, 2009; Simolke, 1991). Outcomes of embolic strokes were reported to be favorable and similar to those of nonpregnant women (Lefert, 2016). hrombolysis for ischemic stroke during pregnancy has been reported (Tversky, 2016).


Obstentrics_Williams

Obstentrics_Williams. In reproductive-age women, a significant proportion of pregnancyrelated ischemic strokes are caused by gestational hypertension and preeclampsia (Jeng, 2004; Miller, 2016). s shown in Figure 60-2, areas of subcortical perivascular edema and petechial hemorrhage may progress to cerebral infarction (Aukes, 2007, 2009; Zeeman, 2004a). Although these are usually clinically manifest by an eclamptic convulsion, a few women will sufer a symptomatic stroke from a larger cortical infarction (Chap. 40, p. 734). Other conditions with findings similar to preeclampsia include thrombotic microangiopathies (Chap. 56, p. 1088) and the reversible cerebral vasoconstriction syndrome (Chap. 40, p. 744). The latter, also termed pospartum angiopathy, can cause extensive cerebral edema with necrosis and widespread infarction with areas of hemorrhage (Edlow, 2013; Katz, 2014; Miller, 2016).


Obstentrics_Williams

Obstentrics_Williams. These strokes usually involve the middle cerebral artery (see Fig. 60-2). he diagnosis can be made with conidence only after thrombosis and hemorrhage have been excluded and is more certain if an embolic source is identified. Hemorrhage may be more diicult to exclude because embolization and thrombosis are both followed by hemorrhagic infarction. Paradoxical embolism is an uncommon cause, even considering that more than a fourth of adults have a patent foramen ovale through which right-sided venous thromboemboli are deported (Scott, 2012). Foraminal closure may not improve outcomes in these patients, however, this procedure has been performed during pregnancy (Dark, 2011). Assorted cardioembolic causes of stroke include arrhythmias-especially atrial ibrillation, valvular lesions, mitral valve prolapse, mural thrombus, infective endocarditis, and peripartum cardiomyopathy.


Obstentrics_Williams

Obstentrics_Williams. Management of embolic stroke in pregnancy consists of supportive measures and antiplatelet therapy. Thrombolytic therapy and anticoagulation in pregnancy are controversial issues (U,r2012). Most thrombotic strokes afect older individuals and are caused by atherosclerosis, especially of the internal carotid artery. Many are preceded by one or more TIAs. hrombolytic therapy with a recombinant tissue plasminogen activator (rt-PAj is recommended. Alteplase is one of these and given within the irst 3-hour window if there is measurable neurological deficit and if neuroimaging has excluded hemorrhage. his recombinant enzyme can be used in pregnancy. A principal risk is hemorrhagic transformation of an ischemic stroke in 3 to 5 percent of treated patients (Smith, 2015; van der Worp, 2007).


Obstentrics_Williams

Obstentrics_Williams. In one study in the United States, 7 percent of cerebral venous thromboses were associated with pregnancy (Wasay, 2008). But, in the Nationwide Inpatient Sample of more than 8 million deliveries, James and associates (2005) reported that venous thrombosis caused only 2 percent of pregnancy-related strokes (Saposnik, 2011). here are numerous predisposing causes, and for gravidas, late pregnancy and the puerperium are times of greatest risk. Thrombosis of the lateral or superior sagittal venous sinus usually occurs in the puerperium and often in association with preeclampsia, sepsis, or thrombophilia (see Fig. 60-2). It is more common in patients with inherited thrombophilias or antiphospholipid antibodies (Chaps. 52, p. 1006 and 59, p. 1143). Headache is the most frequent presenting symptom, neurological deficits are common, and up to a third of patients have convulsions (Wasay, 2008). he diagnosis is made using MR venography (Saposnik, 2011).


Obstentrics_Williams

Obstentrics_Williams. Management includes anticonvulsants for seizures, and although heparinization is recommended by most, its eicacy is controversial (Saposnik, 2011; Smith, 2015). Antimicrobials are given if there is septic thrombophlebitis, and fibrinolytic therapy is reserved for those women failing systemic anticoagulation. The acute prognosis for venous thrombosis in pregnant women is better than in nonpregnant subjects, and mortality rates are less than 10 percent (McCaulley, 2011). In women with a prior cerebral venous thrombosis, one systematic review found only one recurrence in 217 pregnancies and five noncerebral venous thrombotic events in 186 pregnancies (Aguiar de Sousa, 2016). In a study of 52 women on prophylactic anticoagulation with prior cerebral venous thrombosis, there were no cases of recurrent thrombosis or bleeding, however 24 percent had late obstetrical complications (Martinelli, 2016). Recurrence Risk of Ischemic Stroke


Obstentrics_Williams

Obstentrics_Williams. Recurrence Risk of Ischemic Stroke Women with prior ischemic stroke have a low risk for recurrence during a subsequent pregnancy unless a specific, persistent cause is identiied. During a 5-year follow-up of 373 women with arterial ischemic strokes, there were 187 pregnancies in 125 women. Thirteen women had a recurrent ischemic stroke, and of these, only two were associated with pregnancy. The authors concluded that the risk of stroke recurrence is low and a previous ischemic stroke is not a contraindication to pregnancy (Lamy, 2000). In one study of 1770 nonpregnant women with anti phospholipid-related ischemic stroke, investigators reported no diference in the recurrence risk as long as preventative treatment was given with warfarin or aspirin (Levine, 2004).


Obstentrics_Williams

Obstentrics_Williams. Currently, no irm guidelines define prophylaxis in pregnant women with a stroke history (Helms, 2009). The American Heart Association stresses the importance of controlling risk factors such as hypertension and diabetes (Furie, 201l). Women with anti phospholipid syndrome or certain cardiac conditions should be considered for prophylactic anticoagulation as discussed in Chapter 49 (p. 954) and 52 (p. 1008). The two distinct categories of spontaneous intracranial bleeding are intracerebral and subarachnoid hemorrhage. The symptoms of a hemorrhagic stroke are similar to those of an ischemic stroke, and their diferentiation is only possible with CT or MR imaging (Morgenstern, 2010; Smith, 2015). Bleeding into the brain parenchyma most often is caused by spontaneous rupture of small vessels previously damaged by chronic hypertension (see Fig. 60-2). Thus, pregnancy-associated hemorrhagic strokes such as the one shown in Figure 60-3 are


Obstentrics_Williams

Obstentrics_Williams. FIGURE 60-3 A 37-year-old gravida with intrapartum eclampsia at term. A noncontrast computed tomography axial head image demonstrates a large intraparenchymal hemorrhage. oten associated with chronic hypertension and superimposed preeclampsia (Cunningham, 2005; Martin, 2005). Because of its location, this type of hemorrhage has much higher morbidity and mortality rates than does subarachnoid hemorrhage (Smith, 2015). Pressure-induced rupture causes bleeding into the putamen, thalamus, adjacent white matter, pons, and cerebellum. In the 28 women described by Martin and associates (2005), half died and most survivors had permanent disabilities. his cautions for the importance of proper management for gestational hypertension-especially systolic hypertension-to prevent cerebrovascular pathology (Chap. 40, p. 738).


Obstentrics_Williams

Obstentrics_Williams. In a study of 639 cases of pregnancy-related subarachnoid hemorrhage from the Nationwide Inpatient Sample, the incidence was 5.8 per 100,000 pregnancies, with half occurring postpartum (Bateman, 2012). A remarkably similar incidence was reported in Japanese women (Yoshida, 2017). hese bleeds are more likely caused by an underlying cerebrovascular malformation in an otherwise norml patient (see Fig. 60-2). Ruptured saccular or "berry" aneurysms cause 80 percent of all subarachnoid hemorrhages. The remaining cases are caused by a ruptured arteriovenous malformation, coagulopathy, angiopathy, venous thrombosis, infection, drug abuse, tumors, or trauma. Such cases are uncommon, and a ruptured aneurysm or angioma or bleeding from a vascular mlformation has an incidence of 1 in 75,000 pregnancies. Although this frequency is not diferent from that in the general population, the mortality rate during pregnancy is reported to be as high as 35 percent (Yoshida, 2017).


Obstentrics_Williams

Obstentrics_Williams. Intracranial Aneurysm. Approximately 1 to 2 percent of adults have this lesion (Lawton, 2017). Fortunately, only a small percentage rupture. he rate approximates 0.1 percent for aneurysms <10 mm and 1 percent for those >10 mm (Smith, 2015). Most aneurysms identified during pregnancy arise from the circle of Willis, and in 20 percent of case, there are multiple lesions. Pregnancy does not raise the risk for aneurysmal rupture. However, because of their high prevalence, they are more likely to cause subarachnoid bleeding than other etiologies (Hirsch, 2009; Tiel Groenestege, 2009). A systematic review of 44 women with 50 aneurysms in pregnancy reported that 72 percent ruptured during pregnancy, and 78 percent of these did so during the third trimester (Barbarite, 2016). his proclivity for rupture late in pregnancy was also reported by Yoshida and colleagues (2017).


Obstentrics_Williams

Obstentrics_Williams. The cardinal symptom of a subarachnoid hemorrhage from an aneurysm rupture is sudden severe headache that is accompanied by visual changes, cranial nerve abnormalities, focal neurological deicits, and altered consciousness. Patients typically have signs of meningeal irritation, nausea and vomiting, tachycardia, transient hypertension, low-grade fever, leukocytosis, and proteinuria. Prompt diagnosis and treatment may prevent potentially lethal complications. The American Heart Association recommends noncontrast cranial CT imaging as the irst diagnostic test, although MR imaging may be superior (Connolly, 2012; Smith, 2015).


Obstentrics_Williams

Obstentrics_Williams. Treatment of subarachnoid hemorrhage includes bed rest, analgesia, and sedation, with neurological monitoring and strict blood pressure control. Repair of a potentially accessible aneurysm during pregnancy depends in part on the risk of recurrent hem orrhage versus the surgical risks. At least in nonpregnant patients, the risk of subsequent bleeding with conservative treatment is 20 to 30 percent for the irst month and then 3 percent per year. The risk of rebleeding is highest within the irst 24 hours, and recurrent hemorrhage leads to death in 70 percent.


Obstentrics_Williams

Obstentrics_Williams. The risk of rebleeding is highest within the irst 24 hours, and recurrent hemorrhage leads to death in 70 percent. Early repair after the sentinel hemorrhage is done by surgi cal clipping of the aneurysm. Also, an endovascular coil can be placed using luoroscopic angiography, while attempting to limit fetal radiation exposure. Barbarite and colleagues (2016) report lower complication rates with coil embolization than clipping. For unruptured aneurysms, surgical management resulted in a third fewer complications than no treatment. For gravidas remote from term, repair without hypotensive anes thesia seems optimal. For women near term, cesarean delivery followed by aneurysm repair is a consideration, and we have successfully done this in several cases.


Obstentrics_Williams

Obstentrics_Williams. For aneurysms repaired either before or during pregnancy, mal repair. Problems arise in defining "remote," and although some recommend 2 months, the time for complete healing is unknown. For women who survive subarachnoid hemor rhage, but in whom surgical repair is not done, we agree with another way, we favor cesarean delivery.


Obstentrics_Williams

Obstentrics_Williams. Arteriovenous Malformations. hese are congenital focal abnormal conglomerations of dilated arteries and veins with sub arteriolar disorganization (see Fig. 60-2). hey lack capillaries and have resultant arteriovenous shunting. Although unclear, the risk of bleeding may rise with gestational age. When arteriovenous malformations (A VMs) bleed, half do so into the subarachnoid space, whereas half are intraparenchymal with subarachnoid extension (Smith, 2015). hey are uncommon and are estimated to occur in 0.01 percent of the general population. Of 65 identiied cases of A VM in pregnancy, 83 percent ruptured during pregnancy or postpartum, and more than 80 percent of these ruptured in the second or third trimester. Hemorrhage upon presentation is associated with poor maternal outcome (Lu, 2016).


Obstentrics_Williams

Obstentrics_Williams. Bleeding does not appear to be more likely during pregnancy. lthough these malformations are correspondingly rare during pregnancy, A VM bleeding accounted for 17 percent of hemorrhagic strokes in one study (Yoshida, 2017). At Parkland Hospital in a 33-year period during which there were about 466,000 births, 57 women had a CVA, and five of these strokes were due to a bleeding A M (Simolkie, 1991; Zokie, 2018).


Obstentrics_Williams

Obstentrics_Williams. Treatment of AVMs in nonpregnant patients is largely individualized. No consensus guides whether all accessible lesions should be resected. Factors include AVM symptoms; its anatomy and size; presence of an associated aneurysm, which is found in up to 60 percent of cases; and especially, prior A VM bleeding. Mter hemorrhage, the risk of recurrent bleeding in unrepaired lesions is 6 to 20 percent within the first year, and 2 to 4 percent per year thereater (Friedlander, 2007; Smith, 2015). The mortality rate with a bleeding AVM is 10 to 20 percent. In pregnancy, the decision to operate is usually based on neurosurgical considerations, and Friedlander (2007) recommends strong consideration for treatment if bleeding occurs. Because of the high risk of recurrent hemorrhage from an unresected or inoperable lesion, we favor cesarean delivery.


Obstentrics_Williams

Obstentrics_Williams. The demyelinating diseases are neurological disorders characterized by immune-mediated focal or patchy destruction of myelin sheaths accompanied by an inflammatory response. The degenerative diseases are multifactorial and are characterized by progressive neuronal death. In the United States, multiple sclerosis (MS) is second only to trauma as a cause of neurological disability in middle adulthood (Hauser, 2015b). The disease afects women twice as often as men, and it usually begins in the 20s and 30s. he familial recurrence rate of MS is 15 percent, and the incidence in ofspring is increased IS-fold. Studying California deliveries, Fong and colleagues (2018) reported that 0.03 percent of deliveries were complicated by MS between 2001 and 2009.


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Obstentrics_Williams. The demyelinating characteristic of this disorder results predominately from T cell-mediated autoimmune destruction of oligodendrocytes that synthesize myelin. here is a genetic susceptibility and likely an environmental trigger such as exposure to certain bacteria and viruses. Of these, Chlamydophila pneumoniae, human herpesvirus 6, or Epstein-Barr virus are implicated (Frohman, 2006; Goodin, 2009). There are four clinical types of MS: 1. Relapsing-remitting MS accounts for initial presentation in 85 percent of afected individuals. With it, unpredictable recurrent episodes of focal or multifocal neurological dysfunction usually are followed by full recovery. Over time, however, relapses lead to persistent deficits. 2. Secondary progressive MS disease is relapsing-remitting disease that begins to pursue a progressive downhill course after each relapse. All patients likely develop this type eventually. 3. Primary progressive MS accounts for 15 percent of cases.


Obstentrics_Williams

Obstentrics_Williams. 3. Primary progressive MS accounts for 15 percent of cases. With it, disability gradually progresses from the time of initial diagnosis. 4. Progressive-relapsing MS refers to primary progressive vIS with apparent relapses. Classic findings of MS include sensory loss, visual symptoms from optic neuritis, weakness, paresthesias, and a host of other neurological symptoms. Almost 75 percent of women with isolated optic neuritis develop MS within 15 years. Clinical diagnosis is confirmed by MR imaging and cerebrospinal fluid analysis. In greater than 95 percent of cases, MR imaging shows characteristic multifocal white matter plaques that represent discrete areas of demyelination (Fig. 60-4). Their appearance and extent are less helpful for predicting treatment response. Similarly, identification of serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein is not predictive of recurrent disease activity (Kuhle, 2007). Efects of Pregnancy


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Obstentrics_Williams. Efects of Pregnancy The PRegnancy In Multiple Sclerosis-PlMS-study was a European prospective multicenter study in which 254 pregnancies were described (Vukusic, 2006). Relapse risk was reduced 70 percent during pregnancy, but with a significantly greater relapse rate postpartum. This may be related to higher pregnancy-induced numbers of T-helper lymphocytes and an increased T2/Tl ratio (Airas, 2008). In a metaanalysis of women with more than 1200 pregnancies complicated by lvIS, their relapse rate was 0.4 per year before pregnancy; 0.26 per year during pregnancy; and this increased to 0.7 per year


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Obstentrics_Williams. FIGURE 60-4 Magnetic resonance cranial images from a woman with mUltiple sclerosis. A.T2-weighted axial image shows bright signal abnormalities in white matter, typical for multiple sclerosis. B. Sagittal T2-FLAIR image shows hyperintense areas within the corpus callosum that are representative of demyelination in multiple sclerosis. (Reproduced with permission from Hauser SL, Goodin DS: Multiple Sclerosis and other demyelinating diseases. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. McGraw-Hili, New York, 201o5b.) after delivery (Finkelsztejn, 2011). Bove and associates (2014) reached similar conclusions after a systematic review. Factors associated with postpartum relapse include a high relapse rate before pregnancy, relapses during pregnancy, and a high MS disability score (Portaccio, 2014; Vukusic, 2006). Breastfeeding has no apparent efect on postpartum relapses (Hellwig, 2015; Portaccio, 2011).


Obstentrics_Williams

Obstentrics_Williams. Efects of Multiple Sclerosis on Pregnancy With uncomplicated disease, there are usually no adverse efects on pregnancy ourcome (Bove, 2014). Some women may become fatigued more easily, those with bladder dysfunction are predisposed to urinary infection, and women with spinal lesions at or above T 6 are at risk for autonomic dysrelexia. In one study of 449 pregnancies in afected women, the labor induction rate was higher, and second-stage labor was longer (Dahl, 2006). he greater induction rate and elective operations contributed to the overall higher cesarean delivery rate. In an analysis of 649 afected women, the mean birthweight was lower but the perinatal mortality rate was similar compared with that of controls (Dahl, 2005). Other studies have corroborated that MS does not significantly afect obstetrical and neonatal outcomes (Finkelsztejn, 2011; Fong, 2018).


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Obstentrics_Williams. Goals are to arrest acute or initial attacks, employ diseasemodiying agents, and provide symptomatic relief. Some treatments may need to be modiied during pregnancy. Acute or initial attacks are treated with high-dose intravenous methylprednisolone-500 to 1000 mg daily for 3 to 5 days, followed by oral prednisone for 2 weeks. Plasma exchange may be considered. Symptomatic relief can be provided by analgesics; carbamazepine, phenytoin, or amitriptyline for neurogenic pain; baclofen for spasticity; :Tadrenergic blockade for bladder neck relaxation; and cholinergic and anticholinergic drugs to stimulate or inhibit bladder contractions.


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Obstentrics_Williams. Several disease-modiying therapies can be used for relapsing MS or for exacerbations. Examples include in terferons 31 a (Rebi), 31 b (Betaseron), and glatiramer acetate (Copaxone), which lower relapse rates by a third (Rudick, 201l). Data concerning safety in pregnancy are limited but overall reassuring (Amato, 2010; Salminen, 2010). In clinical trials, natalizumab (Tysabri), an :4-integrin antagonist, especially when combined with interferon 31a, significantly reduced MS clinical relapse rates (Polman, 2006; Rudick, 2006). In a review of 35 pregnancies, irst-trimester drug exposure did not worsen outcomes (Hellwig, 2011). If these drugs are used in pregnancy, the neonate should be monitored for thrombocytopenia and anemia (Alroughani, 2016).


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Obstentrics_Williams. Fetal exposure in 89 pregnancies to ingolimod (Gilenya), another immune-modulating drug, was associated with six fetal malformations and nine spontaneous losses. Because of this and associated animal teratogenicity, its use in pregnancy is not recommended. Due to its prolonged persistence, contraception is recommended for 2 months ater drug cessation (Alroughani, 2016; Karlsson, 2014). Prevention of relapses postpartum is aforded by treatment with intravenous immunoglobulin (I I G) , given in a dose of 0.4 g/kg daily for 5 days during weeks 1, 6, and 12 (Argyriou, 2008).


Obstentrics_Williams

Obstentrics_Williams. Prevention of relapses postpartum is aforded by treatment with intravenous immunoglobulin (I I G) , given in a dose of 0.4 g/kg daily for 5 days during weeks 1, 6, and 12 (Argyriou, 2008). his adult-onset neurodegenerative disease stems from an autosomal dominant expanded CAG trinucleotide repeat within the Huntington gene on chromosome 4. It is characterized by choreoathetotic movements, progressive dementia, and psychiatric manifestations. Because the mean age of onset is 40 years, Huntington disease rarely complicates pregnancy. Prenatal diagnosis is discussed in Chapter 14 (p. 288). Prenatal screening is controversial, and because this usually is a late-onset adult disease, extensive counseling is important (Schulman, 2015).


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Obstentrics_Williams. approximately 1 in 7500 persons. It is more common in women, and its incidence peaks in their 20s and 30s. he eti ology is unknown, but genetic factors likely playra role. Most patients demonstrate antibodies to the acetylcholine receptor, although 10 to 20 percent are seronegative (Drachman, 2015). he latter often have antibodies to muscle-specific tyrosine kinase (MuSK), which regulates assembly of the acetylcholine receptor subunits at the neuromuscular junction (Pal, 201l).


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Obstentrics_Williams. he latter often have antibodies to muscle-specific tyrosine kinase (MuSK), which regulates assembly of the acetylcholine receptor subunits at the neuromuscular junction (Pal, 201l). Cardinal features of myasthenia are weakness and easy fatigability of facial, oropharyngeal, extraocular, and limb muscles. Deep tendon reflexes are preserved. Cranial muscles are involved early and disparately, and diplopia and ptosis are common. Facial muscle weakness causes diiculty in smiling, chewing, and speaking. In 85 percent of patients, the weakness becomes generalized. Other autoimmune diseases may coexist, and hypothyroidism should be excluded. The clinical course is marked by exacerbations and remissions, especially when it first becomes clinically apparent. Remissions are not always complete and are seldom permanent. Systemic diseases, concurrent infections, and even emotional upset may precipitate exacerbations, of which there are three types: 1.


Obstentrics_Williams

Obstentrics_Williams. Myasthenic crises-characterized by severe muscle weakness, inability to swallow, and respiratory muscle paralysis. 2. Rtactory crises-characterized by the same symptoms but unresponsive to the usual therapy. 3. Cholinergic crisesexcessive cholinergic medication leads to nausea, vomiting, muscle weakness, abdominal pain, and diarrhea. All three of these can be life threatening, but a refractory crisis is a medical emergency. Those with bulbar myasthenia are at particular risk because they may be unable to swallow or even ask for help.


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Obstentrics_Williams. Myasthenia is manageable but not curable. Oral pyridostigmine is the first-line treatment. Thymectomy is recommended but postponed until ater pregnancy (Sanders, 2016). Anticholinesterase medications improve symptoms by impeding acetylcholine degradation but seldom produce normal muscle function. Ironically, overdose is manifest by increased weness-cholinergic crisisthat may be diicult to diferentiate from myasthenic symptoms. Most of those refractory to anticholinesterase therapy respond to immunosuppressive therapy with glucocorticoids, azathioprine, or cyclosporine in pregnancy. When short-term, rapid clinical improvement is needed-such as for a surgical procedure or a myasthenic crisis-high-dose IVIG or plasma exchange is usually efective (Barth, 2011; Cortese, 2011; Sanders, 2016).


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Obstentrics_Williams. Because the greatest period of risk is within the first year following diagnosis, postponing pregnancy until there is sustained improvement is reasonable. Antepartum management of myasthenia includes close observation with liberal rest and prompt treatment of infections (Heaney, 2010; Kalidindi, 2007). Women in remission who become pregnant while taking corticosteroids or azathioprine should continue these. hymectomy has been successfully performed during pregnancy in refractory cases (Ip, 1986). Acute onset of myasthenia or its exacerbation demands prompt hospitalization and supportive care. Plasmapheresis and high-dose IVIG are options for emergency situations (Drachman, 2015).


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Obstentrics_Williams. Although pregnancy does not appear to afect the overall course of myasthenia, fatigue common to most pregnancies may be exacerbated, and the expanding uterus may compromise respiration. Maternal hypotension or hypovolemia are ideally avoided as they can trigger crises. he clinical course of myasthenia during pregnancy is unpredictable, and frequent hospitalizations are the norm. Up to a third of women have worsening myasthenia during pregnancy, and exacerbations occur equally in all three trimesters (Djelmis, 2002; Podciechowski, 2005). In women with stable disease, most will remain stable throughout pregnancy but likely worsen in the first few months postpartum (Sanders, 2016).


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Obstentrics_Williams. Myasthenia gravis has no significant adverse efects on pregnancy outcomes (Wen, 2009). Preeclampsia is a concern because magnesium sulfate may precipitate a severe myasthenic crisis (Hamaoui, 2009; Heaney, 2010). Although phenytoin use is also problematic in this regard, its adverse efects are less troublesome. hus, many choose it for neuroprophylaxis in women with severe preeclampsia.


Obstentrics_Williams

Obstentrics_Williams. Because smooth muscle is unafected, most women have normal labor. Oxytocin is given for the usual indications, and cesarean delivery is reserved for obstetrical indications. Narcotics may cause respiratory depression, and close observation and respiratory support are essential during labor and delivery. Curariform drugs are avoided-examples include magnesium sulfate discussed above, muscle relaxants used with general anesthesia, and aminoglycosides. Neuraxial analgesia is accomplished with amide-type local agents. Regional analgesia is preferred unless there is signiicant bulbar involvement or respiratory compromise (Almeida, 2010; Blichfeldt-Lauridsen, 2012). During second-stage labor, some women may have impaired voluntary expulsive eforts that may warrant operative vaginal delivery.


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Obstentrics_Williams. As discussed above, 80 percent of mothers with myasthenia gravis have anti-acetylcholine-receptor immunoglobulin G (IgG) antibodies. These and anti-MuSK antibodies cross transplacentally, and the fetus can be afected. Poor fetal swallowing may yield hydramnios (Heaney, 2010). Similarly, 10 to 20 percent of neonates manifest myasthenia symptoms (Jovandaric, 2016). Transient symptoms usually include a feeble cry, poor suckling, and respiratory distress. Symptoms usually respond to cholinesterase inhibitors and resolve within a few weeks as maternal IgG antibodies clear. Peripheral neuropathy is a general term used to describe disorders of peripheral nerve(s) from various sources. Poyneuropathies can be axonal or demyelinating as well as acute, subacute, or chronic (Amato, 2015). hese are often associated with systemic diseases such as diabetes, with drug or environmental toxin exposure, or with genetic disease.


Obstentrics_Williams

Obstentrics_Williams. Mononeuropathies are relatively common in pregnancy and signiY focal involvement of a single nerve trunk. These imply local causation such as trauma, compression, or entrapment. Traumatic pudendal, obturator, femoral, and common fibular mononeuropathies are usually caused by childbirth and are discussed in Chapter 36 (p. 661). In 75 percent of cases, this acute demyelinating polyradiculoneuropathy has clinical or serological evidence for an acute infection. Commonly associated are infections with Campylobacter jjuni, cytomegalovirus, Zika virus, and Epstein-Barr virus; surgical procedures; and immunizations (Haber, 2009; Hauser, 2015a; Pacheco, 2016). Guillain-Barre syndrome is thought to be immune-mediated from antibodies formed against nonself antigens. Demyelination causes sensory and motor conduction blockade, and remyelination yields recovery in most cases.


Obstentrics_Williams

Obstentrics_Williams. Clinical features include areflexic paralysis-usually ascending-with or without sensory disturbances. Autonomic dysfunction is common. The full syndrome develops over 1 to 3 weeks. Some manifest as chronic inlammatoy demyelinating poyneuropathy, and our experiences indicate that this may be relatively common in these young women.


Obstentrics_Williams

Obstentrics_Williams. Guillain-Barre syndrome is not more common in pregnancy, and its clinical course mirrors that for nonpregnant individuals. After an insidious onset, paresis and paralysis most oten continue to ascend to cause ventilatory weakness. Management is supportive and incorporates venous thromboembolism prophylaxis, pressure ulcer prevention, and enteral nutrition. In the worsening phase, patients are hospitalized, and a fourth requires ventilatory assistance. IVIG or plasmapheresis is beneficial if begun within 1 to 2 weeks of motor symptoms, however, neither decreases mortality rates (Cortese, 2011; Gwathmey, 2011; Pritchard, 2016). Up to 10 percent of patients deteriorate after initial improvement on therapy, and retreatment with 2 g/kg IVIG over 5 days is recommended. Although most patients recover fully within several months to a year, the mortality rate is 5 percent, mainly due to pulmonary complications and arrhythmias (Hauser, 20 15a; Pacheco, 2016).


Obstentrics_Williams

Obstentrics_Williams. FIGURE 60-5 Bell facial nerve palsy developing on the day of cesarean delivery for dichorionic twins. This woman was treated with prednisone and antiviral medication, and the palsy had almost resolved 3 weeks postpartum. his disfiguring palsy is usually a mononeuropathic acute facial paralysis that is relatively common in reproductive-aged women (Fig. 60-5). It has a female predominance, and pregnant women carry a fourfold risk compared with nonpregnant women (Cohen, 2000; Heaney, 2010). The disease is characterized by facial nerve inlammation and often is associated with reactivation of herpes simplex virus or herpes zoster virus.


Obstentrics_Williams

Obstentrics_Williams. Bell palsy usually has an abrupt and painful onset with maximum weakness by 48 hours. In some cases, hyperacusis and loss of taste accompany paralysis (Beal, 2015). Management includes supportive care with facial muscle massage and eye protection against corneal lacerations from drying. here is general consensus that prednisone, 1 mg/kg given orally daily for 5 days, will improve outcomes and shorten the recovery period (Salinas, 2016; Sullivan, 2007). It is controversial whether addition of an antiviral medication will add benefits (de Almeida, 2009; Gagyor, 2015; Quant, 2009).


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Obstentrics_Williams. It is unclear if pregnancy alters the prognosis for spontaneous facial palsy recovery. Gillman and associates (2002) found that only half of pregnant women recovered to a satisfactory level after 1 year, compared with approximately 80 percent of nonpregnant women and men. Some prognostic markers for incomplete recovery are bilateral palsy, recurrence in a subsequent pregnancy, greater percentage of nerve function loss, and a faster rate of loss (Cohen, 2000; Gilden, 2004). Other than a ivefold greater rate for gestational hypertension or preeclampsia, women with Bell palsy do not have increased adverse pregnancy outcomes rates (Katz, 2011; Shmorgun, 2002).


Obstentrics_Williams

Obstentrics_Williams. This syndrome results from compression of the median nerve and is the most frequent mononeuropathy in pregnancy (Padua, 2010). Symptoms include burning, numbness, or tingling along the inner half of one or both hands. Others are wrist pain and numbness extending into the forearm and sometimes into the shoulder (Katz, 2002). Symptoms are bilateral in 80 percent of gravidas, and 10 percent have evidence for severe denervation (Seror, 1998). Diferential diagnosis includes cer vical radiculopathy of C6-C7 and de Quervain tendonitis. he latter is caused by swelling of the conjoined tendons and their sheaths near the distal radius. Nerve conduction studies may be helpful for clariication (Alfonso, 2010).


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Obstentrics_Williams. In pregnancy, the reported incidence of carpal tunnel syn drome is 7 to 43 percent and varies greatly because the range of symptoms is marked (Meems, 2015; Padua, 2010). Symp tomatic treatment with a splint applied to a slightly lexed wrist during sleep lightens pressure and usually provides relief. Although symptoms typically are self-limited, occasionally sur gical decompression and corticosteroid injections are necessary (Keith, 2009; Shi, 2011). Symptoms may persist in more than half of patients at 1 year and in a third at 3 years (Padua, 2010).


Obstentrics_Williams

Obstentrics_Williams. According to the National Spinal Cord Injury Statistical Center (2017), there are approximately 17,000 new spinal cord injuries each year. he average age is 42 years, and males account for 80 percent of new cases. Cord injury severity determines the short-and long-term prognosis as well as that for pregnancy. For women, many have altered sexual function and transient hypothalamic pituitary hypogonadism. hat said, pregnancy is not uncommon if menstruation resumes (Bughi, 2008). In a review of nearly 2000 women in the National Spinal Cord Injury Database, 2 percent reported pregnancy in the prior 12 months (Iezzoni, 2015).


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Obstentrics_Williams. Gravidas with spinal cord injury have an increased frequency of pregnancy complications that include preterm and low-birth weight neonates. Recent observations in nonpregnant women note that the vaginal microbiota is altered in these women (Pires, 2016). Perhaps related, most have asymptomatic bacteriuria with sporadic symptomatic urinary infections. Bowel dysfunction causes constipation in more than half, and anemia and pressure-necrosis skin lesions are also common. Two serious and life-threatening events can complicate spinal cord injuries. First, if the cord is transected above T 10' the cough reflex is impaired, respiratory function may be compromised, and pneumonitis from covert aspiration can be serious. Pulmonary function tests are considered to assess this risk, and some women may need ventilatory support in late pregnancy or in labor.


Obstentrics_Williams

Obstentrics_Williams. Second, women with lesions above T 5-T6 are at risk for autonomic dysrlexia. With this, stimuli from structures innervated below the level of the spinal lesion lead to massive, disordered sympathetic stimulation. Abrupt catecholamine release can cause vasoconstriction with severe hypertension and symptoms that include throbbing headaches, facial flushing, sweating, bradycardia, tachycardia, arrhythmias, and respiratory distress . Dysrelexia can be precipitated by various stimuli. hese include urethral catheterization, bladder distention from urinary retention, rectal or cervical stretch during digital examinations, uterine contractions and cervical dilation, or any manipulation of other pelvic structures (American College of Obstetricians and Gynecologists, 2016; Krassioukov, 2009). In one report, 12 of 15 women at risk for autonomic dysreflexia sufered at least one episode during pregnancy (Westgren, 1993).


Obstentrics_Williams

Obstentrics_Williams. Because uterine contractions are not afected by spinal cord lesions, labor is usually easy-even precipitous, and comparatively painless. If the lesion is below T12' uterine contractions are felt normally. For lesions above T 2, the risk of out-of 1rhospital delivery is substantial and can be minimized by teaching women to palpate for uterine contractions. This is especially important because up to 20 percent of women deliver preterm (Westgren, 1993). Some recommend tocodynamometry and weekly cervical examinations beginning at 28 to 30 weeks. Another reasonable option that we frequently employ at Park land Hospital is elective hospitalization after 36 to 37 weeks' gestation (Hughes, 1991).


Obstentrics_Williams

Obstentrics_Williams. Spinal or epidural analgesia extending to TIO prevents autonomic dysrelexia and should be instituted at the start of labor. If there are severe symptoms before epidural placement, steps are taken to abolish the provoking stimulus. A parenteral antihypertensive agent such as hydralazine or labetalol is given. Labor and vaginal delivery with epidural or spinal analgesia is preferable and will minimize autonomic dysrelexia (Kuczkowski, 2006). Operative vaginal delivery is frequently necessary.


Obstentrics_Williams

Obstentrics_Williams. Also known as pseudotumor cerebri, this disorder is typified by increased intracranial pressure without hydrocephalus. The cause is unknown, but it may result from overproduction or under absorption of cerebrospinal luid (CSF). Symptoms include headache in at least 90 percent of cases, visual disturbances such as loss of a visual field or central visual acuity in 70 percent, and commonly occurring papilledema that may be sight-threatening (Evans, 2000; Heaney, 2010). Other complaints are stif neck, back pain, pulsatile tinnitus, and cranial nerve palsies. he syndrome is oten found in young women and is prevalent in those who are obese, who recently gained weight, or both (Fraser, 201r1). Along with symptoms, other criteria for diagnosis include elevated intracranial pressurer> 25 em H20, normal CSF composition, normal cranial CT or MR imaging indings, papilledema, and no evidence for systemic disease. If papilledema is not present, other criteria are required (Friedman, 2013).


Obstentrics_Williams

Obstentrics_Williams. Idiopathic intracranial hypertension is usually self-limited. Visual defects can be prevented by lowering the CSF pressure, and agents include acetazolamide to reduce fluid production, furosemide, or topiramate. Corticosteroids are now rarely used. Surgical intervention is occasionally necessary and is accomplished by either lumboperitoneal shunting of spinal fluid or optic nerve sheath fenestration. It is controversial if pregnancy is a risk factor for idiopathic intracranial hypertension. Certainly, symptoms may first appear in pregnancy, and women previously diagnosed may become symptomatic. Symptoms usually develop by midpregnancy, tend to be self-limited, and usually resolve postpartum.


Obstentrics_Williams

Obstentrics_Williams. Pregnancy does not alter management. Some recommend serial visual field testing to forestall permanent vision loss. In a report of 16 pregnant women, visual ield loss developed in four, and it became permanent in one (Huna-Baron, 2002). Visual ield loss is often coincident with the development of papilledema, for which acetazolamide is given. Lee and associates (2005) reported successful treatment of 12 pregnant women. Although outmoded for treatment of nonpregnant individuals, repeated lumbar punctures are generally successful in providing temporary relief throughout pregnancy. In some pregnant women, surgical therapy becomes necessary, and we and others have had promising results with optic nerve sheath fenestration (hambisetty, 2007).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy complications are likely due to associated obesity and not to intracranial hypertension. In a review of 54 pregnancies, rates of adverse perinatal outcomes were not elevated (Katz, 1989). he route of delivery depends on obstetrical indications, and conduction analgesia is safe (Aly, 2007; Karmaniolou, 2011).


Obstentrics_Williams

Obstentrics_Williams. Pregnancies in women with previously placed ventricular shunts for obstructive hydrocephalus usually have satisfactory outcomes (Landwehr, 1994). Shunts may be ventriculoperitoneal, ventriculoatrial, or ventriculopleural. Partial obstruction of a shunt is common, especially late in pregnancy (Schiza, 2012). In one report of 17 such pregnancies, neurological complications were reported in 13 (Wisof, 1991). Findings included headaches in 60 percent, nausea and vomiting in 35 percent, lethargy in 30 percent, and ataxia or gaze paresis, each in 20 percent. Most symptoms respond to conservative management. However, if CT scanning during symptom evaluation discloses acute hydrocephaly, then the shunt is tapped or pumped several times daily. In some cases, surgical revision is necessary and may be emergently indicated (Murakami, 2010).


Obstentrics_Williams

Obstentrics_Williams. Another shunting procedure is placement of an endoscopic third ventriculostomy for hydrocephalus (de Ribaupierre, 2007). With this, a small hole is created in the loor of the third ventricle to allow CSF to low directly into lower cisterns. One report described successful results in ive pregnant women who underwent endoscopic ventriculostomy (Rifaud, 2006). In a review, however, reproductive function and miscarriage rates were found to significantly worsen in these women (Bedaiwy, 2008). Vaginal delivery is preferred in women with shunts, and unless there is a meningomyelocele, conduction analgesia is permitted. Antimicrobial prophylaxis is indicated if the peritoneal cavity is entered for cesarean delivery or tubal sterilization.


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Obstentrics_Williams. Brain death is rare in obstetrics. Life-support systems and parenteral alimentation for up to 15 weeks while awaiting delivery have been described (Hussein, 2006; Powner, 2003; Souza, 2006). Some women were treated with aggressive tocolysis and antimicrobial therapy. In one review of 17 women with persistent vegetative state who were given various levels of support, five women died after delivery, and most of the others remained in their vegetative state (Chiossi, 2006). With a diagnosis of brain death using the uniform Determination of Death Act definition, there are no published reports of neurological recovery (Wijdicks, 2010). Few institutional brain-death policies address pregnancy (Lewis, 2016). The ethical, inancial, and legal implications, both civil and criminal, that arise from attempting or not attempting such care are profound (Farragher, 2005; Feldman, 2000). In some women, perimortem cesarean delivery is performed as discussed in Chapter 47 (p. 931).


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Obstentrics_Williams. Adab N: Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful? CNS Drugs 20:791, 2006 Aegidius K, Anker-Zwartt], Hagen K, et al: he efect of pregnancy and parity on headache prevalence: the head-HUNT study. Headache 49:851,t2009 Aguiar de Sousa 0, Canhao P, Ferro ]M: Safety of pregnancy after cerebral venous thrombosis: a systematic review. Stroke 47(3):713,t2016 Airas L, Saraste M, Rinta S, et al: Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin Exp Immunol 151 :235, 2008 Airola G, Allais G, Castagno Ii I, et al: Non-pharmacological management of migraine during pregnancy. Neurol Sci 31(1):S63, 2010 Alfonso C, ]ann S, Massa R, et al: Diagnosis, treatment and follow-up of the carpal tunnel syndrome: a review. Neurol Sci 31 :243, 20t10


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Obstentrics_Williams. Alfonso C, ]ann S, Massa R, et al: Diagnosis, treatment and follow-up of the carpal tunnel syndrome: a review. Neurol Sci 31 :243, 20t10 Allais G, Castagnoli Gabellari 1, Borgogno P, et al: The risks of women with migraine during pregnancy. Neurol Sci 31(Supplt1):S59, 2010 lmeida C, Coutinho E, Moreira 0, et al: Myasthenia gravis and pregnancy: anaesthetic management-a series of cases. Eur] AnaesthesioI27:985, 2010 Alroughani R, Altintas A, Al ] umah M, et al: Pregnancy and the use of diseasemodiying therapies in patients with multiple sclerosis: beneits versus risks. Mult Scler Int 2016:1034912,t2016 Aly EE, Lawther BK: Anaesthetic management of uncontrolled idiopathic intracranial hypertension during labour and delivery using an intrathecal catheter. Anaesthesia 62: 178, 2007 Amarenco P, Lavallee PC, Labreuche], et al: One-year risk of stroke after transient ischemic attack or minor stroke. N Engl] Med 374(16):1533, 2016


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Obstentrics_Williams. Amarenco P, Lavallee PC, Labreuche], et al: One-year risk of stroke after transient ischemic attack or minor stroke. N Engl] Med 374(16):1533, 2016 Amato A, Barohn R]: Peripheral neuropathy. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. McGraw-Hill Education, New York, 2015 Amato MP, Portaccio E, Ghezzi A, et al: Pregnancy and fetal outcomes after interferon-beta exposure in multiple sclerosis. Neurology 75: 1794, 2010 American College of Obstetricians and Gynecologists: Obstetric management of patients with spinal cord injuries. Committee Opinion No. 275, September 2002, Reairmed 2016 Argyriou A, Makris N: Multiple sclerosis and reproductive risks in women. Reprod Sci 15(8):755,t2008 Aukes AM, de Groot ]C, Aarnoudse ]G, et al: Brain lesions several years after eclampsia. Am] Obstet GynecoI200(5):504.e1, 2009


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Obstentrics_Williams. Reprod Sci 15(8):755,t2008 Aukes AM, de Groot ]C, Aarnoudse ]G, et al: Brain lesions several years after eclampsia. Am] Obstet GynecoI200(5):504.e1, 2009 Aukes A, Wessel I, Dubois M, et al: Self-reported cognitive functioning in formerly eclamptic women. Amt] Obstet Gynecol 197:365.e1, 2007 Barbarite E, Hussain S, Dellarole A, et al: he management of intracranial aneurysms during pregnancy: a systematic review. Turk Neurosurg 26(4):465,t2016 Barth 0, Nouri M, Ng E, et al: Comparison of IVIG and PLEX in patients with myasthenia gravis. Neurology 76:2017, 2011 Bateman BT, Olbrecht VA, Berman MF, et al: Peripartum subarachnoid hemorrhage. Anesthesiology 116:242, 2012 Beal MF, Hauser SL: Trigeminal neuralgia, Bell's palsy, and other cranial nerve disorders. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles ofInternai Medicine, 19th ed. McGraw-Hill Education, New York, 2015


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Obstentrics_Williams. Bedaiwy MA, Fathalla MM, Shaaban OM, et al: Reproductive implications of endoscopic third ventriculostomy for the treatment of hydrocephalus. Eur ] Obstet Gynecol Reprod BioI 140(1):55,t2008 Blackwell DL, Lucas ]W, Clarke TC: Summary health statistics for U.S. adults: National Health Interview Survey, 2012. Vital Health Stat (260):1, 2014 Blichfeldt-Lauridsen L, Hansen BD: Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand 56(1):17, 2012 Bove R, Alwan S, Friedman ]M, et al: Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review. Obstet Gynecol 124(6):1157,t2014 Brandes ]L, Kudrow 0, Stark SR, et al: Sumatriptan-naproxen for acute treatment of migraine.t]AMA 297:t1443,t2007 Briggs GG, Freeman RK: Drugs in Pregnancy and Lactation, 10th ed. Philadelphia, Lippincott Williams & Wilkins, 2015 Brodie M], Dichter MA: Antiepileptic drugs. N Engl] Med 334:168,t1996