Table 1.
Case reports, case series and review articles for descriptions of SuS patients during pregnancy, postpartum or after termination of pregnancy.
| Case | SuS diagnosis before pregnancy | Age at diagnosis of SuS | Age at pregnancy | Gestational age or postpartum | Presenting symptoms | Audiometry | Ophtalmology | MRI | CSF | Treatment | Outcome | Pregnancy outcome | Reference | Prior symptoms and/or pregnancies |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | N | 22 | 21 | postpartum | headache and hearing impairment, confusion, personality change, unsteady gait | bilateral hearing loss | Fundoscopy: cotton-wool spots FA: multiple BRAO bilateral | increased protein (187 mg/dl) | steroids | remarkable improvement | stillbirth at term (anencephalic child) | Coppeto 1984 | delivery of a healthy child 6 years prior; first symptoms started the month before pregancy, with personality change and high protein levels in CSF | |
| 2 | N | 31 | 31 | first trimester | numbness in the extremities, segmental visual loss, diplopia, lethargy, memory loss, change in personality, dysarthria, gait unsteadiness, tinnitus, and hearing loss | bilateral low frequency SNHL, left more than right | Fundoscopy: retinal arteriolar occlusions | 0 wbc/µl increased protein (252 mg/dl) OCB absent | no treatment | speech, memory, gait, personality improved | healthy baby | MacFadyen 1987 | 3 prior pregnancies | |
| 2 | postpartum | sudden deterioration left hearing, fatigue, dysarthria, incoordination in writing and gait, memory problems | Fundoscopy: small intraretinal hemorrhages, adjacent artery narrowing, perivascular sheathing and artery narrowing | 0 wbc/µl increased protein (116mg/dl) | steroids | improvement speech, dizziness and memory, further visual loss | N/A | MacFadyen 1987 | ||||||
| 3 | N | 28 | 28 | 28 | sudden, painless visual loss right eye, periodic imbalance; deterioration over the next month with severe encephalopathy | mild bilateral SNHL | Fundoscopy: retinal arteriolar occlusion, cotton-wool spot | multifocal T2 hyperintensitiesintensity in the deep white matter, anterior corpus callosum, and brain stem | 2 wbc/µl increased protein (207 mg/dl) OCB absent | heparin, warfarin followed by aspirin | gradual improvement after delivery in mental status and walking, persistent visual field deficits | pre-term (33 weeks gestation) healthy boy | Gordon 1991 | no prior symptoms or pregnancies |
| 4 | N | 36 | 36 | immediately postpartum | visual loss, tetrapyramidal signs, confusion | right-sided hearing loss | Fundoscopy: normal | T2 hyperintensities in the supratentorial white matter and basal ganglia | 6 wbc/µl increased protein (264 mg/dl) | during pregnancy: aspirin monotherapy until 26 weeks GA, thereafter low molecular weight heparin; after delivery oral anticoagulants | psychological sequelae and hearing loss despite treatment with hyperbaric oxygen | induction of delivery with prostaglandin gel a terme; urgent caesar section, delivery of healthy girl | Cador-Rousseau 2002 | 3 previous pregancies, of which 1 voluntary abortion, 1 spontaneous abortion and 1 at term pregnancy prior symptoms: 6 years prior sudden left, hearing loss, 2 years prior thrombosis of a branch of the right central retinal artery, 3 months prior to pregnancy thrombosis of a branch of the left central retinal artery |
| 5 | Y | 35 | 35 | pregnancy discovered during cyclophosphamide treatment (before 10 weeks GA) | steroids, anticoagulation,cyclophosphamide,aspirin | therapeutic abortion | Aubart-Cohen 2007 | |||||||
| 6 | N | 25 | 25 | behavioral disturbances | new retinal occlusions | steroids, anticoagulation | therapeutic abortion | Aubart-Cohen 2007 | ||||||
| 6 | Y | 25 | 29 | no relapse during pregnancy | aspirin | healthy baby at term | Aubart-Cohen 2007 | |||||||
| 7 | Y | 30 | 33 | postpartum | confusion, vertigo, and hearing loss | aspirin | healthy baby at term | Aubart-Cohen 2007 | ||||||
| 8 | N | 28 | 28 | 37 | confusion, forgetfulness, hypersomnolence, headaches, hearing difficulties, and episodic visual loss | low frequency SNHL | Fundoscopy: bilateral BRAO with retinal infarcts.FA: bilateral retinal infarcts, BRAO, and arteriolar hyperfluorescence | multiple T2 hyperintensities in the cerebellum and cerebral white matter, including corpus callosum. Many lesions were hypointense on T1-weighted imaging and some demonstrated restricted diffusion | 3 wbc/µl increased protein (121 mg/dl) | aspirin, steroids (IV pulse and oral taper), IVIg, mycophenolate mofetil | Seven months postpartum: short-term memory problems,right eye visual problems, hearing loss in left ear, easy fatiguability | healthy baby girl | Grinspan 2009 | 4 previous pregnancies: 2 healthy children, 1 abruption at 23 weeks, and 1 electiveabortion |
| 9 | N | 23 | 23 | 10 days after voluntary abortion | retro-bulbar headache, photophobia, vomiting andlethargy | bilateral low frequency SNHL | Fundoscopy and FAA: sporadic segmental retinalarterial occlusions in both eyes | multiple punctate foci of restricted diffusion and T2 hyperintensities in the deep white matter of both frontal lobes, a larger lesion in the splenium of the right corpus callosum | 8 wbc/µl increased protein 183 mg/dl | steroids (IV pulse and oral taper), single dose of infliximab, IVIg, cyclophosphamide, aspirin, nifedipine; later cyclophosphamide stopped and switch to azathioprin | After twelve months: tinnitus and hearing loss persisted, cognition continued to improve, ongoing deficits in spontaneous recall, working memory and verbal fluency | voluntary termination of pregnancy at GA of 7 weeks | Hardy 2011 | |
| 10 | N | 25 | 25 | 20 | confusion, difficulty walking, and vision and hearing loss, intermittent headaches | left-sided SNHL | Fundoscopy: left-sided BRAO and cotton wool spots FA not done | T2 hyperintensities in the deep and periventricular white matter, corpuscallosum, pons, and cerebellar peduncles; a 2-3 mm hypointense ‘hole’ in the midportion of the corpus callosum | 16 wbc/µl increased protein (63 mg/dL) | steroids (IV pulse and oral taper), IVIg, aspirin | Improvement of mental status, gait, hearing and visual loss persisted | Deane 2011 | ||
| 10 | 33 | abrupt confusion and worsening gait, new bilateralhearing loss, and new right vision changes | Fundoscopy: retinal ischemia on the right | several new lesions | repeat IV steroids, IVIg, ;postpartum cyclophosphamide and rituximab added; after 3 doses of cyclophosphamide oral azathioprin | Significant improvement; development of livedo reticularis | induction of premature delivery at 35 weeks gestation; delivery of healthy baby girl | Deane 2011 | ||||||
| 11 | N | 35 | 35 | 31 | bilateral visual loss and right hearing loss, cognitive symptoms | SNHL right ear, left side normal | Fundoscopy: bilateral narrowing of arterioles punctiform hemorrhage FA: leakage in multiple arterioles in both eyes | supra- and infra-tentorial T2 hyperintensities in white matter | lymphocytic pleiocytosis increased protein OCB absent | steroid pulse; repeated ; plasma exchange; postpartum cyclophosphamide, followed by mycophenolate; due to ongoing disease activity changed to methotrexate and etanercept | Bilateral hearing loss, visual field defects; ongoing disease activity (retinal vasculitis) after pregnancy for 5 years | caesarean section, premature delivery of health baby boy | Finis 2011 | |
| 12 | N | 30 | 30 | 3 weeks postpartum | headache, hearing loss, attention deficit, personality and mental changes, impaired cognition and memory | SNHL, low and middle tones, right more than left side | Fundoscopy and FA: bilateral BRAO with retinal ischemia, arteriolar shunts, and small vascular dilatations | small T2 hyperintensities, atrophic corpus callosum | normal OCB absent | steroids (IV pulse and oral taper), aspirin, nimodipine | no recurrence after 6 months and 1 year; no improvement in hearing | normal baby | Karelle 2012 | Three episodes of aseptic meningitis (age of 5, 14, and 27 years). Between these events,the patient suffered from migraine-like headache and atypical polyarthritis. |
| 13 | N | 34 | 34 | third trimester | Headaches,numbness andtingling ofhands and face,visual fielddefect, hearingloss, tinnitus | T2 hyperintensities and corpus callosum involvement | 2 wbc/µl increased protein (101 mg/dl) | steroids (oral) , aspirin, plasmapheresis | postpartum symptoms stabilised, recurrence after steroid taper | not reported | Mateen 2012 | |||
| 14 | N | 32 | 32 | postpartum | Vertigo, diplopia,visual loss,tingling ofhands and feet,and amnesticepisodes | Low- to mid-frequencySNHL | T2 hyperintensities and corpus callosum involvement , gadolinium enhancement | 11 wbc/µl increased protein (161 mg/dl) OCB absent | steroids (IV and oral), aspirin, plasmapheresis | improved, later episodes of visual and hearing loss | Mateen 2012 | |||
| 15 | N | 32 | 32 | 32 | change in personality, unsteadiness of gait, slurred speech, evolving to severe disorientation and confusion | multiple small T2 hyperintensities in both supra- and infratentorial locations, some of which exhibited diffusion restriction, several of which in corpus callosum | 13 wbc/µl increased protein (180 mg/dl) OCB absent | steroids (IV and oral), IVIG and mycophenolate and methotrexate | 1 year after the diagnosis the patient was well with markedly improved gait and cognition | emergency caesarean section | Engeholm 2013 | |||
| 16 | N | 28 | 28 | 9 | lower limb weakness, drowsiness and dysarthria | T2 hyperintensities with an unusual pattern of meningeal enhancement after Gadolinium administration; serialMRI showed progressive lesions in the deep white matter, including the basal ganglia and cerebellar peduncles withenhancing lesion in the corpus callosum that progressed to volume loss | 9 wbc/µl increased protein (200 mg/dl) OCB absent | steroids (IV pulse and oral taper), plasma exchange, IVIg | cognitive deficits persisted, hearing and vision remain impaired | at 13 weeks GA 1 viable fetus; therapeutic abortion at 15 weeks GA | Ioannides 2013 | |||
| 17 | N | 21 | 21 | 35 | walking impairment and evolving hearing loss, lack of concentration and disorientation | bilateral moderate low frequency SNHL in the low frequency range, leftmore than right side | FA: normal | multiple small T2 hyperintensitiesin the corpus callosum, periventricular white matter, centrum semiovale, posterior arm of the left internal capsule, pons and cerebral peduncles; some lesions demonstrated restricted diffusion on DWI, as well as hypointensity on T1-weighted imaging | 4 wbc/µl increased protein (109 mg/dl) | low-molecular-weight heparin, IVIg; after delivery start of oral azathioprine and warfarin | After two months: hearing loss persisted, discrete activity on FAAwithout functional visual impairment; no new symptoms; MRI showed new lesions | induction of labour at 37 weeks | Antulov 2014 | |
| 18 | N | 35 | 35 | 37 | hearing loss and tinnitus in the left ear, attacks of vertigo and slight difficulty in finding words | mild hearing loss in theleft ear | normal OCB absent | postpartum: aspirin, steroids (IV and oral taper), cyclophosphamide | BRAO in the right eye 2.5 months after having given birth | Feresiadou 2014 | At the age of 12: encephalopathy, sudden deafness of the right ear and visual field defects in the left eye at the age of 12, followed by permanent hearing and visual defects. Second pregnancy. | |||
| 19 | N | 25 | 25 | 14 | acute onset of right leg shooting pain, followed by complaints of vertigo, blurry vision, headache and gait instability; severe encephalopathy | multiple T2 hyperintensities in the bilatera lwhite matter, deep gray matter,corpus callosum and posterior fossa with corresponding restricted diffusion and T1 hypointensities for the observed corpus callosum lesions | 6 wbc/µl increased protein ( 95 mg/dl)OCB absent | steroids (IV pulse) repeated approx.2 weeks later (oral) when symptoms reoccurred | One month postpartum: hearing difficulty (right sensorineural hearing loss), two months later cognitive difficulties. 1,5 years after initial presentation residual cognitive deficits consisting of visual spatial deficits and difficulty with word recall and vocabulary | healthy baby | Hua 2014 | |||
| 20 | N | 25 | 11 | confusion, short term memory loss, headache and uncoordinated gait | multiple periventricular and deep white matter T2 hyperintense lesions in a perpendicular distribution to the ventricles | steroids (pulse) | healthy baby | Tashman 2014 | ||||||
| 20 | 24 | repeated symptoms | steroids (pulse) | Tashman 2014 | ||||||||||
| 20 | 3 months postpartum | confusion, headache, and lethargy | bilateral low frequency hearing loss, rising to normal at higher frequencies | bilateral BRAOs with retinal infarcts | small, multifocal T2 hyperintensities in the white matter involving the corpus callosum | increased protein | steroids (pulse), mycophenylate | Tashman 2014 | ||||||
| 21 | N | 18 | 24 | visual loss right eye, followed by severe headache | normal | No FA, central retinal artery occlusion | small T2 hyperintensities | steroids (pulse and oral taper), LMWH | symptom free in 4 days, except vision right eye; recurrence of disease activity 1 year after starting estrogen replacement therapy at the age of 50 years (Petty 2001) | Khan 2014 | ||||
| 22 | Y | 37 | 6 weeks postpartum | mild hearing loss right ear, visual aura | FA: BRAO with leakage | steroids (oral), azathioprine ( azathioprine discontinued during pregnancy due to anemia) | full recovery | healthy baby | van der Kooij 2015 | |||||
| 23 | N | 29 | 8 | right hearing loss, vertigo, and mild headache | steroids (oral, pulse) | London 2016 | ||||||||
| 23 | 19 | left visual field deficit, headache | FA: bilateral multiple BRAO | multiple T2 hyperintensities in the deep white matter including the splenium of the corpus callosum and the left cerebellum | mildly elevated protein OCB absent | steroids (pulse and oral taper), antiplatelet therapy; cyclophosphamide 1 g every 4 weeks (initiated at 28 weeks gestational age, due to relapses) | persistent bilateral hypoacousia requiring hearing aid | healthy baby | London 2016 | |||||
| 23 | postpartum | dizziness and visual loss | gadolinium-enhancing lesions | steroids (pulse) | London 2016 | |||||||||
| 24 | N | 21 | 3 months | visual and hearing loss; after currettage rapid onset of encephalopathy | no SNHL | Fundoscopy: retinal edema FA: leakage, no BRAO | increased protein | steroids (oral taper) | complete recovery 2 weeks later | missed abortion | Bhattu 2017 | |||
| 25 | N | 25 | 7 months | visual loss left eye, hearing loss and tinnitus, mild headache | SNHL right ear | Fundoscopy: ischemic retinal edema infero-temporal and cherry-red spot | periventricular and callosal T2 hyperintensities | not reported | steroids (pulse and oral taper) | improvement in headache, some recovery of vision | Manik 2018 | |||
| 26 | N | 19 | 14 | headache, somniloquy | SNHL low frequencies | FA: multiple BRAO | multiple diffusion restrictive T2 hyperintensities, also in corpus callosum | increased protein OCB absent | steroids (pulse) and aspirin | no fetal anomaly | Can Usta 2018 | |||
| 27 | N | 34 | 15 | apathy and behavioral changes; vertigo 6 months prior and an episode of right ear tinnitus 2 months prior | bilateral SNHL | retinal vasculitiscorroborated by FA | hyperintense periventricular white matter lesions in T2 andFLAIR sequences also involving bilateral basal ganglia and with pre-dominant affection of the corpus callosum, in addition to infratentorialcerebellar lesions. Lesional restriction of diffusion but no contrast en-hancement was observed. T1 weighted images showed hypointenselesions in the same topography | CSF values showed proteins of 77 mg/dl,glucose of 52 mg/dl (serum glucose of 89 mg/dl), and no cells. | 5 pulses of methylprednisolone were administeredwithout obvious clinical improvement. Immunomodulatory treatmentwas escalated to intravenous immunoglobulin (IVIg) at 0.4 g/kg/dayfor 5 days; prednisone orally and CCF after abortion | partial remission | therapeutic abortion | Gomez-Figueroa 2018 | ||
| 28 | Y | 23 | 45 | no relapse during pregnancy or postpartum | no treatment since 8 years, 2 years relapse free after delivery | IVF four cycles of GnRH antagonist, ganirelix | healthy twins at 35 weeks GA | Qiu 2020 | ||||||
| 29 | N | 24 | 23 | 11 months postpartum | ataxia, vomiting, minor cognitive impairment and blurred vision in theright eye | T2 hyperintensities inthe deep and subcortical white matter, brainstem and cerebellumassociated with restricted diffusion, callosal snowball lesions | 9wbc/µl increased protein 120 mg/dl | aspirin, steroids (pulse and oral taper), IVIg | After 1 month symptoms resolved, patient fell pregnant, resulting in a spontaneous miscarriage two months later. | Qiu 2020 | ||||
| 30 | N | 24 | 1 month post- spontaneous abortion | subacute severebilateral hearing impairment requiring hearing aids, and partial visualloss in the left eye | mild bilateral low frequency SNHL | FA: bilateral BRAOs | MRI six months post-rituximab was stable | Steroids (oral), rituximab | Qiu 2020 | |||||
| 30 | Y | 25 | 22 months after initial presentation | 11 months after last rituximab dose | healthy baby at 38 weeks | Qiu 2020 | ||||||||
| 31 | N | 34 | 34 | 7 | moderate encephalopathy, vertigo | unilateral SNHL | bilateral | T2 hyperintensities in the supratentorial white and gray matter areas | 14 wbc/µl increased protein (125mg/dl) | aspirin, IV steroids, cyclophosphamide, mycophenolate, | SNHL, visual field deficits, no residual central nervous system symptoms | therapeutic abortion | Wilf-Yarkoni 2020 | |
| 32 | N | 40 | 20 | migraine, bradypsychia, disorientation and behavioral changes | SNHL | bilateral papillitis and ischemic retinal areas | T2 hyperintensities in the supratentorial white matter and corpus callosum with diffusion restriction | IVIG and oral prednisone; after pregnancy add-on of azathioprin | resolution of symptoms | healthy baby at 36-weeks GA after premature rupture of membranes and caesarean section | Ramos-Ruperto 2020 | 1 previous pregnancy without complications | ||
| 32 | 6 months postpartum | bilateral scotomas | retinal infarctions | steroids (pulse), IVIG and cyclophosphamide | improvement | Ramos-Ruperto 2020 | ||||||||
| 33 | N | 37 | puerperium | scotoma | SNHL | branch arterial retinal infarctions | T2 hyperintensities in supratentorial white matter, right internal capsule and splenium of the corpus callosum | steroids (pulse), oral prednisone and azathioprine | no relapses | healthy baby | Ramos-Ruperto 2020 | 2 previous pregancies; self-limited dysarthria and tinnitus during first pregnancy , as well as episodes of headache preceding the scotoma |
AZA, azathioprin; BRAO, branch retinal artery occlusions; CSF, cerebrospinal fluid; CYC, cyclophosphamide; FA, fluorescein angiography; GA, gestational age; IVIG, intravenous immunoglobulins; MMF, mycophenolate mofetil; MRI, magnetic resonance imaging; OCB, oligoclonal bands; SNHL, sensorineural hearing loss; SuS, Susac syndrome; wbc, white blood cells.