Neurosurg Focus 23 (5):E8, 2007

A review of ocular manifestations in intracranial hypotension

GABRIEL ZADA, M.D., THOMAS C. SOLOMON, B.A., AND STEVEN L. GIANNOTTA, M.D. Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California

Object. Intracranial hypotension (ICH) can present with a wide variety of visual symptoms and findings. Deficits in visual acuity and visual fields as well as ophthalmoplegia due to cranial nerve dysfunction have been frequently described. The aim of this review was to identify the most commonly reported ocular manifestations associated with ICH. Methods. The authors conducted a review of the literature to date to identify all studies of patients with ICH and ocular manifestations. Results. The most commonly encountered cranial nerve deficit resulting from ICH (Ͼ 80% of reported cases) is an paresis, which may occur unilaterally or bilaterally. Although less common, oculomotor and trochlear nerve palsies have been reported as well. The complex is frequently involved in ICH and may manifest as deficits in visual acuity and field cuts. Visual deficits and ophthalmoplegia improved following appro- priate management in 97% of reported cases. Conclusions. Intracranial hypotension can present with a wide spectrum of visual deficits, the causes of which are multifactorial. Cranial nerve paresis, especially of the abducens nerve, is frequently reported. The majority of symptoms and cranial nerve deficits reviewed respond favorably to conservative management, epidural blood patch administration, or in a minority of cases, surgical intervention. (DOI: 10.3171/FOC-07/11/E8)

KEY WORDS • abducens nerve • cerebrospinal fluid leak • cranial nerve • epidural blood patch • intracranial hypotension • ophthalmoplegia

EREBROSPINAL fluid exerts a necessary buoyant force ble vision, and visual field obscurations.22 A variety of cra- on the cranial contents, suspending the and nial nerve palsies, frequently resulting in ophthalmoplegia, C and protecting them from downward can be associated with symptomatic spontaneous ICH. In traction. When CSF volume is depleted via the spinal me- this report, we review the incidence, distribution, and pa- ninges, a condition called ICH results. This condition is thophysiology of ocular manifestations, with an emphasis most commonly encountered due to iatrogenic causes, such on cranial nerve ophthalmoplegia, resulting from ICH. as . Other times, spontaneous leakage of CSF occurs via the spinal , resulting in a condi- tion called spontaneous ICH. Clinical Material and Methods Spontaneous ICH is usually characterized by a benign, A search of PubMed (National Library of Medicine) and self-limited course. Patients typically present with postural reference lists of all relevant articles was conducted to iden- or exertional headaches that can be temporarily relieved by tify all studies of patients with ICH and ocular manifesta- lying in a supine or recumbent position. Other common tions. Patients with objective ocular manifestations and in- signs and symptoms include nausea, vomiting, vertigo, tracranial hypotension were included in the review. A meningismus, and altered hearing.35,38 In some cases, how- database was created and subsequently analyzed. ever, the condition may progress to more significant neuro- logical secondary to downward brainstem displace- ment. Spontaneous ICH is frequently associated with a Results: Review of the Literature variety of visual disturbances, including blurry vision, dou- Incidence of Visual Involvement in Intracranial Hypotension Abbreviations used in this paper: CSF = cerebrospinal fluid; The majority of patients presenting with spontaneous ICH = intracranial hypotension; SOV = superior ophthalmic vein. ICH report postural headaches that worsen with exertion.

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TABLE 1 Review of literature involving opthalmoplegia in ICH*

Age (yrs), Cranial Nerve Authors & Year Sex Presenting Symptoms/Signs Affected Side Treatment Resolved?

Bell et al., 1960 45, F abducens lt NR NR Gibson et al., 1988 44, F diplopia abducens bilat NR NR Molins et al., 1990 36, F diplopia abducens rt NR NR Pannullo et al., 1993 23, F postural headache, n/v, tinnitus, neck abducens bilat epidural blood patch yes stiffness, diplopia 36, F postural headache, seizures, diplopia abducens bilat carbamazepime, bur hole yes evacuation for SDH Berlit et al., 1994 43, F postural headache, nausea, tinnitus, diplopia abducens bilat prednisone yes 59, F postural headache, nausea, vomiting, diplopia abducens bilat none yes Horton & Fishman, 1994 41, F postural headache, diplopia abducens lt oral hydration yes Blank et al., 1997 42, M headache, diplopia abducens lt bed rest, hydration yes Mokri et al., 1997 35, M headache, nausea, cervical/epigastric pain abducens rt conservative management yes 57, F headache, nausea abducens bilat prednisone, conservative yes management 45, M neck/shoulder pain, hearing changes abducens rt conservative management yes 41, M headache, nausea abducens lt surgical management of yes CSF diverticula 51, F neck/arm pain, headache, , abducens lt epidural blood patch yes tinnitus 40, F headache abducens bilat epidural blood patch yes 35, F headache abducens lt epidural blood patch ϫ 3, yes surgical repair Anonymous, 1998 50, F headache, diplopia abducens lt NR NR Christoforidis et al., 1998 33, M headache, diplopia abducens lt oral hydration, caffeine yes Apte et al., 1999 63, M postural headache, diplopia, photophobia, abducens lt epidural blood patch yes eye pain, Luijckx & De Jaegere, 2001 44, F postural headache, n/v, diplopia abducens lt epidural blood patch yes Mikawa & Ebina, 2001 41, M postural headache, memory loss oculomotor lt epidural blood patch, yes evacuation of SDH Garcia-Morales 70, M headache, diplopia abducens NR surgical repair yes et al., 2001 Brady-McCreery 42, M diplopia oculomotor, bilat† eye muscle surgery no et al., 2002 trochlear Warner, 2002 26, M headache, n/v, unilateral hearing loss, oculomotor rt none yes blurred vision Beck et al., 2003 40, F headache, n/v, diplopia abducens rt surgical repair yes Baryshnik & Farb, 2004 19, F postural headache abducens bilat epidural blood patch yes Ferrante et al., 2004 NR diplopia abducens NR NR NR NR abducens NR NR NR NR abducens NR NR NR NR abducens NR NR NR NR abducens NR NR NR NR oculomotor, bilat NR NR trochlear Guigon et al., 2004 50, F headache, nausea, diplopia abducens lt epidural blood patch yes Ohta et al., 2004 71, M headache, nausea, diplopia trochlear rt conservative management yes Grueb et al., 2005 39, F postural headache, n/v, tinnitus, diplopia abducens rt epidural blood patch yes Kose et al., 2005 38, M headache, n/v, diplopia abducens bilat none yes Merlo et al., 2005 35, F postural headache, meningismus, dizziness, abducens rt methylprednisolone, yes diplopia hydration Akkawi et al., 2006 66, M postural headache, diplopia, stupor, dyarthria oculomotor rt epidural blood patch yes Khemka & Mearza, 2006 43, M postural headache, diplopia abducens lt epidural blood patch yes Mathews et al., 2006 51, F headache abducens rt epidural blood patch yes Béchard et al., 2007 45, F headache, n/v, diplopia abducens bilat epidural blood patch yes Zada et al., 2007 44, M postural headache, n/v, dizziness, diplopia oculomotor bilat epidural blood patch yes *NR = not reported; n/v = nausea/vomiting; SDH = subdural hematoma. † Bilateral trochlear nerves; unilateral oculomotor nerve.

Associated visual complaints include blurred vision, dou- sented with diplopia, and 5 (12%) presented with visual de- ble vision, and visual field deficits. A review of the litera- ficits other than diplopia. Ferrante et al.16 reported a series ture regarding spontaneous ICH revealed several clinical of 18 cases of spontaneous ICH, of which 6 (33%) present- series in which the authors reported the incidence of ocular ed with diplopia. In a literature review, Horton and Fish- manifestations of spontaneous ICH. In a series of 40 pa- man22 reported visual symptoms in 42.5% of patients pre- tients reported on by Christoforidis et al.,13 12 (30%) pre- senting with spontaneous ICH; diplopia occurred in 30% of

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Unauthenticated | Downloaded 09/23/21 01:38 PM UTC Review of ocular manifestations in intracranial hypotension all cases. In a series reported by Mokri et al.,30 27% of bing may result from injury to the brainstem at the pontine patients had diplopia secondary to abducens nerve paresis. level. According to our review of the literature, the incidence Ophthalmoplegia Due to Cranial Nerve Dysfunction in of ophthalmoplegia secondary to cranial nerve paresis as- ICH sociated with spontaneous ICH is ~ 30–35%. By far, the most common ophthalmoplegia encountered is an abdu- A review of the pertinent literature on ICH revealed 29 cens nerve paresis, occurring in ~ 80% of reported patients studies involving 42 patients with cranial nerve manifesta- with spontaneous ICH–related ophthalmoplegia. The tions resulting in ocular deficits secondary to ICH (Table 1–10,13,16–20,22–28,30,32,33,36,40,41 majority of these patients were noted to have unilateral ab- 1). The majority of patients (35 ducens nerve palsies, whereas more than 1 in 4 cases of [83%]) with reported ophthalmoplegia presented with ab- abducens nerve paresis was noted bilaterally. The abducens ducens nerve palsies. Unilateral abducens nerve palsies nerve is more likely to be susceptible to traction-related were reported in 25 patients (60%), whereas 10 patients injury secondary to its long intracranial course along the were reported to have bilateral abducens nerve palsies clivus and through the Dorello canal, as well as its attach- (24%). Oculomotor nerve palsies were reported in 6 ment to the Gruber ligament.8,22 Although less common, patients (14%). Of these 6 patients, palsies occurred bilat- both unilateral and bilateral paresis of the third and fourth erally in 2. Trochlear nerve paresis was reported in 3 cranial nerves has also been noted to occur with sponta- patients (7%) and was bilateral in 2. Two patients present- neous ICH.10,15,16,28,33,40,41 Once again, in the majority of cases ed with both oculomotor and trochlear nerve paresis. these findings have been reported to reverse completely following resolution of the CSF leak. Response to Therapy Visual acuity and field deficits have been reported and Of the 30 patients with ophthalmoplegia secondary to may result from stretching of the optic complex over the spontaneous ICH in whom there were available data, 12 pituitary fossa, or perhaps vascular congestion of the optic underwent conservative treatment alone. Fifteen patients nerves and tracts.22,29,38 Low-grade ischemic injury to the underwent epidural blood patch administration, with suc- occipital lobes secondary to pressure on the posterior cere- cessful outcomes and correction of ophthalmoplegia re- bral arteries has been suggested as another potential mech- ported in 14 (93%) of 15 cases. Four patients underwent anism of visual field deficits.13,21 Cerebral vasospasm, surgical repair of a CSF leak. Additionally, 2 patients un- potentially resulting in cortical ischemic deficits, may be derwent craniotomy for evacuation of subdural fluid col- another potential mechanism.11 Finally, cortical disturban- lections. In all cases except for 1 (98%), the symptoms and ces secondary to the frequent development of subdural cranial nerve paresis resolved completely. In 1 case report, hematomas associated with spontaneous ICH may result in a patient who was in a coma with bilateral trochlear nerve visual field obscuration.39 There has been no definite pat- palsies and a unilateral failed to tern of visual field deficits associated with spontaneous improve following standard management. These condi- spontaneous ICH, yet authors of some case reports have tions were believed to be secondary to brainstem injury. suggested a predilection for visual field deficits in the supe- The bilateral was repaired with extrocular mus- rior nasal quadrants.22,31 cle surgery.10 In accordance with the Monro–Kellie doctrine, engorge- ment of the cerebral venous system ensues following reple- Discussion tion of CSF observed with spontaneous ICH. Radiographic manifestations of this phenomenon include venous sinus Spontaneous ICH was first reported by Schaltenbrand in 37 engorgement, pachymeningeal enhancement, subdural ef- 1938, who coined the term “aliquorrhea.” Over the last 2 fusions, enlargement of the pituitary gland, and reduced decades, this condition has been diagnosed more frequent- diameter of the ophthalmic venous system.12,35 In a recent ly, especially in patients with underlying systemic connec- study, Chen et al.12 assessed the mean diameter of the SOV tive tissue diseases such as Marfan disease. A precipitating in patients with spontaneous ICH by using Doppler ultra- traumatic event, often a relatively minor traumatic injury, sonography. In a group of 13 patients with spontaneous can also be associated with the onset of symptoms. Spon- ICH, the mean SOV diameter was significantly smaller taneous ICH can present with a variety of ocular manifes- than in a similar group of controls (0.9 versus 1.85 mm, tations, including visual acuity and field deficits, nystag- p Յ 0.001). The authors attributed this finding to the in- mus, and photophobia. Cranial nerve palsies, often re- creased pressure gradient established across the SOV ex- sulting in ophthalmoplegia, have been reported to occur tracranial–intracranial anastamosis, resulting in increased with symptomatic spontaneous ICH. The precise patho- blood velocity and flow.12 The same study also demonstrat- physiology of cranial nerve paresis in spontaneous ICH re- ed partial resolution of this finding following treatment of mains to be determined. Depending on the affected cranial SIH, which correlated with improved MR imaging find- nerve, potential causes include traction on cranial nerves ings. due to downward displacement of the cranial contents, cranial nerve compression, or vascular congestion of the Response to Therapy nerve.22,29,35 In advanced cases, progressive herniation may result in irreversible injury to the brainstem and cranial Patients with spontaneous ICH will frequently respond nerve nuclei.10,34 Various forms of can result in favorably to conservative treatment alone. This may in- severe cases of ICH. Tonsillar herniation may result in clude recumbent positioning, intravenous fluids, and intra- downbeat or gaze-evoked nystagmus. Injury to the medul- venous caffeine administration. When conservative man- la or vermis may result in upbeat nystagmus. Ocular bob- agement fails, the gold-standard treatment for spontaneous

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ICH has been autologous epidural blood patch administra- cranial hypotension: clinical and magnetic resonance imaging tion. This therapy has been extremely effective, and has characteristics. Clin Neurol Neurosurg 99:199–204, 1997 been noted to work even if the precise level of spinal dural 10. Brady-McCreery KM, Speidel S, Hussein MA, Coats DK: Spon- leakage is unknown. Only 1 patient was noted to have con- taneous intracranial hypotension with unique strabismus due to third and fourth cranial neuropathies. Binocul Vis Strabismus Q tinued symptoms following epidural blood patch adminis- 17:43–48, 2002 tration. At times, repeated epidural blood patch therapy 11. Chaves C, Freidberg SR, Lee G, Zerris V, Ries S, Chavali R: Cere- may be required for persistent symptoms. Surgical inter- bral vasospasm following intracranial hypotension caused by vention for primary repair of a CSF leak is rarely required, cerebrospinal fluid leak from an incidental lumbar durotomy. yet has been described in other series.14 Recently, a group Case report. J Neurosurg 102:152–155, 2005 at our institution reported the benefit of intracranial pres- 12. Chen WT, Fuh JL, Lirng JF, Lu SR, Wu ZA, Wang SJ: Collapsed sure monitoring as an adjunct to diagnosis and therapy for superior ophthalmic veins in patients with spontaneous intracra- spontaneous ICH.41 nial hypotension. 61:1265–1267, 2003 In the majority of cases, repairing CSF leakage at its 13. Christoforidis GA, Mehta BA, Landi JL, Czarnecki EJ, Pias- source and thus repleting the CSF volume will improve kowski RA: Spontaneous intracranial hypotension: report of four cases and review of the literature. Neuroradiology 40:636–643, symptoms. According to our review, most cases of sponta- 1998 neous ICH–related ophthalmoplegia will reverse following 14. Cohen-Gadol AA, Mokri B, Piepgras DG, Meyer FB, Atkinson standard treatment. In advanced cases, if significant down- JL: Surgical anatomy of dural defects in spontaneous spinal cere- ward brainstem injury or ischemic injury has occurred, irre- brospinal fluid leaks. Neurosurgery 58 (4 Suppl): ONS238– versible central cranial nerve deficits can be observed that ONS245, 2006 may not be reversible. 15. Ferrante E, Savino A, Brioschi A, Marazzi R, Donato MF, Riva M: Transient oculomotor cranial nerves palsy in spontaneous in- tracranial hypotension. J Neurosurg Sci 42:177–180, 1998 Conclusions 16. Ferrante E, Wetzl R, Savino A, Citterio A, Protti A: Spontaneous Intracranial hypotension can present with a wide variety cerebrospinal fluid leak syndrome: report of 18 cases. Neurol Sci 25 (3 Suppl): S293–S295, 2004 of visual symptoms and findings. Deficits in visual acuity, 17. García-Morales I, Porta-Etessam J, Galán L, Lagares A, Molina visual fields, and ophthalmoplegia have been frequently JA: Recurrent subdural haematomas in a patient with spontaneous described. By far, the most commonly encountered cranial intracranial hypotension. Cephalalgia 21:703–705, 2001 nerve deficit is an abducens nerve paresis, which may oc- 18. Gibson BE, Wedel DJ, Faust RJ, Petersen RC: Continuous epidur- cur unilaterally or bilaterally. Although less common, ocu- al saline infusion for the treatment of low CSF pressure headache. lomotor and trochlear nerve palsies have been reported as Anesthesiology 68:789–791, 1988 well. The optic nerve complex is frequently involved in 19. Grueb M, Besch D, Mielke J, Reinthal E, Herzau V: Abducens spontaneous ICH, and may manifest as deficits in visual nerve paresis in spontaneous intracranial hypotension syndrome. acuity and field cuts. The pathophysiology for the variety Acta Ophthalmol Scand 83:269–270, 2005 of visual deficits encountered is multifactorial. The major- 20. Guigon B, Tailla H, de la Marnière E, Macarez R, Bazin S, Madzou M: [Abducens nerve palsy in spontaneous intracranial ity of symptoms and cranial nerve deficits reviewed res- hypotension.] J Fr Ophtalmol 27:392–396, 2004 pond favorably to standard management, which in the 21. Hochman MS, Naidich TP, Kobetz SA, Fernandez-Maitin A: majority of cases requires epidural blood patch administra- Spontaneous intracranial hypotension with pachymeningeal en- tion. hancement on MRI. Neurology 42:1628–1630, 1992 22. Horton JC, Fishman RA: Neurovisual findings in the syndrome of References spontaneous intracranial hypotension from dural cerebrospinal fluid leak. Ophthalmology 101:244–251, 1994 1. Akkawi N, Locatelli P, Borroni B, Agosti C, Pezzini A, Stefini R, 23. Khemka S, Mearza AA: Isolated sixth nerve palsy secondary to et al: A complicated case of intracranial hypotension: diagnostic spontaneous intracranial hypotension. Eur J Neurol 13: and management strategies. Neurol Sci 27:63–66, 2006 1264–1265, 2006 2. Anonymous: Case records of the Massachusetts General Hospital. 24. Kose KC, Cebesoy O, Karadeniz E, Bilgin S: Eye problem fol- Weekly clinicopathological exercises. Case 2–1998. A 50-year- lowing foot surgery—abducens palsy as a complication of spinal old woman with increasing headache and a left abducent-nerve anesthesia. MedGenMed 7:15, 2005 palsy. N Engl J Med 338:180–188, 1998 25. Luijckx GJ, De Jaegere T: Magnetic resonance imaging findings 3. Apte RS, Bartek W, Mello A, et al: Spontaneous intracranial hy- before and after treatment of spontaneous intracranial hypoten- potension. Am J Ophthalmol 127:482–485, 1999 sion. J Neurol Neurosurg Psychiatry 71:411, 2001 4. Baryshnik DB, Farb RI: Changes in the appearance of venous 26. Mathews MK, Frohman L, Lee HJ, Sergott RC, Savino PJ: Spinal sinuses after treatment of disordered . Neu- fluid leak after chiropractic manipulation of the cervical spine. rology 62:1445–1446, 2004 Arch Ophthalmol 124:283, 2006 5. Béchard P, Perron G, Larochelle D, Lacroix M, Labourdette A, 27. Merlo P, Clerici AM, Stival B, Rebecchi V, Noce M, Mazza S: Dolbec P: Case report: epidural blood patch in the treatment of Spontaneous intracranial hypotension: case report. J Headache abducens palsy after a dural puncture. Can J Anaesth 54: Pain 6:477, 2005 146–150, 2007 28. Mikawa S, Ebina T: [Spontaneous intracranial hypotension com- 6. Beck J, Raabe A, Seifert V, Dettmann E: Intracranial hypotension plicating subdural hematoma: unilateral oculomotor nerve palsy after chiropractic manipulation of the cervical spine. J Neurol caused by epidural blood patch.] No Shinkei Geka 29:747–753, Neurosurg Psychiatry 74:821–822, 2003 2001 (Jpn) 7. 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31. Mokri B, Posner JB: Spontaneous intracranial hypotension: the 38. Schievink WI: Spontaneous spinal cerebrospinal fluid leaks and broadening clinical and imaging spectrum of CSF leaks. Neu- intracranial hypotension. JAMA 295:2286–2296, 2006 rology 55:1771–1772, 2000 39. Schievink WI, Maya MM, Moser FG, Tourje J: Spectrum of sub- 32. Molins A, Alvárez J, Sumalla J, Titus F, Codina A: Cisternograph- dural fluid collections in spontaneous intracranial hypotension. J ic pattern of spontaneous liquoral hypotension. Cephalalgia 10: Neurosurg 103:608–613, 2005 59–65, 1990 40. Warner GT: Spontaneous intracranial hypotension causing a par- 33. Ohta H, Genmoto T, Yokota A: [Spontaneous intracranial hypo- tial third cranial nerve palsy: a novel observation. Cephalalgia tension associated with trochlear nerve palsy and bilateral chron- 22:822–823, 2002 ic subdural hematoma.] No To Shinkei 56:169–172, 2004 (Jpn) 41. Zada G, Pezeshkian P, Giannotta S: Spontaneous intracranial 34. Openshaw H: Kernohan notch lesion after spinal tap. Neurology hypotension and immediate improvement following epidural 64:1631, 2005 blood patch placement demonstrated by intracranial pressure 35. Paldino M, Mogilner AY, Tenner MS: Intracranial hypotension monitoring. Case report. J Neurosurg 106:1089–1090, 2007 syndrome: a comprehensive review. Neurosurg Focus 15(6): ECP2, 2003 Manuscript submitted September 10, 2007. 36. Pannullo SC, Reich JB, Krol G, Deck MD, Posner JB: MRI Accepted September 27, 2007. changes in intracranial hypotension. Neurology 43:919–926, Address correspondence to: Gabriel Zada, M.D., Department of 1993 Neurosurgery, University of Southern California, 1200 North State 37. Schaltenbrand G: Neuere Anschauungen zur Pathophysiologie der Street, Suite 5046, Los Angeles, California 90089 email: gzada Liquorzirkulation. Zentrablbl Neurochir 3:290–300, 1938 @usc.edu.

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