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Table 1. 
Etiology of Complete Bilateral Ophthalmoplegia
Etiology of Complete Bilateral Ophthalmoplegia
Table 2. 
Location of Lesions Causing Complete Ophthalmoplegia
Location of Lesions Causing Complete Ophthalmoplegia
1.
Gowers  WR A Manual of Diseases of the Nervous System.  Philadelphia, Pa: P Blakiston, Son & Co; 1888
2.
Keane  JR Acute bilateral ophthalmoplegia: 60 cases. Neurology 1986;36279- 281
PubMedArticle
3.
Mori  MKuwabara  SFukatake  TYuki  NHattori  T Clinical features and prognosis of Miller Fisher syndrome. Neurology 2001;561104- 1106
PubMedArticle
4.
Phillips  RETheakston  RDWarrell  DA  et al.  Paralysis, rhabdomyolysis and haemolysis causes by bites of Russell's viper (Vipera russelli pulchella) in Sri Lanka: failure of Indian (Haffkine) antivenom. Q J Med 1988;68691- 715
PubMed
5.
Grattan-Smith  PJMorris  JGJohnston  HM  et al.  Clinical and neurophysiological features of tick paralysis. Brain 1997;1201975- 1987
PubMedArticle
6.
Jayme-Goyaz  GG Cephalic tetanus following injury to the eyeball. Am J Ophthalmol 1941;241281- 1299
7.
Keane  JR Multiple cranial nerve palsies: analysis of 979 cases. Arch Neurol 2005;621714- 1717
PubMedArticle
8.
Cammarata  SSchenone  APasquali  GFTabaton  M Complete bilateral relapsing ophthalmoplegia in a diabetic patient with a sensory-motor distal polyneuropathy. Eur Neurol 1986;25278- 280
PubMedArticle
9.
Raflo  GTFarrell  TASioussat  RS Complete ophthalmoplegia secondary to amyloidosis associated with multiple myeloma. Am J Ophthalmol 1981;92221- 224
PubMed
10.
Hermans  GRetif  JPerier  O Acute bilateral ophthalmoplegia caused by median tumor of the base of the skull [in French]. Bull Soc Belge Ophtalmol 1964;138593- 601
PubMed
11.
Jonkhoff  ARHuijgens  PCSchreuder  WOTeule  GJJHeimans  JJ Hypophyseal non-Hodgkins lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy. J Neurooncol 1993;17155- 158
PubMedArticle
12.
Tsuda  HKashima  YIshikawa  HIkeda  MSawada  U Malignant lymphoma in the cavernous sinus with bilateral total ophthalmoplegia and tonic pupils. Neuroophthalmology 2004;28237- 243Article
13.
Nudleman  KLChoi  BKusske  JA Primary pituitary carcinoma: a clinical pathological study. Neurosurgery 1985;1690- 95
PubMedArticle
14.
Cakmak  OErgin  TNAydin  VM Isolated sphenoid sinus adenocarcinoma: a case report. Eur Arch Otorhinolaryngol 2002;259266- 268
PubMedArticle
15.
Anderson  DFAfshar  FToma  N Metastatic prostatic adenocarcinoma presenting as complete ophthalmoplegia from pituitary apoplexy. Br J Ophthalmol 1994;78315- 316
PubMedArticle
16.
Bitoh  SHasegawa  HOhtsuki  HObashi  JKobayashi  Y Parasellar metastases: four autopsied cases. Surg Neurol 1985;2341- 48
PubMedArticle
17.
Eurelings  MFrijns  CJJeurissen  FJ Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: case study and review of the literature. Neuro-oncol 2002;444- 48
PubMedArticle
18.
Lau  JJOkada  CYTrobe  JD Galloping ophthalmoplegia and numb chin in Burkitt lymphoma. J Neuroophthalmol 2004;24130- 134
PubMedArticle
19.
Alam  AChander  BN Craniofacial fibrous dysplasia presenting with visual impairment. Med J Armed Forces India 2003;59342- 343Article
20.
Kamel  HAMChoudhari  KAGillespie  JSJ Bilateral traumatic caroticocavernous fistulae: total resolution following unilateral occlusion. Neuroradiology 2000;42462- 465
PubMedArticle
21.
Vaphiades  MSBrock  WBrown  HHPetursson  GWestfall  CT Catastrophic antiphospholipid antibody syndrome manifesting as an orbital ischemic syndrome. J Neuroophthalmol 2001;21260- 263
PubMedArticle
22.
Kastenbauer  SPfister  H-W Pneumococcal meningitis in adults. Brain 2003;1261015- 1025
PubMedArticle
23.
Visudtibhan  AVisudhiphan  PChiemchanya  S Cavernous sinus thrombophlebitis in children. Pediatr Neurol 2001;24123- 127
PubMedArticle
24.
Schwartz  JNDonnelly  EHKlintworth  GK Ocular and orbital phycomycosis. Surv Ophthalmol 1977;223- 28
PubMedArticle
25.
Kasper  LHBernat  JLNordgren  REReeves  AG Bilateral rhinocerebral phycomycosis. Ann Neurol 1979;6131- 133
PubMedArticle
26.
Mylonakis  EPaliou  MSax  PESkolnik  PRBaron  MJRich  JD Central nervous system aspergillosis in patients with human immunodeficiency virus infection: report of 6 cases and review. Medicine (Baltimore) 2000;79269- 280
PubMedArticle
27.
Holland  NRDeibert  E CNS actinomycosis presenting with bilateral cavernous sinus syndrome. J Neurol Neurosurg Psychiatry 1998;644
PubMedArticle
28.
Tomecek  FJMorgan  JK Ophthalmoplegia with bilateral ptosis secondary to midbrain hemorrhage: a case with clinical and radiologic correlation. Surg Neurol 1994;41131- 136
PubMedArticle
29.
de Mendonca  APimentel  JMorgado  FFerro  JM Mesencephalic haematoma: case report with autopsy study. J Neurol 1990;23755- 58
PubMedArticle
30.
Harvey  FHCarlow  TJ Brainstem abscess and the syndrome of acute tegmental encephalitis. Ann Neurol 1980;7371- 376
PubMedArticle
31.
Sarma  SSekhar  LN Brain-stem abscess successfully treated by microsurgical drainage: a case report. Neurol Res 2001;23855- 861
PubMedArticle
32.
Kalita  JMisra  UK Neurophysiological changes in Japanese encephalitis. Neurol India 2002;50262- 266
PubMed
33.
Centers for Disease Control and Prevention, Outbreak of Powassan encephalitis: Maine and Vermont, 1999-2001. JAMA 2001;2861962- 1963
PubMedArticle
34.
Dietl  HWPulst  St-MEngelhardt  PMehraein  P Paraneoplastic brainstem encephalitis with acute dystonia and central hypoventilation. J Neurol 1982;227229- 238
PubMedArticle
35.
Rees  JHHain  SFJohnson  MR  et al.  The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders. Brain 2001;1242223- 2231
PubMedArticle
36.
Barnett  MProsser  JSutton  I  et al.  Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J Neurol Neurosurg Psychiatry 2001;70222- 225
PubMedArticle
37.
Victor  MAdams  RDCollins  GH The Wernicke-Korsakoff Syndrome.  Philadelphia, Pa: FA Davis Co; 1971: 27
38.
Cogan  DGWitt  EDGoldman-Rakic  PS Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans. Arch Ophthalmol 1985;1031212- 1220
PubMedArticle
39.
Puri  VChaudhry  N Total external ophthalmoplegia induced by phenytoin: a case report and review of literature. Neurol India 2004;52386- 387
PubMed
40.
Friedman  DIForman  SLevi  LLavin  PJDonahue  S Unusual ocular motility disturbances with increased intracranial pressure. Neurology 1998;501893- 1896
PubMedArticle
Neurological Review
February 2007

Bilateral Ocular ParalysisAnalysis of 31 Inpatients

Author Affiliations

Author Affiliation: Department of Neurology, University of Southern California, Los Angeles.

Arch Neurol. 2007;64(2):178-180. doi:10.1001/archneur.64.2.178
Abstract

To my knowledge, no general study of complete ophthalmoplegia is available. This study was performed to determine the seats and causes of bilateral ocular paralysis. The personal records of 13 440 neurology and neurosurgery inpatients were reviewed. Eighteen (58%) of 31 patients had Fisher syndrome (13 cases) or Guillain-Barré syndrome (5 cases). Four cases resulted from midbrain infarction, 3 from myasthenia, and 1 each from pituitary apoplexy, skull base metastasis, botulism, mucormycosis, phenytoin toxicity, and trauma. Many conditions produce complete ophthalmoplegia on rare occasions, but Fisher syndrome, which paralyzes the eyes in nearly one third of cases, was by far the commonest cause.

In 1888, W. R. Gowers wrote

Paralysis of all the muscles of both eyes, internal and external, while theoretically conceivable from disease at the neighborhood of the orbital fissure and optic foramen on each side . . . is practically only met with in cases of nuclear disease. . . . Whether acute multiple neuritis ever involves the ocular nerves we do not know; the possibility that such peripheral neuritis may simulate central disease must be borne in mind.1

Complete bilateral ocular paralysis is a rare condition, usually reported as single cases. As no general study is available to my knowledge, I reviewed my experience to determine the causes and locations of conditions immobilizing both eyes.

METHODS

From personal records of 13 440 inpatients who were personally examined in the wards of the Los Angeles County/University of Southern California Medical Center during a 34-year period, I selected those without perceptible movement in either eye. Comatose patients were excluded. Seven of the patients have been described previously.2 Photographs available for review included 21 slides, 4 video segments, 1 movie clip, and 1 fundus photograph. Diagnoses were established by history, physical examination, and contemporary laboratory and radiological tests. Guillain-Barré syndrome was distinguished from Fisher syndrome by the presence of definite limb weakness. Clinical and radiographic findings provided localization.

RESULTS

Complete ophthalmoplegia occurred in 31 patients (0.2% of my patients). Their ages ranged from 3 to 73 years, with a mean age of 49 years; 22 (71%) were men. The pupils were fixed in 16 cases (>5 mm in 13 cases), partially involved in 8, and spared in 7. Two patients with Fisher syndrome developed oval, reactive pupils. Ptosis was complete in 25 cases, partial in 5, and absent in 1.

Cranial nerve involvement, aside from the ocular motor nerves, occurred in 17 patients and included optic neuropathy in 4 cases bilaterally and 2 unilaterally; unilateral 5th-nerve impairment in 1 case; and bilateral involvement of the 7th nerves in 9 cases, the 10th nerves in 4 cases, the 11th nerves in 3 cases, and the 12th nerves in 2 cases.

Fisher syndrome (13 cases) and Guillain-Barré syndrome (5 cases) were the leading causes of ophthalmoplegia, together composing 18 (58%) of 31 cases. (Ocular paralysis occurred in 31% of my cases with Fisher syndrome and 3% of those with Guillain-Barré syndrome [Table 1].) Midbrain-thalamic infarcts were responsible for 4 cases (3 from atherosclerosis and 1 with cryptococcal meningitis associated with dermatomyositis), 3 cases had myasthenia, and there was 1 case each with orbitosinus mucormycosis, foodborne botulism, pituitary apoplexy, renal carcinoma metastasizing to the skull base (clivus-cavernous sinuses and posterior orbits), acute phenytoin toxicity, and automobile trauma with fractures through the cavernous sinuses and orbits.

Sites of involvement included polyneuropathy in 18 cases, the brainstem in 5, the neuromuscular junction in 4, cavernous sinuses and posterior orbits in 3, and the cavernous sinuses in 1 (Table 2).

COMMENT
POLYNEUROPATHY

The high proportion of patients with Fisher and Guillain-Barré syndromes in this series reflects the fact that nearly one third of patients with Fisher syndrome develop complete ophthalmoplegia3 (Table 1). Indeed, Fisher syndrome is one of the few conditions—along with neurotoxic snake4 and tick5 bites—that commonly produce complete ocular paralysis. Cephalic tetanus6 is an occasional cause of bilateral ocular paralysis, but diabetic cranial neuropathy, one of the commonest causes of diplopia and an occasional cause of cranial polyneuropathy,7 very rarely causes complete bilateral ophthalmoplegia.8

MUSCLE AND NEUROMUSCULAR JUNCTION

Impairment of neuromuscular transmission would seem to be a parsimonious route to ophthalmoplegia, but only 1% of my patients with myasthenia and 6% of those with botulism (Table 1) had complete ocular paralysis. Neurotoxins are more effective at blocking the neuromuscular junctions of eye muscles, acting presynaptically in tick bite paralysis5 and through presynaptic or postsynaptic effects in snake envenomation.4

Thyroid eye disease, among the commonest causes of diplopia in eye clinics, rarely produces sufficient tethering and weakness of the extraocular muscles to eliminate all eye movements. In contrast, amyloidosis is an uncommon condition that paralyzes the eyes out of proportion to its rarity.9 Many cases of congenital ocular fibrosis and congenital myopathic ophthalmoplegia exhibit minimal or absent eye movement whereas progressive external ophthalmoplegia exhibits slowly progressive ocular limitation that occasionally becomes complete.

CAVERNOUS SINUS AND ORBITS

A 1964 review10 of skull base lesions found 14 cases of complete bilateral ocular paralysis caused by tumors and 5 cases with vascular causes. Tumors included 5 originating in the pituitary or hypophysis, 3 metastases (lung, breast, and ovarian primary tumors), 2 sinus malignancies, 2 of indeterminate nature, 1 lymphoma, and 1 nasopharyngeal malignancy. Vascular causes consisted of 2 cases of carotid-cavernous fistulae, 1 case with combined effects of fistula and repair, 1 supraclinoid carotid aneurysm crossing the midline (with incomplete paralysis), and 1 case of paired cavernous carotid aneurysms.10

More recent reports include malignancies involving the cavernous sinuses (lymphoma,11,12 pituitary carcinoma,13 sphenoid sinus adenocarcinoma,14 and metastases from prostate carcinoma15 and mesenteric liposarcoma16), skull base (parathyroid metastasis17), and meninges (lymphoma18). Exceptionally, benign involvement of the skull base with fibrous dysplasia can result in ocular paralysis.19

Vascular causes include carotid-cavernous fistulae20 and bilateral orbital infarction associated with antiphospholipid antibody syndrome.21 Meningitis is a surprisingly rare cause of complete bilateral ophthalmoplegia,22 as is bacterial cavernous sinus thrombophlebitis,23 but sino-orbital-cavernous fungal diseases (mucormycosis,24,25 or less commonly, aspergillosis26 or actinomycosis27) disproportionately paralyze the eyes through infarction and inflammation.

BRAINSTEM

Coma often obscures ophthalmoplegia in central lesions of the midbrain, but rarely, strokes,28,29 abscess,30,31 viral encephalitis,32,33 and paraneoplastic encephalitis3436 paralyze both eyes. Occasionally, progressive supranuclear palsy, Whipple disease, and even multiple sclerosis render the eyes immobile, largely through supranuclear mechanisms. Wernicke disease produced complete ophthalmoplegia in 3% of cases in a large series,37 and experimental Wernicke disease typically progresses to complete ophthalmoplegia.38 The rare ophthalmoplegic brainstem toxicity of drugs (especially phenytoin and carbamazepine) frequently produces caloric-fast, reversible ocular paralysis with sparing of the pupils and often the eyelids.39 Finally, a few curious cases document the unexplained association of increased intracranial pressure with complete ophthalmoplegia.40

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Article Information

Correspondence: James R. Keane, MD, Department of Neurology, University of Southern California Medical School, Room 5641, 1200 N State St, Los Angeles, CA 90033 (jkeane@usc.edu).

Accepted for Publication: January 15, 2006.

Financial Disclosure: None reported.

References
1.
Gowers  WR A Manual of Diseases of the Nervous System.  Philadelphia, Pa: P Blakiston, Son & Co; 1888
2.
Keane  JR Acute bilateral ophthalmoplegia: 60 cases. Neurology 1986;36279- 281
PubMedArticle
3.
Mori  MKuwabara  SFukatake  TYuki  NHattori  T Clinical features and prognosis of Miller Fisher syndrome. Neurology 2001;561104- 1106
PubMedArticle
4.
Phillips  RETheakston  RDWarrell  DA  et al.  Paralysis, rhabdomyolysis and haemolysis causes by bites of Russell's viper (Vipera russelli pulchella) in Sri Lanka: failure of Indian (Haffkine) antivenom. Q J Med 1988;68691- 715
PubMed
5.
Grattan-Smith  PJMorris  JGJohnston  HM  et al.  Clinical and neurophysiological features of tick paralysis. Brain 1997;1201975- 1987
PubMedArticle
6.
Jayme-Goyaz  GG Cephalic tetanus following injury to the eyeball. Am J Ophthalmol 1941;241281- 1299
7.
Keane  JR Multiple cranial nerve palsies: analysis of 979 cases. Arch Neurol 2005;621714- 1717
PubMedArticle
8.
Cammarata  SSchenone  APasquali  GFTabaton  M Complete bilateral relapsing ophthalmoplegia in a diabetic patient with a sensory-motor distal polyneuropathy. Eur Neurol 1986;25278- 280
PubMedArticle
9.
Raflo  GTFarrell  TASioussat  RS Complete ophthalmoplegia secondary to amyloidosis associated with multiple myeloma. Am J Ophthalmol 1981;92221- 224
PubMed
10.
Hermans  GRetif  JPerier  O Acute bilateral ophthalmoplegia caused by median tumor of the base of the skull [in French]. Bull Soc Belge Ophtalmol 1964;138593- 601
PubMed
11.
Jonkhoff  ARHuijgens  PCSchreuder  WOTeule  GJJHeimans  JJ Hypophyseal non-Hodgkins lymphoma presenting with clinical panhypopituitarism successfully treated with chemotherapy. J Neurooncol 1993;17155- 158
PubMedArticle
12.
Tsuda  HKashima  YIshikawa  HIkeda  MSawada  U Malignant lymphoma in the cavernous sinus with bilateral total ophthalmoplegia and tonic pupils. Neuroophthalmology 2004;28237- 243Article
13.
Nudleman  KLChoi  BKusske  JA Primary pituitary carcinoma: a clinical pathological study. Neurosurgery 1985;1690- 95
PubMedArticle
14.
Cakmak  OErgin  TNAydin  VM Isolated sphenoid sinus adenocarcinoma: a case report. Eur Arch Otorhinolaryngol 2002;259266- 268
PubMedArticle
15.
Anderson  DFAfshar  FToma  N Metastatic prostatic adenocarcinoma presenting as complete ophthalmoplegia from pituitary apoplexy. Br J Ophthalmol 1994;78315- 316
PubMedArticle
16.
Bitoh  SHasegawa  HOhtsuki  HObashi  JKobayashi  Y Parasellar metastases: four autopsied cases. Surg Neurol 1985;2341- 48
PubMedArticle
17.
Eurelings  MFrijns  CJJeurissen  FJ Painful ophthalmoplegia from metastatic nonproducing parathyroid carcinoma: case study and review of the literature. Neuro-oncol 2002;444- 48
PubMedArticle
18.
Lau  JJOkada  CYTrobe  JD Galloping ophthalmoplegia and numb chin in Burkitt lymphoma. J Neuroophthalmol 2004;24130- 134
PubMedArticle
19.
Alam  AChander  BN Craniofacial fibrous dysplasia presenting with visual impairment. Med J Armed Forces India 2003;59342- 343Article
20.
Kamel  HAMChoudhari  KAGillespie  JSJ Bilateral traumatic caroticocavernous fistulae: total resolution following unilateral occlusion. Neuroradiology 2000;42462- 465
PubMedArticle
21.
Vaphiades  MSBrock  WBrown  HHPetursson  GWestfall  CT Catastrophic antiphospholipid antibody syndrome manifesting as an orbital ischemic syndrome. J Neuroophthalmol 2001;21260- 263
PubMedArticle
22.
Kastenbauer  SPfister  H-W Pneumococcal meningitis in adults. Brain 2003;1261015- 1025
PubMedArticle
23.
Visudtibhan  AVisudhiphan  PChiemchanya  S Cavernous sinus thrombophlebitis in children. Pediatr Neurol 2001;24123- 127
PubMedArticle
24.
Schwartz  JNDonnelly  EHKlintworth  GK Ocular and orbital phycomycosis. Surv Ophthalmol 1977;223- 28
PubMedArticle
25.
Kasper  LHBernat  JLNordgren  REReeves  AG Bilateral rhinocerebral phycomycosis. Ann Neurol 1979;6131- 133
PubMedArticle
26.
Mylonakis  EPaliou  MSax  PESkolnik  PRBaron  MJRich  JD Central nervous system aspergillosis in patients with human immunodeficiency virus infection: report of 6 cases and review. Medicine (Baltimore) 2000;79269- 280
PubMedArticle
27.
Holland  NRDeibert  E CNS actinomycosis presenting with bilateral cavernous sinus syndrome. J Neurol Neurosurg Psychiatry 1998;644
PubMedArticle
28.
Tomecek  FJMorgan  JK Ophthalmoplegia with bilateral ptosis secondary to midbrain hemorrhage: a case with clinical and radiologic correlation. Surg Neurol 1994;41131- 136
PubMedArticle
29.
de Mendonca  APimentel  JMorgado  FFerro  JM Mesencephalic haematoma: case report with autopsy study. J Neurol 1990;23755- 58
PubMedArticle
30.
Harvey  FHCarlow  TJ Brainstem abscess and the syndrome of acute tegmental encephalitis. Ann Neurol 1980;7371- 376
PubMedArticle
31.
Sarma  SSekhar  LN Brain-stem abscess successfully treated by microsurgical drainage: a case report. Neurol Res 2001;23855- 861
PubMedArticle
32.
Kalita  JMisra  UK Neurophysiological changes in Japanese encephalitis. Neurol India 2002;50262- 266
PubMed
33.
Centers for Disease Control and Prevention, Outbreak of Powassan encephalitis: Maine and Vermont, 1999-2001. JAMA 2001;2861962- 1963
PubMedArticle
34.
Dietl  HWPulst  St-MEngelhardt  PMehraein  P Paraneoplastic brainstem encephalitis with acute dystonia and central hypoventilation. J Neurol 1982;227229- 238
PubMedArticle
35.
Rees  JHHain  SFJohnson  MR  et al.  The role of [18F]fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders. Brain 2001;1242223- 2231
PubMedArticle
36.
Barnett  MProsser  JSutton  I  et al.  Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J Neurol Neurosurg Psychiatry 2001;70222- 225
PubMedArticle
37.
Victor  MAdams  RDCollins  GH The Wernicke-Korsakoff Syndrome.  Philadelphia, Pa: FA Davis Co; 1971: 27
38.
Cogan  DGWitt  EDGoldman-Rakic  PS Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans. Arch Ophthalmol 1985;1031212- 1220
PubMedArticle
39.
Puri  VChaudhry  N Total external ophthalmoplegia induced by phenytoin: a case report and review of literature. Neurol India 2004;52386- 387
PubMed
40.
Friedman  DIForman  SLevi  LLavin  PJDonahue  S Unusual ocular motility disturbances with increased intracranial pressure. Neurology 1998;501893- 1896
PubMedArticle
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