Acute Bilateral Ophthalmoplegias

JOHN 8. SELHORST, M.D.

Assistant Professor, Department of Neurology, Medical College of Virginia, Health Sciences Division of Virginia Commonwealth University, Richmond, Virginia

Introduction Bilateral ophthalmoplegia is that condition of distinctive patterns of ophthalmoplegia or are at­ weakness or paralysis involving one or more ocular tended by telltale neurologic findings. These disorders muscles in each eye. Its sudden appearance due to an are more easily identified and require less deliberation. acute ocular myopathy is indeed unusual. Swash re­ ported a single patient with acute necrotizing orbital I. Disorders Affecting Neuromuscular Junctions myositis and carcinomatosis neuromyopathy.1 The Botulism is the linchpin to the differential diag­ more common bilateral ocular muscle diseases, such nosis of acute bilateral ophthalmoplegia because this as dysthyroid exophthalmopathy, orbital myositis, disease primarily affects ocular and bulbar muscles. and progressive external ophthalmoplegia, develop Furthermore it is both an individual and public insidiously and are restricted to the orbit. health emergency, making its detectio_n doubly neces­ In general, acute bilateral ophthalmoplegias afford sary. a unique differential diagnosis of disorders affecting Although its epidemic occurrence is well known infranuclear and supranuclear pathways for the con­ to physicians, several facets of the disease are less well trol of eye movements (Table). They present more recognized. Sporadic outbreaks frequently occur. On­ abruptly than the myopathies and seriously jeopard­ set of symptoms appears up to eight days after inges­ ize respiratory and/ or neurologic function. Among tion of spoiled food.2 Wound botulism which presents these acute bilateral ophthalmoplegias are disorders in the same manner as food-borne botulism was once which diffusely affect neuromuscular junctions or thought rare, but is now more frequently diag­ the nerves to ocular muscles (Table, Parts I and II). nosed.3·4 A vailable neurophysiologic techniques as­ Occasionally these diseases are troublesome to diag­ sist in its recognition; however, the presence of nose because additional neurologic signs are sparse. botulin is only confirmed by a biologic assay. There­ In these instances progressive bulbar and respiratory fore diagnosis rests heavily upon clinical suspicion. weakness may develop unexpectedly. Familiarity with The following patient presentation typifies the their differential diagnosis allows for timely thera­ disease. peutic intervention. This discussion focuses on recog­ A 42-year-old fish meal plant employee vomited nition of this group of acute bilateral ophthalmo­ and complained of pain in his throat while eating plegias and their treatment. homemade vegetable soup. Shortly thereafter his vi­ Those disorders (Table, Parts III and IV) which sion was blurred. The following day he came to the involve only the intracranial portions of the nerves to Medical College of Virginia Hospitals because of dys­ ocular muscles or their brain stem origins have either phagia, diplopia, and hoarseness. He was not in any distress. Vital signs were normal. There was mild ptosis of each eyelid. His pupils were dilated to 8 mm and did not react to light or accommodation Correspondence and reprint requests to Dr. John B. Selhorst, Department of Neurology, Box 698, Medical College of Virginia, (Figure). Near card assessment of visual acuity was Richmond, Virginia 23298. 20/ I 00 in each eye. Moderate abduction and mild

88 MCV QUARTERLY 13(3): 88-92, 1977 SELHORST: ACUTE BILATERAL OPHTHALMOPLEGIAS 89 downgaze paresis of external ocular muscles was Acute Bilateral Ophthalmoplegias present. Schirmer's I test showed deficient tear forma­ I. Disorders affecting neuromuscular junctions tion in each eye. Facial muscles were mildly weak I. Botulism bilaterally, the mouth was dry, and the gag reflex was 2. Myasthenia gravis slightly impaired. Motor, sensory, and reflex examina­ 11. Disorders of ocular nerves tions of the limbs were normal. I. Acute id iopathic polyneuropathy Diagnostic studies began in the emergency room 2. Diphtheria with a Tensilon test which was twice negative. Ill. Disorders within the meninges A lumbar puncture yielded cerebrospinal fluid I. Infection (CSF) under normal pressure which contained sugar 2. Aneurysm of 71 mg%, protein of 28 mg%, and three RBC's. J. Trauma Routine laboratory data were normal. A clinical IV. Disorders of the brain stem diagnosis of botulism was made, and serum was sent I. Wernicke encephalopathy to the Center for Disease Control (CDC) in Atlanta, 2. Multiple sclerosis Ga. Bivalent (A,B) and trivalent (A,B,E) antitoxin J. Poliomyelitis 4. Infarction prepared from horse serum was administered. Fol­ 5. Hemorrhage lowing a mild urticaria! reaction, antitoxin therapy 6. Trauma was discontinued. Weakness soon progressed to in­ volve respiratory more than extremity muscles. Vital capacity dropped to 1100 cc. Tracheostomy was per­ that botulin is the most potent toxin known to man formed. Neurophysiologic tests were consistent with and that ingestion of one spoiled bean is reported to a diagnosis of mild botulism. Muscle potentials in the have led to death.5 face were low in amplitude and short in duration, and Since botulin interferes with the release of acetyl­ rapid repetitive nerve stimulation (30 Hz) produced choline from the distal nerve terminals of skeletal and an incremental increase in muscle potentials recorded smooth muscles, signs and symptoms referable to over the thenar eminence. Mouse-toxin neutral­ parasympathetic blockade are helpful. Dry eyes and ization tests performed by the CDC were positive for dry mouth occur due to secretomotor inhibition of type B Clostridium botulinum toxin. Injection of the lacrimal and salivary glands. Blurred vision results patient's serum killed all the mice not protected with from accommodation failure of a weakened ciliary antitoxin 8. Although the most frequent cause of sporadic botulism occurs with home-processed foods, the source of this patient's exposure was not located. His family had eaten the same vegetable soup with him on two occasions and cultures of the soup did not grow C botulinum. The patient's course was marked by a moder­ ately severe aspiration pneumonia. He responded within one week to antibiotics and frequent suction­ ing. Four weeks after admission, he was discharged with mild hoarseness. Recovery was, otherwise, com­ plete. A pattern of weakness descending from bulbar regions to respiratory and extremity muscles charac­ terizes botulism. Ideally the diagnosis is made before this descending paralysis occurs so that the option to use mechanical ventilation and antitoxin therapy is available. In the early stage of diagnosis several addi­ tional findings are helpful. A history of ingestion of putrid or home-processed food, exposure to Fig-Botulism is suggested by the presence of dilated pupils (top) epidemic botulism, or a recent outdoor wound or which are fixed to light, and accommodation and bilateral abduc­ extremity surgery is important. To be kept in mind is tion paresis (middle and bottom). Ptotic lids are manually retracted. 90 SELHORST: ACUTE BILATERAL OPHTHALMOPLEGIAS muscle. Nonreactive pupillary light responses are fatigue in extraocular muscles upon requesting the caused by paralysis of the pupillary sphincter muscle. patient to maintain upgaze. In this position palpebral The involvement of the pupil coupled with acute and elevator muscles of the eye gradually weaken. bulbar and extraocular muscle weakness makes a Another distinctive ocular sign in myasthenia gravis diagnosis of botulism almost certain. However, pu­ is the lid twitch phenomenon described by Cogan." pillary paralysis occurs infrequently and is not to be Rapid shift of the eyes from a downward position to depended upon for the diagnosis. quick upgaze results in a brief contraction or twitch Once the diagnosis of botulism is suspected, of the levator palpebral muscle before it weakens and specimens from serum and gastric contents are ob­ returns to its ptotic position. Claims of pupillary tained for analysis and typing by mouse-toxin neu­ involvement in myasthenia gravis are poorly docu­ tralization tests. Six pathogenic toxins have been mented and unexpected .since this is a disease of identified (A, 8, C, D, E, F).6 Food suspected of striated muscle. contamination and stools from the patient are cul­ Ordinarily the urgency of a diagnosis in myas­ tured for C botulinum. Recent use of stool cultures thenia gravis does not occur because of its typically have shown botulism poisoning to cause a floppy in­ insidious onset. However, an acute fulminating form fant syndrome.7 An indication of botulism is obtaineq of ocular and bulbar weakness with early respiratory by standard neurophysiologic techniques. In severe muscle involvement has been described.10 In either cases size and duration of motor units are reduced instance the diagnosis of myasthenia gravis is usually and low-rate repetitive nerve stimulation (3 Hz) made by intravenous injection of edrophonium causes decremental muscle potentials, but at high chloride (Tensilon ). Caution in the interpretation rates of stimulation (50 Hz) an incremental re­ of this test in relation to the differential diagnosis sponse occurs. Mild cases show only the incremental of acute ophthalmoplegias is warranted by the response of muscle potentials at high rates of stim~i~­ report of Cherington,12 who described improved tion.8 In botulism these phenomena are more likely to muscle strength and resolution of ptosis following be found in the weakened muscles, and in some in­ intravenous Tensilon in two patients with proven stances are not present in the early course of the botulism. Clinica lly these patients also demonstrated disease.9 Careful screening by the electromyog­ fatigability, but neither responded to sustained rapher is required for incremental responses caused amounts of anticholinesterase medication. In those by artifacts. unusual instances in 'which diagnosis of myasthenia Therapy begins with gastric lavage, cathartics, gravis is not clearly established by intravenous and enemas. Purgation of the gastrointestinal track is Tensilon, repetitive nerve stimulation is recom­ now recommended since stool cultures of C bot­ mended. A decremental response of muscle potentials ulinum have preceded detection of botulin in the is found with slow and rapid sequential stimulation serum. Administration of antitoxin involves risk of of the nerve. Control of acute muscle weakness is adverse reaction, particularly serum sickness, which usually gained by anticholinesterase medication. is comparable to that for tetanus antitoxin.6 There­ Steroids and possibly thymectomy are useful in later fore, use of antitoxin is weighed against the rapidity of stages. development and degree of respiratory failure. More­ over, antitoxin therapy has not resulted in a major II. Disorders of Ocular Nerves decline in mortality rates. Guanidine hydrochloride In patients with acute idiopathic poly­ enhances the release of acetylcholine from the nerve neuropathy (Landry-Guillain-Barre syndrome), in­ terminal and is used to reverse the neuromuscular volvement of ocular nerves occurs in less than one blockade cif botulism. It is helpful in reducing extra­ quarter of the cases while bulbar and facial weak­ ocular and limb weakness but unfortunately is least ness are found in over one half the patients in large effective in reversing paralysis of respiratory muscles.9 series.13•14 Pupils are usually but not invariably spared. It also tends to depress the bone marrow. Ordinarily, ocular muscle weakness follows extremity In myasthenia gravis 40% of the patients have weakness. This ascending paralysis in acute idiopathic diplopia and ptosis either alone or accompanied by polyneuropathy constitutes a major distinction with bulbar or extremity weakness.10 The patte.rn of ocular the descending pa'ralysis that occurs in botulism. muscle involvement is variable. Diagnosis of myas­ Acute idiopathic polyneuropathy is also suggested by thenia gravis is often suggested by the observation of the presence of sensory loss and early disappearance SELHORST: ACUTE BILATERAL OPHTHALMOPLEGIAS 91 of deep tendon reflexes. Laboratory evidence favor­ nerve palsies19 are described in closed head injuries ing acute idiopathic polyneuropathy is obtained by and are thought to occur through injury of the non­ finding elevated protein in the CSF with no more fixed portion of the nerve in its meningeal com­ than a mild pleocytosis and detection of slowed mo­ partment. Bilateral sixth nerve palsies due to trauma tor nerve conduction velocities. These tests are not are usually associated with basilar skull fractures. always a.bnormal in the early course of this disease. Delayed onset of ocular muscle palsies is described Recognition of an -dphthalmoplegia due to acute with fractures of the clivus,20 presumably from hem­ idiopathic polyneuropathy is not always simple. orrhage beneath the d ura. Although others before him had described such a condition, Fisher in 1956 drew attention to a more IV. Disorders of the Brain Stem restricted form of acute idiopathic polyneuropathy.15 Structural alterations in infranuclear and/ or He described an acute polycranial neuritis mani­ supranuclear regions of the brain stem, which con­ fested by an ophthalmoplegia with only generalized trol eye movements, cause acute ophthalmoplegias. areflexia and ataxia. CSF protein was elevated. Others Supranuclear deficits include gaze palsies and intra­ have since described this acute bilateral ophthalmo­ nuclear ophthalmoplegia (JNO) or combinations of plegia and pointed out that subsequent weakness of both, which are recognized by their distinct pattern the extremities does occur.16 Pupils are usually spared, of involvement of ocular muscles. Paralysis of con­ which has led to disputes regarding the central vs jugate horizontal gaze with consequential contralat­ peripheral nature of acute polycranial neuritis. Suc­ eral deviation of the eyes occurs with a lesion in the cess with prednisone therapy has not been shown, ipsilateral pontine paramedian reticular formation. 21 but its use is worthy of consideration early in the Paralysis of adduction with abduction nystagmus is an course of the disease. INO and indicates a lesion in the medial longitudinal Mention of diphtheria today as a cause of oph­ fasciculus (M LF).22 Distinction of an INO from an thalmoplegia is nearly a historical matter. Weakened infranuclear medial rectus palsy is evident by the ocular muscles occur in diphtheria due to a toxic preservation of adduction during convergence. I psi la­ motor neuropathy. Cases are reported in which a teral gaze and adduction paralysis was termed by mild nasopharyngitis went undetected before the par­ Fisher the "one and a half" syndrome because of alytic stage appeared. Recognition is further compli­ the coexistence of a unilateral pontine gaze center cated by the tendency of the exudative membrane and MLF lesion.23 of diphtheria to clear off the larynx before paralysis Bilateral involvement of the fasciculi or nuclei develops. Usually the palate and ciliary muscles are of oculomotor nerves is uncommon and is usually the first to be affected. 11 Paralysis of ocular motor attended by additional neurologic findings. Altered muscles generally follows dysphagia and loss of ac­ consciousness and ataxia with ocular palsies are commodation within several days to several weeks. caused by thiamine deficiency in alcoholic patients Paralysis of respiratory and extremity muscles also with Wernicke encephalopathy. Neuronal degenera­ follows palate or ciliary muscle weakness. Respiratory tion, capillary proliferation, and hemorrhages are failure leads to death if the systemic polyneuropathy diffusely found in periventricular regions of the brain is severe. If the patient survives the toxic phase, all in­ stem including nuclear and fascicular portions of volved nerves usually recover in several months. ocular nerves. Similiar infranuclear lesions with long tract deficits occur in white matter regions involved Ill. Disorders Within the Meninges with the demyelinating plaques of multiple sclerosis. Infection of the leptomeninges, especially tuber­ Both Wernicke encephalopathy and multiple sclerosis culous meningitis, is known to disrupt nerves to ocular also cause sup ran uclear oculomotor palsies. Murray muscles bilaterally. Onset is sometimes sudden and and Walsh described infranuclear ocular muscle the course fulminant. Fever, stiff neck, and typical palsies in several patients with poliomyelitis.24 Iso­ CSF findings lead directly to the diagnosis. Neurosy­ lated bilateral nuclear or fascicular lesions are de­ philis with ' CSF pleocytosis, elevated protein, and scribed only with infarction of third nerve fasciculi positive serology is another frequent cause of men­ and are indeed rare. ingeal ocutar palsies. Abrupt expansion or rupture of Acute supranuclear gaze palsies in this discus­ a posterior fossa aneurysm is reported to cause bilat­ sion include unilateral or bilateral horizontal gaze eral sixth nerve palsies.18 Bilateral third and fourth palsy, the "one and a half" syndrome, and bilateral 92 SELHORST: ACUTE BILATERAL OPHTHALMOPLEGIAS

INO. Contralateral pyramidal tract signs and facial description of lid twitch as a characteristic sign. Arch Ophthal­ paresis due to a lesion within the pons often accom­ mol 74:217-221, 1965. pany an ipsilateral horizontal gaze palsy. Acute up­ 12. CHER IN GTON M: Bot uli sm. Ten-year experience. Arch Neural gaze palsy due to a lesion in the pretectal region25 or 30:432-437, 1974. sudden downgaz;e palsy26 from disruption of the para­ median prerubral field occur rarely. In both horizontal 13 . PL EASU RE DE, LOVELACE RE, D UV OISIN RC: The prognosis of and vertical gaze palsies of abrupt onset, additional acute polyradiculoneuritis. Neurology ( Min neap) 18: I 143- 1148, 1968. neurologic deficits are the rule. They are most frequently caused by infarction, hemorrhage, and 14. McFA RLAND HR, HELLER G: Guillain-Barre disease complex. trauma. The one supranuclear disorder frequently A rch Neuro/ 14:196-201, 1966. not associated with contiguous neurologic signs is bilateral INO. In such instances bilateral !NO 15. FISHER M: An unusual variant of acute idiopathic poly­ neuritis (sy ndrome of ophthalm oplegia, ataxia and arefl exia). strongly suggests multiple sclerosis.21 N Engl J Med 255:57- 65, 1956.

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