key: cord-1044351-bw7i2yu2 authors: Rodrigo-Rey, S.; Gutiérrez-Ortiz, C.; Muñoz, S.; Ortiz-Castillo, J.V.; Siatkowski, R.M. title: What did he eat? date: 2020-09-30 journal: Surv Ophthalmol DOI: 10.1016/j.survophthal.2020.09.007 sha: 65d31ce4221c9b53aaffa97180812316750a3a5f doc_id: 1044351 cord_uid: bw7i2yu2 A 13-year-old boy reported acute horizontal binocular diplopia and headache. Ten days prior to these symptoms, he suffered from a gastrointestinal infection. Ophthalmological examination revealed bilateral ophthalmoparesis and diffuse hyporeflexia. Magnetic resonance imaging of the brain was normal. Lumbar puncture revealed albumin-cytological dissociation. There were no anti-GQ1b antibodies, but serum anti-GM1 antibodies were raised. He received intravenous immunoglobulins and had fully recovered two weeks later. Miller Fisher syndrome and its atypical variants are uncommon in childhood; nevertheless, they should be considered in the differential diagnosis of bilateral acute ophthalmoparesis. A 13-year-old boy was referred for acute horizontal binocular diplopia. His psychomotor development was normal, and his past medical history was unremarkable. He denied head trauma or exposure to toxins. Ten days before he had experienced diarrhea and a low-grade fever, as well as asthenia. On admission, temperature was 99.3ºF. and other vital signs were normal. Cardio-pulmonary auscultation and abdominal examination were normal. His visual acuity (VA) was 20/20 in each eye. Ocular examination revealed a dilated pupil that reacted poorly to light in the left eye. No relative afferent pupillary defect was observed. There was a complex pattern of extrinsic ocular motility abnormalities. He had an incomitant esophoria measuring 12 prism diopters (PD) at distance and 4 PD at near associated with limited abduction of both eyes. In addition, there was a left ptosis (Figure1). He did not relate diurnal variation. Slit lamp biomicroscopy, intraocular pressure, and funduscopy were normal in both eyes. . Comments by R. Michael Siatkowski, MD This patient presents with acute onset of bilateral ophthalmoplegia following a presumed viral illness. The photo shows clear abduction deficits in each eye, as well as an adduction deficit in the right eye. Left-sided ptosis and anisocoria are not easily appreciable in these pictures, but we are told that there is an efferent pupillary defect OS. Bilateral diffuse ophthalmoplegia, whether complete or incomplete, may result from problems anywhere from the brainstem to the neuromuscular junction. From a topical diagnosis standpoint, these include intrinsic brainstem disease such as stroke or demyelination, infectious or non-infectious meningitis, ischemic, inflammatory, or autoimmune disorders of the cranial nerves, cavernous sinus or orbital lesions, and myasthenia gravis or botulism. We are not told whether this patient has any motor or sensory problems that could occur with brainstem or autoimmune disease, but he has no evidence of optic neuropathy, proptosis, or other signs that would be expected with orbital involvement. The presence of anisocoria and/or abnormally reacting pupils is not consistent with myasthenia. Wernicke disease or other vitamin deficiency may present similarly, but this patient's history (or lack thereof) makes it unlikely. Diabetes mellitus has rarely been reported to cause bilateral simultaneous cranial neuropathies, but this is generally in Type 2 patients who are several decades older than this patient. Thus, the differential at this point is brainstem disease, some type of meningitis, a cavernous sinus mass or inflammatory/autoimmune cranial neuropathies. In a previously healthy teenage boy, the most common entities would be a low-grade brainstem tumor, a parasellar mass (craniopharingioma, pituitary adenoma) extending into the cavernous sinus, or parainfectious cranial nerve inflammation (idiopathic post-viral, Miller Fisher syndrome or variant thereof). The appropriate initial workup would consist of neurologic examination, magnetic resonance imaging (MRI) of the brain and posterior fossa with and without gadolinium, and lumbar puncture. If there is any question that the anisocoria may be physiologic or the asymmetric pupillary reactivity is minimal, serum acetylcholine receptor antibodies should be drawn as well (or, alternatively, an edrophonium or prostigmine test if available), as myasthenia is always a great masquerader. The clinical diagnosis of incomplete left third nerve with pupillary involvement and bilateral abducens nerve and palsies was made. Neurological examination revealed no abnormalities in consciousness or corticospinal tract signs. There was no dysmetria, ataxia, limb muscles weakness or sensory deficits. Deep tendon reflexes were diminished. Cranial nerve examination was normal except the previously described ocular motility disturbances. Brain and orbit MRI was unremarkable. Routine biochemistry and hemogram tests were also normal. Serologic test for syphilis, tuberculosis, Borrelia, J o u r n a l P r e -p r o o f cytomegalovirus, Epstein-Barr virus, Herpes simplex virus type 1 and 2, Varicella-Zoster virus and adenovirus were negative. Edrophonum test was also negative. With normal neuroimaging and a negative edrophonium test, autoimuune/inflammatory cranial neuropathies rise to the top of the differential diagnosis. Since the patient is systemically well, infectious meningitis is unlikely, but lumbar puncture is required to assess for non-infectious inflammation. Although there are no clinical trials to support any treatment strategies, management is similar to that for classic Guillain-Barre syndrome, namely intravenous immunoglobulins or plasmaspheresis. Steroids have not been proven to be useful in GBS, so they would not be appropriate in this case. Fortunately, the prognosis for these patients is generally good, with improvement beginning a few weeks after symptom onset, and complete or near-complete recovery within several months. Relapses occur only in 2-3% of patients. Acute ophthalmoplegia accounts for an incomplete form of MFS that might also be associated with hypo or areflexia 17, 29 . Diagnosis is generally based on clinical features, lack of abnormalities in consciousness or corticospinal tract signs, absence of limb weakness, monophasic illness pattern, and the absence of any identifiable alternative diagnosis. Moreover, there may be supportive findings such as CSF albumin-cytological dissociation, electrophysiological abnormalities, and serum anti-GQ1b autoantibodies 25 . Just few cases have been previously reported in adults 29 , even less in childhood 7, 10, 11, 15, 23, 24, 27 . There were serum anti-GQ1b antibodies in all the cases, and occasionally antibodies against ganglioside complex. Antiganglioside antibodies are strongly related to MFS, being present in approximately 80% of patients 3 . They induce an autoimmune cross reaction due to a molecular similarity between host ganglioside protein and surface pathogen epitopes 9, 30 . Clinical manifestations of spectrum anti-GQ1b syndrome depend on the different expression sites of the target molecules in the nervous system. GQ1b and GT1a antigens are mainly located in paranodal regions of the extramedullary portion of the oculomotor, trochlear and abducens cranial nerves 2,6 . Fukami and coworkers described a significant association between anti-GQ1b or anti-GT1a titers and ophthalmoplegia, but it can also appear related to other ganglioside autoantibodies, as in the present case. On the other hand, anti-GM1, anti-GM1b and anti-GD1 has been related to limb weakness 6 . MFS and its variants are usually self-limiting and spontaneous recovery without residual deficits occurs in most cases; however, medical supportive care may be necessary. Corticosteroids, intravenous immunoglobulin or plasmapheresis are recommended to speed-up the recovery of symptoms. Acute ophthalmoplegia in childhood is a mayor diagnostic challenge for clinicians. The most frequent clinical picture is bilateral abducens nerve palsy 17, 29 . It also may present as pure horizontal, pure vertical or with mixed palsy pattern, as intrinsic ophthalmoplegia, ptosis, or ptosis without limited eyed movements. Anti-GQ1b or anti-GT1a have been identified in all cases. In addition, serum anti-GM1 was also detected in two cases 1, 4 . Our patient would be the first described associated with isolated anti-GM1 positive titers J o u r n a l P r e -p r o o f Some potentially dangerous diseases may present with multiple or bilateral acute nerve palsies. Therefore, pituitary apoplexy, mesencephalic ischemia, neuromuscular junction disorders, cavernous sinus disease, trauma, drug toxicity, infections, metastatic or paraneoplastic diseases, and autoimmune diffuse polyneuropathies should be ruled out 12, 16 . To conclude, MFS and especially its atypical forms may be potentially severe and challenging to diagnosis, so a high clinical suspicion is needed. This case underlines the relevance of a complete screening of all the anti-ganglioside antibody complex. 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