key: cord-287043-53oy5w34 authors: Reyes‐Bueno, José Antonio; García‐Trujillo, Lucía; Urbaneja, Patricia; Ciano‐Petersen, Nicolás Lundahl; Postigo‐Pozo, María José; Martínez‐Tomás, César; Serrano‐Castro, Pedro J title: Miller‐Fisher syndrome after SARS‐CoV‐2 infection date: 2020-06-05 journal: Eur J Neurol DOI: 10.1111/ene.14383 sha: doc_id: 287043 cord_uid: 53oy5w34 On March 11th, 2020, the WHO declared the SARS‐Cov‐2 pandemic. Syndromes have been detected in relation to COVID‐19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement. Our case would be the 3rd patient with MFS associated with COVID‐19 as far as we know. We present a 51 years old female diagnosed with MFS two weeks after COVID‐19. RT‐PCR to SARS‐CoV‐2 was negative but IgG was positive. Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post‐infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid‐19 disease. On March 11 th , 2020, the WHO declared the SARS-Cov-2 pandemic. The disease can go unnoticed in asymptomatic infected patients or a Severe Acute Respiratory Syndrome (SARS) with high lethality, especially in older patients with other comorbidities like This article is protected by copyright. All rights reserved cardiovascular risk factors (1) . Since then, we have learned of multiple effects on the nervous system. SARS-Cov-2 has been proposed to have an infective capacity on the nervous system through the Angiotensin-converting enzyme 2 (ACE2) receptor and the type II transmembrane serine protease (TMPRSS2), both necessary for the virus to get into the cells [2] , which can be identified in neurons, glial cells and respiratory epithelial cells. Neurological signs have been described in up to 36.4% of a series of 214 hospitalized patients (3) . Most of the neurological symptoms in acute patients are non-specific and probably have a systemic origin (e.g. headaches, myalgia, fatigue, dizziness). On the other hand, anosmia and ageusia appear to be very prevalent in the series so far. Other syndromes have been detected in relation to COVID-19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications (4) . There are also cases of peripheral March 30 th , she started having intense root-type pain in all four limbs, especially in the legs as well as dorsal and lumbar back pain. On April 4 th she started with weakness in his lower limbs which progressed to the point of preventing her from walking in a few days, associated with double binocular vision. She was admitted to our department on April 11 th . The neurological exploration showed paresis of the left external rectus muscle with horizontal diplopia when looking to the left, discrete predominantly inferior bilateral facial paresis, symmetrical paraparesis with 3+/5 weakness in psoas, hamstrings, gluteus and quadriceps, 3/5 in gastrocnemius, 2/5 in posterior tibial and peroneal; and global areflexia. She also presented symptoms of autonomic dysfunction such as dry mouth, diarrhea and unstable blood pressure. She did not refer ageusia or anosmia. On admission, RT-PCR to SARS-CoV-2 was negative but IgG was positive using the ELISA technique. This article is protected by copyright. All rights reserved The cerebrospinal fluid showed high protein levels with albumin-cytological dissociation (70mg/dl of proteins and 5 leukocytes). Antiganglioside antibodies were negative. The rest of neuroimaging studies and analysis of infectious and autoimmune pathologies were negative. The neurophysiological study carried out on April 14 th showed F-wave anomalies such as asymmetric latency for the lower limbs and low A-wave amplitude on the left leg, alteration of bilateral R1 responses in the Blink-Reflex and in the intermediary standard electromyography poor activity in right rectus-anterior femoral muscle and little spontaneous denervation activity in left rectus-anterior femoral (RAF) muscle; all of this was compatible with an acute Guillain-Barre type demyelinating polyneuropathy in a very early stage. A control neurophysiological study on April 30 th showed low F-wave amplitude and disintegrated morphology, similar alteration of Blink-Reflex and spontaneous denervation activity in bilateral RAF and left anterior tibialis, compatible with polyradiculoneuropatia with proximal and brainstem involvement. The patient was treated with IVIG 0.4mg/Kg/24h for 5 days (April 12 th to 16 th ) and gabapentin 900 mg/24h, showing a progressive improvement in facial and limb paresis, diplopia and pain. She is still on neurological rehabilitation. She was diagnosed with Miller-Fisher Syndrome after SARS-CoV-2 infection. The patient accepted and gave her consent for this paper to be carried out. No ethics committee approval has been required as there is no identifiable patient data. The patient has given her express consent for the publication of this paper. Guillain-Barré syndrome (GBS) is a group of pathologies that are clinically characterized by flaccid paralysis of the extremities, sensory and autonomic disorders of an autoimmune nature, usually 3 to 6 days after an infectious process. When ophthalmoparesis is associated with predominantly lower limb involvement, it is called Miller-Fischer Syndrome (MFS). The physiopathological mechanism is based on molecular mimicry and antiganglioside antibodies (Anti-GQ1B in the case of MFS) in people genetically predisposed after a bacterial or viral infectious process (6). We know that human coronaviruses have neuroinvasive capacity, present neurotropism and can induce GBS-type dysimmune phenomena in certain patients (7) as previously seen in the MERS-CoV epidemic (8) . SARS- This article is protected by copyright. All rights reserved Cov-2 also presents this capacity to affect the nervous system, either directly (neuroinvasive capacity) or indirectly by the inflammatory mechanism (4). The clinical picture of our patient was compatible with a MFS, known anti GQ1b syndrome, although the antibody study was negative. To date, 11 cases of GBS have been published after COVID-19 (9) (10) (11) (12) (13) (14) (15) (16) . Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases, although some required mechanical ventilation and ICU management. Our case fits most of the cases documented to date. The absence of antiganglioside antibodies in all cases determined is remarkable. Although it is still early, this could indicate that the molecular mimicry phenomenon by which SARS-Cov-2 precipitates GBS could be different from that of the other germs already known as Campylobacter jejuni, Mycoplasma... Recently, 2 cases of Miller Fisher syndrome and cranial polyneuropathy have been described after , which presented Anti-GD1b-IgG antibodies, with good response to treatment with immunoglobulins. During the evaluation we conducted an interview where she was asked directly about the presence of ageusia or anosmia and she denied the presence of such symptoms. In the papers reviewed, the presence of anosmia and/or ageusia was only present in one case of Guillain-Barré syndrome (11) and in the two patients described with Miller-Fisher syndrome (5) . According to the studies, up to 85.6% of patients reported dysosmia or anosmia and up to 88% presented taste alterations (4). Our case would be the 3rd patient with MFS associated with COVID-19 as far as we know. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post-infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid-19 disease. It will be necessary to be attentive to the possible appearance of the same after the hospital discharge of the patients. The data that support the findings of this study are available from the corresponding author upon reasonable request. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study Coronavirus Disease 2019: What We Know So Far Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease Neurological complications of coronavirus and COVID-19. Complicaciones neurológicas por coronavirus y COVID-19 Miller Fisher Syndrome and polyneuritis cranialis in COVID-19 Guillain-Barré syndrome: pathogenesis, diagnosis, treatment and prognosis Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans Neurological Complications during Treatment of Middle East Respiratory Syndrome Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Guillain-Barré Syndrome Associated with SARS-CoV-2 Guillain Barre syndrome associated with COVID-19 infection: A case report S0967-Accepted Article This article is protected by copyright Guillain-Barré Syndrome associated with SARS CoV-2 infection COVID-19 may induce Guillain-Barré syndrome Guillain-Barré syndrome related to COVID-19 Guillain-Barré syndrome following COVID-19: new infection, old complication?