key: cord-0739088-e6kgwg7n
authors: Bilen, Nimet Melis; Sahbudak Bal, Zumrut; Yildirim Arslan, Sema; Kanmaz, Seda; Kurugol, Zafer; Ozkinay, Ferda
title: Multisystem Inflammatory Syndrome in Children Presenting With Pseudotumor Cerebri and a Review of the Literature
date: 2021-09-17
journal: Pediatr Infect Dis J
DOI: 10.1097/inf.0000000000003327
sha: 0c1ce5742408bc7d2f660abeb20e3a07c06fc68f
doc_id: 739088
cord_uid: e6kgwg7n

Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening inflammatory immune response associated with severe acute respiratory syndrome coronavirus 2 infection. The majority of patients have been presented with hypotension, shock, gastrointestinal, cardiovascular and mucocutaneous symptoms. The incidence of neurologic symptoms in MIS-C is of rising concern as they are not well described and reported in fewer patients. An 8-year-old boy was admitted to the hospital with headache, fever, conjunctivitis, and hyperinflammatory findings diagnosed as MIS-C. Fundus examination performed with complaints of headache, vomiting, and conjunctivitis showed bilateral papilledema. Pseudotumor cerebri is a rare manifestation of MIS-C that can lead to vision loss and may not only be resolved with the standard treatment for MIS-C. We report a case of MIS-C presented with neurologic symptoms due to pseudotumor cerebri and successfully treated with intravenous immunoglobulin and acetazolamide.

T he first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported in China at the end of 2019. Subsequently, SARS-CoV-2 spread worldwide, and the World Health Organization (WHO) declared a pandemic on March 11, 2020 1 SARS-CoV-2 infection is generally asymptomatic or mildly symptomatic in children, and mortality rates are lower than in adults. 2 At the end of April 2020, the Pediatric Intensive Care Society (PICS) reported cases with hyperinflammatory findings and severe multisystemic inflammation similar to Kawasaki disease and toxic shock syndrome. 3 This new syndrome is named multisystem inflammatory syndrome in children (MIS-C). It is a rare but lifethreatening inflammatory immune response associated with SARS-CoV-2 infection. 4 Centers for Disease Control and Prevention (CDC), WHO and Royal College of Pediatrics and Child Health defined diagnostic criteria for MIS-C. 1, 5, 6 The main aspects of diagnosis are persistent fever, symptoms of two or more organ dysfunction, laboratory evidence of inflammation, lack of alternative diagnosis and evidence of recent or current SARS-CoV-2 infection or exposure. 1, 5, 6 The majority of patients have been presented with hypotension, shock, gastrointestinal, cardiovascular and mucocutaneous symptoms. The incidence of neurologic symptoms in MIS-C was 13%-21% of patients, and they are not well described. [7] [8] [9] Headache, altered mental status, seizures, brain edema, encephalopathy, aseptic meningitis and intracranial hypertension are some of the reported neurologic findings. 4, 9, 10 Therefore, we report a case of MIS-C presented with neurologic symptoms due to pseudotumor cerebri (PTC).

A previously healthy 8-year-old boy was admitted to the emergency room with a high fever and fatigue history for 7 days of the duration. He was initially managed as an upper respiratory tract infection but readmitted to the emergency room after 3 days because of persistent fever, headache, vomiting, abdominal pain, redness and swelling in both eyes. His father had a history of SARS-CoV-2 infection 1 month ago, but the patient was not tested for SARS-CoV-2. On admission, his physical examination revealed a fever (38.1 o C) and tachycardia (heart rate, 130/min). He had bilateral nonpurulent conjunctivitis. On neurologic examination, his mental status and cranial nerve examination were normal, bilateral papilledema was detected by fundus examination. Detailed ophthalmologic examination showed stage 3 papilledema, and visual functions were as follows: visual acuity as a counting finger from 4 meters, and minimal enlargement of the blind spot. Initial laboratory results were as follows: total leukocyte count: 15.3 × 10 3 /μL (neutrophil 64.8%, monocyte 4.9 % and lymphocyte 22.9%), hemoglobin 9.7 g/dL, platelet count: 506 × 10 3 /μL, C-reactive protein 

We present an MIS-C case with symptoms of increased intracranial pressure. Several studies reported that most MIS-C patients present with gastrointestinal, cardiovascular and mucocutaneous symptoms. [7] [8] [9] [11] [12] [13] Neurologic symptoms in MIS-C are rare manifestations when compared with other organ system involvements. Dufort et al 9 reported headache, altered mental status and confusion as neurologic symptoms were present in 13% of the patients 0-5 years of age and 38% of patients 13-20 years of age.

Feldstein et al 11 also demonstrated that 21% of 186 MIS-C cases had neurologic symptoms.

The etiology of neurologic symptoms in SARS-CoV-2 infection and MIS-C have not been well described. Laboratory studies have shown that angiotensin-converting enzyme 2 (ACE2) is expressed in the brain. 14,15 Therefore, it is a potential target for the virus. Besides, the virus causes coagulation disorder, which increases the risk of thrombosis. 16 Schupper et al 17 presented two cases of MIS-C with neurologic manifestations due to a stroke caused by thrombosis. Therefore, we performed an MRI and MR venography to rule out a stroke and other neurologic disorders caused by thrombosis. Abdel-Mannan et al 18 presented four cases of severe MIS-C with encephalopathy. Their MRI findings were consistent with lesions in the splenium of the corpus callosum, which may also be observed in ischemia. Our patient had a headache and papilledema and elevated D-dimer levels at the presentation. His MRI showed signs of intracranial hypertension without thrombosis.

Papilledema is the swelling of optic nerves due to increased intracranial pressure, and if untreated, it may cause optic nerve damage and lead to loss of vision. 19 It is usually the hallmark of pseudotumor cerebri syndrome. Diagnostic criteria for definite pseudotumor cerebri syndrome are papilledema, regular neurologic examination except for abducens palsy, normal MRI findings and elevated opening pressure in LP. In some cases, like our case, LP opening pressure can be within expected ranges. In these cases, the diagnosis is considered probable pseudotumor cerebri. 20 Inflammatory disorders such as systemic lupus erythematosus and Kawasaki disease may present with increased intracranial pressure. [21] [22] [23] Becker et al 4 presented 4 cases of MIS-C with clinical, LP, and neuroimaging findings of increased intracranial pressure, and one of them had papilledema. Baccarella et al 23 also reported two MIS-C cases with symptoms of increased intracranial pressure and papilledema, all of their patients had neurologic symptoms including headache, altered mental status and nuchal rigidity at presentation, as our patient, suggesting that increased intracranial pressure may be an etiologic reason for neurologic symptoms of MIS-C. A review of the MIS-C cases with increased intracranial pressure in the literature is presented in Table 1 .

In contrast to previous cases, our patient was well and hemodynamically stable. 4, 18, 22 It made it easier to perform an LP which did not reveal any significant results. The patient's headache resolved, and his vision improved after LP, but papilledema was not entirely resolved. We treated the patient with acetazolamide for his papilledema. The hyperinflammatory process was resolved with IVIG in our patient, and visual functions improved on the second day. His papilledema completely regressed on follow-up. Steroids may be reserved for patients without a rapid improvement in visual functions. Fundus examination should be performed in MIS-C patients, mainly showing symptoms compatible with pseudotumor cerebri syndrome. Papilledema is a rare manifestation of MIS-C that can lead to vision loss and may be resolved with standard anti-inflammatory treatment for MIS-C and acetazolamide.

In conclusion, PTC should be kept in mind in MIS-C patients with neurologic symptoms, and treatment should be started immediately to prevent vision loss even in mild cases of MIS-C.

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