Wong et al., Arch Autoimmune Dis 2020; Archives of AutoImmune Diseases 1(2):54-57.

Case Report

Opsoclonus myoclonus syndrome and hyper IgM syndrome in the pediatric patient: A non- immunosuppressive approach

Cynthia M. Wong*, Irim Salik

Department of Pediatric Abstract at Westchester Medical Center, New York Medical College, Opsoclonus myoclonus syndrome (OMS), also known as Kinsbourne Syndrome, is a rare disorder affecting the central nervous system. It presents clinically with ataxia, diffuse or focal muscle spasms, Valhalla NY, USA and rapid, irregular eye movements. Hyper-IgM (HIGM) syndrome is a rare primary immunologic disorder which causes susceptibility to repeated opportunistic due to lack of immunoglobulin *Author for correspondence: class switching. We present the case of a 5-year-old male with both OMS and HIGM syndrome who Email: [email protected] underwent general anesthesia for an emergency appendectomy. The goals and challenges of anesthetic management that attenuates immunosuppression for these two infrequent conditions in a Received date: August 22, 2020 single pediatric patient are discussed. Accepted date: December 03, 2020 Introduction

Copyright: © 2020 Wong CM, et al. This Opsoclonus myoclonus syndrome (OMS), first described by Marcel Kinsbourne in 1962, occurs is an open-access article distributed following , a paraneoplastic process, or in association with neuroblastoma. Myoclonus under the terms of the Creative may involve the limbs, trunk, and face, varying from tremulousness to coarse multifocal jerks, and Commons Attribution License, which is often exacerbated by movement or emotional distress. Opsoclonus refers to conjugate, rapid, and permits unrestricted use, distribution, intermittent oscillating eye movements. Hyper-IgM (HIGM) syndrome is an X-linked disorder and reproduction in any medium, which causes primary immunologic deficiency. Patients present with repeated opportunistic provided the original author and infections due to deficient immunoglobulin class switching. The anesthetic implications of each source are credited. of these rare syndromes should be carefully understood in order to optimize perioperative care of a patient with both, particularly in regard to immunosuppression in an immunocompromised patient with an elevated cancer predisposition. The patient’s family has provided written informed consent for publication of this case report. Case Description A 5-year-old, 20 kg male presented to the emergency department at Westchester Medical Center with a 2-day history of right lower quadrant pain and was subsequently diagnosed with acute appendicitis on ultrasound. His past medical history was significant for OMS, which was diagnosed at 17 months due to gait instability, drooling, upper extremity myoclonus and new onset nystagmus. His motor skills have subsequently improved, however he still has minor delays in gross motor skills such as unsteadiness when walking. Subsequent genetic testing also revealed HIGM syndrome, requiring monthly intravenous immunoglobulin (IVIG) . He was previously treated with granulocyte-colony stimulating factor for . Lab results revealed a hemoglobin of 8.5g/dL, platelets of 41x109/L, white cell count of 2.9x109/L, neutrophils of Citation: Wong CM, Salik I. Opsoclonus 7.5x109/L, lymphocytes of 13.9x109/L, and monocytes of 12.9x109/L. His last dose of IVIG was Myoclonus Syndrome and Hyper IgM over five weeks ago. Syndrome in the Pediatric Patient: A Non-Immunosuppressive Approach. He was taken emergently to the operating room for a laparoscopic appendectomy. Standard Arch Autoimmune Dis 2020; 1(2):54-57. ASA (American Society of Anesthesia) monitors were applied, and the patient was induced via

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Arch Autoimmune Dis 2020; 1(2):54-57. 54 Citation: Wong CM, Salik I. Opsoclonus Myoclonus Syndrome and Hyper IgM Syndrome in the Pediatric Patient: A Non-Immunosuppressive Approach. Arch Autoimmune Dis 2020; 1(2): 54-57.

his peripheral IV with propofol 3mg/kg and rocuronium 1.2mg/ myoclonus disappeared as the target concentration was achieved. kg. He was intubated without difficulty with direct laryngoscopy Following treatment, relapse of disease can occur with anesthesia, using a Miller 1.5 blade and a 5.0mm cuffed endotracheal tube. fever, stress, discontinuation of immunotherapy, or following Platelets were transfused prior to surgical incision at 20 mL/ immunizations [6]. kg. A complete blood count was sent off following induction to Hyper-IgM syndromes are a very rare group of X-linked disorders guide the patient’s IVIG therapy. Anesthesia was maintained with which cause primary immunological deficiency, first described by total intravenous anesthesia (TIVA) using propofol to attenuate Rosen et al., in 1961 [7]. Data from the national registry in Spain the immunosuppressive effects of . Similarly, opioids were suggests a prevalence of 1 in 2,000,000 live births [8]. X-linked avoided to decrease the risk of immunosuppression. Prophylactic HIGM syndrome, which accounts for 60-75% of cases, is caused antibiotics were given prior to incision. At the conclusion of surgery, by a variation in the gene CD40LG, which results in a reduction the patient was reversed with 2mg/kg of sugammadex and extubated or abnormal formation in CD40 [9,10]. Overall prognosis is poor, without incident. A transverse abdominis plane block was performed with a survival rate of 29.2% at age 40 in one study and 20% survival as a nonopioid analgesic management option. by age 25 in another [10]. Due to this altered CD40 production, During the surgery, an incidental mass was found near the the T-cells of these patients are not able to bind with CD40 on the appendix, with histology confirming florid follicular lymphoid surface of B-cells, which prevents sequential production of other hyperplasia. He was seen by pediatric - and his immunoglobulins. As a result, patients have an excessive quantity IgM B cells were noted to be increased and incapable of responding of IgM, and deficient quantities of IgG, IgA, and IgE. This lack to immunization antigens. His pneumococcal titers were negative, of class switching of immunoglobulins makes patients with HIGM indicating his susceptibility to pneumococcal infections. Flow syndromes very susceptible to repeated opportunistic infections, cytometry revealed markedly decreased IgG and IgA carrying B particularly sinopulmonary and gastrointestinal infections [10]. cells. Helper cells were increased and CD4/CD8 ratio was increased. Consistent with other primary immune deficiencies, these These results were all consistent with HIGM syndrome. He was patients have poor response to pathogens, which makes them also started on IVIG, to make up for his missed scheduled dose. He less effective at identifying and suppressing cancerous growth experienced no post-procedure complications. [11]. Malignancies associated with HIGM syndrome include Discussion leukemias, gastrointestinal tract and hepatocellular carcinomas, cholangiocarcinomas, neuroectodermal and pancreatic tumors [11]. Age of onset for OMS is usually between 18-24 months and it In a patient with co-existing OSM, there is a particularly high risk for affects 1 in 10,000,000 people annually, with a slight predilection neuroblastoma. HIGM syndrome is linked to autoimmune diseases for the female sex [1]. It occurs in about 3% of all children with such as neutropenia, hemolytic anemia, , , neuroblastomas [2]. Brain histology reveals widely distributed inflammatory bowel disease, and renal disease [10,11]. The diagnosis perivascular lymphocyte infiltration [3]. Prognosis for OMS tends is largely based on clinical and family history. to be poor; most children have significant learning disabilities and moderate to severe cognitive impairment. OMS patients exhibit The anesthetic management of HIGM syndrome involves irritability, inconsolable crying, loss of developmental milestones, careful application of sterile technique for infection prevention and dysarthria, sleep disturbances, and reduced sociability. Three surveillance [12]. Due to patients’ immunocompromised status, out of the following four criteria are required for diagnosis: (1) antibiotic prophylaxis should be considered for most procedures opsoclonus, (2) myoclonus/ataxia, (3) behavioral change or sleep [13]. Of note, HIGM patients may not be able to mount a classic disturbance, and (4) neuroblastoma. Mainstay of therapy includes immune response with fever or neutrophilia. Patients on regular corticosteroids, immunosuppressive treatments such as intravenous IVIG (half-life of 2-3 weeks) therapy should receive this treatment immunoglobulin (IVIG), corticotropin, cyclophosphamide, in the perioperative period, as it reduces the risk of infection and cyclosporine, azathioprine, plasmapheresis, and rituximab [3]. lymphoid hyperplasia. HIGM patients are at increased risk of Surgical resection is indicated if a tumor is present. Differential hemolytic anemia, autoimmune thrombocytopenia, or idiopathic diagnosis includes Sydenham chorea, cerebellar ataxia, seizure thrombocytopenic purpura [9,10]. IVIG can be helpful in these disorder, brain injury, viral infections, and metabolic or toxic situations, and although the rise in platelets may only last for disorders. a few days to weeks, this may provide a window for safe surgical intervention [14]. In emergent cases where IVIG treatment is not There are numerous anesthetic considerations in a child with feasible preoperatively, performing minimally invasive surgery may OMS. Preoperative evaluation of all children with OMS should potentially decrease the risk of bleeding. Splenectomy or treatment preclude the presence of a neuroblastoma. The anesthesiologist with rituximab may be necessary in some cases [12]. Ultimately, the should rule out lung consolidation, pleural effusions and deviation only curative therapy is allogeneic hematopoietic stem cell transplant or compression of the trachea and great vessels. Catecholamine levels [11]. Post-operatively, IgG levels may be diminished, especially if should be checked in the setting of a neuroblastoma prior to surgical the patient is hypovolemic secondary to hemorrhage, burn injury manipulation to avoid hemodynamic instability. A central neuraxial or fluid loss. anesthetic should be avoided if there is invasion of the intravertebral space by a paravertebral tumor. Chronic corticosteroid therapy Patients with poor respiratory function should undergo may necessitate perioperative steroid supplementation. Burrows spirometry studies prior to elective surgery, as they may et al. [4] described worsening of opsoclonus and myoclonus with exhibit bronchiectasis from chronic respiratory insult due to ketamine, etomidate and meperidine, which should be avoided in [12]. Chronic and liver cirrhosis from these patients. Lee et al. [5] utilized propofol and remifentanil for infections such as cryptosporidium parvum may cause hepatic total intravenous anesthesia and noticed that both opsoclonus and failure, which can affect clearance and metabolism of anesthetic

Arch Autoimmune Dis 2020; 1(2):54-57. 55 Citation: Wong CM, Salik I. Opsoclonus Myoclonus Syndrome and Hyper IgM Syndrome in the Pediatric Patient: A Non-Immunosuppressive Approach. Arch Autoimmune Dis 2020; 1(2): 54-57.

agents. Liver function tests should also be considered for elective References procedures in such patients [10]. 1. Jasminekalyani P, Saravanan S, Sriramakrishnan V, Radha M. Surgical stress releases hormones such as catecholamines, Dancing eyes dancing feet syndrome-a report of two cases. Journal adrenocorticotropic hormones, and cortisol, which inhibit of Clinical and Diagnostic Research: JCDR. 2014 May;8(5):MD03. proinflammatory cytokines such as interleukin (IL)-12 and tumor 2. Pike M. Opsoclonus–myoclonus syndrome. In: Handbook of clinical necrosis factor (TNF)-alpha, while stimulating angiogenic factors 2013 Jan 1 (Vol. 112, pp. 1209-1211). Elsevier. that can cause initiation or recurrence of cancer [15,16]. In an 3. Mitchell WG, Wooten AA, O’Neil SH, Rodriguez JG, Cruz RE, Wittern immunocompromised patient with HIGM and increased cancer R. 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