Early switch from cladribine to alemtuzumab in highly-active relapsing-remitting multiple sclerosis: A case report

Background Management of patients with multiple sclerosis (MS) and evidence of disease activity during treatment with cladribine tablets represents a challenging point. Objectives To report a patient with highly active multiple sclerosis (HAMS) who has been early switched from cladribine to alemtuzumab owing to tumultuous clinical and radiological activity Methods A single retrospective case report. Results. Treatment with alemtuzumab has led to a complete suppression of disease activity without any evidence of infections or acquired autoimmune diseases. Conclusion Our report suggests that an early switch from cladribine to alemtuzumab, may be safe and efficacious in selected HAMS cases.Copyright © 2022 The Authors

Acute flaccid myelitis diagnosed after IVIG: a diagnostic dilemma

Case Report: A 4-year-old African American male presented to an outside emergency department (ED) following sudden inability to move left upper extremity. Past medical history was unremarkable and routine vaccinations were up to date. Radiograph of affected extremity ruled out fractures and patient was discharged to follow up with primary care physician. Two days later mother brought him to our ED due to persistent left upper extremity paralysis, poor appetite, and subjective fever. On exam his left arm was warm and tender to dull and sharp touch;he had definite loss of active movement, hypotonia and absence of deep tendon reflexes. The patient had winging of left scapula and could not shrug left shoulder. MRI of cervical and thoracic spine showed enlargement of spinal cord from C2-C6 level with gray matter hyperintensity, slightly asymmetric to the left. Laboratory studies showed leukocytosis (14 000/mcL) and CSF studies showed pleocytosis of 89 WBC/mcL (93.3% mononuclear cells and 6.7% polymorphonuclear cells), 0 RBCs, normal glucose and protein, and a negative CSF meningoencephalitis multiplex PCR panel. Due to high suspicion of demyelinating or autoimmune condition he was treated with high dose steroids and IVIG. Subsequently neuromyelitis optica was ruled out as aquaporin-4 receptor antibodies (AB) and myelin oligodendrocyte glycoprotein AB were normal. CSF myelin basic protein and oligoclonal bands were absent ruling out demyelinating disorders. CSF arboviruses IgM and West Nile IgM were negative. He showed minimal improvement in left upper extremity movement but repeat spinal cord MRI one week later showed improved cord thickness with less hyperintensity. Respiratory multiplex PCR was negative including enteroviruses. Repeat CSF studies after IVIG showed increased IgG index and IgG synthesis suggestive of recent spinal cord infection, consistent with acute flaccid myelitis (AFM). Pre-IVIG blood PCR was invalid for enteroviruses due to PCR inhibitors found in the sample. Blood post-IVIG was negative for mycoplasma IgM, West Nile IgM, and arboviruses IgM. Enterovirus panel titers (post-IVIG) were positive for coxsackie A (1:32), coxsackie B type 4 (1:80) and 5 (1:320), echovirus type 11 (1:160) and 30 (1:80) as well as positive for poliovirus type 1 and 3. These titers could not distinguish acute infection from patient's immunity or false-positives as a result of IVIG. He was discharged with outpatient follow-up visits with neurology, infectious disease, occupational and physical therapy, showing only mild improvement after discharge. Discussion(s):With the anticipated resurgence of AFM after the peak of COVID-19 pandemic, our case illustrates the need to consider this diagnostic possibility in patients with flaccid paralysis. It is important to remember CSF IgG synthesis is not affected by IVIG. In addition when treatment plans include IVIG, appropriate samples should be collected before IVIG to facilitate accurate work-up for infectious diseases. Copyright © 2023 Southern Society for Clinical Investigation.

Multiple sclerosis associated with Balo-like lesions post-Coronavirus disease 2019

Background and Purpose: Balo's concentric sclerosis (BCS) is a rare inflammatory demyelinating disorder of the central nervous system (CNS) characterized pathologically and radiologically by concentric lamella of alternating demyelinated and partially myelin-preserved white matter. Whether BCS is a variant of multiple sclerosis (MS) or a distinct entity remains debatable. Here, we report an unusual case of MS complicated by Balo's lesions, post-Coronavirus disease 2019 (COVID-19), focusing on the evolution ofMRI findings. Methods: Single-case study. Results: The patient is a 42-year-old woman with relapsing-remitting MS diagnosed at age of 19 who was treated with teriflunomide for the past 5 years. She developed a febrile illness and arthralgia for a week;however, COVID-19 testing was deferred. Two weeks later, she presented with vertigo followed by profound right-hemiparesis, gait impairment, and encephalopathy. Cerebrospinal fluid analysis revealed a protein of 56 mg/dl, increased immunoglobulinG(IgG) index, and>l10 unique oligoclonal bands. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG was detected in serum, but viral ribonucleic acid was absent in the CSF. BrainMRI demonstrated, for the first time, several Balo-like and tumefactive lesions, with contrast enhancement and restricted diffusion. She received plasma exchange alternating with pulse steroids, yet was left with ataxic hemiparetic gait. She was later switched to an anti-CD20 monoclonal antibody therapy. Followup brain MRIs showed continuous regression of the tumefactive and Balo-like lesions. Conclusion: This case adds to the emerging spectrum of COVID-19- associated radiological findings regarding inflammatory demyelination in the CNS. It remains unknown whether potential neurotropism of SARS-CoV-2 or parainfectious mechanisms might have contributed to the fulminant disease in our patient.

Association of Multiple Sclerosis and COVID-19 Infection: A Case Report

Introduction: Since the declaration of COVID-19 pandemic, several cases of demyelination of both peripheral and central nervous systems have been reported. The association of viral infection and the development of CNS demyelination has long been studied, and this link has recently been reported following SARS-CoV-2 infection as well. Material(s) and Method(s): We report a case of a 36-year-old male who developed CNS demyelinating disease, that fulfilled the diagnostic criteria of multiple sclerosis (MS), 2 months after laboratory-confirmed infection with SARS-CoV-2. Result(s): A 36-year-old male developed CNS demyelination, 2-months following a laboratory-confirmed SARS-CoV-2 infection, that fulfilled the revised 2017 McDonald diagnostic criteria for MS. He presented with ataxia, and MRI showed multiple demyelinating lesions in the brain, and positive oligoclonal bands in CSF. Conclusion(s): To our knowledge, this is the second case report of MS in association with COVID-19 infection, and the first case from Middle East and North Africa (MENA) region. This case report adds to the growing body of evidence of a probable causal relationship between SARS‐CoV‐2 infection and the development of MS. SARS-CoV-2 could potentially trigger a demyelinating process, through an acute or delayed immune-mediated CNS inflammatory response.

GETTING TO THE HEART OF THE MATTER

CASE: 45-year-old woman with PMHx systemic sclerosis presents with fever, weight loss, chest tightness, weakness and altered mental status for 2 weeks. Home meds are prednisone, mycophenolic acid, lasix. On presentation she is febrile to 38.9C, HR 110, BP 97/64, SpO2 96% on RA. Exam shows telangiectasis, normal cardiopulmonary exam, mild sclerodactyly. Oriented only to self, has bilateral LE 3/5 weakness. Labs with WBC 2.6K, Hgb 7.1, plts 126K. Cr normal. Liver enzymes mildly elevated. BNP 3900. Trop 251. Lactate 4.9 Blood cultures negative, CMV/EBV negative, COVID-19 negative, Ferritin > 15,000, Triglycerides 274 LDH 495, Fibrinogen 274, D-Dimer 755, ANA 1:1280, + dsDNA, low titer Smith, + RNP, + SSA, + RNA Pol III. TTE with EF 27% and diffuse hypokinesis. Cardiac MRI with myocardial fibrosis no active myocarditis, suggestive of scleroderma. Lumbar puncture with high protein, borderline increased oligoclonal bands, elevated IgG index but elevated synthesis rate, suggestive of CNS inflammation. Patient is in cardiogenic shock secondary to hemophagocytic lymphohistiocytosis/macrophage activating syndrome (HLH/MAS) related to systemic sclerosis/scleroderma with SLE overlap requiring inotropes and aggressive diuresis. She develops severe pain and bright red purpura on bilateral legs. Hypercoagulable w/u showed low protein C/S, low complement, negative cryoglobulin. Skin biopsy showed vaso-occlusive process c/w HLH/MAS. Receives IV methylprednisolone for empiric treatment of HLH/MAS and IV cyclophosphamide for possible lupus cerebritis. Patient improves and is discharged on long-term milrinone, Plaquenil, and steroids. IMPACT/DISCUSSION: Secondary HLH or MAS is a life-threatening condition of extreme inflammation that can occur in autoimmune conditions, infection, or malignancy Diagnosing HLH requires high clinical suspicion - >10K ferritin level is highly sensitive and specific for diagnosis of HLH This patient has multisystem involvement of autoimmune disease given history of scleroderma The LP studies raise concern for lupus cerebritis, specifically the IgG index and IgG synthesis rate are helpful for this diagnosis Underline subtype of systemic sclerosis-overlap syndromes and here particularly scleroderma lupus overlap Highlight the utility of cardiac MRI in characterizing myocarditis / fibrosis Discuss need for high alert for necrotizing fasciitis with painful palpable purpura Overview treatment of HLH/MAS with high dose steroids Reflection on high mortality of HLH/MAS and question of recovered heart function CONCLUSION: Teaching Point 1: Secondary HLH is a syndrome of extreme inflammation caused by underlying malignancy, autoimmune condition, or infection. Teaching Point 2: HLH and MAS have a great deal of symptom/clinical presentation overlap. Ferritin level > 10,000 is highly sensitive and specific for diagnosis of HLH Teaching Point 3: Systemic sclerosis can present in a variety of ways including cardiac, lung, skin involvement.

Guillain-Barre and Miller Fisher Overlap Syndrome: A Masked Neurological Consequence of COVID-19

Objective: This case is presented to help clinicians recognize the potentially deadly association of COVID-19 and GBS/MFS overlap. Background: The neurologic sequelae of SARS-CoV-2 (COVID-19) are becoming better known, though much still needs elucidated. Growing reports demonstrate an association between COVID-19 and Guillain-Barre syndrome (GBS), including Miller Fisher syndrome (MFS) variant. Design/Methods: A 64-year-old male with a past medical history of hypertension and obesity developed nonspecific viral symptoms in January 2021, which abated after a few days without treatment. Two weeks later, he presented to the ED with left facial droop and numbness, diplopia, bilateral leg weakness, and bilateral numbness and paresthesias of lower extremities ascending to the upper extremities. Physical exam showed left facial droop with impaired left eye closure, and abnormal finger-to-nose testing bilaterally. A stocking-and-glove pattern of decreased sensation in the hands and feet, 4/5 strength in both arms and legs, and absent lower extremity deep tendon reflexes was noted. MRI brain showed bilateral facial nerve meatal segments and facial ganglion enhancement. Labs showed CSF albuminocytologic dissociation and a positive nasopharyngeal PCR COVID-19 test, with a negative viral meningitis panel, VDRL, Lyme, and oligoclonal bands. Results: The patient was treated with 5 days of remdesivir and 10 days of corticosteroids for hypoxia due to COVID-19. Prednisone and acyclovir for initial Bell's palsy diagnosis demonstrated minimal improvement. After lumbar puncture, he was diagnosed with COVID-19 related GBS/MFS overlap. Intravenous immunoglobulin was administered for 5 days, leading to stabilization and gradual improvement of his neurologic symptoms. He was discharged to a skilled nursing facility with a walker. At 1-month outpatient follow up, he had minimal residual weakness and numbness in his proximal arms, legs, and bilateral hands. Conclusions: This case highlights the importance of prompt recognition and treatment of postCOVID-19 complications, such as GBS. Diagnosis of this syndrome is critical for improved patient outcomes.

Two Cases of Neurological Complications After mRNA Vaccination for COVID-19

Objective: We present two patients with neurological complications following COVID-19 mRNA vaccination. Background: Post-vaccinal myelitis and demyelination is well described. We investigated two patients presenting inflammatory demyelination following mRNA based vaccination against COVID-19. Design/Methods: Patients were referred to the treating neurologist for a second opinion as possible cases of multiple sclerosis. Clinical neurological evaluation, MRI imaging of brain and spine as well as serum and cerebrospinal fluid (CSF) analysis was performed. Results: In case 1, the patient developed left-side numbness and difficulty walking six weeks post-second dose of the Moderna mRNA COVID-19 vaccine. She was found to have an enhancing thoracic cord lesion on MRIs, and CSF ELISA studies showed highly elevated IgG levels against the spike protein receptor-binding domain (S1-RBD) of COVID 19. In case 2, the patient began to hiccup and vomit, developed diplopia, and right-side weakness and numbness around two days post-second dose of the Moderna vaccine. MRIs showed two lesions on her brain and a C4 enhancing lesion on her spinal cord. CSF showed oligoclonal bands. However, further analysis of her spinal fluid showed highly elevated IgG antibodies to the S1-RBD. Conclusions: Initially, case 1 was diagnosed with transverse myelitis and possible multiple sclerosis, and case 2 with multiple sclerosis. Both patients likely would have received long-term immunosuppressive therapy had vaccine complications not been suspected. The presence of CSF antibodies to the S1-RBD protein suggests an immune response to the mRNA COVID-19 vaccinations crossing over to the CNS as the likely cause of these neurological complications. In patients developing acute neurological complaints in the period following vaccination, even with the presence of oligoclonal bands, CSF should be analyzed for reactivity against the S1-RBD. Further investigation is required to explain the mechanism of this response and subsequent complications. Both patients are clinically improving and will continue to be managed by a neurologist.

An Unusual Case of CLIPPERS

Objective: To present an unusual presentation of CLIPPERS that was responsive to rituximab Background: CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a neuroinflammatory disorder typically affecting the brainstem and cerebellum with clinical and radiographic improvement with steroids. One reported case showed improvement with rituximab. We present a case of CLIPPERS with supra- and infratentorial involvement that improved with rituximab. Design/Methods: A 30-year-old male presented with several months of headaches, dizziness, and face and arm numbness, then developed diplopia and gait ataxia. Serial MRI's showed worsening punctate enhancing and T2-hyperintense lesions in the brainstem and supratentorial white matter over months. Workup showed normal CSF cell count, and negative CSF cytology, ACE, VDRL, oligoclonal bands, serologic IgG4, Coccidioidomycosis, Lupus, rheumatoid arthritis, and COVID. Vascular imaging showed no evidence of vasculitis. Biopsy showed a dense perivascular lymphocytic infiltrate including B and T cells, without evidence of vasculitis or lymphoma. He received IVIG and IV solumedrol, with symptom resolution and some improvement on imaging. Rituximab was started with subsequent resolution of the lesions on MRI. Results: NA Conclusions: CLIPPERS has a variable clinical presentation but typically includes gait ataxia and diplopia. MRI shows multiple punctate/curvilinear enhancing lesions in the brainstem and cerebellum, rarely in the spinal cord or supratentorially. Differential diagnoses include neurosarcoidosis, Behcet's disease, vasculitis, lymphoma, chronic infections, glioma, and demyelinating disease. It is characterized by responsiveness to steroids, and patients require long-term steroid or steroid-sparing agent treatment, at least until resolution of enhancement. Methotrexate, hydroxychloroquine, and cyclophosphamide are most commonly used. There was one report of treatment with rituximab with 4 years stability. Our case was unusual as he had supra and infratentorial lesions, and he had good response to rituximab. Rituximab should be considered in the treatment of CLIPPERS.

Longitudinal Extensive Transverse Myelitis:rare immunotherapy related adverse effect vs COVID19-related immunization complication

Objective: To report an acute presentation of long extensive transverse myelitis (LETM) in the setting of Atezolizumab monotherapy and COVID-19 mRNA immunization Background: Patients being treated with immune checkpoint inhibitors (ICI) for advanced malignancy have an increased propensity of developing neuro-immune complications. With the advent of the COVID-19 pandemic there have been reported cases of TM following COVID-19 immunization. The reported infrequency of TM with both aforementioned causes makes delineating the etiology challenging. Design/Methods: A 58-year-old male with metastatic SCLC completed 4 cycles of Atezolizumab, Carboplatin and Etoposide and was transitioned to Atezolizumab maintenance. He previously underwent Atezolizumab infusion and was administered the second dose of COVID-19 mRNA vaccine one day prior to developing acute lower extremity paralysis, sensory loss from chest down and overflow incontinence. MRI spine illustrated centromedullary enhancing lesions from C7-T7. CSF analysis showed 25 WBC, 116/uL RBC, 94 mg/dL protein, normal glucose, negative oligoclonal bands and normal IgG index. CSF bacterial and virology studies were negative. Additionally, serum anti-myelin oligodendrocyte glycoprotein (MOG) and antiaquaporin receptor 4 (AQP4) antibodies were unremarkable. Results: 5-day course of pulsed methylprednisolone followed by three therapeutic plasma exchanges produced minimal improvement in lower extremities strength and sensory level. Conclusions: This case demonstrates the complication and symptomatology of TM in the setting of anti-PD-L1 monoclonal antibody with the co-incidental COVID-19 mRNA vaccine administration. The causal relationship between the vaccine and TM is difficult to establish due to limited data and the presence of a known inciting factor but hints at a possible exaggeration of the existing neuroinflammatory process. Currently, CDC recommends that individuals who are moderately to severely immunocompromised receive an additional dose of an mRNA COVID-19 Vaccine (Pfizer-BioNTech or Moderna) at least 28 days after the completion of the initial mRNA COVID-19 vaccine series. Caution should be given for those patients who are on ICI therapy.

New-Onset Refractory Status Epilepticus After Pfizer-BioNTech COVID-19 Vaccination

Objective: NA Background: Previous case reports have described 3 cases of autoimmune encephalitis and 1 case of new-onset refractory status epilepticus (NORSE) following COVID-19 viral vector vaccinations. However, no cases have been documented in association with COVID-19 mRNA vaccinations. We describe a case of NORSE after vaccination with Pfizer-BioNTech COVID-19 vaccine. Design/Methods: Case report. Results: A 56 year old healthy man presented with three days of fever, fatigue, and aphasia beginning 2 weeks after he received his first dose of the Pfizer-BioNTech COVID-19 vaccine. Video EEG showed temporally predominant seizures occurring independently bilaterally (right greater than left). Clinical seizures were characterized by head turn to the left and right hand movements. He then developed sustained right frontotemporal spike and slow wave activity consistent with non-convulsive status epilepticus. CSF demonstrated mild lymphocytic pleocytosis with WBC 16 cells/mm3, protein 24, glucose 76, and an opening pressure of 47. CSF bacterial and viral encephalitis panels, HSV, lyme, West Nile virus, and VDRL were all negative. Oligoclonal bands, paraneoplastic panel, and encephalopathy panel were negative. Systemic malignancy workup was negative. Initial MRI brain was unremarkable, but 1 week after symptom onset he developed bilateral hippocampal edema. The patient was empirically treated with broad spectrum antibiotics and antivirals which were later discontinued. Due to presumed diagnosis of autoimmune encephalitis, he was treated with high dose steroids, plasmapheresis, IVIG, and rituximab. He was treated with progressively escalating anti-seizure medications including midazolam, propofol, and ketamine continuous infusions and eventually stabilized on levetiracetam, lacosamide, phenobarbital, clobazam, zonisamide, oxcarbazepine, and perampanel. At the time of discharge, mental status had improved and aphasia resolved. Conclusions: To our knowledge, this is the first case of NORSE reported after Pfizer COVID-19 vaccination. While no test exists to definitively establish causality, these findings warrant further investigation of the possible association between COVID-19 vaccination and autoimmune encephalitis.

A case of a 14 year old male with MOGAD (Myelin Oligocyte Glycoprotein Antibody Disease) post-COVID-19 infection responsive to high dose corticosteroids and intravenous immunoglobulin (IVIG) therapy

Objective: NA Background: The etiology of MOGAD post-COVID-19 infection is not well understood and there are limited publications describing cases in pediatric patients. Here we report a case of a 14-year-old male with MOG antibody positive ADEM (Acute Disseminated Encephalomyelitis) and positive COVID-19 PCR. Design/Methods: NA Results: The patient presented to our hospital in December of 2020 with acute onset of ataxia and lower extremity weakness. His exam was pertinent for mild and symmetric weakness in bilateral hip flexors, dysmetria with ataxic gait, as well as bilateral patellar and ankle hyporeflexia. MRI brain showed symmetric areas of T2 signal hyperintensity, predominantly adjacent to the fourth ventricle as well as the peri-insular and frontal regions. MRI of the lumbosacral spine demonstrated T2 signal hyperintensity within the conus medullaris without enhancement. CSF studies revealed an increased white blood cell count of 74 (90% lymphocyte), elevated protein of 51, elevated kappa free light chain (0.12) and positive oligoclonal bands (3). He was also found to be serum anti-MOG antibody positive (1:100) and COVID-19 positive (PCR). He received 1000 mg of intravenous methylprednisolone daily for 5 days and 2 g/kg IVIG. He was subsequently placed on a 6 week taper of oral prednisone. 2 months after his initial presentation, his neurologic symptoms have completely resolved, and he has been asymptomatic since. Repeat MRI brain 4 months later showed improvement in his multifocal supratentorial FLAIR signal abnormalities. Conclusions: Here we describe a case of a 14-year-old male with MOGAD post-COVID-19, with complete resolution of his symptoms after high dose corticosteroid and IVIG treatment.