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

P156. Mortality of operative spinal fractures in COVID-19 positive patients using data from a national database

BACKGROUND CONTEXT: The ever-evolving COVID-19 pandemic has presented critical surgical management challenges. Increases in COVID-19 positive patients and subsequently, patients sustaining spinal fractures who test positive for COVID-19, raises the question of whether these individuals are at an increased risk of mortality and subsequent complications. PURPOSE: The purpose of this study was to characterize the cohort of COVID-19-positive patients who required surgery following a spinal fracture and investigate if these patients are at increased risk of all-cause mortality and further complications. STUDY DESIGN/SETTING: Retrospective cohort study of prospectively collected data performed from March 15, 2020 to December 12, 2021 using a national database with clinical data from 56 sites. PATIENT SAMPLE: Patients with a diagnostic test for COVID-19, who sustained spinal fractures and required operative intervention. OUTCOME MEASURES: The primary outcome was all-cause mortality. Additional outcomes included acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE) and sepsis. METHOD(S): A total population of 8.4 million patients was examined using the National COVID Cohort Collaborative (N3C) data enclave. The N3C is a centralized national data resource that compiles data using electronic health care records from over 8 million patients. Inclusion criteria consisted of adults 18 years old or older with a diagnostic test for COVID-19, who sustained spinal fractures and required operative intervention. Patients' information from this database was collected and grouped according to lab-confirmed COVID-19-positive and negative testing which was acquired via the "SARS-CoV-2 RT-PCR and Antigen" test. Those who tested positive for COVID-19 were compared to a control group that was COVID-19-negative using the same standardized PCR and antigen testing methods. RESULT(S): A total of 2,745 patients with operative spinal fractures were identified. A group of 207 (8%) patients tested COVID-19 positive at the time of surgery. At baseline, the groups were comparable in age (57 vs 58 years), gender (41% women in each group), body mass index (28 in each group), cervical spinal cord injury (9.8% vs 8.1%) and length of stay (8 days in each group) (all p>0.05). The COVID-19positive cohort had a higher all-cause mortality than the COVID-19 negative group (14% vs 7%, p<0.001). There were increased odds for AKI [1.62(1.15, 2.26)], ARDS [2.78(2.07, 3.73)], VTE [1.65(1.18, 2.30)], and sepsis [2.58(1.88,3.53)] [Odds Ratio (Lower Limit, Upper Limit)] in patients testing positive for COVID-19. CONCLUSION(S): This national analysis of operative spinal fractures and COVID-19 showed increased mortality and perioperative events (AKI, ARDS, VTE, Sepsis). Further research is needed to investigate potential interventions for testing and management related to COVID-19 in the context of operative spinal fractures. FDA DEVICE/DRUG STATUS: This does not discuss or include any applicable devices or drugs. Copyright © 2022

Older patients with multiple sclerosis have greater enlargement of the brain ventricles following COVID-19

Introduction: The effect of COVID-19 on brain pathology in multiple sclerosis patients is currently unknown. Objective(s):To describe changes in brain lesion activity as well as brain and spinal cord volumes following COVID-19. Method(s): We included 181 MS patients (McDonald 2017 criteria) with available MRI scans (N=650) before (#scans>=2) and after (>=1) COVID-19. All patients were clinically stable (no relapsing activity or disability progression), did not received highdose steroids, and did not change treatment status. All patients were scanned on a single 3T scanner (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). Brain MRI activity was assessed manually by neuroradiologist using automatic subtraction. Global and regional brain volumes were evaluated using the MorphoBox prototype software, and the mean upper cervical cord area (MUCCA) was assessed using ScanView software. Linear mixed models (with random intercept for patient) adjusted for sex age, disease duration, Expanded Disability Status Scale (EDSS), treatment status at infection, severity of COVID-19, and use of anti-covid treatment were used to analyze the difference in MRI measures before and after COVID-19. Result(s): The sample consisted of 75.7% of women, the mean duration of the age was 45.5 years, the mean disease was 15.1 years, and median EDSS was 2.0 (range 0-6.5). A total of 7.2% patients had not immunomodulatory treatment, 39.8% were on platform, 37.0% were on oral, and 16.0% were on high-efficiency monoclonal antibody immunomodulatory therapy. Together, 3.3% of the patients were asymptomatic, 82.3% had a mild infection, 14.4% had suspected or confirmed pneumonia. Patients with a higher age had a greater enlargement of the total ventricle volume (interaction age vs. COVID-19: b=0.0029;p=0.0027), right and left lateral ventricles (b=0.0012-0.0013;p=0.0069-0.0015), third ventricle (b=0.0002;p=0.027) and a greater reduction of mesencephalon volume (b=-0.0004;p=0.013) following the infection. In eleven patients on anti-CD20 treatment we found reduction of normalized white matter (b=-0.58;p=0.044) and hippocampal white matter volume (b=-1.73;p=0.0063). The brain lesion activity (occurrence of new and enlarging T2 lesions) was not influenced by the infection. Conclusion(s): Older MS patients had greater enlargement of brain ventricles after COVID-19. We did not find clear changes in lesion activity or brain tissue volumes following the infection.

Persistent central and peripheral nervous system inflammation following Johnson & Johnson vaccine: a case series

Introduction: Transverse myelitis has previously been reported following administration of the Johnson and Johnson (J&J) vaccine against SARS-CoV-2. Brain and peripheral nervous system involvement is less well described. Aims/Methods: We report on a case series of 3 patients who developed neuro-inflammation following administration of the J&J vaccine (Ad26.COV2.S). Spinal cord was involved in all 3 patients, brain - in 2, and peripheral nervous system involvement (facial nerve enhancement, radiculitis) in 2. Result(s): Case 1: A 43F developed progressive gait difficulty and ascending paresthesias in bilateral lower extremities ~4 weeks after J&J COVID-19 vaccination. MRI revealed multiple enhancing cervical and thoracic cord lesions and 1 small enhancing subcortical brain lesion. Workup included extensive serum and CSF testing that was unremarkable, except for matching bands in CSF and serum. 3 months later she developed symptom recurrence with persistent enhancement and enlargement of one cord lesion. Case 2: A 39M developed bilateral ascending numbness, tingling, gait instability, urinary hesitancy/urgency and bilateral peripheral facial weakness 10 days after J&J COVID-19 vaccination. MRI revealed bilateral facial nerve enhancement, patchy cervical and thoracic cord and cauda equina enhancement. CSF revealed lymphocytic pleocytosis and elevated protein, with no oligoclonal bands. Extensive serum/CSF testing was otherwise unremarkable. Patient developed recurrent symptoms during steroid taper 3 months later;MRIs showed persistent enhancement and enlarging lesions. Case 3: A 34F developed blurred vision, body aches, paresthesias and urinary retention 2 weeks after J&J COVID-19 vaccination. MRI revealed large, mostly enhancing fluffy occipital/parietal lesions, cervical lesion, longitudinally extensive thoracic lesion and lumbar nerve root enhancement. CSF revealed neutrophilic pleocytosis and elevated protein. 3 months later she developed new enhancing brain lesions with persistent enhancement in the spine. Conclusion(s): Our case series highlights that central and peripheral nervous system inflammatory involvement without clear alternative explanation can rarely be seen in close temporal relationship to administration of the J&J COVID-19 vaccine. Unusual feature of our cases was clinical/radiographic worsening and persistent enhancement several months after initial presentation.Two patients required second-line immunotherapy for disease control.

MULTIPLE SCLEROSIS AFTER COVID-19: A SIGN OF THINGS TO COME?

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: We present a patient with left-sided eye pain and headache developing 3 weeks after hospitalization for COVID-19. MRI showed inflammation of the left optic nerve and other demyelinating lesions in the brain and cervical spinal cord consistent with multiple sclerosis. CASE PRESENTATION: Our patient is a 36-year-old female with a history of migraines who presented to the emergency department (ED) with complaints of right-sided eye pain and throbbing intractable headache for the past week. The pain was worse on eye movement and the patient reported color changes in her vision. She had been hospitalized for coronavirus disease 2019 (COVID-19) 3 weeks previously. Her workup in the ED revealed white matter changes in the right frontal lobe on computer tomography (CT) scan of the head. She subsequently had a Magnetic resonance imaging (MRI) scan of her brain, cervical and thoracic spine showing left optic peri-neuritis, and scattered foci in the periventricular white matter, corpus callosum, and cervical spine. She was diagnosed with multiple sclerosis (MS) and treatment started with high-dose corticosteroids. The patient had a good response, with a resolution of her symptoms, and was discharged, on a tapering course of steroids, to follow up with neurology in the clinic. DISCUSSION: There is a well-known association between MS and viral infections capable of causing a neuroinflammatory response. COVID-19 includes several neurological manifestations both in the acute and chronic phase (Long COVID). It seems possible that an immune mechanism induced by COVID-19, which can activate lymphocytes and an inflammatory response, can induce the clinical onset of the disease. Other authors have reported an association between recent COVID and MS symptoms onset as well as exacerbations in MS symptoms in patients with established disease. CONCLUSIONS: In patients presenting with neurological symptoms after a recent COVID 19 infection, we should consider demyelinating disease as a possible diagnosis. Reference #1: Palao, M., Fernández-Díaz, E., Gracia-Gil, J., Romero-Sánchez, C. M., Díaz-Maroto, I., & Segura, T. (2020). Multiple sclerosis following SARS-CoV-2 infection. Multiple sclerosis and related disorders, 45, 102377. Reference #2: Bellucci, G., Rinaldi, V., Buscarinu, M. C., Reniè, R., Bigi, R., Pellicciari, G., … & Ristori, G. (2021). Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?. Frontiers in Immunology, 3850. Reference #3: Garjani A, Middleton RM, Hunter R, Tuite-Dalton KA, Coles A, Dobson R, Duddy M, Hughes S, Pearson OR, Rog D, Tallantyre EC, das Nair R, Nicholas R, Evangelou N. COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies. Mult Scler Relat Disord. 2021 Jul;52:102939. doi: 10.1016/j.msard.2021.102939. Epub 2021 May 5. PMID: 34010764. DISCLOSURES: No relevant relationships by Adrian Estepa No relevant relationships by Neelima Manda No relevant relationships by Rehan Saeed

Combined central and peripheral demyelination syndrome after COVID-19 vaccination with brisk response to plasma exchange and steroids

Objective: - Report a case of combined central and peripheral combined demyelination (CCPD) syndrome after COVID19 vaccine with brick improvement to steroids and PLEX - Provide a brief literature review of CCPD etiology and management Background: Combined central and peripheral demyelination (CCPD) is a rare, immunemediated disorder that presents with concurrent demyelination in the central and peripheral nervous system. Known clinical course and radiologic/electrodiagnostic features stem only from a limited number of case reports and small case series. The disease course can be monophasic or chronic. Response to immunomodulatory treatment is variable. Design/Methods: N/A Results: 59-year-old female presented with progressive lower extremity pain, weakness and urinary incontinence four weeks after receiving her second COVID-19 vaccine. Exam was notable for mild somnolence, restricted lateral gaze, right eye red desaturation without APD, ocular ataxia, left lower facial weakness, and lower extremity paresis with decreased reflexes. MRI of the brain and spinal cord showed multifocal supratentorial, intratentorial, cervical and thoracic cord white matter signal abnormalities with trace enhancement in combination with marked cauda equina enhancement. CSF showed albuminocytologic dissociation (protein of 184 and 2 nucleated cells). NMO, Anti-MOG and neurofascin-155 antibodies were negative. Electromyelogram and nerve conduction studies were consistent with a demyelinating polyneuropathy. The patient was treated with a 1 gram IV methylprednisolone daily and five treatments of plasma exchange. At six months, the patient had nearly returned to her previous baseline. Conclusions: CCPD is a rare inflammatory neurologic condition of peripheral and central demyelination. The etiology remains unclear, though viral infections and immunizations have been reported to proceed CCPD in some patients. Limited data is available to guide treatment but PLEX, IVIG and steroids are the most common. Outcomes are heterogeneous and methods to predict long term course remains uncertain. To our knowledge, this is the first reported case of CCPD after the COVID 19 vaccine.

Transverse Myelitis associated with COVID-19 in adults

Objective: To describe cases of transverse myelitis (TM) associated with mild COVID-19 in adults. Background: Post-infectious TM is described after various infections but is not as well-known after COVID-19. Design/Methods: We present a series of 2 cases who developed TM after infection with SARS-CoV-2. Case 1: 55-year-old male with coronary artery disease presented with worsening paraparesis over 4 months, T4 sensory level and urinary retention, starting two weeks after mild COVID-19 illness. MRI showed T2 hyperintensity extending from the lower medulla to T3 spinal cord. CSF analysis revealed elevated protein and pleocytosis. His functional status improved after plasma exchange. Subsequently, his symptoms worsened and was treated with multiple courses of glucocorticoids. He recently started Rituximab and continues to have leg weakness with urinary retention. Case 2: 66-year-old male with diabetes mellitus presented in a wheelchair with rapidly progressive paraparesis over 10 days, starting six weeks after mild COVID-19 illness. He was initially diagnosed with GBS and received IVIG with no improvement. MRI revealed T2 hyperintensity in the lateral corticospinal tracts of cervical and thoracic spinal cord. Somatosensory evoked potential testing showed mild bilateral demyelinating lesions involving the dorsal columns between the C6-parietal cortex. CSF analysis was normal. Plasma exchange therapy provided minimal improvement. He remains wheelchair bound with urinary urgency. In both cases, other causes of TM including neuromyelitis optica, myelin oligodendrocyte associated disease, neurosarcoidosis and paraneoplastic myelopathy were ruled out. Conclusions: SARS-CoV2 may cause a post-infectious TM. While causation remains difficult to prove, our cases suggest TM was precipitated by COVID-19 given the temporal association and no other identified etiology. Our cases continued to have significant neurologic deficits likely due to delayed diagnosis. These cases add to the growing body of evidence of neurologic complications associated with COVID-19. Further studies are needed to establish the incidence and outcomes of post-infectious TM after COVID-19.

A rare case of an acute ascending longitudinally extensive necrotizing transverse myelitis in a young woman: a severe post-COVID-19 infection neurological complication

Objective: N/A Background: Neurological injuries from severe acute respiratory syndrome coronavirus 2 (COVID-19) are becoming recognized in the central and peripheral nervous systems. Pathophysiology processes include a hyperinflammatory immune response due to the affinity of COVID-19 to human ACE2 receptors and multi-organ failure. CASE REPORT: This report highlights a unique presentation of a rapidly progressive, hyperacute to chronic, necrotizing transverse myelitis with associated COVID-19 long haul syndrome in a 31-year-old Venezuelan obese woman without other vascular risk factors. There was a preceding symptomatic COVID-19 infection. Symptoms included headaches, dysgeusia, asymmetric ascending proximal more than distal paresis, lumbago with dysesthesias, autonomic dysautonomia, hyperreflexia with clonus, and severe functional mobility impairment. Results: Neuraxis imaging showed a longitudinally extensive transverse myelitis (LETM) with T7-T9 enhancement and expansion throughout the thoracic spine (T4-T11). CSF studies showed lymphocytic pleocytosis with elevated protein. Aggressive empiric treatment included 1G of IV methylprednisolone, plasmapheresis (PLEX), and high-dose cyclophosphamide given the life-threatening progression of clinical symptoms. Repeat imaging post-treatment showed expansion of lesions to the cervical cord with sparing of the brainstem, stabilizing after cyclophosphamide initiation. Clinically, there was partial recovery of upper extremity sensation and strength. A T5-T6 tissue biopsy showed evidence of necrotizing myelitis with extensive neutrophil and lymphocyte infiltration. Given clinical progression, a repeat round of immunosuppression, including a monoclonal complement antibody, was pursued. Post-rehabilitation, the patient's symptoms improved above the thoracic spine but not below it. Conclusions: To our knowledge, this is the most severe form of COVID-19 associated necrotizing myelitis ever reported. Future research may clarify the molecular pathways that trigger neurological injury in patients with severe COVID-19 infection-associated spinal cord complications and increase therapeutic options.

Abstracts from the IFESS 2021 conferences

The proceedings contain 53 papers. The topics discussed include: evoked sensations with sinusoidal transcutaneous electrical stimulation at different frequencies;IMU triggered FES for robotic gait training;trans-spinal electrical stimulation for improving trunk and sitting function in tetraplegics with cervical cord injury;a combined approach to CNS excitation for hand rehabilitation: a case study using spinal stimulation and BCI;analysis of the movements generated by a multi-field FES device for upper extremity rehabilitation;and neuromuscular and functional electrical stimulation for motor recovery after COVID-19: systematic review.

Acute Disseminated Encephalomyelitis Secondary to Rubeola Infection Masquerading as New Onset Multiple Sclerosis in an Elderly Woman: Case Report

Introduction: Following an alarming surge of measles cases from declining immunization rates, it is important that clinicians recognize measles as a possible cause of otherwise unexplained symptoms, especially in patients with uncertain immunological status. Case: Over a 4-month period, a 76-year-old woman with a history of treated breast cancer experienced rapidly progressive and fluctuating focal weakness and numbness primarily affecting her lower extremities. Initially complaining of vague gastrointestinal symptoms upon returning from an extended stay in Florida, she was found to have active demyelinating lesions of her brain, cervical, and thoracic cord on MRI. This was initially thought to be new onset multiple sclerosis. CSF analysis showed critically high protein and, upon repeat analysis, positive rubeola and herpes IgM, which were elevated despite high dose steroid infusions and a steroid taper. Alternative diagnoses were ruled out, including: other infectious etiologies;endocrine/metabolic disorders;drug toxicity;malignancy;paraneoplastic disorders;transverse myelitis;multifocal cord infarction;stroke;seizure;and others. Repeat images displayed improvement of lesions and the patient was discharged to acute rehab with close neurological follow-up without steroids. Discussion: Acute disseminated encephalomyelitis is more likely in children, though cases are rare. This case of disseminated measles underscores the critical need for continued vaccination of at-risk populations, especially in those who are elderly or immunocompromised. Previous titers for immunity were not known, a potential limitation. Recent evidence demonstrates measles' ability to cause immune system "amnesia," potentially explaining this patient's concomitant herpes. As COVID-19 cases continue to present, recent evidence has linked the protective effect of the MMR vaccine against COVID-19's spread and severity. Conclusion: It is imperative that measles and other severe, preventable diseases continue to be closely monitored. Clinicians should assess benefits of proactively measuring rubeola titers in patients of all ages or in those who have previously received extensive immunosuppressive therapy.

A web-based interface for monitoring hand use in people with cervical spinal cord injury living in the community

Background: Functional use of the upper limbs (ULs) is the top recovery priority in individuals with cervical spinal cord injury (cSCI). Wearable cameras and computer vision have the potential to produce outcome measures that reflect hand function in a natural context. However, there is a need to identify ways to summarize and report video data in meaningful ways to support clinical decision-making. Objective: To determine the most effective way to summarize hand information collected with wearable cameras to report metrics of hand function to clinicians and community-dwelling individuals with cSCI. Participants: 7 clinicians (2 physiatrists, 2 physiotherapists, 3 occupational therapists) and 4 individuals with cSCI (AIS C-D, C3-C5). Individuals with cSCI had previous experience with wearable cameras, as they participated in a related study for developing computer vision techniques for monitoring hand function at home. Methods: Clinicians were split into 2 focus groups to discuss ways of reporting hand function information collected from people with cSCI living in the community. Due to the COVID-19 pandemic, discussion with individuals with cSCI was conducted individually via remote interviews. The discussion focused on what pieces of information are relevant to clinical practice, how data can be summarized and presented in practical and convenient ways, what types of information could help better express how hands are functioning at home, and how the collected information can improve care delivery. A web-based interface prototype was designed after the first round of meetings and refined after follow-up interviews. Results: Three rounds were required to reach a consensus among participants regarding the content to report in the web-based interface. Reports of hand function were divided into 2 pages: quantity of hand use (i.e., number and duration of hand-object interactions) and quality of hand use (i.e., type of hand grasps). Physiatrists expressed a preference for high-level information, such as plots of measures of hand function, whereas therapists preferred to watch short chunks of video recordings. Conclusion: A modular web-based interface that allows users to select the information to show (videos or summary plots of hand function) was designed. In conjunction with wearable cameras and artificial intelligence, this interface will make it possible to bridge the gap between rehabilitation centers and patients' homes to monitor hand function remotely and optimize UL therapy in individuals with cSCI.