[Transverse myelitis and cauda equina syndrome followed by varicella in a patient with varicella-zoster virus infection].

A 74-year-old man was admitted to our hospital with complaints of weakness in the lower extremities, urinary retention for 10 days, and generalized vesicular rash for 7 days. Spinal magnetic resonance imaging showed contrast enhancement at the Th12-L1 level of the spinal cord and cauda equina. Serum and cerebrospinal fluid varicella-zoster virus (VZV)-immunoglobulin (Ig) G antibody titers were markedly elevated, and VZV-IgM was detected in cerebrospinal fluid. The patient was diagnosed with VZV transverse myelitis and cauda equina syndrome with subsequent varicella and was treated with acyclovir and prednisolone. Two months later, muscle weakness, and dysuria had almost completely resolved. We hypothesize that latent VZV in the ganglia reactivated and caused transverse myelitis, which subsequently spread to the body via the bloodstream, resulting in the development of varicella.

Rhombencephalitis and longitudinal extensive myelitis associated with dinutuximab use in high-risk neuroblastoma.

BACKGROUND: Dinutuximab is a monoclonal antibody that targets the GD2 antigen used in the treatment of high-risk neuroblastoma. Dinutuximab-associated rhombencephalitis and myelitis is a rare, steroid-responsive, serious, but reversible pathology. To date, three transverse myelitis cases and one rhombencephalitis case due to dinutuximab have already been reported. Moreover, a recently published article identified five inflammatory CNS demyelination cases (four myelitis and one rhombencephalitis). We present a 5-year-old patient with rhombencephalitis and myelitis following dinutuximab-beta treatment. CASE: A 5-year-old patient with a left-sided retroperitoneal mass infiltrating the left kidney and multiple lytic bone lesions was diagnosed with neuroblastoma with a percutaneous biopsy from the abdominal mass. Surgery was performed after a prominent treatment response was detected on the abdominal CT. Radiotherapy was applied to the abdomen. While she was still undergoing maintenance treatment with 13-cis retinoic acid, a metaiodobenzylguanidine (MIBG) scan detected new bone lesions, and brain MRG identified pachymeningeal involvement. A new chemotherapy regimen was started and decreased MIBG uptake was seen in all previous bone lesions. However, newly developed eighth rib metastasis was seen in the following MIBG scan. Autologous stem cell transplantation was done. Soon after, dinutuximab-beta, together with temozolomide and irinotecan, was initiated. Following the third cycle hypotension, somnolence, paraparesis, and unilateral fixed dilated pupil were developed. Afterward, hemiballismus-like irregular limb movements were observed. Work-up studies were unremarkable, except for hypodensity in the brain stem on the brain CT. MRI revealed T2 hyperintensity of the brainstem and spinal cord extending from the cervicomedullary junction to the T7 level. Moreover, incomplete contrast enhancement and facilitated diffusion were observed. Imaging findings suggested demyelination. Steroids and intravenous immune globulin (IVIG) treatment were initiated. Both imaging abnormalities and clinical symptoms resolved partially at one month and disappeared at six months. CONCLUSIONS: Awareness of the radiological findings of dinutuximab toxicity will lead to prompt diagnosis and treatment.

Tuberculous myelitis: a prospective follow-up study.

BACKGROUND: Prospective studies regarding tuberculous myelitis are lacking. We aimed to prospectively evaluate patients with tuberculous myelitis to identify the features that distinguish tuberculous myelitis from other myelitis. METHODS: This was a prospective study. Patients presenting with paraparesis/quadriparesis, and MRI showing myelitis were included. All patients were subjected to clinical, neuroimaging, and laboratory evaluation. Diagnosis of definite tuberculous myelitis was made if GeneXpert test in CSF was positive. Probable tuberculous myelitis was diagnosed if there was evidence of tuberculosis elsewhere in the body. Patients were treated with methylprednisolone and antituberculosis treatment. Patients were followed for 6 months. We compared the clinical, laboratory, and neuroimaging parameters and response to treatment of tuberculous myelitis with other myelitis. P values were adjusted using the Benjamini-Hochberg (BH) procedure to control false discovery rate. RESULTS: We enrolled 52 patients. Eighteen (34.6%) patients had tuberculous myelitis. Headache (P = 0.018) was significantly more common in tuberculous myelitis. The CSF protein (P < 0.001), and CSF cell count (P < 0.001) were significantly higher in tuberculous myelitis. On neuroimaging, a LETM was common in tuberculous myelitis. Spinal meningeal enhancement (14; 77.8%), extra-axial collection, and CSF loculation (6; 33.4%), arachnoiditis (3;16.7%), and concomitant spinal tuberculoma (2;11.1%) were other common imaging features of tuberculous myelitis. Tuberculous myelitis patients showed a better response (P = 0.025) to treatment. CONCLUSION: Tuberculous myelitis was seen in approximately 35% of all myelitis cases, in a high tuberculosis endemic zone. Headache, markedly elevated CSF protein and spinal meningeal enhancement were distinguishing features. Tuberculous myelitis patients responded well to corticosteroids.

GR-α and GR-ß mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect.

Acute myelitis (AM) is a rare neuro-immune spinal cord disease. This study sought to explore the transcription level of glucocorticoid (GC) receptors α and ß (GR-α/GR-ß) in peripheral blood mononuclear cells (PBMCs) and their correlation with GC efficacy and sensitivity in AM patients. AM patients were grouped into the GC-sensitive group (N = 80) and GC-refractory group (N = 67). The GR-α and GR-ß mRNA levels in PBMCs were detected. The differentiating value of GR-α, GR-ß, and GR-α + GR-ß on GC sensitivity and resistance in AM patients was assessed. The independent correlation between GR-α and GR-ß mRNA levels and GC sensitivity in AM patients,t and the correlation between GR-α and GR-ß mRNA levels and spinal function after GC treatment were analyzed. GR-α mRNA level in PBMCs of GC-refractory patients was lower than that of GC-sensitive patients, while GR-ß mRNA level was higher than that of GC-sensitive patients. GR-α + GR-ß mRNA had a high diagnostic value for GC sensitivity and resistance in AM patients (area under the ROC curve = 0.881, sensitivity = 79.1%, specificity = 85.0%). GR-α and GR-ß mRNA levels were independently correlated with GC sensitivity. GR-α and GR-ß mRNA levels were correlated with the spinal function of AM patients after GC treatment. Overall, GR-α and GR-ß mRNA levels in PBMCs of AM patients can assist in the identification of GC sensitivity and are correlated with GC efficacy.

Pearls & Oy-sters: Diagnosis and Subtyping of Listeria Ventriculitis in an Immunocompetent Host.

Listeria monocytogenes is a Gram-positive food-borne pathogen that causes gastrointestinal symptoms and CNS infection in susceptible hosts. Two lineages of Listeria cause the majority of neurolisteriosis in humans. In this report, we discuss a case of a 23-year-old previously healthy woman who presented with acute-onset rapidly progressive altered mental status after eating undercooked meats at a local restaurant. Given her age and lack of comorbidities, bacterial meningitis was suspected, and she was treated with ceftriaxone, vancomycin, and steroids. MRI of the brain was consistent with meningitis and ventriculitis; CSF analysis also suggested bacterial meningitis. Despite mechanical ventilation, pressors, and ventricular drain placement, she quickly decompensated and died 12 hours after arrival. CSF culture later returned positive for Listeria monocytogenes We used whole-genome sequencing and near-source comparison to identify the Listeria subtype that led to her unexpected presentation. The results suggest that her CSF isolate was consistent with a lineage II Listeria serotype, which is known to exhibit greater genetic variation than the more commonly isolated lineage I serotypes. We conclude the discussion with diagnostic and treatment approaches to neurolisteriosis. In susceptible hosts, namely immunocompromised, pregnant, neonatal, or elderly patients, Listeria infection may result in CNS invasion, causing meningoencephalitis and, rarely, ventriculitis and rhombencephalitis. Although neurolisteriosis most commonly affects individuals with known risk factors, CNS infection is nevertheless possible in otherwise healthy young patients. Suspicion should be raised in patients with an exposure history who do not improve with empiric antibiotics.

Acquired immunodeficiency syndrome-related acute longitudinal myelitis involving the entire spinal cord.

INTRODUCTION: As acquired immunodeficiency syndrome (AIDS) becomes more widespread, there will be an increasing need for diagnostic AIDS-related neurological syndromes. AIDS-related myelitis is easy to be ignored, and AIDS-related longitudinal myelitis has not yet been reported. CASE PRESENTATION: A 45-year-old male patient was admitted to our hospital after 3 days of progressive slurred speech and limb weakness. Neurologic examination revealed near-complete four-limb paralysis with dyspnea, dysarthria, and neck rigidity. Contrast-enhanced T2-weighted magnetic resonance imaging showed hyperintensities within the entire spinal cord. Cerebrospinal fluid analysis showed elevated white blood cell count and protein level. He was administered high-dose immunoglobulin and methylprednisolone. There was rapid regression in his symptoms after a month of therapy. CONCLUSIONS: This unique presentation of AIDS with longitudinal myelitis involving the entire spinal cord enriches our understanding of the clinical spectrum of this condition. Our case provides essential information for the diagnosis and treatment of longitudinal myelitis in AIDS patients.

Clinical characteristics and outcome of neurosarcoidosis-associated myelitis: A retrospective cohort study and review of the literature.

BACKGROUND AND PURPOSE: Neurosarcoidosis can affect all parts of the nervous system of which myelitis is relatively frequent. The aim of this study was to describe clinical characteristics, treatment and prognosis of patients with myelitis attributable to neurosarcoidosis. METHODS: We performed a retrospective cohort study and a systematic review and meta-analysis of neurosarcoidosis-associated myelitis. RESULTS: Myelitis was identified in 41 of 153 (27%) neurosarcoidosis patients seen at our clinic from 2015 to 2020. Classification of neurosarcoidosis was definite in three (7%), probable in 29 (71%) and possible in nine patients (22%). The median (interquartile range) age at onset was 49 (41-53) years and 20 of the patients were female (49%). The presenting symptoms included muscle weakness in 31 of 41 patients (78%), sensory loss in 35 (88%) and micturition abnormalities in 30 (75%). Spinal magnetic resonance imaging showed longitudinally extensive myelitis in 27 of 36 patients (75%) and cerebrospinal fluid examination showed an elevated leukocyte count in 21 patients (81%). Initial treatment consisted of glucocorticoids in 38 of 41 patients (93%), with additional methotrexate or azathioprine in 21 of 41 patients (51%) and infliximab in 10 of 41 patients (24%). Treatment led to remission, improvement or stabilization of disease in 37 of 39 patients (95%). Despite treatment, 18 of 30 patients (60%) could not walk independently at the end of follow-up (median 36 months). A review of the literature published between 2000 and 2020 identified 215 patients with comparable clinical characteristics and results of ancillary investigations. CONCLUSION: Sarcoidosis-associated myelitis is observed in 27% of neurosarcoidosis patients. Although treatment often led to a decrease in disease activity, residual neurological deficits leading to loss of ambulation occurred frequently.

Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder.

Background: Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive. Objective: We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis. Methods: Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS). Results: Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013). Conclusion: Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

[Recurrent myelitis in a case of IgG4-related respiratory disease].

We report an 80-year-old man with IgG4-related pleuritis who had been treated with a low dose oral steroid for two years and developed recurrent myelitis. He was admitted to our hospital with gradually worsening numbness in the lower body and difficulty in walking due to mild weakness and loss of proprioception in the legs. T2-weighted MR images of the spinal cord showed a high signal intensity lesion, located centrally in the spinal cord at the Th2-4 spine levels. Laboratory data revealed an elevated serum IgG4 level and cerebrospinal fluid protein level. Anti-aquaporin 4 antibody, anti-myelin oligodendrocyte glycoprotein antibody and other autoantibodies were negative. He showed a good response to the administration of steroid pulse therapy with almost resolution of the neurological symptoms and MRI findings. He was followed with the maintenance therapy with a low dose oral steroid. After one year, he developed recurrence of myelitis in the lower end of the medulla oblongata and in the central to dorsal area at the C2 spine level. Each lesion of recurrent myelitis was located within 3 vertebral segments length and improved without focal spinal atrophy. Recently, IgG4-related disease (IgG4-RD)-associated inflammation involving brain parenchyma and spinal cord were reported. Further investigations are needed to elucidate the relationship between IgG4-RD and seronegative recurrent myelitis.

Ixekizumab exposure associated with myelitis: A case report and a literature review.

We describe a case of a 28-year-old man who developed a cervical myelitis while exposed to ixekizumab (IL-17 inhibitor) for psoriatic arthritis. Spinal MRI showed a T2 hyperintense lesion at the C4-C5 level while brain MRI was unspecific. Oligoclonal bands were absent and extensive screening for autoimmunity was negative. Rechallenge with ixekizumab was positive corroborating a relation between drug exposure and the neurological event. To the best of our knowledge, this is the first case of CNS inflammatory adverse event associated with ixekizumab. We also provide a review of case reports of demyelinating disorders associated with the use of biologic drugs for the treatment of psoriasis and psoriatic arthritis.

Uncommon inflammatory/immune-related myelopathies.

The differential diagnosis for immune-mediated myelopathies is broad. Although clinical manifestations overlap, certain presentations are suggestive of a particular myelopathy etiology. Spine MRI lesion characteristics including the length and location, and the pattern of gadolinium enhancement, help narrow the differential diagnosis and exclude an extrinsic compressive cause. The discovery of specific antibodies that serve as biomarkers of myelitis such as aquaporin-4-IgG and myelin-oligodendrocyte -glycoprotein-IgG (MOG-IgG), has improved our understanding of myelitis pathophysiology and facilitated diagnosis. In this review we will focus on the pathophysiology, clinical presentation, imaging findings and treatment and outcomes of uncommon immune-mediated myelopathies.

Human herpesvirus 6 myelitis after chimeric antigen receptor T-cell therapy.

This article reports a fatal case of human herpesvirus 6 (HHV-6) myelitis following CD19-targeted chimeric antigen receptor T-cell therapy. Infection from HHV-6 reactivation after haematopoietic stem cell transplant is established, and outside of this population is limited to case reports. The patient developed cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome that responded to corticosteroids both clinically and on imaging. Subsequently, ascending flaccid paralysis developed, leading to neuromuscular respiratory failure and, ultimately, death. Disease progression was refractory to foscarnet and multiple immunomodulating agents. HHV-6 should be considered in patients with encephalitis and myelitis after adoptive T-cell therapy.

Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab.

We present the case of a young woman being treated with rituximab for rheumatoid arthritis who developed a severe enteroviral meningoencephalitis and acute flaccid myelitis (AFM). Cerebrospinal fluid (CSF) and stool reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis and additional sequencing studies performed at the CDC further characterized the enterovirus as enterovirus A71 (EV-A71). After treatment with intravenous immunoglobulin (IVIg) and fluoxetine (based on previous reports of possible efficacy) the patient experienced a remarkable improvement over time. This case highlights the importance of considering enteroviral infection in patients treated with rituximab, depicts a possible clinical course of enteroviral meningoencephalitis and AFM, and illustrates the importance of testing multiple sites for enterovirus infection (CSF, stool, nasopharyngeal swab, blood). Here we present the case with a brief review of the literature pertaining to EV-A71.

VZV myelitis with secondary HIV CSF escape.

A 52-year-old woman with HIV and recent antiretroviral therapy non-adherence presented with a 5-day history of widespread painful vesicular skin lesions. Direct fluorescent antibody testing of the skin lesions was positive for varicella zoster virus (VZV). On day 3, she developed profound right upper extremity weakness. MRI of the brain and cervical spine was suggestive of VZV myelitis. Lumbar puncture was positive for VZV PCR in the cerebrospinal fluid (CSF) and CSF HIV viral load was detected at 1030 copies/mL, indicating 'secondary' HIV CSF escape. She was treated with intravenous acyclovir for 4 weeks and subsequent oral therapy with famciclovir then valacyclovir for 6 weeks. She also received dexamethasone. The patient had an almost full recovery at 6 months. Myelitis is a rare complication of reactivated VZV infection that can have atypical presentation in immunocompromised patients. Such 'secondary' HIV CSF escape should be considered in immunosuppressed patients with concomitant central nervous system infection.

Idiopathic myelitis presenting as Brown-Séquard syndrome: two case reports and a review of the literature.

BACKGROUND: Brown-Séquard syndrome often occurs in spinal cord injury, and few myelitis patients present with Brown-Séquard syndrome. CASE PRESENTATION: A 33-year-old Han man was admitted with neck pain plus numbness in the right limbs for 2 days and weakness in the left limbs for 1 day. Examination was significant for left limbs with grade 4 muscle power, positive left Babinski sign, diminished vibration sensation in the left limbs and decreased pain below the right clavicle dermatome. The cerebrospinal fluid (CSF) cell count was 24 × 106/L, and the protein count was 185 mg/L. Cervical magnetic resonance imaging (MRI) indicated abnormal swelling signals in the medulla-cervical cord long segment and enhanced signals in the C2-3 region. In the second case, a 47-year-old Han woman was admitted with weakness in the right lower limb and numbness in the left lower limb for more than 20 days. Examination was significant for the right lower limb with grade 4 muscle power, left knee hyperreflexia, positive left Babinski sign, diminished vibration sensation in the right lower limb and decreased pain below the right T2 dermatome. Cervical MRI indicated hyperintense and enhanced signals in the C7-T2 region. In these two cases, CSF culture, oligoclonal band (OB) and aquaporin 4 (AQP4) antibody were negative. Brain MRI was normal. Their symptoms and MRI results improved after treatment with methylprednisolone. CONCLUSIONS: Myelitis can present as Brown-Séquard syndrome, providing an extended reference in terms of the differential diagnosis for clinical physicians.

Slice Culture Modeling of CNS Viral Infection.

The complexity of the central nervous system (CNS) is not recapitulated in cell culture models. Thin slicing and subsequent culture of CNS tissue has become a valued means to study neuronal and glial biology within the context of the physiologically relevant tissue milieu. Modern membrane-interface slice culturing methodology allows for straightforward access to both CNS tissue and feeding medium, enabling experimental manipulations and analyses that would otherwise be impossible in vivo. CNS slices can be successfully maintained in culture for up to several weeks for investigation of evolving pathology and long-term intervention in models of chronic neurologic disease.Herein, membrane-interface slice culture models for studying viral encephalitis and myelitis are detailed, with emphasis on the use of these models for investigation of pathogenesis and evaluation of novel treatment strategies. We describe techniques to (1) generate brain and spinal cord slices from rodent donors, (2) virally infect slices, (3) monitor viral replication, (4) assess virally induced injury/apoptosis, (5) characterize "CNS-specific" cytokine production, and, (6) treat slices with cytokines/pharmaceuticals. Although our focus is on CNS viral infection, we anticipate that the described methods can be adapted to address a wide range of investigations within the fields of neuropathology, neuroimmunology, and neuropharmacology.

Anti-MOG antibody associated long segment myelitis presenting as anterior cord syndrome.

A patient having clinical features reminiscent of anterior cord syndrome (ACS) was found to have long segment myelitis on MRI. Investigations revealed serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody positivity. He was treated with pulse methylprednisolone followed by immunosuppressant therapy with mycophenolate mofetil, which led to clinical recovery. Anterior cord syndrome has so far not been reported in the context of anti-MOG antibody associated disease.

Delayed diagnosis of myelitis in a patient with Vogt-Koyanagi-Harada disease: a case report.

A case of myelitis following Vogt-Koyanagi-Harada (VKH) disease is reported, in which diagnosis and treatment were delayed. A 43-year-old male patient diagnosed with VKH disease presented at the Spine Centre of Yeungnam University Hospital, Daegu, Republic of Korea, with motor weakness, sensory deficit in both lower extremities, and dysuria for the previous 3 months. VKH disease had been diagnosed 15 months previously, based on vision loss in both eyes and the presence of bilateral nontraumatic granulomatous iridocyclitis, exudates, and retinal oedema. The patient exhibited severe motor weakness (right lower extremity, Medical Research Council (MRC) muscle scale, grade 2-0; left lower extremity, MRC grade 0). On cervical magnetic resonance imaging, a high-intensity T2 signal was observed in the spinal cord C4-C7 segments. Cerebrospinal fluid analysis revealed slightly elevated white blood cell counts. The patient was diagnosed with myelitis complicating VKH disease. Intravenous and oral corticosteroid therapy was administered. After steroid treatment, the patient's motor function in the right lower extremity was significantly improved (MRC grade 4-3). However, the left lower extremity did not show any improvement (MRC grade 0). To achieve a good treatment outcome, the diagnosis and treatment of myelitis in VKH disease should not be delayed.