Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma.

Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

Neurological complications of excessive recreational nitrous oxide use: a case series based on a text mining algorithm.

BACKGROUND: The recreational use of nitrous oxide (N2O) has gained popularity over recent years. We present a case series of excessive N2O users with neurological complications. METHODS: In this retrospective three-centre study, we used a text mining algorithm to search for patients who used N2O recreationally and visited a neurologist. RESULTS: We identified 251 patients. The median duration of N2O use was 11 months (interquartile range [IQR], 3-24) and the median amount of N2O used per occasion 1.6 kg (IQR 0.5-4.0). Clinically, polyneuropathy (78%), myelopathy (41%), and encephalopathy (14%) were the most common diagnoses. An absolute vitamin B12 deficiency of < 150 pmol/L was found in 40% of cases. In 90%, at least one indicator of functional vitamin B12 status (vitamin B12, homocysteine, or methylmalonic acid) was abnormal. MRI showed signs of myelopathy in 30/55 (55%) of cases. In 28/44 (64%) of those who underwent electromyography, evidence of axonal polyneuropathy was found. Most (83%) patients were treated with vitamin B12 supplementation, and 23% were admitted to the hospital. Only 41% had follow-up for ≥ 30 days, and 79% of those showed partial or complete recovery. CONCLUSIONS: In this case series of excessive N2O users, we describe a high prevalence of polyneuropathy, myelopathy, and encephalopathy. Stepwise testing for serum levels of vitamin B12, homocysteine, and methylmalonic acid may support the clinical diagnosis. Due to low sensitivity, MRI of the spinal cord and electromyography have limited value. Effective treatment should incorporate supplementation of vitamin B12 and strategies to prevent relapses in N2O use.

'White Cord Syndrome': A Rare Catastrophic Complication Following Anterior Cervical Discectomy and Fusion.

Background: 'White-cord syndrome' is an extremely rare entity following decompression of cervical cord in which post-operative reperfusion injury results in worsening of patient's neurology and MRI reveals signal changes in spinal cord in absence of cord compression. We wish to report a case of 'white-cord syndrome' following a 'routine' ACDF. Case Description: A 39-year-old woman with paresthesias and spastic quadriparesis was found to have C5-C6 PIVD on MRI. ACDF was performed at C5-C6, after which worsening of quadriparesis was noted, for which intravenous high-dose steroids were started. An urgent MRI was done, which revealed findings of white-cord syndrome, without compression on underlying cord. With conservative management, her ASIA grade improved from C to D and the features of white-cord syndrome disappeared on follow-up imaging. Conclusion: It is important for surgeons and patients to be aware of this rare but potentially catastrophic entity as this needs to be discussed while taking consent for surgery.

Spontaneous intramedullary abscesses caused by Streptococcus anginosus: two case reports and review of the literature.

BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.

A potential role of preexisting inflammation in the development of acute myelopathy following CAR T-cell therapy for diffuse large B-cell lymphoma.

The event of anti-CD19 chimeric antigen receptor (CAR)-T therapy inducing serious neurotoxicity in patients with diffuse large B-cell lymphoma (DLBCL) is recognized; however, the patterns of symptoms and severity vary greatly from patient to patient. We report an exceptional presentation of acute myelopathy in a refractory DLBCL following successful CAR-T treatment along with grade 3 cytokine release syndrome (CRS) and neurotoxicity. The patient was initiated on high-dose methylprednisolone (MPS) resulting in rapid improvement of neurological symptoms. Yet the myelopathy patient (MP) experienced severe lower limb motor deficit, and a subsequent spinal cord MRI revealed myelopathy with a sensory level at segment T2. Multimodal therapy consisting of MPS, intravenous immunoglobulin and anakinra therapy resulted in complete reversal of myelopathy condition and the patient remained cancer free. The assessment of time trends of serum cytokines at baseline and post CAR-T infusion in MP compared to other 4 DLBCL complete responder patients with varying degree of CRS following CAR-T infusion, suggested pre-existing baseline inflammatory conditions in MP with altered levels of cytokines. These findings, if corroborated by similar case studies, have the potential to generate novel insights into the manifestation of myelopathy following CAR-T therapy and the successful clinical management of such complications.

Case Report: Post-Chikungunya-Associated Myeloneuropathy.

Chikungunya virus (CHIKV) is an arbovirus endemic to South Asia with frequent outbreaks. A wide spectrum of neurological complications has been described in Chikungunya infections. Myeloneuropathy is a rare complication seen in Chikungunya and is proposed to have an underlying immune mediated pathogenesis. We report a case of a 45-year-old man presenting to the emergency services with acute onset of quadriparesis, breathlessness, urinary retention, profound pain, and sensory disturbances 6 weeks after the onset of high-grade fever and arthralgia. On examination, the patient had Medical Research Council grade 1 flaccid quadriparesis with prominent wasting and areflexia with distinct sensory level at T4. Immunoglobulin M CHIKV antibodies were positive, tested twice at a 1-week interval. He had notable magnetic resonance imaging (MRI) findings in the form of patchy T2 hyperintensities involving the entire length of the cervical and thoracic cord with normal brain imaging and extensive short tau inversion recovery hyperintense signal changes on muscle MRI. He was treated with five cycles of plasmapheresis and intravenous methylprednisolone followed by oral steroids for 8 weeks. At 20-week follow-up, the patient had improvement in upper limb weakness, but paraparesis persisted. The case highlights the presence of unusual MRI findings and also the importance of early recognition of after infective neurological complications, and prompt treatment with immunomodulation may be beneficial.

Clinical Features, Laboratory, and Radiological Findings of Patients With Acute Inflammatory Myelopathy After COVID-19 Infection: A Narrative Review.

ABSTRACT: The objective of this review was to analyze the existing data on acute inflammatory myelopathies associated with coronavirus disease 2019 infection, which were reported globally in 2020. PubMed, CENTRAL, MEDLINE, and online publication databases were searched. Thirty-three acute inflammatory myelopathy cases (among them, seven cases had associated brain lesions) associated with coronavirus disease 2019 infection were reported. Demyelinating change was seen in cervical and thoracic regions (27.3% each, separately). Simultaneous involvement of both regions, cervical and thoracic, was seen in 45.4% of the patients. Most acute inflammatory myelopathy disorders reported sensory motor and bowel bladder dysfunctions. On cerebrospinal fluid analysis, pleocytosis and increased protein were reported in 56.7% and 76.7% of the patients, respectively. Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction was positive in five patients. On T2-weighted imaging, longitudinally extensive transverse myelitis and short-segment demyelinating lesions were reported in 76% and 21%, respectively. Among the patients with longitudinally extensive transverse myelitis, 61% reported "moderate to significant" improvement and 26% demonstrated "no improvement" in the motor function of lower limbs. Demyelinating changes in the entire spinal cord were observed in three patients. Most of the patients with acute inflammatory myelopathy (including brain lesions) were treated with methylprednisolone (81.8%) and plasma-exchange therapy (42.4%). An early treatment, especially with intravenous methylprednisolone with or without immunoglobulin and plasma-exchange therapy, helped improve motor recovery in the patients with acute inflammatory myelopathy associated with coronavirus disease 2019.

Inhaled nitrous oxide-induced functional B12 deficiency.

Recreational nitrous oxide (N2O) is commonly used among young people partly due to its low cost and accessibility, and awareness of its potential adverse effects is poor in this group. One such adverse effect is degeneration of the spinal cord due to its disruption of DNA synthesis by inactivating cobalamin (B12).A 19-year-old man presented to the emergency department with a 4-week history of worsening paraesthesia in his fingers and lower limbs, and weakness in the hands and lower limbs for 2 weeks. On examination, he had an ataxic gait, reduced power of grip strength and ankle movements, and impaired sensation in the lower limbs. An MRI brain and spine revealed myelopathy of the cervical and thoracic cord.On further questioning, he reported recreational N2O inhalation. His symptoms improved after stopping this and he was treated with supplementation of B vitamins. Education strategies regarding the risks of N2O misuse are indicated.

Risk Factors for Hypoglycemia with the Use of Enteral Glyburide in Neurocritical Care Patients.

OBJECTIVE: Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide. METHODS: We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ2 test or the Fisher exact test for categorical variables. RESULTS: Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective. CONCLUSIONS: Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema.

Effect of Topical Steroid on Swallowing Following ACDF: Results of a Prospective Double-Blind Randomized Control Trial.

STUDY DESIGN: Randomized, double-blinded, controlled trial. OBJECTIVE: To investigate the effectiveness of local intraoperative corticosteroids at decreasing the severity of swallowing difficulty following multilevel anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Dysphagia is a common complication after ACDF, and while for most patients the symptoms are mild and transient, some patients can suffer from severe dysphagia resulting in significant postoperative morbidity. Previous studies investigating the local application of corticosteroids are limited. METHODS: This was a prospective, randomized, double-blinded, controlled trial of patients undergoing 2, 3, or 4 level ACDF for radiculopathy and/or myelopathy. Patients undergoing multilevel ACDF were randomized to receive local corticosteroid in the retropharyngeal space or placebo (no steroid). Dysphagia was assessed using validated outcomes including the Eating Assessment Tool-10 (Eat-10) and Swallowing Quality of Life (SWAL-QOL) Questionnaire both preoperatively and at 1 day (POD1), 2 days (POD2), and 1-month postoperatively. RESULTS: One-hundred nine patients had a complete dataset available for analysis. Eat-10 scores were significantly lower in the Steroid group on POD2 (8 vs. 16, P = 0.03) and 1-month postoperatively (2 vs. 5, P = 0.03). A comparison of the individual SWAL-QOL subscale scores demonstrated that patients in the Steroid group had better scores than the Control group in various subscales at all postoperative time points. Significant differences were noted (always in favor of the Steroid group) in 40% of subscales on POD1, 60% of subscales on POD2, and 50% of subscales at 1-month postoperatively. The Control group never had a better SWAL-QOL subscale score at any time point postoperatively. CONCLUSION: Local administration of corticosteroid after multilevel ACDF can decrease postoperative severity and symptomatology of dysphagia during the immediate postoperative period to 1-month postoperatively. The long-term effects of local steroid administration on fusion and other complications will need to be established in future studies.Level of Evidence: 1.

Ruptured long intramedullary spinal cord abscess successfully treated with antibiotic treatment.

Intramedullary spinal cord abscess (ISCA) is an extremely rare infection of the central nervous system. We report a 17-year old man with ISCA that suggested rupture confirmed by magnetic resonance imaging (MRI). The patient presented with meningeal signs, severe paraplegia, sensory impairment with a sensory level, and urinary retention. The cerebrospinal fluid (CSF) study showed pleocytosis with polymorphonuclear cells and a decreased glucose level suggesting bacterial meningitis. Computed tomography showed maxillary sinusitis and a lower respiratory tract infection. Spinal MRI showed an ISCA from Th5 to Th12. Part of the abscess seemed to have ruptured into the medullary cavity. Streptococcus intermedius was cultured from CSF, sputum, and the maxillary sinus abscess. It appeared that Streptococcus intermedius transferred from the respiratory tract to the spinal cord hematogenously, formed the ISCA, and the ISCA ruptured. The patient was treated with ampicillin, vancomycin, and meropenem. After 56 days of treatment, he could walk with a walker. In the present case, the MRI findings were helpful for early diagnosis and follow-up of the pathogenic condition. Although the present case suggested rupture of ISCA, he recovered with antibiotic therapy alone. This suggested earlier diagnosis with MRI and aggressive antibiotic therapy appear to be critical factors that determine the prognosis of patients with ISCA.

A randomized, double-blind, placebo-controlled trial for Yi-Qi Hua-Yu tong-sui granule in the treatment of mild or moderate cervical spondylotic myelopathy.

BACKGROUND: Neck pain, sensory disturbance and motor dysfunction in most patients suffered cervical spondylotic myelopathy (CSM). However, some conservative treatments are limited by their modest effectiveness. In the other hand, surgical treatment is necessary when symptoms are refractory to conservative treatments and neurological function of the patients has deteriorated. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. The purpose of the present study is to examine effectiveness and safety of Yiqi-Huayu-Tongsui (YQHYTS) granule, a compound traditional Chinese herbal medicine, on symptoms in patients with mild or moderate CSM. METHODS/DESIGN: A randomized, double blinded, placebo-controlled clinical trial to evaluate the efficacy and safety of YQHYTS granule is proposed. 72 patients in Longhua Hospital with the diagnosis of mild or moderate CSM will be randomly allocated into 2 groups, and treated with YQHYTS granule or placebo. The prescription of the trial drugs (YQHYTS granule/placebo) is 20 grams twice a day for 3 months. The primary outcome measurements include visual analog scale, Japanese Orthopedic Association, and Neck Disability Index score. The secondary outcome measurements are electromyogram and Pfirrmann classification. DISCUSSION: YQHYTS granule has been established and applied in Longhua Hospital for many years. As it has a potential benefit in treating mild or moderate CSM, we designed a double-blind, prospective, randomized controlled trial and would like to publish the results and conclusions later. If YQHYTS granule can alleviate neck pain, sensory disturbance, and even motor dysfunction without adverse effects, it may be a unique strategy for the treatment of mild or moderate CSM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ID: ChiCTR1900028192. Registered 15 December 2019, Available at: http://www.chictr.org.cn/edit.aspx?pid=46913&htm=4.

Icariin ameliorates the progression of experimental autoimmune encephalomyelitis by down-regulating the major inflammatory signal pathways in a mouse relapse-remission model of multiple sclerosis.

This study aimed at investigating whether treatment with icariin (ICA) could modulate the progression of experimental autoimmune encephalomyelitis (EAE) and its potential mechanisms in SJL/J mice. Female SJL/J mice were immunized with PLP139-151 peptide to induce relapse-remitting EAE and the immunized mice were treated with vehicle alone (EAE) or ICA (12.5 or 25 mg/body weights) by gavage daily for 42 days. Compared with the control, the EAE mice developed relapse-remitting EAE and reduced body weights (15.76 ± 0.61 vs. 17.60 ± 0.98 g on day 13; 17.35 ± 0.44 vs. 18.46 ± 0.66 g on day 26), accompanied by severe inflammation with many microglia infiltrates and obvious demyelination in the spinal cord tissues. Conversely, ICA treatment significantly reduced the clinical scores (on day 13, 1.00 ± 0.16 and 1.10 ± 0.33 for ICA 12.5 and 25 mg/kg group, respectively vs. 1.62 ± 0.41 in the EAE group; on day 26, 0.50 ± 0.23 and 0.40 ± 0.24 for ICA 12.5 and 25 mg/kg group, respectively, vs. 1.56 ± 0.29 in the EAE group), mitigated the body weight reduction, spinal cord inflammation and demyelination in EAE mice (pathological scores of 2.33 ± 0.82 and 1.11 ± 0.57 for ICA 12.5 and 25 mg/kg, respectively; vs. 4.78 ± 1.13, P < 0.0001). Furthermore, ICA treatment significantly mitigated the EAE-increased iNOS, TNF-α, CD206 and TGF-ß1, but further reduced IL-10 mRNA transcripts in the brain mice. More importantly, ICA treatment significantly mitigated the inflammation-related NF-κB, AKT, ERK1/2, p38, c-Jun and MEK phosphorylation in the brain of EAE mice. ICA treatment ameliorates the progression of EAE by down-regulating the major inflammation-related signal pathways in mice.

Autonomic dysreflexia in a case of radiation myelopathy and cisplatin-induced polyneuropathy.

INTRODUCTION: While autonomic dysreflexia caused by severe spinal cord lesions can be life-threatening, relevant reports on non-traumatic spinal lesions are rare. Furthermore, modes of innervation of the supraspinal inhibitory pathways at each spinal sympathetic segment remain unknown. Herein, I report the case of a patient with autonomic dysreflexia and radiation myelopathy. The laterality of autonomic dysreflexia was investigated with special reference to the sudomotor function. CASE PRESENTATION: A 51-year-old man with a history of epipharynx carcinoma, radiotherapy, and cisplatin chemotherapy was referred for the evaluation of autonomic function. He was ambulant but displayed spastic tetraparesis, areflexia of the extremities, sensory disturbance below C4 dermatome, dysuria, and impotence. Spinal magnetic resonance imaging demonstrated a cervical lesion involving the lateral portion of C2-C5, bilaterally. The thermal sweating test showed that sweating was lower on the left side of the face and neck, left shoulder, and arm than the corresponding parts on the right side. The rest of the body was anhidrotic. Sweating due to autonomic dysreflexia was symmetric, but more abundant on the left side of the face. Acetylcholine-induced sweating was markedly reduced on the left leg. DISCUSSION: This might be the first documentation of autonomic dysreflexia observed in a patient with radiation myelopathy. The present observations suggested that the supraspinal inhibitory pathway to spinal preganglionic neurons may descend on the same side as thermal sudomotor facilitatory pathways at the cervical level. Furthermore, autonomic dysreflexia was more prominent in the standing position suggesting that the pressure stimulus might enhance autonomic dysreflexia.

Monitoring Arteriovenous Malformation Response to Genotype-Targeted Therapy.

Arteriovenous malformations (AVMs) have recently been reported to have a high incidence of somatic KRAS mutations suggesting potential for treatment with mitogen-activated protein kinase inhibitors. In this case report, we describe genotype-targeted treatment of a KRAS mutant metameric AVM in a patient with Cobb syndrome using the mitogen-activated protein kinase inhibitor trametinib. Therapeutic response was monitored with phase-contrast magnetic resonance angiography to quantify AVM arterial inflow as an imaging biomarker. Treatment with trametinib resulted in a substantial decrease in blood flow to the AVM, with a >75% reduction in arterial inflow after 6 months of trametinib therapy.

Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model.

Cervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.