Neurological Manifestations Induced by Nitrous Oxide Abuse: A Case Series and Review of Literature.

INTRODUCTION: Nitrous oxide (NO) abuse is increasing among young people. This can result in severe neurological disorders such as myelopathy and/or peripheral neuropathy. We report the clinical presentations, biological, radiologic and electrophysiological findings of 5 patients hospitalized with neurological symptoms consecutive to NO abuse. In addition, a literature review was conducted to describe the neurological characteristics and to identify factors associated with a poor recovery. CASE REPORT: Among the 5 patients included, 2 had a myeloneuropathy, 2 had a sensorimotor neuropathy, and 1 had a normal spinal cord magnetic resonance imaging and electromyography despite neurological manifestations consistent with myeloneuropathy. After vitamin B 12 supplementation, recovery was reported in 4 patients, and 1 was lost to follow-up.From the literature review, 154 patients were included [94 males; median age 22 (19 to 26) y; NO exposure 9 (3 to 18) mo]. A myelopathy was identified in 116 patients (75%) and a peripheral neuropathy was documented in 89 patients (58%). Compared with patients who recovered, those with sequelae were more likely to have a motor deficit at presentation ( P <0.001), to use NO regularly ( P <0.001), to have a lower vitamin B 12 level ( P =0.04), and a higher concentration of homocysteine ( P =0.04). A less extensive myelopathy was more frequently found in the group with favorable outcomes ( P =0.002). CONCLUSION: Neurological disorders caused by NO may be challenging with severe clinical patterns. We identified several factors associated with a poor recovery, to make clinicians aware of NO-induced neurotoxicity.

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.

Methotrexate-induced subacute myelopathy: a serious but treatable complication.

Subacute myelopathy is a rare but serious complication of methotrexate (MTX) that may cause paraplegia. Although its underlying mechanisms have not been fully elucidated, homocysteine is thought to play a role in the pathogenesis of this adverse effect. Herein, we report the case of a 34-years old female patient with diffuse large B-cell lymphoma who developed progressive paraplegia accompanied by dysfunctional bladder and bowel movements after treatment with a modified CODOX-M/IVAC regimen, including high-dose intravenous MTX and intrathecal (IT-) MTX. Neurological symptoms gradually improved to almost normal levels within 4.5 months of onset following treatment with a combination of S-adenosylmethionine, methionine, cyanocobalamin, and folate. During chemotherapy, including high-dose MTX and IT-MTX for hematological malignancies, MTX-induced subacute neuronal damage should be carefully evaluated, and appropriate treatment should be initiated as early as possible.

Delayed myelopathy in a child following organic phosphate poisoning.

We report a rare manifestation of delayed organophosphate (OP) poisoning in a male patient in his early childhood. After initially presenting with a cholinergic crisis after OP exposure, the patient returned 3 weeks later with paraparesis and difficulty with bladder control. The results of the MRI of the spine and brain as well as the nerve conduction studies were normal. Myelopathy induced by OP poisoning should be considered in any patient with a history of OP exposure and a presentation of paraparesis. At most recent follow-up, the patient had full bladder control and could walk without assistance. However, he demonstrated circumduction while walking with upper motor neuron signs. Furthermore, he had mild Achilles tendon contractures on both sides. To enable early detection, neurologists and paediatricians should be aware of this uncommon complication of OP poisoning which may influence neurological outcome.

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment.

Use of the Rehabilitation Treatment Specification System (RTSS) in the management of nitrous oxide (N2O)-induced spinal cord injury.

Nitrous oxide (N2O) is an inhaled anaesthetic gas and a popular intoxicant. Excessive recreational use can cause spinal cord myelopathy. Previous studies have discussed the medical management. However, none have specified the sensorimotor rehabilitation management. This case report documents the investigations, physical rehabilitation and functional outcomes in two cases of N2O-associated myelopathy. Both presented with lower limb strength and sensorimotor integration impairments resulting in ataxic ambulation. Dorsal column signal abnormality was observed on T2-weighted MRI in one case. Myelopathy was diagnosed based on clinical presentation and both were treated with vitamin B12 Rehabilitation was conceived and specified using the Rehabilitation Treatment Specification System (RTSS). Both cases achieved independent indoor gait on hospital discharge, and full function at 9 months in one case. Appropriate and timely medical management and reasoned rehabilitation provided excellent functional outcomes for N2O-related myelopathy. By using the RTSS, reasoned rehabilitation efficacy can be tested in the future.

Nelarabine-induced myelopathy in patients undergoing allogeneic hematopoietic cell transplantation: a report of three cases.

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

[Cervical myelopathy due to nitrous oxide inhalation]. / Omfattande inhalationsbruk av lustgas gav ryggmärgsskada.

A 19 year old male presented to his GP with bilateral numbness and stiffness of hands and lower limbs, as well as muscle weakness and poor balance. The patient admitted recreational use of nitrous oxide (laughing gas) some days earlier. He was hospitalised and underwent a series of plasmapheresis treatments due to an initial suspicion of inflammatory myelitis. Further investigation gave evidence of cervical myelopathy which was deemed secondary to heavy use of nitrous oxide. Substitution therapy with hydroxycobalamine was initiated and the patient gradually recovered, although he was later found to have hyperhomocysteinaemia. The adverse effects of recreational nitrous oxide use are discussed, as well as potential pitfalls in diagnosis.

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.

Myelopathy associated with intrathecal methotrexate.

A 21-year-old man developed progressive and bilateral lower limb numbness, gait impairment and urinary incontinence over 10 days. He had received intrathecal methotrexate 20 days previously for acute lymphoblastic B-cell leukaemia, following 7 months of systemic chemotherapy. MR scan of the spinal cord showed bilateral symmetric and extensive T2/fluid attenuated inversion recovery (FLAIR) increased signal involving the dorsal columns in the thoracic cord. His serum folate concentration was at the lower end of the normal range. We stopped the intrathecal chemotherapy and gave folate; after a few days, he progressively improved. Myelopathy is an important adverse effect of intrathecal methotrexate, which may cause clinical and imaging features resembling subacute combined degeneration of the spinal cord. CNS infiltration must be excluded, intrathecal chemotherapy stopped and deficiency of folate or vitamin B12 treated as appropriate.

Saturday Night Myelopathy: Flexion Myelopathy Related to Drug Intoxication.

INTRODUCTION: Myelopathy is a common condition with a variety of causes, often eluding diagnosis for some time. Prolonged flexion after surgical procedures has been described. CASE REPORT: A 20-year-old female presented with acute paraparesis after polysubstance drug intoxication and a period of prolonged neck flexion while unconscious. Imaging demonstrated extensive cervicothoracic central cord signal change, in addition to posterior neck musculature hyperintensity. Additional workup directed to other causes was negative. The patient was diagnosed with flexion myelopathy and was treated with a course of steroids, with marked improvement. CONCLUSIONS: The clinician should consider the possibility of flexion-related myelopathy particularly in cases of drug intoxication or prolonged unconsciousness. Signal change within cervical musculature may provide additional clues and allow diagnosis in a timely manner.

[Cervical myelopathy secondary to recreational nitrous oxide use: an emergent pathology]. / Mielopatía cervical secundaria al consumo recreativo de óxido nitroso. Una afección emergente.

We describe the case of a 27-year-old female patient who presented to the emergency ward with hypoesthesia and paresthesia developing over the last two months, initially in both feet and progressing to the knees in a few days without associated gait disorders. Dystonia in the thumb and index finger of both hands was noted. Blood tests including toxic drugs were negative. The spinal magnetic resonance imaging was consistent with (C3-C5) myelopathy or myelitis without other abnormalities suggestive of systemic diseases. The biochemical and bacteriological analysis of the cerebrospinal fluid was normal. Because of these findings, the patient was re-interviewed to determine the consumption of unusual drugs, and nitrous oxide consumption was referred. The patient was admitted for further studies, which confirmed the diagnosis.

Se describe el caso de una paciente de 27 años que se presentó al servicio de urgencias por hipoestesia y parestesia de dos meses de evolución. El cuadro se inició en ambos pies, progresó en pocos días hasta las rodillas sin trastornos de la marcha y se acompañó de distonías en pulgar e índice de ambas manos. La analítica sanguínea incluyendo tóxicos fue negativa. La resonancia magnética medular mostró una imagen sugestiva de mielopatía o mielitis (C3-C5) sin otras anomalías sugestivas de enfermedad sistémica. El análisis bioquímico y el bacteriológico del líquido cefalorraquídeo fueron normales. Ante estos elementos se re-interrogó a la paciente en busca de consumo de tóxicos inusuales con la confirmación de consumo de óxido nitroso. La paciente fue internada para la realización de otros estudios que confirmaron la hipótesis diagnóstica del servicio de urgencias.

Mielopatía cervical secundaria al consumo recreativo de óxido nitroso una afección emergente / Cervical myelopathy secondary to recreational nitrous oxide use: an emergent pathology

Resumen Se describe el caso de una paciente de 27 años que se presentó al servicio de urgencias por hipoestesia y parestesia de dos meses de evolución. El cuadro se inició en ambos pies, progresó en pocos días hasta las rodillas sin trastornos de la marcha y se acompañó de distonías en pulgar e índice de ambas manos. La analítica sanguínea incluyendo tóxicos fue negativa. La resonancia magnética medular mostró una imagen sugestiva de mielopatía o mielitis (C3-C5) sin otras anomalías sugestivas de enfermedad sistémica. El análisis bioquímico y el bacteriológico del líquido cefalorraquídeo fueron normales. Ante estos elementos se re-interrogó a la paciente en busca de consumo de tóxicos inusuales con la confirmación de consumo de óxido nitroso. La paciente fue internada para la realización de otros estudios que confirmaron la hipótesis diagnóstica del servicio de urgencias.

Abstract We describe the case of a 27-year-old female patient who presented to the emergency ward with hypoesthesia and paresthesia developing over the last two months, initially in both feet and progressing to the knees in a few days without associated gait disorders. Dystonia in the thumb and index finger of both hands was noted. Blood tests including toxic drugs were negative. The spinal magnetic resonance imaging was consistent with (C3-C5) myelopathy or myelitis without other abnormalities suggestive of systemic diseases. The biochemi cal and bacteriological analysis of the cerebrospinal fluid was normal. Because of these findings, the patient was re-interviewed to determine the consumption of unusual drugs, and nitrous oxide consumption was referred. The patient was admitted for further studies, which confirmed the diagnosis.