RESUMO
A man in his late 40s with no known past medical history was unresponsive for an unknown period of time. Crushed pills and white residue were found on a nearby table. On presentation he was obtunded and unresponsive to verbal commands but withdrawing to painful stimuli. The initial urine drug screen was negative, but a urine fentanyl screen was subsequently positive with a level of 137.3 ng/mL. MRI of the brain showed reduced diffusivity and fluid attenuated inversion recovery (FLAIR) hyperintensity symmetrically in the bilateral supratentorial white matter, cerebellum and globus pallidus. Alternative diagnoses such as infection were considered, but ultimately the history and workup led to a diagnosis of fentanyl-induced leukoencephalopathy. Three days after admission the patient became able to track, respond to voice and follow basic one-step commands. The patient does not recall the mechanism of inhalation. While there are case reports of heroin-induced leukoencephalopathy following inhaled heroin use and many routes of fentanyl, this is the first reported case of a similar phenomenon due to fentanyl inhalation.
Assuntos
Fentanila , Leucoencefalopatias , Imageamento por Ressonância Magnética , Humanos , Fentanila/efeitos adversos , Masculino , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Adulto , Administração por Inalação , Analgésicos Opioides/efeitos adversos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacosRESUMO
Toxic leukoencephalopathy and myelopathy are common neurologic complications of a wide range of chemotherapeutic and substance abuse agents. During the last decade, there has been a significant change in the profile of white matter toxins, primarily driven by the development and usage of new chemotherapeutic and immunotherapeutic agents and by the continuous increase in illicit drug abuse with contaminants. Neuroimaging in the form of MR imaging forms the cornerstone in the diagnosis of these entities, many of which are reversible and amenable to rapid correction. Chronic white matter changes are also seen with these toxins with gradually progressive clinicoradiological findings.
Assuntos
Leucoencefalopatias , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , NeuroimagemRESUMO
BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.
Assuntos
Leucoencefalopatias , Neoplasias , Síndromes Neurotóxicas , Humanos , Metotrexato/efeitos adversos , Estudos Retrospectivos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/patologiaAssuntos
Infliximab , Leucoencefalopatias , Neurite Óptica , Psoríase , Humanos , Masculino , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Infliximab/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico , Imageamento por Ressonância Magnética , Neurite Óptica/induzido quimicamente , Neurite Óptica/diagnóstico , Neurite Óptica/tratamento farmacológico , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , AdultoRESUMO
Central nervous system relapse prevention through intrathecal and intravenous methotrexate (MTX) administration is a crucial aspect of treatment in acute lymphoblastic leukemia. However, neurotoxicity-induced leukoencephalopathy is a significant concern. Neurological symptoms associated with MTX can appear as subacute leukoencephalopathies, which manifest as a stroke-like syndrome, consisting of paralysis, seizures, consciousness disturbances, and dysarthria. These symptoms persist for a few days, presenting with fluctuating severity and location. Characteristic findings in bilateral white matter are observed on diffusion-weighted magnetic resonance imaging. Symptoms typically improve naturally within a few days although supportive therapy remains the primary treatment. The efficacy of drug administration is not established. Therapy should be continued if clinical improvements are achieved following the initial neurological event regarding MTX re-administrations after symptom improvement. However, careful consideration is required for each patient because symptoms may reoccur or persist and long-term effects remained unclear.
Assuntos
Leucoencefalopatias , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucoencefalopatias/induzido quimicamente , Sistema Nervoso Central , Metotrexato , Administração IntravenosaRESUMO
Toxic leukoencephalopathy (TLE) is a rare pathology caused by various substances including opioids (notably heroin), immunosuppressants, chemotherapy agents, cocaine, alcohol and carbon monoxide. However, although heroin is metabolised by the body into morphine, there is a striking paucity in cases of primary oral morphine-induced TLE, especially in the adult population. We present the case of a man in his 40s admitted to hospital in respiratory depression with a Glasgow Coma Scale (GCS) score of 6 after taking an overdose of oral morphine sulphate. Following a complete recovery to baseline, he was then readmitted with an acute deterioration in his neurobehavioural condition. Initial investigations returned normal but MRI showed changes characteristic for TLE.In cases of opioid toxicity such as ours, TLE is difficult to differentiate from delayed post-hypoxic leukoencephalopathy, due to their similar clinical presentation, disease progression and radiological manifestation. We explore how clinicians can approach this diagnostic uncertainty.
Assuntos
Overdose de Drogas , Leucoencefalopatias , Masculino , Adulto , Humanos , Morfina/efeitos adversos , Heroína/efeitos adversos , Sulfatos/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Hipóxia/induzido quimicamente , Hipóxia/complicações , Overdose de Drogas/complicações , Analgésicos Opioides/efeitos adversosRESUMO
Methotrexate-induced neurotoxicity is a well-defined side-effect of high-dose and intrathecal methotrexate with characteristic clinico-radiological findings and transient nature. Our experience in managing this entity in children with acute lymphoblastic leukemia(ALL) is reported here. All children with de novo ALLregistered from January 2016 through December 2021 who developed methotrexate-induced neurotoxicity were included. Of children with ALL treated during the study period, thirty-three experienced methotrexate induced neurotoxicity with an incidence of 1.25%. Stroke-like symptoms(36.36%; 12/33) were the most common clinical manifestation followed by seizures(30.3%, 10/33). Twenty-three patients had radiological features consistent with methotrexate-induced leukoencephalopathy. With emerging evidence, thirty-one patients were re-challenged with methotrexate (IV/IT), of whom 4 patients had recurrence of symptoms. No long-term neurological sequalae were noted in our cohort, despite rechallenging. Therefore in our study, methotrexate induced neurotoxicity is a self-limiting toxicity and methotrexate can be re-challenged safely without compromising theintensity of CNS-directed therapy.
Assuntos
Leucoencefalopatias , Metotrexato , Síndromes Neurotóxicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Seguimentos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Metotrexato/efeitos adversos , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , RadiografiaRESUMO
INTRODUCTION: Organotin compounds are widely used in the plastic industry. We demonstrate the role of brain magnetic resonance imaging in a patient with leukoencephalopathy. CLINICAL COURSE: A 38-year-old man who worked with trimethyltin and dimethyltin in a polyvinyl chloride factory reported a two-week progression of impaired memory, loss of balance, apathy, tinnitus, scaly darkened skin, and psychomotor slowing that rendered him unable to continue his daily activities. Magnetic resonance imaging revealed diffuse bilateral white matter lesions. Tin concentrations in both blood (344 µ/L) and urine (3,050 µg/L) were elevated. Removal from exposure and treatment with succimer were associated with clinical, laboratory, and imaging improvements. DISCUSSION: The high lipid content of myelin is a likely target for lipid-soluble alkyl tin compounds. CONCLUSIONS: This patient demonstrates the clinical and magnetic resonance imaging findings of organotin toxicity. The contribution of chelation to the patient's recovery is uncertain and warrants further study.
Assuntos
Leucoencefalopatias , Compostos Orgânicos de Estanho , Humanos , Masculino , Adulto , Compostos Orgânicos de Estanho/toxicidade , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , LipídeosRESUMO
INTRODUCTION: Acute toxic leukoencephalopathy (ATL) is a rare complication of cancer treatment, with symptoms varying from mild cognitive impairment to coma. Recognition and management of ATL are important because in most cases, the cessation of the responsible agent is essential. CASE REPORT: We report a case of a 57-year-old male with relapsed right colon cancer who had multiple steps of chemotherapy, admitted to the emergency department (ED) with confusion and inability to talk, 4 days after FOLFIRI and bevacizumab treatment. To exclude cerebrovascular events cranial computed tomography and diffusion-weighted magnetic resonance imaging were evaluated. There was bilateral and symmetric diffusion restriction on white matter, which was consistent with ATL. MANAGEMENT AND OUTCOME: Supportive treatment such as optimization of blood pressure and metabolic control was applied since there is no specific treatment for ATL other than cessation of the responsible agents. 12 days after the admission to the ED his neurologic symptoms were normalized and there was no diffusion restriction on control imaging. DISCUSSION: ATL is a rare complication of cancer treatment and responsible agents are increasing in number due to the development of cancer treatment. ATL is associated with drugs that are used frequently such as 5-fluorouracil. ATL is mostly reversible, but the progression of neurologic symptoms was also reported. The diagnosis and cessation of the responsible agent are important in management.
Assuntos
Leucoencefalopatias , Masculino , Humanos , Pessoa de Meia-Idade , Bevacizumab/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Fluoruracila/efeitos adversos , Imagem de Difusão por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Fluorouracil-induced leukoencephalopathy is a rare complication and has been reported to present as confusion, oculomotor abnormality, ataxia, and parkinsonism; however, there is no previous report of a presentation mimicking neuroleptic malignant syndrome. Acute cerebellar syndrome may occur, which can be explained by the extremely high accumulation of the drug in the cerebellum. However, presentation mimicking neuroleptic malignant syndrome similar to our case has never been reported. CASE PRESENTATION: Here, we describe a 68-year-old Thai male presenting with advanced-stage cecal adenocarcinoma, as well as symptoms and signs indicative of neuroleptic malignant syndrome. He received two doses of intravenous metoclopramide 10 mg 6 hours before his symptoms occurred. Magnetic resonance imaging scan revealed signal hyperintensity within the bilateral white matter. Further evaluation showed that his thiamine level was extremely low. Thus, he was diagnosed with fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome. The concomitant fluorouracil-induced thiamine deficiency eventually leads to rapid depletion of thiamine and was considered a risk factor for fluorouracil-induced leukoencephalopathy. CONCLUSION: Fluorouracil-induced leukoencephalopathy is believed to be caused by insult causing mitochondrial dysfunction. However, the exact mechanism remains unknown, but our finding suggests that thiamine deficiency plays a crucial role in fluorouracil-induced leukoencephalopathy. Diagnosis is usually delayed due to a lack of clinical suspicion and results in significant morbidity requiring unnecessary investigations.
Assuntos
Neoplasias do Colo , Leucoencefalopatias , Síndrome Maligna Neuroléptica , Deficiência de Tiamina , Humanos , Masculino , Idoso , Síndrome Maligna Neuroléptica/diagnóstico , Síndrome Maligna Neuroléptica/etiologia , Fluoruracila/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagemRESUMO
INTRODUCTION: Capecitabine is a pre-metabolite of 5-fluorouracil and is used as a chemotherapeutic agent. Among the common side effects of capecitabine, there are gastrointestinal side effects including nausea, vomiting, and diarrhea, and dermatological side effects including hand-foot syndrome and skin pigmentation change. However, neurological side effects of capecitabine are very rare. We describe herein a patient who developed neurological side effects in the form of agraphia and dysarthria on the 7th day of capecitabine treatment. CASE REPORT: A 34-year-old male patient, who was being followed up with the diagnosis of colon cancer, presented with speech and writing disorder that developed while under capecitabine treatment. Dysarthria and agraphia were detected in his neurological examination. Diffusion-weighted magnetic resonance imaging (MRI) revealed acute diffusion restriction in the splenium of the corpus callosum and at the level of the bilateral centrum semiovale. Brain MRI revealed symmetrical T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) signal increases at the right temporoparietal medial, corpus callosum level, and bilateral white matter level. MANAGEMENT & OUTCOME: The capecitabine treatment was terminated, and methylprednisolone treatment was administered and plasmapheresis procedure was carried out. Subsequently, significant improvement was observed in the clinical findings and neuroimaging. DISCUSSION: Capecitabine is used as an oral agent; thus, it provides ease of use. Neurological side effects associated with the use of capecitabine reportedly occur very rarely. The findings of this case demonstrated that leukoencephalopathy can be seen during the use of capecitabine, imaging results are very important in the diagnosis of leukoencephalopathy, and improvement can be achieved with the termination of the capecitabine treatment.
Assuntos
Agrafia , Leucoencefalopatias , Masculino , Humanos , Adulto , Capecitabina/efeitos adversos , Agrafia/tratamento farmacológico , Disartria/induzido quimicamente , Fluoruracila/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/tratamento farmacológicoRESUMO
This is the case of a 26-year-old male who developed Anton Babinski syndrome (ABS), quadriplegia, and delayed post-hypoxic leukoencephalopathy (DPHL) after an opioid overdose. He exhibited cortical blindness, visual anosognosia, and confabulation upon awakening. Several days later, he experienced acute psychosis and agitation. T2-FSE MRI revealed extensive supratentorial leukoencephalopathy involving both cerebral hemispheres, extending to the posterior corpus callosum due to cerebral anoxia. This case report will discuss different types of encephalopathy from opioid abuse, ABS, visual anosognosia, and confabulation's pathogenic mechanisms. It underscores the necessity of researching substance-induced neuropsychiatric disorders and their pathogenic mechanisms for effective treatments.
Assuntos
Leucoencefalopatias , Quadriplegia , Adulto , Humanos , Masculino , Analgésicos Opioides/intoxicação , Hipóxia Encefálica/complicações , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/etiologia , Imageamento por Ressonância Magnética , Overdose de Opiáceos/complicações , Quadriplegia/etiologiaAssuntos
Leucoencefalopatias , Síndrome da Leucoencefalopatia Posterior , Humanos , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
AIM: To study the clinical and radiologic features of patients with capecitabine neurotoxicity. METHODS: We performed a retrospective analysis and systematic review on the clinical and radiologic characteristics of all patients with capecitabine neurotoxicity reported in literature between 2003 and 2020. RESULTS: 24 cases including our patient were retrospectively analysed, with their clinical and radiologic features summarized. Their median age was 59 years old (ranges from 31 to 82 years old). Encephalopathy was the predominant clinical symptom affecting more than half (15/24, 63%) of the patients. This was followed by cerebellar ataxia (10/24, 42%). Amongst the patients who had magnetic resonance imaging(MRI) brain imaging performed, majority of them (18/23, 78%) had acute radiologic abnormalities. Leukoencephalopathy was the commonest radiologic abnormality seen in more than half of the patients (15/23,65%). Despite the preponderance of female patients in our study, there were no significant statistical differences in the clinical and radiologic features. Short term prognosis was excellent with complete resolution of neurologic symptoms observed in nearly all of the patients (22/23, 96%). CONCLUSION: Capecitabine-related neurotoxicity is an uncommon cause of toxic encephalopathy, with a predilection for females. Clinical features are non-specific, with encephalopathy being the commonest. Prognosis remains good with timely recognition, and cessation of capecitabine. Future research looking into other pathogenic pharmacogenetic processes should be conducted for further elucidation of these associations.
Assuntos
Leucoencefalopatias , Síndromes Neurotóxicas , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/efeitos adversos , Estudos Retrospectivos , Antimetabólitos Antineoplásicos/efeitos adversos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/complicações , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: Abuse of opiates, cocaine, and lipophilic inhalants (e.g., toluene) can damage brain myelin and cause acute toxic leukoencephalopathy (TL), but little is known about recovery or prognosis in this condition. In light of the ongoing opiate epidemic in the United States, it is important to understand the natural history of patients who have acute neurological complications from illicit drug exposure. Our aim was to conduct a scoping review of the literature regarding prognosis in described cases of substance abuse-related TL. METHODS: A strategic search of PubMed, Ovid, Cumulative Index to Nursing, and Allied Health Literature (CINAHL) databases yielded adult cases of acute TL from opiates, cocaine, or inhalants. Cases and case series were eligible for inclusion if they described acute leukoencephalopathy with a clear temporal association with opiate, cocaine, or inhalant abuse. Inclusion was contingent on availability of clinical descriptions until death or ≥ 4 weeks follow-up with neuroimaging consistent with TL. RESULTS: Among 52 cases from 14 articles, 21 (40.4%) individuals died with mean time to death of 28.2 days; with mean follow-up of 12.8 months, 10 (19.2%) survived with no recovery, 17 (32.7%) had partial recovery, and 4 (7.7%) individuals had full recovery. CONCLUSION: Substance abuse-related acute TL often has a poor prognosis, but partial or even full recovery is possible in a subgroup of individuals over months to years.