Ketamine as an Adjunct for Treatment of Methotrexate-induced Neurotoxicity.

Methotrexate (MTX) is used in the treatment of several childhood cancers and is a main component of the treatment regimen for osteosarcoma. MTX has been linked with side effects of varying severity; headaches, nausea, emesis, lethargy, blurred vision, aphasia, hemiparesis, paresis, convulsions, leukoencephalopathy, and arachnoiditis are symptoms of MTX toxicity. MTX-induced neurotoxicity can occur in up to 15% of patients receiving high-dose MTX. The effects may be transient but can have life-threatening implications, sometimes requiring intubation for respiratory support and airway protection. Elevated homocysteine levels in the cerebrospinal fluid are documented in cases of MTX-induced neurotoxicity; dextromethorphan is used as an initial treatment for MTX-induced neurotoxicity as it works as a noncompetitive antagonist for the N-methyl D-aspartate receptors and suppresses homocysteine activity. In severe cases requiring intubation, medications for sedation are utilized. Ketamine is also an N-methyl D-aspartate receptor antagonist, and as such, may be considered as an optimal treatment choice when sedation is required. We describe the use of ketamine in a pediatric patient with MTX-induced neurotoxicity. The use of ketamine in the treatment of MTX-induced neurotoxicity has not been described in the literature.

SARS-CoV-2 Encephalitis in a 20-year old Healthy Female.

We report a 20-year-old female with SARS-CoV-2 encephalitis who presented with 4 days of upper respiratory symptoms, fevers and sudden acute altered mental status. An extensive work up led to the most likely cause for the neurologic decompensation to be viewed as SARS-CoV-2 symptomology.

Newborn brain infarction: clinical aspects and magnetic resonance imaging.

OBJECTIVE: We describe the clinical and imaging studies of 11 full-term babies with neonatal stroke. We classify the neonatal non-hemorrhagic strokes as thrombotic, embolic, or global vascular insufficiency and determine if this classification is improved by adding magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) to conventional magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). METHODS: Clinically, eight of the 11 babies presented with seizures, one with apnea, and two with lethargy. Conventional MRI and DWI were used to classify each infarct as being either borderzone or vascular distribution. The location of infarction revealed the presumed vascular pathophysiology. RESULTS: Infants were classified as having either embolic (bilateral middle cerebral artery,n=1), global ischemic (bilateral borderzone, n=2), or thrombotic infarction (unilateral middle cerebral artery, n=7; bilateral posterior cerebral arteries, n=1). DWI and MRS detected a small infarct better than conventional MRI in one patient. MRA showed abnormal intracranial arteries in three, all of who were in the thrombotic group. Even though MRS was more sensitive than conventional MRI in detecting ischemia/infarction in one patient, in another there was no detectable lactate in the stroke region found on conventional MRI. Clinical presentation was similar in global ischemia and focal infarctions, but newborn stroke was more likely to present with lateralizing focal motor seizures. Seizures were the most common presenting sign, with a paucity of other focal neurological deficits. CONCLUSION: MRI is the best approach to determine stroke pathophysiology. Brain infarction frequently presents with seizures. We speculate that the location and distribution of infarction might determine stroke timing, pathophysiology and outcome. Ongoing clinical studies will likely clarify this speculation.

Neurologic complications of sickle cell disease.

Sickle cell disease (SCD) is a group of genetic blood disorders that vary in severity, but the most severe forms, primarily homozygous sickle cell anemia, are associated with neurologic complications. Over the last 90 years it has become established that some patients will develop severe arterial disease of the intracranial brain arteries and suffer brain infarction. Smaller infarctions and brain atrophy may also be seen and over time there appear to be negative cognitive effects in some patients, with or without abnormal brain imaging. Focal mononeuropathies and pneumococcal meningitis are also more common in these patients. Brain infarction in children can largely be prevented screening children beginning at age 2 years and instituting regular blood transfusion when the Doppler indicates high stroke risk (>200cm/sec). Iron overload and the uncertain duration of transfusion are disadvantages but overall this approach, tested in a randomized clinical trial, reduced first stroke by over 90%. Secondary stroke prevention has not been subjected to a randomized controlled trial except for one recently stopped comparison of regular transfusions compared to hydroxuyrea (results favored transfusion). The usual stroke prevention agents (such as aspirin or warfarin) have not been rigorously tested. Magnetic resonance imaging and positron emission tomography give evidence of subtle and sometimes overt brain injury due to stroke in many adults, but a preventive strategy for adults with SCD has not been developed. Bone marrow transplantation is the only cure, but some non-neurologic symptoms can be controlled in adults with hydroxuyrea.