Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Delayed Radiographic Finding in a Case of Toxic Metabolic Leukoencephalopathy from Polysubstance Use: A Case Report

Rishit J. Patel, BS 1 ; Ameeta Karmarkar, MD 2 1 Edward Via College of Osteopathic Medicine-Carolinas, Spartanburg, SC 2 Spartanburg Medical Center, Spartanburg, SC

Abstract

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Clinical Presentation

o Drug-induced leukoencephalopathy is rare and heterogeneous in its clinical manifestations. This poses a prognostic challenge in patients who present with a history of polysubstance use and a morbid clinical presentation, but diminutive imaging findings which may be falsely reassuring in the acute setting. o It is crucial to perform a thorough neurologic evaluation to exclude mimics. No evidence-based disease modifying treatments are currently available for this condition. o The delayed appearance of radiographic abnormalities poses a significant diagnostic and prognostic challenge. It may be helpful in specific clinical scenarios to obtain serial neuroimaging and close neurologic follow-up to elucidate the full extent of injury. o 40-year-old woman with a history of polysubstance use (cocaine, methamphetamines, fentanyl) was found to be minimally responsive in an overheated car surrounded by drug paraphernalia o Vitals: Temp 105°F, BP 145/94, HR 121, RR 21 o Relevant Lab: BUN 47 mg/dL; Cr 3.26 mg/dL; CK 875 IU/L; ALT 42 IU/L;AST 48 UIU/L; UDS + amphetamine (last 3 tests were + for opiates); CSF: 0 WBC, glucose 58, protein 30, negative filmarray panel and cultures o EEG: disorganized diffuse lateralized periodic discharges (LPDs) o MRI: symmetric increase in DWI signal in the bilateral external capsule along the subcortical white matter of the right anterior cingulate gyrus without corresponding ADC correlate o Examination: frail, spontaneous eye opening, no volitional tracking, intact pupillary, cough and gag reflexes, non-verbal and unable to follow commands. Intermittent weak spontaneous movements; 2/5 withdrawal to noxious stimuli in B/L UE/LE; DTR 2+ o Discharged after 26-day hospitalization with a gastrostomy tube for nutritional support with 24-hour caregiver support o Small improvements noted by family including visual tracking, mild improvement in dysphagia but remained minimally verbal with spastic quadriplegia o Re-hospitalized 23 days after discharge with worsened encephalopathy, acute onset tremors, generalized stiffening, tachycardia, and fever after receiving a dose of venlafaxine and fluconazole, suspected serotonin syndrome o EEG: severe diffuse bilateral slowing o MRI: diffuse bilateral white matter T2/FLAIR hyperintensities bilaterally with bifrontal predominance, milder involvement of basal ganglia o Examination: lethargic with weak eye-opening to noxious stimulation, weak cough and gag reflexes and sluggish pupils. Quadriplegia with flexion contractures and hyperreflexia o Transitioned to comfort care and she died 3 days later in comfort care Conclusion

o Toxic leukoencephalopathy involves structural white matter injury triggered by a variety of endogenous and exogenous derangements, including drugs of abuse, alcohol, inhaled gases, industrial agents, neurotoxic medications, and uremia. o We present a case of a young woman with multifactorial toxic leukoencephalopathy whose MRI at acute presentation and a subsequent hospitalization 7 weeks after the initial insult showed marked evolution of the white matter injury. o This case demonstrates the delayed radiographic evolution of extensive structural damage secondary to toxic leukoencephalopathy attributed to polysubstance abuse. o Heterogeneity of clinical presentations and outcomes and the limited reliability of imaging findings during acute presentations can pose a prognostic challenge in this patient population. o Longitudinal follow-up with repeat neuroimaging and clinical examination can be more informative in assessing the degree of injury. o Leukoencephalopathy and neurologic symptoms associated with inhaled heroin abuse were initially described in 1982 o Pathogenesis of white matter injury is not completely understood. Hypotheses include: -Lipophilic toxin-induced injury secondary to heroin or contaminants -Hypoxic insult secondary to vasospasm or vasculitis triggered by an inflammatory response -Excitotoxic injury secondary to excessive release of glutamate in the synaptic cleft in receptor-rich regions such as the basal ganglia and thalami, cortical gray matter, periventricular white matter, and the corpus callosum o No definite correlation of the severity of damage with dose or duration of exposure o The neurobehavioral consequences of toxic leukoencephalopathy range from mild, transient cognitive dysfunction to stupor, coma, and death o Prognostication is challenging given the great diversity of clinical presentations and outcomes o Good functional outcomes have been reported but confounded by medical comorbidities, malnutrition and other psychosocial factors commonly associated with substance abuse Introduction

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Figure(s). (a) MRI brain on Day 2 of the first admission. Linear elevated DWI signal along the lateral aspect of the bilateral putamen in the region of external capsules (b) MRI brain on Day 2 of first admission. T2/FLAIR hyperintensity in the right anterior cingulate gyrus subcortical white matter (c) MRI brain on Day 1 of the second admission. Diffuse white matter T2 changes consistent with progressive toxic leukoencephalopathy

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References

1.Oliveira AMd, Paulino MV, Vieira APF, et al. Imaging Patterns of Toxic and Metabolic Brain Disorders. RadioGraphics. 2019;39(6):1672-1695. 2. Büttner A, Mall G, Penning R, Weis S. The neuropathology of heroin abuse. Forensic Sci Int. Sep 11 2000;113(1-3):435-42. 3. Filley CM, Kleinschmidt-DeMasters BK. Toxic Leukoencephalopathy. New England Journal of Medicine. 2001;345(6):425-432. 4. Macchi ZA, Carlisle TC, Filley CM. Prognosis in substance abuse-related acute toxic leukoencephalopathy: A scoping review. J Neurol Sci. Nov 15 2022;442:120420. 5. McKinney AM, Kieffer SA, Paylor RT, SantaCruz KS, Kendi A, Lucato L. Acute toxic leukoencephalopathy: potential for reversibility clinically and on MRI with diffusion-weighted and FLAIR imaging. AJR Am J Roentgenol. Jul 2009;193(1):192-206. 6. Shah NR, Tavana S, Opoku A, Martin D. Toxic and metabolic leukoencephalopathies in emergency department patients: a primer for the radiologist. Emerg Radiol. Jun 2022;29(3):545 555.

I would like to acknowledge and thank the patient’s family for letting us share her medical journey through this poster. This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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2024 Research Recognition Day