Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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October 27, 2022
Levamisole Leukoencephalopathy
•Background:
- Levamisole is an adulterant that has been reported in 69% of cocaine entering the United States (Drug Enforcement Agency), and is also used for adjuvant chemotherapy or recurrent aphthous ulcer treatment.
- Although the mechanism is unclear, it is hypothesized that levamisole may activate macrophages and lymphocytes, triggering a delayed hypersensitivity reaction that causes inflammation and demyelination.
•Clinical Presentation:
- Variable, but may include confusion, aphasia/dysphasia, gait ataxia, hemiparesis, cognitive impairment, diplopia, facial palsy, incontinence, or parasthesia.
- In this case, the patient presented with levamisole-induced leukoencephalopathy and cutaneous vasculopathy, along with a neuroleptic malignant syndrome-type appearance from cocaine use.
•Key Diagnostic Features:
- Labs: Urine toxicology, CSF studies demonstrating lymphocytic pleocytosis +/- red blood cells or oligoclonal bands
- Imaging: MRI with predominantly T2/FLAIR hyperintense, ovoid white matter lesions, often supratentorial in the periventricular or subcortical areas, along with corresponding T1 hypointensities, +/- restricted diffusion on DWI and ring enhancement. CT may initially be normal, but over time progressive hypodense lesions can be seen.
- Brain biopsy: Demyelination with infiltration of macrophages and perivascular lymphocytes
•Differential Diagnosis:
- Multiple sclerosis: Periventricular and subcortical white matter lesions in perivenular distribution, with active lesions demonstrating a “leading edge” of incomplete peripheral enhancement and restricted diffusion. Optic nerve involvement is common.
- Posterior reversible encephalopathy syndrome (PRES): Patchy subcortical white matter lesions commonly involve parietal and occipital lobes. Diffusion restriction on DWI is rare.
- Acute disseminated encephalomyelitis: Postinfectious clinical course with self-resolving lesions. Usually deep and subcortical white matter is involved, while periventricular lesions are less common.
- Progressive multifocal leukoencephalopathy: Seen in immunocompromised patients with JC virus reactivation. Patchy, asymmetric T2 hyperintense lesions typically in the parieto-occipital white matter with prominent subcortical U-fiber involvement. Usually non-enhancing, +/- surrounding punctate lesions (“Milky Way sign”) and corpus callosum involvement. Little to no mass effect.
- CNS lymphoma: Hyperdense on CT with solid enhancement on MRI and restricted diffusion.
- Glioblastoma: Irregular mass lesion with vasogenic edema, and enhancement and restricted diffusion of solid component. Necrosis and hemorrhage are common.
•Treatment:
- Currently no definitive treatment.
- Discontinuation of levamisole-containing cocaine and supportive care including steroids, plasmapheresis, and/or IVIG have been shown to improve clinical courses in case reports.
Suggested Reading
- Liu HM, Hsieh WJ, Yang CC, et al. Leukoencephalopathy induced by levamisole alone for the treatment of recurrent aphthous ulcers. Neurology 2006;67:1065–67
- Vosoughi R, Schmidt BJ. Multifocal leukoencephalopathy in cocaine users: a report of two cases and review of the literature. BMC Neurology 2015;15:1–6
- Wu VC, Huang JW, Lien HC, et al. Levamisole-induced multifocal inflammatory leukoencephalopathy: clinical characteristics, outcome, and impact of treatment in 31 patients. Medicine 2006;85:203–13
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