To the Editor:
We thank Robert S. Hoffman and Alexandre Larocque for sharing their interesting case and helping us to increase the awareness of complications from levamisole-containing cocaine. While the clinical diagnosis of multifocal inflammatory leukoencephalopathy (MIL) can be established with reasonable certainty, defining its etiology is clearly more problematic. As highlighted here, the differential diagnosis is broad, many patients have complex comorbidities (such as HIV) and the definitive diagnosis requires brain biopsy, which is often highly undesirable. While we accept that this case might be consistent with levamisole-induced MIL, we caution readers about assigning causation, given that there are distinct differences between what is known about levamisole-induced MIL and the present case.
To begin with, we are told that the patient is an active cocaine user, yet, because of timing, levamisole cannot be confirmed in a biological specimen. While we accept that between 70 and 90% of cocaine supply in the United States contains levamisole,Citation1,Citation2 we debate the statistical argument used to suggest that this patient was definitively exposed to levamisole. The authors advance an oversimplified model that uses a random distribution of levamisole such that as the number of suppliers increases the likelihood of exposure increases, which is distinct from the distribution pattern of cocaine, which is more regional.
Furthermore, and more importantly, two clinical features of this case are atypical for levamisole-induced MIL. Since MIL is, by definition, an inflammatory process, most patients with levamisole-induced MIL have white cells in their CSF.Citation3–5 Yet the lumbar puncture was acellular in this patient. Additionally, whereas the natural history of most reported cases of levamisole-induced MIL demonstrates improvement or recovery over short periods of time, once exposure is terminated,Citation3–6 this patient had no improvement.
In summary, we have a patient with severe AIDS who is at risk for leukoencephalopathy from varied etiologies who happens to be a cocaine user. There is no proof of exposure to levamisole, no brain biopsy, and both the laboratory evaluation and clinical course of patient are atypical for levamisole-induced MIL. Thus, while we appreciate the addition of the case and the discussion and awareness that follow, we are concerned that the information provided is too limited to even suggest association, much less causation.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
- Centers for Disease Control and Prevention (CDC). Agranulocytosis associated with cocaine use – four States, March 2008–November 2009. MMWR Morb Mortal Weekly Rep 2009; 58:1381–1385.
- Lynch KL, Dominy SS, Graf J, Kral AH. Detection of levamisole exposure in cocaine users by liquid chromatography-tandem mass spectrometry. J Anal Toxicol 2011; 35:176–178.
- Xu N, Zhou W, Li S, Zhou G, Zhang N, Liang J. Clinical and MRI characteristics of levamisole-induced leukoencephalopathy in 16 patients. J Neuroimaging 2009; 19:326–331.
- Wu VC, Huang JW, Lien HC, Hsieh ST, Liu HM, Yang CC, . Levamisole-induced multifocal inflammatory leukoencephalopathy: clinical characteristics, outcome, and impact of treatment in 31 patients. Medicine 2006; 85:203–213.
- Kimmel DW, Wijdicks EF, Rodriguez M. Multifocal inflammatory leukoencephalopathy associated with levamisole therapy. Neurology 1995; 45:374–376.
- Cheng YC, Po HL. Leukoencephalopathy after levamisole for the treatment of verrucae. Acta Neurol Taiwan 2011; 20:262–6.