Multifocal inflammatory leukoencephalopathy associated with cocaine abuse: Is levamisole responsible?

To the Editor:

Larocque and Hoffman’s recent review of levamisole, which has emerged as a ubiquitous adulterant of cocaine, noted that this immune-modulatory drug is clearly linked to agranulocytosis and cutaneous vasculitis, which typically occur independently of each other, but also cautioned that multifocal inflammatory leukoencephalopathy (MIL), a well-established stand-alone complication of therapeutic levamisole administration, also should be suspected as a cocaine-levamisole adverse effect.¹ In sounding this appropriate warning, the authors allow that “No formal case of leukoencephalopathy in the setting of cocaine use has been reported so far.” We wish to report such a case, pointing out the limitations inherent in assessing this association.

Case report

A 29-year-old female with AIDS (CD4 count 5) not on current anti-retroviral therapy presented with fever, malaise, and focal spinal pain, for which morphine had been administered at another facility one day previously. She was an active crack cocaine abuser reporting months of multi-time daily abuse and obtaining her supply from at least three separate dealers. She denied other inhalant or IV drug abuse. She appeared chronically ill, with multiple excoriated, hyper-pigmented skin lesions consistent with delusional parasitosis and focal spinal tenderness (neck to upper back) and left shoulder pain. The neurological examination was unremarkable. A lumbar puncture was acellular, without elevated protein, and showed five well-defined gamma restriction bands. The peripheral polymorphonuclear leukocyte concentration was 3.8 × 10³ per microliter. A urine drug screen on admission was cocaine and opiate positive. Magnetic resonance imaging (MRI) guided needle aspiration established a MRSA infection of the perispinal musculature. A dermatological consultation found no evidence of cutaneous vasculitis. A brain MRI demonstrated lesions consistent with MIL (Fig. 1). Serum from hospital day two was negative for both cocaine and levamisole by liquid chromatography-tandem mass spectrometry. Antibiotic treatment achieved clinical-radiographic resolution of the MRSA infection. Anti-retroviral therapy was initiated. Repeat brain MRI at four weeks demonstrated no significant worsening or improvement in the white matter abnormalities.

Fig. 1. Axial T2 sequences of the brain demonstrate extensive multiple bilateral hyper-intense lesions within the (A) left basal ganglia (arrow) and splenium of the corpus callosum (arrowhead); (B) the bilateral internal capsules (arrows) and (C) within the bihemispheric white matter diffusely and more focally within the right corona radiate (arrow). The lesions are compatible with a demyelinating process. Lymphoma and infection are considered less likely given the lack of enhancement with gadolinium administration (See colour version of this figure in the online version www.informahealthcare/ctx).

Discussion

The possibility that levamisole contamination may be responsible for MIL in cocaine abuse has been raised previously, although without any details provided for the cases in question.^2,3 Two other recent case reports of cocaine-associated MIL did not raise the specter of levamisole adulteration.^4,5 In none of these cases was concomitant vasculitis or agranulocytosis reported. Our case had HIV, but was without progressive MIL. There was not, however, marked radiographic improvement after one month either. A pattern of rapid remission is frequent, although not universal, in medicinal levamisole-related MIL;⁶ remission has also been reported with cocaine abstinence.⁴ Unfortunately, urine contemporaneous to cocaine detection was no longer available for levamisole testing by the time MIL was documented. Because 88% of local samples positive for cocaine also test positive for levamisole⁷ and because the patient used three different suppliers, the probability of drugs from all sources being levamisole-free is negligible (0.12³ or 0.2%) and thus adulterant exposure is a near certainty in this case. From a public health perspective, it would be prudent to add MIL to the list of potential levamisole adulterant-associated cocaine abuse complications and to presume that this complication can be independent of agranulocytosis or vasculitis.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.