Multiple Sclerosis (MS) is an inflammatory demyelinating disease characterized by progressive motor deficits. Behavioral problems have previously been linked to the use of illicit drugs such as cocaine and amphetamine. We present 4 patients with frequent abuse of illicit sympathomimetics who presented with symptomatic White Matter Lesions (WML). Three patients had positive Oligoclonal Bands (OCB), one patient without OCB revealed marked pleocytosis. In this case-series we present clinical and radiological features and discuss possible mechanisms underlying substance abuse in patients with demyelinating lesions. Previous case reports in illicit sympathomimetic substance abusers highlight leukoencephalopathy rather than focally demyelinating WML. We hypothesize a two hit model with drug abuse exacerbating an unknown underlying diagnosis of MS.