Selected entities often mistaken for RIS
| Entity | Distinguishing Clinical Features | Distinguishing Imaging Features | Important Keys to Diagnosis |
|---|---|---|---|
| Toxins/drug-related | Altered mental status changes during intoxication, history of substance abuse | Deep gray matter frequently involved, symmetric lesions | Urine and serum toxicology tests |
| Age-related leukoaraiosis | Older individual, cardiovascular risk factors | Small (<3 mm), nonenhancing lesions in periventricular and deep white matter, coexistent striatocapsular lacunar disease, absence of callososeptal lesions/Dawson fingers–type lesions | Lacunar disease and atypical white matter lesions for RIS in an older individual |
| Migraines | Headache or aura predominates | Predominantly subcortical white matter lesions that are small (<3 mm) and do not enhance, few periventricular lesions | Headache history and lack of typical imaging features consistent with RIS |
| Vasculitis | Episodic neurologic symptoms with superimposed strokes | Gray and white matter lesions coexist, may have enhancing vessel wall and/or leptomeningeal enhancement, MRA with stenoses | Systemic symptoms present, elevated erythrocyte sedimentation rate and/or C-reactive protein level, extra-/intracranial vessels abnormal, brain biopsy |
| CADASIL | Strokelike episodes, family history of similar clinical syndrome | White matter disease favoring anterior temporal tip subcortical regions, external capsule, presence of lacunar infarcts | Genetic testing diagnostic |
| Collagen vascular diseases | Clinical history of arthritis, long-standing chronic disease, episodic | Gray and white matter lesions ± vasculitis, occasional encephalitis | Clinical symptoms of a systemic disorder and presence of serologic autoantibodies/inflammatory markers |
| ADEM | Encephalitis, seizures, children > adults, history of viral/vaccine prodrome | Gray matter disease predominates, more diffuse enhancement, may have positive findings on DWI | History of prodromal virus infection or vaccination, encephalopathic |
| Posttraumatic | History of ≥1 traumatic, sports-related event | Favors gray-white matter junction, hemorrhagic products present, classic tears in splenium-brain stem deep gray matter | Hemorrhage and stereotypical locations of disease at shearing sites |
Note:—ADEM indicates acute disseminated encephalomyelitis.