To underscore a distinctive case of CSF1R leukoencephalopathy in which the patient initially sought care through a TBI clinic due to concerns regarding post-TBI sequelae and a complex clinical phenotype mimicking primary progressive aphasia (PPA) with behavioral changes.

CSF1R leukoencephalopathy represents an infrequent, autosomal dominant genetic etiology of neurodegeneration characterized by behavioral symptoms with progressive cognitive decline frequently mimicking behavioral variant frontotemporal dementia (bvFTD) along with parkinsonian or ataxic motor manifestations. Language involvement is uncommon. It is associated with pathogenic mutations in the CSF1R gene, triggering the formation of axonal spheroids and glial pathology. Brain MRI often reveals white matter abnormalities, lateral ventricular enlargement, and thinning of the corpus callosum.

A 56-year-old female presented with a two-year history of worsening word-finding difficulties and language comprehension with behavioral changes. Clinical examination revealed language impairment and pseudobulbar affect, seemingly attributed to mild traumatic brain injury (TBI) from a recent accident several months prior. No motor deficits were appreciated. Despite speech therapy, her language capabilities worsened, and additional behavioral changes prompted further evaluation. Neuropsychological testing demonstrated severely low scores on tests of language, executive function, and memory with relatively preserved visuospatial function. Brain MRI showed extensive frontal atrophy and thinning of the genu of corpus callosum, suggesting a neurodegenerative process predating her TBI. Family history was notable for early-onset dementia (mother) with symptom onset in her late 50s. Genetic testing confirmed a likely pathogenic CSF1R variant. 

This case highlights CSF1R leukoencephalopathy presenting as language and behavioral changes without motor manifestations, masquerading as TBI sequelae. Timely recognition of the spectrum of CSF1R clinical phenotypes especially among patients with a family history of early-onset dementia is crucial for early diagnosis, symptom management, and genetic counseling, enhancing the patient's and their family's quality of life.