Clinical and pathological heterogeneity of neuronal intermediate filament inclusion disease

To report new cases of neuronal intermediate filament inclusion disease (NIFID).

Case report.

Pathologically proved NIFID was found in 2 patients from the Universitat de Barcelona-Hospital Clínic Brain Bank. The findings of a neuropathological examination in both patients revealed intracellular inclusions that were detected with hematoxylin-eosin and stained positive for antineurofilament and alpha-internexin antibodies, variably for ubiquitin, and negatively for tau, alpha-synuclein, and TAR-DNA binding protein 43.

Medical records were retrospectively reviewed.

The first patient developed progressive behavioral changes characterized by apathy and indifference at the age of 37 years, and frontotemporal dementia was diagnosed. The second patient developed progressive tremor and mild speech disturbances at the age of 70 years. Her neurological examination results showed mild dysarthria, hypomimia, a mild rigid-akinetic left-predominant parkinsonism, and bilateral rest and postural tremor. The clinical impression was atypical parkinsonism. No response was obtained with levodopa, and the disease progressed rapidly, with falls and frontal-subcortical cognitive impairment.

Late-onset presentation may be the clinical debut of NIFID. These 2 cases confirm the clinical and pathological heterogeneity of NIFID and suggest its inclusion in the differential diagnosis of several neurodegenerative disorders, including frontotemporal dementia and atypical parkinsonism.