Frontotemporal dementia as a comorbidity to idiopathic normal pressure hydrocephalus (iNPH): a short review of literature and an unusual case

Abstract

Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present with similar symptoms. These include decline in executive functions, psychomotor slowness, and behavioural and personality changes. Ventricular enlargement is a key radiological finding in iNPH that may also be present in bvFTD caused by the C9ORF72 expansion mutation. Due to this, bvFTD has been hypothesized as a potential comorbidity to iNPH but bvFTD patients have never been identified in studies focusing in clinical comorbidities with iNPH. Here we describe a patient with the C9ORF72 expansion-associated bvFTD who also showed enlarged ventricles on brain imaging. The main clinical symptoms were severe gait disturbances and psychiatric problems with mild cognitive decline. Cerebrospinal fluid removal increased the patient's walking speed, so a ventriculoperitoneal shunt was placed. After insertion of the shunt, there was a significant improvement in walking speed as well as mild improvement in cognitive function but not in neuropsychiatric symptoms relating to bvFTD. Comorbid iNPH should be considered in bvFTD patients who have enlarged ventricles and severely impaired gait.

Keywords: C9ORF72 repeat expansion; CSF shunt; Dementia; Idiopathic normal pressure hydrocephalus; Neurodegeneration.

Fig. 1

a A brain CT scan that was performed because of an episode of syncope 5 years before the onset of symptoms shows no atrophy (Evans’ index 0.33), but some asymmetry of the occipital horns of the lateral ventricles is apparent. b The first T1weighed MRI, which was performed 1 year after the onset of symptoms, shows the development of frontal cortical atrophy and central atrophy (Evans’ index 0.42) c with some progression over the follow-up time of 1 year (Evans’ index 0.45). d The CT control scan that was performed 6 months after shunt placement shows stable ventricular size (Evans’ index 0.45). e The coronal slice shows hippocampal atrophy (Scheltens grade 2/4) but no disproportionate obliteration of the parasagittal sulci. f The FLAIR sequence shows only minor changes in the white matter. The parasagittal images show that frontal cortical atrophy is more prominent on the right (g) compared to the left side (h)

Fig. 2

a Hematoxylin and eosin staining of a 1.6 cm biopsy of the frontal cortex that contained both grey and white matter. b Abundant TDP-43 pathology (arrows) was present, mostly in the form of thin neurites and varying shapes of inclusions, in both grey and white matter. Scale bar 100 µm. c There was moderate p62 (arrows) staining, mostly in thin neurites. Scale bar 100 µm