AUTHOR=Hoffmann Michael , Rossi Fabian , Benes Lima Lourdes , King Christian 

TITLE=Frontotemporal disorders: the expansive panoply of syndromes and spectrum of etiologies

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1305071

DOI=10.3389/fneur.2023.1305071

ISSN=1664-2295

ABSTRACT=Frontotemporal lobe disorders (FTD) are amongst the most common brain neurodegenerative disorders. Their relatively covert, frequently subtle presentations and diverse etiologies, pose major challenges in diagnosis and treatments. Recent studies have yielded insights that the etiology in the majority are due to environmental and sporadic causes, rather than genetic in origin. The design is a retrospective, observational registry, case series with the collection of epidemiological, clinical, cognitive, laboratory and radiological data on people with cognitive and behavioral disorders. Inclusion criteria for entry were veterans evaluated exclusively at Orlando VA Medical Center, neurology section, receiving a diagnosis of FTD by standard criteria, during the observation period dated from July 2016 to March 2021. Frontotemporal disorders (FTD) were delineated into five clinical 5 subtypes. Demographic, cardiovascular risk factors, cognitive, behavioral neurological, neuroimaging data and presumed etiological categories, were collected for those with a diagnosis of frontotemporal disorder.Of the 200 patients with FTD, further cognitive, behavioral neurological evaluation with standardized, metric testing was possible in 105 patients. Analysis of the etiological groups revealed significantly different younger age of the traumatic brain injury (TBI) and Gulf War Illness (GWI) veterans who also had higher Montreal Cognitive Assessment (MOCA) scores. The TBI group also had significantly more abnormalities of hypometabolism, as noted on the PET brain scans. Behavioral neurological testing was notable for the findings that once a frontotemporal disorder had been diagnosed, the four different etiological groups consistently had abnormal FRSBE scores for the 3 principal frontal presentations of i) abulia/apathy, ii) disinhibition and iii) executive dysfunction, as well as abnormal Frontal Behavioral Inventory (FBI), scores with no significant difference amongst the etiological groups. The most common sub-syndromes associated with frontotemporal syndromes were the Geschwind-Gastaut syndrome (GGS), Klüver-Bucy syndrome (KBS), involuntary emotional expression disorder (IEED), cerebellar cognitive affective syndrome (CCA), traumatic encephalopathy syndrome (TES) and prosopagnosia. Comparisons with the three principal frontal lobe syndrome clusters (abulia, disinhibition, executive dysfunction) revealed a significant association with abnormal disinhibition FRSBE T-scores with the GGS. The less common subsyndromes in particular, were notable, as they constituted the initial overriding, presenting symptoms and syndromes characterized into 16 separate conditions.