ORLANDO, FL — Frontotemporal lobe disorders (FTD), which affect personality, behavior and language, are among the most common brain neurodegenerative disorders. A new study found that veterans with traumatic brain injury (TBI) and Gulf War Illness (GWI) present very differently with FTD.
“Their relatively covert, frequently subtle presentations and diverse etiologies, pose major challenges in diagnosis and treatments,” wrote researchers from the University of Central Florida and the Orlando, FL, VA Healthcare System. “Recent studies have yielded insights that the etiology in the majority are due to environmental and sporadic causes, rather than genetic in origin.”
With results published in Frontiers in Neurology, the study sought to retrospectively examine the cognitive and behavioral impairments in the veteran population. The goal was to identify the range of differing syndrome presentations and etiological subcategories, with a primary focus on frontotemporal lobe disorders.1
The retrospective, observational registry involved a case series with the collection of epidemiological, clinical, cognitive, laboratory and radiological data on patients with cognitive and behavioral disorders. Included were veterans evaluated exclusively at the Orlando VA Healthcare System, neurology section, who received a diagnosis of FTD by standard criteria, during the observation period of July 2016 to March 2021.
Frontotemporal disorders (FTD) were delineated into five clinical subtypes, and demographic, cardiovascular risk factors, cognitive, behavioral neurological, neuroimaging data and presumed etiological categories were collected for those with a diagnosis of the condition.
Of the 200 patients with FTD, further cognitive and 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 researchers wrote. “The TBI group also had significantly more abnormalities of hypometabolism, noted on the PET brain scans.”
They added that 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 among the etiological groups.”
The most common sub-syndromes associated with frontotemporal syndromes were found to be:
- Geschwind-Gastaut syndrome (GGS),
- Klüver-Bucy syndrome (KBS),
- Involuntary emotional expression disorder (IEED),
- Cerebellar cognitive affective syndrome (CCA),
- Traumatic encephalopathy syndrome (TES) and
- Prosopagnosia.
The study advised that 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 regression analysis supported the potential contribution of disinhibition behavior that related to this complex, relatively common behavioral syndrome in this series. The less common subsyndromes in particular, were notable, as they constituted the initial overriding, presenting symptoms and syndromes characterized into 16 separate conditions.”
The authors suggested that, by deconstructing FTD into the multiple sub-syndromes and differing etiologies, their study could provide foundational insights. That might enable “a more targeted precision medicine approach for future studies, both in treating the sub-syndromes, as well as the underlying etiological process,” they pointed out/
- Hoffmann M, Rossi F, Benes Lima L, King C. Frontotemporal disorders: the expansive panoply of syndromes and spectrum of etiologies. Front Neurol. 2024 Jan 9;14:1305071. doi: 10.3389/fneur.2023.1305071. PMID: 38264092; PMCID: PMC10803619.