Frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration (FTLD) is an umbrella term covering aheterogeneous set of neurodegenerative disorders whose clinical presentation may becognitive, behavioural., motor, or mixed. These syndromes frequently combine duringthe course of the disease. FTLD syndromes show considerable phenotypic overlap andvariable histopathological and genetic correlations. Current neuropathologicalclassification is based on specific types of protein deposits and their related genes.Although infrequent in the general population, FTLD is nearly as common asAlzheimer's disease in patients below 65 years of age. Its scope extends from sporadic(60%) to familial forms (40%), some of the latter having an autosomal dominantinheritance pattern. Numerous mutations of several implicated genes have beendescribed.FTLD represents a diagnostic challenge owing to its mixed features. Implementationof various methods is required and consists of a clinical assessment, neuropsychologicaltesting, structural or functional neuroimaging and, sometimes, genetic analysis lookingfor mutations. Additional CSF and blood biomarkers, some of them still under study, mayprovide information about FTLD genetic risk factors or exclude other diseases. To date,only an autopsy allows a definite diagnosis.No therapies are currently available to cure or alter the evolution of FTLD disorders.Management strategies include pharmacological treatment of the signs and symptoms andnon-pharmacological interventions for the patients, for instance skill-based compensationmethods, environmental modifications or activity groups. Caregivers should be integratedin the process and offered support when needed (educational programmes, psychologicalfollow-up, respite facilities, etc.). Genetic counselling may prove useful.Research aims at a better understanding of the biochemical pathways of theproteinopathies which will potentially lead to more efficient diagnosis tools andinnovative drug strategies.