Elka Stefanova

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Acta Clin Croat,  Vol. 50,  (Suppl) No. 2,  2011 25Acta Clin Croat (Suppl. 2) 2011; 4th international epilepsy symposium in Pula – how to start seizure treatmentSOFT BOUNDARIES BETWEEN FRONTOTEMPORAL DEMENTIAS AND ATYPICAL PARKNSONISMS Elka StefanovaClinic of Neurology, CCS, University of Belgrade, SerbiaFrontotemporal dementia (FTD) encompasses a group of neurodegenerative diseases characterized by focal atrophy of frontal and anterior temporal lobes and non-Alzheimer pathology. In people under 65 years of age, FTD is as common as Alzheimer’s dis-ease (AD) and its prevalence has been estimated in 15 per 100,000 patients between 45 to 64 years of age.Patients with FTD display a heterogeneous clinical picture, which may include behavioral, cognitive, and motor manifestations. However, based on the predominant initial symptoms, FTD can be read-ily separated into two groups: the behavioral variant (bv -FTD), which is characterized by loss of insight, personality changes, and disturbances in social cogni-tion and the language variant, also referred as primary progressive aphasia (PPA). Th e latter can be further divided into a well-deﬁ ned clinical-pathological enti-ty, semantic dementia (SD) and progressive nonﬂ uent aphasia (PNFA). However, logopenic/phonological (LPA) variant has been recently described, showing a distinctive pattern of brain atrophy and often associ-ated to Alzheimer’s disease pathology. Th e diagnosis of FTD is challenging, since there is clinical, pathological, and genetic overlap between the variants and other neurodegenerative diseases, such as motoneuron disease (MND) and corticobasal degeneration (CBD). Despite this classiﬁ cation, there is a clinical, pathological, and genetic overlap. For instance, SD cases may develop features of bv-FTD, and patients with the clinical variant often have com-mon areas of brain atrophy and family history of an-other variant. Moreover, there is increasing evidence of overlap between FTD and other neurodegenerative disease, notably Motor Neuron disease (MND), Pro-gressive Supranuclear Palsy (PSP), and Corticobasal degeneration (CBD). For example, cases initially di-agnosed as PNFA may end up showing a clinical pic-ture and pathology of CBD. Indeed, some argue that those entities should all be included under the rubric of Pick’s complex.Diﬀ erentiating one variant of FTD from another, as well as from other neurodegenerative and nonde-generative diseases (particularly psychiatric condi-tions) remains challenging. Fortunately, recent ad-vances in molecular pathology and genetics, improved imaging techniques, and better clinical descriptions have contributed enormously to our understanding of these conditions and are oﬀ ering new insights, which we hope will be helpful for improved diagnosis and management of patients with these devastating dis-orders. In addition, patients with gene mutations (tau and progranulin) display an inconsistent clinical phe-notype and the correspondence between the clinical variant and its pathology is unpredictable. New cog-nitive tests based on social cognition and emotional recognition together with advances in molecular pathology and genetics have contributed to an im-proved understanding. Th ere is now a real possibility of accurate biomarkers for early diagnosis. In the last twenty years, a great deal of progress on molecular genetic and imaging has led to new insights about FTD syndromes. New imaging methods, for instance voxel based morphometry (VBM), has given a de-tailed account of pattern of brain atrophy, allowing an unbiased comparison of patients groups, while the development of radiotracers, such as PiB has enabled to identify the accumulation of extracellular beta-am-yloid, and therefore, rule out cases of AD. Patients with bv-FTD show atrophy of the orbitobasal and medialfrontal lobes, together with anterior temporal Acta Clin Croat (Suppl. 2) 2011; 4th international epilepsy symposium in Pula – how to start seizure treatment26 Acta Clin Croat,  Vol. 50,  (Suppl) No. 2,  2011and insular involvement. SD is associated with atro-phy of the anterior temporal lobe involving particu-larly polar, anterior parahippocampal, and fusiform regions including the perirhinal cortex. Th e atrophy is bilateral, but typically asymmetric and often more se-vere on the left. In PNFA, the changes are subtler and involve the left inferior frontal lobe and anterior insula cortex. In logopenic/phonological variant the atrophy involves the left hemisphere, particularly the poste-rior temporal lobe (superior and middle temporal gyri) and inferior parietal lobe and lesser involvement of the precuneus. Th ese changes can also be detected using simpler MRI-based visual rating scales, which simply use standard coronal cuts. Th ese scales aid diagnosis and monitoring of progression. Ligands speciﬁ c to tau and TDP-43 are eagerly awaited. Around 40% of patients report a family history of dementia, although in many instances this is almost certainly unrelated, but 10–20% have a clear pattern of autosomal dominant inheritance, with at least two relatives having young onset dementia or MND. Th e heritability, however, varies according to the variant FTD: SD showing the least, whereas bv-FTD and FTD with MND the most inheritable. Th e common-est identiﬁ ed mutations are MAPT and progranuline (PGRN), both in chromosome 17q21. Although the prevalence of mutations varies among studies, the two mutations have a similar frequency, being found in around 5–10% of patients. Other mutations involve the Valosin-containing protein (VCP) and CHMP2B genes, but are very rare. Advances in neuropsycholog-ical assessment have also led a better understanding of the language and social cognitive diﬃ  culties seen in FTD. Many issues remain unresolved. Th e relation-ship between genetic, pathologic, and clinical pheno-type is of key importance as is the ability to identify pathological subtypes in vivo by the use of biomark-ers.

Soft Boundaries Between Frontotemporal Dementias and Atypical Parknsonisms

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