Diagnosing Progressive Supranuclear Palsy: Role of Biological and Neuroimaging Markers Borroni B 1* , Benussi A 1 , Pilotto A 1 , Gazzina S 1 , Turrone R 1 , Gardoni F 2 , Di Luca M 2 and Padovani A 1 1Centre for Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy 2Centre of Excellence in Neurodegenerative Disorders, University of Milan, Milan, Italy * Corresponding author: Barbara Borroni, Clinica Neurologica, Università degli Studi di Brescia Pza Spedali Civili, 1 - 25100 Brescia, Italy, Tel. +39-0303995632; E- mail: bborroni@inwind.it Received date: Aug 04, 2014, Accepted date: Nov 05, 2014, Published date: Nov 12, 2014 Copyright: © 2014 Borroni B et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorders characterised by a kinetic-rigid syndrome with ocular motor dysfunction, postural instability, and frontal lobe and bulbar dysfunction. In most of the cases, especially at early disease stages, diagnosis is still challenging. PSP signs and symptoms may indeed overlap with both dementing neurodegenerative syndromes and movement disorders. In the last few years, a better definition of clinical picture along with the identification of biological and neuroimaging markers have increased diagnostic accuracy. In the present work, we reviewed the current literature on PSP diagnosis and the usefulness of potential diagnostic markers. Keywords: Progressive supranuclear palsy; Biological markers; Neuroimaging Introduction Progressive Supranuclear Palsy (PSP) is an adult-onset progressive neurodegenerative disorder leading to an akinetic-rigid syndrome with ocular motor dysfunction, postural instability, and frontal lobe and bulbar dysfunction [1]. PSP usually occurs in the sixth decade, with clinical features that are often subtle and difficult to distinguish from other neurodegenerative disorders such as Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA) and Cortico Basal Syndrome (CBS) [2]. Early diagnosis can hence be challenging and the definite diagnosis is frequently deferred for many months. Neuropathologically, PSP is characterized by accumulation of Tau protein, neurofibrillary tangles and tufted astrocytes [3] in subcortical areas with a variable involvement of brain cortex. The aetiology still remains elusive, but genetic background has a key-role in disease pathogenesis. Although the majority of PSP cases are sporadic, recent studies have reported high familial aggregation in PSP patients, and it has been widely demonstrated that Microtuble Associated Protein Tau (MAPT) gene mutations are causative of rare monogenic autosomal dominant PSP [4,5]. In sporadic cases, genetic advances have further confirmed the role of MAPT in increasing disease risk, and the H1 MAPT haplotype has been consistently associated with PSP, while the H2 haplotype seems protective [6]. Conversely, no major environmental risk factors have been reported so far [7]. A proper evaluation of known susceptibility factors related to PSP pathogenesis may help in defining neuroprotective therapeutic approaches [8]. In most cases PSP presents clinically as Richardson's syndrome (RS), or Steele-Richardson-Olszewski syndrome, with prominent postural instability, supranuclear vertical gaze palsy and frontal dysfunction [9,10].The classical description of RS, although, did not include all neuropathologically confirmed cases of PSP. To justify this heterogeneity, PSP was recently divided clinically and pathologically into two main phenotypes: classical RS and PSP-parkinsonism (PSP- P), the latter characterised by bradykinesia, rigidity and sometimes tremor, which tends to be asymmetric and modestly responsive to levodopa therapy [11-13]. Clinical heterogeneity is furthermore augmented by PSP presenting as CBS (PSP-CBS), as pure akinesia with gait freezing (PSP-PAGF), or, rarely, as PSP associated to bvFTD (PSP-FTD) or progressive non- fluent aphasia (PSP-PNFA)[14]. These subtypes are not included in the currently used diagnostic criteria [9,15]. The National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) clinical diagnostic criteria were compiled to reliably identify patients who had underlying PSP-tau pathology [9,15]. Briefly, the NINDS-SPSP criteria depend on the identification of a progressive disorder with onset after age 40 combining the two cardinal features (i.e. postural instability with falls during the first year of the disease and slow vertical saccades or supranuclear gaze palsy). A list of exclusion criteria aims to sort out look-alike disorders [1,16]. The sensitivity, specificity, and positive predictive value of the NINDS-SPSP criteria have been evaluated retrospectively in a pathologically confirmed series of patients, showing specificity and sensitivity of clinician diagnosis, which can be as high as 90% [17]. Because the specificity and PPV of the probable NINDS-SPSP clinical criteria have been found to be near perfect, and the specificity and PPV of the possible criteria to be high, a redefinition of this set of criteria has been proposed [15]. Recently, the Neuroprotective and Natural History in Parkinson Plus Syndromes (NNIPPS) consortium has proposed modified clinical diagnostic criteria, aiming to facilitate the clinical diagnosis of PSP. Briefly, the NNIPPS criteria allow an age of onset after 30 and postural instability or falls within 3 years from disease onset [16,18]. A recent study has evaluated the efficacy of both criteria for the diagnosis of PSP. The authors conclude that the total NINDS-SPSP criteria, accepting both possible and probable for diagnosis, yielded the Alzheimers Disease & Parkinsonism Borroni B et al., J Alzheimers Dis Parkinsonism 2014, 4:6 http://dx.doi.org/10.4172/2161-0460.1000168 Review Article Open Access J Alzheimers Dis Parkinsonism ISSN:2161-0460 JADP, an open access journal Volume 4  Issue 6  1000168