Progressive Supranuclear Palsy (PSP) and Parkinson's Disease (PD), especially in their early stages, show overlapping clinical manifestations. The criteria for the diagnosis of PSP, released in 2017, indicate four basic features of the disease—postural instability (P), akinesia (A), oculomotor dysfunction (O) and cognitive and lingual disorders (C), which clarify the interpretation of the disease. There is growing interest in the second most common variant of PSP—parkinsonism predominant PSP-P. It is observed in up to 35% of cases. The diagnosis of PSP-P requires the presence of akinetic-rigid predominantly axial and levodopa resistant parkinsonism (A2) or parkinsonism with tremor and/or asymmetric and/or levodopa responsive (A3). The development of supplementary methods of examination added new insights to observations related to PSP-P. Among the methods recently analyzed are freezing of swallowing and speech breathing assessment, transcranial sonography, and various methods using magnetic resonance imaging, such as pons/midbrain area ratio and magnetic resonance parkinsonism index (MRPI), fractional anisotropy or mean diffusivity. The proper examination of overlapping parkinsonian syndromes, regardless of the development of the method of examination, remains an incompletely explored issue. The aim of this review is to elucidate which factors may be interpreted as influential in the differential diagnosis of PSP-P, PSP-RS and postural instability and gait difficulty (PIGD) subtype of Parkinson's disease (PD).

Progressive supranuclear palsy (PSP) is a neurodegenerative disease based on four-repeat tauopathy pathology. Currently, this entity is not fully recognized in the context of pathogenesis or clinical examination. This review evaluates the association between neuroinflammation and microglial activation with the induction of pathological cascades that result in tauopathy pathology and the clinical manifestation of PSP. Multidimensional analysis was performed by evaluating genetic, biochemical, and neuroimaging biomarkers to determine whether neurodegeneration as an effect of neuroinflammation or neuroinflammation is a consequence of neurodegeneration in PSP. To the best of our knowledge, this review is the first to investigate PSP in this context.

Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson’s disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers’ growth, and its expression may be associated with some tumors’ suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

Parkinson’s disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world’s aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome based on tau pathology; its clinical phenotype differs, but PSP with Richardson’s syndrome (PSP-RS) and the PSP parkinsonism predominant (PSP-P) variant remain the two most common manifestations. Neuroinflammation is involved in the course of the disease and may cause neurodegeneration. However, an up-to-date cytokine profile has not been assessed in different PSP phenotypes. This study aimed to evaluate possible differences in neuroinflammatory patterns between the two most common PSP phenotypes. Serum and cerebrospinal fluid (CSF) concentrations of interleukin-1 beta (IL-1β) and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA) kits in 36 study participants—12 healthy controls and 24 patients with a clinical diagnosis of PSP-12 PSP-RS and 12 PSP-P. Disease duration among PSP patients ranged from three to six years. All participants underwent basic biochemical testing, and neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were calculated. Due to a lack of neuropathological examinations, as all patients remain alive, total tau levels were assessed in the CSF. Tau levels were significantly higher in the PSP-P and PSP-RS groups compared to the healthy controls. The lowest concentrations of serum and CSF interleukins were observed in PSP-RS patients, whereas PSP-P patients and healthy controls had significantly higher interleukin concentrations. Furthermore, there was a significant correlation between serum IL-6 levels and PLR in PSP-RS patients. The results indicate the existence of distinct neuroinflammatory patterns or a neuroprotective role of increased inflammatory activity, which could cause the differences between PSPS phenotypes and clinical course. The causality of the correlations described requires further studies to be confirmed.

Neurologia i Neurochirurgia Polska