Andrzej Friedman

• MD, PhD, Professor
• Head of Department at Medical University of Warsaw

Plain Language Summary Background Levodopa is an important treatment for Parkinson’s disease (PD). As the disease gets worse, levodopa’s effects change. A common problem is “wearing off,” where the medicine stops working sooner than expected. Some advanced PD patients say this happens faster after they exercise. Study goals The study aimed to fin...

Introduction. Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson’s Disease (PD)...

Introduction: Multilingualism is a poorly understood phenomenon. There is conflicting data on whether the location of each language in the brain in sequential multilinguals is identical or (partially) separate. It has been observed that certain multilinguals with injuries to the language centers developed selective aphasia, a subset even losing the...

Progressive Supranuclear Palsy (PSP) is an atypical parkinsonism. Major subtypes of the disease: PSP-Richardson’s Syndrome (PSP-RS) and PSP Parkinsonism Predominant (PSP-P) vary in clinical features, the pathomechanism remains unexplored. The aim of this work is to analyze the relevance of glial cell line-derived neurotrophic factor (GDNF) evaluati...

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 neurode...

Introduction: The pathogenesis of parkinsonisms is not fully understood. Among possible factors which may influence the course of neurodegenerative diseases, endocrine abnormalities may be interpreted as having been underevaluated. State of the art: Growing interest is associated with the role of neuropeptides such as orexin. Orexin is a neurope...

Introduction. Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are clinical manifestations of tauopathies. They are commonly associated with rapid motor and cognitive deterioration. Sleep disturbances are less frequently described as a feature of these diseases, though they are reported among 50-75% of PSP patients. State of the...

Introduction: Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Ste...

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review’s aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota compos...

Progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS) are clinical manifestations of tauopathic Parkinsonian syndromes. Due to their overlapping symptomatology, the differential diagnosis of these entities may be difficult when bounded to clinical assessment. The manifestations are commonly associated with pathological enti...

Aim of the study. To assess the usefulness of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in evaluating the inflammatory process in alpha-synucleinopathies. Clinical rationale for the study. The role of neuroinflammation in PD and MSA pathogenesis is indisputable. However, there is no method available in everyday use...

Multiple System Atrophy-Parkinsonism Predominant (MSA-P) and Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P) are the clinical manifestations of atypical parkinsonism. Currently, there are no efficient in vivo methods available relating to neuroimaging or biochemical analysis in the examination of these entities. Among the advanced m...

Introduction: Neuroimaging play an increasingly important role in the diagnosis of parkinsonian syndromes. Aim of the study: In this paper, the authors elaborate on the necessity of using magnetic resonance imaging (MRI) in Parkinson's Disease (PD) and its potential role in differential diagnosis versus other neurodegenerative parkinsonian syndr...

Parkinson’s disease (PD) is a progressive neurodegenerative disorder. It affects many organs. Lewy bodies—a histopathological “hallmark” of PD—are detected in about 75% of PD submandibular gland samples. We hypothesize that saliva can be a source of biomarkers of PD. The aim of the study was to evaluate and compare the salivary proteome of PD patie...

Introduction Approximately 10% of patients with Parkinson disease (PD) present with early-onset disease (EOPD), defined as diagnosis before 50 years of age. Genetic factors are known to contribute to EOPD, with most commonly observed mutations in PRKN, PINK1, and DJ1 genes. The aim of our study was to analyze the frequency of PRKN, PINK1, and DJ1 m...

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 characteri...

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are clinical syndromes classified as atypical parkinsonism. Due to their overlapping symptomatology, recent research shows the necessity of finding new methods of examination of these clinical entities. PSP is a heterogenic disease. PSP Richardson-Steele Syndrome (PSP-RS) and park...

Introduction: Genetic forms of Parkinson's disease (PD) often cluster in different ethnic groups and may present with recognisable unique clinical manifestations. Our aim was to summarise the current state of knowledge regarding the genetic causes of PD and describe the first Polish patient with SNCA duplication. Methodology: We searched the ele...

Aim of the study. To examine possible features of neuroinflammation in progressive supranuclear palsy — Richardson syndrome and corticobasal syndrome (CBS). Clinical rationale for the study. Neutrophil-to-lymphocyte ratio (NLR) is a parameter reflecting inflammation used in numerous branches of medicine. The search for pathogenesis of the diseases...

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a valuable alternative to pharmacotherapy alone in an advanced Parkinson's disease (PD). Given the growing number of patients with STN-DBS, its impact on the comorbidities should be considered. Aim: The aim of this study was to evaluate the influence of bilateral STN-DBS on the lip...

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 tha...

Introduction Speech disorder is a common clinical manifestation in patients with Parkinson's disease and atypical parkinsonian syndromes and tends to occur before the onset of the axial parkinsonian symptoms. Due to parkinsonian features that overlap those of Parkinson's disease, the differentiation of voice and a speech disorder is a challenge for...

The aim of this work is to present whether SPECT 99mTc-HMPAO can be a method of examination to possibly differentiate the syndromes. 21 patients with PSP syndrome and 14 patients with corticobasal syndrome (CBS) were examined using SPECT 99mTc-HMPAO. Perfusion single photon emission computed tomography (SPECT) as a method of examination of progress...

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder, characterized by motor and non-motor symptoms. Among non-motor symptoms we distinguish psychotic disorders, memory disorders, autonomic disorders. The aim: In this article, we want to draw attention to the most common symptoms of dysautonomy in Parkinson's disease, and the methods...

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)...

Neurodegeneration in Parkinson's disease (PD) includes processes of chronic inflammation and oxidative stress which are related to dysregulation in the homeostasis of iron metabolism. Hepcidin is a peptide hormone responsible for systemic iron homeostasis and simultaneously the inflammatory response protein, induced in response to interleukin 6 (IL...

Next Generation Sequencing (NGS), has now become a very powerful tool for decoding variants of genes involved in pathogenesis of number of human disorders. One of the challenges of this method is to decipher the real pathogenic variants from a number of identified, not related to the disorder in analyzed case. Another issue is recognition of new ph...

The aim of this study was to assess quantitatively sweating in PD patients. In the study, the galvanic-skin reaction (GSR) was used. The GSR was tested using eSense Skin Reaction device. The results show that sweating in patients with Parkinson’s disease on drugs (PD ON) and control patients is similar, while patients with PD without levodopa (PD O...

Neuroimaging in the context of examining atypical parkinsonian tauopathies is an evolving matter. Positron emission tomography and single photon emission computed tomography (SPECT) bring tools, which may be reasonable in supplementary examination, however, cannot be interpreted as a criterion standard for correct diagnosis. The aim of this observa...

Background: Perfusion single photon emission computed tomography (SPECT) as a method of examination of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) as its clinical manifestation was not extensively analyzed in contemporary literature. Recent criteria of PSP and CBS do not describe this method of examination as primary or add...

The authors have withdrawn this preprint due to author disagreement.

Objective: This pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI). Methods: Adult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) wer...

Neuroimaging in the context of examining atypical parkinsonian tauopathies is an evolving matter. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) bring tools, which may be reasonable in supplementary examination, however cannot be interpreted as a gold standard for correct diagnosis. The review presents adv...

The identification of reliable biomarkers of Parkinson's disease (PD) is a pivotal step in the introduction of causal therapies. Saliva is a biofluid which may be involved in synuclein pathology in PD. We have reviewed current studies on salivary proteins and compounds in PD patients and healthy controls, and their potential application as biomarke...

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) has been an established method in improvement of motor disabilities in Parkinson's disease (PD) patients. It has been also claimed to have an impact on balance and gait disorders in PD patients, but the previous results are conflicting. Objective: The aim of this prospective controlle...

Objective: The pivotal double-blind, randomised Phase III SIAXI study (NCT02091739), assessed the efficacy and safety of incobotulinumtoxinA 75 or 100U for sialorrhoea. Co primary endpoints of the placebo-controlled main period (MP) are presented elsewhere. Here we report MP data from the modified Radboud Oral Motor Inventory for Parkinson’s diseas...

Objective: SIAXI (NCT02091739), a pivotal, double-blind, randomised, placebo-controlled study with an extension period (EP), assessed the efficacy and safety of incobotulinumtoxinA 75 and 100U in patients with sialorrhoea due to Parkinson’s disease (PD), atypical parkinsonism, stroke or traumatic brain injury. This subgroup analysis assessed the im...

Fragile X Tremor Ataxia Syndrome (FXTAS) is a syndrome based on expansion of the repeats of CGG triplets. The symptoms include action tremor and cerebellar gait ataxia. Additionally symptomatology of FXTAS may be associated to parkinsonism, executive function deficits, dementia, neuropathy and dysautonomia. We present a case of a patient who after...

Corticobasal Degeneration Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) are types of four repeats (4R) tauopathies, which are associated to parkinsonian syndromes. The aim of the work is to analyze cases of patients of the Department of Neurology, overlapping of syndromes related to both pathologies and to show that most likely CBS an...

Background: Mutations in the recessive genes PINK1 and PARKIN are the most common causes of early-onset Parkinson’s disease (PD). The mitochondrial ubiquitin (Ub) kinase PINK1 mediates, together with the cytosolic E3 Ub ligase PARKIN, mitochondrial quality control. Thereby, damaged mitochondria are identified to prevent their accumulation and event...

Background Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson’s disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a complex regulated, sequential mitochondrial quality control. Thereby, damaged mitochondria are identified and targeted to degr...

Diencephalic-mesencephalic junction dysplasia (DMJD) is very rare congenital brain malformation. We present a 66-years-old man with mild cognitive impairment, dysarthria, deafness, gait abnormality, and involuntary movements of the trunk. The first symptoms, psychomotor excitation and anxiety begun when he was over thirty years old however the symp...

The possible role of iron in neurodegeneration may be related to the oxidative stress, triggered by Fenton reaction. In this reaction hydroxyl free radical production is generated by divalent iron. Motor symptoms of Parkinson’s disease depend on the destruction of substantia nigra (SN). As the substantive questions were: 1/ what is the concentratio...

SIAXI: Efficacy and safety of incobotulinumtoxinA for the treatment of sialorrhea in Parkinson’s disease (PD) and other neurological conditions: Results of a Phase III, placebo-controlled, randomized, double-blind study

Mössbauer spectroscopy is not routinely used for the determination of the concentration of iron. However, as this method does not need any pre-treatment of samples before measurements, it may be of extreme importance for the assessment of iron in samples, which can then be used for further investigations. Biological samples are a good example, howe...

See Gandhi and Plun-Favreau (doi:10.1093/aww320) for a scientific commentary on this article. It has been postulated that heterozygous mutations in recessive Parkinson’s genes may increase the risk of developing the disease. In particular, the PTEN-induced putative kinase 1 (PINK1) p.G411S (c.1231G>A, rs45478900) mutation has been reported in famil...

Iron may play important role in neurodegeneration. The results of comparative studies of human brain areas (control and pathological) performed by Mössbauer spectroscopy (MS) and magnetic resonance imaging (MRI) techniques are presented. Mössbauer spectroscopy demonstrated a higher concentration of iron in atypical parkinsonism (progressive supranu...

Background and purpose: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identi...

Basis of the Parkinson’s disease are the chronic neurodegenerative changes, manifesting themselves in the asymmetric bradykinesia, the muscular rigidity and the resting tremor (the so-called triad of symptoms). Along with the advancement of the disease, there occur symptoms within the autonomic nervous system, speech and swallowing disorders, demen...

Oxidative stress is one of the possible mechanisms of neurodegeneration. One of the elements of this mechanism are altered iron homeostasis and changes concerning of iron metabolism regulatory proteins. The primary iron storage protein in cells is ferritin, composed of heavy (H) and light (L) chains. In brain tissue neurons contain mainly ferritin...

Background: The aim of his study was to evaluate the frequency of two most frequent GBA gene mutations in heterozygote state in patients with early and later onset Parkinson's disease in Polish populations. Methods and findings: Patients with Parkinson's disease; 115 non-demented with early onset disease (<45 year-old) and 155 patients with onset o...

Iron may play deleterious role in neurodegeneration by triggering oxidative stress via Fenton reaction. Iron was studied in Parkinson’s disease (PD) with controversial results. In other neurodegenerations, e.g., Alzheimer disease (AD) and progressive supranuclear palsy (PSP), it still needs evaluation. We present the results of our long lasting stu...

Iron may play important role in neurodegeneration. The results of comparative studies of human brain areas (control and pathological) performed by Mössbauer spectroscopy (MS) and magnetic resonance imaging (MRI) techniques are presented. Mössbauer spectroscopy demonstrated a higher concentration of iron in atypical parkinsonism (progressive supranu...

The aim of this study was to assess the small bowel transit time in patients with Parkinson's disease (PD). Ten patients with PD with no gastrointestinal complaints and ten healthy control subjects were investigated using single photon emission computed tomography fused with computed tomography after swallowing of a specially prepared capsule conta...

Background The role that oestradiol and testosterone play in Parkinson's disease and their potential to influence the course of the disease has been covered in medical literature. The aim of this work was to compare oestradiol, testosterone, sex hormone-binding protein and prolactin blood levels in males affected with Parkinson's disease and in an...

Sex and blood level of sex hormones play a key role not only in the susceptibility to develop Parkinson's disease (PD) but also influence the natural course of the disease. The aim of this study was to compare reproductive lifespan events in females affected with PD and in "non-parkinsonian" age matched subjects and to evaluate whether the whole li...

Accumulating data confirm the usefulness of transcranial sonography (TCS) in the diagnosis of Parkin-son's disease. The relevance of basal ganglia abnormalities depicted by TCS in atypical parkinsonian syndromes still needs further assessment. In the present study, 20 patients with progressive supranuclear palsy (PSP) and 13 patients with corticoba...

Mutations localized in THAP1 gene, locus 18p11.21 have been reported as causative of primary dystonia type 6 (DYT6). Disease which is characterized mainly by focal dystonia, frequently involving the craniocervical region, however associated also with early-onset generalized dystonia and spasmodic dysphonia. Here we report a novel mutation in the TH...

There is rapidly growing evidence for the influence of inflammation on the development and progression of Parkinson's disease (PD). N-terminal pro C-type Natriuretic Peptide (NT-proCNP) is a novel potential inflammatory biomarker and has been recently correlated in PD with pro- and anti-inflammatory cytokines, especially TNF-α and IL-10. The study...

The diagnosis of Parkinson's disease, and also other neurodegenerative disorders, is based on clinical examination. Many attempts are undertaken to find a test that could confirm this clinical diagnosis. Many hopes were attributed to magnetic resonance imaging but its importance remains obscure. The aim of this study was to compare T1 and T2 relaxa...

Background Sex and blood level of sex hormones play a key role not only in the susceptibility to develop Parkinson's disease (PD) but also influence the natural course of the disease. The aim of this study was to compare reproductive lifespan events in females affected with PD and in “non-parkinsonian” age matched subjects and to evaluate whether t...

This chapter presents results of studies on the role of iron in neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and progressive supranuclear palsy (PSP) using main tool Mössbauer spectroscopy, but also other complementary techniques such as electron microscopy, enzyme-linked immunosorbent assay (ELISA), and at...

Background and purpose: Parkinson disease (PD) is a complex disease, comprising genetic and environmental factors. Despite the vast majority of sporadic cases, three genes, i.e. PARK2, PINK1 and PARK7 (DJ-1), have been identified as responsible for the autosomal recessive form of early-onset Parkinson disease (EO-PD). Identified changes of these g...

To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature sea...