To know or not to know? Opinions of patients with Parkinson's Disease on disclosing risk of phenoconversion in RBD.

INTRODUCTION: The aim of our study was to find out the opinion of patients with Parkinson's Disease (PD) whose disease was preceded by REM sleep behaviour disorder (RBD) regarding early information about the high risk of phenoconversion in RBD. CLINICAL RATIONALE FOR THE STUDY: RBD is an early clinical manifestation of α-synucleinopathies with a more than 90% risk of phenoconversion to PD, dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). It remains a subject for debate as to whether and how RBD patients should be informed about the high risk of phenoconversion. The patient's right to full knowledge regarding his or her health conflicts with the potentially destructive impact of this information on his or her mental state and quality of life of them and their relatives. MATERIAL AND METHODS: Thirty-nine patients with PD whose disease was preceded by RBD were surveyed. Data on the course of RBD and PD was collected. Questions were asked about early information about the high risk of phenoconversion to patients with RBD and factors determining the opinion of the surveyed persons. RESULTS: The majority ( > 60%) of respondents gave a positive answer when asked whether patients should be informed about their high risk of developing PD once diagnosed with RBD. Only a few (7.7%) respondents believed that disclosing such information to the patient should be possible only after obtaining his or her consent. Respondents associated consent to information about the high risk of developing PD in people with RBD with high expectations of the healthcare system. We were unable to determine whether factors such as the gender of the subject, the clinical course of the PD, and the RBD duration had an impact on patients' opinions regarding disclosing knowledge about phenoconversion. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study provides important information that should influence physicians' communication with patients with RBD, especially regarding how they communicate about the high risk of phenoconversion.

The eccentric mechanotransduction, neuro-muscular transmission, and structural reversibility of muscle fatty infiltration. An experimental advanced disuse muscle-wasting model of rabbit supraspinatus.

INTRODUCTION: Full-thickness rotator cuff tear is present in almost 50% of patients over age 65 years, and its degree is known to be a good predictor of the severity of muscle-wasting (MW) sarcopaenia, also known as fatty degeneration (FD). A FD CT grade > 2° is recognized as a borderline of its reversibility. A disuse model of supraspinatus FD (grade 2) in rabbits provides clinically relevant data. Therefore, the present study evaluates the correlation between eccentric mechanotransduction, neuromuscular transmission (NT), and reversibility of muscle fatty infiltration (MFI) in rabbit supraspinatus FD > 2°. MATERIAL AND METHODS: The supraspinatus tendon was detached from the greater tubercle, infraspinatus, and subscapularis in 16 rabbits. The tendon was reinserted after 12 weeks, and the animals were euthanized 24 weeks after reconstruction. MFI was measured in the middle part of the supraspinatus. Single-fibre EMG (SFEMG) examination of the supraspinatus NT was performed on 4 animals. RESULTS: The power of analysis was 99%. Significant differences in MFI volume were found between the operated (4.6 ±1.1%) and the opposite control sides (2.91 ±0.61%) (p < 0.001). SFEMG revealed no significant differences between the disuse and the control supraspinatus muscles (p > 0.05); however, 6.5% of the examined muscle fibres exhibited NT disorders combined with blockade of conduction in 2.5% of muscle fibres. CONCLUSIONS: Critical MFI in a disuse model of rabbit supraspinatus FD, CT grade > 2°, is substantially reversible by eccentric training despite subclinical impairment of neuromuscular transmission. In addition, 0.63% reversal of MFI is correlated with 1% hypertrophy of type I and II muscle fibre diameter.

Botulinum toxin type-A preparations are not the same medications - basic science (Part 1).

Botulinum neurotoxin type A (BoNT/A) formulations are widely used in clinical practice. Although they share a common mechanism of action resulting in presynaptic block in acetylocholine release, their structure and pharmacological properties demonstrate some similarities and many differences. Bioequivalence has been discussed since the onset of the clinical use of BoNT/A. In this review, we provide an update on the studies and compare the molecular structure, mechanisms of action, diffusion and spread, as well as immunogenicity and dose equivalence of onabotulinumtoxinA, abobotulinumtoxinA and incobotulinumtoxinA.

Botulinum toxin type-A preparations are not the same medications - clinical studies (Part 2).

The growing number of Botulinum neurotoxin type A (BoNT/A) preparations on the market has resulted in a search for pharmacological, clinical and pharmacoeconomic differences. Patients are occasionally switched from one botulinum toxin formulation to another. The aim of this paper was to review studies that have made direct comparisons of the three major BoNT/A preparations presently on the market: ona-, abo- and incobotulinumtoxinA. We also review the single medication Class I pivotal and occasionally Class II-IV studies, as well as recommendations and guidelines to show how effective doses have been adopted in well-established indications such as blepharospasm, hemifacial spasm, cervical dystonia and adult spasticity. Neither direct head-to-head studies nor single medication studies between all preparations allow the formation of universal conversion ratios. All preparations should be treated as distinct medications with respect to their summary of product characteristics when used in everyday practice.

Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks.

BACKGROUND: Botulinum neurotoxin (BoNT) is an effective treatment for chronic sialorrhea; however, reliable and robust evidence supporting long-term efficacy and safety is lacking. This study investigated the efficacy and safety of repeated incobotulinumtoxinA injections for chronic sialorrhea over 64 weeks. METHODS: Adults with sialorrhea were randomized (2:2:1) to incobotulinumtoxinA 75 U, incobotulinumtoxinA 100 U (n = 74 each), or placebo (n = 36) in the double-blind, placebo-controlled main period (NCT02091739). Eligible subjects entered the extension period and received dose-blinded incobotulinumtoxinA 75 or 100 U in three further 16±2-week injection cycles. Efficacy and safety assessments in subjects who received incobotulinumtoxinA throughout the study included unstimulated salivary flow rate (uSFR), subjects' Global Impression of Change Scale (GICS), Drooling Severity and Frequency Scale (DSFS), modified Radboud Oral Motor Inventory for Parkinson's Disease (mROMP) drooling, speech, and swallowing symptom scores, and incidence of adverse events (AEs). RESULTS: In total, 173/184 subjects (94%) completed the main period and entered the extension period; 141 subjects received incobotulinumtoxinA 75 U (n = 69) or 100 U (n = 72) in both periods. Mean uSFR decreased consistently with repeated incobotulinumtoxinA 75 and 100 U treatment and by -0.16 and -0.17, respectively, at the end-of-study visit. Subjects' GICS, DSFS, and mROMP drooling scores also improved at all assessments. mROMP speech and swallowing scores remained stable. The most common treatment-related AEs during the extension period were dry mouth (4.4% and 11.1%) and dysphagia (1.5% and 4.2%). CONCLUSIONS: Data support long-term efficacy and safety of repeated incobotulinumtoxinA treatment for sialorrhea, with no additional safety concerns reported over 64 weeks.

The symptoms asymmetry of drug-induced parkinsonism is not related to nigrostriatal cell degeneration: a SPECT-DaTSCAN study.

AIM: Drug-induced parkinsonism (DIP) is the most common form of parkinsonism after Parkinson's disease (PD) itself. It has been widely believed that DIP is characterised by symmetry of symptoms. Studies of patients with DIP in whom PD had been ruled out by SPECT-DaTSCAN have shown that symptom asymmetry is a common element of DIP clinical presentation. The aim of our study was to determine whether the asymmetry of symptoms in DIP is related to any abnormality within the presynaptic part of the nigrostriatal dopaminergic system. MATERIALS AND METHODS: Eleven patients with the diagnosis of DIP and asymmetric symptoms were studied. Their individual SPECT-DaTSCANs were normal. Indices calculated for the whole group of radiotracer uptake in the whole striatum, putamen and caudate contralateral to more severe DIP symptoms were compared to values obtained in the opposite hemisphere. RESULTS: We did not find significant differences in radiotracer uptake in structures contralateral to more severe clinical symptoms when compared to the homolateral hemisphere. CONCLUSIONS: Our results have not confirmed the presence of a presynaptic nigrostriatal deficit which could be related to asymmetry of DIP. The factors responsible for the asymmetry of DIP symptoms should be sought in the postsynaptic part of the nigrostriatal dopaminergic system.

Should non-movement specialists refer patients for SPECT-DaTSCAN?

BACKGROUND: SPECT with radioligand DaTSCAN (SPECT-DaTSCAN) is a sensitive tool used for assessing the functional integrity of the presynaptic part of the nigrostriatal dopaminergic system. The procedure is useful whenever there is a need to distinguish between neurodegenerative parkinsonism and other parkinsonian syndromes in subjects with equivocal signs and symptoms. It can be assumed that the neurologist's decision to perform SPECT-DaTSCAN depends on his or her experience and skill in the diagnosis of parkinsonian and tremor syndromes. AIMS: To assess the accuracy of referrals to SPECT-DATSCAN made by non-movement disorders specialists. MATERIAL AND METHODS: Sixty seven patients referred for SPECT-DaTSCAN by a general neurologist were studied. In all subjects, a movement disorder specialist performed the neurological examination, collected medical history, and analysed previous treatments and the results of diagnostic tests. RESULTS: Evaluation carried out by a movement disorder specialist did not confirm an indication for SPECT-DaTSCAN in 31 patients (46.3%). General neurologists needed support for clinical diagnosis with SPECT-DaTSCAN most frequently in subjects with parkinsonism even though they were presenting a full-blown disease manifestation and even though the patients met the diagnostic criteria for Parkinson's disease or one of the atypical parkinsonian syndromes. CONCLUSIONS: Our presented results probably reflect the limited experience of general neurologists in the evaluation of parkinsonian syndromes and tremor. The use of SPECT-DaTSCAN by non-movement disorders specialists is associated with a significant risk of overuse of this tool. To minimise this risk, the skills of general neurologists in diagnosing parkinsonian and tremor syndromes should be improved. Moreover, patients should be provided with access to movement disorders specialists.

SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea.

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%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout. RESULTS: A total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients). CONCLUSIONS: IncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults. CLINICALTRIALSGOV IDENTIFIER: NCT02091739. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI.

Supramolecular Complexes of Graphene Oxide with Porphyrins: An Interplay between Electronic and Magnetic Properties.

Graphene oxide (GO) was modified by two modified porphyrins (THPP and TCPP) to form GO⁻porphyrin hybrids. Spectroscopic measurements demonstrated the formation of stable supramolecular aggregates when mixing two components in solution. The Fourier transform infrared (FTIR) and Raman scattering measurements confirm π-stacking between hydrophobic regions of GO nanoflakes and porphyrin molecules. On the number and the kind of paramagnetic centers generated in pristine GO samples, which originate from spin anomalies at the edges of aromatic domains within GO nanoflakes. More significant changes in electronic properties have been observed in hybrid materials. This is particularly evident in the drastic increase in the number of unpaired electrons for the THPP-GO sample and the decrease in the number of unpaired electrons for the TCPP-GO. The difference of paramagnetic properties of hybrid materials is a consequence of π-stacking between GO and porphyrin rings. An interesting interplay between modifiers and the surface of GO leads to a significant change in electronic structure and magnetic properties of the designed hybrid materials. Based on the selection of molecular counterpart we can affect the behavior of hybrids upon light irradiation in a different manner, which may be useful for the applications in photovoltaics, optoelectronics, and spintronics.

The Therapeutic Effect of Nordic Walking on Freezing of Gait in Parkinson's Disease: A Pilot Study.

Introduction. The effectiveness of the currently utilized therapies for FoG is limited. Several studies demonstrated a beneficial impact of Nordic walking (NW) on several gait parameters in Parkinson's disease, but only one paper reported reduction of freezing. Research Question. In the present study, the question is whether NW is an effective therapeutic intervention in FoG. METHODS: Twenty PD subjects trained NW for 12 weeks, with a frequency of twice per week. Each session lasted about 60 minutes. Twenty patients in the control group did not use any form of physiotherapy (no-intervention group). Freezing of Gait Questionnaire (FOGQ), the Timed Up and Go (TUG) test, and the Provocative Test for Freezing and Motor Blocks (PTFMB) were performed at baseline, immediately after the end of NW program, and three months later. RESULTS: The results of FOGQ, TUG, and total PTFMB revealed significant improvement after completing the exercise program, and this effect persisted at follow-up. The results of the PTFMB subtests showed a different effect of NW on particular subtypes of FoG. Start hesitation, sudden transient blocks that interrupt gait, and blocks on turning improved considerably, while motor blocks, when walking through narrow space and on reaching the target, did not respond to NW training. Significance. The results show, for the first time, that FoG during turning and step initiation, two most common forms of this gait disorder, has been significantly reduced by NW training. Different responses of particular subtypes of FoG to NW probably reflect their different pathophysiologies. CONCLUSIONS: The present study showed that NW training had a beneficial effect on FOG in PD and that the achieved improvement is long-lasting. Future research should clarify whether the observed improvement limited to FoG triggered by only some circumstances reflects different pathomechanisms of FoG subtypes.

Electron microscopic and confocal laser microscopy analysis of amyloid plaques in chronic wasting disease transmitted to transgenic mice.

We report here on the ultrastructure of amyloid plaques in chronic wasting disease (CWD) transmitted to Tg20 transgenic mice overexpressing prion protein (PrPc). We identified three main types of amyloid deposits in mCWD: large amyloid deposits, unicentric plaques similar to kuru plaques in human prion diseases and multicentric plaques reminiscent of plaques typical of GSS. The most unique type of plaques were large subpial amyloid deposits. They were composed of large areas of amyloid fibrils but did not form "star-like" appearances of unicentric plaques. All types of plaques were totally devoid of dystrophic neuritic elements. However, numerous microglial cells invaded them. The plaques observed by confocal laser microscope were of the same types as those analyzed by electron microscopy. Neuronal processes surrounding the plaques did not show typical features of neuroaxonal dystrophy.

Functional Evaluation of Small Fiber Pathways in Primary Restless Legs Syndrome: Aδ Pathway Study.

STUDY OBJECTIVES: The aim of this study was to provide a neurophysiological evaluation of the function of large and small fibers, particularly the peripheral part of the thermonociceptive Aδ pathway in patients with primary restless legs syndrome (RLS). METHODS: The main evaluation was based on an analysis of the parameters of laser-evoked potentials (LEPs), N2 and P2 components, and an assessment of thermonociceptive thresholds (pain thresholds; PThs). Routine nerve conduction studies (NCS) were also performed. RESULTS: No essential or important differences of clinical significance were observed in the parameters of large fiber conduction between the study and the control groups. Prolonged latencies of N2 and P2 potentials were obtained during foot stimulation in patients with primary RLS when compared to controls (N2, P2-lower right limb, and N2-lower left limb). We also observed higher amplitudes of LEPs evaluated as P2 and N2-P2 potentials in patients with primary RLS in comparison with the control group. Significantly higher (normal distribution P < .05) thermonociceptive thresholds in both lower and upper limbs were found in the RLS group. CONCLUSIONS: On the basis of the analysis of LEPs and their comparison with the respective results from the control group, the presence of functional disability of the thermonociceptive Aδ pathway was confirmed in patients with primary RLS. The results indicated the presence of changes in the conduction of small fiber pathways in the pathomechanism of idiopathic RLS.

Is nigrostriatal dopaminergic deficit necessary for Holmes tremor to develop? The DaTSCAN and IBZM SPECT study.

Holmes's tremor (HT) is assumed to be the result of coexistence of nigrostriatal dopaminergic system impairment and the lesion of cerebello-thalamic pathways. It was suggested that dopaminergic deficiency is responsible for rest tremor, and lack of compensatory cerebellar function leads to spill of tremor into voluntary movements. Cases of HT with and without abnormalities of the presynaptic part of dopaminergic nigrostriatal were published and these findings raised the question of possibility of the postsynaptic lesion. Three patients with HT diagnosed according to criteria of Consensus Statement on Tremor were studied. In all of them SPECT imaging with ligands of presynaptic (I 123-FP CIT-DaTSCAN) and postsynaptic (I 123-iodobenzamide-IBZM) nigrostriatal dopaminergic neurons was performed. Indices of uptake in caudate and putamen normalized to nonspecific uptake in occipital cortex and indices of asymmetry for each whole striatum as well as for putamen and caudate separately were calculated. SPECT studies did not reveal asymmetry of DaTSCAN and IBZM binding in striatum in all studied subjects. The current clinical diagnostic criteria of HT are presumably insufficiently specific and when using them we identify patients both with and without the involvement of dopaminergic system. These two groups may represent tremor disorders of similar phenomenology but of different pathomechanism.

Generation of Low-Dimensional Architectures through the Self-Assembly of Pyromellitic Diimide Derivatives.

Small π-conjugated molecules can be designed and synthesized to undergo controlled self-assembly forming low-dimensional architectures, with programmed order at the supramolecular level. Such order is of paramount importance because it defines the property of the obtained material. Here, we have focused our attention to four pyromellitic diimide derivatives exposing different types of side chains. The joint effect of different noncovalent interactions including π-π stacking, H-bonding, and van der Waals forces on the four derivatives yielded different self-assembled architectures. Atomic force microscopy studies, corroborated with infrared and nuclear magnetic resonance spectroscopic measurements, provided complementary multiscale insight into these assemblies.

Robust autophagy in optic nerves of experimental Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker disease.

We report here autophagy in the optic nerve in experimental Gerstmann-Sträussler-Scheinker disease (GSS) (Fujisaki-1) in mice and experimental Creutzfeldt-Jakob disease (CJD) (Echigo-1) in hamsters. Lesions of both experimental GSS in mice and experimental CJD in hamsters were practically indistinguishable. Briefly, they consisted of widespread Wallerian degeneration, spongiform change and a glial reaction. Numerous axonal swellings were seen. The latter were filled with numerous mitochondria and lysosomal electron-dense bodies. Autophagic vacuoles defined as structures bound in double membranes were readily found in many neuronal processes. The following description is organized as a sequence; however, the changes were all observed in the same specimens. First several empty double membrane-bound autophagic vacuoles were seen. In several of those vacuoles, the inner membrane was separated from the outer membrane and enclosed cargo. At the final stage, a mixture of empty autophagic vacuoles and electron-dense lysosomal vesicles was seen. Dystrophic neurites filled with a mixture of mitochondria, empty autophagic vacuoles and electron-dense lysosomal vesicles were interpreted as the final stage of autophagy. Of note, several areas were replaced with dense astrocytic gliosis..

Unilateral progressive muscular atrophy with fast symptoms progression.

Progressive muscular atrophy (PMA), or the lower motor neuron disease, is a sporadic disorder characterized by onset in adulthood, pure lower motor neuron involvement and relatively benign course. Muscle atrophy and weakness may be symmetrical or asymmetrical, but they are always bilateral. We present a male patient with exclusively left-side flaccid paresis due to lower motor neuron disease without electromyographic evidence of neurogenic lesion of contralateral muscles and with no signs of corticospinal tracts involvement. The rapid disease progression was typical of the generalized phenotype of PMA and it suggested the relation to the aggressive course of classical ALS.

Screening for THAP1 Mutations in Polish Patients with Dystonia Shows Known and Novel Substitutions.

The aim of this study was to assess the presence of DYT6 mutations in Polish patients with isolated dystonia and to characterize their phenotype. We sequenced THAP1 exons 1, 2 and 3 including exon-intron boundaries and 5'UTR fragment in 96 non-DYT1 dystonia patients. In four individuals single nucleotide variations were identified. The coding substitutions were: c. 238A>G (p.Ile80Val), found in two patients, and c.167A>G (p.Glu56Gly), found in one patient. The same variations were present also in the patients' symptomatic as well as asymptomatic relatives. Mutation penetration in the analyzed families was 50-66.7%. In the fourth patient, a novel c.-249C>A substitution in the promoter region was identified. The patient, initially suspected of idiopathic isolated dystonia, finally presented with pantothenate kinase 2-associated neurodegeneration phenotype and was a carrier of two PANK2 mutations. This is the first identified NBIA1 case carrying mutations in both PANK2 and THAP1 genes. In all symptomatic THAP1 mutation carriers (four probands and their three affected relatives) the first signs of dystonia occurred before the age of 23. A primary localization typical for DYT6 dystonia was observed in six individuals. Five subjects developed the first signs of dystonia in the upper limb. In one patient the disease began from laryngeal involvement. An uncommon primary involvement of lower limb was noted in the THAP1 and PANK2 mutations carrier. Neither of these THAP1 substitutions were found in 150 unrelated healthy controls. To the contrary, we identified a heterozygous C/T genotype of c.57C>T single nucleotide variation (p.Pro19Pro, rs146087734) in one healthy control, but in none of the patients. Therefore, a previously proposed association between this substitution and DYT6 dystonia seems unlikely. We found also no significant difference between cases and controls in genotypes distribution of the two-nucleotide -237-236 GA>TT (rs370983900 & rs1844977763) polymorphism.

Intractable headaches, ischemic stroke, and seizures are linked to the presence of anti-ß2GPI antibodies in patients with systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common and potentially fatal manifestation of SLE. Antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL) and antibodies to ß2glycoprotein I (anti-ß2GPI), the most important aPL antigen, are thought to play a role in some forms of NPSLE. As of yet, their specific roles in NPSLE manifestations remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: 57 SLE patients (53 women) were assessed for LA, aCL and anti-ß2GPI twice, to determine persistent positivity. All patients were examined by neurology and psychiatry specialists. 69 healthy subjects were assessed as controls. NPSLE was diagnosed in 74% of patients. Headaches were the most prevalent manifestation of NPSLE (39%), followed by cerebrovascular disease (CVD) (23%), depressive disorders (19.0%), and seizures (14%). NPSLE and non-NPSLE patients showed comparable SLE activity and corticosteroid use. In 65% of patients neuropsychiatric manifestations preceded SLE diagnosis. aPL profiles of NPSLE patients and non-NPSLE patients were similar. Headaches and ischemic stroke were independently associated with anti-ß2GPI-IgM (OR=5.6; p<0.05), and seizures were linked to anti-ß2GPI-IgG (OR=11.3; p=0.01). CONCLUSIONS: In SLE patients, neuropsychiatric manifestations occur frequently and early, often before the disease is diagnosed. Autoantibodies to ß2GPI are linked to non-specific headaches, ischemic stroke and seizures, and show a better predictive value than aCL and LA. These findings may help to improve the diagnosis of NPSLE and should prompt further studies to characterize the role of anti-ß2GPI in the pathogenesis of this condition.

High variability of clinical symptoms in a Polish family with a novel THAP1 mutation.

BACKGROUND: Mutations in the THAP1 gene are associated with a broad spectrum of dystonia including focal and generalized forms. Missense, nonsense and frameshift mutations, including small insertions/deletions within the THAP1 gene, have been reported and majority of them cause autosomal dominant disease with limited penetrance of approximately 60%. Here, we describe a novel THAP1 mutation. MATERIALS AND METHODS: Blood samples were collected from consenting family members for extraction of genomic DNA. As controls, we analyzed 150 individuals without neurological disorders. THAP1 coding sequences were amplified with PCR and sequenced. RESULTS: We describe a Polish family with a novel heterozygous substitution: c.167A>G (p.Glu56Gly) in THAP1 exon 2. This is the largest reported family with the mutation in THAP1 exon 2. The mutation was found in four of five genetically studied family members, including two clinically affected male individuals and two asymptomatic carriers (male and female). Data on one deceased male symptomatic subject were available and two assumed carriers were identified. The substitution was not present in any of the analyzed healthy controls. The high variability of phenotype included age of onset, localization of the initial symptom as well as the rate and degree of generalization. CONCLUSIONS: Our findings strongly suggest the role of other genetic factors or environmental triggers in the pathogenesis of dystonia related to mutations in THAP1 gene.