Search

Parkinson’s disease is the only neurodegenerative disease that can be effectively treated symptomatically. Treatment of motor symptoms is based primarily on the use of drugs that increase the activity of the nigrostriatal dopaminergic system and compensate for dopamine deficiency. Levodopa remains the gold standard of dopaminergic therapy. It is the most effective and best tolerated anti-parkinsonian drug, it causes the fewest side effects, also in the elderly patients. Oral preparations of levodopa additionally contain one of the aromatic L-amino acid decarboxylase inhibitors: benserazide or carbidopa. Inhibitors have a beneficial effect on the bioavailability of levodopa in the central nervous system, its clinical efficacy and tolerability. In practice, according to common opinion, the preparations of levodopa with carbidopa and levodopa with benserazide are clinically equivalent and can be used interchangeably. The case of a 69-year-old patient treated for 6 years for Parkinson’s disease is presented. The patient presented motor symptoms of advanced Parkinson’s disease: wearing-off motor fluctuations and peak dose dyskinesia. The was treated with levodopa in a dose of 5 × 200 mg (preparation of levodopa with benserazide) as a monotherapy. Due to the worsening availability of the drug used so far in pharmacies, it was changed to a preparation containing levodopa and carbidopa, while maintaining the same dose of levodopa. During the next visit, the patient reported that the change of the formulation had a beneficial effect in the form of a slight but significant reduction in the incidence and severity of peak dose dyskinesia. Pharmacokinetic studies showed that the mean maximum concentration of levodopa after administration of levodopa + benserazide was significantly higher than after administration of levodopa + carbidopa. The preparation containing benserazide caused a rapid increase and then a rapid decrease of the lewodopa plasma concentration. When levodopa was combined with carbidopa, the concentration of levodopa increased and decreased slowly. The results of these pharmacokinetic studies may explain the patient’s observation of the amelioration of peak dose dyskinesia after switching from a levodopa + benserazide formulation to a levodopa + carbidopa combination.

Background. In 2008, the Movement Disorders Society published the Unified Dyskinesia Rating Scale (UDysRS). This has become the established tool for assessing the severity and disability associated with dyskinesia in patients with Parkinson’s Disease (PD). We translated and validated the Polish version of the UDysRS, explored its dimensionality, and compared it to the Spanish version, which is the Reference Standard for UDysRS translations. Material and methods. The UDysRS was translated into Polish by a team led by JS and GO. The back-translation, completed by colleagues fluent in both Polish and English who were not involved in the original translation, was reviewed and approved by the Executive Committee of the MDS Rating Scales Programme. Then the translated version of the UDysRS underwent cognitive pretesting, and the translation was modified based on the results. The approved version was considered to be the Official Working Document of the Polish UDysRS and was tested on 250 Polish PD patients recruited at movement disorder centres. Data was compared to the Reference Standard used for validating UDysRS translations. Results. The overall factor structure of the Polish version was consistent with that of the Reference Standard version, as evidenced by the high Confirmatory Fit Index score (CFI = 0.98). The Polish UDysRS was thus confirmed to share a common factor structure with the Reference Standard. Conclusions. The Official Polish UDysRS translation is recommended for use in clinical and research settings. Worldwide use of uniform rating measures offers a common ground to study similarities and differences in disease manifestations and progression across cultures.

Neurotoksyna botulinowa typu A (BoNT-A, botulinum neurotoxin type A ) jest od 30 lat stosowana w leczeniu dystonii ogniskowych i segmentalnych. W tym czasie ewoluowaly poglądy na temat leczenia oraz przybylo wiele nowych publikacji. Szczegolna zmiana dotyczy dystonii szyjnej. Wprowadzenie dekade temu koncepcji collum-caput (Col-Cap) spowodowalo zmiane paradygmatu leczenia tej postaci dystonii ogniskowej, a takze rozwiniecie metod podawania leku pod kontrolą ultrasonografii. Obecnie w Polsce są dostepne trzy preparaty BoNT-A. Nazwy uznane przez amerykanską Agencje ds. Żywności i Lekow oraz nazwy handlowe preparatow to odpowiednio: onabotulinumtoxinA : Botox ® , abobotulinumtoxinA : Dysport ® , incobotulinum toxinA : Xeomin ® . Są to leki o zroznicowanych charakterystykach produktu leczniczego i zakresie wskazan klinicznych oraz dawkowania. Leczenie dystonii w Polsce odbywa sie w ramach programu lekowego i jest w pelni refundowane. Wiedza na temat rozpoznawania dystonii oraz mozliwości jej leczenia poglebila sie w ostatnim czasie, ale chorzy nadal dośc dlugo czekają na ustalenie diagnozy i wlączenie do leczenia. Celem niniejszych rekomendacji jest przegląd aktualnej wiedzy na temat leczenia dystonii ogniskowych oraz polowiczego kurczu twarzy za pomocą iniekcji BoNT-A.

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 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.

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.

Background. In 2008, the Movement Disorders Society (MDS) published a new Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson’s Disease (PD). We have translated and validated the Polish version of the MDS-UPDRS, explored its dimensionality, and compared it to the original English one. Methods. The MDS-UPDRS was translated into Polish by a team of Polish investigators led by JS and GO. The back-translation was completed by colleagues fluent in both languages (Polish and English) who were not involved in the original translation, and was reviewed by members of the MDS Rating Scales Programme. Then the translated version of the MDS-UPDRS underwent cognitive pretesting, and the translation was modified based on the results. The final translation was approved as the Official Working Document of the MDS-UPDRS Polish version, and was tested on 355 Polish PD patients recruited at movement disorders centres all over Poland (at Katowice, Gdansk, Łodź, Warsaw, Wroclaw, and Krakow). Confirmatory and explanatory factor analyses were applied to determine whether the factor structure of the English version could be confirmed in the Polish version. Results. The Polish version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Polish version was satisfactory. In the confirmatory factor analysis, all four parts had greater than 0.90 comparative fit index (CFI) compared to the original English MDS-UPDRS. Explanatory factor analysis suggested that the Polish version differed from the English version only within an acceptable range. Conclusions and clinical implications. The Polish version of the MDS-UPDRS meets the requirements to be designated as the Official Polish Version of the MDS-UPDRS, and is available on the MDS web page. We strongly recommend using the MDS-UPDRS instead of the UPDRS for research purposes and in everyday clinical practice.

Objectives: The aim of the paper was to: (1) evaluate the effectiveness of the physiotherapeutic program in writer’s cramp, (2) compare the brain activity while writing in patients with writer’s cramp and in healthy controls, (3) compare the brain activity of subjects with writer’s cramp before and after the physiotherapy. Material and methods: Nine patients with diagnosed writer’s cramp and nine age-matched healthy controls were studied. The functional magnetic resonance imaging while writing was performed in the writer’s cramp subjects and in the controls. The patients with writer’s cramp participated in a 3-week therapeutic program of individualised exercises in combination with the immobilisation of the affected limb. The functional magnetic resonance imaging was repeated after completing the therapeutic program. Results: Only the results of the coil drawing test significantly improved after completing the therapeutic program. All other clinical tests did not reveal any significant changes after the therapy. Activation of primary motor cortex, premotor cortex and primary sensory cortex was observed while writing in the subjects with writer’s cramp and in the controls. Brain activation in clusters located in the areas BA4, BA7, BA18 and BA37 was more pronounced in the writer’s cramp group. Individual analysis revealed a significantly increased activation of the cerebellum in the writer’s cramp patients and it decreased after physiotherapy. Conclusion: In the writer’s cramp subjects, functional magnetic resonance imaging revealed increased – when compared to the controls – activity of several brain structures while writing. This activity was modified by individualised physiotherapeutic program.

Objectives: The purpose of our study was to determine the probability of developing Parkinson’s disease in various syndromes of isolated tremor. Material and methods: We performed a retrospective analysis of the diagnostic process in patients with isolated upper limb tremor where single-photon emission computed tomography (SPECT)-DaTSCAN was performed. Twenty-four consecutive subjects (9 males, 15 females) with isolated tremor of one or both upper limbs were studied. The patients were referred for SPECT by neurologists from various centres. Cases of diagnosed structural, metabolic or druginduced tremor were not included in the study. All patients were examined by a movement disorder specialist before and 1–3 years after SPECT-DaTSCAN. All subjects were classified according to the Consensus Statement on the Classification of Tremors (2018). Results: The lowest probability of developing Parkinson’s disease was found in patients with rest and action (postural and kinetic) tremor, both unilateral and bilateral. The risk was also low in subjects with postural and kinetic tremor. In cases of a combination of rest and postural tremor (both unilateral and bilateral), the likelihood of neurodegenerative parkinsonism was high. Conclusion: Performing SPECT-DaTSCAN in selected cases of isolated of tremor with a high probability of Parkinson’s disease avoids the unnecessary use of drugs recommended in the therapeutic algorithms applicable in essential tremor.

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.

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.

International audience; 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.

International audience; Combination of DFT calculations and solid-state temperature-dependent infrared spectroscopy has confirmed that the central core of recently developed bipyrimidine-based mesogens is not flat, i.e. do not adopt a disc shape, inside the columnar liquid-crystalline phase. For this purpose, the intensities and the frequency shifts of the most sensitive C–N and C–C bands of the central bipyrimidine core have been studied as a function of the temperature and of the dihedral angle. The results support the reported packing model in which the molecules are interdigitated alternatively along their long axis and their short axis to form columns inside the mesophase.

Graphene oxide (GO) was modified by two modified porphyrins (THPP and TCPP) to formGO–porphyrin hybrids. Spectroscopic measurements demonstrated the formation of stablesupramolecular aggregates when mixing two components in solution. The Fouriertransform infrared (FTIR) and Raman scattering measurements confirm π-stackingbetween hydrophobic regions of GO nanoflakes and porphyrin molecules. An interesting interplay between modifiers andthe surface of GO leads to a significant change in electronic structure and magneticproperties of the designed hybrid materials. Based on the selection of molecularcounterpart 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.

Graphene oxide (GO) was modified by two modified porphyrins (THPP and TCPP) to form GO&ndash, 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 &pi, 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 &pi, 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.

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.

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.

10.1016/j.toxicon.2018.11.209

Objective: SIAXI (NCT02091739), a pivotal double-blind, randomised, placebo-controlled study with an extension period (EP), assessed the efficacy and safety of incobotulinumtoxinA 75 or 100 U in patients with sialorrhea due to Parkinson's disease (PD), atypical parkinsonism, stroke or traumatic brain injury. This subgroup analysis assessed the impact of injection guidance technique. Background: Literature suggests that ultrasound (US) guidance of botulinum neurotoxin injections, especially into the submandibular glands, may be needed to improve efficacy and safety. Methods: Patients were randomized (2:2:1) to incobotulinumtoxinA 75 or 100 U, or placebo, distributed in bilateral parotid and submandibular glands in a single injection cycle (IC) in the main period (MP). All eligible patients completing the MP received three further incobotulinumtoxinA ICs (75 or 100 U; each 16+/-2 weeks) in the EP. Injections were consistently guided by US or anatomical landmarks (AL) at investigators' discretion. Outcomes included unstimulated salivary flow rate (uSFR) and patients' Global Impression of Change Scale (GICS). The incidence of adverse events (AEs) was reported. Results: 184 patients were randomised and received either incobotulinumtoxinA 75 U (n=74) or 100 U (n=74), or placebo (n=36) in the MP; 173 completed the MP and entered the EP. In the MP, injections were guided by US in 56.5% of patients and by AL in 43.5%. Among patients treated with incobotulinumtoxinA in all 4 ICs, with US and AL guidance mean uSFR decreased with 75 U and 100 U from study baseline to 4 weeks post-injection, (mean [SD] change from study baseline to end of study: US, -0.15 [0.20] and -0.17 [0.25]; AL, -0.19 [0.22] and -0.17 [0.20]). Patients' GICS also showed improvement at 4 weeks post-injection with both US and AL guidance. The incidence of AEs over all ICs with incobotulinumtoxinA treatment was similar with US and AL guidance (67.0% and 61.0%). The most frequent treatment-related AEs were dry mouth (10.7% and 6.5%) and dysphagia (3.9% and 2.6%). No new safety concerns with respect to guidance technique were reported. Conclusions: In contrast to current literature, repeated incobotulinumtoxinA injections under either US or AL guidance are similarly effective and well tolerated for sialorrhea in patients with PD or other neurological disorders.

Objective Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. Methods The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. Results Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p Conclusion Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE.

An effective method for the synthesis of novel adenine amides was developed and successfully implemented, leading to 4-propyloxy-N-(9H-purin-6-yl)benzamide (1) and 4-dodecyloxy-N-(9H-purin-6-yl)benzamide (2). The compounds were fully characterised by means of spectroscopic (1H NMR, 13C NMR, FT-IR) and thermal (TG, DSC) analysis. The crystallographic analysis revealed that the formation of supramolecular chains relies on hydrogen bonding between amide functionalities. All supramolecular synthons found in the crystal structure of 1 were confirmed with the temperature-dependent IR method. The temperature-dependent IR method is useful in determining supramolecular interactions for compound 2, for which the crystal structure could not be obtained. A detailed analysis of temperature-dependent FT-IR spectra was used for the first time to identify the hydrogen bonds that exist in the solid state of our compounds; it can therefore be considered a promising method for the pattern recognition of hydrogen bonding in ...

iWe 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./i.

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).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.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 distributionOn 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.

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.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.We describe a Polish family with a novel heterozygous substitution: c.167AG (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.Our findings strongly suggest the role of other genetic factors or environmental triggers in the pathogenesis of dystonia related to mutations in THAP1 gene.

The paper deals with thermodynamic and spectroscopic characterization of Langmuir layers of phthalocyanines substituted with different peripheral groups: copper(II) 2,9,16,23-tetra-tert-butyl-29H,31H-phthalocyanine, copper(II) 2,3,9,10,16,17,23,24-octakis(octyloxy)-29H,31H-phthalocyanine, copper(II) tetrakis(4-cumylphenoxy)phthalocyanine. The isotherms, compressibility and stability of the Langmuir layers are investigated. Molecular arrangement of the molecular skeleton on water substrate is also evaluated. The essential influence of the substituents attached to the phthalocyanine macroring on dye thermodynamic properties is shown. The in-situ absorption of the phthalocyanine monolayers and electronic absorption spectra of dye solution in chloroform support existence of aggregates which architecture depends on the dye molecular structure.

Introduction: Intractable sialorrhea results from various causes, including Parkinson's disease (PD). The pivotal, double-blind, randomized, Phase 3 SIAXI study (NCT02091739) assessed the efficacy and safety of incobotulinumtoxinA (botulinum neurotoxin type A [BoNT-A] free from complexing proteins) 75 U and 100 U for the treatment of sialorrhea. Methods: Adults included in the main phase (MP) had chronic, troublesome sialorrhea due to PD, atypical Parkinsonism, stroke, or traumatic brain injury (TBI) and were randomized (2:2:1) to a single injection cycle (16±2 weeks) of incobotulinumtoxinA 75 U or 100 U, or placebo (PBO) distributed in bilateral parotid and submandibular glands (dose ratio of 3:2). Co-primary endpoints were change in unstimulated salivary flow rate (uSFR) and subjects' Global Impression of Change Scale (GICS) at Week 4. Safety was also assessed. Results: One hundred eighty-four subjects were randomized to either incobotulinumtoxinA 75 U (n=74), 100 U (n=74), or PBO (n=36) in the MP. Primary drooling etiologies were: PD (70.7%), atypical Parkinsonism (8.7%), stroke (17.9%), and TBI (2.7%). Injection was guided by anatomic landmarks in 39.2%, 44.6%, and 50.0%, and ultrasonography in 60.8%, 55.4%, and 50.0% of subjects in the incobotulinumtoxinA 75 U, 100 U, and PBO groups, respectively. At week 4, incobotulinumtoxinA 100 U significantly improved uSFR, and subjects' GICS scores were significantly higher vs PBO (both, P

Both disease progression and pulsatile stimulation of dopaminergic receptors are responsible for development of fluctuations and dyskinesia in about 50% of patients with Parkinson disease (PD) after 4-6 years of therapy with levodopa. In order to prevent motor complications, the ideal therapy should secure continuous dopaminergic stimulation (CDS). The concept of CDS is supported by the results of both experimental and clinical studies. Several treatment options are available to achieve CDS. Dopamine agonists have a longer half-life than levodopa and the development of dyskinesia is delayed when they are used as monotherapy in early PD. Continuous delivery of agonists can be improved with prolonged-release oral preparations, a transdermal delivery system or continuous subcutaneous infusion. Continuous enteral infusion of levodopa is another way to achieve CDS and it is very effective in reducing motor complications in advanced PD.

Medical treatment of advanced Parkinson disease complicated with fluctuations and dyskinesias remains difficult or in some patients totally ineffective. Recently, new methods were introduced to manage those problems: deep brain stimulation, subcutaneous apomorphine infusion and the Duodopa system for intrajejunal continuous delivery of gel containing levo-dopa/carbidopa (through percutaneous gastrostomy). This last method was proven to be very effective in reducing the fluctuations of levodopa plasma levels and furthermore in reducing the off periods and dyskinesias. The Duodopa system is used in patients with contraindications to deep brain stimulation or apomorphine infusions. According to recently published studies, it may also be more effective in reducing motor complications than other methods. The authors present the current knowledge on the Duodopa system, its effectiveness (also in relationship to other methods, specially deep brain stimulation and apomorphine) and possible complications (mostly due to gastric tube failures) along with the indications and contraindications.

The goal of the article is to collect and discuss spectral data for the dyads and reference molecules in the large spectral range, using various methods of investigations. We present information on change of configurations, electronic and vibrational properties of both parts of the dyads after their formation, and their possible relationship with electron transfer mechanism. From the conformational and spectral investigations, a strong correlation between the molecular structure of investigated species and their electronic as well as vibrational spectra arises. It testifies a significant redistribution of the charges upon the covalent linkage of a dyad.

The paper deals with IR absorption and reflection–absorption examinations of Langmuir–Blodgett layers of zinc porphyrins covalently linked to fullerene C 60 . The spectra were recorded with unpolarized and polarized light (p-polarization and s-polarization) at various incident angles to receive data on interactions of the systems with the solid substrates and on orientation of the systems with respect to the solid substrate. A comparison of the calculated and experimental IR absorption data were discussed in terms of the normal modes assigned for the porphyrins. All alternations in the shape or localization of the absorption bands represented normal modes after porphyrin oligomer or porphyrin–fullerene dyad formation reflect the changes of the charge density distribution and configuration of the bonded molecular moieties. We have shown that the polarized reflection–absorption spectra of thin films are strongly dependent on the light polarization. However, the reflection–absorption spectra of LB films of the porphyrin, porphyrin oligomer and their dyads with fullerene recorded with unpolarized light approximate the absorption spectra of adequate compounds dispersed in KBr matrix. A similarity between the p-polarized and unpolarized spectra suggests that both porphyrins and dyads are nearly perpendicularly oriented to the surface of the gold substrate.

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.

We report easy preparation of recently discovered highly chlorinated fullerenes Th–C60Cl24, C1–C60Cl28, and D3d–C60Cl30 in high-temperature reactions of C60 with PCl5 and ICl. Formation and interconversion of chlorofullerenes was investigated in details for C60–ICl system. C60Cl28 is the least stable chlorofullerene that undergoes rearrangement (accompanied by partial chlorine elimination) into more stable Th-C60Cl24 under more drastic reaction conditions (increased temperature and time of chlorination). Th-C60Cl24 yields D3d–C60Cl30 at temperatures above 220 °C via a sequence of rearrangements and further addition of chlorine. In contrast to the fullerene reaction with ICl, interaction of C60 with PCl5 is very selective with respect to formation of C60Cl24 in a wide temperature range. Solid-state electronic (UV–Vis) and vibrational (IR) spectra of chlorinated fullerenes C60Cl24, C60Cl28, C60Cl30 and fluorinated fullerenes C60F18 and C60F36 were recorded in the spectral range between 30 and 45,000 cm−1. Raman spectra were also acquired for all investigated compounds. Moreover, molecular geometry of the C60Cl24 and its theoretical IR-absorption spectrum were calculated using B3LYP/STO-3G chemistry model.

The unique shape and physical properties of the fullerene C 60 , makes it a good candidate for preparation of large aggregates with organic chromophores such as porphyrins or perylenediimides. In order to provide information on structural and electronic properties of selected C 60 -organic chromophore systems, we have performed conformational and spectral investigations of selected monomers and dyads. The correlation between the structure of the molecular systems and their spectral properties has been found.

Electronic absorption, fluorescence, photothermal and vibrational spectra of several fullerene-porphyrin dyads have been investigated. Thermal deactivation of porphyrin moieties are markedly influenced by fullerene. Participation of the excited singlet states in thermal relaxation in fullerene-porphyrin dyads is evident although the contribution of the triplet states cannot be excluded. Our experiments show the existence of a fullerene-porphyrin excimer created from the porphyrin second excited state. The observed differences in spectroscopic properties are discussed in terms of strong interaction between fullerene and porphyrins in dyads.

Current antispastic medications are unsatisfactory for spasticity treatment, but botulinum toxin type A (BTX-A) shows promise as a new therapeutic option. This open-label, prospective study aimed to assess the effectiveness of BTX-A in improving functional mobility in the early post-stroke population using an individualised, flexible range of doses and targeted muscle groups. Twenty-one stroke patients (13 male, 8 female) were enrolled and injected with BTX-A (Botox, Allergan, mean dose: 255 U; range: 185-300) according to individual spasticity patterns. Assessments were made at baseline and weeks 2, 4, 6, 10 and 16 post-treatment. Outcome measures comprised: Modified Ashworth Scale (MAS), finger flexion scale (Bhakta), MRC scale, Physician's Rating Scale (PRS), Nine Hole Peg Test (9HPT), Motor Assessment Scale, Clinical Global Impression (CGI), Global Assessment of Spasticity (GASS) and Visual Analogue Scale (VAS) for pain assessment. Statistically significant improvements in muscle tone as determined by the MAS were found in all areas (except arm) till week 16 (p