Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers.

The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6 years (SCA1 +) aged 27.8 ± 8.1 years; 12 with expected disease onset > 6 years (SCA1-) aged 26.6 ± 3.1 years and 26 age and sex matched healthy controls (HCs) underwent static posturography during 5 years of observation. The movements of the centre of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were quantified by calculating the mean radius (R), developed surface area (A) and mean COP movement velocity (V). Ataxia was evaluated by use of the Scale for Assessment and Rating of Ataxia (SARA).SCA1 + exhibited significantly worse quality of stance with EC vs. SCA1- (p < 0.05 for V) and HCs (p < 0.001) even 5 to 6 years before estimated disease onset. There were no statistically significant differences between SCA1- and HCs. A slow increase in Cohen's d effect size was observed for VEO up to the clinical manifestation of ataxia. VEO and AEC recorded in preclinical SCA1 individuals correlated slightly but statistically significantly with SARA (r = 0.47).The study confirms that static posturography detects COP sway changes in SCA1 preclinical gene carriers even 5 to 6 years before estimated disease onset. The quantitative evaluation of stance in preclinical SCA is a sensitive biomarker for the monitoring of the disease progression and may be useful in clinical trials.

Functional Characteristics of the Nav1.1 p.Arg1596Cys Mutation Associated with Varying Severity of Epilepsy Phenotypes.

Mutations of the SCN1A gene, which encodes the voltage-dependent Na+ channel's α subunit, are associated with diverse epileptic syndromes ranging in severity, even intra-family, from febrile seizures to epileptic encephalopathy. The underlying cause of this variability is unknown, suggesting the involvement of additional factors. The aim of our study was to describe the properties of mutated channels and investigate genetic causes for clinical syndromes' variability in the family of five SCN1A gene p.Arg1596Cys mutation carriers. The analysis of additional genetic factors influencing SCN1A-associated phenotypes was conducted through exome sequencing (WES). To assess the impact of mutations, we used patch clamp analysis of mutated channels expressed in HEK cells and in vivo neural excitability studies (NESs). In cells expressing the mutant channel, sodium currents were reduced. NESs indicated increased excitability of peripheral motor neurons in mutation carriers. WES showed the absence of non-SCA1 pathogenic variants that could be causative of disease in the family. Variants of uncertain significance in three genes, as potential modifiers of the most severe phenotype, were identified. The p.Arg1596Cys substitution inhibits channel function, affecting steady-state inactivation kinetics. Its clinical manifestations involve not only epileptic symptoms but also increased excitability of peripheral motor fibers. The role of Nav1.1 in excitatory neurons cannot be ruled out as a significant factor of the clinical phenotype.

Impact of one HF-rTMS session over the DLPFC and motor cortex on acute hormone dynamics and emotional state in healthy adults: a sham-controlled pilot study.

Studies indicate that high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) can lower cortisol concentration or output, with some evidence suggesting a link to testosterone. Together, these stress and social hormones might help regulate the emotional response to HF-rTMS. This pilot study evaluated the effect of HF-rTMS on acute testosterone and cortisol dynamics and emotional state in eleven healthy adults. Using a sham-controlled, single-blind, crossover design, participants completed a HF-rTMS session targeting the dorsolateral prefrontal cortex (DLPFC) and motor cortex on separate days. Stimulation (250 total pulses) was applied at 90% of the resting motor threshold. Salivary testosterone and cortisol, mood, motivation, anxiety, and heart rate (HR) were assessed before (T1) and 1 (T2), 15 (T3), and 30 min (T4) after each session. There were no significant session differences in testosterone and cortisol concentration, mood, motivation, and HR. Although DLPFC stimulation produced less anxiety (vs. motor cortex), and testosterone output was stable across both treatments (vs. sham-related decline in testosterone), neither differed from the sham. Within-person fluctuations in testosterone, mood, motivation, and/or anxiety were significantly related across the DLPFC and motor cortex trials only. In conclusion, a single sub-maximal session of HF-rTMS did not affect the hormonal, emotional, or physiological state of healthy adults, relative to a sham. However, the emergence of stimulation-specific testosterone and/or emotional linkages suggests that the repeated effects of HF-rTMS may also manifest at the individual level. This offers another pathway to explain the therapeutic efficacy of rTMS and a model to explore interindividual variability in health-related outcomes.

Reduced Expression of PD-1 in Circulating CD4+ and CD8+ Tregs Is an Early Feature of RRMS.

Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing-remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers-CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103-on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-γ, IL-17, IL-17F, TGFß-1, TGFß-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control.

Dose escalation study of targeted alpha therapy with [225Ac]Ac-DOTA-substance P in recurrence glioblastoma - safety and efficacy.

Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [225Ac]Ac-DOTA-SP therapy. MATERIAL AND METHODS: A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1-6 doses of [225Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging. RESULTS: Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [225Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [225Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [225Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups. CONCLUSIONS: Treatment of recurrent glioblastoma with [225Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.

The prevalence of depressive and anxiety symptoms in Polish epilepsy patients - The context of pharmaco-resistance.

PURPOSE: Patients with epilepsy (PWE) are at a higher risk of experiencing depressive and anxiety symptoms than the general population; these symptoms are more prevalent in patients with drug-resistant epilepsy (DRE) compared to those with non-drug-resistant epilepsy (NDRE). The aim of the present study was to compare the level of reported depressive and anxiety symptoms in patients with DRE and patients with NDRE and to examine the relationships between demographic and epilepsy-related variables and severity of depression and anxiety symptoms. MATERIAL AND METHODS: A total of 193 adult PWE, divided into a DRE group (n = 87), and an NDRE group (n = 106), completed the Beck Depression Inventory (BDI) and the Stat-Trait Anxiety Inventory (STAI-Sand STAI-T). Data analysis included sociodemographic and disease-related variables such as the type of epilepsy syndrome, age at onset of disease, and duration of the disease. RESULTS: The DRE group presented a higher score of BDI than the NDRE group (p = 0.04). Age correlated with the score of STAI-S in the NDRE group (r = 0.22). Sex was the only significant predictor of the score of STAI-T in the NDRE group. Men from the DRE group presented higher scores in BDI, STAI-S, and STA-T compared with the NDRE group. CONCLUSIONS: Patients with DRE reported more severe depressive symptoms than patients with NDRE. In NDRE patients, the level of anxiety, considered as a state, was correlated with age. Sex was a significant predictor of the level of anxiety in DRE patients. Pharmaco-resistance was significantly associated with severity of depression and anxiety in male patients.

Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma.

Treatment options for recurrent glioblastoma multiforme (GBM) are very limited. GBM cells express high levels of the GPCR neurokinin type 1 receptor (NK-1R), and a modified substance P can be used as its ligand for the tumor cell targeting. Targeted alpha therapy with DOTA-Substance P labeled with the short range alpha emitter 213Bi allows for selective irradiation and killing of tumor cells. MATERIAL AND METHODS: Twenty patients with recurrent GBM were included into the study following a standard therapy. 1-2 intracavitary or intratumoral port-a-cath systems were stereotactically inserted. Patients were treated with 1-7 doses of 213Bi-DOTA-Substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-Substance P (68Ga-DOTA-SP) was co-injected with 213Bi-DOTA-SP to assess the biodistribution using PET/CT. Therapeutic response was monitored with performance status and MRI imaging. RESULTS: Treatment with activity up to 11.2 GBq 213Bi-DOTA-SP was well tolerated with only mild and transient adverse reactions. The median progression free survival was 2.7 months. The median overall survival from the first diagnosis was 23.6 months and median survival after recurrence was 10.9 months. The median survival time from the start of 213Bi-DOTA-SP was 7.5 months. CONCLUSIONS: Treatment of recurrent GBM with 213Bi-DOTA-SP is safe and well tolerated. The median overall survival after recurrence of 10.9 months compares favorably to the available alternative treatment options. Once the supply of high activity 225Ac/213Bi radionuclide generators is secured, targeted alpha therapy with 213Bi-DOTA-SP may evolve as a promising novel option to treat recurrent GBM.

Prediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia.

BACKGROUND: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. OBJECTIVE: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. METHODS: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. RESULTS: Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18-1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12-1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19-1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11-1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: "severe" (n = 13; 12%), "intermediate" (n = 31; 29%), and "moderate" (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. CONCLUSION: Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society.

Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with 213Bi-substance P analogue.

BACKGROUND: Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures. MATERIAL AND METHODS: Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1-6 doses of 0.9-2.3 GBq 213Bi- DOTA-[Thi8,Met(O2)11]-substance P (213Bi-DOTA-SP) in 2-month intervals. 68Ga-DOTA-[Thi8,Met(O2)11]-substance P (68Ga-DOTA-SP) was co-injected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI. RESULTS: Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 213Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy. CONCLUSIONS: Targeted alpha therapy of secondary GBM with 213Bi-DOTA-SP is safe and well tolerated and may evolve as a promising novel therapeutic option for secondary GBM.

Enzymatic replacement therapy in patients with late-onset Pompe disease - 6-Year follow up.

INTRODUCTION: Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy, affecting skeletal muscles, which, if untreated, leads to disability and/or respiratory failure. The enzyme replacement therapy (ERT) improves muscle strength and respiratory function and prevents disease progression. We present a 6-year follow-up of 5 patients with LOPD treated with ERT. METHODS: Five patients with LOPD received ERT: two started treatment in 2008, other two in 2010 and one in 2011. All patients received recombinant human alpha-glucosidase in dose 20mg/kg intravenously every two weeks. Physical performance was assessed in 6-minute walk test (6MWT) and spirometry was performed to examine FVC and FEV1. Liver enzymes, CK levels were also assessed. RESULTS: The walking distance in 6MWT increased by average 16.9±2.26% in the first three years of treatment. Similar changes were detected in spirometry: the most significant FVC increase was observed in two patients with the highest FVC values before treatment, which increased to normal values adjusted for age and sex in three years of treatment, that is by 28% and 34%. In two other patients FVC reached 88% and 76% of predicted values. ERT also improved the liver and muscle enzymes levels. CONCLUSION: The improvements of exercise tolerance and FVC were observed in all patients in the first three years of treatment and were the most pronounced in the longest-treated patients and with the least severe neurological and respiratory symptoms. Our research suggests that early start of the ERT results in higher improvement of respiratory and ambulation functions.

An unusual presentation of Listeria monocytogenes rhombencephalitis.

We describe a case of 52-year-old woman with a medical history of Crohn's disease presented abrupt fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem. The patient was initially diagnosed with ischaemic stroke, because of acute clinical course and results of neuroimaging. Cerebrospinal fluid analysis revealed mild infection with negative Gram staining and culture. Final diagnosis of Listeria monocytogenes brainstem infection (rhombencephalitis) was set up on the basis of further clinical course and positive blood cultures. Listerial rhombencephalitis should be kept in mind in immunocompromised adult patients who develop fever, asymmetrical multiple cranial nerve palsies and focal neurological symptoms localized to the brainstem even without typical neuroimaging, cerebrospinal fluid findings and negative cultures. Early diagnosis and adequate antibiotic treatment is of crucial importance.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Development of a method based on ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for studying the in vitro metabolism of phosphorothioate oligonucleotides.

Ultra high performance liquid chromatography hyphenated with quadrupole time-of-flight mass spectrometry was used to determine the products of the in vitro metabolism of phosphorothioate oligonucleotides. These compounds may be used during antisense therapy as synthetic fragments of genes. For this reason, both a sample preparation method and a qualification method were developed during this study. Liquid-liquid extraction, protein or oligonucleotide precipitation, and solid-phase extraction were tested and compared in order to select the method that yielded the highest recoveries. Ion pair chromatography was used for separation while mass spectrometry was applied for metabolite identification. The influence of the type of ion pair reagent used on the resolution and sensitivity was investigated. Results indicated that a mixture of 1,1,1,3,3,3-hexafluoro-2-propanol, N,N-dimethylbutylamine, and methanol was the best mobile phase for maximizing both of these parameters. The developed method was applied to investigate the compounds that form during the incubation of phosphorothioate oligonucleotides with human liver microsomes. Metabolites with short sequences were created after 8 hours, while oligonucleotides constructed from a large number of nucleotide units were obtained after 12 hours of incubation. Moreover, regardless of the length of the polynucleotide chain, metabolites were produced by the same mechanism: enzymatic cleavage at the 3' end of the sequence.

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

BACKGROUND: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. METHODS: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. RESULTS: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. CONCLUSIONS: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. CLINICALTRIALSGOV, NUMBER: NCT01037777 and NCT00136630 for the French patients.

[Cardiac abnormalities in patients with myotonic dystrophy--preliminary results]. / Zaburzenia kardiologiczne u pacjentów z dystrofia miotoniczna--doniesienie wstepne.

INTRODUCTION: Myotonic dystrophy (DM) is an inherited multisystem disorder associated with myotonia, progressive skeletal muscle weakness and atrophy, involvement of peripheral and central nervous system and sudden death likely due to atrioventricular block and/or ventricular arrhythmia. AIM OF THE STUDY: to assess the type and degree of cardiac and neurological involvement in patients (pts) with DM. MATERIALS AND METHODS: 10 pts (6 male), in mean age of 35 +/- 13 years, treated for DM type I (DM1)--7 pts and type II (DM2)--3 pts. All pts underwent a neurological examination including muscle strength assessment as well as cardiac diagnostics including: standard and 48-hour ambulatory electrocardiogram, echocardiographic examination, magnetic resonance imaging (MRI) of the heart and late potentials assessment. RESULTS: Muscle strength was moderately diminished (46-48 points in MRC sub score) in 3 pts with DM1 and mildly diminished (56-58 points in MRC sub score) in 2 pts with DM2. These patients showed clinical symptoms of myopathy. Cardiovascular examinations revealed: QRS duration above 110 ms in 5 pts, clinically significant supraventricular arrhythmia or atrioventricular block in 3 pts, focal myocardial fibrosis in 3 pts, asymmetric hypertrophy of inter-ventricular septum in 1 patient, presence of late potentials in 5 pts. We have not observed correlation between impaired muscle strength and cardiac abnormalities. However, most pronounced cardiac abnormalities were observed in 2 male DM1 patients with clinical symptoms of myopathy and lowest MRC score. At a mean follow up of 3.2 +/- 1.4 years none of the pts died. CONCLUSIONS: Cardiac involvement in pts with myotonic dystrophy is frequent and is characterized by phenotypic heterogeneity. Detection of cardiac abnormalities may require extensive diagnostics. The most important is the assessment of ECG. Cardiac and neurological abnormalities vary in intensity between patients without close relationship to each other.

Sexual dysfunctions and sexual quality of life in men with multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is one of the most frequent diseases of the central nervous system and usually occurs at the age when people would be expected to be in the prime of their sexual lives. Clinicians working in this field commonly concentrate on the classical neurological deficits and often overlook symptoms that seriously affect the quality of life, such as sexual dysfunction (SD). Sexual functioning of MS patients remains poorly understood. AIM: The aim of this study was to assess the prevalence of SDs, their relationship with demographic factors, and sexual quality of life in men with multiple sclerosis (MS). METHODS: Sixty-seven patients from the National Multiple Sclerosis Center were interviewed, completed the questionnaires, and underwent neurological assessment. MAIN OUTCOME MEASURES: Primary outcome measures included the International Index of Erectile Function (IIEF), the Sexual Quality of Life Questionnaire (SQoL), and the Expanded Disability Status Scale (EDSS). RESULTS: The most common complaints were erectile dysfunction (52.9%), decreased sexual desire (26.8%), and difficulties in reaching orgasm (23.1%) or ejaculation (17.9%). The severity of SD had a clear impact on sexual quality of life, especially in the domains of erectile function and intercourse satisfaction. However, neither IIEF nor SQoL scores were correlated with age, time since onset of MS symptoms, or EDSS scores. Only 6% of the patients had ever discussed their concerns with a medical professional or undergone sexual therapy. CONCLUSIONS: SD is highly prevalent but commonly overlooked in MS patients and has a significant impact on their sexual quality of life. The data support a multifactorial etiology of SD in MS. More focus on SD and use of appropriate screening tools in clinical practice with MS patients are recommended.

Correlates of sexual function in male and female patients with multiple sclerosis.

INTRODUCTION: Many factors have been suggested to contribute to sexual dysfunction (SD) in multiple sclerosis (MS) patients, but the research on their impact on sexual functioning (SF) and sexual quality of life (SQoL) remains scant. AIM: The aim of this study was to investigate correlates of SF and SQoL in MS patients, as well as possible gender differences. METHODS: 204 MS patients were interviewed, completed the questionnaires, and underwent neurological assessment. MAIN OUTCOME MEASURE: Primary outcome measures included the International Index of Erectile Function, the Female Sexual Function Questionnaire, the Sexual Quality of Life Questionnaire, the Beck Depression Inventory, and the Expanded Disability Status Scale. RESULTS: The course and duration of the disease did not predict patients' SF. Negative correlations were found for brainstem symptoms with orgasmic function and overall satisfaction in men and between cognitive functioning and the partner domain in women. Interestingly, brainstem symptoms correlated positively with the arousal domain in women. More than half (52.1%) of patients fulfilled Beck Depression Inventory criteria for depression, and these patients showed more SD than nondepressive individuals. The strongest negative correlations with depressive symptoms were found for desire, erectile function, and overall satisfaction with sexual life in men and for orgasm and sexual enjoyment in women. Deterioration in particular domains of SF was clearly related with diminished SQoL. The main gender difference was a strong influence of decreased desire on SQoL in women and no such correlation in men. Negative assessment of the relationship with partner significantly affected all domains of SF and SQoL in MS women and the desire domain in MS men. CONCLUSIONS: Several correlates of SF in MS patients were found. The role of brainstem symptoms needs further investigation. Clinicians should pay close attention to depressive symptoms and relationship factors in MS patients who suffer from SD.

Seroprevalence of Toxoplasma gondii and Borrelia burgdorferi infections in patients with multiple sclerosis in Poland.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that affects mainly young people. It is believed that the autoimmune process observed in the pathogenesis of MS is influenced by a complex interaction between genetic and environmental factors, including infectious agents. The results of this study suggest the protective role of Toxoplasma gondii infections in MS. Interestingly, high Toxoplasma IgM seropositivity in MS patients receiving immunomodulatory drugs (IMDs) was identified. On the other hand, Borrelia infections seem to be positively associated with MS. Although the interpretation of our results is limited by the retrospective nature of the studies, the results strongly indicate that further experimental and clinical studies are needed to explain the role of infectious agents in the development and pathophysiological mechanisms of MS.

Locoregional Treatment of Glioblastoma With Targeted α Therapy: [ 213 Bi]Bi-DOTA-Substance P Versus [ 225 Ac]Ac-DOTA-Substance P-Analysis of Influence Parameters.

BACKGROUND: Glioblastoma (GB) is the most malignant primary brain tumor. Therefore, introduction of new treatment options is critically important. The aim of this study was to assess local treatment with α emitters [ 213 Bi]Bi-DOTA-substance P (SP) and [ 225 Ac]Ac-DOTA-SP. METHODS: Treatment was performed as salvage therapy in patients with recurrent primary and secondary GB. [ 213 Bi]Bi-DOTA-SP with injected activity 1.85 GBq per cycle was used in 20 primary (48.2 ± 11.8 years old) and in 9 secondary (38.8 ± 10.8 years old) GB patients and [ 225 Ac]Ac-DOTA-SP in 15 primary (45.1 ± 9.9 years old) and in 6 secondary (37.8 ± 6.4 years old) GB patients with a dose escalation scheme (10, 20, and 30 MBq). RESULTS: Local treatment with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP was well tolerated with only few adverse effects. There was no statistically significant difference between [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP groups in survival parameters. For primary GB, survival parameters of patients treated with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP were as follows(in months): progression-free survival time, 2.7 versus 2.4; OS-d (overall survival from time of diagnosis to death from any cause), 23.6 versus 21.0; OS-t (overall survival from the start of treatment to death from any cause), 7.5 versus 5.0; and OS-r (overall survival from recurrence in primary tumors to death from any cause), 10.9 versus 12.0. Survival parameters of secondary GB patients treated with [ 213 Bi]Bi-DOTA-SP and [ 225 Ac]Ac-DOTA-SP were as follows (in months): progression-free survival time, 5.8 versus 2.4; OS-d, 52.3 versus 65.0; OS-t, 16.4 versus 16.0; and OS-c (overall survival from conversion into secondary GB multiforme to death from any cause), 18.4 versus 36.0. CONCLUSIONS: The similarity results of 213 Bi or 225 Ac may suggest that the local treatment of brain tumors can be greatly simplified. The experience to date shows that local radioisotope treatment of brain tumors requires further dosimetry studies, taking into account the complexity of biological processes.