Health-Related Quality of Life Outcomes from Botulinum Toxin Treatment in Spasticity.

OBJECTIVE: The effects of botulinum toxin injections (BoNT) on health-related quality of life along the complex spectrum of spasticity needs further characterization to guide practitioners in a real-life therapeutic environment. METHODS: In this study, we analyzed 50 consecutive and unselected patients with spasticity before and four weeks after re-injection of botulinum toxin. Health-related quality of life in terms of the EuroQol (EQ) as well as further motor and non-motor characteristics were assessed. RESULTS: BoNT improved the EQ visual analog scale (EQ VAS). In addition, state of health and pain maxima improved. The EQ VAS improvement correlated with pre-injection characteristics of the EQ VAS and life satisfaction in the "movement disorders" domain. CONCLUSION: EQ VAS is sensitive for monitoring HR-QoL outcomes in an unselected real life observational cohort. This study may inform future studies intended to validate prediction variables that could inform on HR-QoL effects of BoNT treatment in spasticity.

Long-Term Effect of GPi-DBS in a Patient With Generalized Dystonia Due to GLUT1 Deficiency Syndrome.

Treatment outcomes from pallidal deep brain stimulation are highly heterogeneous reflecting the phenotypic and etiologic spectrum of dystonia. Treatment stratification to neurostimulation therapy primarily relies on the phenotypic motor presentation; however, etiology including genetic factors are increasingly recognized as modifiers of treatment outcomes. Here, we describe a 53 year-old female patient with a progressive generalized dystonia since age 25. The patient underwent deep brain stimulation of the globus pallidus internus (GPi-DBS) at age 44. Since the clinical phenotype included mobile choreo-dystonic features, we expected favorable therapeutic outcome from GPi-DBS. Although mobile dystonia components were slightly improved in the long-term outcome from GPi-DBS the overall therapeutic response 9 years from implantation was limited when comparing "stimulation off" and "stimulation on" despite of proper electrode localization and sufficient stimulation programming. In order to further understand the reason for this limited motor symptom response, we aimed to clarify the etiology of generalized dystonia in this patient. Genetic testing identified a novel heterozygous pathogenic SLC2A1 mutation as cause of glucose transporter type 1 deficiency syndrome (GLUT1-DS). This case report presents the first outcome of GPi-DBS in a patient with GLUT1-DS, and suggests that genotype relations may increasingly complement phenotype-based therapy stratification of GPi-DBS in dystonia.

Bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells.

INTRODUCTION: Human mesenchymal stromal cells (MSCs) can be isolated from different sources including bone marrow and term placenta. These two populations display distinct patterns of proliferation and differentiation in vitro. Since proliferation and differentiation of cells are modulated by cell-matrix interactions, we investigated the attachment of MSCs to a set of peptide-coated surfaces and explored their interactions with peptides in suspension. METHODS: Human MSCs were isolated from bone marrow and term placenta and expanded. Binding of MSCs to peptides was investigated by a cell-attachment spot assay, by blocking experiments and flow cytometry. The integrin expression pattern was explored by a transcript array and corroborated by quantitative reverse transcription polymerase chain reaction and flow cytometry. RESULTS: Expanded placenta-derived MSCs (pMSCs) attached well to surfaces coated with fibronectin-derived peptides P7, P15, and P17, whereas bone marrow-derived MSCs (bmMSCs) attached to P7, but barely to P15 and P17. The binding of bmMSCs and pMSCs to the peptides was mediated by ß1 integrins. In suspension, expanded bmMSCs barely bind to P7, P13, P15, and less to P14 and P17. Ex vivo, bmMSCs failed to bind P7, but displayed a weak interaction with P13, P14, and P15. In suspension, expanded pMSCs displayed binding to many peptides, including P4, P7, P13, P14, P15, and P17. The differences observed in binding of bmMSCs and pMSCs to the peptides were associated with significant differences in expression of integrin α2-, α4-, and α6-chains. CONCLUSIONS: Human bmMSCs and pMSCs show distinct patterns of attachment to defined peptides and maintain differences in expression of integrins in vitro. Interactions of ex vivo bmMSCs with a given peptide yield different staining patterns compared to expanded bmMSCs in suspension. Attachment of expanded MSCs to peptides on surfaces is different from interactions of expanded MSCs with peptides in suspension. Studies designed to investigate the interactions of human MSCs with peptide-augmented scaffolds or peptides in suspension must therefore regard these differences in cell-peptide interactions.

GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson's Disease and Lewy Body Dementia.

Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson's disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders.