Serum heat shock protein 70 levels as a biomarker for inflammatory processes in multiple sclerosis.

BACKGROUND: Inflammatory and neurodegenerative processes are hallmarks of multiple sclerosis (MS). The synthesis of the major stress-inducible heat shock protein 70 (Hsp70) is induced by inflammation. OBJECTIVE: The purpose of this study is to determine whether Hsp70 in serum can serve as a potential biomarker to distinguish inflammatory and neurodegenerative processes in MS. METHODS: Serum was obtained from 94 patients: 26 clinically isolated syndrome (CIS), 40 relapsing-remitting MS (RRMS), 19 secondary progressive MS (SPMS), and nine primary progressive MS (PPMS). As controls, serum samples were collected from patients with non-inflammatory neurological diseases (NINDs, n = 41), other inflammatory neurological diseases (OINDs, n = 28) and healthy donors (HDs, n = 114). Serum levels of Hsp70 were quantified using the enzyme-linked immunosorbent assay detecting free and liposomal Hsp70 (lipHsp70 ELISA). RESULTS: Patients with MS displayed significantly higher Hsp70 serum levels than HDs (p < 0.001) and significantly lower levels than OINDs (p = 0.001). A subgroup analysis revealed that Hsp70 serum levels of CIS/RRMS patients are significantly higher than those of patients with progressive MS (SPMS/PPMS) (p < 0.05). CONCLUSION: Inflammation causes the release of Hsp70 into the blood. As CIS/RRMS are associated with higher Hsp70 serum levels than progressive MS, serum Hsp70 levels might provide a marker for inflammatory processes.

White matter integrity of premotor-motor connections is associated with motor output in chronic stroke patients.

Corticocortical functional interactions between the primary motor cortex (M1) and secondary motor areas, such as the dorsal (PMd) and ventral (PMv) premotor cortices and the supplementary motor area (SMA) are relevant for residual motor output after subcortical stroke. We hypothesized that the microstructural integrity of the underlying white matter tracts also plays a role in preserved motor output. Using diffusion-tensor imaging we aimed at (i) reconstructing individual probable intrahemispheric connections between M1 and the three secondary areas (PMd, PMv, SMA) and (ii) examining the extent to which the tract-related microstructural integrity correlates with residual motor output. The microstructural integrity of the tract connecting ipsilesional M1 and PMd was significantly associated with motor output (R = 0.78, P = 0.02). The present results support the view that ipsilesional secondary motor areas such as the PMd might support M1 via corticocortical connections to generate motor output after stroke.

Development of movement-related intracortical inhibition in acute to chronic subcortical stroke.

OBJECTIVE: A prospective longitudinal cohort study in stroke patients was performed to better understand the role of γ-aminobutyric acid-dependent intracortical inhibition (ICI) for recovery after stroke. METHODS: Patients with acute first-ever subcortical stroke and hand paresis were recruited, and motor function as well as ICI were measured up to 1 year after stroke. Motor recovery was defined as the change in hand motor function from the acute to the chronic stage (Δ = recovery over 1 year). Primary outcome measures for hand motor function were the recovery of grip strength (ΔGS) and finger-tapping speed (ΔFT). Using double-pulse transcranial magnetic stimulation, we studied ICI in the ipsilesional primary motor cortex during the preparation of a movement with the paretic hand at different time points during recovery (first week, 7 weeks, 3 months, and 1 year after stroke). RESULTS: Eleven patients were enrolled (mean age 62.9 ± 3.8 years). The results of a multiple regression analysis showed a significant association of movement-related ICI in the acute stage only (first week) with motor recovery over 1 year (ΔGS: R(2) = 0.75, F = 17.6, p = 0.006; ΔFT: R(2) = 0.55, F = 7.3, p = 0.035). More disinhibition of ICI in the acute phase of stroke predicted more improvement in ΔGS (ß = -0.86, p = 0.006) and ΔFT (ß = -0.74, p = 0.035), independent of the initial motor deficit. CONCLUSIONS: Movement-related ICI one week after a subcortical stroke is associated with better outcome of hand motor function. Disinhibition in the ipsilesional primary motor cortex could be a mechanism of how the brain attempts to promote motor recovery after stroke.