Non-invasive electrical brain stimulation for vision restoration after stroke: An exploratory randomized trial (REVIS).

BACKGROUND: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. OBJECTIVE: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. METHODS: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. RESULTS: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. CONCLUSIONS: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials.NCT01418820 (clinicaltrials.gov).

Catechol-O-methyltransferase polymorphism influences outcome after ischemic stroke: a prospective double-blind study.

BACKGROUND: To explore whether a polymorphism in dopamine metabolism influences the effectiveness of neurological rehabilitation and the outcome after ischemic stroke. METHODS: The Barthel Index (BI) and the Rivermead Motor Assessment (RMA) were assessed in 78 moderately affected stroke patients (1) after they had entered a neurological inpatient rehabilitation, (2) after 4 weeks of rehabilitation therapy, and (3) 6 months later. Polymorphisms of the gene encoding catechol-O-methyltransferase (COMT) were determined. BI and RMA results were analyzed with respect to the genetic profiles of COMT. RESULTS: Carriers of COMT Val/Val alleles showed better results in BI and RMA than COMT Met/Met carriers at all 3 time points. Val/Met carriers exhibited results in between the homozygotes, suggesting a gene-dose relationship. Altogether, BI and RMA results were highly correlated. CONCLUSION: Stroke patients with COMT Val/Val alleles had higher motor functions and abilities of activities of daily living even at the beginning of the rehabilitation period. All patient groups improved during the rehabilitation period to a similar degree, suggesting that physical therapy is comparably effective in all polymorphism subtypes.

Sonography of the median nerve in CMT1A, CMT2A, CMTX, and HNPP.

INTRODUCTION: In this study we compare the ultrasound features in the median nerve in patients with different types of Charcot-Marie-Tooth (CMT) disease and hereditary neuropathies with liability to pressure palsies (HNPP) as a typical entrapment neuropathy. METHODS: Median nerve ultrasound and conduction studies were performed in patients with CMT1A (n = 12), MFN2-associated CMT2A (n = 7), CMTX (n = 5), and HNPP (n = 5), and in controls (n = 28). RESULTS: Median nerve cross-sectional area (CSA) was significantly increased in CMT1A, whereas, in axonal CMT2A, fascicle diameter (FD) was enlarged. CSA correlated with nerve conduction slowing in CMT1A and with axonal loss, as shown by motor and sensory nerve amplitudes in both CMT1A and CMT2A. A relatively low wrist-to-forearm-ratio (WFR <0.8) or a relatively high WFR (>1.8) appeared to be unlikely in MFN2 and Cx32 mutations of CMT2A and CMTX, respectively. CONCLUSION: Differences in CSA, FD, and WFR of the median nerve can be helpful in defining subtypes of hereditary neuropathies.

Hippocampal N-acetyl aspartate levels do not mirror neuronal cell densities in creatine-supplemented epileptic rats.

For neuroprotective therapy of neurodegenerative diseases creatine treatment has gained special interest because creatine has been shown to cross the blood-brain barrier, accumulate in the human brain in vivo and cause delayed neuronal cell death in a large number of animal models. Here, we used the pilocarpine model of temporal lobe epilepsy to determine whether creatine administration is able to attenuate the epilepsy-associated decrease in hippocampal N-acetyl aspartate (NAA) concentrations, impairment of mitochondrial function and neuronal cell loss. In vivo1H-NMR spectroscopy showed, in epileptic rats after creatine administration, higher hippocampal NAA concentrations, suggesting improved neuronal survival. However, in vitro observation of hippocampal slices from creatine-treated epileptic rats revealed a more pronounced loss of pyramidal neurons and decrease in activity of mitochondrial enzymes in hippocampal subfields. This indicates that NAA concentrations measured by in vivo1H-NMR spectroscopy reflect alterations of metabolism rather than neuronal cell densities. Our data indicate an adverse effect of creatine on neuronal survival under conditions of enhanced neuronal activity.

Correlation of hippocampal glucose oxidation capacity and interictal FDG-PET in temporal lobe epilepsy.

PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60-90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity. METHODS: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-microm-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus. RESULTS: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (rp = 0.7, p = 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found. CONCLUSIONS: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism.

Delayed striate cortical activation during spatial attention.

Recordings of event-related potentials (ERPs) and event-related magnetic fields (ERMFs) were combined with functional magnetic resonance imaging (fMRI) to study visual cortical activity in humans during spatial attention. While subjects attended selectively to stimulus arrays in one visual field, fMRI revealed stimulus-related activations in the contralateral primary visual cortex and in multiple extrastriate areas. ERP and ERMF recordings showed that attention did not affect the initial evoked response at 60-90 ms poststimulus that was localized to primary cortex, but a similarly localized late response at 140-250 ms was enhanced to attended stimuli. These findings provide evidence that the primary visual cortex participates in the selective processing of attended stimuli by means of delayed feedback from higher visual-cortical areas.