Multidimensional evaluation of changes in limb function following botulinum toxin injection in persons with stroke.

BACKGROUND: There are limited evidence of instrumented measures of gait and balance to determine the functional effects of botulinum toxin injections (BoNT-A) in spasticity after stroke. OBJECTIVE: To evaluate the functional changes in gait and balance following upper limb and lower limb BoNT-A in persons with stroke. METHODS: A pre-post prospective study of 35 stroke patients with upper and/or lower limb spasticity after focal treatment with BoNT-A. Assessments were at baseline (T0), 6-weeks (T1) and 12-weeks (T2), using validated subjective and objective physical activity measures. RESULTS: After BoNT-A injections, significant improvements in most measures of impairments, activity and participation domains were found at T1 (p < 0.05, effect sizes (r) = 0.5-0.9). There was a significant increase in low intensity physical activity (at T1) and sedentary time reductions at both follow-up periods. Instrumented gait/balance measures showed a significant increase in cadence and turn velocity, but no changes in sway measures were found using posturography. Improvements in most outcome measures were maintained at 12-weeks. CONCLUSION: BONT-A improved scores in most clinical measures but only in some of the objective gait/balance and physical activity measures. Further robust studies should utilize a larger sample size to better determine the benefits of BoNT-A for stroke-related spasticity.

Evaluation of the sensitivity and specificity of serum level of prostasin, CA125, LDH, AFP, and hCG+ß in epithelial ovarian cancer patients.

OBJECTIVES: The aim of this work was to compare and analyze the diagnostic value of serum prostasin, cancer antigen 125 (CA125), lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG+ß) in epithelial ovarian cancer (EOC) and evaluate if their serum levels could be used as a potential diagnostic markers of EOC from benign tumors and healthy women. MATERIALS AND METHODS: Preoperative serum samples of 110 women (24 healthy controls, 66 ovarian benign tumors, and 20 EOC) were tested for prostasin, CA125, AFP, and hCG+ß. The level of CA125, AFP, and hCG+ß serum tumor markers were determined by electro-chemiluminescence immunoassay (ECLIA) and the serum level of prostasin was measured using enzyme-linked immunosorbent assay (ELISA) and LDH activity was measured by spectrophotometer and analyzed using SPSS version. RESULTS: The Area Under the Curve (AUC) values of prostasin, CA125, LDH, AFP, and hCG+ß for the discrimination of EOC from benign and healthy controls were, respectively, 0.89, 0.91, 0.77, 0.54, and 0.65, and significant increase in serum levels of prostasin, CA125, and LDH were observed for EOC compared with benign and control groups. CONCLUSION: The present study showed that CA 125 and LDH levels of serum increased in high stages, while prostasin level was decreased in high stages. The present results indicate that prostasin, CA125, and LDH are differentially expressed in EOC than in benign and healthy control population, that may be an indicative of a better diagnostic value, with higher sen- sitivity and specificity. Here the authors used a multimarker approach, consisting of CA125, AFP, beta hCG, prostasin, and LDH that could provide a more accurate tool for a differential diagnosis of patients with EOC.

Within-session repeated a-tDCS: the effects of repetition rate and inter-stimulus interval on corticospinal excitability and motor performance.

OBJECTIVE: This study investigated the effect of rate and stimulation interval of anodal transcranial direct current stimulation (a-tDCS) on CSE and motor performance. METHODS: Twelve healthy individuals participated in this study. CSE was assessed before and after five experimental conditions of one, two or three applications of 10 min of a-tDCS with an interval of 5 or 25 min. a-tDCS was applied with a constant current density of 0.016 mA/cm(2). Purdue pegboard-test was selected for motor performance assessment. RESULTS: Compared to single 10 min stimulation, the magnitude of the within-session repeated a-tDCS induced excitability was enhanced significantly after the second stimulation was performed with an interval of 25 min, but not 5 min. However, by increasing the number of a-tDCS to three repetitions the CSE was significantly increased and lasted for 2h with both 5 and 25 min intervals. Furthermore, CSE enhancement remained significant for up to 24h for within session a-tDCS repetitions with 25 min intervals. Likewise, significant improvement was seen in motor performance following three times repetition with 25 min inter-stimulus intervals. CONCLUSIONS: The results suggest that within session repeated a-tDCS with longer intervals within the lasting effects of the previous stimulations are preferable for increasing induced excitability changes with longer lasting effects. SIGNIFICANCE: It is of particular importance to increase the a-tDCS lasting effects to consolidate the neuroplastic CSE changes.

a-tDCS differential modulation of corticospinal excitability: the effects of electrode size.

BACKGROUND: Novel noninvasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have been developed in recent years. tDCS-induced corticospinal excitability changes depend on two important factors: current density and electrodes size. Despite clinical success with existing tDCS parameters; optimal protocols are still not entirely set. OBJECTIVE: The current study aimed to investigate the effects of anodal tDCS (a-tDCS) with three electrode sizes on corticospinal excitability. METHODS: a-tDCS was applied with three active electrode sizes of 12, 24 and 35 cm(2) with a constant current density of 0.029 mA/cm(2) on twelve right handed healthy individuals (mean age: 34.5 ± 10.32 years) in different sessions at least 48 h apart. a-tDCS was applied continuously for 10 min, with a constant reference electrode size of 35 cm(2). The corticospinal excitability of extensor carpi radialis muscle (ECR) was measured before and immediately after the intervention and at 10, 20 and 30 min thereafter. RESULTS: We found that smaller electrode may produce more focal current density and could lead to more effective and localized neural modulation than the larger ones. Post hoc comparisons showed that active electrode of 12 cm(2) size induces the biggest increase in the corticospinal excitability compared to bigger electrode sizes, 24 cm(2) (P = 0.002) and 35 cm(2) (P = 0.000). There was no significant difference between two larger electrode sizes (24 cm(2) and 35 cm(2)) (P = 0.177). a-tDCS resulted in significant excitability enhancement lasting for 30 min after the end of stimulation in the 12 and 24 cm(2) electrode size conditions (P < 0.005). However, in 35 cm(2) electrode size condition, the MEP amplitudes of the ECR did not differ significantly from baseline value in 20 and 30 min post stimulation (P > 0.005). CONCLUSION: Reducing stimulation electrode size to one third of the conventional one results in spatially more focused stimulation and increases the efficacy of a-tDCS for induction of larger corticospinal excitability. This may be due to the fact that larger electrodes stimulate nearby cortical functional areas which can have inhibitory effects on primary motor cortex.

Does anodal transcranial direct current stimulation enhance excitability of the motor cortex and motor function in healthy individuals and subjects with stroke: a systematic review and meta-analysis.

The primary aim of this review is to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on corticomotor excitability and motor function in healthy individuals and subjects with stroke. The secondary aim is to find a-tDCS optimal parameters for its maximal effects. Electronic databases were searched for studies into the effect of a-tDCS when compared to no stimulation. Studies which met the inclusion criteria were assessed and methodological quality was examined using PEDro and Downs and Black (D&B) assessment tools. Data from seven studies revealed increase in corticomotor excitability with a small but significant effect size (0.31 [0.14, 0.48], p=0.0003) in healthy subjects and data from two studies in subjects with stroke indicated significant results with moderate effect size (0.59 [0.24, 0.93], p=0.001) in favor of a-tDCS. Likewise, studies examining motor function demonstrated a small and non-significant effect (0.39 [-0.17, 0.94], p=0.17) in subjects with stroke and a large but non-significant effect (0.92 [-1.02, 2.87], p=0.35) in healthy subjects in favor of improvement in motor function. The results also indicate that efficacy of a-tDCS is dependent on current density and duration of application. A-tDCS increases corticomotor excitability in both healthy individuals and subjects with stroke. The results also show a trend in favor of motor function improvement following a-tDCS. A-tDCS is a non-invasive, cheap and easy-to-apply modality which could be used as a stand-alone technique or as an adds-on technique to enhance corticomotor excitability and the efficacy of motor training approaches. However, the small sample size of the included studies reduces the strength of the presented evidences and any conclusion in this regard should be considered cautiously.

Modulation of the ipsilateral and contralateral H reflexes following ipsilateral mechanical pressure of the foot in normal subjects.

OBJECTIVE: Mechanoreceptors from the foot sole likely contribute in the reflex regulations. Therefore, it was hypothesized that repetitive low threshold afferents stimulation would have an inhibitory effect on the soleus H-reflexes. METHODS: Sixteen normal subjects voluntarily, participated in the study and were randomly allocated. Subjects were remained in prone position. The Cutaneous Mechanical Pressure (CMP equal to 50% of leg and foot weight) was applied to the ipsilateral lateral and Medial plantar surface by a designed instrument through a square plate (30 x 30 mm). H reflex as an indicator for excitability of motoneurones was bilaterally elicited before and after the application of the CMP. The H-reflex parameters were estimated. RESULTS: Mechanical pressure significantly depressed soleus H-reflex excitability in ipsilateral and contralateral feet in all subjects. CONCLUSION: The demonstration of a decrease in H-reflex excitability as a result of applied pressure to the foot sole suggests that the change in reflex excitability is the result of a common spinal mechanism. The results highlight the modulatory effects that natural stimulation of afferents can have on reflex excitability. SIGNIFICANCE: The placement of a small flat plate, in order to apply pressure to the plantar eminence, may be useful for modulation of muscle tone. In addition, these findings might be useful for reducing spasticity; because spasticity is at least partially caused by hyperexcitability of the motorneuron pool.

Kinetic analysis of cyclic CMP-specific and multifunctional phosphodiesterases by quantitative positive-ion fast-atom bombardment mass spectrometry.

Two enzymes, cyclic CMP-specific phosphodiesterase and multifunctional phosphodiesterase, are responsible for the hydrolysis of cytidine 3',5'-cyclic monophosphate in living cells. Quantitation of both enzymes has been carried out by positive-ion fast-atom bombardment mass spectrometric analysis of the enzyme incubates after termination of the reaction. The kinetic data obtained are in close agreement with parallel data obtained by the conventional radiometric assay. The extra facility of the mass spectrometry based assay to monitor several incubation components simultaneously has been exploited to study the concurrent hydrolysis of alternate cyclic nucleotide substrates and provides kinetic parameters of significance in interpreting substrate-enzyme interactions. This is extended by the use of collisionally-induced dissociation of the protonated molecules of the liberated products to identify the mononucleotide isomers resulting from the cyclic nucleotide hydrolysis.

Serotonin syndrome and fluvoxamine: a case study.

OBJECTIVE: To report a serotonin syndrome reaction in a patient taking fluvoxamine to replace an earlier SSRI agent. CASE REPORT: A female patient with Obsessive Compulsive Disorder on paroxetine after resurgence in her obsessive ruminations was started on fluvoxamine 50 mg daily. One week later she became suicidal and was hospitalized. The fluvoxamine was increased to 50 mg morning and 100 mg bedtime and the paroxetine was discontinued. Over the next few days she began to have trouble with her concentration. A low grade fever set in after she experienced auditory hallucinations. Fluvoxamine was discontinued and she had an uneventful recovery after twenty-four hours. DISCUSSION: Fluvoxamine is a recently approved serotonin selective reuptake inhibitor (SSRI) with few side effect profiles. It is effective in the treatment of Depressive Disorder and Obsessive Compulsive Disorder and is used to potentiate or replace other anti-OCD drugs including already available serotonin specific reuptake inhibitors (SSRI). We wish to draw attention to the potential for serotonin syndrome in patients on fluvoxamine who may have previously been on other SSRIs.