The effect of warfarin administration on platelet aggregation.

BACKGROUND: The aim of this study was to assess the effect of anticoagulation treatment on platelet aggregation. METHODS: The study group consisted of 24 patients on long-term warfarin therapy without any antiaggregation therapy. Platelet aggregation was measured using VerifyNow with arachidonic acid (AA) as an inducer in 23 patients and with light transmission aggregometry (LTA) in 19 patients using four different agonists. All patients had their international normalized ratio (INR) checked regularly. RESULTS: The mean INR value was 2.07 (SD 0.6). The average aggregation measured by VerifyNow was found to be 637.5 (SD 36.6) aspirin reaction units. The values of average aggregability in LTA were 73.3 % (SD 4.5 %), 73.2 % (SD 6 %) and 72.1 % (SD 4.8 %) in case of aggregation induced by AA, ADP, and collagen, respectively. Epinephrine­induced aggregability was 65.3 % (SD 14.7 %). Regression analysis between INR and values of collagen- or epinephrine­induced aggregability (r = 0.654 and 0.575) was found statistically significant (p = 0.004 and 0.016); every increase in INR by 0,1 brings about an increase in collagen- and epinephrine­induced aggregation values by 1.5 and 4, respectively. CONCLUSION: Administration of warfarin does not produce a significant reduction in platelet aggregation. On the contrary, prolonged INR evokes a mild increase in aggregation induced by collagen or epinephrine (Tab. 2, Fig. 3, Ref. 32). Text in PDF www.elis.sk Keywords: platelet aggregation, anticoagulation, warfarin, platelet function tests, chronic ischemic heart disease.

The impact of balance specific physiotherapy, intensity of therapy and disability on static and dynamic balance in people with multiple sclerosis: A multi-center prospective study.

BACKGROUND: A high-quality research identifying the best physiotherapeutic approach for the improvement of balance in people with multiple sclerosis is missing. This study compared aspects of balance improvement such as therapy specificity to balance, therapy method and category, country, intensity and medical conditions. METHODS: A multicentric randomised rater-blinded controlled trial comprised three different physiotherapy programs (Czech and Italian outpatient or inpatient programs). All patients received 20 therapy sessions. Experimental group underwent balance specific physiotherapy (it was Motor Program Activating Therapy in the Czech cohort and Sensory-motor Integration Training in the Italian cohort), control group underwent non-balance specific physiotherapy (it was Vojta reflex locomotion in the Czech cohort and conventional dynamic strengthening exercises in the Italian cohort, respectively). Static balance was evaluated by Berg Balance Scale and dynamic balance was assessed by Timed Up-and-Go Test. RESULTS: A total of 149 patients entered the study. Physiotherapy significantly improved static balance (p < 0.0001, increase by mean 2.6 points (95% confidence interval 2.0-3.5) in BBS score). Balance specific approach had a higher effect than non-specific balance approach (increase in BBS by 1.9 points, 95% confidence interval 0.9-3.7 points). The intensity of the physiotherapy significantly influenced static balance (BBS by 2.7 points higher in the inpatient setting, p= 0.007). Dynamic balance was also improved (TUG decrease by -0.8 s (95% CI -1.4 - -0.1s, p = 0.011)); the balance specificity had no impact. The level of disability played the most important role (p= 0.022). CONCLUSION: Although the overall changes in static and dynamic balance were statistically significant, they were quite small in a clinical sense. A small statistically significant difference between balance specific and non-specific treatment was found. It seems that a high intensity of the therapy is critical to maximize the effectiveness.

Initiation of first disease-modifying treatment for multiple sclerosis patients in the Czech republic from 2013 to 2016: Data from the national registry ReMuS.

BACKGROUND: Proper management of multiple sclerosis (MS) requires feedback from clinical practice via registries. OBJECTIVE: To introduce the Czech national multiple sclerosis registry, ReMuS, and explore the availability and use of disease-modifying drugs (DMD). METHODS: The analysis focused on patients who started their first DMD, either with first-line or second-line medication and was based on reimbursement criteria set by Czech regulators. Baseline information was used to predict relapses after DMD initiation and to compare patients that started DMD in different years. RESULTS: A total of 3,328 patients started DMD treatment for MS between 2013 and 2016; 3,203 on first-line and 125 on second-line medication. The proportion of patients starting on second-line drugs increased from 1.8% in 2013 to 4.7% in 2016. The occurrence of a relapse within one year of DMD initiation was significantly related to (1) the Expanded Disability Status Scale (EDSS) score immediately prior to starting DMD and (2) the number of previous relapses. Both parameters were significantly lower in patients starting in later years of the explored interval. CONCLUSION: Data from the ReMuS registry highlights improvements made in the management of MS in the Czech Republic. However, a relatively low percentage of patients started treatment using second-line drugs, in contrast to trends in other countries.

Electrophysiological and histological changes of paraspinal muscles in adolescent idiopathic scoliosis.

PURPOSE: The pathogenesis of adolescent idiopathic scoliosis (AIS) remains poorly understood. To date, potentially involved local changes in the deep paraspinal muscles still remain unknown. METHODS: Needle electromyography (EMG) and muscle biopsy of paraspinal muscles at convexity and concavity of the AIS main thoracic curve were performed in 25 subjects. In this group, EMG was performed in 16 AIS subjects (12 females, 12-27 years), muscle biopsy in 18 AIS subjects (15 females, 11-31 years) compared to 10 non-scoliotic controls (6 females, 12-55 years). Samples of muscle tissue were removed during corrective surgery and were examined histologically, enzyme histochemically and immunohistochemically. Both methods of EMG and muscle biopsy were performed in 9 subjects (7 women, 12-27 years). RESULTS: Right curve convexity was found in 24 AIS subjects. Amplitudes of motor unit action potentials (MUPs) were significantly increased on the AIS curve convexity versus concavity. Turns, duration and phases of MUPs were without any significant changes. In all 18 subjects, the histological examination revealed muscle fiber redistribution with numerical predominance of type I on the curve convexity which strongly correlated with the progression of the Cobb angle. CONCLUSION: Our findings demonstrate significant changes of muscle fiber redistribution in the paraspinal muscles of AIS with increased proportion of type I on the convexity corresponding to a significantly higher amplitude of MUPs on the same side. A possible explanation of this alteration is a secondary adaptation due to chronic high load demand.

Cutaneous silent periods are not affected by the antihistaminic drug cetirizine.

OBJECTIVE: Noxious digital nerve stimulation leads to transient suppression of the electromyographic activity in isometrically contracted hand muscles, known as the "cutaneous silent period" (CSP). To date, neurotransmitters potentially involved in mediating this electromyographic (EMG) suppression remain unknown. Anecdotal observation lead to the hypothesis that antihistaminic medication may counteract nociceptive EMG suppression, as CSPs in one male subject who was accustomed to CSP recordings were temporarily lost following ingestion of an antihistaminic drug for acute rhinitis. A second otherwise healthy male subject, who was on long-term cetirizine for allergic rhinitis, presented without clearly defined CSPs when volunteering for normal values. METHODS: We undertook a systematic study in five healthy subjects (including the one with temporarily lost CSPs) who underwent serial CSP testing after ingestion of 10 mg cetirizine. CSPs were elicited in thenar muscles following digit II and digit V stimulation (20 times sensory threshold, 100 sweeps rectified and averaged) before and 90, 180, and 360 min following intake of medication. RESULTS: CSP onset latency, CSP end latency and CSP duration, as well as the index of suppression did not change significantly following ingestion of 10 mg cetirizine. Repeat study in the subject with no clearly defined CSPs on long-term treatment revealed persistently absent CSPs after a 5-week withdrawal from cetirizine. CONCLUSION: CSPs are not affected by therapeutic doses of the H1 antihistaminic cetirizine. SIGNIFICANCE: Our findings suggest that histamine plays no major role as a neurotransmitter of CSPs.

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.

Cutaneous and mixed nerve silent periods in syringomyelia.

OBJECTIVES AND METHODS: We studied cutaneous and mixed nerve silent periods (CSP, MNSP) in 4 patients with cervical syringomyelia documented by magnetic resonance imaging who on clinical examination presented with unilateral hypalgesia and hypothermesthesia. In addition, we recorded upper and lower extremity somatosensory and motor evoked potentials (SEP, MEP), and cortical silent periods. RESULTS: In all patients, CSP and the later portion of MNSP were absent or shortened on their affected side, while both were normal on their unaffected side. In all patients, SEP latencies were normal following both median and tibial nerve stimulation. In two patients, the amplitude N13 (median nerve SEP), and in one patient each the amplitudes N20 (median nerve SEP) and P37 (tibial nerve SEP) were reduced. Central motor conduction time was prolonged to abductor digiti minimi muscle in one patient on the affected side, but was normal to tibialis anterior muscle in all patients. Cortical silent periods where present bilaterally in spite of unilateral complete absence of CSP and MNSP in two subjects tested. Loss of CSP and MNSP were a sensitive parameter of spinal cord dysfunction in syringomyelia. The cervical median nerve SEP response N13 reflected gray matter involvement, while corticospinal tract dysfunction was less frequently observed. CONCLUSION: Our data suggest that CSP and later portion of MNSP are generated at the spinal level by the same small myelinated A-delta fibers, and that their central network is distinct from large diameter fiber afferents and efferents.

Nociceptive fingertip stimulation inhibits synergistic motoneuron pools in the human upper limb.

BACKGROUND: Activation of distinct muscle groups organized in a stereotyped manner ("muscle synergies") is thought to underlie the production of movement by the vertebrate spinal cord. This results in movement with minimum effort and maximum efficiency. The question of how the vertebrate nervous system inhibits ongoing muscle activity is central to the study of the neural control of movement. OBJECTIVE: To investigate the strategy used by the human spinal cord to rapidly inhibit muscle activation in the upper limb. METHODS: The authors performed a series of experiments in 10 healthy subjects to assess the effect of nociceptive cutaneous stimulation on voluntarily contracting upper limb muscles. They recorded the electromyogram (EMG) with surface electrodes placed over various upper limb muscles. RESULTS: The authors found evidence of a simple inhibitory strategy that 1) was dependent on the intensity of the stimulus, 2) was maximally evoked when stimulation was applied to the fingertips, 3) preceded the earliest onset of voluntary muscle relaxation, and 4) produced inhibition of EMG activity in specific upper limb muscle groups. Nociceptive fingertip stimulation preferentially inhibited contraction of synergistic muscles involved in reaching and grasping (intrinsic hand muscles, forearm flexors, triceps) while having little effect on biceps or deltoid. CONCLUSIONS: Neural circuitry within the human spinal cord is organized to inhibit movement by rapidly deactivating muscles that constitute distinct muscle synergies. This strategy of selective and concurrent deactivation of the same basic elements that produce synergistic movement greatly simplifies motor control.

Spinal motoneuron excitability after acute spinal cord injury in humans.

BACKGROUND: Few studies in humans have assessed the ability of Ia afferent and antidromic motor volleys to activate motoneurons during spinal shock. Hence, little is known about the excitability state of the spinal motoneuron pool after acute spinal cord injury (SCI) in humans. METHODS: In 14 patients with acute SCI involving anatomic levels T10 and above, we performed clinical and electrophysiologic studies early after injury (within 24 hours in seven subjects) and on day 10, 20, and 30 postinjury. Maximal H:M ratios, F-wave persistence, and tendon tap T-reflexes were recorded. Sixteen normal subjects and eight chronic SCI patients served as control subjects. RESULTS: Ten of 14 patients had spinal shock (complete paralysis, loss of sensation, absent reflexes, and muscle hypotonia below the injury) at the time of initial evaluation. F-waves were absent in patients with spinal shock, reduced in persistence in patients with acute SCI without spinal shock, and normal in persistence in patients with chronic SCI. H-reflexes were absent or markedly suppressed in patients with spinal shock within 24 hours of injury but recovered to normal amplitudes within several days postinjury. This recovery occurred despite absence of F-waves that persisted for several weeks postinjury. Deep tendon reflexes were proportionally more depressed in spinal shock than were H-reflexes. All patients had elicitable H-reflexes for days or weeks before the development of clinical reflexes. CONCLUSIONS: Rostral cord injury causes postsynaptic changes (hyperpolarization) in caudal motoneurons. This hyperpolarization is a major physiologic derangement in spinal shock. The rise in H-reflex amplitude despite evidence of persistent hyperpolarization is due to enhanced transmission at Ia fiber-motoneuron connections below the SCI. Finally, the observation that the stretch reflex is proportionally more depressed than the H-reflex is consistent with fusimotor drive also being depressed after SCI.

Spinal motor neuron excitability during the cutaneous silent period.

The physiologic mechanisms generating the cutaneous silent period (CSP) remain uncertain. It is not known whether the CSP occurs because of inexcitability of the spinal motor neuron. We therefore, assessed excitability of the motor neuron during the CSP using F-wave responses. H-reflexes were also elicited during the CSP. Electrical stimulation to the fifth digit produced the CSP in the voluntarily contracting abductor pollicis brevis muscle (APB). Median nerve stimulation at the wrist elicited control F or H responses during isometric APB contraction (condition 1) and in resting muscle (condition 2). Control amplitudes were compared to those elicited in the midst of the CSP. In Condition 1, F-wave amplitudes and frequency during the CSP were unchanged compared with controls. However, F-waves were increased in amplitude and frequency during the CSP (P < 0.001) relative to responses elicited in resting muscle (condition 2). H-reflexes during the CSP were suppressed (P < 0.001) compared with controls elicited during contraction (condition 1), but facilitated relative to the resting state (condition 2) in which no H-reflexes were elicitable. We conclude that spinal motor neurons remain excitable to antidromic volleys at the same time that the corticospinal volley is inhibited to produce the CSP. Moreover, motor neuron excitability appears to be increased during the CSP compared to the relaxed state.

Characteristics of the silent period after transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) of human cortex during voluntary muscle contraction produces a transient period of inhibition (i.e., silent period, SP) in the electromyographic (EMG) activity. The duration of the SP in relation to the level of muscle force (10%, 50% and 100% of maximum voluntary contraction) as well as possible cumulative effects of sequential TMS on the SP were studied. Methodologic problems were encountered in defining the SP and thus the duration of both an absolute (complete EMG silence) and relative (return of uninterrupted EMG activity) SP was measured. In all subjects, shortening of the SP duration occurred in relation to an increase in force when the criterion for absolute SP was used. Conversely, the relative SP duration suggested a trend toward prolongation with increasing force of contraction. No cumulative effects of TMS were observed on the absolute SP duration, whereas two subjects showed a cumulative effect of TMS on the relative SP. We conclude that the effect of muscle force and sequential TMS on the SP duration is dependent on the methods used to measure the SP. It is therefore essential to agree on methodology before SP measurements are clinically useful.

Somatosensory evoked potentials in workers exposed to toluene and styrene.

Somatosensory evoked potentials (SEPs) were used to evaluate possible subclinical impairment of the nervous system due to occupational exposure to toluene and styrene. A group of 36 rotogravure printers with severe exposure to toluene, 20 workers with severe exposure to styrene in a glass laminate manufacturing plant, and a comparison group of healthy subjects were studied. The severity of exposure was documented by measurements of toluene and styrene concentrations in breathing zone air, by hippuric acid concentration in urine in the group exposed to toluene, and by urinary mandelic acid concentration in the group exposed to styrene. Somatosensory evoked potentials were measured by stimulation of the median nerve at the wrist and the tibial nerve at the ankle. Peripheral conduction velocities (CVs) in both extremities and central conduction time (CCT) after tibial nerve stimulation were significantly decreased in both exposed groups. Significantly prolonged latencies of peripheral and cortical SEPs to median nerve stimulation as well as cortical SEPs to tibial nerve stimulation were found in workers exposed to styrene. Some abnormalities in SEPs at peripheral or spinal and cortical levels were found in eight workers exposed to toluene and six workers exposed to styrene. Of these, in three workers exposed to toluene and two to styrene increased CCT and delayed latencies of cortical responses at normal conduction values in the periphery were found. A trend for increased frequency of abnormal SEPs with duration of exposure to toluene and styrene and alcohol abuse was found. Abnormalities in SEPs in the exposed groups are most probably of multifactorial origin. Central SEP abnormalities in both exposed groups could indicate early signs of subclinical dysfunction at spinal and cortical levels and could be due to toluene or styrene exposure probably potentiated by alcohol consumption in the group exposed to toluene.

Surface and epidural lumbosacral spinal cord evoked potentials in chronic spinal cord injury.

Nine patients were examined in the chronic stage of spinal cord injury (12 to 56 months postinjury). Surface lumbosacral spinal cord evoked potentials (LSEPs) were obtained using electrodes placed over the S1, L2, L4, and T12 vertebral levels, referenced to a T6 surface electrode. Epidural LSEPs were obtained using a multielectrode lead placed percutaneously into the epidural space for evaluation of the efficacy of spinal cord stimulation for modification of pain and spasticity. The LSEPs resulting from supramaximal stimulation of the tibial nerve at the popliteal fossa were composed of propagating and stationary action potential components. Based on the surface LSEP amplitudes and latencies established in healthy subjects, the data was divided into normal (less than 2 SD), marginal (between 2 and 2.5 SD), and abnormal (greater than 2.5 SD) categories. Comparison of surface and epidural LSEPs at the T12 vertebral level for the normal group (n = 6, 4 incomplete and 2 complete) revealed a mean epidural/surface amplitude ratio of 9.44 and a latency for the major negative component of 15.2 +/- 0.6 ms for the epidural versus 14.8 +/- 0.6 ms for the surface LSEP. In cases where the lead was progressively removed and LSEPs recorded (n = 4) the propagating components rapidly attenuated and increased in duration while the stationary components attenuated but did not change in duration. The LSEPs for the marginal group (n = 2, 1 incomplete and 1 complete) showed similar epidural/surface amplitude ratios. In the abnormal case (n = 1, complete) surface LSEPs were absent but epidural LSEPs were present but with stationary and propagating components of low amplitude. This study demonstrates the ability of the epidural LSEP to provide more information than the surface LSEP of the functional condition of the lumbosacral spinal cord, particularly regarding the character of the propagating action potentials and in cases when the surface LSEPs appear to be of very low amplitude or absent.

[Somatosensory evoked potentials in workers exposed to toluene]. / Vysetrení somatosensorických evokovaných potenciálu u pracovníku exponovaných toluenem.

The aim of our study was to evaluated by means of SEPs possible subclinical impairment of the nervous system during long-lasting toluene exposure. A group of 36 rotogravure printers (men, mean age 39.3 +/- 11.6 years) exposed to toluene from a polygraphic plant in Prague was investigated. The severity of toluene exposure was documented by the measurements of toluene concentration in the breathing zone air, by the toluene concentration in blood and by biological monitoring (urinary hippuric acid concentration). The duration of exposure was 0.1-41.0 (mean 12.0) years. Somatosensory evoked potentials (SEPs) elicited by stimulation of the median a tibial nerves, clinical neurological examinations and laboratory tests were performed on each worker. The results of SEPs investigations were compared with findings in a control group of 23 healthy men (mean age 31 +/- 10 years). Most of printers abused alcohol regularly. Peripheral conduction velocities in both extremities and central conduction time in case of lower limb stimulation were decreased statistically significant (P less than 0.05). All abnormalities of SEPs at peripheral and/or spinal and cortical levels were found in 8 cases, of these in 3 workers were found the SEP abnormalities of "central" type (the increased central conduction time at normal conduction values in the periphery). An impairment of all SEP pathways was found in 2 workers. Our results indicate an impairment in both central and peripheral parts of nervous system. Peripheral abnormalities could be interpreted as an incipient ethylic polyneuropathy and central abnormalities as an early sign of subclinical dysfunction at spinal and cortical levels due to toluene exposure potentiated by alcohol consumption.