Andrea M. Humm

Unexplained syncope—is screening for carotid sinus hypersensitivity indicated in all patients aged >40 years?

Objective: To determine the frequency, age distribution and clinical presentation of carotid sinus hypersensitivity (CSH) among 373 patients (age range 15–92 years) referred to two autonomic referral centres during a 10-year period. Methods: Carotid sinus massage (CSM) was performed both supine and during 60° head-up tilt. Beat-to-beat blood pressure, heart rate and a three-lead electrocardiography were recorded continuously. CSH was classified as cardioinhibitory (asystole ⩾3 s), vasodepressor (systolic blood pressure fall ⩾50 mm Hg) or mixed. All patients additionally underwent autonomic screening tests for orthostatic hypotension and autonomic failure. Results: CSH was observed in 13.7% of all patients. The diagnostic yield of CSM was nil in patients aged <50 years (n = 65), 2.4% in those aged 50–59 years (n = 82), 9.1% in those aged 60–69 years (n = 77), 20.7% in those aged 70–79 years (n = 92) and reached 40.4% in those >80 years (n = 57). Syncope was the leading clinical symptom in 62.8%. In 27.4% of patients falls without definite loss of consciousness was the main clinical symptom. Mild and mainly systolic orthostatic hypotension was recorded in 17.6%; evidence of sympathetic or parasympathetic dysfunction was found in none. Conclusions: CSH was confirmed in patients >50 years, the incidence steeply increasing with age. The current European Society of Cardiology guidelines that recommend testing for CSH in all patients >40 years with syncope of unknown aetiology may need reconsideration. Orthostatic hypotension was noted in some patients with CSH, but evidence of sympathetic or parasympathetic failure was not found in any of them.

Quantification of central motor conduction deficits in multiple sclerosis patients before and after treatment of acute exacerbation by methylprednisolone

Objective: To compare the effects of intravenous methylprednisolone (IVMP) in patients with relapsing-remitting (RR-MS), secondary progressive (SP-MS), and primary progressive multiple sclerosis (PP-MS). Methods: Clinical and neurophysiological follow up was undertaken in 24 RR-MS, eight SP-MS, and nine PP-MS patients receiving Solu-Medrol 500 mg/d over five days for exacerbations involving the motor system. Motor evoked potentials (MEPs) were used to measure central motor conduction time (CMCT) and the triple stimulation technique (TST) was applied to assess conduction deficits. The TST allows accurate quantification of the number of conducting central motor neurones, expressed by the TST amplitude ratio. Results: There was a significant increase in TST amplitude ratio in RR-MS (p<0.001) and SP-MS patients (p<0.02) at day 5, paralleling an increase in muscle force. TST amplitude ratio and muscle force remained stable at two months. In PP-MS, TST amplitude ratio and muscle force did not change. CMCT did not change significantly in any of the three groups. Conclusions: In RR-MS and SP-MS, IVMP is followed by a prompt increase in conducting central motor neurones paralleled by improvement in muscle force, which most probably reflects partial resolution of central conduction block. The lack of similar clinical and neurophysiological changes in PP-MS corroborates previous clinical reports on limited IVMP efficacy in this patient group and points to pathophysiological differences underlying exacerbations in PP-MS.

Central motor conduction differs between acute relapsing-remitting and chronic progressive multiple sclerosis.

OBJECTIVE To characterize central motor conduction in relation to the clinical deficits and to the disease duration in 90 patients with acute relapsing-remitting MS (RR-MS) and in 51 patients with chronic primary or secondary progressive MS (P-MS). METHODS The triple stimulation technique (TST) was used to quantify the central motor conduction failure (expressed by the TST amplitude ratio) and conventional motor evoked potentials (MEPs) were used to measure the central motor conduction time (CMCT). RESULTS The TST amplitude ratio was reduced in presence of a clinical motor deficit (p=0.02 for RR-MS, p<0.01 for P-MS), but did not significantly differ in RR-MS and P-MS (p>0.05) when patients with similar clinical motor deficit were compared. The CMCT was not related to the clinical motor deficit in both RR-MS and P-MS. However, the CMCT was markedly prolonged in P-MS, when patients with similar clinical motor deficit and with similar disease duration were compared (p<0.01). The differences were not attributable to differential involvement of the spinal cord, which was similar in RR-MS and P-MS. CONCLUSIONS Our results disclose differences between the central motor conduction in RR-MS and P-MS that are not related to disease severity, spinal cord involvement or disease duration.

Repetitive spinal motor neuron discharges following single transcranial magnetic stimuli: a quantitative study.

OBJECTIVE To quantify repetitive discharges of spinal motor neurons (repMNDs) in response to single transcranial magnetic stimuli (TMS). To assess their contribution to the size of motor evoked potentials (MEPs). METHODS We combined the triple stimulation technique (TST) with an additional nerve stimulus in the periphery (= quadruple stimulation; QuadS). The QuadS eliminates the first action potential descending on each axon after TMS, and eliminates effects on response size induced by desynchronization of these discharges, thereby allowing a quantification of motor neurons (MNs) discharging twice. In some instances, a quintuple stimulation (QuintS) was used, to quantify the number of MNs discharging three times. Recordings were from the abductor digiti minimi of 14 healthy subjects, using two different stimulation intensities and three different levels of facilitatory muscle pre-contractions. RESULTS The threshold to obtain repMNDs was high. Their maximal size differed markedly between subjects, ranging from 8 to 52% of all MNs. Stimulation intensity and facilitatory muscle contraction, but not resting motor threshold, correlated with the amount of repMNDs. QuintS never yielded discernible responses, hence all observed repMNDs were double discharges. RepMNDs contributed to the MEP areas, but did not influence MEP amplitudes. CONCLUSIONS QuadS and QuintS allow precise quantification of repMNDs. The threshold of repMNDs is high and varies considerably between subjects. SIGNIFICANCE repMNDs have to be considered when MEP areas are measured. Their analysis may be of interest in neurological disorders, but standardized stimulation parameters appear essential.

Acute fluid ingestion in the treatment of orthostatic intolerance: important implications for daily practice

Background:  Rapid water ingestion improves orthostatic intolerance (OI) in multiple system atrophy (MSA) and postural tachycardia syndrome (PoTS). We compared haemodynamic changes after water and clear soup intake, the latter being a common treatment strategy for OI in daily practice.

Muscle ischaemia in patients with orthostatic hypotension assessed by velocity recovery cycles

Objective Patients with orthostatic hypotension may experience neck pain radiating to the occipital region of the skull and the shoulders while standing (so-called coat-hanger ache). This study assessed muscle membrane potential in the trapezius muscle of patients with orthostatic hypotension and healthy subjects during head-up tilt (HUT), by measuring velocity recovery cycles (VRCs) of muscle action potentials as an indicator of muscle membrane potential. Methods Eight patients with multiple system atrophy (MSA), orthostatic hypotension and a positive history for coat-hanger pain and eight normal controls (NCs) were included in this study. Repeated VRCs were recorded from the trapezius muscle by direct muscle stimulation in the supine position and during HUT for 10 min. Results Muscle VRC recordings did not differ between MSA patients and NCs in the supine position. During HUT, early supernormality decreased progressively and relative refractory period increased in MSA patients whereas VRC measures remained unchanged in NCs. Ten minutes after the start of HUT, early supernormality was reduced by 44% and relative refractory period was increased by 17%. Conclusions Muscle membranes in patients with orthostatic hypotension become progressively depolarised during standing. Membrane depolarisation is most likely the result of muscle ischaemia, related to the drop in perfusion pressure caused by orthostatic hypotension. Coat-hanger ache is most likely a consequence of this muscle ischaemia.

Velocity recovery cycles of human muscle action potentials: Repeatability and variability

OBJECTIVE Velocity recovery cycles (VRCs) of human muscle action potentials have been proposed as a new technique for assessing muscle membrane function in myopathies. This study was undertaken to determine the variability and repeatability of VRC measures such as supernormality, to help guide future clinical use of the method. METHODS To assess repeatability, VRCs with one and two conditioning stimuli were recorded from brachioradialis muscle by direct muscle stimulation in 20 normal volunteers, and the measurements repeated 1 week later. To further assess variability and dependence on electrode separation, age and sex, recordings from an additional 20 normal volunteers were added. RESULTS There was a high intraclass correlation between repeated recordings of early supernormality, indicating excellent reliability of this VRC measure. However, relative refractory period had a smaller coefficient of repeatability in relation to the changes previously described during ischemia. We found no evidence that any of the excitability measures depended on electrode separation, conduction time or apparent velocity. There were also no significant differences between the recordings from men and women, or between the recordings from older (mean 44.9 y) and younger (26.5 y) subjects. CONCLUSIONS VRC measures are sufficiently consistent to be suitable for comparing muscle membrane function both within subjects and between groups. Early supernormality measurements benefit most from within subject comparisons. SIGNIFICANCE These normative data sets provide a firm basis for planning clinical studies.

Abnormal cardiovascular responses to carotid sinus massage also occur in vasovagal syncope – implications for diagnosis and treatment

Background and purpose:  Carotid sinus massage (CSM) is commonly used to identify carotid sinus hypersensitivity (CSH) as a possible cause for syncope, especially in older patients. However, CSM itself could provoke classical vasovagal syncope (VVS) in pre disposed subjects.

Temperature dependency of human muscle velocity recovery cycles.

Introduction: Velocity recovery cycles (VRCs) of human muscle action potentials have been proposed as a new technique for studying muscle membrane function. This study was undertaken to determine the temperature dependency of VRC parameters. Methods: VRCs with 1 conditioning stimulus were recorded repeatedly from brachioradialis muscle during cooling, and intramuscular temperature was recorded. VRCs in 6 normal volunteers were measured at 1°C intervals from 34°C to 28°C. The effects of temperature on relative refractory period and early and late supernormality were quantified. Results: Muscle VRC curves shift progressively upward and to the right with cooler temperatures. The most sensitive parameter to temperature changes was relative refractory period, whereas early supernormality was rather insensitive. Late supernormality was unaffected by temperature changes. Conclusions: Knowledge of temperature‐induced changes of muscle VRC parameters is essential for future studies. Thus, the results of this study provide a firm basis for clinical studies with this technique. Muscle Nerve 46: 264–266, 2012

Venepuncture during head-up tilt testing in patients with suspected vasovagal syncope – implications for the test protocol

Head‐up tilt (HUT) testing is a widely used diagnostic tool in patients with suspected vasovagal syncope (VVS). However, no gold standard exists for this examination and the various protocols used have a limited sensitivity and specificity. Our aim was to determine the sensitivity of a sequential HUT testing protocol including venepuncture (VP) and sublingual nitroglycerin application.