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.

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.

Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study.

BACKGROUND: Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population. METHODS AND RESULTS: This study prospectively investigated the association between Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14. 9). CONCLUSIONS: Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis. Lp(a) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.

Dopamine D4 receptor polymorphism and idiopathic Parkinson's disease.

Patients with idiopathic Parkinson's disease (IPD) are described as having markedly decreased novelty seeking characteristics. Since recent publications suggest an association between the dopamine D4 receptor polymorphism and novelty seeking, we investigated this polymorphism in a group of 122 patients with IPD and 127 healthy control subjects. We found similar allele and genotype frequencies in both groups and no association with the age of onset of symptoms. Therefore, the dopamine D4 receptor polymorphism does not confer genetic susceptibility to IPD and cannot explain the decreased novelty seeking in IPD patients.

Influence of hematocrit on the measurement of lipoproteins demonstrated by the example of lipoprotein(a).

BACKGROUND: The measurement of many parameters of human blood is usually performed in plasma or serum. Since lipoproteins or apolipoproteins, for example, are found almost exclusively in the plasma fraction after low-speed centrifugation, these parameters can be expected to be distributed in a different plasma volume depending on the hematocrit value. Therefore, the measured plasma levels might be relatively too low or too high in comparison to the whole blood concentrations in the case of abnormal hematocrit levels. The aim of our experiments was to evaluate the extent of differences between whole blood and plasma concentrations, taking as an example lipoprotein(a) [Lp(a)] in hemodialysis patients with documented decreased hematocrit values. METHODS: Lp(a) was measured in plasma as well as whole blood of 15 hemodialysis patients with low hematocrit values (0.29 +/- 0.02) in comparison to 11 control subjects (0.45 +/- 0.04). RESULTS: Plasma concentrations were 27% higher in patients than in controls (19.7 vs. 15.5 mg/dl). The relative difference was twice as high (59%) when measured in whole blood (13.5 vs. 8.5 mg/dl). Similar relative differences were observed when whole blood concentrations of 125 hemodialysis patients and 256 controls were calculated with the formula [Lp(a)plasma * (1-hematocrit)]. CONCLUSIONS: Our findings clearly demonstrate that hematocrit is a strong confounding variable of lipoprotein measurement in epidemiological studies when concentrations are measured in plasma, especially in cases of abnormal hematocrit values. Furthermore, studies investigating the longitudinal changes of lipoproteins should consider potential hematocrit changes.

Modulation of upper extremity motoneurone excitability following noxious finger tip stimulation in man: a study with transcranial magnetic stimulation.

Little is known about nociceptive reflex mechanisms in the upper limb in humans. To investigate nociceptive effects on spinal motoneurone excitability, a conditioning noxious stimulus was applied to the index finger of five healthy subjects. Motor evoked potentials (MEPs) following contralateral transcranial magnetic stimulation (TMS) were recorded from thenar eminence (TE) and biceps brachii (BB) muscles ipsilateral to finger stimulation. TMS was randomly applied alone or combined with preceding finger stimulation at an interstimulus interval of 100 ms. MEP amplitudes were profoundly suppressed in TE and augmented in BB. We conclude that nociception produces a differential effect on different spinal motoneurone pools, which may be part of a complex protective reflex mechanism in the upper limb of humans.

Epileptic seizure associated with intracerebroventricular and intrathecal morphine bolus.

We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.

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.

Epileptic seizures associated with intrathecal baclofen application.

We report the clinical and EEG findings in three patients presenting with seizures associated with intrathecal baclofen application for treatment of spasticity. All patients had a history of traumatic brain injury, while one patient also suffered a spinal cord injury. Two patients experienced their first seizure following intrathecal baclofen test bolus injection. Another patient had convulsions on two occasions: following postoperative baclofen dose adjustment, and after sleep deprivation. Structural brain disease seems prerequisite for baclofen to exert epileptogenic activity, since seizures have not occurred in patients receiving intrathecal baclofen for spasticity of solely spinal origin. Antiepileptic medication permitted the continuation of intrathecal baclofen treatment in the three patients.