P.J. Maccabee

Short latency somatosensory evoked potentials to median nerve stimulation: effect of low frequency filter☆☆☆

The effect of low frequency filter bandpass restriction on median nerve short latency somatosensory evoked potentials was studied in 19 normal adult subjects. Components recorded with open bandpass (5-3000 Hz) were designated by numerical subscript (e.g. N20) and components recorded with restricted bandpass (150 or 300-3000 Hz) were designated by numerical superscript (e.g. N20). In open bandpass recordings, the response consisted of 3 positive potentials, the third of which was sometimes bilobed (P9, P11, P13, P14), followed by negative, positive, and negative potentials (N20, P23, N30). In restricted bandpass recordings the first three positive potentials were well defined and the N20 component was fractionated into 3 components (n16, N18, N20). N20 was followed by P21 and N23. Scalp distribution studies showed that N16 was widely distributed over the scalp but was slightly more prominent over primary somesthetic scalp regions contralateral to the side of stimulation which is consistent with an origin in caudal thalamocortical radiations. N18 and N20 were localized to somesthetic scalp regions contralateral to the side of stimulation suggesting an origin in terminal thalamocortical radiations or cerebral cortex. Open pass P23 and N30 and restricted pass P21 and N23 recorded over somesthetic scalp regions contralateral to the side of stimulation were often associated with components of similar latency but opposite polarity recorded over frontal scalp regions. Low amplitude fast frequency components were sometimes recorded between 25 and 40 msec in restricted bandpass recordings. These findings show that N20 arises in multiple generator sources of both far- and near-field origin and that multiple generators contribute to the SEP within 10-15 msec of the arrival of the volley in cerebral cortical elements. Since bandpass restriction selectively affects slow frequency activity which reflects primarily synaptic events rather than fast frequency activity which reflects axonal events, the use of bandpass restriction may aid in differentiating between these different types of activity.

An analysis of peripheral motor nerve stimulation in humans using the magnetic coil

We compared conventional electrical and magnetic coil (MC) stimulation of distal median nerve in 10 normal subjects and 1 patient. Orthogonal (90 degrees to volar forearm)-longitudinal (the plane of the MC aligned with the long axis of nerve or wire), tilted (to 45 degrees) longitudinal, and tangential edge orientations elicited maximal or near maximal compound motor axon potentials (CMAPs) without simultaneous co-activation of ulnar nerve. Transverse and symmetrical tangential orientations were inefficient. A simulation study of an ideal volume conductor confirmed these findings by predicting that the maximum current density was near the outer edge of the MC and not at the center where the magnetic flux intensity is maximal. An orthogonal-longitudinal MC induces a current in the adjacent volume conductor (for example elbow or wrist), which flows in the same circular direction as in the MC. This differs from a tangentially orientated MC which classically elicits current flow in the volume conductor opposite in circular direction to that in the MC. Amplitude and latency of the CMAP were both altered, but not identically, by changing the intensity of MC and cathodal stimuli. Rotating an orthogonal-longitudinal MC through 180 degrees, thus reversing the direction of current flow, elicited single fiber muscle action potentials whose peak latencies differed at most by 100 microseconds. Thus, the (virtual) cathode and anode are significantly closer (i.e., 5-6 mm) with MC than with electrical stimulation where they are at least 20 mm apart. A disadvantage of MC stimulation is the imprecision in defining exactly where the distally propagating nerve impulse originates. In different subjects, using maximum output and orthogonal or tilted (to 45 degrees) longitudinal orientations, the calculated site of excitation in the median nerve varied 2-15 mm distal to the midpoint of the contacting edge of the MC. This limits the usefulness of the MC in its current configuration for determining distal motor latencies. Future advances in MC design may overcome these difficulties.

In vitro evaluation of a 4-leaf coil design for magnetic stimulation of peripheral nerve

The performance of a 4-leaf magnetic coil was evaluated during magnetic stimulation of a peripheral nerve in vitro. The site of stimulation was below the coil center, and a 90 degrees rotation of the coil was equivalent to a change in current polarity. A hyperpolarizing magnetic stimulus failed to slow or block a propagating action potential.

Cerebello-frontal cortical projections in humans studied with the magnetic coil

Focal stimulation over human cerebellum with a figure 8 magnetic coil (MC) results in an evoked wave recorded from bipolar scalp electrodes on the interaural line and more anteriorly. In 3 subjects, the wave responses along the interaural line had latencies of 8.8-13.8 msec, lasted 17.4-29.0 msec and had a maximum amplitude of 14.4-26.8 microV. The responses were recorded more anteriorly from leads midway between the interaural line and frontal leads; responses recorded from frontal leads were up to 3.5 msec later. The evoked wave was preceded by a diphasic EMG response with a latency of 1.2-2.0 msec. Analysis of the averaged responses recorded by adjoining bipolar leads indicated that the response was predominantly surface positive and crossed. Control experiments eliminated eye movement and somatosensory input as explanations of the evoked response, thereby identifying it as a cortical response. The surface positive wave in humans was compared with the responses recorded in cat and monkey to cerebellar stimulation. The responses in humans could reflect dysfacilitation through MC activation of Purkinje cells, or feed-forward facilitation through transsynaptic or antidromic activation of dentate neurons. The latency of the surface positive wave exceeds that of cerebellar inhibition of MC elicited hand muscle responses, but the discrepancy is at least partly accounted for by the extra delay required to set up the indirect cortico-spinal component required for motoneuron discharge. Estimates made of the cerebello-frontal cortical and peripheral feedback loop times suggest that the central has less than one quarter the delay of the peripheral loop, which would be especially advantageous during fast skilled movements of the fingers.

The polarity of the induced electric field influences magnetic coil inhibition of human visual cortex: Implications for the site of excitation

Human perception of 3 briefly flashed letters in a horizontal array that subtends a visual angle of 3 degrees or less is reduced by a magnetic coil (MC) pulse given, e.g., 90 msec later. Either a round or a double square MC is effective when the lower windings or central junction region, respectively, are tangential to the skull overlying calcarine cortex and symmetrical across the midline. The modeled, induced electric field has peak amplitude at the midline, but the peak spatial derivatives lie many centimeters laterally. Thus, the foveal representation near the midline is closer to the peak electric field than to its peak spatial derivatives, i.e., excitation of calcarine cortex differs from excitation of a straight nerve. With an MC pulse that induces an electric field which is substantially monophasic in amplitude, the lateral-most letter (usually the right-hand letter) in the trigram is preferentially suppressed when the electric field in the contralateral occipital lobe is directed towards the midline. Inferences from using peripheral nerve models imply that medially located bends in geniculo-calcarine or corticofugal fibers are the relevant sites of excitation in visual suppression; end excitation of fiber arborizations or apical dendrites is considered less likely. This conclusion is supported by the fact that the induced electric field polarity in paracentral lobule for optimally eliciting foot movements is opposite to that for visual suppression, the major bends occurring at different portions of the fiber trajectories in the two systems.

Evoked potentials recorded from scalp and spinous processes during spinal column surgery

Peroneal nerve evoked potentials were simultaneously recorded from scalp and from wire electrodes inserted into lumbar and thoracic spinous processes at multiple levels during surgery for correction of spinal column curvature in 43 patients. Spinal potentials progressively increased in latency rostrally. Over cauda equina and rostral spinal cord initially positive triphasic potentials were recorded. Over caudal spinal cord the response consisted of initial positive-negative diphasic potentials that merged with broad large negative and positive potentials. At rapid rates of stimulation, the initial diphasic component was stable but the subsequent potentials significantly diminished in amplitude. This suggests that the diphasic component reflects presynaptic activity arising in the intramedullary continuations of dorsal root fibers and that the subsequent components reflect largely postsynaptic activity. Scalp recordings at restricted bandpass (30-3000 c/sec) revealed well defined positive and negative potentials with mean peak latencies of 25.9 and 29.9 msec (PV-N1). The amplitudes and latencies of PV-N1 remained relatively stable throughout general anesthesia with halogenated agents which suggests that this component may be a reliable monitor of conduction within spinal cord afferent pathways during spinal surgery. Data are presented which suggest that selective filtering may help to distinguish faster frequency, synchronous axonal events from slower frequency, asynchronous axonal or synaptic events.

SHORT‐LATENCY SOMATOSENSORY EVOKED POTENTIALS TO MEDIAN AND PERONEAL NERVE STIMULATION: STUDIES IN NORMAL SUBJECTS AND PATIENTS WITH NEUROLOGIC DISEASE

SSEPs to median nerve stimulation which arise in the brachial plexus, subcortical and cortical structures can be recorded from the scalp. Abnormalities of these potentials have been found in patients with demyelinating disease and focal or diffuse disease of the nervous system. SSEPs to peroneal nerve stimulation which arise in rostral spinal cord, brainstem, and cerebral structures have also been recorded from the scalp. These methods can be expected to provide useful information in patients with certain neurological disorders.

Short latency somatosensory and spinal evoked potentials: Power spectra and comparison between high pass analog and digital filter

Medium nerve somatosensory evoked potentials (SSEPs) and intraoperative spinal evoked potentials were analyzed using different analog and zero phase shift digital high pass filter and by power spectrum. Additionally, high pass analog and digital filtering was performed on various sine, triangular and rectangular waves manufactured by a wave form generator. Recordings were also transformed to the 1st and 2nd time derivatives. The great abundance of spectral energy for scalp recorded median nerve SSEPs was below 125 c/sec but lower energy fast frequency components consistently extended to 500 c/sec. Power spectrum of the Erbs point compound nerve action potential revealed a wide band of spectral energy commencing at about 50-100 c/sec, peaking at about 250-270 c/sec and extending to nearly 1000 c/sec. This suggests that synchronous axonal activity generates predominantly faster frequencies above 100 c/sec. High pass analog filter confers phase non-linearity which results in various distortions including latency shift and a morphological change which may be visually similar to the 1st or 2nd time derivatives. High pass zero phase shift digital filter removes selected low frequencies without accompanying phase distortion. This accentuates fast peaks seen at open bandpass as well as transition points between baseline and component ascent or descent. Zero phase shift digital filter may also generate peaks that are not visualized at open pass but which reflect the sum of frequencies which were not removed by filtering. These peaks do not necessarily correspond to discrete singular neuroanatomical structures. Although peaks observed in high pass analog and digital filter appear similar and comparable, their underlying activity may be of different origin. This is because high pass analog filter projects a considerable amount of overlap from earlier onto later waves. For clinical correlation it is important that restricted bandpass analog or digitally filtered recordings be compared with open pass data. Only those peaks visualized in both open and restricted bandpass can be considered authentic. Examples of spinal and scalp SSEPs indicate that selective filtering may, under certain circumstances, distinguish axonal or lemniscal from synaptic generators.

The neurofilament light chain gene (NEFL) mutation Pro22Ser can be associated with mixed axonal and demyelinating neuropathy

We report the detailed clinical, electrophysiological and molecular analysis of a patient with Charcot-Marie-Tooth (CMT) disease. DNA sequencing of the coding sequences of the neurofilament light chain polypeptide (NEFL) gene revealed a c.64C>T heterozygous, missense mutation resulting in a Pro22Ser amino acid substitution. Clinical and electrophysiological studies revealed a mixed axonal and demyelinating neuropathy, with widespread demyelination involving both proximal and distal nerve segments. Mutations at this site in the NEFL gene have been previously linked to an axonal neuropathy or distal nerve demyelination. Our results emphasize the complexity of genotype-phenotype correlations in CMT and underline the possible importance of host factors and gene interactions in the development of clinical phenotypes.

Upper leg conduction time distinguishes demyelinating neuropathies

Background: The objective of this study was to determine whether differentiation between demyelinating and axonal neuropathies could be enhanced by comparing conduction time changes in defined segments of the total peripheral nerve pathway. Methods: Compound muscle action potentials (CMAPs) were elicited by cathodal stimulation of the tibial nerve at the ankle and popliteal fossa, and by paravertebral neuromagnetic stimulation at proximal and distal cauda equina while recording from muscles of the foot, shin, and thigh. Segmental conduction times were calculated in normal subjects; in patients with lumbosacral radiculopathy, distal symmetric diabetic neuropathy, amyotrophic lateral sclerosis, acute and chronic inflammatory demyelinating polyneuropathy; and in patients with anti–myelin‐associated glycoprotein, myelomatous, and Charcot–Marie–Tooth type 1a polyneuropathies. Results: Distal cauda equina latency and CMAP duration and segmental conduction times in upper leg and cauda equina facilitated differentiation of demyelinating from axonal neuropathies, even in the presence of a range of reduced amplitude CMAPs. Conclusions: Within the demyelinating neuropathy spectrum, it was further possible to distinguish subtypes. Muscle Nerve, 2011