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Biomedical subjects

A Romaniello

Publications and source records attributed to A Romaniello.

At least 19 recordsLinked to original sources
PubMed2006

Experimental skin pain and muscle pain induce distinct changes in human trigeminal motoneuronal excitability.

Seeking information on the physiological properties of the trigeminal motoneuronal pool we investigated changes in the excitability of trigeminal motor system induced by two types of experimental pain (muscle and skin). In one session, we studied the effect of muscle pain induced by hypertonic saline infusion into the masseter muscle on the recovery cycle of the heteronymous H-reflex in the temporalis muscle and the homonymous silent period (SP) in the masseter muscle, both elicited by stimulation of the masseteric nerve in ten-healthy subjects. In another session, we studied the effect of laser stimuli applied to the perioral region, at conditioning intervals from 20 to 160 ms, on the temporalis H-reflex and masseter SP in nine healthy subjects. Whereas laser-induced skin pain significantly inhibited the temporalis H-reflex and facilitated the masseter SP (P < 0.01), muscle pain left the time course of the temporalis H-reflex and masseter SP unchanged (P > 0.05). The timing of temporalis H-reflex suppression and masseter-SP enhancement induced by laser stimuli indicates that facial skin nociceptors inhibit trigeminal motoneurones via multysynaptic reflex pathways. Hypertonic saline, a stimulus that predominantly activates group III and IV afferents, left both variables reflecting trigeminal motoneuron excitability unchanged. Due to the differences between the two experimental models, we cannot conclude that such inhibitory reflex pathway does not exist from muscle nociceptors to trigeminal motoneurones.

Adult↗
PubMed2006

One hour of tongue-task training is associated with plasticity in corticomotor control of the human tongue musculature.

Corticomotor control of the human tongue has been reported to undergo neuroplastic changes following several days of training in a tongue-protrusion task. The aims of the present study were to determine if a 1 h tongue-task training is sufficient to induce signs of neuroplastic changes in the corticomotor pathways, and to obtain preliminary information on the time course of such changes. Corticomotor excitability was assessed by changes in electromyographic activity evoked by transcortical magnetic stimulation (TMS) in 11 healthy subjects. Motor evoked potentials (MEPs) recorded in the tongue musculature and the first dorsal interosseous (FDI) muscle were assessed at four sessions: at baseline before training, 30 min after training, and 1 and 7 days after training. All subjects performed successfully the task (success rate: 38+/-4%). Thresholds for evoking MEPs by TMS in the tongue were decreased at 30 min, 1 and 7 days after training compared with baseline (ANOVA: P<0.001). Tongue MEP amplitudes were significantly increased at 1 day follow-up and had returned to baseline values at 7 days follow-up (ANOVA: P<0.001). No significant effect of tongue-task training on FDI MEPs was observed (ANOVA: P=0.160). Corticomotor topographic maps revealed increases (ANOVA: P<0.001) in area at the 1 day follow-up. The success rate was significantly correlated to the net increases in tongue MEPs at 1 day follow-up (Spearman: 0.615; P=0.0039). The present findings confirm that tongue task training is associated with plasticity of corticomotor excitability specifically related to the tongue musculature and further document that plasticity is evident within 30 min post-training and may last up to at least 7 days.

Adult↗
PubMed2005

Laser-evoked potentials: normative values.

OBJECTIVE: Laser-evoked potentials (LEPs) currently represent the most reliable and widely agreed method of investigating the A delta-fibre pathways. Many studies dealt with the usefulness of LEPs in peripheral and central nervous system diseases. We aimed at gaining normative values for LEP data. METHODS: Using a CO2 laser stimulator we recorded LEPs after face, hand, and foot stimulation in 100 normal subjects. We measured the perceptive threshold, latency and amplitude of the main vertex components, and their side-to-side differences. We also studied the correlations between LEP data and age and body height, as well as gender differences. RESULTS: Laser perceptive threshold increased and LEP amplitude decreased from face to foot (P<0.0001). The latency of hand and foot-LEPs correlated significantly with body height (P<0.0001). The amplitude, though not the latency, correlated with age (P<0.0001). LEP data did not significantly differ between genders (P>0.1). CONCLUSIONS: This study provides normative values for the main LEP data and their absolute and side-to-side limits, highlighting the physiological differences related to, body height, age, gender and stimulation site. SIGNIFICANCE: Our data may help to improve the clinical reliability of LEPs as a diagnostic tool.

Adolescent↗
PubMed2005

Laser evoked potentials and carbamazepine in epileptic patients.

AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve conduction; reports on conventional somatosensory evoked potentials and CBZ are controversial. In a previous study, assessing laser-evoked potentials (LEPs) in CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs were dampened even after stimulation of the non-painful side, with a strong correlation between LEP latency and daily CBZ dose. No other study investigated the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20 patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although the trigeminal LEP mean latency was slightly longer in epileptic patients (P=0.11), we did not find significant differences between epileptic patients and controls for any LEP data. LEP data did not correlate with the daily CBZ dose, CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to large-fibre, might be less susceptible to AED's toxic effect. Although the TN patients in our previous study were older than the epileptic patients in the present study, a possible combined effect induced by drug and age in patients with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ-induced effect in patients with trigeminal neuralgia is possibly related to pathophysiological changes specific to this disease.

Adolescent↗
PubMed2004

Brainstem reflex circuits revisited.

Our current understanding of brainstem reflex physiology comes chiefly from the classic anatomical-functional correlation studies that traced the central circuits underlying brainstem reflexes and establishing reflex abnormalities as markers for specific areas of lesion. These studies nevertheless had the disadvantage of deriving from post-mortem findings in only a few patients. We developed a voxel-based model of the human brainstem designed to import and normalize MRIs, select groups of patients with or without a given dysfunction, compare their MRIs statistically, and construct three-plane maps showing the statistical probability of lesion. Using this method, we studied 180 patients with focal brainstem infarction. All subjects underwent a dedicated MRI study of the brainstem and the whole series of brainstem tests currently used in clinical neurophysiology: early (R1) and late (R2) blink reflex, early (SP1) and late (SP2) masseter inhibitory reflex, and the jaw jerk to chin tapping. Significance levels were highest for R1, SP1 and R2 afferent abnormalities. Patients with abnormalities in all three reflexes had lesions involving the primary sensory neurons in the ventral pons, before the afferents directed to the respective reflex circuits diverge. Patients with an isolated abnormality of R1 and SP1 responses had lesions that involved the ipsilateral dorsal pons, near the fourth ventricle floor, and lay close to each other. The area with the highest probabilities of lesion for the R2-afferent abnormality was in the ipsilateral dorsal-lateral medulla at the inferior olive level. SP2 abnormalities reached a low level of significance, in the same region as R2. Only few patients had a crossed-type abnormality of SP1, SP2 or R2; that of SP1 reached significance in the median pontine tegmentum rostral to the main trigeminal nucleus. Although abnormal in 38 patients, the jaw jerk appeared to have no cluster location. Because our voxel-based model quantitatively compares lesions in patients with or without a given reflex abnormality, it minimizes the risk that the significant areas depict vascular territories rather than common spots within the territory housing the reflex circuit. By analysing statistical data for a large cohort of patients, it also identifies the most frequent lesion location for each response. The finding of multireflex abnormalities reflects damage of the primary afferent neurons; hence it provides no evidence of an intra-axial lesion. The jaw jerk, perhaps the brainstem reflex most widely used in clinical neurophysiology, had no apparent topodiagnostic value, probably because it depends strongly on peripheral variables, including dental occlusion.

Adult↗
PubMed2004

Laser evoked potentials for assessing sensory neuropathy in human patients.

Sensory neuropathy usually impairs tactile sensations related to large myelinated afferents (Abeta) as well as thermal-pain sense related to small myelinated (Adelta) and unmyelinated (C) afferents. By selectively affecting large or small fibres, some sensory neuropathies may also provoke a dissociated sensory loss. Standard nerve conduction studies and somatosensory evoked potentials assess Abeta-fibre function only. Laser pulses selectively excite free nerve endings in the superficial skin layers and evoke Adelta-related brain potentials (LEPs). From earlier studies and new cases we collected data on 270 patients with sensory neuropathy. LEPs often disclosed subclinical dysfunction of Adelta fibres and proved a sensitive and reliable diagnostic tool for assessing small-fibre function in sensory neuropathy.

Evoked Potentials, Somatosensory↗
PubMed2004

Excitability of the Adelta nociceptive pathways as assessed by the recovery cycle of laser evoked potentials in humans.

To investigate the excitability of Adelta nociceptive pathways and the nature of the vertex laser evoked potentials (LEPs), we studied the recovery cycle of the P2-LEP component and compared it with that of the P200 of the somatosensory evoked potential (SEP). Using two identical CO(2)-laser stimulators, we delivered paired stimuli to two adjacent skin spots on the hand at interstimulus intervals ranging from 250 ms to 2 s. The test P2-LEP was strongly inhibited at the 250-ms interstimulus interval ( P<0.01) and progressively recovered by the 2-s interval. The P200-SEP, after paired stimuli to the median nerve, showed a time course even slower than the P2-LEP ( P<0.01). Besides providing the LEP recovery curve in normal subjects, our findings indicate that the P2-LEP relays through a number of synapses similar to (or even lower than) that for the P200-SEP, thus lending further support to the view that the nociceptive P2-LEP is not an endogenous potential equivalent to the P300.

Adult↗
PubMed2004

Cutaneous silent period in hand muscle is evoked by laser stimulation of the palm, but not the hand dorsum.

Painful electrical stimulation of the fingers evokes an inhibitory response in hand muscles (cutaneous silent period, CSP). The aim of this study was to determine whether purely nociceptive thermal stimuli applied to the hand evoke a CSP. High-intensity laser pulses (205 +/- 44 mJ) were delivered to the dorsum and palm of the hand in five volunteers. Electromyographic signals were recorded from the ipsilateral first dorsal interosseous muscle. We then compared the laser-evoked CSP with the CSP induced by electrical stimulation. A clear laser CSP (latency 90 +/- 7 ms) was evoked in all subjects when laser pulses were applied to the palm of the hand, whereas no response was recorded after stimulation of the dorsum. Electrical stimulation of both the dorsum and the palm evoked a CSP (latency 65 +/- 5 ms), although the reflex threshold was significantly lower after stimulation of the palm. This study confirms that the CSP is a nociceptive response specific to limbs that grasp. In humans, palm nociceptors are probably more functionally effective than dorsal nociceptors in inducing the hand-muscle inhibition that interrupts hand prehension (so that a potentially noxious source is dropped) before proximal muscles withdraw the limb.

Adult↗
PubMed2003

Unmyelinated trigeminal pathways as assessed by laser stimuli in humans.

Laser pulses excite superficial free nerve endings innervated by small-myelinated (Adelta) and unmyelinated (C) fibres. Whereas laser-evoked scalp potentials (LEPs) are now reliably used to assess function of the Adelta-fibre nociceptive pathways in patients with peripheral or central lesions, the selective activation of C-fibre receptors and recording of the related brain potentials remain difficult. To investigate trigeminal C-fibre function, we directed laser pulses to the facial skin and studied sensory perception and scalp evoked potentials related to Adelta- or C-fibre activation in healthy humans and patients--one having a bilateral facial palsy, two a trigeminal neuropathy, and two a Wallenberg syndrome. We also measured afferent conduction velocity and, with source analysis, studied the brain generators. Whereas laser pulses of low intensity and small irradiated area elicited pinprick sensations and standard Adelta-LEPs, laser pulses of very-low intensity and large irradiated area elicited warmth sensations and scalp potentials with a latency compatible with C-fibre conduction (negative wave 280 ms, positive wave 380 ms); the estimated conduction velocity was 1.2 m/s. The main waves of the scalp potentials originated from the anterior cingulate gyrus; they were preceded by activity in the opercular region and followed by activity in the insular region. The patient with bilateral facial palsy, who had absent trigeminal-facial reflexes, had normal Adelta- and C-related scalp potentials; the patients with trigeminal neuropathy, characterized by loss of myelinated and sparing of unmyelinated fibres, had absent Adelta- but normal C-related potentials; and the patients with Wallenberg syndrome had absent Adelta- and C-related potentials. We conclude that laser pulses with appropriate characteristics evoke brain potentials related to the selective activation of trigeminal nociceptive Adelta or thermal C fibres. The trigeminal territory yields rewarding LEP findings owing to the high density of thermal receptors and, because the short conduction distance, minimizes the problem of signal dispersion along slow-conducting unmyelinated afferents. The opercular-insular region and the cingulate gyrus are involved in the processing of C-fibre trigeminal inputs. The method we describe may prove useful in patients with lesions affecting the trigeminal thermal pain pathways.

Adult↗
PubMed2003

Trigeminal responses to laser stimuli.

The majority of the studies on laser evoked potentials (LEPs) have been focused on hand and foot stimulations and only lately on the trigeminal system. Because of a high receptor density in the facial skin and the very short conduction distance, LEP recordings after trigeminal stimulation are easier and quicker than those after stimulation of the limb extremities. Laser pulses with a stimulus intensity close to perception threshold can evoke well-defined LEPs. Few trials are sufficient to yield stable and reproducible averages. Even ultralate LEPs related to the C-fibre input are comparatively easily obtained from the trigeminal territory. The brain generators of the main LEP waves are probably very close for the trigeminal and limb stimulations. Trigeminal LEPs have been found absent or delayed in patients with trigeminal neuralgia, trigeminal neuropathies, posterior fossa tumors, and brainstem infarctions or demyelinating plaques. Conversely, trigeminal LEPs appear to be enhanced in patients with migraine. High-intensity pulses directed to any trigeminal division also elicit reflex responses: a blink-like reflex in the orbicularis oculi and a single silent period in the contracting masseter muscle. The availability of a neurophysiological method of assessing function of the trigeminal nociceptive pathways reaching both the cerebral cortex and the brainstem reflex circuits, has provided new opportunities for investigating the pathophysiology of orofacial pain syndromes.

Blinking↗
PubMed2003

Assessment of nociceptive trigeminal pathways by laser-evoked potentials and laser silent periods in patients with painful temporomandibular disorders.

We assessed the trigeminal nociceptive pathways in patients with painful temporomandibular disorders (TMD) and control subjects using a CO(2)-laser stimulator which provides a predominant activation of the nociceptive system. Fifteen patients with unilateral pain were examined in accordance with the Research Diagnostic Criteria for TMD and 30 gender- and age-matched individuals were included as a control group. Laser-evoked potentials (LEPs) and laser silent periods (LSPs) after stimulation of the perioral region (V2/V3) on the painful and non-painful sides were recorded in all subjects. LEPs were evoked by low-intensity pulses (1.5 x perception threshold (PTh)) and recorded from scalp electrodes at the vertex. LSPs were evoked by high-intensity pulses (4 x PTh) and recorded bilaterally from masseter muscles with surface electromyogram (EMG) electrodes. Subjects also assessed the stimulus intensity on a 0-10 rating scale. LEPs had normal latency but smaller amplitude in TMD patients compared to the control group (P<0.001). Side-to-side comparison within patients showed that LEP amplitude was even more reduced after stimulation on the painful than the non-painful side (P<0.001). TMD patients showed a significant side-asymmetry of the pre-stimulus EMG activity, with a smaller value in the muscle on the painful side (P<0.001). LSPs were completely absent bilaterally in 12 TMD patients and unilaterally in two patients; only one patient had normal and bilateral LSPs. TMD patients perceived the laser stimulus less intense on the painful than the non-painful side (P<0.05). We found suppression of cortical responses and brainstem reflexes elicited by a predominantly nociceptive input in TMD patients. These findings are consistent with recent experimental pain studies and suggest that chronic craniofacial pain in TMD patients may be associated with a dysfunction of the trigeminal nociceptive system.

Adult↗
PubMed2003

Laser-evoked potentials in post-herpetic neuralgia.

OBJECTIVE: We evaluated the reliability of laser-evoked potentials (LEPs) as a diagnostic tool in patients with post-herpetic neuralgia (PHN), i.e. a chronic painful condition that causes small-diameter fibre dysfunction. Furthermore, we sought information on pathophysiology of PHN pain. METHODS: We recorded 'late' LEPs after stimulation of the supraorbital, upper cervical, lower cervical, upper thoracic, mid thoracic, and lower thoracic territories in 12 control subjects and 40 patients with PHN. We also determined the correlation of LEP data with age, duration of disease, and severity and quality of pain. RESULTS: At all stimulation sites, laser pulses invariably evoked high-amplitude brain potentials related to small-myelinated (A-delta) fibre activation. The laser perceptive threshold and LEP latency correlated with the distance of the dermatome from the brain (P<0.001). In patients, the perceptive threshold was higher and the LEP amplitude was lower in the affected dermatome than on the contralateral side (P<0.001). We found no significant LEP-clinical correlation except for a correlation between LEP abnormality and age. CONCLUSIONS: Being sensitive and reliable in assessing sensory function also in proximal dermatomes, LEPs are a promising diagnostic tool in radiculopathies. Although PHN severely impairs small myelinated fibres, the lack of a significant correlation between LEP abnormalities and pain suggests that pain in PHN does not chiefly arise from a dysfunction of small-myelinated afferents.

Adult↗
PubMed2003

Evidence of a specific spinal pathway for the sense of warmth in humans.

While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting Adelta nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO(2)-laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with high-resolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470-540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by Adelta nociceptive input (290-320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the Adelta input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.

Adult↗
PubMed2002

Nociceptive quality of the laser-evoked blink reflex in humans.

Laser radiant-heat pulses selectively excite the free nerve endings in the superficial layers of the skin and activate mechano-thermal nociceptive afferents; when directed to the perioral or supraorbital skin, high-intensity laser pulses evoke a blink-like response in the orbicularis oculi muscle (the laser blink reflex, LBR). We investigated the functional properties (startle or nociceptive origin) of the LBR and sought to characterize its central pathways. Using high-intensity CO(2)-laser stimulation of the perioral or supraorbital regions and electromyographic (EMG) recordings from the orbicularis oculi muscles, we did five experiments in 20 healthy volunteers. First, to investigate whether the LBR is a startle response, we studied its habituation to expected rhythmic stimuli and to unexpected arrhythmic stimuli. To assess its possible nociceptive quality, we studied changes in the LBR and the R2 component of the electrical blink reflex after a lidocaine-induced supraorbital nerve block and after intramuscular injection of the opiate fentanyl and the opiate-antagonist naloxone. To characterize the central pathways for the LBR, we investigated the interaction between the LBR and the three components of the blink reflex (R1, R2, and R3) by delivering laser pulses to the perioral or supraorbital regions before or after electrical stimulation of the supraorbital nerve at various interstimulus intervals. Finally, to gain further information on the central LBR pathways, using two identical CO(2)-laser stimulators, we studied the LBR recovery curves with paired laser pulses delivered to adjacent forehead points at interstimulus intervals from 250 ms to 1.5 s. The LBR withstood relatively high-frequency rhythmic stimulations, and unexpected laser pulses failed to evoke larger responses. When lidocaine began to induce hypoalgesia (about 5 min after the injection), the LBR was abolished, whereas R2 was only partly suppressed 10 min after the injection. Fentanyl injection induced strong, naloxone-reversible, LBR suppression (the response decreased to 25.3% of predrug values at 10 min and to 4% at 20 min), whereas R2 remained appreciably unchanged. Whether directed to the perioral or supraorbital regions, preceding laser pulses strongly suppressed R2 and R3 though not R1. Conversely, preceding electrical stimuli to the supraorbital nerve suppressed the LBR. In response to paired stimuli, the LBR recovered significantly faster than R2. These findings indicate that the LBR is a nociceptive reflex, which shares part of the interneuron chain mediating the nonnociceptive R2 blink reflex, probably in the medullary reticular formation. The LBR may prove useful for studying the pathophysiology of orofacial pain syndromes.

Adult↗
PubMed2001

Small-fiber dysfunction in trigeminal neuralgia: carbamazepine effect on laser-evoked potentials.

BACKGROUND: In patients with trigeminal neuralgia, results of clinical examination of sensory function are normal. Reflex and evoked potential studies have already provided information on large-afferent (non-nociceptive) function. Using laser-evoked potentials (LEP), the authors sought information on small-afferent (nociceptive) function. METHODS: The brain potentials evoked by CO(2)-laser pulses directed to the perioral and supraorbital regions were studied in 67 patients with idiopathic or symptomatic trigeminal neuralgia and 30 normal subjects. Of the 67 patients, 49 were receiving carbamazepine. RESULTS: All patients with symptomatic and 51% of those with idiopathic trigeminal neuralgia had frankly abnormal LEP on the painful side. The mean latency was significantly higher and mean amplitude lower on the painful than the nonpainful side. However, even on the nonpainful side, the mean latency was significantly longer than that of the age-matched controls. The nonpainful-side latency correlated significantly with the carbamazepine dose. CONCLUSIONS: LEP detect severe impairment of the nociceptive afferent system on the painful side of patients with idiopathic as well as symptomatic trigeminal neuralgia. A dysfunction of small-myelinated afferents may play an important role in the pathophysiology of neuralgic pain. Carbamazepine markedly dampens these brain potentials. The authors propose that this effect may result from inhibition of nociceptive transmission in the cingulate gyrus.

Afferent Pathways↗
PubMed2001

Motor potentials evoked by transcranial magnetic stimulation during isometric and dynamic masseter muscle contraction in humans.

The facilitation of muscle motor potentials evoked by transcranial magnetic stimulation (TMS) has been demonstrated convincingly during both isometric and dynamic activity in the limbs but not in the jaw muscles. An experimental design involving TMS, surface electromyography and controlled muscle-activity was employed to investigate the motor response of the human masseter during voluntary isometric and dynamic voluntary conditions. During the isometric condition, an increase in muscle facilitation resulted in a progressive increase in motor-evoked potential (MEP) amplitude that was consistently greater on the side contralateral to that subjected to TMS (P < 0.05). No difference in MEP amplitude or laterality of response was revealed for the two dynamic conditions. The sample size may have been too small to reveal any differences. The modulation of MEPs during isometric activity was probably due to cortical and brainstem mechanisms. Putative variation in masseter MEPs during dynamic conditions cannot be discounted.

Adult↗
PubMed2001

Usefulness of dorsal laser evoked potentials in patients with spinal cord damage: report of two cases.

Stimulation of the dorsal skin with brief laser impulses easily evokes brain potentials (laser evoked potentials, LEPs). Dorsal LEPs were first used to study the conduction velocity in the human spinothalamic tract. In this study the diagnostic usefulness of this technique was assessed by recording dorsal LEPs in two patients with focal spinal cord lesions (one intrinsic and the other extrinsic) and spared lemniscal sensitivities. In both cases, the brain evoked potentials were normal after stimulation of the metamers above the lesion but absent after stimulation of those below. Dorsal LEP recordings may prove a useful tool in localising lesions and in the neurophysiological assessment of focal spinal cord lesions involving the anterolateral quadrants of the spinal cord.

Aged↗