Leoluca Parisi

Effects of diffuse noxious inhibitory controls on temporal summation of the RIII reflex in humans

&NA; The aim of this study was to investigate the effects of diffuse noxious inhibitory controls (DNICs) on the temporal summation of the nociceptive flexion reflex (RIII reflex) in humans. Recordings were obtained from 36 healthy adults (16 M, 20 F), and the area and temporal summation threshold (TST) of the RIII reflex were measured. The subjective intensity of the painful sensation was rated on an 11‐point visual analogue scale (VAS). Neurophysiological and VAS measurements were recorded after activation of DNICs by means of the cold pressor test (CPT), which involved immersing the hand in cold water (2–4 °C). A slight significant lower TST was found in the females versus the males. In all the subjects, the CPT induced a significant TST increase and RIII area reduction compared with the control session. The VAS results paralleled those of the RIII reflex area and TST. During the CPT, a significant difference in the percentage TST increase emerged between females and males, being lower in the former. Similarly, we found a significantly lower percentage reduction of the RIII area in women than in men during the CPT. To summarize, activation of DNICs through the CPT significantly increased the TST of the RIII reflex in healthy subjects. This inhibitory effect was gender‐specific. Whereas other findings are based on psychophysical evaluations, the results of this experimental study provide an objective neurophysiological demonstration that DNICs attenuate temporal summation in humans and confirm the presence of significant differences in pain modulation mechanisms between men and women.

Cutaneous afferents mediating the cutaneous silent period in the upper limbs: evidences for a role of low-threshold sensory fibres

OBJECTIVES To evaluate the contribution of the low-threshold afferents to the production of the cutaneous silent period (CSP) in the upper limbs. METHODS The CSP was studied in 10 healthy adults and 4 patients with Friedreichs ataxia. The following neurophysiological aspects were studied: (a) relationship between sensory threshold (ST), sensory action potential (SAP) amplitude and CSP parameters; (b) habituation and recovery cycle of the CSP at different stimulus intensities (2xST and 8xST); (c) pattern of responses in distal and proximal muscles at different stimulus intensities (2xST and 8xST). RESULTS (a) The CSP occurred at low intensities (1xST and 2xST) and increased abruptly between 3.5xST and 4xST (corresponding to the pain threshold). The SAP amplitude was saturated before CSP saturation. In the patients with Friedreichs ataxia, the CSP appeared only at higher stimulus intensities (6xST-8xST). (b) The CSP evoked at 2xST showed a fast habituation and slow recovery cycle whereas the opposite behaviour was found at 8xST. (c) Low-threshold stimuli induced an inhibitory response restricted to the distal muscles. High-intensity stimulation produced an electromyographic suppression, significantly increasing from proximal to distal muscles. CONCLUSIONS Our findings support the notion that low-threshold afferents participate in the production of the CSP in the upper limbs. The different afferents may activate different central neural networks with separate functional significance.

Postural Rearrangement in IDDM Patients With Peripheral Neuropathy

OBJECTIVE To evaluate the influence of diabetic peripheral neuropathy on postural strategy. RESEARCH DESIGN AND METHODS Static posturography and nerve conduction velocity were performed in the following age-matched subjects: 10 IDDM patients with peripheral neuropathy, 23 IDDM patients without peripheral neuropathy, and 21 control subjects. All subjects with signs or symptoms of postural instability were excluded from the study. The following posturographic parameters were drawn: 1) velocity of body sway, expressed as mean velocity and average of the SDs, 2) VFY, the parameter derived from the velocity variance and the anteroposterior mean position of the body (this parameter monitors the postural strategy pursued by the subject), and 3) fast Fourier transformation on the x (FFTX) and y (FFTY) planes, spectral analysis of the frequencies of body oscillation on frontal (x) and anteroposterior (y) planes. RESULTS Mean velocity and its SD were higher in IDDM patients with peripheral neuropathy than in control subjects and IDDM patients without peripheral neuropathy (P < 0.001). VFY was increased in IDDM patients with peripheral neuropathy versus control subjects and IDDM patients without peripheral neuropathy (P < 0.01). A direct relationship was found between parameters of posturography and some parameters of nerve conduction tests. CONCLUSIONS Diabetic patients with peripheral neuropathy demonstrate a shift from physiological ankle control to hip postural control as monitored by specific posturography analysis.

Contribution of Central Neuropathy to Postural Instability in IDDM Patients With Peripheral Neuropathy

OBJECTIVE To evaluate the contribution of central neuropathy on postural impairment observed in diabetic patients with peripheral neuropathy. RESEARCH DESIGN AND METHODS Central sensory and motor nervous propagation, nerve conduction velocity, and static posturography were assessed in the following age-matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM patients without peripheral neuropathy (group D), and 31 control subjects (group C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were recorded, and the spine-to-scalp sensory central conduction time (SCCT) was evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during magnetic transcranial brain stimulation, and the scalp-to-spine motor central conduction time (MCCT) was evaluated. The following posturographic parameters were calculated from the statokinesigram: trace length, trace surface, velocity of body sway with its standard deviation, and VFY (a parameter derived from the velocity variance and the anteroposterior mean position of the body). RESULTS SCCT was significantly higher in the DN group than in the C and D groups (P < 0.001). MCCT was similar in all groups. Posturographic parameters were all significantly impaired in the DN group (P < 0.01). While posturographic parameters showed a direct relationship with some parameters of peripheral nerve conduction, no correlations were observed with SEP and MEP central conduction time. These results were also confirmed by logistic regression, which indicates peripheral neuropathy as the only implicating factor in postural instability (odds ratio 0.22, 95% CI 0.07–0.75) after data reduction by means of factor analysis. CONCLUSIONS Although diabetic patients with peripheral neuropathy show a delay in central sensory conduction, postural instability may be fully explained by the presence of peripheral neuropathy.

Muscular cramps: Proposals for a new classification

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term “cramp” is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise “umbrella” term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

Gabapentin treatment for muscle cramps : An open-label trial

To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (>5 cramps/week), stable, long-lasting cramps, associated with different diseases. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. At the 1 month control (mean dosage, 825 ± 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. After 3 months of therapy (mean dosage, 892 ± 180 mg), cramps disappeared in 100% of patients and this benefit persisted as long as 6 months. Additionally, we evaluated in 10 patients the Cramps Threshold Frequency (CTF) (neurophysiological outcome measure) before and during gabapentin treatment. Gabapentin significantly increased the CTF, returning it to normal values. With the limitation of an open-label methodology, our clinical and neurophysiologic experience suggests that a gabapentin dose of 600–1200 mg/d would be helpful in the treatment of muscular cramps.

Trigemino-cervical-spinal reflexes in humans

INTRODUCTION Electrical stimulation of the supraorbital nerve (SON) induces late reflex responses in the neck muscles; these responses are hypothesised to be polysynaptic reflexes participating in a defensive withdrawal retraction of the head from facial nociceptive stimuli. Such responses may extend to the proximal muscle of the arms. OBJECTIVE (1) to investigate reflexes in the upper limb muscles (trigemino-spinal responses, TSR) and their relationship with trigemino-cervical responses (TCR); and (2) to identify the nociceptive component of such reflexes and their functional significance. METHODS Reflex responses were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the SON in 12 healthy subjects. The sensory (ST), painful (PT) and reflex thresholds, the latency and area of the responses, the effect of heterotopic painful stimulation (HTP), the recovery cycle as well as the effect of the expected and unexpected stimuli were measured. RESULTS Stable reproducible TCR and TSR responses were identified at 2.5+/-0.4 x ST, which corresponded exactly to the PT in all the subjects. The TCR and TSR areas were markedly reduced after HTP. The recovery cycle of the TSR area was faster than that of the TCR. Repeated rhythmic stimulation failed to induce progressive reflex suppression. CONCLUSIONS These results confirm the nociceptive nature of the TCR and indicate that the biceps brachii response (TSR) has the same nocifensive significance as the posterior neck muscle responses. TCR and TSR are mediated different polysynaptic pathways The presence of trigemino-cervical-spinal responses in our study clearly indicates that there is a reflex interaction between nociceptive trigeminal afferents and both upper and lower cervical spinal cord motoneurons.

A simple method for estimating conduction velocity of the spinothalamic tract in healthy humans

OBJECTIVES The object of this study was to establish a method for estimating the conduction velocity (CV) of the spinothalamic tract (STT) in relation to clinical application. METHODS The CV of the STT was estimated by an indirect method based on that reported by Kakigi and Shibasaki in 1991 (Kakigi R, Shibasaki H. Electroenceph clin Neurophysiol 80 (1991) 39). Laser-evoked potentials (LEP) were measured in 8 subjects following hand (LEPH) and foot (LEPF) laser stimulation. The conduction times recorded at the scalp (P340, P400 and N150 potentials) were considered as the summation of peripheral and central components. The peripheral conduction times were calculated by measuring the latency of the electrical cutaneous silent period (from the same stimulus site of LEPs), corrected for F- and M-wave latency values. RESULTS The CV of the STT ranged between 8.3 and 11.01 m/s and its mean value was found to be approximately 9.87+/-1.24 m/s. The CV of the STT obtained by the N150 latencies overlapped that obtained by the P340/P400 latencies. CONCLUSIONS Our data suggest that our method appears appropriate and useful for practical clinical purposes, furnishing an additional tool for investigating the physiological function of small-fiber pathways.

L-Dopa decreases cutaneous nociceptive inhibition of motor activity in Parkinson's disease.

Objectives– To estimate changes in motor inhibitory mechanisms at the spinal level in Parkinsons disease (PD) patients by measuring cutaneous silent responses to nociceptive stimuli in the course of L‐Dopa therapy. Material and methods– Fourteen patients with idiopathic PD (Group 1) and 13 patients with other forms of parkinsonism (Group 2) participated in the study. The cutaneous silent period (CSP) from the hand and clinical scores (UPDRS, part III) were measured “off” therapy (T0), after a single dose of L‐Dopa (T1) and 3 months after the beginning of L‐Dopa daily therapy (T2). Results– At T0 the duration of the CSP was significantly prolonged in Group 1 and Group 2. At T1 and T2 the mean duration of the CSP significantly decreased in Group 1 (P < 0.05) and a significant correlation was found between the shortening of the CSP and the improvement of rigidity and bradikynesia in the upper limb. Conclusions– Our findings show that L‐Dopa decreases the cutaneous nociceptive inhibition of motor activity in PD patients. CSP may be useful to assess L‐Dopa responsiveness during the clinical course of PD.

Electrophysiological assessment of visual function in IDDM patients.

Various electrophysiological tests have been employed to reveal functional abnormalities at different levels of the visual system in insulin-dependent diabetic (IDDM) patients. The aim of our work was to assess, with a comprehensive neurophysiological protocol evaluating the retinal, macular and visual pathways functions, whether and when such electrophysiological abnormalities do appear in IDDM patients free of any fluorangiographic sign of retinopathy with various disease duration. Flash-electroretinogram (ERG), oscillatory potentials (OPs), pattern-electroretinogram (PERG), and visual evoked potentials (VEPs) in basal condition and after photostress were assessed in 12 control subjects (C) and 42 aged-matched IDDM patients without clinical retinopathy (DR-) divided, on the basis of the disease duration, into 4 groups (1-5, 6-10, 11-15, 16-20 years). In addition another age-matched group of IDDM patients with a background retinopathy (DR+; n = 12; duration of disease 18 +/- 49 years) was evaluated. In all IDDM DR-patients PERG and VEP were significantly impaired. In addition, groups 11-15 and 16-20 years displayed impaired OPs. All electrophysiological parameters were further impaired in DR+ patients. In conclusion, retinal, macular and visual pathways functions are differently impaired in IDDM (DR-) patients with different disease duration. Electrophysiological impairment starts in the nervous conduction of the visual pathways with an early involvement, goes on in the innermost retinal layers and in the macula and ends in the middle and outer retinal layers.