Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy

Abstract Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective - methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls ( p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls ( p < 0.001). Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.(AU)

Alteración de las fibras finas A-delta por entrampamiento del nervio mediano en la muñeca utilizando el período silente cutáneo / The impairment of A-delta fibers in median nerve compression at the wrist, using the cutaneous silent period

El síndrome del túnel carpiano (STC) es una neuropatía por entrampamiento a nivel de la muñeca que cursa con dolor, parestesias y disestesias dolorosas. El diagnóstico electrofisiológico se basa en el estudio de la neuroconducción de las fibras gruesas. Nuestra hipótesis consiste en la existencia del compromiso de las fibras nerviosas finas y que este compromiso se correlaciona con el grado de gravedad. Se evaluaron retrospectivamente 69 manos correspondientes a 47 pacientes, varones y mujeres (edad media 53.8, rango 22-87 años) y como grupo contro, 21 manos correspondientes a los lados asintomáticos de estos casos. Se realizaron estudios de neuroconducción motora, sensitiva y ondas F para clasificar a las manos según el grado de gravedad. Se realizó el período silente cutáneo (PSC) en todas las manos. Se evaluaron latencias medias y duraciones medias del PSC. Las latencias medias se hallaron significativamente prolongadas en las manos con neuropatía (84.3 ± 16.3 mseg) con respecto a las manos sin neuropatía (74.8 ± 11.6 mseg), p < 0.05. Las latencias medias se hallaron más prolongadas en las manos con neuropatía de mayor gravedad (p < 0.05). En los 3 pacientes con neuropatía grado más grave no se halló el PSC. Se demostró el compromiso de las fibras finas A-delta en los pacientes con STC, con mayor compromiso a mayor severidad. El PSC puede usarse como complemento de los estudios de neuroconducción motora y sensitiva.

Carpal tunnel síndrome (CTS) is an entrapment neuropathy of the median nerve at the wrist, that leads to pain, paresthesia and painful dysesthesia. The electrophysiological diagnosis is based upon nerve conduction studies which evaluate thick nerve fibers. Our hypothesis is that there is an additional dysfunction of small fibers in CTS, which correlates with the degree of severity of the neuropathy. A retrospective study of 69 hands that belonged to 47 patients of both sexes (mean age 53.8, years, range 22-87) was performed, and, as a control group, 21 hands which corresponded to the asymptomatic side of those patients were evaluated. Motor and sensory conduction studies, as well as F-waves were performed to classify the neuropathy according to the degree of severity. Cutaneous silent period (CSP) was elicited in all hands. Mean onset latencies and durations of CSP were evaluated. Mean onset latencies were significantly prolonged in neuropathic hands (84.3 ± 16.3 msec) compared to asymptomatic hands (74.8 ± 11.6 msec) (p < 0.05). Mean latencies of the CSP were even prolonged (p < 0.05) in hands affected by a more severe neuropathy. In the 3 hands with most severe neuropathy, a CSP could not be elicited. In CTS an impairment of A-delta fibers was recorded through the CSP. The more severe the neuropathy is, the more impairment of A-delta fibers can be found. CSP may be assessed as a complement of motor and sensory nerve conduction studies in this neuropathy.

Importância do período de silêncio cutâneo na fibromialgia e sua relação com as características da doença, distúrbios psicológicos e qualidade de vida dos pacientes / Importance of cutaneous silent period in fibromyalgia and its relationship with disease characteristics, psychological disorders and quality of life of patients

INTRODUÇÃO: O período de silêncio cutâneo (PSC) é um reflexo protetor inibitório da coluna vertebral e seus aferentes consistem em fibras nervosas A-delta. Nosso objetivo foi avaliar pacientes com fibromialgia (FM) e controles saudáveis para determinar as diferenças entre os grupos em relação à duração e latência do PSC, e quando presente, determinar se há alguma relação com as características da doença, distúrbios psicológicos e qualidade de vida. MATERIAIS E MÉTODOS: Trinta e dois pacientes com FM e 32 voluntários saudáveis foram incluídos no estudo. Os dois grupos foram comparados em relação à latência e duração do PSC em ambos os membros superiores e inferiores. Características da doença, distúrbios psicológicos e qualidade de vida dos pacientes foram avaliados utilizando o Fibromyalgia Impact Questionnaire (FIQ), e o Short Form-36 (SF-36). Os pacientes com medida de PSC igual ou inferior às do grupo controle foram comparados com aqueles com valores mais elevados do que os controles em termos de características da doença, estado psicológicos e qualidade de vida. RESULTADOS: Latências significativamente prolongadas de PSC nos membros superiores e inferiores foram determinadas em pacientes comparados com os controles. Observou-se que a prolongamento da latência do PSC no membro inferior estava associado com a gravidade da doença e incapacidade funcional. CONCLUSÕES: Latências do PCS nos membros superiores e inferiores em pacientes com FM são mais longas do que em voluntários saudáveis. Além disso, o prolongamento da latência do PSC no membro inferior está associado com a gravidade da doença e incapacidade funcional física.

INTRODUCTION: Cutaneous silent period (CSP) is an inhibitory spinal protective reflex and its afferents consist of A-delta nerve fibers. We aimed to evaluate patients with fibromyalgia (FM) and healthy controls to determine any differences between the groups in terms of CSP duration and latency, and if present, to determine whether there is any relationship with disease characteristics, psychological disorders and quality of life. MATERIALS AND METHODS: Thirty-two patients with FM and 32 healthy volunteers were included in the study. The patient and control groups were compared in terms of CSP latency and duration in both upper and lower extremities. Disease characteristics, psychological disorders and quality of life of patients were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and Short Form-36 (SF-36). Patients with CSP measurements equal to or lower than those of the control group were compared with those with higher values than controls in terms of disease characteristics, psychological status and quality of life. RESULTS: Significantly prolonged CSP latencies in both upper and lower extremities were determined in patients compared to controls. We found that prolongation of CSP latency in the lower extremity is associated with disease severity and functional disability. CONCLUSIONS: CSP latencies in both upper and lower extremities in patients with FM are longer than in healthy volunteers. Moreover, prolongation of CSP latency in the lower extremity is associated with disease severity and physical functional disability.

The changes of Silent Period before and after training of standing on balance-mat / 体力科学

The purpose of this study was to evaluate the changes of pre-motion time (PMT), pre-motion silent period (PMSP), and switching silent period (SSP) before and after the training using balance-mat. Twenty healthy people aged 21-36 years old (average 26.5 years old) were subjected to a series of experiment. These were randomly divided into two groups (10 subjects each), control and balance-mat group. Activities of M. Soleus and M. Tibialis anterior were recorded by electromyogram (EMG) for the duration subjects were tried to raise their both heels as quick respond to a flashing lamp. Intervention consisted of 3minutes standing on the floor in control group, and 3 minutes standing on the balance-mat in balance-mat group. Then EMG was recorded as the same manner after the intervention in each group. There was no statistical difference of duration of PMSP and SSP between the two groups before intervention. On the other hand, those in balance-mat group were significantly shorter than those in control group after intervention. In addition, in balance-mat group, duration of PMSP and SSP after intervention were significantly shorter than that before intervention. There was no statistical difference of PMT between before and after the intervention. These results suggested balance-mat training was effective for shorten the duration of SSP and PMSP, that lead to control the posture function.

Electrophysiological Tests in Generalized Tetanus

BACKGROUND: Tetanus toxin selectively blocks inhibitory synapses in the brainstem as well as the spinal cord. Therefore, in contradiction to Stiff Person syndrome, patients with generalized tetanus usually show abnormal masseter silent periods as well as abnormal F/M amplitude or H/M amplitude ratios. This study aimed to verify the characteristics of electrophysiological findings of generalized tetanus. METHODS: The authors retrospectively studied clinical and electrophysiological characteristics of 7 patients with generalized tetanus, who were admitted to the neurology department of Hallym Medical Center from 1995 to 2005. RESULTS: All the seven patients showed abnormal masseter silent periods. Three of them showed somewhat improvement in the silent period at follow-up study as trismus was improving. Full NCSs done in two patients did not show any abnormalities except an increased F/M amplitude ratio. One patient with a wound site in his left finger showed an abnormal F/M amplitude ratio only in the right upper extremity without involvement of other extremities. Another patient showed an increased H/M amplitude ratio without an increased F/M amplitude ratio. (In this patient we did not conduct full NCS tests.) CONCLUSIONS: The Masseter silent period could be used as a diagnostic tool and parameter of clinical improvement in patients with generalized tetanus.

The Changes of Motor Evoked Potential and Silent Period after Electrical Stimulation in Stroke Patients

OBEJCTIVE: This study was proposed to evaluate the electrophysiologic changes in motor evoked potentials (MEPs) and silent period after paraspinal electrical stimulation near caudal area of the spinal cord in stroke patients. METHOD: Electrical stimulation was applied to T12 paraspinal area using interferential current therapy (80~100 Hz) in 18 stroke patients. The amplitude and latency of cortical motor evoked potential and duration of silent period were measured before and after the electrical stimulation. RESULTS: The amplitude of MEPs in affected side was low compared with unaffected side. The duration of silent period was variable in affected side. The duration of silent period was increased after the electrical stimulation in stroke patients (p<0.05). Changes of the amplitude and latency of MEPs were not significant. CONCLUSION: These results mean that the central inhibitory mechanism affecting the silent period is activated by a certain electrical stimulation near caudal area of the spinal cord in stroke patients.

CENTRAL FATIGUE DURING CONSTANT CADENCE PEDALING FOR 60 SECONDS-A TRANSCRANIAL MAGNETIC STIMULATION STUDY / 体力科学

Changes in the motor evoked potential (MEP) evoked by transcranial magnetic motor cortex stimulation (TMS) of rectos femoris (RF) and vastus lateralis (VL) was examined during constant cadence cycling tasks for 60 sec. Subjects were 11 normal male volunteers aged between 19 and 25 years. Pedaling load was set at 100% and 80% of the estimated optimal value for maximum anaerobic power output. For the low load task (LL task), the pedaling rate was set at half the value of the maximum pedaling rate with the load set at 80% of the optimal for maximum anaerobic power output. For the high load task (HL task), the pedaling rate was set such that the power was equivalent to the LL task.<BR>The route mean square of the electromyographic (EMG) activity amplitude tended to steeply increase during the latter half of the task. The magnitude of the increase in the RMS was significantly larger in the HL task than the LL task. The area of the MEP also tended to increase in both tasks, though the degree of the increase was significantly larger in the LL task than the HL task. The EMG silent period (SP) after the MEP tended to steeply increase just after the task initiation and to decrease in the latter half of the task in the HL task. However, in the LL task the facilitation of MEP was not found, but it showed a gradual decrease while performing the task. The duration of the MEP tended to increase in both tasks, though the degree of the increase in the VL was significantly larger in the LL task than the HL task. The linear regression analysis between the size of the MEP and the background EMG shows a significant positive correlation coefficient during isometric contraction, but not during the two types of cycling tasks.<BR>These results suggest that the neural circuit responsible for the MEP was controlled differentially during isometric contraction and constant cadence pedaling. Also it is likely that the mechanism of central fatigue differed depending on the cadence and or load in a task-dependent fashion irrespective of the same power output.

Effect of Voluntary Contraction in Motor Evoked Potential and Silent Period by Transcranial Magnetic Stimulation

OBJECTIVE: To determine the effects of the voluntary contraction of muscles and magnetic stimulation intensity on the motor evoked potential (MEP) and the silent period (SP). METHOD: We studied MEPs and SPs in opponens pollicis muscle in 30 healthy adults (male: 16, female: 14) while varying the amount of the voluntary contraction and the stimulation intensity. We analyzed MEPs and SPs in relation to sex, recording site, opposition power and height. RESULTS: 1) During the contraction, the latencies of MEP were significantly shorter than during the relaxation. 2) The amplitudes of MEP reached plateau at 30% of maximal voluntary contraction and increased with increment of stimulation intensity without limitation. The amplitudes of MEP of right hand were bigger than left hand. There were no significant differences according to sex and recording site. 3) The durations of SP were directly proportional to the degrees of voluntary contraction and the stimulation intensity. CONCLUSION: Transcranial magnetic stimulation should be performed under the same voluntary contraction and magnetic stimulation intensity.

Effects of the Divalproex Sodium on Cortical Hyperexcitability in Migraine Patients Chung-Ang University,Pildong Hospital

BACKGROUND: Cortical hyperexcitability is proposed to be the putative basis for the physiological disturbances in migraine. Recent studies have demonstrated that divalproex sodium effectively prevents migraine. The cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) reflects the cortical inhibition of the central motor pathway. METHODS: We studied the CSP of both first dorsal interossei muscles evoked by TMS in 15 migraine patients and 15 normal subjects. As a prophylactic therapy, 15 migraine patients were treated with divalproex sodium 500~750 mg/day. After 3 months, we studied the CSP in migraine patients for the purpose of comparing with results before medication. RESULTS: The CSP was shorter in migraine patients than in controls (135.8+/-27.8 msec vs 203.7+/-32.2 msec, p<0.001). After treatment with divalproex sodium, the CSP was significantly prolonged in migraine patients (196.9+/-31.0msec, p=0.001). CONCLUSIONS: The shortened CSP in migraine patients suggests increased excitability of the cortical neuron in migraine. The prolonged CSP after medication in migraine patients suggests that the divalproex sodium may play a role in the prophylaxis of migraine by decreasing cortical neuronal hyperexcitability. (J Korean Neurol Assoc 19(5):489~493, 2001)

The Neurophysiologic Response of Anterior Horn Cell Activity to Paraspinal Electrical Stimulation

OBJECTIVE: This study was proposed to evaluate the electrophysiologic changes in central motor conduction and in silent period (SP) after paraspinal transcutaneous electrical stimulation near caudal area of the spinal cord. METHOD: Conditioning stimulation was applied to T12 paraspinal area for 20 minutes using interferential current therapy (80~100 Hz) in 11 healthy subjects. The amplitude and latency of central motor conduction and duration of SP were measured in motor evoked potential (MEPs) by using magnetic stimulator, before and after the conditioning stimulation. These variables were recorded in both tibialis anterior muscle, innervated from stimulated spinal area, and both abductor pollicis brevis, innervated from cervical cord not directly stimulated by electrical stimulation. RESULTS: After conditioning stimulation, the amplitudes of central motor conduction decreased (p<0.01), and the latencies did not change in both cervical and lumbar muscles in transcranial and spinal MEP studies, and the duration of SP was decreased in same manner (p<0.01). CONCLUSION: These results mean that the excitability of anterior horn cells decreases and the supraspinal inhibitory mechanism of the central motor conduction is suppressed by a certain conditioned electrical cutaneous stimulation in entire spinal cord.

The Effect of Lorazepam on the Silent Period of the Motor Evoked Potential

OBJECTIVE: The purpose of this study was to find out whether the duration of the silent period evoked by magnetic transcranial stimulation could be modulated by lorazepam. METHOD: Ten healthy volunteers were tested using the transcranial magnetic stimulation. Responses were recorded in the active abductor digiti minimi muscle, and baseline values were compared to the data obtained at 2 and 5 hours after administration of a single oral dose of 2.5 mg lorazepam. RESULTS: The motor threshold and size of the motor evoked potential remained unchanged after administration of lorazepam. The duration of cortical silent period was prolonged from 169.9+/-33.7 msec at baseline study to 248.1+/-50.4 msec at 2 hours and 248.5+/-47.3 msec at 5 hours after administration of the drug (p<0.01), but the peripheral silent period did not show any significant change. CONCLUSION: We have shown that the cortical silent period evoked by magnetic transcranial stimulation can be prolonged by administration of lorazepam. And the lack of effect on the motor threshold and on the size of the motor evoked potential after administration of lorazepam may indicate that these parameters are physiologically distinct from the cortical silent period. Therefore, prolonged cortical silent period may be resulted from the reinforcement of GABA action by lorazepam at the level of the motor cortex.

Influence of Transcutaneous Electrical Nerve Stimulation on Cutaneous Silent Period

OBJECTIVE: To investigate the influence of high frequency transcutaneous electrical nerve stimulation (TENS) on cutaneous silent period. METHOD: Cutaenous silent period was recorded before and after high frequency TENS application in sixteen healthy adults (11 males, 5 females). Onset latency, duration, and minimum stimulation intensity to evoke cutaneous silent period were compared. In 7 male subjects, temporal changes of cutaneous silent period were observed after TENS application. RESULTS: Minimum stimulation intensity to evoke cutaneous silent period was significantly increased after high frequency TENS application (p<0.05) and yet, onset latency and duration showed no significant change. The increase in minimum stimulation intensity to evoke cutaneous silent period was maintained for 30 minutes after TENS and returned to the baseline level thereafter. CONCLUSIONS: These results suggest that high frequency TENS increase the depolarization threshold of A-delta fiber and this peripheral effect may be one of the pain control mechanisms of TENS.

Cerebral Lesions with Shortened Silent Period after Transcranial Magnetic Stimulation in Stroke

BACKGROUND: A silent period (SP), recorded with transcranial magnetic stimulation (TMS) reflects the cortical inhibition of the central motor pathway. In most previous reports involving unilateral cerebral lesions, prolonged cortical SPs recorded with TMS on the affected side compared with SPs on the contralateral hemisphere were observed. However, in only a few studies, a shortened SP has been observed. In the present study, we assumed a shortened SP mechanism in the association with stoke. METHODS: We studied cortical SPs of both first dorsal interossei muscles evoked by TMS in 21 normal subjects and 13 patients with single focal cerebral lesions (lacunar infarct or small hemorrhage). We divided lesions into two groups with prolonged and shortened SP. Interside differences of SP recorded in both groups were compared with that of normal subjects. RESULTS: Shortened SP was observed in 3 thalamic, 3 motor cortical, and 1 caudate nucleus head lesions. Four thalamic and 2 putamenal lesions showed prolonged SP. In patients with thalamic lesions, SPs were shortened in ventrolateral thalamic lesions and prolonged in dorsomedial lesions. Interside differences of both the shortened and prolonged groups were 85.8+/-47.6 msec, and 99.3+/-49.7 msec, respectively (normal control, 7.3+/-5.9 msec). CONCLUSIONS: These results suggest that shortened SP is related to anatomical sites of lesions including motor cortex, caudate nucleus, and ventrolateral thalamus. Divergent results obtained from thalamic lesions also suggest that the thalamocortical pathway plays a significant role in cortical SP induced by TMS.

Clinical Usefulness of Silent Period after Transcranial Magnetic Stimulation in Stroke Patients

Background Transcranial magnetic stimulation(TMS) of the motor cortex is well established as a valuable method for noninvasive examination of the central motor system. The purposes of this study are to establish technical method and normal data and to evaluate clinical usefulness of silent period(SP) study in stroke patients. Methods Central motor conduction time(CMCT) and SP were measured from the first dorsal interossei muscle by TMS. The subjects were 41 normal persons and 15 stroke patients, who were proven radiologically to have unilateral infarction or hemorrhage at various regions of brain. Patients group had lateralizing neurologic signs clinically, but most of them showed no definite motor weakness. Results In the control group we found no statistically significant interside difference in CMCT and duration of the SP, which showed a marked interindividual variation. In patients with prior stroke who showed minor neurologic deficits, there was a significant increase in the interside difference of SP. However, that of CMCT wasn't a sensitive parameter in determining the abnormality. Conclusion These findings suggest that the SP elicited by transcranial magnetic stimulation is a useful and sensitive neurophysiological parameter in the evaluation of stroke, particularly for the detection of subclinical motor dysfunction.

Motor Evoked Potential Study of Mirror Movements in a Patient with Klippel-Feil Syndrome

Mirror movements(MMs) are involuntary movements executed on one side of the body during voluntary movements of the contralateral homologous body parts. Motor evoked potentials(MEP) to focal transcranial magnetic stimulation(TMS) have postulated that abnormal ipsilateral corticospinal tract is active in the patient with congenital MMs. MEP and post-MEP SP following to focal TMS were investigated in a patient with the Klippel-Feil syndrome(KFS) showing MMs and in five normal volunteers. In the patient unilateral transcranial stimulation evoked bilateral motor responses of normal latencies and SP was observed bilaterally, which tended to be shortened in duration. In the condition of KFS, the mechanism of MMs has been attributed to the presence of abnormally activated ipsilateral corticospinal tract, but it does not suffice for explaining the shortened SP. We propose that concurrent activation of both motor cortices be responsible for the mechanism of MMs in this case of KFS, in addition to the abnormality of the corticospinal tracts.

The Usefulness of Cutaneous Silent Period in Diabetic Polyneuropathy

OBJECTIVE: To evaluate the usefulness of cutaneous silent period(CSP) in assessing the pain sensory function mediated by the Adelta fiber in diabetic polyneuropathy and to define the proper CSP parameter and method. METHOD: We studied 18 diabetic polyneuropathy patients and 20 age-matched healthy subjects. CSPs were recorded in the abductor pollicis brevis muscle and soleus muscle with the surface electrodes and a painful electrical stimulation was given to the mixed nerves(median and tibial nerve) and cutaneous nerve(ulnar and superficial peroneal nerve). Onset latency, end point and duration of CSP were compared between two groups. CSP parameters correlated with the motor and sensory nerve conduction parameters in diabetic polyneuropathy patients. RESULTS: CSP onset latency and end point were significantly delayed in diabetic polyneuropathy patients for both mixed nerve and cutaneous nerve stimulations. There was no difference in CSP duration between two groups. CSP onset latency was shortend and duration was prolonged in mixed nerve stimulation due to an antidromic collision, which showed a cutaneous nerve stimulation as the propor method. There was no correlation between the CSP parameters and motor and sensory nerve conduction parameters. In 3 cases, the CSPs were unable to the evoked despite the sensory nerve action potential was normally evoked. This suggests that the CSP would give an information about the Adelta fiber function than the large myelinated fiber. CONCLUSION: This study indicates that the CSP is a useful supportive electrophysiologic study to assess the Adelta fiber function in diabetic polyneuropathy. The CSP onset latency and cutaneous nerve stimulation are the useful parameter and method for the CSP.

Significance of transient decrease in sustained tension preceding rapid muscle contraction in man / 体力科学

The purpose of this study is to investigate significance of transient decrease in sustained tension preceding rapid muscle contraction in elbow flexor muscles.<BR>Before rapid voluntary contraction, steady forces below 20% of the maximum contraction were maintained, and each transient decreas was detected by using high sensitive strain gauge (FD pick-up) with EMG of brachial biceps and triceps muscles. And girth and length changes of the biceps brachii muscle with the tension decrease were detected by using rubber strain-gauge method and X-ray technique, respectively.<BR>The following results were obtained<BR>1) The transient decrease of steady forces were observed during the premotion silent period. Amount and duration of the transient tension decrease were below 20% of each steady force and 100 ms, respectively.<BR>2) Amount of the transient tension decrease inversely correlated to time to half Pmax on the rapid tension development. (p<0.001)<BR>3) Amount of the transient tension decrease was significantly coefficient with decrement of girth of upper arm. (p<0.001)<BR>4) A distance between two Cu wire apexes inserted into biceps brachii muscle shortened with increment of muscle force.<BR>These results suggest that before rapid muscle contraction stretch of biceps brachii muscle transiently occure, and that the stretch accelerate the following shortning velocity of the muscle via a stretch reflex.