桑原 聡

This study compared directly the post-ischaemic behaviour of sensory and motor axons in the human median nerve, focusing on the excitability changes produced by ischaemia and its release and by continuous polarizing DC. The decrease in threshold during ischaemia for 13 min was greater, the post-ischaemic increase in threshold was more rapid, and the return to the pre-ischaemic excitability took longer in sensory axons. However, a transient depolarizing threshold shift developed in sensory axons a few minutes after release of ischaemia. This pattern could not be reproduced by polarizing currents designed to mimic the probable pump-induced changes in membrane potential, even though the applied currents produced greater changes in threshold. Hyperpolarizing currents of equivalent intensity produced a greater increase in threshold for motor axons than sensory axons and, in studies of threshold electrotonus using graded hyperpolarizing DC, accommodation was greater in sensory than motor axons. The post-ischaemic changes in threshold were not uniform for axons of different threshold, whether sensory or motor, the threshold increase was usually less prominent for low-threshold axons. A transient post-ischaemic depolarization could be produced in motor axons with ischaemia of 20 min duration. Greater ischaemic and post-ischaemic changes in threshold for sensory axons could reflect greater dependence on the electrogenic Na+-K+ pump to maintain resting membrane potential and/or greater extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due to extracellular K+ accumulation would then be more likely to trigger a depolarizing shift in membrane potential, the degree of K+ accumulation and pump activity being dependent on the duration of ischaemia. In sensory axons the greater tendency to accommodate to hyperpolarizing stimuli presumably contributes to shaping their post-ischaemic behaviour but is probably insufficient to explain why their behaviour differs from that of motor axons.

Objective To investigate whether glycemic control is associated with reversible changes in axonal excitability in human diabetic nerves. It is known that voluntary contraction or compression ischemia alters nerve Na+/K+ pump activity, and axonal excitability changes due to the pump activity can be estimated by threshold tracking. Methods Threshold, the current required to produce a compound muscle action potential 50% of maximum, was determined from the stimulus-response curve, and threshold changes produced by maximal voluntary contraction or ischemia were measured before and after insulin treatment in 10 diabetic patients. Results Within 3 weeks of the start of treatment, the threshold changes became greater following voluntary contractions (+13+/-4% versus +23+/-5%; mean+/-SEM; p=0.04) and during ischemia (-5+/-2% versus -11+/-2%; p=0.04). Conclusions The extent of threshold fluctuation depends on multiple metabolic factors associated with diabetes such as decreased Na+/K+ ATPase activity, increased anaerobic glycolysis, and tissue acidosis, and nerve excitability can respond quickly to glycemic control in diabetic patients.

To investigate whether there are inter-nerve differences in the extent and pattern of axonal excitability changes produced by voluntary contractions of tibialis anterior (TA) and abductor pollicis brevis (APB), threshold tracking was used to measure axonal excitability parameters [threshold, supernormality and strength-duration time constant (tau(SD))] of peroneal and median motor axons in 11 healthy subjects. Maximal contractions for 1 min resulted in an increase in threshold, an increase in supernormality, a decrease in tau(SD) and an increase in latency, all of which indicate axonal hyperpolarization. The increase in threshold was less in peroneal axons (18 +/- 4%) than median axons (37 +/- 6%, mean SEM, P < 0.001), and was accompanied by smaller absolute changes in latency, supernormality, and tau(SD). Peroneal axons had less supernormality at rest but a greater change in supernormality for the change in threshold. There were major contraction-induced changes in the compound muscle action potential of TA but not that of APB. Voluntary contractions depress axonal excitability, but the changes are quantitatively different for motor axons innervating different muscles. There are three clinical implications. First, weakness and fatigue due to activity-dependent conduction block may vary for different muscles, independent of disease severity, and therapeutic strategies to overcome activity-dependent conduction block may not be equally effective for different muscles. Second, in motor control studies using the H reflex to document motoneuron excitability, a constant stimulus will not produce a constant neural volley if the stimulated axons have been activated by, for example, a voluntary contraction. Third, TA is probably not optimal for testing for activitydependent conduction block. (C) John Wiley Sons, Inc.

Objectives: To investigate the properties of mechanoreceptors in patients with peripheral neuropathy. The skin mechanoreceptor is a terminal organ of the primary sensory neuron, which is likely to be affected earlier and more severely than is the nerve trunk by peripheral neuropathies. Methods: Single sensory unit responses to air-puff and electric stimulation were recorded using the microneurographic technique in the glabrous skin of the hand, Receptor transduction time was estimated by a latency difference between electric- and air-puff-induced responses. Results: A total of 38 mechanoreceptive units were obtained from 14 normal subjects. All the units responded to air-puff stimuli irrespective of the receptor type, and receptor transduction time was approximately 2 ms. A total of 32 units were recorded from 11 patients with neuropathy of variable causes. Seven (22%) of the 32 neuropathic units did not respond to air-puffs despite their ability to respond to electric stimulation. Compared to normal ones. units from patients with peripheral neuropathy had significantly higher mechanical thresholds, but receptor transduction times did not differ significantly. Conclusions: Changes in receptor properties in human neuropathy are characterized by increased mechanical threshold without prolongation of receptor transduction time. possibly due to a high threshold for generating receptor potentials. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. Objective: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. Methods: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-alpha was measured by immunoassay. Results: Patients were classified as having a distal (n= 10), intermediate (n= 13), or diffuse (n= 15) pattern, or were unclassified (n= 4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-alpha concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. Conclusions: COP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP.

Objectives - To investigate whether or not the pattern and extent of autonomic involvement differ between the two subtypes of Guillain-Barre syndrome (GBS), namely acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Methods - Head-up tilt test. R-R interval variation, plasma noradrenaline concentration, skin vasomotor reflex (SVR) and sympathetic sweat response (SSwR) were used to estimate autonomic function in seven AIDP and eight AMAN patients. Results - Heart rate and plasma noradrenaline concentration were significantly high in the AIDP group but not in the AMAN group. Skin vasomotor reflexes were generally preserved and SSwRs were impaired in patients with severe neurological deficits for both AIDP and AMAN groups. Conclusion - The patterns of autonomic involvement are qualitatively different between AIDP and AMAN. Acute inflammatory demyelinating polyneuropathy is characterized by cardio-sympathetic hyperactivity, excessive or reduced sudomotor function and preserved skin vasomotor function, while AMAN is not necessarily generally associated with marked autonomic dysfunction except for the sudomotor hypofunction seen in patients with severe neurological deficits.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle and threshold electrotonus) of the median nerve in 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 25 healthy controls. Stimulus-response curves were significantly different: threshold was much higher, the slope of the curves reduced and the spread of the thresholds greater in the CIDP group. The strength-duration time constant (tau (SD)) was significantly shorter and the rheobase higher in the CIDP group. In the recovery cycle, the CIDP group had less refractoriness, supernormality and late subnormality than healthy controls, but the duration of the relatively refractory period was normal. These changes in tau (SD) and the recovery cycle were not those previously predicted. There were no consistent changes in threshold electrotonus, suggesting that, for the studied axons, there are no consistent changes in accommodation properties that depend on internodal conductances. It is difficult to explain these changes in excitability on the basis of a change in membrane potential, or solely as the result of demyelination, and it is possible that other morphological factors such as variable remyelination and inflammatory oedema affected axonal excitability in the patients.

Recent evidence suggests that two conductances responsible for accommodation to changes in membrane potential (a slow K+ conductance and inward rectification [I-H]) are less active on cutaneous afferents in the sural nerve than on those in the median nerve, and it has been suggested that these axons would therefore respond differently to stress, whether natural or due to disease. The present study was undertaken in eight healthy volunteers to determine whether these afferents respond differently to the depolarizing and hyperpolarizing stresses that accompany ischemia for 13 min and subsequent recovery. During ischemia, the decrease in threshold was quantitatively less for the sural afferents, as were the changes in the other indices of axonal excitability, presumably because the ischemic depolarization was less for sural afferents. Following release of ischemia, there was, as predicted, a divergence in the pattern of threshold change. With median afferents there was evidence of a transient depolarization, believed to be due to inward rectification, superimposed on a longlasting hype rpolarization. The response of sural afferents lacked this transient depolarizing threshold change. Cutaneous afferents in the median and sural nerves behave differently in response to ischemic and postischemic stresses, and it is likely that they will also respond differently to disease processes. in a number of respects the differences between sural and median afferents are analogous to differences between diabetic and normal nerves. (C) 2001 John Wiley & Sons, Inc.

The authors reviewed the clinical features and outcome of Miller Fisher syndrome (MFS) for 50 consecutive patients with MFS including 28 patients who received no immunotherapy. Besides the characteristic clinical triad (ophthalmoplegia, ataxia, and areflexia), pupillary abnormalities! blepharoptosis, and facial palsy are frequent in MFS, whereas sensory loss is unusual despite the presence of profound ataxia. Patients with MFS usually had good recovery and no residual deficits.

Objectives-To investigate whether accommodation to depolarising and hyperpolarising currents differs for motor axons of human upper and lower limb nerves. Methods-The threshold tracking technique was used to measure threshold electrotonus for median and peroneal motor axons. The threshold current that produced a compound muscle action potential 50% of maximum was measured, and membrane potential was altered using subthreshold polarising currents of 330 ms duration but of variable intensity, from +40% (depolarising) to -100% (hyperpolarising) of the unconditioned threshold. Results-The maximal threshold changes (the peak of the S1 phase of threshold electrotonus) were significantly greater in median axons for both depolarising and hyperpolarising currents. The subsequent phases of accommodation to depolarising currents (S2) and to hyperpolarising currents (S3) were also significantly greater in median axons. These findings raised the possibility that greater accommodation (S2 and S3) in median axons resulted from greater changes in membrane potential. However, regression of S2 against S1 to depolarising currents disclosed significantly greater accommodation (27.8%) for median axons, suggesting that slow K+ conductances may be more prominent on median than peroneal axons. By contrast, the relation between S3 and S1 to hyperpolarising currents was similar for the two nerves, suggesting that the difference in inward rectification was merely because the conductance varies with the extent of hyperpolarisation. Conclusions-Slow K+ conductances are more prominent for median motor axons than for peroneal axons. It would therefore be expected that axons innervating the lower limbs have less protection from depolarising stress and could develop ectopic activity more readily.

Background Activated macrophages and T lymphocytes may play a role in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Both cell types secrete tumor necrosis factor-alpha (TNF alpha), which has toxic effects on myelin and endothelial cells. Methods: The serum concentration of TNF alpha was measured by ELISA and compared with clinical and electrophysiological profiles in 20 patients with CIDP. Results: An increased serum level of TNF alpha was detected in 5 (25%) patients and was associated with subacute progression, severe neurologic disabilities, and symmetric weakness involving proximal as well as distal muscles. TNF alpha levels increased during the active phase in this subgroup of patients. The levels of TNF alpha correlated with the severity of demyelinating conduction abnormalities in the intermediate as well as distal nerve segments, suggesting demyelination diffusely distributed along the nerves. Conclusion: Circulating TNF alpha increases during the active phase in a subgroup of CIDP patients and may play a role in the pathogenesis of demyelination and the breakdown of the blood-nerve barrier in CIDP.

1. Voluntary contraction of a muscle causes substantial hyperpolarization of the active motor axons due to activation of the electrogenic Na+-K+ pump. The present study was undertaken to determine whether voluntary effort produces a significant impairment in impulse transmission in normal axone and whether mechanisms other than membrane hyperpolarization contribute to the changes in axonal excitability. 2. The compound muscle action potential (CMAP) was recorded after median nerve stimulation at the wrist using sub- and supramaximal stimuli, delivered singly and in pairs at conditioning-test intervals of 2-15 ms. Axonal excitability parameters (threshold, refractoriness, supernormality, and strength-duration time constant (tau (SD))) were measured using threshold tracking. Impulse transmission was assessed using supramaximal stimuli. 3. Maximal voluntary contractions of the abductor pollicis brevis for 1 min produced a substantial increase in threshold, an increase in supernormality and a decrease in tau (SD), all of which lasted similar to 10 min and indicate axonal hyperpolarization. However, immediately after the contraction there was an unexpected increase in refractoriness. The post-contraction increase in refractoriness could mot be mimicked by an imposed ramp of hyperpolarization that produced changes in the other indices to an extent that was similar to voluntary contraction. 4. The contraction had relatively little effect on the size of the unconditioned maximal CMAP. However, there was failure of transmission of supramaximal conditioned volleys when the conditioning-test interval was short. 5. The relationships between axonal excitability and supernormality and tau (SD) following voluntary contraction differed significantly from those recorded during the hyperpolarization produced by DC current. It is argued that these differences probably result from extra-axonal K+ accumulation with the voluntary contraction but not with the DC polarization. 6. It is concluded that, following maximal voluntary contraction of a normal muscle, the refractory period of transmission is impaired distal to the stimulus site sufficient to cause transmission failure of the second of a pair of closely spaced impulses. The site of transmission failure is: likely to be the terminal axon, presumably at branch points, possibly in the unmyelinated pre-terminal segment.

Motor unit number estimate (MUNE) of the abductor pollicis brevis (APB) was sequentially performed in seven patients with acute motor axonal neuropathy (AMAN). The MUNE markedly decreased (mean, 11)at the peak of the illness. Clinical recovery of APE strength began during week 4, with an increase in amplitude of distal compound muscle action potentials. The MUNE did not change significantly in this early recovery phase and increased slowly with time. The main mechanism for early recovery in AMAN may be collateral reinnervation, with nerve regeneration developing later. (C) 2001 John Wiley & Sons. Inc.

1. To determine whether accommodation to depolarizing and hyperpolarizing stimuli differs for cutaneous afferents in the median and sural nerves, studies were performed in normal human subjects using threshold electrotonus. 2. The changes in threshold for compound sensory action potentials of 50 % of maximum were recorded when the nerves were subjected to long-lasting depolarizing and hyperpolarizing DC. The premise was that the threshold changes largely mirror the underlying electrotonic changes in membrane potential. 3. The maximal threshold changes produced hyperpolarizing and hyperpolarizing currents were greater for median afferents, suggesting that the DC produced greater changes in membrane potential in these afferents. 4. Median afferents underwent greater accommodation to depolarizing currents than sural afferents and a greater threshold undershoot at the end of the currents, suggesting greater activity of a slow K+ conductance. Median afferents also underwent greater accommodation to hyperpolarizing currents, suggesting greater inward rectification. 5. These conductances are voltage dependent, and the differences in accommodation could be due to greater changes in membrane potential for the median nerve. The changes in threshold produced by long-lasting depolarizing and hyperpolarizing currents of graded intensity were therefore measured. When the threshold changes were matched for the two nerves, median afferents underwent 22.4% more accommodation to depolarizing currents and 28.7% more accommodation to hyperpolarizing currents. 6. We conclude that there is greater expression of two internodally located conductances responsible for accommodation on median afferents. The biophysical differences identified in this study might contribute to the finding that sural afferents hare a greater tendency to dysfunction than median afferents.

Voluntary activity produces activity-dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity-dependent conduction block paralleled the activity-dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%, Activity-dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites.

In a number of clinical studies, measurement of axonal strength-duration properties has been used to provide indirect insight into conductances at the node of Ranvier, particularly persistent Na+ conductance. However, the specificity of any changes is limited because other factors can affect strength-duration behavior. The present study was undertaken to define the relationship between different strength-duration measures at rest and at different membrane potentials, and also to determine the limits within which strength-duration behavior can be used as a measure of nodal conductances. The strength-duration time constant (tau (SD)) and rheobase of 20 single motor units in the flexor carpi ulnaris were calculated from thresholds defined using threshold tracking.'True" rheobase and rheobasic latencies were measured using test stimuli of 100 -ms duration. For ten units, the technique of latent addition was used to measure threshold changes directly attributable to nodal conductances, and for six units these were compared with strength-duration properties at different membrane potentials. The data indicate that measurements of tau (SD) and rheobase can provide sensitive indicators of conductances present at the node of Ranvier when membrane potential changes. There is a reciprocal relationship between tau (SD) and rheobase for single motor units at different membrane potentials, and this relationship may allow changes in tau (SD) due to depolarization and demyelination to be differentiated. (C) 2000 John Wiley & Sons, Inc.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle, and threshold electrotonus) of median motor axons at the wrist and peroneal motor axons at the ankle in 12 healthy subjects. Stimulus-response curves and strength-duration properties were similar, though higher stimulus intensities were required for peroneal axons. However, there were significant differences in the recovery cycle of excitability following a conditioning stimulus and in threshold electrotonus. In the recovery cycle, median axons had significantly greater supernormality and late subnormality. In threshold electrotonus, the initial slow threshold changes in response to subthreshold depolarizing and hyperpolarizing currents (S1) were significantly greater in median axons, and there was also greater accommodation to depolarizing currents (S2) and greater threshold undershoot after depolarization. Similar differences in supernormality and the S1 phase of threshold electrotonus were found between peroneal axons at ankle and knee, suggesting that these properties may be dependent on nerve length. When median motor axons at the wrist were compared with peroneal motor axons at the knee, there were no differences in refractoriness and supernormality and only small differences in S1, but the late subnormality and undershoot were significantly greater in the median axons. These findings suggest that, in addition to any length-dependent differences, peroneal axons have a less prominent slow K+ conductance. We conclude that the properties of different motor axons are not identical and their responses to injury or disease may therefore differ. (C) 2000 John Wiley & Sons, Inc.

Objective: To investigate responsiveness of human cutaneous mechanoreceptor to selective tactile stimuli produced by brief air-puff stimulation. Methods: Using percutaneous microneurography, activities of single sensory units innervating glabrous skin of the hand were recorded, and air-puff stimuli with a short rise time (0.5 Ins), generated by a high-speed ail control system, were applied to the receptive field. Receptor activation time was estimated as the latency difference between electrically and air-puff evoked responses. Results: Thirty units were analyzed: all 4 kinds of mechanoreceptors of human glabrous skin (fast adapting type 1 [FA I, II = 7], fast adapting type [FA II, ii = 4], slowly adapting 1 [SA I, II = 5] and slowly adapting 2 [SA II, ii = 14]) were activated by air-puff stimulation. Estimated receptor activation times were 0.6-6.2 ms (mean 2.2 ms). FA II units occasionally responded twice or more to a single air-puff stimulus. Conclusions: Brief air-puffs can activate all 4 human cutaneous mechanoreceptors. and the receptor transduction time is estimated as approximately 2.0 ms. Properties of human mechanoreceptors can be studied using air-puff stimulation and microneurography. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.

To investigate the sensory nerve responses to selective touch stimulation, sensory nerve action potentials after brief air-puffs were recorded with a microelectrode. In patients with peripheral neuropathy, those with impairment of tactile sensations had significantly smaller responses than did those without tactile impairment, suggesting receptor activation failure as well as nerve conduction failure. Brief air-puff stimulation, when combined with microneurography, could be used for evaluating the tactile receptor properties in humans.

We describe a patient who developed Guillain-Barré syndrome (GBS) following hand-foot-and-mouth disease (HFMD) which is known to be caused by enterovirus infection. A 35-year-old man developed acute paraparesis and dysesthesia in the four limbs following typical skin eruption of HFMD. Electrophysiologic studies showed peripheral nerve demyelination predominant in the distal terminals. HFMD is a rare cause of meningitis, encephalitis, and polio-like myelitis, but GBS following HFMD has never been described.

IgG anti-GQ1b antibody was present in a patient with acute ataxia and areflexia without ophthalmoplegia or elementary sensory loss. Sensory nerve conduction studies and somatosensory evoked potentials were normal, but postural body sway analysis showed dysfunction of the proprioceptive afferent system. The clinical presentation and laboratory results for this patient resemble those of Miller Fisher syndrome, except for the lack of ophthalmoplegia. This case may represent part of an IgG anti-GQ1b syndrome.

Griffin and colleagues (Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath DR, Macko C, McKhann GM, Asbury AK, Pathology of motor-sensory axonal Guillain-Barre syndrome. Ann Neurol 1996;39:17-28 [4]) proposed that acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are part of the spectrum of a single type of immune attack on the axon. In contrast, IgG anti-GM1 antibody is associated closely with AMAN, but whether other IgG anti-ganglioside antibodies are associated with this neuropathy is not clear. We investigated whether IgG anti-ganglioside antibodies can be used as immunological markers to differentiate AMAN from acute inflammatory demyelinating polyneuropathy (AIDP) and whether these autoantibodies are present in AMSAN. The frequencies of anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies in 21 AMAN patients were significantly higher than in 19 AIDP patients. Anti-GM1b and anti-GD1a IgG, as well as anti-GM1 IgG antibodies, therefore are immunological markers for AMAN. The patients with AMSAN had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies, indicative that AMAN and AMSAN share a common immunological profile. (C) 1999 Elsevier Science B.V. All rights reserved.

Objectives-To investigate the incidence of hyperreflexia in patients with Guillain-Barre syndrome (GBS), and its relation with electrodiagnosis of acute motor axonal neuropathy (AMAN), antiganglioside GM1 antibody, and Campylobacter jejuni infection. It was reported that patients with AMAN in northern China often had hyperreflexia in the recovery phase. Methods-In 54 consecutive Japanese patients with GBS, sequential findings of tendon reflexes were reviewed. Ey electrodiagnostic criteria, patients were classified as having AMAN or acute inflammatory demyelinating polyneuropathy (AIDP). Anti-GM1 and anti-C jejuni antibodies were measured by enzyme linked immunosorbent assays. Results-Seven (13%) patients developed hyperreflexia with the spread of the myotatic reflex to other segments in the early recovery phase, one of whom already had hyperreflexia in the acute progressive phase. Of the seven patients, six had AMAN and all seven had anti-GM1 antibodies, whereas only two had anti-C jejuni antibodies. Hyperreflexia was more often found in patients with AMAN than AIDP (6/23 v 1/18, p = 0.002), and in patients with anti-GM1 antibodies than without them (7/26 v 0/28, p = 0.01). Hyperreflexic patients had milder peak disabilities than patients without hyperreflexia (p = 0.03). Increased motor neuron excitability in the hyperreflexic patients was supported by increased soleus H-reflex amplitudes and the appearance of II-reflexes in the small hand or foot muscles. Conclusions-Hyperreflexia often occurs in patients with GBS especially with AMAN, anti-GM1. antibodies, and milder disease. Increased motor neuron excitability further characterises the subgroup of patients with GBS with AMAN and anti-GM1 antibodies.

In some patients with amyotrophic lateral sclerosis (ALS), the thenar hand is more severely affected than the hypothenar hand. To quantify the dissociated involvement, we examined the motor unit number estimate (MUNE) of both the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles in 23 patients with ALS. Whereas ALS patients had significantly smaller MUNEs than normal subjects in both muscles, the extent of motor unit loss was significantly greater in the APE than ADM. Moreover, a simple comparison of the amplitude of compound muscle action potentials (CMAPs) showed that ALS patients had significantly smaller APB/ADM ratios than normal subjects and patients with cervical spondylotic amyotrophy, bulbospinal muscular atrophy, or peripheral neuropathy, The more severe involvement of the APE probably reflects the specific pathophysiology in ALS, and possible mechanisms for the dissociated involvement are discussed. (C) 1999 John Wiley & Sons, Inc.

If anti-GM1 antibody plays a role in the axonal damage in Guillain-Barre syndrome, the common entrapment sites may be preferentially involved with evidence of axonal dysfunction. To assess this hypothesis, we studied nerve conduction across the cubital tunnel in 44 patients. Abnormal amplitude reduction of compound muscle action potentials (CMAPs) was found in 45% of 20 immunoglobulin G (IgG) anti-GM1-positive and in 29% of 24 anti-GM1-negative patients. The time course and sequel were distinct between the two groups. In the former group, the amplitude reduction was prominent in weeks 1 to 2 and was followed by a decrease in distal CMAPs (axonal degeneration) or an increase in proximal CMAPs (resolution of conduction block), In contrast, anti-GM1-negative patients showed slower resolution with temporal dispersion. In anti-GM1-positive cases, amplitude reduction at the common entrapment site is frequent and may reflect wallerian degeneration or physiological conduction block at the nodes of Ranvier, both suggesting axonal involvement. (C) 1999 John Wiley & Sons, Inc.

The purpose of this study was to investigate activity-dependent excitability changes in polyneuropathy and their correlation with symptomatology. First, we recorded sensory nerve action potentials (SNAPs) with an intraneural microelectrode during impulse trains in 11 patients with chronic inflammatory demyelinating polyneuropathy, When the stimulus frequency was increased to greater than or equal to 20 Hz, all patients showed marked decreases in the amplitudes of averaged SNAPs (128 responses) associated with latency increases. The amplitude decreases were much greater than those in patients with axonal neuropathies. In single-unit recordings, responses showed latency increases, which were small but sufficient to cause decreases in the averaged responses. Clinical sensory impairment was correlated with the degree of preexisting conduction block or axonal loss, but not with the degree of rate-dependent amplitude decreases. Activity-dependent changes occur preferentially in demyelinating neuropathy and are a sensitive measure of demyelination. The mechanism responsible for the amplitude decreases could be conduction slowing or block caused by activity-dependent hyperpolarization. (C) 1999 John Wiley & Sons, Inc.

Object: To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B-12, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodialysis. An ultra-high dose of vitamin B-12 has been reported to promote peripheral nerve regeneration in experimental neuropathy, Methods: Nine patients received a 500 mu g methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study. Results: Serum concentrations of vitamin B-12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects. Conclusion: Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodialysis patients.

To examine the validity of electrodiagnostic tests to help diagnosis and to evaluate disease activity of juvenile atrophy of unilateral upper limb (Hirayama's disease), we reviewed the results of nerve conduction studies, motor unit number estimates, electromyography, and somatosensory evoked potentials in consecutive 38 patients. There was selective involvement of the C8-T1 myotomes, in which motor unit loss was more prominent in the abductor digiti minimi than in the abductor pollicis brevis muscles, and F wave persistency was decreased out of proportion to the motor unit loss. These findings may help diagnosis. With respect to the disease activity and treatment, denervation potentials in the flexor carpi radialis muscle were more frequent in patients with shorter disease duration than those with longer duration. Median F wave persistency was greater in patients treated with neck brace than in patients without the treatment. These parameters can monitor the disease activity and efficacy of treatment.

To investigate whether ataxia in Miller Fisher syndrome (MFS) is caused by loss of proprioception or cerebellar dysfunction, we studied the power spectrum peak of the body sway frequency in 10 MFS patients, and compared the results with those of patients with cerebellar or sensory ataxia. The cerebellar patients had a peak at 2.4 Hz, whereas sensory ataxia patients had a 1-Hz peak. Nine of the MFS patients had a distinct 1-Hz peak. Clinical sensory loss or abnormal sensory nerve potentials were present in only 3 patients, whereas soleus H-reflexes were absent in all the MFS patients. MFS patients have dysfunction of the proprioceptive afferent system, and the special sensory ataxia may be caused by the selective involvement of muscle spindle afferents.

To assess the clinical and electrophysiological features of n-hexane neuropathy caused by addictive inhalation, 4 patients were studied in the progressive phase. The neurological manifestations were characterized by subacute predominantly motor polyneuropathy and disease progression despite discontinuance of the chemicals, which were similar to those reported in industrial exposure, although with a severer degree associated with anorexia and body weight loss. Electrophysiological studies showed that all showed multifocal conduction block and profound conduction slowing, as well as features of axonal degeneration, Sural nerve biopsy showed axonal loss, axonal swelling, and thin myelin probably due to retraction by axonal swelling. n-Hexane abuse causes severe subacute polyneuropathy. The mixed axonal and demyelinating electrophysiological features were consistent with peculiar pathological findings. Conduction block, probably due to paranodal myelin retraction or ongoing wallerian degeneration, is very frequent and could be responsible for the clinical deficits, especially in the early phase of illness.

Objective: To investigate the prognostic value of anti-GM1 antibody. Background: Whether anti-GM1 antibody is a marker of poor prognosis due to axonal degeneration in Guillain-Barre syndrome (GBS) is a matter of controversy. Methods: The clinical recovery of 41 consecutive GBS patients was analyzed. Results: The Hughes functional grading scores were similar at the peak, and 1, 3, and 6 months after onset for the groups of patients with (n = 19) and without (n = 22) immunoglobulin (Ig) G anti-GM1 antibodies. However, the anti-GM1-positive group included significantly higher proportions of patients with poor recovery (inability to walk independently at 6 months, 5 of 19 versus 0 of 22; p = 0.01) and those with a markedly rapid recovery (improvement by two or more Hughes grades within a month, 9 of 19 versus 4 of 22; p = 0.05). The positivity of IgG anti-GM1 antibody correlated well with the electrodiagnosis of the acute motor axonal neuropathy pattern but was not always associated with poor prognosis. Anti-GM1-positive patients showed two different patterns of clinical recovery-their conditions improved slower or faster than those of the anti-GM1-negative patients, most of whom had acute inflammatory demyelinating polyneuropathy. Conclusions: Anti-GM1 antibody is not always a marker of poor prognosis and, besides axonal degeneration, early reversible effects other than demyelination could be part of the pathophysiology of Guillain-Barre syndrome with IgG anti-GM1 antibody.

Beneficial treatment has not been established for chronic sensory ataxic neuropathy associated with Sjogren's syndrome (CSAN-SS). We describe two patients with CSAN-SS who clinically improved in response to D-penicillamine treatment. Their neuropathic symptoms were lessened after D-penicillamine, and the results of electrophysiologic studies support the clinical improvement. D-Penicillamine can be considered a potentially beneficial agent in the treatment of CSAN-SS.

Thirty-one cases (26 patients) of clinically definite multiple sclerosis with predominant spinal cord involvement were studied retrospectively, focusing in particular on the results of sensory testings which were compared with the findings of spinal cord magnetic resonance imaging (MRI) and somatosensory evoked potentials (SEPs). Factor analysis of the sensory impairments showed two factors corresponding to superficial (pain and light-touch) and deep (position and 'thumb/big toe localizing') sensations. Vibratory sense depended on both Factors, but more on deep sensations. Multiple regression analysis of the SEP abnormalities and sensory deficits showed that impaired deep sensations contributed to abnormal SEPs, but the results of clinical sensory testings and SEPs were dissociated in 31% of the extremities examined. The MRI sagittal images correlated well with the Levels of sensory impairments, whereas the axial images showed a poor relationship to the extent of sensory impairments. We concluded that the use of SEPs as well as MRI is not always superior to such clinical sensory tests as the 'thumb/big toe localizing tests'. (C) 1998 Elsevjer Science B.V. All rights reserved.

To investigate the pathophysiological role of anti-GM1 antibody in Guillain-Barre syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor or acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patients), or as undetermined (1 patient) by electrodiagnostic criteria Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathophysiological mechanisms in IgG anti-GM1-positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.

Eight of 32 patients (25%) with chronic inflammatory demyelinating polyneuropathy (CIDP) had micturitional disturbance, which consisted of voiding difficulty (n = 4), urgency (n = 4), or urgency incontinence (n = 1). Urodynamic studies on four symptomatic patients showed disturbed bladder sensation in two, bladder areflexia in one, and neurogenic changes of the external sphincter in one, indicative of peripheral parasympathetic and somatic nerve dysfunctions. Cystometry also showed detrusor overactivity in two patients but no evidence of CNS involvement, evidence that bladder overactivity occurs by probable pelvic nerve irritation.

A 47-year-old man showed progressive, symmetrical weakness in the limbs for 6 months. There was muscle atrophy, fasciculations, and acute denervation without motor conduction abnormalities below the elbows or knees: and motor neuron disease had once been suspected. However, compound muscle action potentials (CMAPs) after proximal stimulation showed an amplitude reduction between axilla and Erb's point for the median and ulnar nerves on both sides. His weakness as well as the amplitude reduction improved after administration of prednisolone. Demyelinative conduction abnormalities can be limited to the proximal segments for at least several months in a conduction equivalent to chronic inflammatory demyelinating polyneuropathy (CIDP). (C) 1998 Elsevier Science B.V. All rights reserved.