Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group

We performed electrophysiological and serological testing within 15 days of symptom onset on 369 patients with Guillain-Barré Syndrome (GBS) enrolled in a trial comparing plasma exchange, intravenous immunoglobulin, and both treatments. Patients were classified into five groups by motor nerve conduction criteria; 69% were demyelinating, 3% axonal, 3% inexcitable, 2% normal, and 23% equivocal. Six of 10 (60%) patients with axonal neurophysiology had had a preceding diarrheal illness compared with 71 of 359 (20%) in other groups. Antiganglioside GM1 antibodies were present in a higher proportion of patients with axonal physiology or inexcitable nerves than other patients. The number dead or unable to walk unaided at 48 weeks was greater in the group with initially inexcitable nerves (6 of 12, 50%) compared with the rest (52 of 357, 15%), but was not significantly different between the axonal (1 of 10, 10%) and demyelinating (44 of 254, 17%) groups. Sensory action potentials and clinical sensory examination were both normal in 53 of 342 (16%) patients, and these "pure motor GBS" patients were more likely than other GBS patients to have IgG antiganglioside GM1 antibodies and to have had preceding diarrhea but had a similar outcome. The axonal group was more likely than other groups to have normal sensory action potentials. The outcomes in response to the three treatments did not differ in any subgroup (including patients with pure motor GBS or preceding diarrhea) or any neurophysiological category.     

Chronic relapsing brachial plexus neuropathy with persistent conduction block

Idiopathic brachial plexus neuropathy (BPN) is an immune-mediated disorder characterized by an acute onset of painful weakness in one or both upper extremities. The course is usually monophasic with gradual improvement over months; however, occasionally BPN can recur. Electrophysiologic studies suggest the pathogenesis is primarily axonal in the majority of cases. We describe an unusual case of BPN in which the patient had a chronic and relapsing course of painless weakness associated with conduction blocks and other electrophysiologic features of demyelination across the brachial plexus. The patient improved following treatment with intravenous immunoglobulin. The neuropathy falls within the spectrum of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.     

Histomorphometric study in children with idiopathic nephrotic syndrome

There is agreement on the clinical diagnostic criteria for acute inflammatory demyelinating polyneuropathy (AIDP/GBS) however, there is lack of consensus for detection of demyelination. In order to critically evaluate the prevailing criteria, sixty-six patients who fulfilled NINCDS criteria and had typical features of GBS were studied for electrophysiological abnormalities of peripheral nerves by using standard methods (median, common peroneal, sural and ulnar) between 1 to 12 weeks after the onset of symptoms. The commonest abnormality on motor nerve conduction study was prolonged distal latency (75%-83%) followed by reduction in CMAP amplitude (63%-82%), decreased velocity (48%-62%), conduction block (17%-39%) and f-wave abnormalities (37.8%-59%). Sensory conduction abnormalities were detected in over 20% of median, 25% of ulnar and 33% of sural nerves. All the patients had abnormality of at least two motor conduction parameters in one nerve when values beyond 2 SD of the mean were considered abnormal and over 70% of patients had three abnormalities in two nerves or two abnormalities in three nerves. Comparison with the prevailing criteria for demyelination revealed that the number of patients fulfilling them varied widely: Albers et al. (1985): 74.2%, Albers et al. (1989): 40.9% and Cornblath: 30.3%. We believe that the current criteria for detection of demyelination in acute neuropathy are too strict, underestimate the underlying pathology in GBS and need reassessment.     

Heterozygous P0 knockout mice develop a peripheral neuropathy that resembles chronic inflammatory demyelinating polyneuropathy (CIDP)

Demyelinating peripheral neuropathies are clinically divided into inherited and acquired types. Inherited demyelinating neuropathies are caused by mutations in genes expressed by myelinating Schwann cells, whereas acquired ones, including chronic inflammatory demyelinating polyneuropathy (CIDP), are probably caused by autoimmune mechanisms. We find that heterozygous P0 knockout (P0+/-) mice develop a neuropathy that resembles CIDP. By one year of age, P0+/- mice develop severe, asymmetric slowing of motor nerves, with temporal dispersion or conduction block, which are features of acquired demyelinating neuropathies including CIDP. Moreover, morphological analysis of affected nerves reveals severe and selective demyelination of motor fibers, focal regions of demyelination, and inflammatory cells. These data suggest that immune-mediated mechanisms may contribute to the pathogenesis of the neuropathy in P0+/- mice.     

Abnormal sensory nerve conduction in multifocal demyelinating neuropathy with persistent conduction block

Two patients exhibited chronic, slightly asymmetric weakness and wasting with fasciculations of the upper limb and hand muscles. Motor nerve conduction studies showed features of multifocal conduction block in nerve segments other than those usually involved in entrapment syndromes. The F wave was markedly delayed in the median and ulnar nerves. Transcranial cortical and cervical root magnetic stimulation showed bilaterally delayed thenar responses with normal central conduction time. Needle electromyography demonstrated a chronic denervation pattern with large polyphasic motor units in several muscles of the upper limbs. Sensory symptoms were mild and limited to paresthesias in the fingertips. Sensory nerve conduction velocity and sensory nerve action potential amplitudes were normal in elbow-to-wrist and wrist-to-finger segments of the median and ulnar nerves, but there was a delayed cortical response and unrecognizable Erb's point and cervical responses in the somatosensory evoked potentials to median nerve electrical stimulation. Electrophysiologic examination was normal in most nerves of the lower limbs. These two patients, meeting clinical and electrophysiologic criteria of multifocal neuropathy with conduction block, demonstrate that sensory fibers may also be involved in this syndrome.     

Successful endoscopic transpapillary drainage of an infected pancreatic pseudocyst

Multifocal motor neuropathy (MMN) is a disorder with a highly characteristic clinical picture and one which is defined by a specific electrodiagnostic abnormality, namely, multifocal conduction block which is confined to motor axons. Sensory axons which traverse segments of severe or even complete motor conduction block conduct normally. A proportion of patients with MMN also have elevated levels of antibodies to GM1 ganglioside. However, about one half of MMN patients lack elevated levels of these antibodies and many others have only modest elevations, to a degree often seen in other neurological and even non-neurological disorders. Furthermore, clinical and electrophysiological improvement of MMN in response to treatment with high dose intravenous immunoglobulin is achieved in the absence of any change in antiglycolipid levels. Injection of serum from patients with MMN and elevated GM1 antibody levels produces demyelination in recipient rat nerves, suggesting a pathogenetic role for these antibodies in demyelination. However, sera of patients with identical antibody titers in other motor system diseases produced no demyelination, suggesting that the demyelinating factor resides in some other serum fraction. At present, there is insufficient evidence to support the contention that these antibodies play a critical pathogenetic role in MMN. Until more evidence is available it is important to define MMN on the basis of a characteristic clinical picture and a unique electrodiagnostic abnormality rather than on a pattern of serum antibodies.     

Multifocal motor neuropathy. Serum IgM anti-GM1 ganglioside antibodies in most patients detected using covalent linkage of GM1 to ELISA plates

IgM anti-GM1 antibodies occur with increased frequency in the serum of patients with multifocal motor neuropathy (MMN). We tested the ability of serum IgM from patients with MMN to bind to GM1 ganglioside covalently bound to secondary amino groups on ELISA plates (Co-GM1). The Co-GM1 technique detected high titer (> 1,800), selective, serum IgM binding to GM1 ganglioside in 85% of our MMN patients (23/27), a significantly greater frequency compared with figures of 37% and 52% found using our previous testing methods. Selective IgM anti-GM1 antibodies showed disease specificity. The only other patients with selective, high-titer IgM anti-GM1 antibodies had either chronic motor neuropathy without conduction block or acute immune neuropathy in China. No patient from the amyotrophic lateral sclerosis, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré, or systemic immune disorder control groups had selective IgM anti-GM1 antibodies at titers greater than 1,800 detected using Co-GM1 ganglioside as ELISA antigen. Titers of IgM anti-GM1 antibodies in MMN (averaging 31,000 +/- 15,000) were more than fourfold higher with Co-GM1 than with previous anti-GM1 assay methods, using conventional ELISA plates with GM-1 antigen alone (7,200 +/- 4,400) or in a lipid environment (3,600 +/- 1,300). We conclude that using ELISA testing with Co-GM1 antigen, serum anti-GM1 autoantibodies are a useful marker for MMN, because they are present in 85% of MMN patients and, at titers greater than 1,800, have strong specificity for immune-mediated motor neuropathies.     

Quality assurance in palliative care: some of the problems

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.     

Peripherally active analgesia of aminopeptidase-resistant sugar-coupled leucine enkephalin

Suramin, a promising chemotherapeutic agent, causes a dose-limiting sensorimotor polyneuropathy. We undertook a phase 1 study of suramin that included serial neurologic and electrophysiologic examinations as part of the safety evaluation. We found that 6 of 41 (15%) patients developed suramin-induced demyelinating neuropathy which resembled Guillain-Barre syndrome clinically. There was 1 asymptomatic patient with electrophysiologic abnormalities suggestive of a demyelinating neuropathy. In addition, 1 patient with mild axonal neuropathy at baseline had deterioration of his symptoms during suramin treatment. Four asymptomatic patients developed electrophysiologic findings suggestive of a mild axonal neuropathy. We conclude that: (1) serial electrophysiologic monitoring is helpful for early detection of suramin-induced neuropathy; and (2) fixed dosing schedule of suramin without adaptive control does not lead to an increased incidence of demyelinating neuropathy when compared to adaptively controlled dosing schedules.     

Subacute multifocal painful neuropathy with spontaneous remission

We present the cases of two patients with subacute onset of multifocal painful neuropathy with spontaneous remission and no relapse. The distribution of pain in patient 1 was hands (median > ulnar nerve region) and feet (peroneal and terminal tibial nerve regions), and in patient 2, hands (ulnar nerve region) and feet, left worse than in right. Both patients experienced facial numbness. Deep tendon reflexes were intact except for absent ankle jerks in patient 2. Motor nerve conduction studies demonstrated a marked prolongation of the distal motor latencies with normal proximal segment conduction velocities, suggesting distal demyelination. Cerebrospinal fluid protein concentration was elevated in patient 2, but no definite abnormality was found on sural nerve biopsy. A demyelinating neuropathy with a monophasic self-limited course may be consistent with Guillain-Barre syndrome (GBS). However, the multifocal painful sensory symptoms with facial numbness and the marked distal nerve conduction slowing in our cases are not consistent with GBS.     

Root stimulation studies in the evaluation of patients with motor neuron disease

Nerve root stimulation may be employed in patients with motor neuron disease (MND) to rule out motor neuropathy with conduction block. The diagnostic utility of these studies is unknown, in part because the range of amplitude changes across nerve root segments in patients with active neuronal degeneration has not been well studied. We reviewed root stimulation studies in 32 patients (59 nerves) with MND and found segmental amplitude reduction from 0 to 45%, a range similar to values reported for normal subjects; there was no suggestion of conduction block based on our usual criteria.     

Multifocal motor neuropathy

We present a review of the literature on multifocal motor neuropathy (MMN), a rare neurological disorder which has features in common with both chronic inflammatory demyelinating neuropathy and lower motor neuron disease. Clinically, MMN is characterised by slowly progressive asymmetrical limb weakness, usually most prominent in the forearms. Weakness may be associated with muscle wasting, fasciculations and decreased tendon reflexes. Serum anti-GM1 ganglioside antibody titres may be increased. The diagnostic hallmark of MMN is the electrophysiological demonstration of persistent localised motor conduction blocks, with otherwise normal or near-normal motor and sensory conduction velocities. The pathogenesis of MMN has not been elucidated completely. There is, however, substantial evidence for an autoimmune mechanism. Based on the possible involvement of the immune system in the pathogenesis of MMN the therapeutic efficacy of several immunomodulatory drugs has been tested. Treatment of MMN patients with human immunoglobulin or cyclophosphamide is usually followed by a marked improvement of strength. The finding that MMN is a potentially treatable disorder underscores the importance of distinguishing MMN from lower motor neuron disease, for which no effective therapy is currently available.     

Peripheral neuropathies associated with monoclonal proteins

Peripheral neuropathies associated with monoclonal proteins have received considerable attention as a clinically important group of chronic late-onset neuropathies. When a monoclonal protein is found in patients with peripheral neuropathy of unknown cause, as occurs in 10% of such cases, usually no associated disease is discovered; hence MGUS. Less often, disorders such as multiple myeloma, AL amyloidosis, Waldenstr?m's macroglobulinemia, osteosclerotic myeloma, and lymphoma are found. Demyelinating neuropathies associated with MGUS of all classes, but particularly IgM, Waldenstr?m's macroglobulinemia, and osteosclerotic myeloma typically follow an indolently progressive course, and frequently respond to treatments aimed at interfering with putative underlying immune mechanisms. By contrast, axonal neuropathies associated with MGUS, multiple myeloma, and AL amyloidosis have generally shown no response to therapy. Recently, IgM monoclonal and polyclonal antibodies directed against human peripheral nerve antigens including MAG and various glycolipids such as GM1 ganglioside have been found in patients with specific neuropathy syndromes. Anti-MAG antibodies occur in predominantly sensory demyelinating neuropathies, whereas elevated titers of anti-GM1 ganglioside antibodies are associated with lower motor neuron syndromes with multifocal motor conduction block. Although the evidence for autoimmune mechanisms in some monoclonal protein-associated neuropathies is mounting, a causal connection between monoclonal proteins and these neurologic syndromes has yet to be established.     

Antibody panels in idiopathic polyneuropathy and motor neuron disease

We prospectively evaluated patients with idiopathic polyneuropathy (PN) and motor neuron disease (MND) with commercial antibody (Ab) panels. Patients with sensorimotor PN received a "sensorimotor neuropathy profile" [3-sulfated glucuronyl paragloboside (SGPG)/myelin-associated glycoprotein (MAG), GM1, asialo-GM1, GD1b, Hu, sulfatide]. Motor neuropathy or MND patients underwent a "motor neuropathy profile" (SGPG/MAG, GM1, asialo-GM1). Seven of 78 patients (9.0%) with sensorimotor PN and 3 of 44 patients (6.8%) with MND had abnormal panels. None of 60 patients with axonal sensory or sensorimotor PN had antisulfatide Ab. Seven of 13 patients (54%) with multifocal motor neuropathy had abnormal panels, with 6 seropositive to GM1. We found abnormal Ab panels in fewer than 10% of patients with idiopathic sensorimotor PN and MND. Moreover, abnormal Ab tests often did not relate to the clinical context. Our data do not support the use of commercial Ab panels in the evaluation of patients with idiopathic PN or MND.     

Charcot-Marie-Tooth disease. Clinical study in 45 patients

Charcot-Marie-Tooth (CMT) disease is the commonest inherited peripheral neuropathy. The clinical study of 45 patients with CMT is presented. They were derived from Antonio Pedro Hospital of Universidade Federal Fluminense in Niteroi, RJ, Brazil. Such patients could be divided by the motor conduction velocity in two types: a demyelinating form or type I (11 cases) and an axonal form or type II (34 cases). The disease was inherited as an autosomal dominant trait in 23 patients and as an autosomal recessive trait in 7 cases. In 15 patients the disorder was sporadic. The age of onset was in most of our cases before the 20 years. All of them had distal weakness in lower limbs. 38.2% had also distal weakness in upper limbs. 80% had distal wasting of the lower limbs and 50% had distal wasting of upper limbs. The tendon reflexes were absent in 64% in lower limbs and in 28% in upper limbs. The sensitive impairment in the distal regions of the extremities was mild in most patients. We found enlargement of peripheral nerves in 7 patients of type I. Pes cavus was present in 21 cases and scoliosis in 7. We found postural tremor of hands in 6 patients. In 9 cases there were rare features as mental retardation, trigeminal nevralgia, optic atrophy, deafness and calf enlargement. In most of our cases the clinical course was very slow progressive. A greater severity was seen in our sporadic cases.     

The sword of Damocles: the psychosocial impact of familial spinocerebellar ataxia in South Africa

It has been recently recognized that increased titers of serum anti-GM1 antibodies may be associated with motoneurone diseases or with multiple motor neuropathy with or without conduction block and also with chronic sensorimotor neuropathy and Guillain-Barré syndrome. Santoro et al. were the first to note that anti-GM1 antibodies were able to bind to the nodes of Ranvier of the sural nerve of a patient with clinical signs and symptoms mostly resembling amyotrophic lateral sclerosis who also showed, in nerve conduction studies, multifocal motor nerve fibers conduction block and serum IGM anti-GM1 antibodies. The two patients presented in this report had asymetrical motor neurone disease with signs and symptoms of lower motoneurone involvement, and other signs, in the first patient, which suggested the existence of upper motoneurone damage. Besides, the second patient also had clinical sensory impairment in the lower limbs. Electrophysiologically, none of them had nerve conduction block but both showed inexcitable median and sural nerve sensory fibers. Both had high titers of anti-GM1. A sural biopsy of both patients showed immunoglobulins into the sensory fibers. However, we do not know whether the anti-GM1 antibodies bind to a cross-reactive glycolipid other than the GM1 itself. In any case, it seems that the presence of anti-GM1 antibodies might be a marker signalling a potentially treatable immune disorder which may have signs of lower and upper motor neurone disease and, also, clinical and electrophysiological evidences of peripheral sensory involvement.     

Nortropane-3beta-acetic acid, tropaquinuclidine and dehydrotropaquinuclidine (author''s transl)]

The greater decrease of conduction velocity in sensory than in motor fibres of the peroneal, median and ulnar nerves (particularly in the digital segments) found in patients with chronic carbon disulphide poisoning, permitted the diagnosis of polyneuropathy to be made in the subclinical stage, even while the conduction in motor fibres was still within normal limits. A process of axonal degeneration is presumed to underlie occurrence of neuropathy consequent to carbon disulphide poisoning.     

Significance of serum beta-hCG as a tumor marker for stomach carcinoma

We performed BAEP study to evaluate acoustic nerve involvement in 102 patients affected by peripheral neuropathies of different etiology, predominantly hereditary and inflammatory acquired neuropathies. Prolonged latency of early waves, indicative of slowing in VIII nerve conduction, was found in a high percentage of cases. Abnormalities were far more frequent (44% vs 14%) and severe in patients with demyelinating rather than axonal neuropathy. Among demyelinating neuropathy, the most severe latency delay was found in Hereditary Motor and Sensory Neuropathy type III. The pattern of acoustic nerve involvement differed slightly between Hereditary Motor and Sensory Neuropathy type I and acquired inflammatory demyelinating polyradiculoneuropathy, perhaps reflecting different pathogenetic mechanisms and different sites of VIII nerve demyelination.     

Conduction block in vasculitic neuropathy

Vasculitis involving peripheral nerves usually presents as an acute asymmetrical axonal neuropathy. We report a 67-year-old man with a symmetrical subacute neuropathy in which nerve conduction studies showed prominent conduction block, a finding indicative of demyelination. Sural nerve biopsy showed a vasculitic neuropathy with invasion of blood vessel walls by inflammatory cells and a mixture of nerve fiber loss and demyelination. The demyelination in this case was presumably a consequence of subinfarctive nerve ischemia.     

A prospective clinical and electrophysiologic survey of acute flaccid paralysis in Chinese children

We studied 29 children admitted to Beijing Children's Hospital (BCH) with acute flaccid paralysis between June 1991 and June 1993. Twenty-seven patients had Guillain-Barré syndrome--7 with acute inflammatory demyelinating polyneuropathy and 20 with acute motor axonal neuropathy (AMAN). Two had poliomyelitis. The most common cause of acute flaccid paralysis at BCH is the AMAN pattern of GBS.