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To determine the effect of IV immunoglobulin (IVIg) on neurologic function and electrophysiologic studies in multifocal motor neuropathy with conduction block (MMN).

We studied a case of flaccid paraplegia that immediately followed intrathecal injection of cytosine arabinoside diluted in 1.5 bacteriostatic water (1.5 benzyl alcohol in H2O). The complication was reversed by rinsing the CSF space with saline. Autopsy showed fibrosis and remyelination of lumbosacral nerve roots. In acute and chronic animal experiments, we showed that benzyl alcohol in commercially used concentrations can have a local anesthetic and an irreversible toxic effect on nerve fibers. This provides a sufficient explanation for many cases of paraparesis following intrathecal chemotherapy.

In experimental allergic neuritis (EAN) severity of clincal disease and pathology correlate with the dose of antigen (Hahn et al., Lab Invest 59:115–125, 1988). To avoid axonal membrane contamination of the antigen, EAN was induced with a synthetic peptide, corresponding to residues 53–78 of bovine P2 myelin protein. Severity of EAN correlated with the dose of peptide in the inoculate. The relationship between demyelination, inflammation and axonal degeneration was studied. Low doses resulted in pure demyelination. Axonal degeneration occurred only with high doses of inflammation. The role of macrophages in producing axonal damage is discussed.

Passive transfer of experimental allergic neuritis (EAN) lymph node cells (LNC) by intraneural injection did not produce significant demyelination. EAN-LNC stimulated with myelin in vitro produced mild demyelination while those incubated with Concanavalin A had no effect. The lack of demyelination by unstimulated EAN-LNC is in contrast to the marked demyelination produced by intraneural injection of EAN serum. The mononuclear cell infiltration and demyelination of classical EAN seem to require both cellular and humoral immune responses.

The integrity of the blood-nerve barrier (BNB) was studied during the development of experimental allergic neuritis (EAN). Lewis rats immunized with bovine nerve or myelin plus complete Freund's adjuvant developed histological lesions of EAN in nerve roots by 10–12 days and in sciatic nerves by 12–14 days. Evans blue-albumin (EBA) and horseradish peroxidase (HRP) were injected i.v. 1 h prior to killing on days 6–18. Perivascular and diffuse endoneurial leakage of the tracers was seen in nerve roots by 10–12 days post immunization (p.i.) and in sciatic nerves by 12–14 days. This coincided with the appearance of endoneurial infiltration with inflammatory cells and endoneurial proteinaceous edema at a time when Schwann cell and myelin changes were still minimal. Therefore, an alteration in BNB permeability occurs early in EAN, coincident with inflammatory cell infiltration. This could be an expression of delayed hypersensitivity, yet it would also facilitate the entry of anti-myelin antibodies into the endoneurium where they could initiate demyelination.

Serum from rabbits with experimental allergic neuritis (FAN) when injected into rat sciatic nerves produced rapidly evolving demyelination followed by remyelination. Myelinating and non-myelinating Schwann cells as well as myelin itself were damaged by 15 min after injection. Myelin degradation was well advanced prior to involvement by macrophages at 12 h. The demyelinating factor was myelin-specific and complement-dependent. The evidence suggests that the FAN antigen may reside in Schwann cell membranes as well as in myelin.

Serum and lymphocytes from patients with acute Guillain-Barre polyneuropathy were injected into rat sciatic nerves. Serum from 13 of 17 patients produced perivenular demyelination, associated with lymphocytic infiltration. The pattern of demyelination differed from that caused by experimental allergic neuritis serum. The level of serum demyelinating activity was greatest early in the disease and then decreased. The demyelinating factor was heat-labile but not complement-dependent. Circulating lymphocytes did not cause demyelination in eight patients.

Seven patients with optic neuritis were found in a study of 84 families with familial multiple sclerosis (MS). Evidence obtained from neurologic examination and electrophysiologic testing tended to confirm monosymptomatic optic nerve involvement. The presence of isolated optic neuritis in these families implies that MS and at least some cases of isolated optic neuritis have a similar etiology.

We describe monozygotic twins who are either discordant or show extreme variability in the expression of facioscapulohumeral muscular dystrophy (FSHD). One twin was severely incapacitated by FSHD. The asymptomatic twin demonstrated equivocal facial weakness on physical examination, but no difference on quantitative myometry when compared with normal controls. High-resolution cytogenetic analysis showed no chromosomal abnormalities. Five polymorphic 4q35 markers known to be linked to FSHD showed identical RFLP patterns, indicating that submicroscopic chromosomal rearrangement is unlikely. We conclude that this set of twins represents an extreme case of variability in the expression of the FSHD gene.

Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis rats by passively transferring T cells sensitized to SP-26, a peptide fragment of P2 myelin protein. The recipients became sick 4–8 days post transfer and the degree of disability correlated directly with the dose of T cells. Smaller doses caused demyelination of nerve roots and sciatic nerves and larger doses produced more severe demyelination and significant axonal degeneration. Irradiated recipients developed similar clinical EAN and showed macrophage-mediated demyelination despite severe suppression of the host inflammatory response.

Stroke neurologists are commonly asked to review patients who require coronary artery bypass grafting (CABG) but who also have comorbid severe carotid stenosis; such patients may be offered simultaneous carotid endarterectomy (CEA). In Canada, 0.51% of CABG procedures were combined CEA-CABG. The adjusted stroke and death rate was 2.67-fold greater in the combined CEA-CABG group compared to CABG alone. Randomized trials of the combined procedure are needed.

To determine the frequency of the possible association between chronic inflammatory demyelinating polyneuropathy (CIDP) and MS, we did magnetic resonance imaging (MRI) of the brain in 19 patients with CIDP. Only 1 patient had clinical signs suggestive of central involvement. Seven of the 19 scans showed 2 or more brain "lesions." In 1 case the cause was an infarct and in 5 cases the patients were over 55 years of age and the lesions were not typical of MS. One 38-year-old patient had 2 small subcortical lesions. Typical MS lesions on MRI are uncommon in CIDP.

We studied a young woman with MS, myasthenia gravis, and Graves disease. There are at least nine other reported cases with both MS and myasthenia gravis.

To examine whether the demonstrated efficacy of tissue-type plasminogen activator (t-PA) for acute ischemic stroke can be effective in a community setting.

Five patients with a clinical diagnosis of acute Guillain-Barré polyneuropathy (GBP) had electrically inexcitable motor nerves. All were quadriplegic. One patient died and 3 of the 4 survivors showed poor recovery. Autopsy studies on the patient who died showed severe axonal degeneration in nerve roots and distal nerves without inflammation or demyelination. Electrophysiological studies in these patients suggested that the predominant process was axonal degeneration These cases may represent a separate clinicopathological entity, and constitute a variant of GBP characterized by an acute axonal neuropathy.

The clinical and laboratory features of recurrent Guillain-Barré syndrome (RGBS) were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted criteria for Guillain-Barré syndrome (GBS). All patients were asymptomatic or only mildly symptomatic between attacks. In a given patient, the time to reach peak deficit from the onset of symptoms, the functional grade at peak deficit and the duration of the intervals between episodes varied considerably and unpredictably from one episode to the next. Analysis of these parameters across the entire group revealed no significant change as the number of attacks increased. The distribution of weakness varied between episodes with the possible exception of features of the Miller Fisher variant which were more constant Tremor was noted in two patients and enlarged nerves in one patient. There was no evident response to immunosuppressive therapy Results of cerebrospinal fluid (CSF) analysis and nerve conduction studies during recurrences were those expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were sometimes observed after several recurrences. The following characteristics of RGBS may be sufficiently distinctive from those of chronic relapsing polyneuropathy to justify their nosological separation: rapid onset of symptoms with subsequent complete or near complete recovery, high incidence of an antecedent illness, lack of an apparent response to immunosuppressive therapy and normal CSF protein levels at the onset of a recurrence.

Thirty patients with definite or probable chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (16 patients) or relapsing (14 patients) course were randomly assigned to receive intravenous immuno-globulin (IvIg) 0.4 g per kg body weight or a placebo treatment on 5 consecutive days in a double-blind, cross-over trial. Neurological function was monitored by serial quantitative assessments [neurological disability score (NDS); clinical grade (CG) and grip strength (GS) measurements] and by electrophysiological studies before and after each treatment period. Twenty-five patients completed both treatment periods. A comparison of the observed changes in clinical outcome measures revealed statistically significant differences in favour of IvIg, with (mean±SD) improvements in NDS by 24.4±5.4 points (P < 0.002) in CG by 1±0.3 points (P < 0.001) in GS by + 6.3±1.7 kg (P < 0.005), whereas scores were unchanged or worse with placebo. A secondary two-group analysis of the first trial period included all 30 patients; 16 patients had been randomly assigned to Ivlg and 14 to placebo treatments. Again significant differences in favour of Ivlg were observed in all the clinical end-points: improvement in NDS was 35.6±25 points (P < 0.001), in CG it was 1.3±1.9 points (P < 0.002) and in GS +9.8±7.7 kg (P <0.001), whereas all scores worsened with placebo. Of the 30 patients, 19 (63%) improved with IvIg treatments; nine out of 16 patients (56%) with chronic progressive CIDP, and 10 out of 14 patients (71%) with relapsing CIDP (differences were not statistically significant). A placebo response was seen in five patients. Comparison of paired electrophysiological measurements before and 4 weeks after IvIg treatments revealed statistically significant). A placebo response was seen in five patients. Comparision of paired electrophysiological measurements before and 4 weeks after IvIg treatments revealed statistically significant improvements in the summed motor conduction velocities (Σ MCV; P<−0.0001) and in the summed compound muscle action potentials (CMAP) evoked with proximal stimulation (Σproximal CMAP, P<0.03) of median, ulnar, peroneal and tibial nerves. Eight of nine IvIg responders with chronic progressive CIDP improved gradually to normal function with a single 5 day course of IvIg; in five of these, small doses of prednisone were prescribed during follow-up. In 10 IvIg responders with relapsing CIDP, improvement lasted a median 6 weeks (range 3–22 weeks) and was reproducible with open label treatments. All 10 patients have been maintained and stabilized with IvIg pulse therapy of I g per kg body weight or less, given as a single infusion prior to the expected relapse. A beneficial response to IvIg was found to be most likely in patients with acute relapse or with disease of one year or less. Patients with predominantly sensory signs did not improve.

Eighteen patients with definite, untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (nine patients) or relapsing course (nine patients) were randomized prospectively to receive 10 plasma-exchange (PE) or sham plasma-exchange (SPE) treatments over 4 weeks in a double-blind trial. After a wash-out period of 5 weeks or when they returned to baseline scores, patients were crossed over to the alternate treatments. Neurological function was assessed serially using a quantitative neurological disability score (NDS), a functional clinical grade (CG) and grip strength (GS) measurements. Electrophysiological studies were done at the beginning and end of each treatment. A primary ‘intention to treat’ analysis showed significant improvement with PE in all clinical outcome measures: NDS by 38 points, P < 0.001; CG by 1.6 points, P < 0.001; GS by + 13 kg, P < 0.003 and in selected electrophysiological measurements, Σ proximal CMAP, P < 0.01; Σ motor conduction velocities, P < 0.006; Σ distal motor latencies, P < 0.01. Fifteen patients completed the trial and of those, 12 patients (80%) improved substantially with PE; i.e. five out of seven patients with chronic progressive course and seven out of eight patients with relapsing CIDP improved. There were three drop-outs: one patient lost venous access; one patient suffered a stroke and one patient left the trial to receive open treatment elsewhere. The improvement in motor functions correlated with the electrophysiological data, i.e. with improved motor conduction velocities and reversal of conduction block. Eight of 12 PE responders (66%) relapsed within 7–14 days after stopping PE. All improved with subsequent open label PE; all but two patients required long-term immunosuppressive drug therapy for stabilization. The PE non-responders improved with prednisone. We conclude that PE is a very effective adjuvant therapy for CIDP of both chronic progressive and relapsing course; concurrent immunosuppressive drug treatment is required. Exchange treatments should be given two to three times per week until improvement is established; the treatment frequency should then be tapered over several months.

Modern techniques have defined the hereditary motor and sensory neuropathies (HMSN) as a genetically heterogenous group of disorders. This includes a rare variant with X-linked dominant inheritance. We have traced this disorder through 6 generations of a large Canadian kindred; neurological and electrophysiological examinations were performed in 57 family members and nerve biopsies were studied in 2 affected males, early and late in the disease; 42/83 family members were affected. No male-to-male transmission was encountered in 19 sons of affected fathers, whereas all their daughters expressed the disease. Linkage was shown to the DNA loci DXYS1 Z max = 2.87 at θ max = 0.06 and to PGK1 Z max = 1.51 at θ max = 0 (Beckett et al., 1986). The typical clinical features are onset in early childhood, pes cavus, atrophy and weakness of peroneal muscles and intrinsic hand muscles, and sensory abnormalities. Males were severely affected, whereas females had mild or subclinical disease. Electrophysiological observations indicated a substantial loss of distal motor and sensory nerve fibres. Evoked compound muscle action potentials in extensor digitorum brevis were absent or severely reduced in 42% of cases and the peroneal motor nerve conduction velocity was mildly reduced to a mean 36.5 ±7.4 m·s−1. Sural sensory nerve action potentials were absent or severely reduced in 75% of those affected. Nerve biopsies showed loss of myelinated and unmyelinated nerve fibres, regenerative sprouting and secondary demyelination. The findings indicate that this distinct variant of HMSN is the result of primary axonal degeneration.

Article abstract-Objectives: To determine the character, intensity and frequency of pain in Guillain-Barre syndrome (GBS) and to evaluate the response to treatment. Design: A prospective longitudinal study. Setting: Academic hospital-based practices. Patients: Fifty-five consecutive patients with GBS. Interventions: Patients were evaluated on admission and at 2, 4, 8, 16, and 24 weeks. Main outcome measures: Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm) and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10 cm), Disability Grading Scale for GBS. Results: Forty-nine patients (89.1%) described pain during the course of their illness. On admission, mean pain intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The most common pain syndromes observed were deep aching back and leg pain and dysesthetic extremity pain. Pain intensity on admission correlated poorly with neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate pain relief. Conclusions: Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. Pain intensity on admission is not a predictor of poor prognosis. Back and leg pain usually resolves over the first 8 weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients despite motor recovery and the use of adjuvant analgesics.