M. Capasso

Reversible conduction failure in pharyngeal-cervical-brachial variant of guillain-barré syndrome

In two patients with the pharyngeal–cervical–brachial variant (PCB) of Guillain–Barré syndrome (GBS), low amplitude distal compound muscle action potentials and partial motor conduction blocks normalized without development of excessive temporal dispersion within 4 weeks. Sensory nerve action potentials significantly improved in amplitude or, when absent, rapidly became recordable at follow‐up. Besides axonal degeneration, PCB is characterized by reversible conduction failure in both motor and sensory fibers and is in the continuous spectrum of axonal GBS subtypes. Muscle Nerve, 2010

Experimental axonopathy induced by immunization with Campylobacter jejuni lipopolysaccharide from a patient with Guillain-Barré syndrome

New Zealand white rabbits were immunized with a lipopolysaccharide (LPS) extracted from a Campylobacter jejuni HS:19 strain isolated from a GBS patient expressing GM1 and GD1a-like epitopes, Freunds adjuvant (group I) and Freunds adjuvant plus keyhole lympet hemocyanin (KLH) (group II). Both groups showed high titers of anti-LPS and anti-GM1 and lower titers of anti-GD1b and anti-GD1a antibodies. Weakness and axonal degeneration in sciatic nerves was detected in 1/11 of group I and 6/7 of group II. This model replicates, at least in part, the pathogenetic process hypothesized in the human axonal GBS with antiganglioside antibodies post C. jejuni infection and indicates that KLH plays an additional role in neuropathy induction.

Hepatitis C virus infection and myositis: a virus localization study.

We report a case of myositis associated with chronic hepatitis C virus infection. Muscle biopsy and immunohistochemistry showed perifascicular atrophy, few necrotic and regenerating fibres, scarce perivascular infiltrates, deposits of immunoglobulin G, C3, fibrinogen and MAC in muscle vessel walls, and non-uniform expression of major histocompatibility complex-I antigens among muscle fibres. Hepatitis C virus NS3 antigen and hepatitis C virus RNA were detected in infiltrating cells but not within muscle fibres or endothelial cells. Our findings suggest that humoral-mediated immune mechanisms, not directly related to hepatitis C virus infection of muscle structures, may sustain the local inflammatory reaction in this patient.

Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln mutation

OBJECTIVE In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological and histopathological studies have suggested either a demyelinating or an axonal polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve conductions between and within nerves. METHODS Two men and one woman have been studied by conduction velocities, sural nerve biopsy with morphometry (one man) and DNA analysis. RESULTS In both men motor conduction velocities were slowed in the demyelinating range, conduction velocity differences among nerves in the same subject varied from 13 to 24 m/s, and distal median compound muscle action potential (CMAP) amplitudes were 3-5 times reduced compared to ulnar CMAPs. Abnormal area reduction or excessive temporal dispersion of proximal CMAP was present in at least two nerves in all patients. Sural nerve biopsy showed reduction of large myelinated fibres, cluster formations, occasional onion bulbs. Teased fibres study revealed short internodes for fibre diameter, enlarged Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients. CONCLUSIONS In this family conduction slowing and segmental conduction abnormalities, in absence of morphological evidence of de-remyelination, may be related to short internodes, widened Ranvier nodes and the specific effect of the mutation. The occurrence in some CMTX patients of a non uniform involvement between and within nerves, as in acquired demyelinating neuropathies, should be kept in mind to avoid misdiagnoses.

Macrophagic myofasciitis: an infantile Italian case

Macrophagic myofasciitis is a recently identified inflammatory myopathy mostly described in adult French patients complaining of arthro-myalgias and fatigue. It is probably due to intramuscular injection of aluminium-containing vaccines and is characterized by a typical muscular infiltrate of large macrophages with aluminium inclusions. We report a 1-year-old Italian child presenting irritability, delayed motor development, hyperCKemia (up to 10 times the normal value), and typical features of macrophagic myofasciitis on muscle biopsy. The child recovered fully after steroid therapy. Macrophagic myofasciitis is a new treatable cause of motor retardation and hyperCKemia in children, and is probably more common than reported. Diagnosis requires a high index of suspicion and can be missed if biopsy is performed outside the vaccination site.

Recurrent and fatal akinetic crisis in genetic‐mitochondrial parkinsonisms

Akinetic crisis (AC) is the most severe and possibly lethal complication of parkinsonism. It occurs with an incidence of 3‰ Parkinsons disease patients per year, but it is not known whether genetically determined parkinsonism is more or less susceptible to this complication.

Segmental conduction abnormalities and myelin thickenings in Val102/fs null mutation of MPZ gene

The authors report in patients with Val102/fs null mutation a possibly age dependent variability of clinical and electrophysiologic phenotype, segmental conduction abnormalities mainly in ulnar nerves at the elbow, and excessive myelin foldings and thickenings. The authors hypothesize that myelin thickenings at the paranodal region, in concurrence with compression at usual entrapment sites or minor repetitive trauma, may induce segmental conduction abnormalities.

Acute motor conduction block neuropathy or acute multifocal motor neuropathy: An attempt at a nosological systematization

In the February issue, Manganelli et al. reported a patient with an asymmetrical acute motor neuropathy, persistent conduction blocks (CBs), IgM antibodies to GD1a and GQ1b, and recovery in 24 weeks. Similar patients have been reported and variably classified as acute presentations of multifocal motor neuropathy (MMN) or variants of Guillain–Barré syndrome (GBS), thus inducing some terminological and nosological confusion. In 2003, we reported two patients who acutely developed symmetric weakness without sensory symptoms. Both patient had antecedent diarrhea, but Campylobacter jejuni was isolated from one patient. Both patients carried high titers of IgG antibodies to GM1 and GD1a. Electrophysiological studies showed reduction of distal compound muscle action potential (CMAP) amplitudes and partial motor CBs with normal sensory conductions, even across CB sites. Muscle weakness and CBs resolved in 2–5 weeks without development of excessive temporal dispersion of either distal or proximal CMAPs, suggesting a reversible immunomediated conduction failure at the nodes of Ranvier without demyelination. Four similar patients have been reported; all had antecedent diarrhea, and three had evidence of recent C. jejuni infection (Table 1). Three patients had anti-GM1 and one had anti-GM1b IgG antibodies. Three patients recovered rapidly, but one worsened and had progression to axonal degeneration. Because of the symmetrical presentation, monophasic course with fast recovery, antecedent C. jejuni infection, and presence of IgG antibody isotype, we thought it appropriate to classify these patients as a GBS subtype with the name of acute motor conduction block neuropathy (AMCBN). We believe that AMCBN is pathophysiologically related to acute motor axonal neuropathy (AMAN), as both are associated with C. jejuni enteritis and IgG antigangliosides. Moreover, AMCBN patients had the reversible conduction failure pattern described in some nerves of AMAN patients in most tested nerves. Therefore, we hypothesized that AMCBN represents an ‘‘arrested AMAN’’ in which anti-ganglioside antibodies bind to the nodal axolemma and induce a physiologic CB that does not progress to axonal degeneration and has the potential for rapid recovery. The patient reported by Manganelli et al. is more similar to four other patients with acute motor neuropathy, symmetrical or asymmetrical weakness, persistent CBs, and a chronic relapsing course in at least three of the patients (Table 1). All these patients had IgM antibodies to GM1. Antecedent enteritis and recent C. jejuni infection were demonstrated in only one case. Because of disease evolution, persistence of CBs, and IgM antibody isotype, we believe these cases are closer to MMN than to GBS and may represent an acute MMN (AMMN). Thus, a similar clinical presentation with pure motor neuropathy and CB without evidence of excessive temporal dispersion may evolve into two different entities: AMCBN and AMMN. In our opinion, the clinical course, persistence of CBs, and different Ig isotypes allow for this distinction and a proper classification. In AMCBN, AMAN, and AMMN with anti-ganglioside antibodies, the focus of immunopathology is thought to be at the nodal axolemma. The different pathological evolution and course may be due to the intrinsic properties of anti-ganglioside antibodies, such as affinity and capability to activate complement.

The association of chronic hepatitis B and myopathy

In two patients with chronic hepatitis B and myopathy, muscle biopsy showed necrosis and scarce inflammatory infiltrates. CD8+ cells surrounded some non-necrotic fibers. Hepatitis B virus (HBV) DNA and antigens were found inside intact muscle fibers. Major histocompatibility complex class I antigens were coexpressed with viral antigens. In one patient, symptoms improved during antiviral therapy. HBV can infect muscle fibers and an immune-mediated response to viral antigens may cause muscle injury.

Glial fibrillary acidic protein as a marker of axonal damage in chronic neuropathies

We evaluated serum glial fibrillary acidic protein (GFAP) levels by enzyme‐linked immunosorbent assay (ELISA) in controls (n = 30) and in patients with chronic sensory‐motor axonal neuropathy (CSMAN) (n = 30), chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 30), multifocal motor neuropathy (MMN) (n = 30), and primary muscular spinal atrophy (PMSA) (n = 15). GFAP levels, expressed as optical density, were increased in CSMAN (median = 1.05) compared to controls (median = 0.41; P < 0.05) and CIDP (median = 0.53, P < 0.05). They were also increased in PMSA (median = 0.99) compared to controls (P < 0.05) and MMN (median = 0.66; P < 0.05). To differentiate CSMAN from CIDP and PMSA from MMN, we applied a cutoff of GFAP levels at 0.66, and we obtained good sensitivity and specificity. In neuropathies, serum GFAP correlated with summated sensory nerve action potential amplitudes (r = −0.57; P = 0.0006) and disease severity (r = 0.37; P = 0.0011). Thus, we propose serum GFAP as a marker of axonal damage and severity in chronic neuropathies. Muscle Nerve 40: 50–54, 2009