Antonino Uncini

Pitfalls in electrodiagnosis of Guillain–Barré syndrome subtypes

Objective To electrophysiologically classify an Italian Guillain–Barré syndrome (GBS) population into demyelinating and axonal subtypes, to investigate how serial recordings changed the classification and to underline the pitfalls in electrodiagnosis of GBS subtypes. Methods The authors applied two current electrodiagnostic criteria sets for demyelinating and axonal GBS subtypes in 55 patients who had at least two serial recordings in three motor and sensory nerves. Results At first test, the electrodiagnosis was almost identical with both criteria: 65–67% of patients were classifiable as acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 18% were classifiable as axonal GBS, and 14–16% were equivocal. At follow-up, 24% of patients changed classification: AIDP decreased to 58%, axonal GBS increased to 38%, and equivocal patients decreased to 4%. The majority of shifts were from AIDP and equivocal groups to axonal GBS, and the main reason was the recognition by serial recordings of the reversible conduction failure and of the length-dependent compound muscle action potential amplitude reduction patterns as expression of axonal pathology. Conclusions Axonal GBS is pathophysiologically characterised not only by axonal degeneration but also by reversible conduction failure at the axolemma of the Ranvier node. The lack of distinction among demyelinating conduction block, reversible conduction failure and length-dependent compound muscle action potential amplitude reduction may fallaciously classify patients with axonal GBS as having AIDP. Serial electrophysiological studies are mandatory for proper diagnosis of GBS subtypes and the identification of pathophysiological mechanisms of muscle weakness. More reliable electrodiagnostic criteria taking into consideration the reversible conduction failure pattern should be devised.

Outcome and its predictors in Guillain-Barre syndrome.

Despite the use of plasma exchanges and intravenous immunoglobulins, Guillain-Barré syndrome (GBS) still carries non-negligible morbidity and mortality. Furthermore, the psychosocial consequences of GBS may persist longer than expected. Various aetiological, clinical, electrophysiological and immunological factors may carry prognostic predictive value. The objective of this article was to perform a summary of the current knowledge-base on outcome and its determinants in adequately-treated adult-onset GBS. Relevant prospective literature was reviewed through a Medline search of English-language articles published between 1966 and March 2012. GBS causes severe persistent disability in 14% of patients at 1 year. Loss of full strength, persistent pain and need for professional change occurs in about 40%. Mortality is of about 4% within the first year. Analysis of prognostic predictors consistently demonstrates the negative impact of higher age, preceding diarrhoea, greater disability/weaker muscles at admission, short interval between symptom-onset and admission, mechanical ventilation and absent/low amplitude compound muscle action potentials. Further outcome studies will soon be underway and may in future contribute to adequately integrate all potential factors in more reliable predictive models.

Nodopathies of the peripheral nerve: an emerging concept

Peripheral nerve diseases are traditionally classified as demyelinating or axonal. It has been recently proposed that microstructural changes restricted to the nodal/paranodal region may be the key to understanding the pathophysiology of antiganglioside antibody mediated neuropathies. We reviewed neuropathies with different aetiologies (dysimmune, inflammatory, ischaemic, nutritional, toxic) in which evidence from nerve conductions, excitability studies, pathology and animal models, indicate the involvement of the nodal region in the pathogenesis. For these neuropathies, the classification in demyelinating and axonal is inadequate or even misleading, we therefore propose a new category of nodopathy that has the following features: (1) it is characterised by a pathophysiological continuum from transitory nerve conduction block to axonal degeneration; (2) the conduction block may be due to paranodal myelin detachment, node lengthening, dysfunction or disruption of Na+ channels, altered homeostasis of water and ions, or abnormal polarisation of the axolemma; (3) the conduction block may be promptly reversible without development of excessive temporal dispersion; (4) axonal degeneration, depending on the specific disorder and its severity, eventually follows the conduction block. The term nodopathy focuses to the site of primary nerve injury, avoids confusion with segmental demyelinating neuropathies and circumvents the apparent paradox that something axonal may be reversible and have a good prognosis.

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

Polymorphism of CD1 and SH2D2A genes in inflammatory neuropathies

In the quest for susceptibility factors of inflammatory neuropathies, many genes implicated in the pathogenesis of autoimmune diseases have been investigated with negative or conflicting results. We studied, with a gene candidate approach, the CD1 system specialized in capturing and presenting glycolipids to antigen‐specific T cells, and the SH2D2A gene encoding for a T‐cell‐specific adapter protein implicated in control of early T‐cell activation. In Guillain–Barré syndrome, an initially positive association study with polymorphism of CD1A and CD1E genes was not confirmed. In chronic inflammatory demyelinating polyneuropathy, we did not find an association with CD1 genes, but we found an association with a homozygous genotype for a low repeat number of tandem GA in the SH2D2A gene. This genotype could result in defective control and elimination of autoreactive T cells. All the studies were performed on relatively small size populations. Confirmation in larger sized studies is required both for CD1 and SH2D2A genes. Considering the relative rarity of patients with inflammatory neuropathies, this can only be accomplished by international collaboration.

Optimizing the electrodiagnostic accuracy in Guillain-Barré syndrome subtypes: Criteria sets and sparse linear discriminant analysis

OBJECTIVE To optimize the electrodiagnosis of Guillain-Barré syndrome (GBS) subtypes at first study. METHODS The reference electrodiagnosis was obtained in 53 demyelinating and 45 axonal GBS patients on the basis of two serial studies and results of anti-ganglioside antibodies assay. We retrospectively employed sparse linear discriminant analysis (LDA), two existing electrodiagnostic criteria sets (Hadden et al., 1998; Rajabally et al., 2015) and one we propose that additionally evaluates duration of motor responses, sural sparing pattern and defines reversible conduction failure (RCF) in motor and sensory nerves at second study. RESULTS At first study the misclassification error rates, compared to reference diagnoses, were: 15.3% for sparse LDA, 30% for our criteria, 45% for Rajaballys and 48% for Haddens. Sparse LDA identified seven most powerful electrophysiological variables differentiating demyelinating and axonal subtypes and assigned to each patient the diagnostic probability of belonging to either subtype. At second study 46.6% of axonal GBS patients showed RCF in two motor and 8.8% in two sensory nerves. CONCLUSIONS Based on a single study, sparse LDA showed the highest diagnostic accuracy. RCF is present in a considerable percentage of axonal patients. SIGNIFICANCE Sparse LDA, a supervised statistical method of classification, should be introduced in the electrodiagnostic practice.

Non-Alcoholic Partially Reversible Marchiafava-Bignami Disease: Review and Relation with Reversible Splenial Lesions A Case Report and Literature Review

Marchiafava-Bignami disease (MBD) is a rare pathological condition characterized by progressive demyelination and necrosis of the corpus callosum (CC). MBD occurs in patients with chronic alcoholism although a few non-alcoholic cases have been reported. We describe a non-alcoholic, depressed patient, who developed MBD after psycho-active drug abuse. Magnetic resonance imaging (MRI) disclosed bilateral, symmetric, hyperintense regions in the genu, body and splenium of the CC associated with increased water diffusivity. Clinical and MRI findings showed a partial recovery after tapering/modification of psycho-active drugs. We reviewed the nine cases of non-alcoholic MBD reported in the literature. We conclude that most cases should have been diagnosed as a reversible isolated splenial lesion (MERS), a recently described condition semiotically similar to MBD but with a specific localization, restricted water diffusivity and reversibility at MRI. In conclusion, MBD is an extremely rare condition in non-alcoholic patients and the use of MRI for distinguishing between MBD and MERS is crucial.

Persistent multifocal conduction block in vasculitic neuropathy with IgM anti-gangliosides.

A 30‐year‐old man with essential cryoglobulinemia presented with an axonal neuropathy and was found to have vasculitis at nerve biopsy. After 44 months, in accord with clinical deterioration, motor conduction studies showed excessive temporal dispersion multifocally, with partial conduction block persisting for 3 years. Antibody testing showed the presence of IgM anti‐GM1, anti‐GD1a, and anti‐GM2 antibodies. Transitory conduction block has been reported occasionally in patients with vasculitis. The persistent multifocal conduction abnormalities found in this patient were more likely due to a superimposed immunomediated demyelination rather than to chronic nerve ischemia secondary to vasculitis. Muscle Nerve, 2007