Antonino Uncini

Publications of Antonino Uncini

• Outcome and its predictors in Guillain-Barre syndrome.

  Authors: Yusuf A Rajabally, Antonino Uncini

  Journal of neurology, neurosurgery, and psychiatry. 05/2012;

  Despite the use of plasma exchanges and intravenous immunoglobulins, Guillain-Barré syndrome (GBS) still carries non-negligible morbidity and mortality. Furthermore, the psychosocial consequences ofDespite 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.

• Electrodiagnostic criteria for Guillain-Barrè syndrome: A critical revision and the need for an update.

  Authors: Antonino Uncini, Satoshi Kuwabara

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 04/2012;

  Electrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification of the subtypes and in establishing prognosis. In the last three decades, differentElectrophysiology plays a determinant role in Guillain-Barré syndrome (GBS) diagnosis, classification of the subtypes and in establishing prognosis. In the last three decades, different electrodiagnostic criteria sets have been proposed for acute inflammatory demyelinating neuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN). Criteria sets for AIDP varied for the parameters indicative of demyelination considered, for the cut-off limits and the number of required abnormalities (all a priori established) showing different sensitivities. Criteria sets for AMAN and AMSAN were proposed on the initial assumption that these subtypes were pathologically characterised by simple axonal degeneration. However, some AMAN patients show transient conduction block/slowing in intermediate and distal nerve segments, mimicking demyelination but without the development of abnormal temporal dispersion, named reversible conduction failure (RCF). The lack of distinction between RCF and demyelinating conduction block leads to fallaciously classify AMAN patients with RCF as AIDP or AMAN with axonal degeneration. Serial electrophysiological studies are mandatory for proper diagnosis of GBS subtypes, identification of pathophysiological mechanisms and prognosis. More reliable electrodiagnostic criteria should be devised to distinguish axonal and demyelinating subtypes of GBS, taking into consideration the RCF pattern and focussing on temporal dispersion.

• Sensory Guillain-Barré syndrome and related disorders: An attempt at systematization.

  Authors: Antonino Uncini, Nobuhiro Yuki

  Muscle & nerve. 04/2012; 45(4):464-70.

  The possibility that some patients diagnosed with an acute sensory neuropathy could actually have Guillain-Barré syndrome (GBS) has been repeatedly advanced in the literature, but the number of casesThe possibility that some patients diagnosed with an acute sensory neuropathy could actually have Guillain-Barré syndrome (GBS) has been repeatedly advanced in the literature, but the number of cases reported is small. The reports have shown different clinical presentations and electrophysiological findings and are variously named, thus generating terminological and nosological confusion. We operatively defined sensory GBS as an acute, monophasic, widespread neuropathy characterized clinically by exclusive sensory symptoms and signs that reach their nadir in a maximum of 6 weeks without related systemic disorders and other diseases or conditions. We reviewed the literature through searches of PubMed from 1980 to March 2011 and our own files. On the basis of the size of fibers involved and the possible site of primary damage, we propose tentatively classifying sensory GBS and related disorders into three subtypes: acute sensory demyelinating polyneuropathy; acute sensory large-fiber axonopathy-ganglionopathy; and acute sensory small-fiber neuropathy-ganglionopathy. Muscle Nerve, 2012.

• Antiganglioside antibodies are associated with axonal Guillain-Barré syndrome: a Japanese-Italian collaborative study.

  Authors: Yukari Sekiguchi, Antonino Uncini, Nobuhiro Yuki, Sonoko Misawa, Francesca Notturno, Saiko Nasu, Kazuaki Kanai, Yu-ichi Noto, Yumi Fujimaki, Kazumoto Shibuya, Shigeki Ohmori, Yasunori Sato, Satoshi Kuwabara

  Journal of neurology, neurosurgery, and psychiatry. 01/2012; 83(1):23-8.

  Whether or not antiganglioside antibodies are related to axonal or demyelinating Guillain-Barré syndrome (GBS) is still a matter of controversy, as detailed in previous studies conducted in WesternWhether or not antiganglioside antibodies are related to axonal or demyelinating Guillain-Barré syndrome (GBS) is still a matter of controversy, as detailed in previous studies conducted in Western and Asian countries. To clarify whether antiganglioside antibodies are associated with axonal dysfunction in Japanese and Italian GBS patient cohorts. Clinical and electrophysiological profiles were reviewed for 156 GBS patients collected from Japan (n=103) and Italy (n=53). Serum IgG antibodies against GM1, GM1b, GD1a and GalNAc-GD1a were measured by ELISA in the same laboratory. Electrodiagnostic criteria and results of serial electrophysiological studies were used for classification of GBS subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In both Japanese and Italian cohorts, any of the antibodies were positive in 36% of the patients, and antibody positivity had a significant association with the AMAN electrodiagnosis. Approximately 30% of Japanese and Italian antiganglioside positive patients showed the AIDP pattern at the first examination whereas sequential studies showed that most finally showed the AMAN pattern. Clinically, seropositive patients more frequently had preceding diarrhoea and pure motor neuropathy in both Japanese and Italian cohorts; vibratory sensation was normal in 97% of Japanese and in 94% of Italian seropositive patients. In GBS, clinical and electrophysiological features appear to be determined by antiganglioside antibodies, and the antibodies are associated with motor axonal GBS in both Japan and Italy. Classification of the GBS subtypes as a disease entity should be made, combining the results of antiganglioside assays and serial electrodiagnostic studies.

• Guillain-Barré syndrome associated with normal or exaggerated tendon reflexes.

  Authors: Nobuhiro Yuki, Norito Kokubun, Satoshi Kuwabara, Yukari Sekiguchi, Masafumi Ito, Masaaki Odaka, Koichi Hirata, Francesca Notturno, Antonino Uncini

  Journal of neurology. 12/2011;

  Areflexia is part one of the clinical criteria required to make a diagnosis of Guillain-Barré syndrome (GBS). The diagnostic criteria were stringently developed to exclude non-GBS cases but thereAreflexia is part one of the clinical criteria required to make a diagnosis of Guillain-Barré syndrome (GBS). The diagnostic criteria were stringently developed to exclude non-GBS cases but there have been reports of patients with GBS following Campylobacter jejuni enteritis with normal and exaggerated deep tendon reflexes (DTRs). The aim of this study is to expand the existing diagnostic criteria to preserved DTRs. From the cohort of patients referred for anti-ganglioside antibody testing from hospitals throughout Japan, 48 GBS patients presented with preserved DTR at admission. Thirty-two patients had normal or exaggerated DTR throughout the course of illness whereas in 16 patients the DTR became absent or diminished during the course of the illness. IgG antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a were frequently present in either group (84 vs. 94%), suggesting a close relationship between the two groups. We then investigated the clinical and laboratory findings of 213 GBS patients from three hospital cohorts. In 23 patients, eight presented with normal tendon reflexes throughout the clinical course of the illness. Twelve showed hyperreflexia, with at least one of the jerks experienced even at nadir, and exaggerated reflexes returning to normal at recovery. The other three had hyperreflexia throughout the disease course. Compared to 190 GBS patients with reduced or absent DTR, the 23 DTR-preserved patients more frequently presented with pure motor limb weakness (87 vs. 47%, p = 0.00026), could walk 5 m independently at the nadir (70 vs. 33%, p = 0.0012), more frequently had antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a (74 vs. 47%, p = 0.014) and were more commonly diagnosed with acute motor axonal neuropathy (65 vs. 34%, p = 0.0075) than with acute inflammatory demyelinating polyneuropathy (13 vs. 43%, p = 0.0011). This study demonstrated that DTRs could be normal or hyperexcitable during the entire clinical course in approximately 10% of GBS patients. This possibility should be added in the diagnostic criteria for GBS to avoid delays in diagnosis and effective treatment to these patients.

• Chronic inflammatory lumbosacral polyradiculopathy: a regional variant of CIDP.

  Authors: Christina M Caporale, Claudio Staedler, Claudio Gobbi, Claudio L Bassetti, Antonino Uncini

  Muscle & nerve. 11/2011; 44(5):833-7.

  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) affects various components and segments of the peripheral nervous system differently, and thus there can be phenotypic heterogeneity.Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) affects various components and segments of the peripheral nervous system differently, and thus there can be phenotypic heterogeneity. We report a 47-year-old woman with chronic sensory disturbances and proximal weakness limited to the legs. Motor and sensory nerve conduction studies were normal. Somatosensory evoked potentials and imaging indicated a demyelinating process involving the lumbosacral roots. The patient responded favorably to IVIg. Although she did not fulfill the diagnostic criteria for CIDP we believe this patient represents a restricted regional CIDP variant.

• Polymorphism of CD1 and SH2D2A genes in inflammatory neuropathies.

  Authors: Antonino Uncini, Francesca Notturno, Marta Pace, Christina M Caporale

  Journal of the peripheral nervous system : JPNS. 06/2011; 16 Suppl 1:48-51.

  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. WeIn 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.

• Cortical origin of myoclonus in early stages of corticobasal degeneration.

  Authors: Francesca Notturno, Filippo Zappasodi, Valerio Maruotti, Laura Marzetti, Massimo Caulo, Antonino Uncini

  Movement disorders : official journal of the Movement Disorder Society. 04/2011; 26(8):1567-9.

• Involvement of sensory fibres in axonal subtypes of Guillain-Barre syndrome.

  Authors: Margherita Capasso, Francesca Notturno, Claudia Manzoli, Antonino Uncini

  Journal of neurology, neurosurgery, and psychiatry. 03/2011; 82(6):664-70.

  Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are due to an antiganglioside antibody mediated attack, thought to be restricted to motor fibres in AMAN.Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) are due to an antiganglioside antibody mediated attack, thought to be restricted to motor fibres in AMAN. Sensory symptoms and minor sensory conduction abnormalities, however, have been reported in some AMAN patients. To verify whether sensory fibres are truly spared in AMAN and whether AMAN and AMSAN represent a continuum. Serial conduction studies in 13 AMAN and three AMSAN patients were reviewed. To evaluate the variation in sensory nerve action potential (SNAP) amplitude in serial recordings, the least significant change in a test-retest study of 20 controls was calculated. Least significant change for median, ulnar and sural nerves were 44%, 47% and 58%, respectively. In 34% of initially normal sensory nerves of six AMAN patients, SNAP amplitude significantly increased by 57-518%. In three nerves of three AMAN patients, SNAP significantly decreased by 50-69%. Overall, serial recordings allowed detection of sensory fibre involvement in 49% of nerves and in 69% of AMAN patients. In one AMSAN patient, SNAP increased in two nerves by 150-300%; in another patient, SNAPs, unrecordable at baseline in six nerves, reappeared during follow-up and normalised in three nerves. In five nerves of three AMAN and in eight nerves of two AMSAN patients, SNAP amplitudes increased rapidly, suggesting reversible conduction failure of sensory fibres. In other nerves, SNAP increased over months, as for axonal regeneration. Sensory fibres are often involved subclinically in AMAN. Reversible conduction failure may develop in sensory as well as motor fibres in both AMAN and AMSAN. AMAN and AMSAN represent a continuum in axonal GBS.

• Motor and sensory conduction failure in overlap of Guillain-Barré and Miller Fisher syndrome: two simultaneous cases.

  Authors: Yusuf A Rajabally, Ghaniah Hassan-Smith, Francesca Notturno, Penelope J Eames, Thomas Hayton, Margherita Capasso, Antonino Uncini

  Journal of the neurological sciences. 02/2011; 303(1-2):35-8.

  We report 2 patients diagnosed simultaneously with an overlap of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), who had anti-GT1a, anti-GQ1b, anti-GD1a and anti-GD1b antibodies.We report 2 patients diagnosed simultaneously with an overlap of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), who had anti-GT1a, anti-GQ1b, anti-GD1a and anti-GD1b antibodies. There was no identifiable specific preceding infection. Both patients presented with upper and lower limb paresthesias and severe weakness, bulbar and facial weakness, ophthalmoparesis and areflexia. In one, electrophysiology demonstrated multifocal conduction blocks (CBs) and mild motor conduction velocity slowing in intermediate segments and absent sensory nerve action potentials (SNAPs). The patient improved rapidly and fully recovered within 18 days from onset. CBs resolved, distal compound muscle action potential (CMAP) amplitudes increased and SNAPs normalized on subsequent testing. In the other patient, initial studies showed low/normal CMAPs, with absent SNAPs, without demyelinating features. This patient fully recovered within 21 days from onset. CMAPs markedly increased, SNAPs improved marginally. These 2 patients exhibited features indicative of the pathophysiological mechanism of conduction failure in motor and sensory fibers. This phenomenon relates to rapidly resolving CBs possibly induced by the transitory and limited attack of antiganglioside antibodies at the axolemma of the nodes of Ranvier not progressing to axonal degeneration. These cases widen the range of GBS subtypes in which reversible conduction failure has been described, to include overlap syndromes with MFS. The factors determining the electrophysiology, as well as the rate, degree and quality of recovery in GBS subtypes remain uncertain at the present time.

• Reversible conduction failure in pharyngeal-cervical-brachial variant of Guillain-Barré syndrome.

  Authors: Margherita Capasso, Francesca Notturno, Claudia Manzoli, Nobuhiro Yuki, Antonino Uncini

  Muscle & nerve. 10/2010; 42(4):608-12.

  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 blocksIn 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.

• Conduction block in acute motor axonal neuropathy.

  Authors: Norito Kokubun, Momoka Nishibayashi, Antonino Uncini, Masaaki Odaka, Koichi Hirata, Nobuhiro Yuki

  Brain : a journal of neurology. 10/2010; 133(10):2897-908.

  Guillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features ofGuillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features of acute motor axonal neuropathy are reduced amplitude or absence of distal compound muscle action potentials indicating axonal degeneration. In contrast, autopsy study results show early nodal changes in acute motor axonal neuropathy that may produce motor nerve conduction block. Because the presence of conduction block in acute motor axonal neuropathy has yet to be fully recognized, we reviewed how often conduction block occurred and how frequently it either reversed or was followed by axonal degeneration. Based on Ho's criteria, acute motor axonal neuropathy was electrodiagnosed in 18 patients, and repeated motor nerve conduction studies were carried out on their median and ulnar nerves. Forearm segments of these nerves and the across-elbow segments of the ulnar nerve were examined to evaluate conduction block based on the consensus criteria of the American Association of Electrodiagnostic Medicine. Twelve (67%) of the 18 patients with acute motor axonal neuropathy had definite (n=7) or probable (n=5) conduction blocks. Definite conduction block was detected for one patient (6%) in the forearm segments of both nerves and probable conduction block was detected for five patients (28%). Definite conduction block was present across the elbow segment of the ulnar nerve in seven patients (39%) and probable conduction block in two patients (11%). Conduction block was reversible in seven of 12 patients and was followed by axonal degeneration in six. All conduction blocks had disappeared or begun to resolve within three weeks with no electrophysiological evidence of remyelination. One patient showed both reversible conduction block and conduction block followed by axonal degeneration. Clinical features and anti-ganglioside antibody profiles were similar in the patients with (n=12) and without (n=6) conduction block as well as in those with (n=7) and without (n=5) reversible conduction block, indicating that both conditions form a continuum; a pathophysiological spectrum ranging from reversible conduction failure to axonal degeneration, possibly mediated by antibody attack on gangliosides at the axolemma of the nodes of Ranvier, indicating that reversible conduction block and conduction block followed by axonal degeneration and axonal degeneration without conduction block constitute continuous electrophysiological conditions in acute motor axonal neuropathy.

• Pitfalls in electrodiagnosis of Guillain-Barré syndrome subtypes.

  Authors: Antonino Uncini, Claudia Manzoli, Francesca Notturno, Margherita Capasso

  Journal of neurology, neurosurgery, and psychiatry. 10/2010; 81(10):1157-63.

  To electrophysiologically classify an Italian Guillain-Barré syndrome (GBS) population into demyelinating and axonal subtypes, to investigate how serial recordings changed the classification and toTo 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. 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. 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. 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.

• Monospecific high-affinity and complement activating anti-GM1 antibodies are determinants in experimental axonal neuropathy.

  Authors: Francesca Notturno, Piero Del Boccio, Mirella Luciani, Christina Michaela Caporale, Damiana Pieragostino, Vincenza Prencipe, Paolo Sacchetta, Antonino Uncini

  Journal of the neurological sciences. 04/2010; 293(1-2):76-81.

  It has been difficult to replicate consistently the experimental model of axonal Guillain-Barré syndrome (GBS). We immunized rabbits with two lipo-oligosaccharides (LOS1 and LOS2) derived from theIt has been difficult to replicate consistently the experimental model of axonal Guillain-Barré syndrome (GBS). We immunized rabbits with two lipo-oligosaccharides (LOS1 and LOS2) derived from the same C. jejuni strain and purified in a slightly different way. LOS1 did not contain proteins whereas several proteins were present in LOS2. In spite of a robust anti-GM1 antibody response in all animals the neuropathy developed only in rabbits immunized with LOS1. To explain this discrepancy we investigated fine specificity, affinity and ability to activate the complement of anti-GM1 antibodies. Only rabbits immunized with LOS1 showed monospecific high-affinity antibodies which activated more effectively the complement. Although it is not well understood how monospecific high-affinity antibodies are induced these are crucial for the induction of experimental axonal neuropathy. Only a strict adherence to the protocols demonstrated to be successful may guarantee the reproducibility and increase the confidence in the animal model as a reliable tool for the study of the human axonal GBS.

• Acute motor conduction block neuropathy or acute multifocal motor neuropathy: an attempt at a nosological systematization.

  Authors: Antonino Uncini, Claudia Manzoli, Margherita Capasso

  Muscle & nerve. 02/2010; 41(2):283-5; author reply 285.

• Capsular warning syndrome mimicking a jacksonian sensory march.

  Authors: Christina M Caporale, Francesca Notturno, Massimo Caulo, Antonino Uncini

  Journal of the neurological sciences. 09/2009;

  A 57-year-old man, operated eight years before for a left frontal falx meningioma, presented with short lasting, stereotyped episodes of paresthesias ascending from the right foot to the hand. AA 57-year-old man, operated eight years before for a left frontal falx meningioma, presented with short lasting, stereotyped episodes of paresthesias ascending from the right foot to the hand. A diagnosis of somatosensory seizures with jacksonian march was made. The patient was given antiepilectics but 5days later, a few hours after another paresthesic episodes, he developed right hemiplegia, hemianesthesia and dysartria due to an infarct of left capsular posterior limb. We deem that in this patient the paresthesic episodes were more likely an expression of a capsular warning syndrome than of parietal epilepsy because of the frontal localization of the surgical lesion, the absence of motor components in all episodes, the negativity of repeated EEG, and the lack of recurrences after stroke. In capsular warning syndrome sensory symptoms mimicking a jacksonian march can be due to ischemic depolarization progressively recruiting the somatotopically arranged sensory fibers in the posterior capsular limb.

• Electrophysiologic and immunopathologic correlates in Guillain-Barré syndrome subtypes.

  Authors: Antonino Uncini, Nobuhiro Yuki

  Expert review of neurotherapeutics. 07/2009; 9(6):869-84.

  Guillain-Barré syndrome (GBS) includes demyelinating and axonal subtypes with different immunopathologic mechanisms. In acute inflammatory demyelinating polyradiculoneuropathy, segmentalGuillain-Barré syndrome (GBS) includes demyelinating and axonal subtypes with different immunopathologic mechanisms. In acute inflammatory demyelinating polyradiculoneuropathy, segmental demyelination and conduction block are the pathological and electrophysiological correlates of muscle weakness. Slowed conductions and increased temporal dispersion of motor responses are more characteristic of the remyelinative phase and do not affect muscle power. In acute motor axonal neuropathy, muscle weakness has been correlated with an antibody-mediated primary axonal degeneration. Conduction block that recovers without development of increased temporal dispersion or other demyelinating features, however, has been described in some patients with antiganglioside antibodies and related to a physiologic conduction block at the axolemma of the Ranvier node. Severity of axonal damage induced by antiganglioside antibodies may vary from reversible functional impairment of nodal axolemma to complete axonal damage with subsequent Wallerian degeneration. In early GBS, current electrophysiologic criteria are unable to distinguish with certainty different subtypes. Serial electrophysiologic studies are mandatory for identification of GBS subtypes and to elucidate the pathophysiologic mechanisms of muscle weakness among demyelination, axonal degeneration and physiologic conduction block.

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

  Authors: Francesca Notturno, Margherita Capasso, Angelo Delauretis, Marinella Carpo, Antonino Uncini

  Muscle & nerve. 07/2009; 40(1):50-4.

  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)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.

• Glial fibrillary acidic protein in Guillain-Barré syndrome: Methodological issues.

  Authors: A Petzold, L Rosengren, M M Verbeek, Francesca Notturno, Christina M Caporale, Angelo Delauretis, Antonino Uncini

  Muscle & nerve. 06/2009; 39(5):711-2.

• Management of extreme carpal tunnel syndrome: Evidence from a long-term follow-up study.

  Authors: Margherita Capasso, Claudia Manzoli, Antonino Uncini

  Muscle & nerve. 05/2009;

  Extreme carpal tunnel syndrome (CTS) is characterized by severe thenar atrophy, plegia of the abductor pollicis brevis (APB), fixed sensory deficit in the median nerve distribution, and absence ofExtreme carpal tunnel syndrome (CTS) is characterized by severe thenar atrophy, plegia of the abductor pollicis brevis (APB), fixed sensory deficit in the median nerve distribution, and absence of median motor and sensory responses on electrophysiological examination. In this study we report long-term follow-up of 37 patients with extreme CTS. Of the 24 patients with idiopathic extreme CTS, 9 were untreated, and 3 received conservative treatment. At follow-up, none of these patients showed objective or electrophysiological improvement, and all but 1 still reported positive symptoms. Conversely, 12 patients (14 hands) who underwent carpal tunnel release showed: resolution of positive symptoms in all but 1 hand; reappearance of median compound muscle action potentials (4.2 +/- 0.6 mV); reappearance of sensory nerve action potentials in all but 1 (7.9 +/- 0.8 muV); improvement of APB strength to grade 4 or 5 on the Medical Research Council scale in 11 hands; and resolution of hypesthesia in 1 hand. Six of 13 patients with non-idiopathic extreme CTS were operated. Of the 6, we found no or poor reinnervation in 3 patients, restoration of nerve responses and normal APB strength but no relief from pain and/or paresthesia in 2, and full recovery in 1. If untreated, extreme CTS is an irreversible condition. Although the outcome is considered to be disappointing in such cases, carpal tunnel release provides long-term relief, significant sensorimotor reinnervation, and improvement of motor deficit in most patients. It should be considered to be the first-choice treatment for idiopathic extreme CTS. Associated diseases do not necessarily imply a poor surgical outcome. Muscle Nerve, 2009.