Fabio Poglio

Electrophysiological findings of peripheral neuropathy in newly diagnosed type II diabetes mellitus.

Abstract  This study was aimed at assessing the electrophysiological signs of peripheral neuropathy in diabetes mellitus (DM) type II patients at diagnosis. Nerve conduction studies (NCS) of median, ulnar, peroneal, tibial and sural nerves were performed in 39 newly diagnosed DM subjects and compared to those of 40 healthy controls. Metabolic indices were also investigated. Electrophysiological alterations were found in 32 (82%) of the DM patients, and more than half of them (62.2%) showed multiple (two to five) abnormal parameters. Because most of the subjects (84.4%) had from two to five nerves involved, these alterations were widespread in the seven nerves evaluated. Forty‐two percent of the patients had NCS alterations suggestive of distal median mononeuropathy, implying that metabolic factors in DM make the median nerve more susceptible to focal entrapment. A reduced sensory nerve action potential (SNAP) amplitude was observed in the median nerve in 70% of the patients, in the ulnar in 69% and in the sural nerve only in 22%. In the presence of a decrease in the SNAP amplitude of the ulnar or median nerve, the SNAP amplitude of the sural nerve was normal in 82 or 80% of the subjects, respectively. This finding may be in keeping with a distal involvement of the sensory fibres, as explored by routine median or ulnar NCS. No correlation was found between metabolic indices and NCS parameters. In conclusion, a high percentage of newly diagnosed DM patients show signs of neuropathy, and upper limb nerve sensory NCS seem to be more sensitive in detecting it than lower limb NCS.

Multifocal motor neuropathy during treatment with infliximab

Dear Editor, Infliximab (Remicade ) is a chimeric human/murine immunoglobulin G1 (IgG1) anti-tumour necrosis factor-a (TNF) antibody. Although TNF antagonists are among the most potent and rapidly effective treatments for rheumatoid arthritis (RA) (Olsen and Stein, 2004), a number of adverse effects, including induction or worsening of demyelinating central nervous system diseases, have been reported (Mohan et al., 2001; Sicotte and Voskuhl, 2001). Three cases of motor neuropathy with conduction blocks (Singer et al., 2004; Rodriguez-Escalera et al., 2005) have been reported in patients on infliximab; two of these patients had Crohn’s disease and seronegative arthritis, while one had polyarthritis and Hepatitis C with mixed cryoglobulinaemia. Herein, we report yet another patient with onset of multifocal motor neuropathy (MMN) and conduction blocks during infliximab treatment. A 40-year-old woman with a 10-year history of RA was started on infliximab treatment in January 2003 (3 mg/kg intravenous every 8 weeks) with a satisfactory response in the months that followed. However, she developed asymmetric progressive weakness of right forearm flexion and of intrinsic muscles of right hand in October 2003. Neurological evaluation (January 2004) disclosed the presence of severe weakness of the right biceps brachii (0/5 according to Medical Research Scale Score), the right extensor carpi radialis, extensor digitorum communis, extensor indicis, abductor pollicis brevis, abductor digiti minimi, and interossei (3/5) and moderate weakness of the left deltoid, extensor digitorum communis, extensor index, interossei, left tibialis anterior, and gastrocnemius (4/5). Tendon reflexes were normal apart from the absence of response in the right biceps. There was no detectable sensory loss. The neurological examination was otherwise unremarkable. Nerve conduction studies showed the presence of definite conduction block in both median and ulnar nerves, right radial, left peroneus, and tibial nerves. A significant decrease in motor conduction velocity was evident in both the median nerves. Sensory conduction studies of the bilateral median, radial, ulnar and sural nerves were unremarkable. Brain and spinal cord magnetic resonance imaging and cerebrospinal fluid examination were normal. DNA analysis was negative for the presence of the 1.5-Mb deletion in chromosome 17p11.2 associated with hereditary neuropathy with liability to pressure palsy. Routine screening tests for thyroid pathologies, hepatitis, cryoglobulinaemia and vasculitis were negative. IgM anti-GM1 antibodies were positive at high titre (1 : 640) (Antigen Coated Membrane Strips Euroimmun). The patient satisfied the diagnostic criteria for MMN established by Olney (Olney et al., 2003). Infliximab treatment was stopped in March 2004, and the patient was treated with intravenous immunoglobulins (1 g/kg/day for 2 days monthly), and muscle strength progressively improved. At the last follow up, in February 2005, there was a marked increase in the muscle strength, with only residual moderate weakness (4/5) affecting only the biceps, extensors carpi radialis and interossei muscles. Nerve conduction studies demonstrated a reduction in the number of blocks. The timing of the onset of neuropathy reported in literature varies greatly, i.e., after 2 years of infliximab therapy in one case, 3 months in another (Singer et al., 2004), 14 weeks in a case reported by RodriguezEscalera et al. (2005) and after 9 months in our case. The therapeutic schedule also varied in all cases. A spontaneous remission of the neuropathy was observed in the two cases reported by Singer, after suspension of the treatment. Whilst in our case and that of RodriguezEscalera, a therapy with immunoglobulins was administered in both cases with a positive outcome. Lastly, in both our cases and the case reported by RodriguezEscalera, there was a positivity to antiganglioside antibodies. MMN was not a neurologic complication of RA (Nobile-Orazio et al., 2005), and the onset of MMN Address correspondence to: Dr. Dario Cocito, MD, U.O. Neurofisiologia Clinica, Dipartimento di Neuroscienze, Università di Torino, Via Cherasco 15, 10126 Torino, Italy, Tel: þ39-0116-335243; Fax: þ39-0116-963487; E-mail: dariococito@yahoo.it Journal of the Peripheral Nervous System 10:386–387 (2005)

Pain affects the quality of life of neuropathic patients

The aim of this study was to verify the extent to which the presence of pain affects the quality of life (QoL) of neuropathic patients. The patients were selected in our Department of Peripheral Nervous System Diseases. We enrolled 120 consecutive patients with chronic polyneuropathy who had not received continuous pain therapy during the two months preceding study entry, and administered them the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is affected not only by the presence of neuropathy, but also by the presence and intensity of pain: the physical aspect of the QoL correlated only weakly with the TNS, but pain was closely related to a worsening in this parameter; moreover, the mental domains of the SF-36 were only correlated with pain. Pain per se worsens the QoL of neuropathic patients, regardless of disease severity.

A further critical evaluation of requests for electrodiagnostic examinations.

The aim of this study was to evaluate the impact of electrophysiological (EDX) tests in the clinical management and diagnosis of patients, and the appropriateness of the referral diagnosis. A study was carried out in three electrodiagnostic services in the Torino area, over a 12-month period. In our study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients underwent EDX examinations including nerve conduction study, electromyography and repetitive stimulation test. Most patients had been sent for EDX tests by specialists. Specialists suspected mainly polyneuropathy, whilst general practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the requests were correctly formulated, 55% by general practitioners and 77% by specialists. There was a concordance between the results of the EDX tests and diagnostic hypothesis 40% of the time. This study confirms the usefulness and diagnostic impact of EDX examinations and evidences the amount of time and resources wasted as a result of incorrect or incomplete requests.

Differential diagnosis of chronic dysimmune demyelinating polyneuropathies with and without anti-MAG antibodies.

The distinction between chronic demyelinating polyneuropathies associated with IgM paraproteinemia and anti–myelin‐associated glycoprotein (MAG) antibodies (MAG‐PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) relies on the anti‐MAG antibodies assay. The aim of the study was to identify clinical and electrophysiological features suggesting a diagnosis of MAG‐PN. Fourteen patients with MAG‐PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological features suggestive of MAG‐PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were significantly associated with the diagnosis of MAG‐PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmune demyelinating polyneuropathies. Muscle Nerve, 2005

Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's syndrome

We describe a patient who developed an ataxic sensory syndrome associated with xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological findings were consistent with an axonal sensory neuropathy, and superficial peroneal nerve biopsy showed a reduction in number of myelinated fibers with epineurial inflammation. Rheumatoid factor, anti‐SSA/SSB and antinuclear antibodies were positive and a diagnosis of Sjogrens syndrome was made. An endoscopic investigation revealed esophageal achalasia. We suggest that there may be a common autoimmune mechanism directed to different targets on the basis of this rare association. Muscle Nerve, 2007

High prevalence of neuropathies in patients with end-stage liver disease.

Cocito D, Maule S, Paolasso I, Castelli L, Ciaramitaro P, Poglio F, Ottobrelli A, Grimaldi S. High prevalence of neuropathies in patients with end‐stage liver disease.
Acta Neurol Scand: 2010: 122: 36–40.
© 2009 The Authors Journal compilation

Treatment response and electrophysiological criteria in chronic inflammatory demyelinating polyneuropathy

and advice from clinicians experienced in the diagnosis and management of this group of rare inherited metabolic disorders. We are involved in a European Porphyria Initiative whose aim is to develop a common approach to the diagnosis and management of porphyria, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research. Consensus information on diagnosis and treatment, as well as contact details for specialists throughout Europe is available on a website (http:// www.porphyria-europe.com). We hope that by improving access to knowledge and experience we will improve the standard of clinical care for these patients and their families, and avoid the serious and unnecessary consequences as have occurred in this case. References

Subclinical electrophysiological alterations of phrenic nerve in chronic inflammatory demyelinating polyneuropathy.

Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO2 partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.

Predictive value of clinical, electrophysiological and immunological features for response to IVIg in patients with CIDP

Aims: To investigate the features which are most predictive of IVIg response in patients with CIDP. Methods: We included 38 consecutive CIDP diagnosed according to Rotta et al. (2000). Anti‐MAG antibodies (Ab) assay and serum immunofixation were performed in all. IVIg (0.4 g/Kg/day) were the first treatment in all patients. Response to IVIg was defined as increase by at least 1 grade of the Rankin scale score at 1 month. The following features were considered: 1) proximal as well as distal weakness, 2) pure clinical sensory pattern, 3) disease duration lower than 12 months, 4) conduction block in at least 1 motor nerve, 5) mean lower/upper limbs motor nerve CMAP amplitude lower than 50% of lower limit of normal, 6)M monoclonal gammopathy, and 7) anti‐MAG Ab. Likelihood ratio (LR) of the features significantly associated with treatment response was evaluated in order to determine the increase or decrease of response to IVIg probability. Results: Twenty‐six patients were classified as responders and 12 as non‐responders. Age (60.6 ± 9.7 vs. 63.6 ± 9.4 years), disease duration (24 vs. 42 months) and sex ratio (18 vs. 9 male) were not different among the groups. Presence of conduction block in at least one motor nerve was associated significantly with treatment response (responders 50% vs. non‐responders 8.3%, p: 0.02) and presence of anti‐MAG Ab was associated with treatment failure (non‐responders 50% vs. responders 7.6%, p: 0.007). The remaining features were not significantly associated with treatment response. LR of presence on conduction block was 6, whereas LR of anti‐MAG Ab was 0.15. Considering 70% as mean percentage of responders, the finding of conduction blocks increase the probability of response to IVIg to 89%, whereas the finding of anti‐MAG antibody decreases this probability to 25%. Conclusion: Presence of conduction blocks and absence of anti‐MAG antibodies seem to be good predictors of response to IVIg in patients with CIDP.