Dario Cocito

Guillain-Barré syndrome A prospective, population-based incidence and outcome survey

Objective: The authors evaluated the incidence and long-term prognostic factors of Guillain-Barré syndrome (GBS) in a prospective, population-based study. Methods: Patients with GBS diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke criteria in the 2-year period 1995 to 1996 in two Italian regions were prospectively followed up for 2 years after onset of GBS. Results: A total of 120 patients were found, corresponding to a crude annual incidence rate of 1.36/100,000 population (95% CI, 1.13 to 1.63). A total of 7 (5.8%) patients, all but one with axonal or mixed EMG pattern, died acutely within 30 days from the onset of the disease. Acute mortality was due to respiratory involvement and intensive care unit complications. In multivariate analysis, a worse 2-year outcome (Hughes score ≥2) was related to a higher Hughes grade at nadir, axonal or mixed EMG, age ≥50 years, and absence of respiratory infections preceding GBS. The persistence of disability 2 years after the acute phase was related to axonal involvement and a worse status at nadir. Conclusions: After adjustment to US population, the incidence rates for GBS from different countries showed no significant differences. Both acute mortality and long-term disability in GBS seem to be related to an axonal involvement and a Hughes grade ≥2 at nadir.

Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients

The objectives of this study were (1) epidemiological analysis of traumatic peripheral nerve injuries; (2) assessment of neuropathic pain and quality of life in patients affected by traumatic neuropathies. All consecutive patients with a diagnosis of traumatic neuropathies from four Italian centres were enrolled. Electromyography confirmed clinical level and site diagnosis of peripheral nerve injury. All patients were evaluated by disability scales, pain screening tools, and quality of life tests. 158 consecutive patients for a total of 211 traumatic neuropathies were analysed. The brachial plexus was a frequent site of traumatic injury (36%) and the radial, ulnar, and peroneal were the most commonly involved nerves with 15% of iatrogenic injuries. Seventy‐two percent of the traumatic neuropathies were painful. Pain was present in 66% and neuropathic pain in 50% of all patients. Patients had worse quality of life scores than did the healthy Italian population. Moreover, there was a strong correlation between the quality of life and the severity of the pain, particularly neuropathic pain (Short Form‐36 [SF‐36] p < 0.005; Beck Depression Inventory [BDI] p < 0.0001). Traumatic neuropathies were more frequent in young males after road accidents, mainly in the upper limbs. Severe neuropathic pain and not only disability contributed to worsening the quality of life in patients with traumatic neuropathies.

Multi‐center assessment of the Total Neuropathy Score for chemotherapy‐induced peripheral neurotoxicity

Abstract  The aim of this multi‐center study was to assess with reduced versions of the Total Neuropathy Score (TNS), the severity of chemotherapy‐induced peripheral neurotoxicity (CIPN), and to compare the results with those obtained with common toxicity scales. An unselected population of 428 cancer patients was evaluated at 11 different centers using a composite (clinical + neurophysiological, TNSr) or clinical (TNSc) examination and with the National Cancer Institute – Common Toxicity Criteria (NCI‐CTC) 2.0 and Eastern Cooperative Oncology Group (ECOG) scores. A highly significant correlation was demonstrated between the TNSr and the NCI‐CTC 2.0 and ECOG scores; but the TNSr evaluation was more accurate in view of the more extended score range. Also, the simpler and faster TNSc (based only on the clinical neurological examination) allowed to grade accurately CIPN and correlated with the common toxicity scores. The correlation tended to be closer when the sensory items were considered, but also the TNSr motor items, which were not specifically investigated in any other previous study, significantly correlated with the results of the common toxicity scales. In conclusion, this study suggests that the TNSr is a reliable tool for accurately grading and reporting CIPN, with the additional and so far unique support of a formal comparison with known and widely used common toxicity scales. The TNSc is a valid alternative if neurophysiological examination is not feasible. The longer time needed to calculate the TNSr and TNSc in comparison to the ECOG or the NCI‐CTC 2.0 scales is offset by the more detailed knowledge of the CIPN characteristics.

Predictors of response to rituximab in patients with neuropathy and anti–myelin associated glycoprotein immunoglobulin M

Abstract  We evaluated the efficacy and safety of rituximab in an open‐label, uncontrolled study of 13 patients with polyneuropathy associated with antibodies to myelin‐associated glycoprotein (MAG) and correlated the response to therapy with clinical and laboratory features. One year after rituximab therapy, anti‐MAG immunoglobulin M (IgM) titers were significantly reduced. At that time, eight patients (62%) had improved in both the inflammatory neuropathy cause and treatment (INCAT) sensory sumscore and the Medical Research Council sumscore for muscle strength and seven of them also in the INCAT disability score. The improvement in the mean INCAT sensory sumscore was significant at 12 months and correlated with lower anti‐MAG antibody at entry and at follow‐up. This study suggests that rituximab may be efficacious in patients with anti–MAG associated neuropathy and particularly on sensory impairment and in those with moderately elevated antibody titers. These findings suggest that antibody reduction below a critical level may be necessary to achieve clinical improvement.

Altered resting state attentional networks in diabetic neuropathic pain

Background Chronic pain can be considered as a highly salient stimulus that continuously taxes the attentional and salience processing networks, thus interfering with cognitive abilities and, more specifically, consuming attentional resources. The aim of the paper was to explore whether and how diabetic neuropathic pain (NP) affects attentional networks. Methods The authors sought to achieve this by investigating resting state functional connectivity (rsFC) in diabetic NP patients and comparing it with that of matched healthy controls. Results NP patients showed a widespread reduction in connectivity in both the dorsal and ventral attentional networks, as well as in the dorsal anterior cingulated cortex (ACC), typically implicated in salience processing. The authors also found a generalised reduction in the length of functional connections in the NP group: in all the examined networks, the Euclidean distance between connected voxels was significantly shorter in patients than in controls. Conclusion In diabetic NP, a parieto-fronto-cingulate network controlling attention to external stimuli is impaired. In line with previous studies, chronic pain can disrupt the synchrony of a common pool of brain areas, involved in self-monitoring, pain processing and salience detection.

Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain

BackgroundIn this paper we explored thalamocortical functional connectivity in a group of eight patients suffering from peripheral neuropathic pain (diabetic pain), and compared it with that of a group of healthy subjects. We hypothesized that functional interconnections between the thalamus and cortex can be altered after years of ongoing chronic neuropathic pain.ResultsFunctional connectivity was studied through a resting state functional magnetic resonance imaging (fMRI) paradigm: temporal correlations between predefined regions of interest (primary somatosensory cortex, ventral posterior lateral thalamic nucleus, medial dorsal thalamic nucleus) and the rest of the brain were systematically investigated. The patient group showed decreased resting state functional connectivity between the thalamus and the cortex.ConclusionThis supports the idea that chronic pain can alter thalamocortical connections causing a disruption of thalamic feedback, and the view of chronic pain as a thalamocortical dysrhythmia.

Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy

Aim: The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. Subjects and methods: All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d’Aosta (4 334 225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. Results: The crude prevalence rate was 3.58/100 000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting–relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995–2001, the mean annual crude incidence rate was 0.36/100 000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age>60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. Conclusion: Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases.

Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature

Background A few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Objective To analyse the efficacy of rituximab in a large CIDP cohort. Methods A retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders. Results Nine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1–6) and lasted for a median period of 1 year (range, 1–5). Conclusions Rituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.

A nationwide retrospective analysis on the effect of immune therapies in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose:  The guidelines for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) therapy suggest to use immunoglobulins (IVIg) and steroid as first‐line therapies. Patients who do not respond to one of the two drugs should be switched to the other drug. We collected therapeutic outcome data in patients followed at 11 centres in order to document the clinical practice in Italy.

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.