Investigation of clinical and pathogenic heterogeneity in Chronic Inflammatory Demyelinating Polyneuropathy

My aim during the last three years was to create a detailed database of CIDP patients, in order to analyse the data collected in a retrospective manner and to take part to national projects on the disease. In fact, since aspects of CIDP are still unsolved, such as clinical variability, pathogenesis, prognostic factors, outcome measures and response to treatment, and considering that CIDP is a rare disease, a nation-wide collaboration is indispensable. In Section 1 I will describe the clinical and epidemiological features of CIDP patients who referred, in the last 15 years, to our Centre of Neuromuscular Disease at University Federico II of Naples and that I selected among all the patients with disimmune diseases of peripheral nervous system. In Section 2 I will summarise the preliminary conclusions derived from the creation of a web-based national database promoted by the Humanitas Institute that involved more than 500 patients, among which 51 come from our Neuromuscular Centre in Naples. Section 3 is dedicated to the pathogenesis, in particular to the emerging role of antibodies against paranodal proteins in the determination of specific morphologic alterations and clinical phenotypes. In particular, I will speculate on the pathogenesis of CIDP with antibodies against Neurofascin 155. Then I will report the results derived from our collaboration with the IRCCS Mondino Foundation, Pavia, Italy, which analyzed the sera from different national centres, including our centre, in order to identify and characterize the anti-nodal and paranodal antibodies incidence and their correlation with phenotypic aspects in a large cohort of patients

Six-minute walk test is reliable and sensitive in detecting response to therapy in CIDP

Objective: The current clinical measures (ONLS, R-ODS, mRS, and MRC) may not be so sensitive in capturing minimal variations or measuring fatigue in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our aim was to assess if 6-min walk test (6MWT) is able to increase the sensitivity in detecting response to therapy and to capture fatigue in CIDP patients. Methods: We tested 6MWT in 42 CIDP patients. Using both anchor-based and distribution-based approaches, we estimated the meaningful clinical change after therapy by calculating the minimum improvement cutoff (Minimal Clinically Important Difference Score—MCID) required for considering a patient as responder. We calculated the sensitivity of the 6MWT versus the other clinical outcomes. We analysed fatigue by comparing the velocities between first and sixth minutes of the 6MWT and the effect of treatment on fatigue using an ANOVA model for repeated measures. Results: MCID resulted equal to 20 m. The combination of 6MWT-MCID cutoff with the other clinical measures led to identify 74% of responders. The sensitivity of the 6MWT was 90% versus 77% of the other clinical measures. The 6MWT was also sensitive in capturing fatigue-related changes, even though fatigue was not influenced by treatment. Conclusions: The combination of the 6MWT with the other clinical measures increased the chance to detect the quote of responders. We propose to include the 6MWT in the routine assessment of CIDP patients and the MCID cutoff at 20 m could be set for identifying the responders and properly guiding the therapy managemen

Early predictive factors of disability in CIDP

The objective of this study was to identify early clinical, biochemical and electrophysiological prognostic factors of disability in CIDP. We evaluated a dataset from 60 CIDP patients that included sex, age of onset, type of onset, phenotype, disease duration, response to treatment, disability at the time of diagnosis assessed using the modified Rankin Scale (baseline mRS), cerebrospinal fluid protein levels and electrophysiological data. All patients had clinical assessment of disability through the mRS within the last 6 months (last mRS) before enrollment in the study. Stepwise forward logistic regression model was applied to evaluate the impact of clinical, biochemical and electrophysiological parameters on the last mRS, considered as binary outcome (absence or presence of severe disability, i.e., <4/≥4 mRS). Moreover, we used Spearman's rank correlation coefficient to evaluate the relationship between disease duration and last mRS. We observed a significant relationship between last mRS and baseline mRS [p = 0.015, z = 2.44, OR 5.15 (CI 1.38-19.22)] and age of onset [p = 0.017, z = 2.39, OR 1.13 (CI 1.02-1.27) per additional year of age of onset]. There was no correlation between disease duration and last mRS. Our data suggest that a worse clinical status at the beginning of disease and an older age at onset may be negative prognostic factors of long-term disability independent from disease duration

Motor performance deterioration accelerates after 50 years of age in Charcot-Marie-Tooth type 1a patients

The aim of our study was to describe, by a case-control and cross-sectional design, the correlation between clinical impairment and age in CMT1A patients

Non-motor symptoms and cardiac innervation in SYNJ1-related parkinsonism

INTRODUCTION: PARK20 is a rare autosomal recessive parkinsonism related to the SYNJ1 gene and characterized by early-onset of disease and atypical signs such as supranuclear vertical gaze palsy, dementia, dystonia, and generalized tonic-clonic seizures. OBJECTIVE: Non-motor features and cardiac sympathetic innervation were assessed in two siblings affected by parkinsonism who harboured the homozygous Arg258Gln mutation in the SYNJ1 gene. METHODS: The Non-Motor Symptoms, the SCOPA-AUT, the Mayo Sleep Questionnaires and polysomnography were used to investigate non-motor signs (NMS), autonomic dysfunction and REM Behavioural Disorder (RBD). Cognitive functions were examined by an extensive battery of neuropsychological tests. In addition, motor and sensory nerve conduction studies and evoked laser potentials were performed. Cardiac sympathetic innervation was assessed in the two patients by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy, computing early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR). RESULTS: Among the non-motor symptoms and autonomic signs, case 1 had cold intolerance, drooling and dysphagia, while case 2 had pain and urinary dysfunction. Both cases showed mood and behavioural disorders. RBD were not found, whereas the neuropsychological assessment revealed a progressive cognitive impairment. Neurophysiological studies revealed no abnormalities. Indexes of cardiac sympathetic innervation in the two patients did not differ from those of control subjects. CONCLUSIONS: Our findings expand the phenotypic profile of SYNJ1-related parkinsonism. Preserved cardiac sympathetic function and absence of RBD suggest that PARK20 should be explained by a pathogenic mechanism different from Lewy Body pathology, or that the latter is not as widespread as idiopathic Parkinson's disease