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Background: Gait analysis is a reliable tool to characterise ambulation in Charcot-Marie-Tooth, the obtained are complex data makes its use scarce in clinical practice. The use of synthetic measure...

Autologous hematopoietic stem cell transplantation (aHSCT) is used in aggressive relapsing and progressive multiple sclerosis (MS). The multicentre studies and case series reported have relatively short follow-up. To evaluate long-term effect and safety of HSCT in MS. Patients referred to the MS centre of Cagliari and undergoing HSCT were included. Variations in relapses and EDSS before and after HSCT were evaluated by Wilcoxon test. A descriptive analysis was made for other clinical data. Nine patients (female 6, males 3; 5 relapsing–remitting, 2 secondary progressive, 1 primary progressive, and 1 progressive relapsing) performed HSCT (1999–2006). The median follow-up was 11 years (11–18). Eight patients underwent aHSCT, seven using a low intensity conditioning regimen, and one an intermediate intensity. The primary progressive underwent allogeneic HSCT, due to onco hematological disease. The relapses number decreased in the 2 years following the procedure compared to the two preceding years (p = 0.041). New relapses or disease progressions were observed after a range of 7 (low intensity regimen)–118 (intermediate intensity) months. At last follow-up, the EDSS was stable in two patients, improved in two, and worse in five (maximum 2 EDSS in one patient). Six patients showed new lesions, and seven gadolinium-enhancing on brain MRI after a mean of 23.3 and 19.8 months, respectively. Two serious adverse events were reported: melanoma, and progressive multifocal leukoencephalopathy. Our results confirm in a long follow-up the efficacy of HSCT in reducing relapses and disability progression. The risk/benefit profile is better for intermediate intensity regimens.

Charcot–Marie–Tooth disease (CMT) is characterised by great variability of genetic subtypes. This study aimed to assess the genetic subtypes of CMT disease in the Sardinian population. Genetic screening was performed for CMT cases (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]). A total of 1,043 subjects (119 index cases) were evaluated. In CMT1 index cases (69/119; 58%), PMP22 duplication at 17p11.2 was the most frequent genetic diagnosis (60/69; 87%), followed by mutations in the GJB1 gene (5/69; 7.2%), in the SH3TC2 gene (3/69; 4.4%) and PMP22 Gly107Val point mutation (1/69; 1.4%). The CMT2 group (24/119; 20.1%) comprised 10/24 (41.6%) patients carrying MPZ gene Ser44Phe mutation, 6/24 (25%) with mutations in MFN2 and HSPB1, and 1/24 (4.2%) in GJB1 and LRSAM1. In the HNPP group (26/119; 21.9%), the majority of patients reported the PMP22 deletion (25/26; 96.2%). Further studies are needed to comprehend the overall picture of the disease in Mediterranean area.

Background The island of Sardinia features a high incidence of multiple sclerosis (MS) characterized by early age at onset and a progressively increasing trend. The current study was aimed at examining variations in human leukocyte antigen–risk genotypes occurring over time in a cohort of patients. Methods Susceptible and neutral DRB1-DQB1 genotypes were identified in 1660 patients. Age at onset was established in 1436 patients divided into two cohorts, an older cohort (subjects born before 1949, N = 233) and a younger one (subjects born from 1960 to 1989, N = 850). Patients from the older cohort were randomly assigned to patients of the same sex from the younger cohort, matched for age at onset. The final sample included 170 pairs. Logistic conditional analysis was performed to determine the probability of a neutral genotype in both cohorts. Kaplan–Meier analysis was applied to ascertain the influence of predisposing and neutral genotypes in age at onset for both cohorts. Findings The probability of carrying a neutral genotype was 1.76-fold higher in the younger than in the older cohort ( P = 0.02) and 3.67-fold higher in men ( P = 0.005). Kaplan–Meier analysis revealed an earlier age at onset in patients of the young cohort carrying the predisposing genotype ( P = 0.004). Interpretation In the Sardinian population, an environment more prone and propitious to autoimmunity may contribute toward the rising incidence of MS or anticipate overt manifestation of the disease in genetically predisposed subjects.

Background and objective: A critical aspect of multiple sclerosis (MS) treatments is understanding the effect of disease-modifying drugs (DMDs) on the long-term risk of disability and whether the effect is related to disability at start of treatment. Methods: We performed an observational study on 3060 MS patients. The effect of therapy on progression to Expanded Disability Status Scale (EDSS) 3.0 and 6.0 from onset was analysed in treated vs untreated (UTP) patients using Cox regression analysis adjusted for propensity score and immortal time bias. Results: Compared to UTP, the risks of EDSS 3.0 were 94% and 73% lower in immunomodulant (IMTP-) and immunosuppressant (ISTP-) treated patients, respectively, while the risk of EDSS 6.0 was 86% lower in IMTP. The risk of EDSS 6.0 was, respectively, 91% and 75% lower in 1275 IMTP before and 114 after EDSS 3.0 than in 539 UTP; the risk was higher in IMTP starting therapy after EDSS 3.0 than before (HR = 4.42). Conclusions: DMDs delayed long-term disability in MS patients treated either in the early or, to a lesser extent, in the later phase of the disease. Thus, the window of therapeutic opportunity is relatively extended, assuming that early is better than late treatment, but late is better than never.

Sirs: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated neuropathy [13] characterized by symmetrical sensory and/or motor symptoms persisting for more than 8 weeks. The disease course may be progressive or relapsing [13]. On the basis of randomized trials, high dose intravenous immunoglobulin (IVIg), corticosteroids and plasma exchange have been established as effective treatments for CIDP. The main limitations of these approaches are lack of long term efficacy, difficulties in their use and high costs; thus, alternative immunosuppressive treatments have been proposed (azathioprine, cyclosporine and cyclophosphamide) [2, 9, 11]. The immune-mechanisms responsible for CIDP resemble those implicated in multiple sclerosis (MS) [13], thus making CIDP the peripheral counterpart of MS. In addition, similar to MS, neuropathological studies support heterogeneity of CIDP pathogenesis, with concomitant demyelination and axonal damage [13]. Some studies have recently been performed to evaluate the usefulness of Interferon (IFN) β1a in CIDP patients unresponsive to conventional therapies [1, 7, 14]. We present the case of a 43year-old woman, who in July 1997 complained of progressive weakness in both lower limbs, as well as sensory symptoms. Clinical symptoms persisted until December 1997 and a diagnosis of CIDP was made according to INCAT criteria [3]. Neurological examination revealed generalized areflexia, while an electrophysiological study showed partial conduction block for stimulation at the fibular head of peroneal nerves (–50 % amplitude on the right and –49 % on the left) and absent F wave on the left median nerve and right peroneal nerve. Cerebrospinal fluid analysis produced evidence of albuminocytological dissociation (total protein 82 mg/dL without cells) and isoelectrofocusing was within normal limit. After a first treatment schedule of IVIg with a good response, she became refractory to this treatment. She presented nine relapses throughout 27 months (treated with plasma exchange with transient and partial response) despite the specific drugs used (Figure). In July 2001 she started IFNβ-1b (Betaferon) 8MUI with subcutaneous injections every other day. No other relapses occurred. At present, she has been relapsefree for 40 months and shows marked improvement in clinical conditions (Table 1). Nerve conduction studies also showed marked improvement in motor and sensory velocities (Figure). In April 2002, serological examination showed the presence of anti-thyreoglobulin and anti-thyroid peroxidase antibodies, with an increase in free triiodothyronine and free thyroxin. Autoimmune thyreopathy was diagnosed, and the patient started treatment with an antithyroid drug. IFN beta has been proven efficient in treating MS [4, 5, 12] reducing the number of relapses. Due to clinical similarities between MS and CIDP, there is emerging interest in the use of IFN in CIDP. As far as we know, this is the first report in which IFNβ-1b has been used to treat a CIDP patient. Our patient showed good clinical and neurophysiological response to long-term IFNβ1b treatment (40 months). The stabilization observed was judged by the absence of relapses. IFN beta acts as an immunomodulatory agent, exerting its action at different levels in the inflammatory process. Two recombinant forms of IFN beta are used in clinical practice: IFNβ-1a and INFβ-1b. The use of IFNβ-1a in the treatment of CIDP is controversial, and contradictory results have been reported in different studies [1, 6, 12]. It should be noted that LETTER TO THE EDITORS

High-dose cyclophosphamide followed by autologous haematopoietic stem cell transplantation (HDC-AHSCT) is a treatment option for aggressive and refractory multiple sclerosis (MS). Natalizumab is a monoclonal antibody approved for relapsing-remitting (RR) MS unresponsive to immunomodulating drugs. Nothing is known about the use of natalizumab in patients after HDC-AHSCT. We describe five female RR-MS patients with incomplete response to HDC-AHSCT. Natalizumab was then administered with abolition of both MRI and clinical activity. No severe adverse events, in particular opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML), were observed. Our results suggest that the use of natalizumab in aggressive RR-MS after HDC-AHSCT could be effective and safe. The very long-term risk of adverse events due to sequential aggressive immunosuppression has to be established.

Two new cases of acute promyelocytic leukemia following mitoxantrone treatment in patients with multiple sclerosis