Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: A multicentre, Italian, retrospective, observational study.

BACKGROUND: Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs). OBJECTIVES: To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents. METHODS: Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution. RESULTS: In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p < 0.001), and it remained low during the whole follow-up (0.3 ± 0.2, p < 0.001). At last observation, 40% had disability worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years due to MS. One case of natalizumab-related progressive multifocal encephalopathy (PML) was recorded. Starting therapy before 12 years of age resulted in a better course of disease in multivariate analysis. CONCLUSION: Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.

Angiographically proven cervical venous engorgement: a possible concurrent cause in the pathophysiology of Hirayama's myelopathy.

The objective of this study is to discuss the possible role of cervical posterior epidural plexus engorgement during cervical flexion in the pathogenesis of Hirayama myelopathy. In Hirayama disease, MRI during neck flexion often shows that the posterior dura detaches from the posterior arches compressing the spinal cord. Autopsies demonstrated asymmetric changes in the anterior horns consistent with chronic ischemic damage, attributed to arterial insufficiency during flexion or to microcirculatory changes due to compression by the tight dura. In a 15-year-old patient with 5-year history of distal upper limbs weakness, MRI demonstrated marked venous engorgement of the posterior epidural plexus in cervical flexion, confirmed by angiography. Laminectomy from C3 to C6 with duraplasty was performed. At one-year follow-up, the clinical condition of the patient remained stable. In Hirayama myelopathy, compression of the spinal cord by the tight dura is probably the most important pathogenetic factor. However, venous congestion in flexion might play an additional role in determining spinal cord ischemic changes.

Brain macro- and microscopic damage in patients with paediatric MS.

OBJECTIVE: To characterise, using conventional and diffusion tensor (DT) MRI, the nature and distribution of lesions and the extent of damage in the brain normal-appearing white matter (NAWM) and grey matter (GM) from a relatively large population of paediatric multiple sclerosis (MS) patients. METHODS: Brain conventional and DT MRI scans were acquired from 48 patients with paediatric MS (10 clinically isolated syndromes (CIS), 38 relapsing remitting (RR) MS), 30 adult CIS, 27 adult RRMS, 15 paediatric healthy controls (HC) and 18 adult HC. T2-lesion probability maps and DT MRI of lesions, NAWM and GM were compared among controls and MS groups. RESULTS: T2-visible lesion volumes did not differ among patient groups, but T2 lesions were more frequently located in the posterior periventricular regions in adult RRMS patients than in adult CIS and paediatric RRMS patients. Adult RRMS patients had a significantly higher lesion average mean diffusivity than paediatric RRMS patients. No DT MRI changes in the NA tissues were found in paediatric and adult CIS patients. DT MRI abnormalities were limited to the NAWM in paediatric RRMS patients, while they involved the NAWM and GM in adult RRMS patients. The extent of NAWM involvement was similar between adult and paediatric RRMS patients and was significantly correlated with T2-visible lesion burden. CONCLUSIONS: A less severe intrinsic lesion damage, a less frequent lesion occurrence in the posterior periventricular WM and the sparing of GM may help to explain the favourable short-/medium-term disease outcome of paediatric MS.

Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: the Italian experience.

The main objective of this study is to evaluate the effect of immunomodulatory agents (IMAs) (Interferon-Beta, Glatiramer Acetate) in a large cohort of multiple sclerosis (MS) patients with disease onset in childhood or adolescence, treated before 16 years of age, after a long-term follow-up. A total of 130 patients were identified, 77 were treated with Avonex, 39 with Rebif/Betaferon, 14 with Copaxone. After a mean (SD) treatment duration of 53.6 +/- 27.0, 59.9 +/- 39.5 and 74.6 +/- 35.5 months, respectively, the relapse rate decreased significantly. The final EDSS score was unchanged with respect to the initial score. Similar results were also observed in subjects who continued a long-term follow-up after they were included in an observational study in 2004, and in subjects who were treated before 12 years of age. The frequency of clinical and laboratory adverse events was similar to that observed in adult patients. To conclude, IMAs were effective and well tolerated in paediatric patients with MS.

A case of pediatric tumefactive demyelinating lesion misdiagnosed and treated as glioblastoma.

Because of their clinical and neuroradiological features, tumefactive demyelinating lesions, or giant plaques, are easily mistaken for tumors, with a consequent risk of gross errors in the choice of treatment. This article reports a 10-year-old girl who underwent surgery for a left parietal lesion misinterpreted as a glioblastoma which subsequently proved to be a case of giant plaque.

Functional expression of a mammalian olfactory receptor in Caenorhabditis elegans.

The olfactory system in both vertebrates and invertebrates can recognize and distinguish thousands of chemical signals. Olfactory receptors are responsible for the early molecular events in the detection of volatile compounds and the perception of smell. Recently, candidate olfactory receptor genes have been identified in several organisms, but their characterization is far from been completed due to the difficulty to functionally express them in heterologous systems. To circumvent such difficulty, we expressed a mammalian olfactory gene, rat I7, in the nematode. We generated transgenic worms expressing I7 in AWA or AWB chemosensory neurons and performed behavioural assays using different concentrations of the rat I7 receptor agonist octanal. Pure octanal was repellent for wild-type worms whereas a 1:10 dilution was attractant. Expression of I7 in AWB neurons counteracted the volatile attraction to diluted octanal observed in control wild-type worms. Furthermore, expression of I7 in AWA neurons counteracted the volatile avoidance to pure octanal observed in wild-type worms. These results indicate that it is possible to functionally express mammalian olfactory receptors in providing a research tool to efficiently search for specific olfactory receptor ligands and to extend our understanding of the molecular basis of olfaction.