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OBJECTIVE: To assess relapses, disability progression and the role of disease modifying drugs (DMDs) in the year after delivery in women with multiple sclerosis (MS). METHODS: We prospectively followed-up pregnancies occurring between 2002 and 2008 in women with MS, recruited from 21 Italian MS centres. The risk of relapses and disability progression in the year after delivery was assessed using time-dependent Cox regression analysis. RESULTS: 350 out of 423 pregnancies were assessed (pregnancies not resulting in live birth and with a postpartum follow-up period shorter than 1 year were excluded from the analysis). 148 patients (42.3%) had at least one relapse in the year after delivery. An Expanded Disability Status Scale (EDSS) score at conception ≥2.0 (HR=1.4; 95% CI 1.1 to 2.0; p=0.046) and a higher number of relapses before (HR=1.5; 95% CI 1.2 to 1.8; p

Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility.

The major histocompatibility complex (MHC, also called HLA or human leukocyte antigen) and its products have a central role in the immune response. Sharing of the MHC class II region is important for CD4+ (helper) T cell interactions, and sharing of the MHC class I region is important for CD8+ (cytotoxic) T cell interactions. This phenomenon is called MHC restriction of antigen-specific T cell responses.

The study of cerebrospinal fluid (CSF) cells in multiple sclerosis (MS) has been closely linked to progress in the field of general immunology. In the mid-70s, with the advent of the idea that MS was an immunologically-mediated disease (or, at least, that an immunological process was at the basis of its pathogenesis), there was a sudden fluorishing of research on CSF cells. In those years, immunological methods used to distinguish B from T lymphocytes were applied to CSF cells, in order to establish the relative percentage of T and B lymphocyte subsets. The challenge was to find some numerical or functional abnormality to explain the high production of IgG in MS CSF.

The involvement of the C.N.S. in dysmorphic syndromes is very frequent; therefore a systematic analysis of the functions of the nervous system is important in the clinical definition of these syndromes. Besides the morphological aspects, studied by magnetic resonance imaging, investigations should be carried out in the neuroelectrophysiological and neuropsychological fields. For the former, the following examinations are proposed: EEG in wakefulness and sleep, multimodal evoked potentials (VEP, BAEP, SEP), cortical magnetic stimulation and P300 (P3). For the neuropsychological field, a general intelligence test appropriate to the mental age of the subject (the Wechsler, Terman-Merrill, or Brunet-Lezine scale) and, whenever possible, the following complementary tests: Raven's Progressive Matrices, Bender's and Santucci's graphic tests, go-no go, Goodenough draw-a-person, reading and writing tests, Langeot's scale for development of the logical thinking, sorting test and verbal and spatial memory tests. In some cases, the behaviour should be defined, through Conner's scale for attention deficit-hyperactivity disorders, the Autism Diagnostic Interview, the Adaptive Behaviour Scale and the Brief Psychiatric Rating Scale.

The CD45R (2H4) and CDw29 (4B4) molecules are probably involved in the regulation of immunological memory: CD45R functionally defines naive or virgin cells (prior to activation by exposure to antigen), while CDw29 characterizes previously activated (memory) cells. By means of two-colour fluorescence analysis, we studied CD4 and CD8, CD45R and CD4 and CD8 CDw29 cells from the cerebrospinal fluid (CSF) of 27 acute (MSa), and 10 stable (MSs) multiple sclerosis (MS) patients. We also compared 17 patients affected with various non-inflammatory (OND) diseases of the central nervous system (CNS). The most striking finding was the increased percentage of CD4+CD29-, CD4+CD45R- and CD8+CD45R- cells and the decreased percentage of CD4-CDw29+ and CD8- CDw29+ subsets in MSa patients compared to OND and MSs populations. These data suggest a decrease in memory cells (CDw29+) during the acute phase of MS. The modulation of CDw29 receptor could play a role in the genesis of acute MS attacks.

Antigens of the major histocompatibility complex (MHC) class II are known to play a key role in cell-mediated immune response. In the Central Nervous System (CNS), either none or very low percentages of Ia-positive cells have been detected in mouse or man.1–5

To the Editor: We read with interest the article by Marrosu et al. describing a family with a P0 gene missense mutation (Ser44Phe) and a Charcot-Marie-Tooth type 2 (CMT2) phenotype.1 This is an intriguing observation. Mutations in the gene coding for P0, the major protein component of the peripheral nerve myelin, have been primarily associated with demyelinating or hypomyelinating neuropathy, namely CMT1B, Dejerine-Sottas disease (DSD), and congenital hypomyelination.2 We observed a similar family in which a CMT2-like phenotype resulted from mutations in the P0 gene.3 Two brothers had severe neuropathy meeting the diagnostic criteria of DSD. The parents were consanguineous, had very mild neuropathy, and were initially thought to have CMT2. However, both had a frameshift mutation (Val102fs) in the P0 gene, resulting in a nonfunctional P0 protein truncated early in the extracellular domain.2,4 Their two sons were homozygous for the mutation. The paternal grandfather, the maternal grandmother, a paternal aunt, and two other distant relatives were found to have the same mild neuropathy as the heterozygous parents. All of the heterozygous individuals had very mild adult-onset neuropathy. Neurologic examination showed mild pes cavus, mild distal wasting in lower limb muscles, and reduced …

A case of identical twins is reported in which only 1 was affected by subacute sclerosing panencephalitis. The affected twin showed a defect of cellular immunity, mainly a decrease of T lymphocytes. This defect therefore appears to be a consequence and not a genetic determinant of the disease.

Lymphocyte subpopulations in cerebrospinal fluid (CSF) and peripheral blood (PB) were studied using monoclonal antibodies and the common membrane markers. The results in three groups of patients were compared: 36 subjects with 'non-immunological disorders' (NID), 14 subjects with multiple sclerosis (MS) and 6 with subacute sclerosing panencephalitis (SSPE). It was found that, in patients with NID, (1) 90% of cells were T lymphocytes, reactive with OKT3; (2) the helper/suppressor (T4/T8) ratios were the same in the CSF and the PB; (3) the OKIa1 percentage was lower in the CSF than in the PB; and (4) only a few cells were 'immature', reacting with OKT10. Using the membrane markers (E rosettes, Fc IgG receptors and surface immunoglobulins), on the other hand, it was noted that the majority of cells in the CSF were identified as suppressor T lymphocytes and surface immunoglobulin-positive B cells were less common than the Ia1 marker suggested. There were no significant differences between the CSF results in patients with NID and MS but the OKT3 lymphocytes were reduced in CSF samples from patients with SSPE.

Subacute sclerosing panencephalitis (SSPE) occurred in 3 unrelated children affected with different genetic forms of hypoparathyroidism (HPT). Clinical or laboratory evidence of an immunological deficit before SSPE onset was ascertained in cases 1 and 3. At the onset of SSPE, all cases showed signs of increased central nervous system (CNS) excitability due to poorly regulated blood calcium levels, and cases 1 and 2 had papilledema. Epidemiological evaluation suggests that the association of SSPE and HPT is not accidental. In HPT, both a subtle immunological deficit and CNS involvement may be predisposing factors of SSPE.

Surface markers of cerebrospinal fluid (CSF) cells have been studied in comparison with those of peripheral blood lymphocytes. The great majority (about 95%) of CSF cells bear surface markers of thymus-dependent lymphocytes (E rosettes with uncoated sheep red blood cells), while being devoid of bone-marrow derived cell markers (EAC rosettes with complement-coated red blood cells). In contrast with lymphocytes from peripheral blood, CSF cells form predominantly 'early' and 'sphere'-shaped E rosettes, and bear receptors for the complement-fixing segment of immunoglobulins G. Treatment with concentrated CSF does not affect rosette forming ability of peripheral blood lymphocytes.