Emily Dwosh

Over 30 different mutations have now been identified in MAPt that cause frontotemporal dementia (FTD). However, there are several families with FTD that show definite linkage to the region on chromosome 17 that contains MAPt, in which no mutation(s) has been identified. Although these families could have a complex mutation of the MAPt locus that has evaded detection it is also possible that another gene in this region is associated with FTD. This possibility is supported by neuropathological findings in these families, which consist of neuronal inclusions that are immunoreactive for ubiquitin (ub-ir) but not for tau. In addition to neuronal cytoplasmic inclusions, several chromosome 17-linked families are reported to have ub-ir neuronal intranuclear inclusions (NII); a finding which is uncommon in sporadic FTD. Here, we describe detailed clinical and neuropathological findings in a new large, multigenerational family with autosomal dominant FTD and autopsy proven tau-negative, ub-ir neuronal cytoplasmic and intranuclear inclusions. We have demonstrated that this family is linked to a 19.06 cM region of chromosome 17q21 with a maximum multipoint LOD score of 3.911 containing MAPt. By combining the results of our genetic analysis with those previously published for other families with similar pathology, we have further refined the minimal region to a 3.53 cM region of chromosome 17q21. We did not identify point mutations in MAPt by direct sequencing or any gross MAPt gene alterations using fluorescent in situ hybridization. In addition, tau protein extracted from members of this family was unremarkable in size and quantity as assessed by western blotting. Neuropathological characterization of the ub-ir NII in this family shows that they are positive for promyelocytic leukaemia protein (PML) and SUMO-1 that suggests that these inclusions form in the nuclear body and suggests a possible mechanism of neurodegeneration in tau-negative FTD linked to chromosome 17q21.

OBJECTIVE: This study aimed to determine reproductive practices and attitudes of North Americans diagnosed with multiple sclerosis (MS) and the reasons for their reproductive decision making. METHODS: A self-administered questionnaire on reproductive practices was mailed to 13,312 registrants of the North American Research Committee on Multiple Sclerosis (NARCOMS) database who met inclusion criteria for the study. Completed questionnaires were then returned to the authors in an anonymous format for analysis. RESULTS: Among 5949 participants, the majority of respondents (79.1%) did not become pregnant following diagnosis of MS. Of these, 34.5% cited MS-related reasons for this decision. The most common MS-related reasons were symptoms interfering with parenting (71.2%), followed by concerns of burdening partner (50.7%) and of children inheriting MS (34.7%). The most common reason unrelated to MS for not having children was that they already have a "completed family" (55.6%). Of the 20.9% of participants who decided to become pregnant (or father a pregnancy) following a diagnosis of MS, 49.5% had two or more pregnancies. CONCLUSION: This study indicates that an MS diagnosis does not completely deter the consideration of childbearing in MS patients of both genders.

Previous research on the effects of pregnancy on multiple sclerosis (MS) is somewhat flawed, and well-controlled, well-designed studies are needed to validate trial findings. In general, pregnancy appears to have a protective effect on MS course, with fewer, less severe relapses, especially in the third trimester. The exacerbation rate is increased in the first 3 months after delivery, but the overall relapse rate is no different to that observed in non-pregnant MS patients. A woman's past history of relapses may be the best indicator of clinical course during and immediately after pregnancy. Pregnancy does not appear to affect the long-term course of MS.

Two-thirds of multiple sclerosis (MS) patients are women, and the average age of onset overlaps the childbearing years. Clinicians are frequently asked, therefore, about the most appropriate form of contraception and the risk of an MS relapse/exacerbation during pregnancy and the post-partum period. This paper reviews the literature on the immune system and the effects of pregnancy, oral contraceptives and hormone replacement therapy on MS.