Elana Brief

MR evidence of long T2 water in pathological white matter.

To describe what, if any, specific long T2‐related abnormalities occur in the white matter of subjects with either phenylketonuria (PKU) or multiple sclerosis (MS).

Absolute metabolite concentrations calibrated using the total water signal in brain 1H MRS

Magnetic resonance spectroscopy (MRS) has been coupled with a multi‐echo imaging sequence to determine the relaxation corrected signal areas of the metabolites and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR 30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy volunteers were fit using LCModel. Corresponding water signals, measured using a multi‐echo T2 imaging sequence, were fit with a Non‐Negative Least Squares algorithm. Using this approach the water area could be T1 and T2 corrected for all three water compartments: cerebrospinal fluid (CSF), intra‐ and extra‐cellular water, and myelin water. The image‐based water measurement is an improvement over spectroscopy methods because it can be more sensitive to water changes in diseased tissue. Metabolite areas were also corrected for relaxation losses. In occipital gray matter, the concentrations of Cho, Cr, and N‐acetyl aspartate (NAA) were 1.27 (0.06), 8.9 (0.3), and 9.3 (0.3) mmol/L tissue, respectively and in parietal white matter they were 1.90 (0.05), 7.9 (0.2), and 9.8 (0.2) mmol/L tissue. The Cho and Cr concentrations were different in occipital gray compared to parietal white matter (p < 0.0001 and <0.005, respectively). Copyright

Genetic Counseling for Early-onset Familial Alzheimer Disease in Large Aboriginal Kindred from a Remote Community in British Columbia: Unique Challenges and Possible Solutions

A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aboriginal kindred living in dispersed communities throughout British Columbia, Canada. Disseminating genetic information and ensuring that appropriate genetic counseling services are provided to all concerned relatives have posed several unique challenges. These challenges include knowledge exchange and continuity of care in a geographically remote and culturally distinct community. To our knowledge, this is the first time a specific genetic counseling approach has been needed for early-onset familial Alzheimer disease (EOFAD) in a North American Aboriginal community.

Tangles of Neurogenetics, Neuroethics, and Culture

Neurogenetics promises rich insights into how the mind works. Researchers investigating the range of topics from normal brain functioning to pathological states are increasingly looking to genetics for clues on human variability and disease etiology. Is it fair to assume this interest in neurogenetics is universal? How should researchers and clinicians approach ideas of consent to research or prediction of disease when a subject or patient understands the mind with concepts or language incompatible with neurogenetics? In this paper we consider how non-Western philosophies bring complexity to ideas of individual and community consent and confidentiality in the context of neurogenetics.

Proton MRS of large multiple sclerosis lesions reveals subtle changes in metabolite T1 and area

The T1 values of metabolites were measured in eight subjects with clinically definite multiple sclerosis (MS) having at least one large brain lesion (2.6 ± 0.7 mL) and in eight age‐ and sex‐matched healthy controls. MRS examinations were conducted at 1.5 T using point‐resolved spectroscopy (PRESS) (TE = 30 ms, TR = 530, 750, 1200, 1500, 3500, 5000 ms). Spectra were acquired from a voxel placed in the largest lesion in the subject with MS, and in a corresponding voxel (same size and region) in normal white matter (NWM) in the matched control, and were fitted using LCModel. As there are regional variations in metabolite and water T1 and metabolite signal areas, careful placement of the control voxel was necessary to measure subtle differences between the lesions and NWM. The T1 and T1‐corrected signal areas of creatine were the same in MS lesions as in controls. The T1 values of choline were significantly shorter in MS lesions located in occipital and parietal, but not in frontal, white matter. N‐Acetylaspartate (NAA) and myoinositol T1 values in MS lesions were similar to those in NWM; however, the area of myoinositol correlated directly with lesion water T1, and the area of NAA correlated inversely with lesion water T1. MR spectra acquired at short TR require T1 correction of choline for accurate quantification. Careful voxel placement in controls to match lesion location in subjects with MS enables a clearer view of the subtle changes in lesions. Copyright

Early-onset familial Alzheimer's disease and the definition of family: Experience with an indigenous community

genotype. Conclusions: The CNR-MAJ has confirmed the molecular diagnosis in 9% of patients with sporadic early-onset AD. Moreover, the APOE4/E4 genotype could also explain additional 9% of patients. For the remaining cases, we have not found any genetical abnormality. Among them, 3 cases whose both parents are still alive and without dementia are currently enrolled in a research program to identify new genetic de novo causes involved in early-onset AD.

Whose Mutation is It

Background: For clinical research with First Nations, the marriage of cultural ideals and westernmedicine is dynamic. Many issues have arisen while working with a First Nation population in British Columbia who has EOFAD due to a unique mutation in the PS1 gene. This has led to an obligatory need for partnerships. The Nation members are close, interact regularly with one another through community activities on their traditional territory and have information access through various media.Methods:Qualitative evaluation of focus group sessions has revealed longstanding patterns of interactions with First Nations and western systems. In a follow-up community based research meeting, a member stated “I am not worried at all about stigmas because stereotyping has always been part of the First Nations.” At the same time, another remarked that “we won’t be acknowledged for the work we will be contributing if our nation remains anonymous.” Results:Discussion includes ownership: Who has the right to benefit from discovery or to determine use of the discovery? How can a clinical discovery transition to a community benefit, even if the discovery has a potential difficult consequence (EOFAD)? Can the community prepare for this? Does the community want to prepare for this, especially in the face of other priorities? Above all, how can the western ethics norm of protection of individual rights be consistent with and part of communal rights? Keeping the name of participants and their community confidential could undermine the higher ethical principal of relational accountability. Conclusions: Shene (2002) argues that the existence of a mutation should be regarded as familial information, not capable of veto by one family member. Port et al (2008) suggest that in a hierarchical tribal context, rights of the individual may be relinquished in favour of the rights of the tribe. To date, Canadian researchers working with Indigenous peoples are encouraged to followOCAP, which promotes collective Ownership, Control, Access, Possession of data. Reconciliation between OCAP and more usual academic and clinical structures needs a strong partnership. Bringing the groups to common ground reveals ongoing interactive thoughtful discussion.