Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.

Ninety two normal birthweight infants aged 6 months entered a double blind controlled trial which compared a follow on formula milk with no added iron against the same formula milk containing 1*2 mg of iron per 100 ml. There was no significant difference in the social class or demographic characteristics of the two treatment groups or in the proportion of each group completing the trial. There was no difference between the two groups in the quantity of milk taken but the amounts taken lessened between 6 and 18 months of age. There was no difference between the two groups with respect to mean haemoglobin and median serum ferritin at 6, 9, 12, 15, and 18 months of age. Very few infants developed iron deficiency anaemia in either group but there was a tendency for serum ferritin levels to fall between 6 and 18 months of age in both groups. The results suggest that iron added to follow on milk was not an important source of dietary iron in the infants studied. (Arch Dis Child 1995; 73: 216-220)

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Objectives. To investigate whether poor psychological status predicts shorter survival, faster progress of disease and greater disability in patients with ALS/MND (amyotrophic lateral sclerosis/motor neurone disease). Design. A prospective study of mood as a predictor of 6‐month outcome in a consecutive cohort of patients with ALS/MND. Methods. A cohort of 38 consecutive patients completed mood, self‐esteem, wellbeing and disability measures at the time of diagnosis and 6 weeks later. Survival and disability were assessed at 6 months. Results. The 10 patients who died had poorer overall mood at the 6‐week interviews. Low mood early in disease also predicted greater disability at 6 months. The poor outcomes of patients with poor psychological well‐being were not due to confounding associations between mood and disease severity. Conclusions. The data confirm McDonald, Weidenfeld, Hillel, Carpenter & Walter's (1994) finding that poor psychological status predicts poor survival in ALS/MND. This study also extend their findings by (a) recruiting patients at the point of diagnosis and therefore controlling for effects due to the duration of disease, and (b) demonstrating that mood also predicts disease progression and disability. The findings are unlikely to be due to simple spurious association of the psychological status measures with recognized indices of disease or of expected survival. Explanations for the results can be considered in the context of other findings of mood predicting outcomes of life‐threatening disease and the possible value of psychological interventions may be considered.

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