In 1918 Fleischer reported that after transmission from one generation to the next, myotonic dystrophy has an earlier onset and is more severe. The hypothesis put forward by Penrose in 1948 that 'anticipation' is caused by bias of index case selection was based on theoretical arguments only and has not been supported by clinical observations. This hypothesis was tested in a clinical and genetic study of 14 families with myotonic dystrophy. Excluding index patients, an earlier onset in the child was found in 98% of 61 parent-child pairs. A greater mean difference in age of onset was found with transmission via the father than via the mother. The comparison of the severity of the disease between parents and children was difficult because of the variation in symptoms but, in general, the disease was more severe in the child than in the parent. The penetrance of the abnormal gene was nearly complete in the 14 families combined, leaving little room for the observation of 'complementary' parent-child pairs in the future. Also in retrospect no complementary parent-child pairs were found in the first generations. Fertility was severely reduced only in the very early onset patient group and this selective infertility cannot be responsible for the total amount of anticipation observed. It is therefore concluded that anticipation may be inherent in the transmission of myotonic dystrophy. This has important consequences for genetic counselling.

SUMMARYThe interobserver agreement for the diagnosis of a cerebral transient ischemic attack (TIA) was investigated in a pool of eight senior and interested neurologists from the same department. They interviewed 56 patients in alternating pairs. The diagnosis was based on internationally accepted criteria. The agreement rates were corrected for chance (kappa statistics). Both neurologists agreed that 36 patients had a TIA and 12 had not, but they disagreed about 8 patients (kappa = 0.65; for perfect agreement kappa would be 1.0). The Vascular territory (carotid or vertebrobasilar) was agreed upon in only 24 of the 36 patients in whom both diagnosed TIA's (kappa = 0.31). We concluded that currently the diagnosis of a TIA, made by a single neurologist, is a poorly defined entity.Stroke Vol 15, No 4, 1984

To try and improve the interobserver agreement for the diagnosis of TIA, we used a checklist in which the symptoms were recorded in plain language, instead of in abstract diagnostic terms such as amaurosis fugax. Criteria for a diagnosis of TIA were similarly phrased and recommended to all observers. Eight senior neurologists and ten neurology residents interviewed 72 patients in random pairs. In 64 cases the observers agreed on the diagnosis (kappa value = 0.77). After a short discussion between the two observers the agreement increased to a maximum (kappa = 1.0). However, in 29 of the 144 interviews the diagnosis would have been different, had the recommended criteria been fully applied. In 28 of these the observer had diagnosed TIA on insufficient evidence. Six "misinterpretations" led to disagreement for the diagnosis and only these were corrected by the observers during their discussion. The present design has led to a maximal agreement for the diagnosis of TIA between two observers, but the agreement between such a pair and the common diagnostic criteria was not yet ideal. The precision of the diagnosis could be improved if details of the required symptoms are discussed in general as well as for each patient.

In a cooperative study in The Netherlands 22 patients with lissencephaly type I were collected. In the period 1980–1988, the prevalence of lissencephaly type I in the Netherlands was 11.7 per million births (12.2 for females and 11.0 for males). The 5-year survival rate of patients with a complete or nearly complete agyria (grade 1 or 2) in this study was 54% compared to 91% in patients with a mixture of agyria with pachygyria or complete pachygyria (grade 3 or 4).

We studied the interrater variability among three neurologists of the diagnosis of a seizure in 100 patients evaluated for a possible "first seizure." We found that use of simple descriptive diagnostic criteria and discussion among the neurologists themselves improved the diagnostic agreement.