Herpes simplex virus thymidine kinase (HSV tk) gene therapy combined with ganciclovir (GCV) medication is a potential new method for the treatment of malignant glioma. We have used both retrovirus-packaging cells (PA317/tk) and adenoviruses (Adv/tk) for gene therapy for malignant glioma. Retrovirus-packaging cells were used for eight tumors in seven patients and adenoviruses were used for seven tumors in seven patients. As a control group, seven tumors in seven patients were transduced with lacZ marker gene 4-5 days before tumor resection. Safety and efficacy of the gene therapy were studied with clinical evaluation, blood and urine samples, MRI follow-up, and survival of the patients. Four patients with adenovirus injections had a significant increase in anti-adenovirus antibodies and two of them had a short-term fever reaction. Frequency of epileptic seizures increased in two patients. No other adverse events possibly related to gene therapy were detected. In the retrovirus group, all treated gliomas showed progression by MRI at the 3-month time point, whereas three of the seven patients treated with Adv/tk remained stable (p < 0.05). Mean survival times for retrovirus, adenovirus, and control groups were 7.4, 15.0, and 8. 3 months, respectively. The difference in the survival times between the adenovirus and retrovirus groups was significant (p < 0.012). It is concluded that HSV tk gene therapy is safe and well tolerated. On the basis of these results further trials are justified, especially with adenovirus vectors.

Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

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Background and Purpose-The purpose of the present study was to calculate the prevalence and relative risk of unruptured incidental intracranial aneurysms (IAs) among families with IA case(s) compared with the general population in one geographically defined area in East Finland and to identify the risk group that could benefit most from screening for IAs. We compared these results with our earlier study results of familial IA (FIA) cases, with two or more known IA cases in the same family. Methods-The study groups were collected from the catchment area of the University Hospital of Kuopio in East Finland. The inclusion criteria were age 30 to 70 years and unruptured incidental IAs Ն3 mm. Patients with previous subarachnoid hemorrhage or in whom a ruptured IA was found to be the cause of death were excluded from all study groups. During routine forensic autopsies the circle of Willis was studied for IAs to estimate the number of IAs in the general population. In the families with one known IA case and in FIA families, MR angiography was used as a preliminary screening method for IAs, followed by intra-arterial angiography to verify suspected IAs. Study populations were age and sex adjusted for the statistical calculations. Results-The relative risk for IAs among first-degree relatives in FIA families was 4.2 (95% confidence interval, 2.2 to 8.0) and among first-degree relatives in families with only one affected family member was 1.8 (95% confidence interval, 0.7 to 4.8) compared with the general population in East Finland. Conclusions-First-degree relatives in FIA families constitute a high-risk group for incidental IAs, and this group would benefit from screening studies for IAs. Screening for IAs in families with only one affected member or in the general population is not recommended. (Stroke. 1998;29:359-362.)

Early hydrocephalus is a risk factor of shunt-dependent late hydrocephalus (SDHC). In the CT era 1980-1990 we had 835 consecutive patients operated on because of aneurysm and subarachnoid haemorrhage (SAH); 294 had an early hydrocephalus and 67 finally required a shunt. There were 14 patients with normal early CT and SDHC, in all 81 patients needed a shunt (10%). Patients with shunt did worse, they were older (53 vs 49) than the non-shunted group and there was a female preponderance. Pre-operative Grade correlated significantly with the need for a shunt operation; no one in Grade I developed SDHC, incidence in Grades III and IV was high (18% and 10%, respectively). Location was important; in vertebrobasilar area 28% and in anterior communicating area 14% but in middle cerebral area only 4% of the patients had SDHC. The amount of cisternal bleeding correlated significantly with SDHC; in 155 patients with non detectable or minimal cisternal blood only one developed SDHC, with severe cisternal bleeding the incidence was 16%. Ventricular bleeding increased the risk of SDHC, but intracerebral haematoma did not. Timing of surgery had no correlation with the risk of SDHC. Postoperative complications, haematomas and infections increased the risk of late SDHC. Delayed ischaemia correlated with the risk, but so did the treatment with nimodipine. Severe bleeding was the common predictor for the risk of SDHC. Location of the bleeding and postoperative problems are the other major causes. Outcome is, however, not so gloomy; 54% of patients with SDHC are independent one year later.