Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by the selective degeneration of motor neurons in the spinal cord, brainstem and motor cortex, resulting in muscle atrophy and weakness. Its course is relentlessly progressive, impairing ambulation, upper extremity function, speech and swallowing. After three to five years, the disease is almost uniformly fatal, respiratory failure being the most frequent cause of death. Currently there is no treatment for ALS. The effect of riluzole, a glutamate release inhibitor and the only FDA-approved drug for ALS, is limited and indiscernible to individual patients. Recent evidence from cellular and animal studies has provided several new insights relevant to developing treatment options for ALS. First, motor neuron degeneration in ALS appears to be non-cell autonomous, meaning that non-neuronal cells contribute to its pathogenesis. Understanding the communication between the markedly proliferating astrocytes, microglial cells and motor neurons in the ALS spinal cord is therefore essential, as interfering with it may constitute a pharmacological target. Furthermore, glial cells may be a more realistic target for stem cell approaches, as compared to the substitution of the degenerating neurons. Second, the development of methods to deliver potentially therapeutic compounds to motor neurons directly, such as viral vector delivery of genes encoding proteins that can interfere with pathogenic cascades, or the intracerebroventricular administration of drugs, has demonstrated that the course of ALS can be drastically changed, at least in animal models. Finally, in vitro and in vivo models allowing the rapid screening of drugs and modifying genes have been introduced in ALS research. This makes testing of a large number of compounds in a short time-span possible. Furthermore, the identification of genes modifying the ALS phenotype, allows the study of pathophysiological cascades, constituting novel therapeutic targets.

A 22-year-old woman (index case) presented at the department of ophthalmology with progressive visual loss for the past 3 years. Ophthalmological examination revealed a visual acuity of 20/100 in each eye. At funduscopy, a dull macular reflex was noted. Family history revealed spinocerebellar ataxia type 7 (SCA7) in three generations. We describe the ophthalmological findings in this family. Insidious visual problems can be the presenting sign of spinocerebellar ataxia type 7. In examining a negative family history, the diagnosis can be very difficult.

Intravascular lymphomatosis is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system. Most cases are not diagnosed until postmortem because of variable clinical presentation and non-specific laboratory findings. We studied a 41-year-old lady who presented with progressive neurological symptoms. MR showed multifocal grey and white matter lesions. Brain biopsy showed an intravascular lymphoma of the B-cell lineage. This report illustrates the ischaemic origin of the radiological lesions, as they are all hyperintense on the diffusion-weighted images. This has, to our knowledge, never been published before. MR did not show any enhancement after intravenous Gadolinium-DTPA (parenchymal or meningeal)which is a very uncommon finding in this entity. Intravascular lymphomatosis should be taken into account in the differential diagnosis of repeated cerebral ischemia of unclear aetiology.

We demonstrate focal leptomeningeal enhancement along the chiasm on MRI in a 28-year-old man presenting with blurred vision and bitemporal visual field defects. The diagnosis of clinically definite multiple sclerosis was confirmed by laboratory investigations and brain MR findings.

The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoencephalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss.

Conventional magnetic resonance imaging, as a non-invasive technique should be considered as the imaging modality of choice in the radiological diagnosis of deep cerebral venous thrombosis. Although different technical aspects of MR angiography are certainly not yet optimized, this example clearly shows the potential of this technique as a non-invasive alternative to conventional angiography

Rat pituitary cell aggregates cultured in serum-free chemically defined medium, single cells, and hemipituitaries were used in a perifusion system to study the influence of angiotensin II (AII) on GH release. In aggregates the peptide displayed both stimulatory and inhibitory effects on GH release, depending on the hormonal conditions of the culture medium and the age of the animal. When cultured in the absence of glucocorticoid, a modest but statistically significant stimulation was seen in aggregates from immature as well as adult animals. In aggregates from 5-day-old animals, dexamethasone (DEX) strongly enhanced the GH-releasing activity of AII in a dose-dependent way; in aggregates from 14- and 25-day-old rats, the same pattern was found, although the stimulatory action was weaker than the effect in 5-day-old rats. In aggregates from adult animals, the glucocorticoid established an inhibitory effect of AII on GH release, an effect seen with both low and high concentrations of DEX. These age- and DEX-dependent effects were not found for AII stimulation of PRL release. In the presence of DEX, AII also inhibited GRF-induced GH release in aggregates from adult animals, while it was synergistic with GRF in aggregates from developing animals. The effects of AII on GH release disappeared when aggregates were redispersed into single cells. However, in these single cell preparations AII strongly stimulated PRL release. In hemipituitaries from 1-, 5-, and 14-day-old animals, AII also stimulated GH release, but no effect was seen in hemipituitaries from 25-day-old and adult animals. These data indicate that AII has dual effects on GH release depending on the developmental stage of the animal and the hormonal environment. Furthermore, since no effect of AII was seen after redispersion of aggregates into single cells, both stimulatory and inhibitory effects seem to be based on an intercellular signaling system.