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We report on, 1 36-year-old man of Swedish descent who had teenage onset of a progressive disorder with features of Charcot-Marie-Tooth disease (CMT) and cerebellar ataxia. Cognition was normal. The polyneuropathy was of axonal type. Magnetic resonance imaging of his brain showed cerebellar atrophy. Cerebellar atrophy and CMT has been reported in one French-Canadian family and in several Japanese families, Mental impairment was a feature of the disorder in the Japanese families. A disorder with CMT and cerebellar atrophy is rare in the western world.

Traumatic spinal cord injury is followed by infiltration of leukocytes, influenced by endothelial adhesion molecules such as ICAM-1 and P-selectin. In order to evaluate the pathogenetical role of these molecules, wild-type mice and mice lacking ICAM-1 and P-selectin were subjected to an experimental spinal cord compression of two degrees of severity. Hind limb motor function decreased after injury in all animals but the groups of injured ICAM-1/P-selectin knockout animals had a better functional outcome during the entire observation period of 14 days. This difference was statistically significant on day 1. Our results indicate that adhesion molecules influence the functional outcome after spinal cord injury in a negative way and may be a target for future therapy of neurotrauma.

beta-Amyloid precursor protein immunoreactivity (APP) was studied after a mild compression contusion trauma to rat parietal cortex. Neurones in the periphery of the cortical lesion, i.e. tissue subjected to shear stress, showed markedly reduced immunoreactivity 1 and 3 days after injury. Numerous axons in the ipsilateral subcortical white matter and thalamus became immunoreactive. At 21 days, small rounded profiles appeared in the neuropil of the damaged cortex and in the thalamus. Thus, traumatic brain injury appears to induce several types of APP changes. The accumulation in neuronal processes is probably caused by disturbed axonal transport induced by trauma. Since APP is assumed to be excitoprotective, modulating intracellular Ca2+ responses, the decreased immunoreactivity noticed in the periphery of the lesion may render the neurones in this region more vulnerable to secondary injury mechanisms.

Background: The antinociceptive effects of somatostatin (SST) after intrathecal administration in rats and dogs and analgesic effects after intrathecal or epidural administration in humans were described previously. In this study, we seek to determine the efficacy of SST in cancer pain management and its potential neurotoxicity., Methods: Eight patients with intractable cancer pain were studied. Pain intensity was assessed by patients on a four-grade scale (severe, moderate, mild, none). Additional analgesic drug requirements before and concomitant with SST treatment were used to evaluate the pain relief and assessed on a four-grade scale (poor, fair, good, or excellent). Spinal cords of five patients were autopsied., Results: The mean duration of SST treatment was 11.3 days. The mean daily dose was 1,252 micrograms (range 250-3,000 micrograms). In six patients the pain relief was rated "excellent" or "good" and in two patients it was assessed "poor" or "fair". None of the patients demonstrated any evidence of neurologic deficit related to the SST treatment. At autopsy, two patients exhibited a moderate demyelination of some spinal dorsal roots and one patient also had a slight demyelination of the dorsal columns., Conclusions: SST administered intrathecally and epidurally was an effective analgesic in patients with terminal cancer. Because the described neuropathologic changes could also be cancer-related or result from chemotherapy or radiation therapy we suggest that further judicious use of SST is justified in this category of patients, if their pain remains unrelieved despite large doses of opioid analgesics.

The expression of endothelin-1-like immunoreactivity in astrocytes of the human brain was investigated by the avidin-biotin-peroxidase complex method in post mortem material. A marked immunoreaction was present in reactive astrocytes around infarcts, lacunes, traumatic injuries, the lesions of progressive multifocal leuco-encephalopathy and in the cerebral cortex and white matter of Alzheimer's disease. The brains of patients who had neither history nor signs of cerebral disease exhibited only occasional immunoreactive astrocytes. A hypothesis is presented that endothelin-1 may be released from reactive astrocytes in many organic diseases of the human brain with considerable pathogenic consequences. It is known from experimental investigations that endothelin-1 may for instance cause severe vasoconstriction resulting in cell injury and that it may act as a growth factor for glial cells.

A new method was developed whereby close comparisons can be made between components of a computed tomography (CT) image and neuropathological findings. This was achieved by a combination of intravital (terminal) CT, postmortem CT, and whole brain sectioning of formalin-fixed tissue. The method was applied in seven cases of malignant supratentorial astrocytic gliomas (Kernohan Grades III and IV) and in one case of thalamic ependymoma. The glioblastoma-like parts of the astrocytic gliomas were usually correctly delineated by postcontrast CT, although there were exceptions to this rule. Tumor components consisting of diffusely growing malignant astrocytoma were difficult or impossible to delineate by CT. Necrotic areas within the tumors were accurately outlined by postcontrast CT. Peritumoral edema was correctly delineated by CT, but growth of diffuse astrocytoma or the presence of astrocytic gliosis within this edematous area seems difficult or impossible to evaluate by current CT techniques.

In four of six patients with methanol intoxication, computed tomography (CT) showed necrotic changes in the area of the putamina. Hemorrhages were also seen in some cases. There was a clear relationship between the severity of the clinical symptoms and the CT findings, indicating the potential of CT for prognosis and possible therapy guidance.

Selective nerve cell degeneration was induced in the trigeminal ganglion of the mouse by injecting doxorubicin (Adriamycin) around intact sensory nerve terminals of the head. The drug apparently reached the neurons by retrograde axonal transport after its uptake in nerve branches. A direct fluorescence microscopic method revealed that the compound accumulated in the neurons. Electronmicroscopy showed degeneration of these cells, beginning in the nucleolus and the nucleus. Doxorubicin injected around sensory nerve terminals appears to be a useful compound for selective destruction of mouse sensory neurons. Retrograde axonal transport of neurotoxic compounds is probably an important pathogenetic mechanism in certain forms of intoxication which give rise to lesions in the nervous system.

Clonidine has been reported to produce analgesia in man after epidural and intrathecal administration. In the present investigation the alpha 2-adrenoceptor agonists clonidine and guanfacine were tested to evaluate their potential spinal neurotoxic effects. Rats were injected daily for 14 consecutive days via catheters implanted in the intrathecal space. Clonidine was administered at a dose of 1.63 micrograms or 16.3 micrograms, and guanfacine at 16.3 or 75 micrograms. After perfusion with a buffered 3% glutaraldehyde solution, the spinal cords and nerve roots were taken for neuropathological analysis using light and electron microscopy. Compared to animals injected with 0.9% saline, clonidine and guanfacine gave rise to no detectable neurotoxic changes in the doses employed. An additional group of rats had intrathecal injections of a substance P-antagonist (D-Arg1, D-Trp7,9, Leu11)-substance P (spantide) with known neurotoxic effect as a test of the histotechnical methods used. Degenerative lesions, with a preference for the ventral horns, were consistently present in the grey matter of the cord in these animals. We conclude that the absence of detectable changes in rats given clonidine and guanfacine is probably a real expression of the low degree of toxicity for these compounds on rat spinal cord and nerve roots and not an artifact of the sensitivity of the histotechniques applied. The doses of clonidine administered were considerably greater than those reported to produce clinical greater than those reported to produce clinical analgesia.