Wallerian degeneration was studied in the phrenic or sciatic nerves of mice following transplantation into Millipore diffusion chambers of 0.22 micron pore size which were implanted in the peritoneal cavity and kept for up to eight weeks. This method positively eliminates the access of nonresident cells to the tissue, at the same time providing proper conditions for tissue survival. Such nerves showed no proliferation of Schwann cells and no evidence for their active role in the removal or digestion of myelin. Schwann cells rejected their sheaths and the latter persisted for weeks, leading either to sheath distension (the sheath becoming wider and thinner) or to collapse (the sheath becoming thicker, collapsing upon the empty axis cylinder). The outer envelope of Schwann cytoplasm separated into pseudopodia rich in microtubules. Sheath rejection led to a slow decay of the myelin in the absence of active phagocytosis. There was profuse fibroblastic proliferation from the epineurium and perineurium, from which cells migrated into the chambers developing fatty change. No evidence was found to link the fatty change in fibroblasts to sheath decay. Diffusion chambers of 5.0 micron pore size were invaded by leukocytes and monocytes. Nerves kept in such chambers showed active phagocytosis of myelin leading to its removal, similar to Wallerian degeneration in situ. Phagocytes were shown to attack selectively the rejected myelin sheaths, distinguishing the latter from the surviving Schwann cells, even though both structures derive from the same cell. The activity of phagocytes in digesting myelin was mediated by a signal which diminished in intensity with time; there was very little active phagocytosis of myelin in nerves that had been predegenerated in 0.22 micron pore chambers. Various modifications of the experiment, including studies with co-cultured peritoneal macrophages or bone marrow, indicate a need for additional activating factors to induce myelin phagocytosis.

Objectives/Hypothesis: The study investigates the effect of local injections of botulinum toxin type A (Botox) into the major salivary glands of the head in various states of hypersalivation. In particular, we studied pathological states with permanent as well as passing hypersalivation disorders and present new indications for local application of botulinum toxin to the salivary glands. Study Design: Retrospective clinical investigation. Methods: A total of 55 to 65 units of Botox were injected under sonographic control into the left and right parotid and submandibular glands of four patients with hypersalivation resulting from head and neck carcinoma, tracheostomy, and "idiopathic" hypersalivation disorder. At defined time intervals following injection, flow rate, total protein and immunoglobulin A content, and the enzymatic activities of amylase, acid phosphatase, and kallikrein were determined in the saliva. The patients were clinically examined to assess the severity of their symptoms, including sonographic control of the major salivary glands. Results: All four patients reported distinct improvement of their symptoms within 1 week after injection. Salivary flow rate had considerably dropped, whereas the concentrations of the salivary components were much increased. Sonography did not reveal any changes of the salivary gland parenchyma. Therapeutic side effects were absent. Conclusions: Treatment of hypersalivation by local injections of Botox into the salivary glands of the head is a reliable and efficient therapy without side effects for certain otolaryngological diseases, especially if injections are performed under sonographic control. Extension of this therapeutic concept to other indications is suggested.

Matrix metalloproteinase-9 (MMP-9) and its specific inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), were analysed by enzyme-linked immunosorbent assay (ELISA) and by zymography in serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS). In contrast to patients with inflammatory diseases, MMP-9 levels were not elevated in CSF of ALS patients. In serum, however, compared to healthy donors, MMP-9 was significantly (p = 0.0003) increased up to levels as high as those of viral meningoencephalitis (VM) or bacterial meningitis (BM) patients. MMP-9 levels remained elevated during long-term observation of ALS patients. In the absence of an inflammatory response, the results indicate that the increase of MMP-9 in serum of ALS patients might be caused by upregulation of MMP-9 in denervated muscles or in degenerating peripheral nerves following motor neurone loss.

We sought to determine the activity of inhibiting and facilitating cortical circuits in areas surrounding a hand muscle motor representation in focal dystonia and in controls. In 15 patients with hand dystonia, 16 patients with blepharospasm, and age-matched controls, we applied suprathreshold transcranial magnetic stimuli with a figure-eight coil over the optimal representation of the relaxed abductor digiti minimi muscle of the dominant hand. Additional conditioning stimuli were given through a second figure-eight coil that was held either above the test coil or 2 cm or 4 cm apart in the anterior, posterior, lateral, or medial direction. We measured intracortical excitability in each of the nine positions of the conditioning coil. Intracortical inhibition was reduced in both patient groups at all conditioning coil positions. With both coils centered, the intracortical facilitation did not differ between patients and controls. After shifting the conditioning coil, the intracortical facilitation tended to be less diminished in patients than in controls, this difference between patients and controls was significant for the anterior, posterior, and medial 4-cm conditioning coil shift. Our results demonstrate decreased intracortical inhibition in the cortical hand muscle representation not only in patients with hand dystonia, but also in patients with blepharospasm. In addition, our findings in both patient groups show a trend toward a relatively increased intracortical facilitation in surrounding motor areas.

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