Intrathecal immunoglobulin synthesis in multiple sclerosis: effect of corticosteroids and azathioprine.

The objective of this study was to investigate quantitative and qualitative intrathecal IgG synthesis in 51 patients with clinically definite multiple sclerosis, taking previous immunosuppressive treatment into account. Four formulae were used to assess quantitative synthesis. Oligoclonal bands (OB) were investigated using isoelectric focusing (IEF) and silver staining. Abnormal quantitative values were detected in 42 (82%) patients, whereas OB occurred in 38 (74.5%) patients. Steroid therapy lowered quantitative synthesis in 6 out of 9 patients when given within 3 months before lumbar puncture (LP). Untreated patients with OB systematically had abnormal formulae. Patients treated with corticosteroids 10 or more months prior to LP had abnormal formulae. This fact suggests a transient depressor effect of steroids on quantitative synthesis. OB were present in patients recently treated with corticosteroids. Quantitative synthesis was higher in patients with OB than in those without OB. Azathioprine treatment did not significantly lower quantitative synthesis. We conclude that for routine purposes evaluation of intrathecal immunoglobulin synthesis could begin by performing quantitative tests. IEF seems to be mandatory for patients with normal formulae who have recently been treated with steroids.     

Regulation of Schwann cell numbers in tellurium-induced neuropathy: apoptosis, supernumerary cells and internodal shortening

We have used an experimental model of tellurium(Te)-induced demyelinating neuropathy in the rat to study cellular mechanisms involved in regulating Schwann cell (SC) numbers during remyelination. Starting at postnatal day 21, weaned rats were fed a diet containing 1.1% elemental Te. Following 7 days of Te treatment and at several time points of post-tellurium treatment (PTe), the animals were processed for ultrastructural analysis, SC nuclei quantification and teased fibre preparations. It is well-established that Te induces a transient demyelinating/remyelinating sequence in sciatic nerves. The loss of the myelin sheath in this neuropathy produces active proliferation and overproduction of immature SCs. By electron microscopy analysis most mitotic SCs were located along demyelinated segments. Quantitative determination of SC nuclei per transverse section of sciatic nerve revealed a dramatic increase of SCs at 2 days PTe relative to control nerves. The number of SC nuclei then decreased progressively during the long-term period of recovery studied (330 days PTe). In Te-treated rats, SCs undergoing cell death were regularly found within the nerve fibre compartment, especially on demyelinated segments. Dying cells exhibited morphological features of apoptosis and appeared enclosed by lamellar processes of adjacent healthy SCs in extracellular compartments. Both healthy immature SCs and endoneurial macrophages were involved in the phagocytosis of apoptotic SCs. Particularly during remyelination, supernumerary endoneurial SCs were observed surrounding myelinated fibres. These cells progressively became atrophic with a morphological phenotype similar so that of “onion bulb” cells. On the other hand, teased fibre measurements revealed a remarkable permanent internodal shortening in remyelinated fibres from Te-treated sciatic nerves. These results indicate that a portion of redundant immature SCs are susceptible to elimination by apoptosis. However, other distinct biological mechanisms such as the persistence of supernumerary SCs in the endoneurium and the shortening of internodal lengths are also involved in regulating SC numbers during the remyelination stage. Received: 26 May 1997 / Revised: 12 September 1997 / Accepted: 1 October 1997     

Tenth Meeting of the European Neurological Society 18–22 June, 2000, Jerusalem,Israël

Journal of Neurology -     

Posterior column ataxia and retinitis pigmentosa: a distinct clinical and genetic disorder.

Autosomal recessive posterior column ataxia and retinitis pigmentosa (PCARP) is a movement disorder that was genetically mapped to a disease locus (AXPC1) on chromosome 1q32-q31 in an inbred population of Dutch-German ancestry in the continental United States. We performed genetic linkage analysis and haplotype reconstruction on a different family from Spain with an identical phenotype to determine if the neurologic signs of an early-onset ataxia, retinitis pigmentosa, and a sensory neuropathy also mapped to the AXPC1 locus. The disease phenotype was linked in the candidate interval with a maximum lod score of 3.56 at a recombination fraction of 0.0 for locus D1S414. Haplotypes were discordant and suggested that the disease mutation arose independently from at least two populations. These results refine the classification of early-onset ataxia, abrogate a founder effect for this recessive disorder, and provide evidence that PCARP is a distinct, homogeneous, clinical, and genetic disorder.