FXTAS presents with upregulation of the cytokines IL12 and TNFα.

INTRODUCTION: Fragile X Tremor and Ataxia Syndrome is a progressive neurodegenerative disorder that develops in some FMR1 premutation carriers. The objective of this study is to characterize how cytokine levels are altered in the FXTAS brain. METHODS: Fresh frozen cerebellar tissue from FXTAS cases and controls was homogenized and analyzed for 12 different cytokines using a commercially available ELISA panel. RESULTS: Relative to controls, FXTAS cases showed large and significant increases in the cytokines IL-12 and TNFα. There were large but non-significant increases in the levels of IL-2, IL-8, and IL-10 in FXTAS cases. The cytokines IL-1A, IL-1B, IL-4 IL-6, IL-17A, IFNγ, and GM-CSF were not different between FXTAS and control subjects. CONCLUSIONS: For the first time, we demonstrate an increase in the pro-inflammatory cytokines TNFα and IL-12 in the FXTAS brain, both of which are implicated in the pathogenesis of Multiple Sclerosis, another neurodegenerative disorder that predominantly consists of white matter disease.

Excretion of aqueous myelographic contrast media in animals undergoing a repeat myelogram.

The rate of elimination of contrast media may be a factor in side effects and complications of aqueous myelography. The authors studied the effect of a previous myelogram and arachnoiditis on the elimination of aqueous contrast media from the subarachnoid space. Serum and cisternal CSF iodine concentrations were measured after experimental myelography in subhuman primates. The transfer of the aqueous contrast media from CSF to serum was slowed and the circulation with the cerebrospinal fluid into the intracranial cisterns was increased by a previous myelogram or arachnoiditis.

Brain beta-endorphin and spinal-cord enkephalin concentrations in experimental arachnoiditis.

Arachnoiditis was produced experimentally in male albino ICR mice by intrathecal injection of meglumine iocarmate . A control group received intrathecal injection of an electrolyte solution resembling CSF. Eight weeks after injection, the brains and spinal cords were removed for brain beta-endorphin and spinal cord met-enkephalin measurement by radioimmunoassay, and the dural sacs were removed for histologic examination to confirm the presence or absence of arachnoiditis. Brain beta-endorphin content was significantly reduced and spinal-cord enkephalin concentration was significantly elevated in iocarmate-treated animals. The dura and arachnoid in the treated mice were thickened and infiltrated with lymphocytes. These studies indicate that arachnoiditis alters endogenous polypeptide concentrations.

[The activity of the rheumatic process in children with neurological forms of rheumatism]. / Ob aktivnosti revmaticheskogo protsessa pri nervnykh formakh revmatizma u detei

The authors studied the biochemical indices characterizing the activity of the rheumatic process in 121 patients with neurological forms of rheumatism and in 28 patients with neurological forms of rheumatism and in 28 patients with rheumocarditis without expressed changes on behalf of the CNS (all the children were from 5 to 15 years). Besides, a control group of 15 normal children of the same age were studied as well. In all patients with neurological signs of rheumatism and rheumocarditis without expressed changes of the nervous system there was a distinct increase in the content of seromucoids, hexosamines, uromucoids during all periods of examination. The diphenylamine index and cyalic acid content in the blood plasma was changed to a less degree. A full correlation between the biochemical changes and neurological state was not found. However, even in moderately expressed neurological signs the patients are in need of an observation on behalf of the rheumatologist and preventive therapy.

Nutritional supply to the cauda equina in lumbar adhesive arachnoiditis in rats.

Laminectomy-induced cauda equina adhesion has been proved by rat experiments and postoperative serial MRI in humans. A degenerative change of the cauda equina has been proved when cauda equina adhesion has been prolonged. Since it has not been reported how the nutritional supply is changed in such a condition, we evaluated the glucose supply to the adhered cauda equina in rats. Wistar rats were divided into the following three groups: the control group which received no operation, the laminectomy group which underwent L5-L6 laminectomy only, and the koalin group which received 5 mg of kaolin on the dorsal extradural space following L5-L6 laminectomy. Based on 3H-methyl-glucose uptake study, we analyzed (1) glucose transport from the intraneural vessels to the nerve tissue, and (2) glucose transport from the cerebrospinal fluid to the nerve tissue. We evaluated the relation between the severity of cauda equina adhesion and 3H uptake into the cauda equina. Cauda equina adhesion was observed in 2 of 12 rats in the control group, in 3 of 12 rats in the laminectomy group, and in 18 of 20 rats in the kaolin group. In the 3H-methyl-glucose uptake study, at 12 weeks the glucose transport to the cauda equina from the vessels increased by 44%, and that from the cerebrospinal fluid decreased by 64% in the kaolin group compared with the control group. In the condition of complete cauda equina adhesion, the glucose transport to the cauda equina from the vessels increased by 53% and that from the cerebrospinal fluid remarkably decreased by 72% compared with the normal cauda equina. Considering the greater nutritional importance of the cerebrospinal fluid in the cauda equina, it is most likely that the impairment of nutritional supply to adhered cauda equina may lead to eventual neural degeneration.

Catecholamines in experimental spinal cord lesions associated with spinal arachnoiditis.

Catecholamines in the spinal cord and cerebrospinal fluid of dogs with arachnoiditis induced by cisternal kaolin injection were measured by radioenzymatic assay. The levels of noradrenaline in the gray matter of the cervical cord and the cerebrospinal fluid were highest in 1st week (mean values, 127.8 ng/g and 856.0 pg/ml), whereas those in the gray matter of the thoracic and thoracolumbar cord increased to 175.0 and 210.0 ng/g in average respectively in 12th week. The increase in the level of noradrenaline in the gray matter seemed to be related with degenerative cord lesions in almost all segments, while most segments with cavitation indicated low noradrenaline level.

[Sulfalene kinetics in the blood and cerebrospinal fluid in arachnoiditis]. / Kinetika sul'falena v krovi i spinnomozgovoi zhidkosti bol'nykh arakhnoiditom.

The kinetics of free sulfalene in the blood and cerebrospinal fluid was studied in patients suffering from chronic arachnoiditis without marked inflammation signs on the part of arachnoid after a single intake of 2 g of the drug. It was found that administration of the drug in this dose once a week is quite justified and that sulfalene penetrates well in the cerebrospinal fluid. Upon administering large doses of the drug its absorption from the gastrointestinal tract declines. Sulfalene is eliminated from the cerebrospinal fluid more slowly than from the blood. High enough drug concentration is maintained in the cerebrospinal fluid for 7 days.