Decrease In Motor Nerve Conduction Velocity Research Articles

Role of Parathyroid Hormone in the Decreased Motor Nerve Conduction Velocity of Chronic Renal Failure

Certain data support the notion that chronic exposure to excess parathyroid hormone (PTH) is associated with decreased motor nerve conduction velocity, while other studies failed to confirm such an effect. Also, chronic renal failure of 4 months duration in dogs did not elicit changes in MNCV or calcium content of nerve. These discrepancies may be due to differences in other metabolic parameters, such as degree of uremia, serum levels of calcium, phosphorus, or magnesium, and acid-base parameters, or in duration of chronic renal failure. To examine the effect of PTH on peripheral nerve function in renal failure in a more defined biochemical setting, we studied the changes in MNCV and nerve calcium content in dogs with and without excess PTH and with prolonged and similar duration of chronic renal failure (57 +/- 1.7 weeks) and comparable biochemical parameters. Dogs with chronic renal failure displayed a significant (P less than 0.01) decrease in MNCV (before renal failure, 65 +/- 1.5 m/sec; after renal failure, 49 +/- 3.5 m/sec) and marked elevation in calcium content of peripheral nerve (444 +/- 45 mg/kg dry wt). These derangements were not observed in parathyroidectomized chronic renal failure animals; MNCV before renal failure was 66 +/- 1.5 m/sec and after renal failure was 65 +/- 1.5 m/sec, and nerve calcium content after renal failure was 229 +/- 3 mg/kg dry wt. Also, parathyroidectomy of three dogs with preexisting chronic renal failure of 52 weeks was associated with reversal of the abnormalities in MNCV and calcium content of nerve despite an additional period of renal failure of 52 weeks in two of the dogs and 40 weeks in the third. Our data are consistent with the proposition that excess PTH plays a major role in the genesis of peripheral nerve dysfunction in chronic renal failure. This adverse effect of the hormone is most likely mediated by the PTH-induced accumulation of calcium in peripheral nerve.

Zinc status and peripheral nerve function in guinea pigs

Guinea pigs fed a diet low in zinc develop clinical signs of apparent neurological origin. The signs include abnormal posture and locomotion as well as hypersensitivity to touch. In this study, electrophysiological and biochemical measurements were made on sciatic nerves from zinc-deficient and repleted animals as well as on controls fed either ad libitum or restricted to maintain weight comparable to those consuming the deficient diet. Both in vivo and in vitro measurements showed decreased motor nerve conduction velocity (NCV) in nerves of deficient animals. A longitudinal study showed excellent correlation of NCV and severity of clinical signs. Nerves from zinc-deficient guinea pigs had decreased Na,K-ATPase activity, but the number of sodium channels, as determined by saxitoxin binding, was not affected. It was concluded that the clinical signs of neuropathy in zinc deficiency are associated with impaired NCV and decreased Na,K-ATPase activity of peripheral nerves. The zinc-deficient guinea pig provides a useful model to study the biochemical defect in a peripheral neuropathy.

In vivo activities of aldose reductase inhibitors having a 1-(arylsulfonyl)hydantoin structure

Two potent aldose reductase inhibitors, 1-[(2,5-dichlorophenyl)sulfonyl]hydantoin (Di-Cl-PSH) and 1-[β-naphthyl)sulfonyl]hydantoin (β-NSH), were tested for usefulness in the treatment of diabetic and galactosemic complications in animal experiments. Both drugs were effective for the treatment of diabetic neuropathy characterized by decreased motor nerve conduction velocity, that is, slowing of tail and sciatic-tibial motor nerve conduction velocities in streptozocin-induced diabetic rats was prevented during 3 weeks by intubating Di-Cl-PSH or β-NSH at 50 mg/kg/day. Lenticular vacuole formation in rats fed a 30% galactose diet was blocked completely for at least 2 weeks by oral administration of Di-Cl-PSH or β-NSH at both 30 and 100 mg/kg/day, whereas all of the eyes of vehicle-treated rats showed vacuole formation by day 4 on the galactose diet. The ED 50 values of Di-Cl-PSH and β-NSH for inhibition of sorbitol accumulation in the sciatic nerve and lens of streptozocin-induced diabetic rats were also estimated; the values of Di-Cl-PSH and β-NSH were 1.1 and 3.4 mg/kg/day, respectively, for inhibition in the sciatic nerve and 4.8 and 16.0 mg/kg/day, respectively, for that in the lens. This study indicates that Di-Cl-PSH and β-NSH have high potential for future clinical use as aldose reductase inhibitors.

Effect of Prostaglandin E1 Analogue TFC 612 on Diabetic Neuropathy in Streptozocin-Induced Diabetic Rats Comparison With Aldose Reductase Inhibitor ONO 2235

The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.

A case of late variant form of infantile krabbe disease with a partial deficiency of galactocerebrosidase

A female was diagnosed as a late variant form of infantile Krabbe disease at 1 year and 3 months because of the late onset of regressive clinical course, decreased motor nerve conduction velocities, high cerebrospinal protein concentration and partial deficiency of galactocerebrosidase (15.6%) in the cultured skin fibroblasts. She showed normal development until 8 months when she lost her ability of sitting alone after febrile infection, and died accidentally at 2 years and 4 months. A considerable residual enzyme activity may correlate to the milder clinical course of this case.

Altered blood-nerve barrier permeability to small molecules in experimental diabetes mellitus.

Permeability-surface area products (PA) were determined with a quantitative in vivo injection technique at the blood-nerve barrier of tibial nerve, and at the blood-brain barrier, in control and streptozotocin-induced diabetic rats. The PA product for [14C]mannitol at the blood-nerve barrier was increased by 100% in diabetic animals, 3.12 +/- 0.15 X 10(-5) ml X s-1 X g-1, compared with controls, 1.61 +/- 0.10 X 10(-5) ml X s-1 X g-1. In contrast, PA for [14C]mannitol at the blood-brain barrier was unaltered in the diabetic animals. Following intravenous injection, no leakage of microperoxidase across the perineurium or endoneurial vessels of diabetic rats could be demonstrated by morphological techniques. Nerve blood-space, as determined with intravenous [3H]inulin, and blood-nerve barrier surface area as determined by morphometric methods, did not differ in diabetic when compared to control animals. Thus, the calculated permeability coefficient for [14C]mannitol at the blood-nerve barrier was about 100% greater in diabetic nerve compared to control nerves. The increased permeability was accompanied by a 7% increase in nerve-water content and a 32% decrease in motor-nerve conduction velocity. The results demonstrate a specific vulnerability of nerve as compared to brain in an animal model of diabetes mellitus. Chronically altered permeability to small water-soluble molecules reduces the protective effect of salt impermeability at the blood-nerve barrier against nerve edema, and may be an important pathogenic mechanism in diabetic neuropathy.

Sensitive indicators of inorganic mercury toxicity.

Forty-two workers from a chemical plant producing inorganic mercury compounds were evaluated for neurologic, nephrotic, and ophthalmologic toxicity. Despite elevated blood and urinary mercury levels, routine clinical testing such as physical examination, blood chemistries, and urinalysis were generally normal. These findings from the routine examination are in contrast to the complaints of neuropsychological symptoms, elevated urinary n-acetyl B-D-glucosaminidase (NAG) levels, decreased motor nerve conduction velocities, and the presence of lenticular opacities on slit-lamp examination that were found, when organ systems known to be affected by mercury were targeted. More sensitive but objective indicators of toxicity need to be included in routine medical screening so as to help diagnose the etiology of neuropsychological symptoms and prevent long-term sequelae in workers exposed to mercury.

Experimental porphyric neuropathy: a preliminary report.

An experimental model for the study of porphyric neuropathy is presented. Injection of either tetraphenyl-porphinesulfonate (TPPS), hematoporphyrin derivative (HpD), or delta-amino-levulinic acid (ALA) into mice resulted in markedly decreased motor nerve conduction velocity (MNCV). THe MNCV returned to normal within one week following the injection of large doses of ALA, and within three weeks following the injection of close to lethal doses of HpD, but there was no recovery of nerve function within 50 days following injection of substantially smaller doses of TPPS. Ultrastructural examination of motor nerves at various times following TPPS injection revealed the gradual development of structural abnormalities. Ultrastructural examination of the same nerves after a single dose of either ALA or HpD failed to demonstrate any abnormalities. The present observations call for precaution as to the use of TPPS as photosensitizer in human cancer treatment.

1150 A PROGRESSIVE NEUROLOGIC SYNDROME IN SIX CHILDREN WITH CHRONIC LIVER DISEASE AND ALPHA-TOCOPHEROL (αT) DEFICIENCY

We have followed six children with prolonged obstructive jaundice of infancy (biliary atresia) who are now 6 yrs to 12 y/o. Two can no longer walk unaided. A striking paresis of vertical gaze and wide-based gait developed in two children. Serial neurological exams revealed marked hyporeflexia (6/6) and decreased proprioception in the four cooperative patients. However, touch (4/6) and pin (5/6) sensation was intact. 2 of 3 cases tested had decreased motor nerve conduction velocities but normal electromyograms. Psychometric testing and school performance indicated a wide range of intellectual function.Serum vitamin E levels were low (range <0.1-0.8 mg/dl; mean 0.2 mg/dl; normal 0.8-1.2 mg/dl) in all cases despite long-term oral administration of ≥T-polyethylene glycol-1000-succinate.Post-mortem neuropathologic and morphometric findings in one child with biliary atresia whose serum vitamin E level was 0.1 mg/dl were similar to those observed by one of us (J.S.N.) in chronic vitamin E deficient monkeys and rats with focal neuronal loss in dorsal root ganglia, degeneration of axons in Clarke's column and in the fasciculus gracilis and cuneatus, and a decrease in large myelinated axons in the sural nerve. Further studies are needed to elucidate what role decreased vitamin E plays in this syndrome.

Peripheral neuropathy in mutant diabetic mouse [C57BL/Ks (db/db)

A new animal model for the study of diabetic neuropathy is presented. The homozygote (db/db) of the mouse strain C57BL/Ks shows severe diabetes with longstanding hyperglycemia. Electrophysiological studies showed severely decreased motor nerve conduction velocity. Morphometric examination of sensory and motor nerves at different levels revealed absence of large myelinated fibers, with morphological features indicative of axonal atrophy.

Triethyltin Sulfate-Induced Neuropathy in Rats

Adult rats given high orally administered doses of triethyltin (TET) sulfate lost weight, developed hind limb wasting, and became paraplegic or quadriplegic within three weeks of intoxication. A 33% reduction in the motor nerve conduction velocity (MNCV) of the sciatic nerve in the absence of significant demyelination was observed. There was observed, however, intramyelinic edema formation and an increased number of axonal neurofilaments and neurotubules; changes that paralleled the decrease in MNCV during the period of intoxication. Although the animals became asymptomatic and the MNCV normalized within two to three weeks of discontinuing the TET intoxication, the intramyelinic vacuoles and the increased numbers of neurofilaments and neurotubules persisted.

Erythrocyte transketolase activity in dialysis patients with neuropathy

Erythrocyte transketolase activity (ETKA) has been studied in a group of uremic patients exhibiting neuropathy on clinical grounds and demonstrating decreased motor nerve conduction velocities in the right peroneal nerve. Single or multiple hemodialyses did not affect ETKA in these patients nor did uremic plasma have any inhibitory effect on ETKA in erythrocytes from nonuremic patients. The enzyme activity actually tended to be greater than normal in uremic patients when related to the erythrocyte count. These results indicate that ETKA is unrelated to the peripheral neuropathy found in uremia.