Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

Effect of muscle mass on V(O(2)) kinetics at the onset of work.

The dependence of O(2) uptake (V(O(2))) kinetics on the muscle mass recruited under conditions when fiber and muscle recruitment patterns are similar following the onset of exercise has not been determined. We developed a motorized cycle ergometer that facilitated one-leg (1L) cycling in which the electromyographic (EMG) profile of the active muscles was not discernibly altered from that during two-leg (2L) cycling. Six subjects performed 1L and 2L exercise transitions from unloaded cycling to moderate [VT) exercise. The 1L condition yielded kinetics that was unchanged from the 2L condition [the phase 2 time constants (tau(1), in s) for 0.05; for >VT: 1L = 26.8 +/- 12.0; 2L = 27.8 +/- 16.1, P > 0.05]. The overall V(O(2)) kinetics (mean response time) was not significantly different for the two exercise conditions. However, the gain of the fast component (the amplitude/work rate) during the 1L exercise was significantly higher than that for the 2L exercise for both moderate and heavy work rates. The slow-component responses evident for heavy exercise were temporally and quantitatively unaffected by the 1L condition. These data demonstrate that, when leg muscle recruitment patterns are unchanged as assessed by EMG analysis, on-transient V(O(2)) kinetics for both moderate and heavy exercise are not dependent on the muscle mass recruited.

Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene.

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

Kinetics of oxygen uptake during supine and upright heavy exercise.

It is presently unclear how the fast and slow components of pulmonary oxygen uptake (VO(2)) kinetics would be altered by body posture during heavy exercise [i.e., above the lactate threshold (LT)]. Nine subjects performed transitions from unloaded cycling to work rates representing moderate (below the estimated LT) and heavy exercise (VO(2) equal to 50% of the difference between LT and peak VO(2)) under conditions of upright and supine positions. During moderate exercise, the steady-state increase in VO(2) was similar in the two positions, but VO(2) kinetics were slower in the supine position. During heavy exercise, the rate of adjustment of VO(2) to the 6-min value was also slower in the supine position but was characterized by a significant reduction in the amplitude of the fast component of VO(2), without a significant slowing of the phase 2 time constant. However, the amplitude of the slow component was significantly increased, such that the end-exercise VO(2) was the same in the two positions. The changes in VO(2) kinetics for the supine vs. upright position were paralleled by a blunted response of heart rate at 2 min into exercise during supine compared with upright heavy exercise. Thus the supine position was associated with not only a greater amplitude of the slow component for VO(2) but also, concomitantly, with a reduced amplitude of the fast component; this latter effect may be due, at least in part, to an attenuated early rise in heart rate in the supine position.

Electrophysiological features of central motor conduction in spinocerebellar atrophy type 1, type 2, and Machado-Joseph disease.

OBJECTIVES: To characterise electrophysiologically the central motor conduction of spinocerebellar atrophy type 1 (SCA1), type 2 (SCA2), and Machado-Joseph disease (MJD). METHODS: Motor evoked potentials (MEPs) triggered by transcranial magnetic stimulation (TMS) was used to investigate the functions of corticospinal tracts of 10 patients with SCA1, 10 with MJD, and eight with SCA2 in addition to pathological study of the spinal cord in a patient with SCA1. RESULTS: Central motor conduction time (CMCT) was extremely prolonged and the MEP threshold increased in all patients with SCA1, whereas both were normal in patients with SCA2 or MJD. The MEP size in MJD was larger than normal, but was normal in SCA1 and SCA2. A pathological investigation of the corticospinal tract of the spinal cord of a patient with SCA1 showed selective loss of large diameter fibres. CONCLUSIONS: SCA1, SCA2, and MJD differ in their pathophysiological features of the central motor tract and can be differentiated from each other by MEP values for the lower limb muscles, even though their neurological symptoms are sometimes similar.

Effect of increased muscle temperature on oxygen uptake kinetics during exercise.

To test whether increased muscle temperature (Tm) would improve O2 uptake (VO2) kinetics, seven men performed transitions from rest to a moderate work rate [below the estimated lactate threshold (LTest)] and a heavy work rate (VO2 = 50% of the difference between LTest and peak VO2) under conditions of normal Tm (N) and increased Tm (H), produced by wearing hot water-perfused pants before exercise. Quadriceps Tm was significantly higher in H, but rectal temperature was similar for the two conditions. There were no significant differences in the amplitudes of the fast component of VO2 or in the time constants of the on and off transients for moderate and heavy exercise between the two conditions. The increment in VO2 between the 3rd and 6th min of heavy exercise was slightly but significantly smaller for H than for N. These data suggest that elevated Tm before exercise onset, which would have been expected to increase O2 delivery and off-loading to the muscle, had no appreciable effect on the fast exponential component of VO2 kinetics (invariant time constant). These data further suggest that elevated Tm does not contribute to the slow component of VO2 during heavy exercise.

Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene.

The alpha-tocopherol transfer protein (alpha-TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of alpha-tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich-like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for alpha-TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich-like ataxia and retinitis pigmentosa caused by a defect in the alpha-TTP gene.

The effect of change in skin temperature due to evaporative cooling on sweating response during exercise.

The purpose of this study was to investigate whether there are any effects of skin temperature changes on sweating response in the first few minutes of mild exercise. Six healthy males performed a bicycle exercise at 100 W (50 rpm) for 30 min under an ambient temperature of 23 degrees C (40% RH). Esophageal temperature (Tes), mean skin temperature (Tsk), local skin temperature at the lower left scapula (Tsl), local sweating rate (Msw) and cutaneous blood flow by laser-Doppler flowmetry (LDF) were measured continuously. Although Tsl decreased markedly just after the onset of sweating, Tsk did not change. Msw did not increase constantly in the early stages of exercise, and there was a temporary interruption in the increase of Msw. This interruption in sweating was affected by the rate of change in Tsl rather than by the absolute value of Tsl, since there was a positive and significant correlation between the time of the interruption in the increase of Msw and the rate of decrease in Tsl (y = 6.47 x +0.04; r = 0.86, P < 0.05). The results suggest that sweating response in the early stages of exercise may be influenced by changes in local skin temperature due to evaporative cooling.

Effects of reduced muscle temperature on the oxygen uptake kinetics at the start of exercise.

The purpose of this study was to examine the effects of reduced muscle temperature (Tm) on gas exchange kinetics and haemodynamics at the start of exercise. Six male subjects performed moderate cycle exercise under reduced (C) and normal (N) Tm conditions. Tm and rectal temperature were significantly reduced by immersion in cold water (by 6.6 degrees C and 1.8 degrees C, respectively). The increases in oxygen uptake (Vo2) and oxygen pulse (Vo2/HR) during phase 1 (abrupt increase after the start of exercise) were significantly lower under C than under N. The time constant for O2 under C (36.0 +/- 7.7 (SD)s) was significantly greater than under N (27.5 +/- 4.4 s); however, the time constants of cardiac output under C (38.3 +/- 16.6 s) and N (33.7 +/- 18.5 s) were similar. These results suggest that the slower Vo2 on-response under reduced Tm conditions is caused by decreased O2 extraction in working muscle and/or by impairment of oxidative reactions by reduced muscle temperature.

X-linked spinal and bulbar muscular atrophy with myasthenic symptoms.

We describe a patient with X-linked spinal and bulbar muscular atrophy (X-SBMA) and myasthenic symptoms. The diagnosis of X-SBMA was established by demonstration of the increased number of CAG repeats in the androgen receptor gene on the X chromosome. This patient was characterized by the clinical symptoms of fatigability, decremental motor responses to repetitive nerve stimulation, and improvement of the myasthenic symptoms with oral administration of pyridostigmine. No serum antibody to acetylcholine receptor was detected. It is suggested that, in the process of chronic denervation and reinnervation of X-SBMA, reinnervated motor endplates may be associated with the defect of neuromuscular transmission.

Kinetics of oxygen uptake and cardiac output at onset of arm exercise.

Pulmonary oxygen uptake (V O2) kinetics at onset of exercise is reported to be slower for arm than for leg exercise. This could be attributed to reduced cardiac output (Q) or reduced arteriovenous O2 content difference or both. To test this, V O2 mean tissue oxygen consumption (V O2T) and Q kinetics in arm cranking were compared with corresponding values found in leg cycling. The increase in V O2 during phase 1 (abrupt increase after onset of exercise) was less in arm than in leg exercise, suggesting that immediate Q adjustments to arm exercise were less pronounced. Mean response times (MRT, the relative rates at which a steady state was attained) for V O2, V O2T, and Q were prolonged during arm exercise. The MRT of VO 2 in arm exercise at a given blood lactate increase was higher than in leg exercise. The delayed V O2 kinetics in arm exercise might be due to delayed Q kinetics and higher anaerobic glycolysis occurring early during arm exercise.

Pulmonary oxygen uptake kinetics in nonsteady state.

The body does not always achieve a steady state and is more often kept in a nonsteady state. It is important not only in terms of physiological anthropology but also in its application to rehabilitation and training to clarify whether oxygen transport or utilization is the limiting factor in oxygen uptake in the nonsteady state. Hypotheses concerning the limiting factor in oxygen uptake have their own rationales, and it is still controversial as to which is actually responsible. The limiting factor in oxygen uptake may vary according to exercise conditions. Under certain conditions, oxygen transport would be responsible for limiting the oxygen uptake, and under others, oxygen utilization or both oxygen transport and utilization would be responsible. These conditions differ according to the type of exercise (e.g. step exercise vs. cycling, leg vs. arm exercise, and dynamic vs. static exercise), posture, recruited muscle fibers, and other experimental conditions. Considering that oxygen uptake is regulated by coupling among respiration, circulation, and metabolism, it may be possible that interactions among these functions vary in a complicated manner according to exercise conditions, which may require a different limiting factor in regulating oxygen uptake.

The effect of diurnal variation on the regional differences in sweating and skin blood flow during exercise.

The aim of the present study was to examine changes in the control of heat-dissipation responses to exercise associated with the diurnal variation in core temperature from the viewpoint of the regional response patterns. We studied seven men during exercise on a cycle ergometer at 100 W for 40 min at 25 degrees C at 0630 (morning) 1630 (evening) hours on 2 separate days. Oesophageal temperature (T(oes)), local skin temperature, local sweating rate (msw) on the forehead, back, forearm and thigh, and skin blood flow by laser Doppler flowmeter (LDF) on the back and forearm were measured continuously. The T(oes) at rest was significantly higher in the evening than in the morning, the difference averaging approximately 0.4 degrees C (P < 0.05). The T(oes) thresholds for each site in msw and that for back in LDF were significantly different between the two times of day (P < 0.05). The change in T(oes) thresholds for sweating and vasodilatation for morning and evening were similar to T(oes) at rest. Although msw on the forehead was significantly higher in the morning than in the evening, msw on the back was significantly higher in the evening than in the morning (P < 0.05). Total local sweating rate (msw,tot) for each site during exercise was significantly higher on the forehead than on the forearm in the morning, and on the back than on the forearm in the evening, respectively (P < 0.05). The results would suggest that the diurnal variation of heat-dissipation responses to exercise is influenced not only by a central controlling mechanism but also by changes in the regional differences.