Contribution of transcranial magnetic stimulation in restless legs syndrome: pathophysiological insights and therapeutical approaches

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration.If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results.Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS.     

Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Load-induced proteoglycan orientation in bone tissuein vivo andin vitro

Summary Previous studies of Alcian blue-induced birefringence in adult avian cortical bone showed that a short period of intermittent loading rapidly produces an increased level of orientation of proteoglycans within the bone tissue. In the absence of further loading, this persists for over 24 hours. We have proposed that this phenomenon could provide a means for “capturing” the effects of transient strains, and so provide a persistent, constantly updated strain-related influence on osteocyte populations related to the bones' averaged recent strain history, in effect, a “strain memory” in bone tissue. In our present study, we use the Alcian blue-induced birefringence technique to demonstrate that proteoglycan orientation also occurs after intermittent loading of both cortical and cancellous mammalian bonein vivo andin vitro. We also show that the change in birefringence is proportional to the magnitude of the applied strain, and that the reorientation occurs rapidly, reaching a maximal value after only 50 loading cycles. Examination of electron micrographs of bone tissue after staining with cupromeronic blue allows direct visualization and quantification of the change in proteoglycan orientation produced by loading. This shows that intermittent loading is associated with a realignment of the proteoglycan protein cores, bringing them some 5 degrees closer to the direction of collagen fibrils in the bone matrix.     

Free plasma magnesium following glucose loading in healthy humans

The recognized existence of a circadian pattern in extracellular magnesium balance might mirror either an inherent rhythm in the homeostasis of this ion or dietary factors. Since in vitro insulin enhances cellular magnesium uptake, the circadian rhythm in extracellular magnesium metabolism might be modulated at least in part by carbohydrate intake. To assess this hypothesis, the effects of oral glucose loading on plasma total and ionized magnesium were investigted in lean healthy humans with a negative family history for essential hypertension and diabetes mellitus. Plasma total and ionized magnesium was similar before glucose loading and 30, 60, 90, 180, and 210 min thereafter. It is therefore concluded that in healthy humans the circadian pattern of extracellular magnesium is not modulated by the metabolic and hormonal mechanisms that adjust the concentration of glucose. Received: 5 February 1997 / Accepted in revised form: 14 April 1997     

战士体内VitB_1、VitB_2储备水平检测

选择南方热区某特种部队战士５２人，分两组分别口服５ｍｇＶｉｔＢ１和ＶｉｔＢ２，收集４ｈ尿液，用荧光法进行负荷试验。结果：ＶｉｔＢ１组，所测２９人中，１５人缺乏，９人不足，２人正常，３人充裕；ＶｉｔＢ２组，所测２３人中，１１人缺乏，１２人不足，反映该部队全年约５％的发病是由于ＶｉｔＢ１、ＶｉｔＢ２缺乏不足所致。其原因为膳食摄入不够     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

POTASSIUM ACCELERATES URINARY SODIUM EXCRETION DURING SALT LOADING WITHOUT STIMULATING ATRIAL NATRIURETIC POLYPEPTIDE SECRETION

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.     

Quadro-pulse stimulation is more effective than paired-pulse stimulation for plasticity induction of the human motor cortex

OBJECTIVE: Repetitive paired-pulse transcranial magnetic stimulation (TMS) at I-wave periodicity has been shown to induce a motor-evoked potential (MEP) facilitation. We hypothesized that a greater enhancement of motor cortical excitability is provoked by increasing the number of pulses per train beyond those by paired-pulse stimulation (PPS). METHODS: We explored motor cortical excitability changes induced by repetitive application of trains of four monophasic magnetic pulses (quadro-pulse stimulation: QPS) at 1.5-ms intervals, repeated every 5s over the motor cortex projecting to the hand muscles. The aftereffects of QPS were evaluated with MEPs to a single-pulse TMS, motor threshold (MT), and responses to brain-stem stimulation. These effects were compared to those after PPS. To evaluate the QPS safety, we also studied the spread of excitation and after discharge using surface electromyograms (EMGs) of hand and arm muscles. RESULTS: Sizes of MEPs from the hand muscle were enhanced for longer than 75min after QPS; they reverted to the baseline at 90min. Responses to brain-stem stimulation from the hand muscle and cortical MEPs from the forearm muscle were unchanged after QPS over the hand motor area. MT was unaffected by QPS. No spreads of excitation were detected after QPS. The appearance rate of after discharges during QPS was not different from that during sham stimulation. CONCLUSIONS: Results show that QPS can safely induce long-lasting, topographically specific enhancement of motor cortical excitability. SIGNIFICANCE: QPS is more effective than PPS for inducing motor cortical plasticity.     

Fracture frequency of all-ceramic crowns during dynamic loading in a chewing simulator using different loading and luting protocols

OBJECTIVE: The purpose of this laboratory study was to compare the frequency of failures (complete fractures or partial cracks) of molar crowns made of two different all-ceramic materials during dynamic loading in a chewing simulator, as well as the fracture load when subjected to static loading, in relation to different dynamic loading and luting protocols. METHODS: One hundred and forty-four molar crowns fabricated with IPS Empress or an experimental e.max Press material with high translucency (e.max Press Exp) were luted on CAD/CAM milled PMMA abutments (first lower molar, circular chamfer) either with Variolink or glass-ionomer cement (GIC). All crowns were loaded according to three different loading protocols (n=12 per group) and two force profiles (sinusoidal, rectangular) in a pneumatically driven chewing simulator with a steel stylus (? 8mm) and they underwent simultaneous thermocycling (5 degrees C/55 degrees C). After each phase the crowns were evaluated with regard to fractures or cracks. After dynamic testing, the crowns that did not fail were subjected to compression loading until complete fracture in a universal testing machine (UTM). As control groups, unloaded crowns were also subjected to a UTM. Survival statistics with log-rank tests were applied for the results of the dynamic loading, while ANOVA with post hoc Tukey B was used for the fracture load results and two-way ANOVA was carried out for logarithmically transformed data. Weibull statistics were calculated for pooled fracture load data of the dynamically loaded and control groups. RESULTS: In the 144 IPS Empress crowns, complete fractures were observed in 9 crowns and partial cracks in another 3 crowns. When the data was pooled, a statistically significant increase in fractures occurred when the sinusoidal force profile was applied compared to a rectangular force profile (log-rank, p<0.05). No fractures occurred in the e.max Press Exp crowns. The two-way ANOVA showed that the type of luting protocol used had the most significant effect on the fracture load of both materials. In conjunction with Empress, however, the luting material influenced the variability twice as much as in e.max Press Exp. There was no statistically significant difference in the fracture load of GIC-luted e.max Press Exp crowns and that of the Variolink luted Empress crowns. The force profile had a significant effect on the fracture load only of the Empress crowns but not of the e.max Press Exp crowns. Weibull statistics revealed a higher scattering of the data of dynamically loaded crowns compared to that of the control groups. CONCLUSIONS: For testing all-ceramic materials, dynamic loading is indispensable to draw valid conclusions on clinical performance of all-ceramic molar crowns. A sinusoidal profile is advisable, while a gradual increase of the force amplitude does not significantly affect the results.