Stress lactate in mitochondrial myopathy under constant, unadjusted workload

As it is under debate if determination of lactate during cycle ergometry (lactate stress testing, LST) under a continuous, unadjusted, low workload is a valuable diagnostic tool for mitochondrial myopathy (MMP), the present study aimed to investigate how sensitive the LST is in a large cohort of patients with indications for MMP (MMP patients). Serum lactate was determined once before, three times during, and once after a 15-min, constant 30 W-workload on a bicycle ergometer in 115 healthy controls, 166 patients with neurological disorders other than MMP, and 291 MMP patients. Serum lactate's upper reference limit at rest, 5, 10, 15 min after starting, and 15 min after finishing the exercise was 2.0, 2.0, 2.1, 2.0 and 1.7 mmol/l, respectively. Resting lactate was increased in 75 MMP patients (26%). The specificity of resting lactate determination was 84%. The sensitivity of the LST was 66% and the specificity 84%. Among the 192 MMP patients with abnormal LST, 120 (63%) had a normal resting lactate. The LST is abnormal in two thirds of the MMP patients. The sensitivity of the LST is higher than that of resting lactate determination. The LST is a simple and cheap but effective and reliable screening method for detecting the impaired oxidative metabolism in MMP.     

Lactate-stress testing in 54 patients with mitochondriopathy

Since there are only few data available about the lactate stress test in a group of patients with mitochondrial myopathy, we investigated the sensitivity of this test in a larger cohort of such patients. Serum lactate was determined before, during and after a 15 minute, constant 30 W workload on a bicycle ergometer in 47 controls, aged 15 to 72 years and 54 patients with mitochondrial myopathy, aged 15 to 74 years. Lactate’s upper reference limits at rest, 5, 10, 15 minutes after starting, and 15 minutes after finishing the exercise were 2.0, 2.1, 2.1, 2.1 and 1.8 mmol/l respectively. The sensitivity of the lactate-stress test was 69%. The lactate-stress test complements electrophysiological and bioptical findings and proved to be helpful in diagnosing mitochondrial myopathy. Received: 2 March 1999 / Accepted: 25 October 1999     

LACTATE STRESS TESTING IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS

Mitochondrial dysfunction is frequently observed in ALS. Mitochondrial dysfunction may result in increased serum lactate at rest or low levels of exercise, being used for diagnostic purposes. The study investigated if resting-lactate-determination is superior to lactate-stress-testing (LST) in demonstrating mitochondrial dysfunction in ALS. Included were 15 ALS patients, 4 women, 11 men, aged 37–72. Severity of the disease was assessed by the Norris-score. The control group comprised 66 healthy subjects, 40 women, 26 men, aged 36–76. Serum lactate was determined before, three times during, and once after a constant workload with 30 W on a bicycle ergometer. According to the EIEscorial criteria 8 patients had definite, 4 probable, 3 possible ALS. Resting lactate was increased in 2 patients, 1 with definite and 1 with possible ALS. The LST was abnormal in 5 patients with definite, 1 with probable and 1 with possible ALS. The mean Norris-score was 67.8 in patients with abnormal LST and 74.6 in patients with normal LST. In conclusion, the LST is more suitable than resting-lactate-determination in demonstrating mitochondrial dysfunction in ALS. The LST suggests mitochondrial dysfunction in half of the ALS patients. Mitochondrial dysfunction in ALS is related to the clinical severity of the disease.     

Lactate stress testing in sporadic amyotrophic lateral sclerosis

Mitochondrial dysfunction is frequently observed in ALS. Mitochondrial dysfunction may result in increased serum lactate at rest or low levels of exercise, being used for diagnostic purposes. The study investigated if resting-lactate-determination is superior to lactate-stress-testing (LST) in demonstrating mitochondrial dysfunction in ALS. Included were 15 ALS patients, 4 women, 11 men, aged 37-72. Severity of the disease was assessed by the Norris-score. The control group comprised 66 healthy subjects, 40 women, 26 men, aged 36-76. Serum lactate was determined before, three times during, and once after a constant workload with 30 W on a bicycle ergometer. According to the EIEscorial criteria 8 patients had definite, 4 probable, 3 possible ALS. Resting lactate was increased in 2 patients, 1 with definite and 1 with possible ALS. The LST was abnormal in 5 patients with definite, 1 with probable and 1 with possible ALS. The mean Norris-score was 67.8 in patients with abnormal LST and 74.6 in patients with normal LST. In conclusion, the LST is more suitable than resting-lactate-determination in demonstrating mitochondrial dysfunction in ALS. The LST suggests mitochondrial dysfunction in half of the ALS patients. Mitochondrial dysfunction in ALS is related to the clinical severity of the disease.     

Diagnostic yield of the lactate stress test in respiratory chain disorders under absolute and relative workload.

Usually, the lactate stress test is carried under a constant, low workload maintained for 15 min, although there are indications that the lactate response to exercise is a function of the relative workload, and that a workload for only 5 min does not decrease its sensitivity. Thus, this study compared the diagnostic yield of the lactate stress test when carried out under a constant workload of 30 W (LSTA) and under a workload of 30% of maximum (LSTR), and when the workload was maintained for 5 and 15 min. In 16 patients with respiratory chain disorders, 12 women, four men, aged 27--88 years, the LSTA and LSTR were carried out on 2 different days, within 48 h. For both tests serum lactate was determined before, during and after a 15-min workload on a bicycle. Upper reference limits at rest, 5, 10, 15 min after starting, and 15 min after finishing the exercise were 1.9, 2.0, 2.0, 2.0, and 1.6 mmol/l for the LSTA, and 2.3, 3.0, 3.2, 3.4 and 2.7 mmol/l for the LSTR. The sensitivity was 88% for the LSTA and 63% for the LSTR. The specificity of the LSTA was 94%. The diagnostic yield of both tests was similar when the workload was maintained for 5 or 15 min. In conclusion, the LSTA should be preferred to the LSTR. Three lactate determinations during 15 min have no advantage over a single lactate determination after a 5 min workload of 30 W.     

Lactate increase and oxygen desaturation in mitochondrial disorders – Evaluation of two diagnostic screening protocols

Background Mitochondrial disorders are characterized by an accumulation of lactate and an insufficient oxygen extraction from blood during exercise. Therefore, both parameters (lactate and oxygen saturation) can be used as screening tests in mitochondrial disorders. However, conflicting results regarding sensitivities and specifities of both tests have been reported. Method We examined 27 patients with genetically defined mitochondrial disorders (single deletions n = 15,multiple deletions n = 5, A3243G mutation n = 7), patients with other neuromuscular disorders, and healthy controls. In the first test subjects performed intermittent isometric handgrip exercise (0.5 Hz) at 80 % (3 minutes) and 30 % (3 and 15 minutes) of maximal contraction force (MCF). Oxygen saturation and partial pressure in cubital venous blood from the exercising arm were measured. In the second test subjects underwent cycle ergometry at 30 W for 15 minutes. Venous lactate at rest, during and 15 minutes postexercise was determined. Result Both tests showed specificities of 92–96%. Sensitivities for changes of venous oxygen partial pressure and oxygen saturation ranged from 21–26% at 80% MCF for 3 minutes to 47–58% at 30% MCF for 15 minutes. Sensitivities for venous resting, peak, and post–exercise lactate was 33%, 58%, and 67%, respectively. The degree of deoxygenation, however,was independent of the intensity and duration of the applied forces. Oxygen desaturation and lactate increase in patients with mitochondrial disorders were not different in patients with and without clinical symptoms of myopathy. There were significant correlations between the heteroplasmy and both the degree of oxygen desaturation and lactate increase in patients with single deletions. In patients who performed both protocols (n = 16) a combination of both tests increased sensitivity up to 87%. Conclusion Oxygen desaturation in forearm exercise tests and lactate increase in cycle ergometry tests show a high specifity but only moderate sensitivity. Combination of the two screening test clearly increases the sensitivity.     

Modified exercise test in screening for mitochondrial myopathies--adjustment of workload in relation to muscle strength

The aim of this study was to evaluate the usefulness of a modification of the bicycle ergometer test, the subanaerobic threshold exercise test (SATET), as a screening test for patients with mitochondrial myopathies. Since the original SATET is frequently found to be strenuous for weak patients, a new variable (relative muscle strength) was added to the workload formula. Plasma lactate levels were recorded at rest, then after 5 and 15 min of cycling on an ergometer, with constant workload. Nine patients with mitochondrial myopathy, 10 patients with other neuromuscular diseases and 9 healthy but sedentary volunteers undertook the test. An upper reference limit after exercise for plasma lactate was settled at 2.9 mmol/l. The modified SATET showed a sensitivity of 78% and a specificity compared to the healthy subjects of 100%. Compared to patients with other neuromuscular diseases, the specificity was lower (60%). All subjects completed the test without severe fatigue or pain.     

阿尔茨海默病的扩瞳试验研究

目的验证扩瞳试验能否用于诊断阿尔茨海默病（AD）。方法用非接触型双侧瞳孔红外同步记录分析仪对滴入0.01%托吡卡胺后的瞳孔变化进行测定,并自动分析瞳孔直径扩大（按对照侧校正）的百分比。共测定AD患者52例、血管性痴呆（VD）患者34例、老年精神分裂症（S）19例和老年健康人（对照组）57名。比较并找出最能明显区别AD与对照组的瞳孔扩大值,以此作为试验结果阳性与否的分界线。结果AD患者的瞳孔在滴药7～10min后便明显扩大,与VD、S或对照组的差异有非常显著性（P<0.01）。如以第18min时扩大值≥15%作为分界线,AD、VD、S及对照组的阳性例数/总例数分别为42/52、6/34、1/19和12/57;用以诊断AD时的敏感性为0.81,特异性为0.79～0.82,一致性Kappa值为0.60～0.62。结论扩瞳试验可以作为筛选AD的诊断标志之一,也可在鉴别AD与VD时作为参考。     

A useful electrophysiological test for diagnosis of minimal conduction block.

OBJECTIVE: To evaluate the usefulness, sensitivity and specificity of a new neurophysiological test for partial conduction block. METHODS. In 17 patients (17 nerves) with clinical pictures strongly suggesting the presence of motor conduction block and 20 healthy subjects (40 nerves), motor nerve conduction studies were performed with the conventional surface technique and with a new technique developed by us: the single fiber EMG (SFEMG) conduction block test. Moreover, we also evaluated patients with other neurological diseases. The recent American Association of Electrodiagnostic Medicine (AAEM) consensus criteria for partial conduction block were used for the standard conduction block tests. RESULTS: According to AAEM consensus criteria, 5/17 cases presented 'definite' partial conduction block and 6 presented 'probable' partial conduction block. In contrast, 16/17 cases (94%) presented evidence of conduction block at the SFEMG conduction block test. The 5/6 cases that did not fulfill in the AAEM criteria and that presented abnormal findings at SFEMG nerve conduction test could be considered affected by minimal conduction block. The sensitivity of this new test was greater than conventional test. The specificity was 100% (no abnormal findings in healthy subjects or patients with diseases other than neuropathy). CONCLUSIONS: The SFEMG conduction block test is a sensitive, complementary, technique for diagnosis of minimal conduction block in patients with normal findings in standard nerve conduction studies.     

Yield of transcranial Doppler in acute cerebral ischemia.

BACKGROUND AND PURPOSE: The objective of this study was to evaluate the yield of emergent transcranial Doppler (TCD) for the evaluation of acute cerebral ischemia. METHODS: We performed urgent bedside non-contrast-enhanced TCD in patients with acute cerebral ischemia before or immediately after baseline CT scanning. A fast-track scanning protocol (相似文献   

Sensitivity and specificity of the new international diagnostic criteria for migraine with aura

OBJECTIVES: Since 1998, migraine with aura (MA) has been diagnosed according to the operational diagnostic criteria of the International Headache Society (ICHD-1). Here we present the data underlying the new criteria for MA in the ICHD-2 classification. METHODS: Sensitivity of the new criteria was tested in patients with MA and specificity in patients with reversible non-aura visual disturbances. The diagnoses in both groups of patients were made in a validated semistructured physician-conducted interview. We tested five sets of criteria for sensitivity and specificity comparing with the diagnosis according to the ICHD-1 in 200 patients and the selected set of criteria in 274 additional patients. RESULTS: Four sets of criteria had sensitivity/specificity of 46%/100%, 71%/100%, 62%/95%, and 99%/76%. Sensitivity of the selected set of criteria was 84% (95% CI 79% to 90%) and specificity 97% (95% CI 95% to 99%). According to these criteria at least two of the following should be fulfilled: homonymous visual or unilateral sensory symptoms; at least one aura symptom develops gradually over > or =5 minutes and/or different symptoms occur in succession over > or =5 minutes; each symptom lasts > or =5 and < or =60 minutes. In the additional sample sensitivity of the selected criteria was 90% (95% CI 86% to 94%) and specificity 96% (95% CI 91% to 100%). CONCLUSIONS: The diagnostic criteria for MA selected for ICHD-2 had high sensitivity and specificity. The ICHD-2 criteria are more operational and probably delineate a more homogeneous sample of patients than the ICHD-1. The ICHD-2 for MA is intended equally for research and clinical practice and can be used at different levels of specialisation.     

Individual voxel-based morphometry adjusting covariates in multiple system atrophy

IntroductionThis study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD).MethodsWe included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI.ResultsOn iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD.ConclusioniVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.     

The diagnostic value of vestibular-evoked myogenic potential in patients with vestibular schwannoma

ObjectiveThis study examined the diagnostic value of the vestibular-evoked myogenic potential (VEMP) in comparison with the caloric test in patients with vestibular schwannoma (VS).MethodsData were retrospectively collected from 803 consecutive patients who visited our vertigo clinic and underwent vestibular tests. Amongst them, 78 patients were diagnosed as having untreated unilateral VS. VEMP was performed using click and short-tone burst stimulation. The caloric test was performed using ice water. The sensitivity and specificity of each test were evaluated.ResultsOf the 78 patients with VS, 63 had abnormal VEMPs as well as abnormal caloric responses. Of the 725 patients without VS, 382 had normal VEMPs and 416 had normal caloric responses. The sensitivity and specificity of VEMP were 80.8% (95% CI: 72.0–89.5%) and 52.7% (95% CI: 49.1–56.3%), respectively; those of the caloric test were 80.8% (95% CI: 72.0–89.5%) and 57.4% (95% CI: 53.8–61.0%), respectively.ConclusionsThe sensitivity and specificity of VEMP and the caloric test showed no significant differences.SignificanceIn patients with VS, although the specificity of VEMP was not very high, its sensitivity was high and comparable to that of the caloric test.     

Cycle ergometry is not a sensitive diagnostic test for mitochondrial myopathy

Cycle exercise has repeatedly been used to diagnose patients suspected of having mitochondrial myopathy (MM), in whom exercise intolerance and lactic acidosis are common. No standardized test, however, has been established. We evaluated the diagnostic value of incremental and constant workload (20 min at 65 % VO(2max)) cycle tests for the diagnosis of MM. Plasma lactate and oxidative capacity (VO(2) and workload) were measured in 15 well-characterized MM patients during cycling. Findings were compared with those in 10 myotonic dystrophy patients and 18 sedentary, healthy subjects.All MM patients had ragged red or COX-negative fibers on muscle biopsy. VO(2max) and maximal workload were lower in MM than in control groups (P < 0.02). Resting plasma lactate was higher in MM than in control groups (P < 0.005; sensitivity = 93 %; specificity = 85 %), while exercise-induced increases in plasma lactate were only higher during the constant workload protocol in MM patients vs. control groups (P < 0.05; sensitivity = 27 %; specificity = 86 %). The findings indicate that the diagnostic value of a constant workload protocol is superior to an incremental cycle test, but that the test is less sensitive for MM than simple testing of resting lactate and muscle morphology. Cycle testing of MM patients remains an important research tool, but should not be a standard diagnostic procedure for MM.     

The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure

Metoclopramide (MCP), a central and peripheral dopaminergic blocker with cholinergic activity, has been proposed to treat orthostatic hypotension (OH) on the basis that it could antagonize the vasodilator and natriuretic effects of dopamine. The authors evaluated cardiovascular responses to MCP in 11 subjects with OH: 6 with multiple system atrophy (MSA) and 5 with pure autonomic failure (PAF), along with 6 healthy control subjects. Supine blood pressure (BP), heart rate (HR), and breathing were continuously monitored before, during, and after MCP infusion. The pre-MCP head-up tilt test was tolerated at 65° for 10 minutes in all subjects except in one with PAF, who tolerated 30° for only 5 minutes. Tilting confirmed the OH in patients with MSA (change in mean arterial pressure [ΔMAP]=−31±13 mm Hg) and PAF (ΔMAP=−34±8 mm Hg). Infusion of MCP was given in four 5-mg doses every 5 minutes, with the subject in a supine position. Infusion of MCP induced the following effects: (1) A transient hypotensive effect occurred after each infusion in both patients and control subjects, the fall in MAP being counteracted by an increase in HR in control subjects but not in patients; this acute MAP fall was more severe in patients. (2) A progressive reduction of MAP occurred during the test, which never returned to preinfusion levels in patients; this effect was so pronounced in two PAF patients as to prevent them from receiving the last dose. Post-MCP tilting was tolerated in control subjects but in only in 5 MSA patients and 4 PAF patients. In those patients who tolerated the test, the MAP fall was similar to, or worse than, that before MCP (MSA: ΔMAP=−28±16 mm Hg; PAF: ΔMAP=−38±16 mm Hg). The cardiovascular effect of MCP in normal subjects was a transient hypotension counterbalanced by reflex tachycardia. The lack of an HR increase and the progressive fall in supine BP in MSA and PAF patients, together with worsening orthostatic tolerance after MCP infusion, are effects that should strongly discourage the use of this drug in the treatment of OH.     

The diagnostic value of water immersion skin wrinkling and Neuropads® in small fiber neuropathy

Objective

To investigate the diagnostic yield of two simple tests for small fiber neuropathy (SFN): Neuropads® and water immersion skin wrinkling (WISW).

Methods

We studied 35 patients clinically diagnosed with SFN and 61 age- and sex-matched healthy controls. Wrinkling was judged as absent (abnormal), or present (normal) after immersion of the hands for 30 min. Neuropads® are plasters impregnated with cobalt blue that are applied with to the soles of the feet. These remain blue when feet are dry (abnormal) or turn pink when there is some moisture (normal).

Results

The sensitivity of the Neuropad® was 29% and its specificity 93%. The sensitivity of WISW was 66% and its specificity 70%. Regarding abnormality of at least one test to define the combination as abnormal yielded a sensitivity of 71% and specificity 67%. When both tests had to be abnormal to judge the combination abnormal, sensitivity was 23% and specificity 97%.

Conclusions

The Neuropad® has a high specificity, so an abnormal result can be used to confirm SFN. WISW has a moderate sensitivity and specificity. Combining these two tests can be helpful: when both tests are abnormal the diagnosis SFN is highly likely.

Significance

The Neuropad® and WISW can be helpful in daily practice by supporting the diagnosis SFN.     

Diffusion-weighted imaging and proton magnetic resonance spectroscopy in perinatal hypoxic-ischemic encephalopathy: association with neuromotor outcome at 18 months of age

We evaluated early diffusion-weighted imaging findings, the quantitative apparent diffusion coefficient, and magnetic resonance spectroscopy (the presence of lactate and ratios of N-acetylaspartate to total creatine and choline to total creatine) in the prediction of the 18-month neuromotor outcome of term newborns with hypoxic-ischemic encephalopathy. Conventional T1- and T2-weighted and diffusion-weighted imaging was performed in 20 asphyxiated term newborns, with additional basal ganglia magnetic resonance spectroscopy in 15 newborns between 2 and 18 days of life (mean 7.3 days). Neuromotor outcome was dichotomized into normal and abnormal for statistical analysis. Statistically significant differences in the ratios of N-acetylaspartate to total creatine, but not apparent diffusion coefficient values and ratios of choline to total creatine, were found between infants with a normal and an abnormal outcome (Mann-Whitney U-test, P = .010). There was a significant association between the presence of a lactate peak and an abnormal outcome (chi-square test, P = .017). The presence of a lactate peak for predicting an abnormal outcome had a sensitivity of 100% and a specificity of 80%, and the odds ratio was 37.4. Ischemic lesions were more conspicuous and/or extensive on diffusion-weighted imaging in all except one neonate. The presence of normal findings on both diffusion-weighted imaging and conventional magnetic resonance imaging is predictive of a normal neuromotor outcome, whereas lactate and a reduced ratio of N-acetylaspartate to total creatine in the basal ganglia, but not an apparent diffusion coefficient, are associated with an abnormal outcome at 18 months of age.     

Diagnostic value of quantitative sensory testing (QST) in carpal tunnel syndrome

The initial sensory symptoms of carpal tunnel syndrome (CTS) are usually intermittent and the clinical neurological examination is often normal. The aim of the present study was to determine the rate of impairment of different somatosensory modalities in CTS by means of the following tests: vibrametry, tactile pulses, von Frey hairs, two-point discrimination (2-PD), graphesthesia and warm and cold perception thresholds. The material consisted of 33 hands with CTS from 22 patients. Each of the first 3 tests was abnormal with elevated thresholds in 17 CTS hands (52%), 2-PD was abnormal in 10 hands (30%), graphesthesia in 8 hands (24%), and warm and cold thresholds in only 5 hands (15%). There was an overlap so that at least one test was abnormal in 27 of the 33 CTS hands (82%). Thus, impairment of sensibility can be demonstrated in a majority of patients with CTS if more than one test is applied. Vibrametry and von Frey hairs are recommended instead of the commonly used 2-PD, since abnormality was more often revealed and since they are equally easy to apply. No individual test was sensitive enough to qualify as a diagnostic criterion when it was applied with the hand in resting position. A significant increase in both sensitivity and specificity can be expected for any test if it is combined with provocation, such as wrist flexion, as has been demonstrated for vibrametry.     

Improvement of screening in exertional myalgia with a standardized ischemic forearm test

An ischemic forearm test with simultaneous measurement of both lactate and ammonia can be used as a screening method for myoadenylate deaminase deficiency (MADD) and for various glyco(geno)lytic defects. A standardized and a nonstandardized test have been compared in a group of 186 patients with exertional myalgia. Standardization of the ischemic forearm test has led to greater yields of both lactate and ammonia in venous return blood of patients and controls. The sensitivity of the proposed test procedure in detecting MADD patients was 100%, whereas the specificity amounted to 98.8% among exertional myalgia patients.