Quantitative thermal sensory testing in patients with monomelic amyotrophy

BACKGROUND: Quantitative thermal sensory testing (QST) is a non-invasive method to assess somatic small fibre dysfunction, which is not evaluated with routine nerve conduction studies (NCS). Monomelic amyotrophy (MMA), is a pure motor disorder with no sensory abnormalities on routine NCS, and has not been evaluated using QST. AIMS AND OBJECTIVE: Present study aimed to evaluate somatic small fibre involvement in MMA patients. Forty patients with MMA with no sensory abnormalities or routine NCS were evaluated using QST for thresholds of cold sensation (CS), warm sensation (WS), cold pain (CP) and warm pain (WP), using method of limits. These were compared with 40 age-matched controls. RESULTS: No abnormalities in thresholds for CS, WS, CP and WP were found in MMA group as compared to controls. CONCLUSION: QST thus failed to demonstrate any abnormality. Hence we conclude that MMA is a pure motor disorder, with no involvement of somatic small sensory fibres (A delta and C).     

糖尿病性周围神经病的定量感觉检查

目的:探讨定量感觉检查(QST)对糖尿病性周围神经病(DPN)诊断的临床应用价值.方法:应用QST仪检测118名正常人与136例DPN病人的冷觉(CS)、热觉(WS)和振动觉(VS)阈值及神经传导速度(NCV).结果:DPN组和单纯糖尿病(DM)组与正常对照组比较,手指和足背QST的CS、WS、VS阈值差异均有统计学意义(P＜0.05).DPN组和单纯DM组之间比较,手指和足背CS、WS、VS阈值差异也有统计学意义(P＜0.05).DPN组和单纯DM组之间比较手指和足背不同部位的CS、WS、VS阈值差异均有显著意义(P＜0.05).DPN组CS、WS、VS的异常率高于运动神经传导速度(MCV)、感觉神经传导速度(SCV)的异常率(P＜0.05),CS、WS的异常率高于VS的异常率(P＜0.05);DPN组患者的MCV、SCV、CS、WS和VS异常率均高于单纯DM组的异常率,其间差异有显著意义(P＜0.01);病程＞5年组的MCV、SCV、CS、WS和VS的异常率均高于病程≤5年组的异常率,其间差异亦有显著意义(P＜0.01);HbAlC正常组和HbAlC异常组MCV、SCV、CS、WS和VS异常率之间比较差异均无统计学意义(P＞0.05).结论:QST能为DPN的早期诊断提供可靠依据,是常规NCV检查的必要补充.     

定量感觉测定对有感觉异常的焦虑症患者的研究

目的：观察定量感觉测定（QST）在有感觉异常的焦虑症患者中的应用价值。方法：用QST检测有主观感觉障碍的20例焦虑症患者和20例正常对照组的感觉阈值,包括四肢的冷觉（CS）、温觉（WS）、冷痛觉（CP）、热痛觉（HP）的值进行分析,并作比较。结果：焦虑症组中的四肢的CP、HP异常较CS、WS更明显,焦虑症组中CS、WS、CP、WP的异常率分别是10％,15％,51％,53％。结论：焦虑组的QST的感觉阈值改变,说明焦虑症所产生的感觉障碍可能与周围和中枢神经敏感性增高有关。     

Hypoxia induces no change in cutaneous thresholds for warmth and cold sensation

Hypoxia can affect perception of temperature stimuli by impeding thermoregulation at a neural level. Whether this impact on the thermoregulatory response is solely due to affected thermoregulation is not clear, since reaction time may also be affected by hypoxia. Therefore, we studied the effect of hypoxia on thermal perception thresholds for warmth and cold. Thermal perception thresholds were determined in 11 healthy overweight adult males using two methods for small nerve fibre functioning: a reaction-time inclusive method of limits (MLI) and a reaction time exclusive method of levels (MLE). The subjects were measured under normoxic and hypoxic conditions using a cross-over design. Before the thermal threshold tests under hypoxic conditions were conducted, the subjects were acclimatized by staying 14 days overnight (8 h) in a hypoxic tent system (Colorado Altitude Training: 4,000 m). For normoxic measurements the same subjects were not acclimatized, but were used to sleep in the same tent system. Measurements were performed in the early morning in the tent. Normoxic MLI cold sensation threshold decreased significantly from 30.3 +/- 0.4 (mean +/- SD) to 29.9 +/- 0.7 degrees C when exposed to hypoxia (P < 0.05). Similarly, mean normoxic MLI warm sensation threshold increased from 34.0 +/- 0.9 to 34.5 +/- 1.1 degrees C (P < 0.05). MLE measured threshold for cutaneous cold sensation was 31.4 +/- 0.4 and 31.2 +/- 0.9 degrees C under respectively normoxic and hypoxic conditions (P > 0.05). Neither was there a significant change in MLE warm threshold comparing normoxic (32.8 +/- 0.9 degrees C) with hypoxic condition (32.9 +/- 1.0 degrees C) (P > 0.05). Exposure to normobaric hypoxia induces slowing of neural activity in the sensor-to-effector pathway and does not affect cutaneous sensation threshold for either warmth or cold detection.     

神经电生理检查在肌萎缩侧索硬化症中的应用

目的:观察神经电生理检查在肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)中的应用价值。方法:分别对28例临床确诊ALS、6例临床拟诊ALS、4例临床可能ALS患者进行4个区域的共8块肌肉肌电图(EMG)分析,四肢的磁运动诱发电位(MEP),上肢正中神经、尺神经、下肢胫神经F波检查,在双侧腓肠肌记录H波,四肢远端神经传导测定,包括运动传导速度(MCV)、感觉传导速度(SCV)、复合运动神经动作电位(CMAP)、感觉神经动作电位(SNAP)以及运动末梢潜伏期(DML)进行测定并分析,并与健康对照组30例进行比较。结果:临床确诊ALS的神经电生理测定各值异常均高于拟诊ALS和可能ALS(P<0.05),拟诊ALS和可能ALS组比较没有明显统计学差异。ALS组EMG异常率85%,MEP异常率72.4%,神经传导异常主要表现为CMAP降低36.2%,SCV基本正常,F波出波率下降33.3%,F波振幅增高26.3%,H波振幅增高26.3%。结论:EMG对ALS患者下运动神经元损害有定位诊断价值,EMG是ALS诊断的重要依据;MEP对ALS患者上运动神经元损害有诊断价值,但特异性不高;F波、H波对ALS患者上下神经元神经损害定位有补充诊断价值,神经传导测定用于ALS的鉴别诊断。     

Cutaneous sensibility and peripheral nerve function in patients with unmedicated essential hypertension

Sensorimotor deficits in patients with essential hypertension may be due to impaired nerve function. Cutaneous sensory thresholds, median nerve sensory and motor conduction velocities, and median nerve sensory action potential amplitudes were assessed in 30 patients with unmedicated essential hypertension and 29 normotensives. Cutaneous sensory thresholds were higher and sensory action potential amplitudes smaller in hypertensives than normotensives whereas sensory and motor nerve conduction velocities did not differ between groups. These data suggest that hypertension may reduce the number of active sensory nerve fibers without affecting myelination. Sensory action potential amplitudes were inversely related to cutaneous sensory thresholds, suggesting that subclinical axonal neuropathy of sensory afferents may help account for perceptual deficits that characterize hypertension.     

Insulin sensitivity and sensory nerve function in non-diabetic human subjects

The direct effect of reduced insulin sensitivity (measured by insulin tolerance test and fasting plasma insulin) on sensory nerve function was examined in non-diabetic human subjects. Thermal sensation (measured by warm and cold perception thresholds) deteriorated with fasting hyperinsulinaemia in the presence of normoglycaemia and normal glucose tolerance. The results suggest a possible role for insulin in sensory nerve function, also that deficits in insulin action per se may adversely affect the function of small sensory nerves independent of glycaemic levels, and may thus be implicated in the aetiology of diabetic neuropathy.     

Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Abstract

Peripheral neuropathy (PN) is the most common neurological complication of HIV infection,affecting over one third of patients. The research diagnosis of PN is complicated by the need for expensive, time-consuming, and noxious diagnostic tests. We investigated whether nerve conduction studies (NSC) and quantitative sensory tests (QST) provide added value for the diagnosis of PN for research purposes or whether the easily obtainable clinical measures (sensory and motor symptoms, sensitivity to pain and vibration, tendon reflexes, motor function) are sufficient.     

Effects of chronic median nerve compression at the wrist on sensation and manual skills

 The aim of this study was to analyse the functional impairments caused by chronic median nerve compression at the wrist on hand sensation and manual skill. Hand function was assessed in 11 patients (8 women and 3 men) with severe carpal tunnel syndrome (CTS) and compared with that of an age- and sex-matched control group. Apart from CTS, the subjects were healthy and the electrodiagnostic examination was normal. The pressure and vibration detection thresholds of the index finger were partially impaired and statistically different (P<0.05) when compared with controls, suggesting a reduction of tactile acuity in the territory of the median nerve. The thermal thresholds were identical in both groups, suggesting that the small-diameter fibres were not affected. When a small object was lifted and positioned in space, the coordination between the grip force and the vertical lifting force did not seem to be affected in our patients. They were able to modify their grip force according to the friction between the fingertips and the object, i.e. the more slippery the object, the higher the grip force. The unimanual Purdue Pegboard subtest results suggest that digital dexterity was also not significantly perturbed in our sample of CTS patients when compared with controls. Despite the severe abnormalities of median nerve conduction, our results suggest that chronic median nerve compression occurring in CTS induces partial impairment of tactile sensibility with minor impact on grasp force regulation and digital dexterity. Received: 25 September 1998 / Accepted: 10 December 1998     

Trigemino-cervical response in patients with amyotrophic lateral sclerosis

PURPOSE: The trigemino-cervical response (TCR) was investigated in the patients with amyotrophic lateral sclerosis (ALS) to evaluate its effect for disclosing the bulbar involvement in this disorder. METHODS: We studied 100 normal subjects and 45 patients with ALS. In all normal subjects, stimulation of the infraorbital nerve on one side produced bilateral short latency waves, which consisted of a positive/negative wave described with the mean peak latency (P20/N30). The mean square root of the ratio between the amplitude of P20/N30 and the mean rectified surface EMG activity preceding the stimulus was described by A value. RESULTS: The latency of P20 in controls was 18.5 +/- 1.4 ms, N30 was 28.8 +/- 2.8 ms, and the A value was 1.6 +/- 0.5, respectively. In ALS patients, twelve showed absent, seventeen were delayed in the latencies, six were above normal asymmetry on two sides, and ten showed normal. The latency of P20 in ALS patients was 22.9 +/- 9.4 ms, N30 was 33.7 +/- 11.2 ms, and the A value was 1.5 +/- 0.8, respectively. The parameters of the latencies of TCR between ALS patients and the normal controls were statistically different (P < 0.05). CONCLUSIONS: TCR can be reliably measured in all normal subjects and help in disclosing lower brainstem lesions in ALS patients, even without bulbar symptoms.     

Electrophysiological findings in poliomyelitis patients at the subacute phase.

Electrodiagnostic tests-needle EMG, nerve conduction and somatosentory evoked potential (SEP) studies of the upper and the lower limbs were performed in three patients during the subacute phase of poliomyelitis. Although poliomyelitis is traditionally considered a "pure motor" disease, involvement of the sensory system was demonstrated by prolonged sensory nerve conduction and by delayed latencies and amplitude asymmetries of SEPs obtained from the lower limbs. Sensory deficit in poliomyelitis is well known to exist during the acute phase of illness. The present report describes the electrophysiological findings in patients during the subacute phase, several months after onset of illness. Sensory nerve action potentials and sensory evoked potentials were abnormal, especially those elicited by lower limb stimulation although the patients had no overt signs of sensory loss at that time. The associated EMG findings are described, and the probable pathologic changes of the motor unit are discussed.     

Electrically elicited short and long-latency responses of intrinsic hand muscles in hereditary ataxias. Effects of isometric and ballistic isotonic voluntary contractions.

Short- and long-latency responses (HR and LLR) from thenar muscles were studied in patients with Friedreich's ataxia and pure cerebellar ataxia with later onset by applying electrical stimuli on the median nerve at the wrist. HR and LLR were examined during two different voluntary activities of the opponens pollicis muscle: isometric ("hold") and isotonic ballistic ("move") conditions. A preliminary conventional study of motor and sensory conduction of the median nerve was also carried out. Patients with Friedreich's ataxia had reduced or absent HR and LLR. Furthermore, those who preserved both responses had prolonged HR-LLR interpeak latency. All patients with Friedreich's ataxia also showed peripheral nerve conduction abnormalities, mainly in sensory fibers. These data can be accounted for by the widespread degeneration of many neural structures in this disorder. No abnormalities in HR were observed in pure cerebellar ataxia with later onset, whereas LLR was grossly enlarged in most patients, notably during "move" condition. Since cerebellar structures (especially the cerebellar cortex) are the only ones involved in this disorder, the cerebellum may play a role in modulating LLR. In particular, this effect could be more evident in isotonic ballistic movements.     

The F response parameters in Behçet's disease

The F response parameters may provide a sensitive method for detection of mild neuropathy in patients with otherwise normal nerve conduction studies. We investigated conventional nerve conduction studies and F response parameters in patients with Beh?et's disease (BD), but without neurologic involvement. The results indicate that ulnar motor and sensory, tibial motor and sural sensory nerve conduction studies failed to differentiate the patients with BD and controls. In the ulnar nerve, the F response parameters were not significantly different for the populations. In the tibial nerve, the F response latency and chronodispersion were increased while F amplitude, duration, and persistence were all decreased in patients with BD. The results suggests that, (1) peripheral nerve dysfunction occurred especially in lower extremities in patients with Beh?et's disease. (2) The F response parameters were considered the most sensitive method for the detection of neuropathy in Beh?et's disease.     

感觉定量和神经传导速度联合检测对糖尿病周围神经病的诊断价值

目的:探讨感觉定量检测(QST)、神经传导速度检测(NCV)联合应用对糖尿病(DM)周围神经病(PNP)的诊断价值。方法:对37例DM患者进行常规NCV检测;并且对这37例DM患者和20例正常人进行QST检测。结果:在37例DM患者中,QST异常32例(86％),与对照组比较差异有极显著意义(P<0．001);NCV检测异常23例(62％),与正常值对照差异有极显著意义(P<0．001)。这两种检测方法阳性率对比,差异亦有统计学意义(P<0．05)。结论:NCV可作为DM-PNP的常规检测方法,但NCV仅能反映粗有髓神经纤维的功能,阳性率低,而QST可反映细神经纤维的功能,且操作简便,无创伤,无痛苦,老年人易接受。两种方法联合使用可提高DM患者PNP的检出率,为DM-PNP的诊断提供有力依据,也可作为治疗及预后观察的客观指标。     

Incidence of subclinical trigeminal and facial nerve involvement in diabetes mellitus.

We investigated the frequency of subclinical trigeminal and facial nerve involvement in 40 patients with diabetes mellitus and without clinical signs of cranial nerve lesions. 60% of the patients had distal symmetric sensory polyneuropathy which was confirmed by nerve conduction studies. Trigeminal and facial nerve functions were evaluated electrophysiologically using the blink-reflex R1 component (BlinkR-R1), masseter reflex (MassR), the first exteroceptive suppression of the masseter muscle (Mass-ES1), and distal motor latency of the facial nerve (DML VII). Latencies were significantly prolonged for the BlinkR-R1 (p < 0.0001), the Mass-ES1 (p < 0.05), and DML VII (p < 0.005) in diabetics compared with controls. No significant difference was found for the MassR. Prolonged latencies (> mean + 2.5 SD of age-matched controls) were demonstrated for the Mass-ES1 in 12.5%, BlinkR-R1 in 10%, DML VII in 6.2%, and MassR in 5% in individual of patients. Our findings indicate that trigeminal and facial nerve involvement is not infrequent in diabetics, although it is significantly less frequent than limb nerve involvement.     

Psychophysical correlates in children with sensory modulation disorder (SMD)

Sensory modulation disorder (SMD), affecting ~ 5% of children, is characterized by sensory over or under-responsiveness to a range of stimuli in several modalities. Children with over-responsiveness (SOR) demonstrate increased aversion to certain natural stimuli that manifests as increased distress and avoidance behaviors to common stimuli, accompanied by abnormal electrodermal responses and brain evoked potentials to various stimuli. This study is the first to use quantitative sensory testing to characterize the somatosensory sub-modalities of children with SMD. Seventy eight children aged 6-10 years (44 SMD children and 34 classmate controls) were tested. A diagnosis of SMD and SMD-free using the Short Sensory Profile was ascertained by the Sensory Profile Questionnaire, both completed by participants' mothers. Sensory detection thresholds for skin warming, cooling, punctate dynamic tactile sensation, vibration and thermal pain thresholds for heat and cold were determined at several body sites. Pain and prickle intensities for pinprick and prickly stimuli and the duration and intensity of the after-sensations of prickliness and pain evoked by the prickle stimuli were assessed. Compared to the control children, SMD children showed significant cool hypoesthesia, higher pain intensity to pinprick and to prickly stimuli, and significantly more pain after-sensation to the prickly stimuli. No significant differences between groups were found in most of the sensory and pain thresholds at any tested site. These results indicate, for the first time, that children with SMD perceive more pain, and that their pain lasts longer. Our results demonstrate that SOR does not imply lowered sensory thresholds but abnormal processing suprathreshold noxious stimuli.     

Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells

Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the motor neurons degenerate. The discovery of new drugs for treating ALS has been hampered by a lack of access to motor neurons from ALS patients and appropriate disease models. We generate motor neurons from induced pluripotent stem cells (iPSCs) from familial ALS patients, who carry mutations in Tar DNA binding protein-43 (TDP-43). ALS patient-specific iPSC-derived motor neurons formed cytosolic aggregates similar to those seen in postmortem tissue from ALS patients and exhibited shorter neurites as seen in a zebrafish model of ALS. The ALS motor neurons were characterized by increased mutant TDP-43 protein in a detergent-insoluble form bound to a spliceosomal factor SNRPB2. Expression array analyses detected small increases in the expression of genes involved in RNA metabolism and decreases in the expression of genes encoding cytoskeletal proteins. We examined four chemical compounds and found that a histone acetyltransferase inhibitor called anacardic acid rescued the abnormal ALS motor neuron phenotype. These findings suggest that motor neurons generated from ALS patient-derived iPSCs may provide a useful tool for elucidating ALS disease pathogenesis and for screening drug candidates.     

Thermal sensation and comfort in women exposed repeatedly to whole-body cryotherapy and winter swimming in ice-cold water

Whole-body cryotherapy (WBC; -110 degrees C) and winter swimming (WS) in ice-cold water are severe ambient cold exposures, which are voluntarily practiced by humans in minimal clothing. The purpose was to examine thermal sensation and thermal comfort associated with WBC and WS. Twenty women similar in body mass index, age, physical activity, and use of hormonal contraception were pairwise randomized either to the WBC group or the WS group. The duration of each WBC exposure was 2 min, which was repeated three times per week for 3 months (13 weeks). Similar exposure frequency was used for the WS group, but each exposure lasted 20 s in outdoor conditions. Thermal sensation and comfort were asked with standard scales. After WBC, 65% of the thermal sensation votes were 'neutral' or 'slightly cool.' After WS, 81% of the thermal sensation votes were 'warm,' 'neutral,' or 'slightly cool.' Majority of comfort votes immediately after exposures in WBC group (98%) and in the WS group (93%) were 'comfortable' or 'slightly uncomfortable.' Thermal sensation and comfort became habituated in both groups at an early stage of trials, but the changes were less conclusive in WS group due to variable conditions outdoors. In the WBC group, cold sensation was less intense already after the second exposure. In conclusion, repeated exposures to WBC and WS in healthy women were mostly well tolerated and comfortable. The results indicate that during repeated severe whole-body cold stress of short duration, thermal sensation and comfort become habituated during the first exposures.     

Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated with defects in microtubule polymerization and axonal transport

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now recognized as multi‐system disorders also involving various non‐motor neuronal cell types. The precise extent and mechanistic basis of non‐motor neuron damage in human ALS and ALS animal models remain however unclear. To address this, we here studied progressive motor neuronopathy (pmn) mice carrying a missense loss‐of‐function mutation in tubulin binding cofactor E (TBCE). These mice manifest a particularly aggressive form of motor axon dying back and display a microtubule loss, similar to that induced by human ALS‐linked TUBA4A mutations. Using whole nerve confocal imaging of pmn × thy1.2‐YFP16 fluorescent reporter mice and electron microscopy, we demonstrate axonal discontinuities, bead‐like spheroids and ovoids in pmn suralis nerves indicating prominent sensory neuropathy. The axonal alterations qualitatively resemble those in phrenic motor nerves but do not culminate in the loss of myelinated fibers. We further show that the pmn mutation decreases the level of TBCE, impedes microtubule polymerization in dorsal root ganglion (DRG) neurons and causes progressive loss of microtubules in large and small caliber suralis axons. Live imaging of axonal transport using GFP‐tagged tetanus toxin C‐fragment (GFP‐TTC) demonstrates defects in microtubule‐based transport in pmn DRG neurons, providing a potential explanation for the axonal alterations in sensory nerves. This study unravels sensory neuropathy as a pathological feature of mouse pmn, and discusses the potential contribution of cytoskeletal defects to sensory neuropathy in human motor neuron disease.     

Altered cortical activation with finger movement after peripheral denervation: comparison of active and passive tasks

We wished to contrast cortical activation during hand movements in profoundly weak patients with motor neuropathy and in normal controls using a paradigm that is behaviourally matched between the two groups. Previous work has suggested that a passive movement task could be appropriate. Using functional magnetic resonance imaging (fMRI), we first characterised patterns of brain activation during active and passive index finger movements in healthy controls (n=10). Although the relative activation differences were highly variable, there was a trend for the mean number of significantly activated voxels in the primary motor cortex contralateral to the hand moved (CMC) to be lower for the passive than for the active task (40% relative decrease, P=0.09). There was a small posterior shift in the centre of mass of the CMC (mean, 8 mm, P<0.02) and of the ipsilateral sensorimotor cortex (IMC) (mean, 11 mm, P<0.05). No activation with passive movement was found in the patients with severe distal sensory neuropathy (n=2), suggesting that activation with passive movements is dependent on sensory feedback and unlikely to be due to mental imagery alone. In contrast, patients with severe pure motor neuropathies (MN, n=2) showed substantial increases in the volumes of activation compared to controls. The relative increases in numbers of voxels activated above threshold in different regions of interest for both the active (MN/controls: CMC, 2.1; IMC, 8.1; supplementary motor area [SMA], 5.2) and passive (CMC, 2.6; IMC, 8.0; SMA, 5.1) tasks were similar. These results confirm expansion of cortical representation for finger movement in patients with motor neuropathy and demonstrate central reorganisation as a consequence of the motor nerve loss. An expanded representation for finger movement in the primary motor cortex with peripheral weakness suggests the possibility that the primary motor cortex may encode motor unit activation rather directly. Electronic Publication