Early diabetic neuropathy: thermal thresholds and intraepidermal nerve fibre density in patients with normal nerve conduction studies

Objectives   To determine whether neuropathy in diabetic patients with normal nerve conduction studies could be detected by measurements of thermal thresholds and quantification of intraepidermal nerve fibre (IENF) density, and to evaluate differences in parameters between patients with and without neuropathic symptoms. Methods   A total of 22 patients with and 37 patients without sensory symptoms suggesting distal neuropathy were included. Measurements of warm and cold perception thresholds and skin biopsy for quantification of IENFs were performed distally on the leg. Reference data were used to normalize test results for age and height or gender of individual patients by calculating the Z-scores. Results   IENF density was significantly reduced in both symptomatic and asymptomatic patients compared to controls (p < 0.001), and in patients with symptoms compared to those without (p = 0.01). Thermal thresholds were significantly elevated (more abnormal) in patients with symptoms compared to controls (p < 0.01), but only for cold perception threshold (CPT) (p < 0.001) in the asymptomatic group. When comparing symptomatic and asymptomatic patients, there was no statistically significant difference in thermal thresholds. Depletion of IENFs in skin biopsy was the most frequent abnormal finding in the subgroup of patients with neuropathic symptoms (36 %) followed by abnormal CPT (27 %). Conclusion   Patients with diabetes and normal nerve conduction studies had significantly lower IENF density and higher CPT than controls, whether they had symptoms of polyneuropathy or not. In patients with neuropathic symptoms, abnormal IENF density predominated and seemed thus to be the most sensitive tool of detecting small diameter nerve fibre involvement.     

Clinical study of FK506 in patients with myasthenia gravis

Focal demyelinating lesions typically occur within a 1-cm segment of a nerve. In electrodiagnostic studies, measurements over longer distances decrease the chance of detecting such lesions, but measurements over shorter distances result in greater experimental error. Our objective was therefore to determine the optimal screening distance for ulnar neuropathy at the elbow (UNE) incorporating previously derived experimental errors for calculating nerve conduction velocity (NCV). Using a lesion model wherein prolongation of 0.4 ms was added to the expected latency of a 1-cm nerve segment, new NCVs were derived for distances between 1 and 10 cm for nerves normally conducting between 40 and 65 m/s. Lesion detection, or sensitivity, was defined as the likelihood of calculating a decrease of 10 m/s from the normal NCV while including the experimental error. Specificity was related to the likelihood of an inadvertent calculation of such a decrease in NCV in a segment without a lesion. Sensitivity and specificity were derived at multiple distances with varying NCVs. The total percentage error was the sum of the false-negative and false-positive percentages. The least total percentage error occurred at 3-4 cm, 4-6 cm, and 6-8 cm for nerves normally conducting at 40-50 m/s, 50-60 m/s, and 60-65 m/s, respectively. We conclude that the optimal distance for screening UNE, considering both sensitivity and specificity, is significantly less than 10 cm, perhaps as low as 4-6 cm; considering in addition the likely locations of focal lesions, the best distance is 6-8 cm.     

Changes in nerve conduction velocity across the elbow due to experimental error

One diagnostic criterion for ulnar nerve mononeuropathy at the elbow (UNE) is a decrease in across-elbow nerve conduction velocity (NCV) > 10 m/s compared to the forearm segment. Distance and latency measurement errors are an inherent part of NCV calculations. Twenty electromyographers measured the latencies of stored ulnar compound muscle action potentials and measured the forearm and across-elbow distances along the ulnar nerve. Based on previously published equations, experimental error in NCV was calculated for various NCVs. The mean distances and standard deviations for the forearm and elbow segments were 212.5 +/- 2.1 mm and 86.7 +/- 4.2 mm, respectively. For an NCV of 55 m/s, a difference of 14 m/s between the two segments can occur from measurement error alone. Distance measurements about the elbow are fraught with interobserver errors rendering the resultant NCV of that segment of limited value as a sole criterion for the diagnosis of UNE.     

Peripheral nerve conduction velocity in normal infants and children

Maximum motor conduction velocity of the median, ulnar and peroneal nerves and maximum sensory conduction velocity of the median nerve have been studied in 635 children, below 12 years of age, free from peripheral nervous system disease. The children fell into four age-group: from 0 to 1 year; from 1 to 3 years: from 3 to 6 years; from 6 to 12 years. No normal values were recorded for the sensory conduction velocity of the median nerve under the age of one year. The motor conduction velocity values significantly rise for the median and ulnar nerves up to 1 year, for the peroneal nerve up to 3 years. The sensory conduction velocity values of median nerve increase significantly up to 6 years.

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Sommario La velocità di conduzione motoria massima nei nervi mediano, ulnare e peroneale e la velocità di conduzione massima sensoriale nel solo nervo mediano sono state studiate in 635 bambini al di sotto dei 12 anni senza alcun segno di sofferenza del sistema nervoso periferico. L'analisi ha permesso di riconoscere 4 gruppi di età: da 0 a 1 anno; da 1 a 3 anni; da 3 a 6 anni; da 6 a 12 anni. I valori della velocità di conduzione motoria aumentano significativamente fino a 1 anno per i nervi mediano ed ulnare e fino a 3 anni per il nervo peroneale. I valori della velocità di conduzione sensitiva del nervo mediano aumentano significativamente fino a 6 anni.

     

Intraepidermal nerve fibre density, quantitative sensory testing and nerve conduction studies in a patient material with symptoms and signs of sensory polyneuropathy

Small diameter nerve fibre (SDNF) neuropathy is an axonal sensory neuropathy affecting unmyelinated (C) and thin myelinated (A-delta) fibres. We have evaluated 75 patients with symptoms and signs suggesting SDNF dysfunction with or without symptoms and signs of co-existing large diameter nerve fibre involvement. The patients were examined clinically and underwent skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS). The purpose of this study was to compare the relationship between the different methods and in particular measurements of thermal thresholds and intraepidermal nerve fibre (IENF) density in the same site of the distal leg. The main subdivision of the patient material was made according to the overall NCS pattern. Patients with normal NCS (38) had 6.4 +/- 3.8 and patients with abnormal NCS (37) had 4.4 +/- 3.4 IENF per mm (P = 0.02). Limen (difference between warm and cold perception thresholds) was significantly higher (more abnormal) in those with abnormal than in those with normal NCS (22.1 +/- 9.1 vs. 13.4 +/- 5.6, P < 0.0001). Cold perception threshold was more abnormal (P < 0.0001) than warm perception threshold (P = 0.002). Correlation between IENF and QST was statistically significant only when NCS was abnormal, and thus dependent of a more severe neuropathic process in SDNFs.     

Optimal distance for segmental nerve conduction studies revisited

In 1972, Maynard and Stolov showed that the experimental error in calculating nerve conduction velocity (NCV) depends on errors of latency and distance measurements. Their data suggested that a minimum distance of 10 cm should be used when calculating NCV because of an increase in error >/= 25% at shorter distances. The object of this study was to reestablish the minimum distance using current technology. Twenty physicians measured the proximal and distal onset latencies of the same stored ulnar compound muscle action potentials, as well as the forearm skin distance. The mean and standard deviation of the errors in conduction time and distance were determined. A spreadsheet was constructed, determining the error in NCV for a variety of distances and NCVs. The average conduction time between proximal and distal stimulation was 3.23 ms, with a standard deviation of 0.09 ms. The mean distance measurement was 212.6 +/- 2.1 mm. The errors in NCV were significantly less than previously reported. The experimental error increased as distance decreased, reaching 20% with distances less than 6 cm. The latency error accounted for 71% of the total experimental error, as opposed to 90% in the previous study. With advances in electrodiagnostic equipment, NCV can reasonably be calculated at distances less than 10 cm, perhaps as low as 5-6 cm.     

Digit distribution of proper digital nerve action potential.

Antidromic sensory nerve action potential testing is well characterized and commonly used to assess the sensory component of the upper limb median and ulnar nerves. The final terminal segments of these nerves are the proper digital nerves. Ring recording electrodes are commonly used to detect the proper digital nerves' antidromic responses. Attempts to record the separate contributions of individual digital nerves along the lateral aspects of each finger, using small surface electrodes, is shown to be unreliable for determining the integrity of a single terminal digital branch. We found between 50% to 77% of the stimulated terminal branch's response amplitude when recorded at electrodes positioned over the nonstimulated branch located 180 degrees from the activated terminal branch. Detecting a single terminal nerve response was achieved by using the fourth digit and the second digit with one of the second digit's branches neurophysiologically blocked by local anesthetic. The volume-conducted response from the opposite side of the finger resulted in this relatively large recorded response, which remains within the range of reference values precluding the simple use of antidromic techniques to assess injury to a single proper digital nerve. Techniques are proposed to avoid such pitfalls and to assess most accurately the desired response.     

Peripheral sensory abnormalities in patients with multiple sclerosis.

Although multiple sclerosis primarily affects myelin within the central nervous system, both pathologic and physiological studies suggest that mild deficits in peripheral nervous system myelin may be common. To evaluate this question further, we performed near nerve studies on sural nerves of 14 patients with multiple sclerosis. Peak-to-peak amplitude and maximum conduction velocity were normal in 9 of 14 patients, while minimum conduction velocity, or the velocity of the slowest-conducting component of the sensory action potential, was abnormally reduced in 9 patients. In addition, the supernormal period was evaluated for patients and compared with a control sample; multiple sclerosis patients showed a significant reduction in the amplitude of supernormality. Both the reduction in minimum conduction velocity and the alteration in the supernormal period are consistent with a mild defect in peripheral myelin.     

糖尿病患者周围神经传导速度的研究

目的:通过周围神经传导速度(NCV)的研究,早期诊断糖尿病(DM)患者的糖尿病性周围神经病变。方法:应用上海海军医学研究所NDI-200F神经电检诊仪,对DM组95例患者行尺神经、正中神经、胫神经和腓神经运动传导速度(MCV)及尺神经、正中神经、腓肠神经感觉传导速度(SCV)检测与30例健康人组对照。结果:DM组95例, NCV异常率为77.89%(74/95)。共检测665条神经,MCV380条,异常率55.26%,SCV285条,异常率50.88%,差异无显著性意义(P>0.05)。上肢检测380条神经,异常率45.53%,下肢检测285条神经,异常率63.86%,差异有显著性意义(P<0.05)。DM组SCV波幅减低率为53.66%。DM组按病程分为三组,<5年,30例,异常率28.10%;≥5年,31 例,异常率为54.84%;≥10年,34例,异常率74.37%,组间差异均有非常显著性意义(P<0.01)。DM组中29例无周围神经病变症状与体征,NCV异常11例(37.93%)。结论:周围神经传导速度检测不但可以早期诊断糖尿病患者的糖尿病性周围神经病变,而且此方法可靠、简便、无创。     

Peripheral nerve function during hyperglycemic clamping in insulin-dependent diabetic patients

The influence of hyperglycemia on peripheral nerve function was studied in 9 patients with long-term insulin-dependent diabetes. Blood glucose concentration was raised 13.5 +/- 0.5 mmol/l (mean +/- SEM) within 15 min and kept approximately 15 mmol/l over basal level for 120 min by intravenous glucose infusion. Hyperglycemia was accompanied by increased plasma osmolality. Sensory and motor nerve conduction and distal motor latency in the ulnar nerve were determined before, immediately after induction of hyperglycemia, and again after 120 min hyperglycemia. Distal (5th finger - wrist) and proximal (wrist - elbow) sensory nerve conduction showed an insignificant increase as hyperglycemia was induced. During hyperglycemia mean distal sensory conduction decreased from 53.1 m/s to 50.4 m/s (P less than 0.05) and mean proximal sensory conduction decreased from 56.0 m/s to 54.2 m/s (P less than 0.01). A mean of distal and proximal sensory conduction increased (53.5 m/s vs 54.6 m/s) (P less than 0.05) as hyperglycemia was induced and decreased (54.6 m/s vs 52.3 m/s) (P less than 0.01) during clamping. Motor nerve conduction decreased insignificantly throughout the study. Mean distal motor latency decreased from 3.1 ms to 2.8 ms (P less than 0.005) immediately after induction of hyperglycemia. During hyperglycemia it increased from 2.8 ms to 3.1 ms (P less than 0.001). We conclude that acute induction of hyperglycemia in long-term diabetics seems to increase sensory conduction and decrease distal motor latency, while 120 min hyperglycemia seems to decrease sensory conduction and increase distal motor latency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation by somatosensory evoked potentials of the neurotoxicity of cisplatin alone or in combination with glutathione

The use of high doses of cisplatin (DDP) in the treatment of different solid tumors is often prevented by the onset of a disabling sensory neuropathy. In an attempt to minimize DDP-induced neurotoxicity different schedules of DDP administration have been tested. Moreover, during the past few years some putative neuroprotective drugs have been reported as reducing DDP neurotoxicity. In this prospective, randomized study we evaluated in a series of 33 patients affected by relapsing ovarian cancer the effect on the sensory pathway of a non-conventional schedule of DDP administration as monochemiotherapy or in combination with one of the neuroprotective drugs (i.e. glutathione). The results of the neurophysiologic examinations performed before and immediately after chemotherapy suggest that these schedules besides being safe and effective in the treatment of the ovarian cancer, have an extremely low peripheral neurotoxicity. Paper presented at the National Congress at Sorrento in 1991 and selected by the Editorial Board of the Journal.     

Peripheral nerve electrophysiology studies in relation to fatigue in patients with chronic inflammatory demyelinating polyneuropathy

ObjectiveTo explore the relationship between fatigue, standard electrophysiological parameters and number and size of functioning motor units in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).MethodsExperienced fatigue was assessed using the linearly-weighted, modified Rasch-built fatigue severity scale (R-FSS) and the multidimensional Checklist of Individual Strength (CIS). Averaged electrophysiology values were calculated from multiple nerves. Motor Unit Number Index (MUNIX) technique was utilised to assess motor unit function. Assessments were repeated in 15 patients receiving regular intravenous immunoglobulin therapy, with changes in parameters calculated.ResultsR-FSS and CIS scores did not correlate MUNIX or MUSIX sum scores from 3 different muscles. Inverse correlation was observed only between distal CMAP area and R-FSS but not CIS scores. However, changes in distal CMAP area and R-FSS scores on repeat assessment were not correlated.ConclusionsExperienced fatigue does not appear to correlate with loss of functioning motor units in patients with CIDP. Changes in experienced fatigue on repeat assessment did not correlate with changes in any of the electrophysiological parameters, suggesting fatigue experienced in CIDP is not strongly correlated with peripheral nerve dysfunction.SignificanceNerve conduction studies and MUNIX values do not appear to be useful surrogate markers for fatigue in CIDP.     

Peripheral Neuropathy Associated with Ulcerative Colitis

Abstract: This is a report of two cases of peripheral neuropathy associated with ulcerative colitis (UC). Patient 1 developed asymmetric neuropathy two weeks after the onset of UC. Subsequent neurological improvement paralleled the improvement in the active UC as revealed by colonoscopy. Patient 2 exhibited sensory ataxic neuropathy with deposits of IgG and Λ chain in the sural nerve. Both patients showed axonal neuropathy, and corticosteroid therapy improved the neurological symptoms. These types of neuropathy have not previously been reported in association with UC.     

定量感觉及神经传导检测在糖尿病患者中的应用比较

目的:分析定量感觉检查(QST)及神经传导检测(NCS)在糖尿病患者中的应用价值.方法:用QST对100例2型糖尿病(T2DM)组和50例正常对照组分别进行四肢的冷觉(CS)、温觉(WS)、冷痛觉(CP)、热痛觉(HP)的感觉阈值测定并进行比较分析;并对T2DM患者进行上肢的正中神经、尺神经,下肢的胫神经、腓神经运动和感觉支的NCS、复合肌肉动作电位(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.T2DM患者分为有症状组和无症状组,分别对QST及NCS的异常率进行分析并比较.结果:T2DM组QST和NCS结果与正常对照组比较差异有显著意义(P＜0.01); QST与NCS异常率比较差异有显著意义(P＜0.01),QST的异常率均显著大于NCS;提示糖尿病周围神经病(DPN)患者中周围神经小纤维受损比大纤维更明显,T2DM患者有症状组和无症状组各值比较差异均有显著意义(P＜0.01).结论:QST对DPN的早期诊断提供可靠依据,QST对DPN的诊断敏感性高,但特异性低,需与NCS结合对糖尿病周围神经状况进行评价更为完善.QST和NCS不能相互替代,全面了解DPN病情需QST和NCS结合,并密切结合临床.     

Peripheral and central conduction times in hereditary pressure-sensitive neuropathy

Summary Seven members of a family with histologically proven hereditary pressure-sensitive neuropathy (HPSN) agreed to be examined clinically and electrophysiologically. A sural nerve biopsy specimen taken from the propositus who suffered from a partial brachial plexus palsy showed typical sausage-like myelin sheath thickenings reflecting a failure of axon-adjusted myelination. Reduced motor and sensory conduction velocities involving several nerves were found in the four family members with clinical signs of HPSN. In addition, central conduction times in the auditory and somatosensory pathways were determined measuring the interwave latency I–V in brainstem auditory-evoked potentials and the interpeak latency N14–N20 in median nerve sensory-evoked potentials. Central conduction times in both afferent systems were within normal limits. The absolute delay of peak N14 and N20 in median and P40 in tibial nerve-evoked potentials was probably due to an impaired conduction in the peripheral branch of the bipolar ganglion cell. Whether the central axon branch in the dorsal columns was also involved could not be decided.

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Zusammenfassung Sieben Mitglieder einer Familie mit hereditärer druckempfindlicher Neuropathie wurden klinisch und elektrophysiologisch untersucht. Im Suralis-Bioptat des Propositus, der sich wegen einer inkompletten Armplexusparese vorstellte, zeigten sich die charakteristischen tomaculären (wurstförmigen) Myelinverdickungen als Hinweis auf eine gestörte Axon-Myelin-Relation. Bei den vier Familienmitgliedern mit den klinischen Zeichen der Erkrankung fanden sich verlangsamte motorische und sensible Leitgeschwindigkeiten an verschiedenen Nerven. Zusätzlich wurde die zentrale Leitungszeit in auditiven und somatosensorischen Bahnen bestimmt, wobei die Latenzdifferenzen von Welle I–V im akustisch evozierten Hirnstammpotential und von Peak N14–N20 in Medianus-SEP berechnet wurden. Die zentralen Leitungszeiten in beiden Systemen lagen im Normbereich. Die absolute Verzögerung von N14 und N20 in Medianus- sowie P40 in Tibialis-SEP ist wahrscheinlich Folge einer verlangsamten Leitung im peripheren Ast der bipolaren Ganglienzelle. Ob auch eine Affektion des zentralen Axonastes in den Hintersträngen vorliegt, kann anhand der Resultate dieser Arbeit nicht entschieden werden.

     

Peripheral nerve neurolymphomatosis: Clinical features,treatment, and outcomes

Introduction: This series characterises nine patients with neurohistopathologically proven peripheral nerve neurolymphomatosis. Methods: A search of the hospital neuropathology database from 2002 to 2019 identified biopsy proven cases. Clinical data, investigation modalities, treatments, and outcomes were collated. Median age at neuropathy onset was 47 y, the neuropathy commonly as the initial lymphoma disease manifestation. Most (8/9) presented with painful asymmetrical sensory disturbance, with additional cranial nerve involvement in three. Neurophysiology typically demonstrated multiple axonal mononeuropathies. Cerebrospinal fluid protein was often raised (6/8). Magnetic resonance imaging suggested peripheral nerve infiltration in 6/9 and positron emission tomography CT in 4/9. Bone marrow biopsy was abnormal in 6/8. Treatment involved systemic or intrathecal chemotherapy and radiotherapy. Median survival was 23 mo. Discussion: Neurolymphomatosis is a rare but important cause of neuropathy, particularly in those lacking systemic evidence of lymphoma as correct aggressive treatment can prolong survival. Nerve biopsy is essential to classify lymphoma type and rule out alternatives.