Long-term nervous system damage from radiation of the spinal cord: An electrophysiological study

Summary A group of 13 patients suffering from Hodgkin's disease who had undergone chemotherapy and radiotherapy (above and below the diaphragm) approximately 10 years earlier was studied. The total chemotherapeutic dose was similar for all patients; the radiotherapy dose, however, was standard for 7 patients, while the other 6 received much higher dosages over limited regions of the spinal cord. Although most of these patients appeared normal both clinically and on magnetic resonance imaging, a neurophysiological study was performed to determine whether there was any involvement of the central or peripheral nervous system. Motor conduction velocity and sensory conduction velocity were measured in the lower limbs as well as spinal- and scalprecorded somatosensory evoked potentials (SEPs) in response to stimulation of the posterior tibial and sural nerves at the ankle. In addition, motor evoked potentials were recorded from the upper and lower limbs during cortical stimulation. All neurophysiological data were normal in patients who had received a standard radiation dose, while most of those who had been exposed to higher doses showed altered cortical SEPs and a slowing of central conduction time (D10-P1). Thus even though they were asymptomatic, these patients appeared to have sustained CNS damage, mainly at the level of the spinal cord.     

Nerve conduction and electromyography studies

Nerve conduction studies (NCS) and electromyography (EMG), often shortened to 'EMGs', are a useful adjunct to clinical examination of the peripheral nervous system and striated skeletal muscle. NCS provide an efficient and rapid method of quantifying nerve conduction velocity (CV) and the amplitude of both sensory nerve action potentials (SNAPs) and compound motor action potentials (cMAPs). The CV reflects speed of propagation of action potentials, by saltatory conduction, along large myelinated axons in a peripheral nerve. The amplitude of SNAPs is in part determined by the number of axons in a sensory nerve, whilst amplitude of cMAPs reflects integrated function of the motor axons, neuromuscular junction and striated muscle. Repetitive nerve stimulation (RNS) can identify defects of neuromuscular junction (NMJ) transmission, pre- or post-synaptic. Needle EMG examination can detect myopathic changes in muscle and signs of denervation. Combinations of these procedures can establish if motor and/or sensory nerve cell bodies or peripheral nerves are damaged (e.g. motor neuronopathy, sensory ganglionopathy or neuropathy), and also indicate if the primary target is the axon or the myelin sheath (i.e. axonal or demyelinating neuropathies). The distribution of nerve damage can be determined as either generalised, multifocal (mononeuropathy multiplex) or focal. The latter often due to compression at the common entrapment sites (such as the carpal tunnel, Guyon's canal, cubital tunnel, radial groove, fibular head and tarsal tunnel, to name but a few of the reported hundred or so 'entrapment neuropathies').     

Latencies of peripheral nerve and cerebral evoked responses to air-puff and electrical stimuli

This study examined the latency relationship between mechanically and electrically elicited sensory nerve action potentials (SNAPs) and the somatosensory-evoked potentials (SEPs) they produce. Brief air-puff and electrical stimuli were applied to the tip of the index finger in separate trials and SNAPs from the median nerve at the wrist and SEPs from the scalp were recorded for each stimulus presentation. Air-puff evoked SNAPs were polyphasic, usually consisting of 2 to 4 separate waves, unlike triphasic activity elicited by electrical stimulation. The SEPs produced by these 2 distinct forms of inputs, however, were similar in morphology. The latencies of the initial components of SNAPs and SEPs were longer for air-puff stimulation. The conduction time, however, of the fastest afferent volleys from the wrist to cortex was not significantly different for air-puff (20.52 +/- 1.06 ms, mean +/- SD) and electrical stimulation (20.17 +/- 0.66 ms). It is therefore concluded that the latency delays for air-puff evoked SNAPs and SEPs are due solely to a transduction time at the skin receptors and not due to differences in conduction velocities as suggested in the previous literature.     

Quantitative electrophysiological study of alcoholic neuropathy.

Thirty-one chronic alcoholic patients were investigated using quantitative electrophysiological techniques. Estimates of the numbers of functioning motor units in the extensor digitorum brevis muscles and measurements of the parameters of the potentials of these units are presented along with the values for motor nerve conduction velocities in the innervating lateral popliteal nerves. Motor conduction velocities and sensory nerve action potential amplitudes were also measured in the ulnar nerves. The results and their inter-relationships lead us to conclude that the slowing of motor nerve conduction and reduction in sensory nerve action potential amplitudes in alcoholic neuropathy are a consequence of axon loss. We found no evidence of pathological slowing of conduction in surviving axons. Reinnervation by functioning motor axons is poor compared to a number of other neuropathic conditions. In our patients there was no evidence of preferential involvement of sensory axons. The results support a predominant axonal dysfunction in alcoholic neuropathy.     

Multiple measures of axonal excitability in peripheral sensory nerves: an in vivo rat model

Excitability measurements on human motor and sensory nerves have provided new insights into axonal membrane changes in peripheral nerve disorders. The aim of this study was to establish an in vivo rat preparation suitable for threshold tracking of sensory nerve action potentials (SNAPs) to model clinical sensory nerve excitability studies. In Sprague-Dawley rats anesthetized with ketamine and xylazine, current stimuli were applied to the base of the tail and SNAPs recorded from distal needle electrodes. Multiple excitability data were obtained as previously described for human nerves and compared to recordings from the motor tail axons and to sensory recordings from human median and ulnar nerves. The pattern of excitability changes in rats was broadly similar to that in humans, although some parameters differed significantly. Individual recordings were stable for at least 3 h. These data show that the rat tail enables excitability properties of sensory as well as motor axons to be studied experimentally, e.g., in models of nerve disease and during pharmacological interventions.     

Electrophysiological features of patients with POEMS syndrome.

OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome is a rare cause of polyneuropathy. Although the polyneuropathy component is essential for the diagnosis of the disease, the pattern of associated electrodiagnostic abnormalities has not been characterized in detail. The purpose of this study was to elucidate the features of nerve conduction abnormalities in POEMS syndrome. METHODS: We reviewed the medical records and nerve conduction studies (NCS) of 12 consecutive patients with POEMS. RESULTS: A total of 68 motor and 46 sensory nerves were examined. Compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) were not elicited in lower limbs more frequently compared with in upper limbs (P<0.05, in both motor and sensory nerves), and the CMAP amplitude was more attenuated in lower limbs than in upper limbs (P<0.05). Abnormal conduction slowing was frequently observed in motor (95%) and sensory (76%) nerves. Distal motor latencies were abnormally prolonged in 75% of the motor nerves, and terminal latency indices were significantly higher in patients than in normal controls (P<0.05). CONCLUSIONS: NCS in POEMS syndrome showed characteristic patterns, in which conduction abnormalities were more frequently and severely affected in the lower limbs, and more predominantly in the intermediate nerve segments than in the distal portions. SIGNIFICANCE: The recognition of these characteristic patterns may be helpful for the early diagnosis of polyneuropathy in POEMS syndrome.     

Differential conduction and CGRP release in visceral versus cutaneous peripheral nerves in the mouse

Cutaneous afferent nerves convey sensory information from the external, visceral nerves from the internal environment. The saphenous nerve arising from lumbar dorsal root ganglia and the vagus nerve originating in the nodosum ganglia are prototypic examples of such cutaneous and visceral nerves. Despite a common sensory role, these two nerves have distinct embryonic origin and vary in neuropeptide expression. Because of their distinct physiological roles, it is plausible that they differ also in conductive properties. We have tested calcitonin gene‐related peptide (CGRP) release in these nerves in response to electrical and chemical stimulation. Electrical stimulation at 3, 6, and 9 Hz increased the release in saphenous but not vagus nerves, with 6 Hz being the most potent stimulus. Similarly, both capsaicin and a depolarizing solution of 60 mM KCl evoked CGRP release in saphenous but not vagus nerves. Simultaneous recording of the superimposed (compound) action potentials of these nerves revealed that only saphenous nerves exhibit a progressive and marked activity‐dependent slowing of conduction velocity in response to electrical stimulation at 3, 6, and 9 Hz (30%, 44%, and 50%, respectively). Capsaicin caused an unexpected decrease in conduction latency (i.e., speeding) in contrast to the slowing seen in other nerves. Exposure of axons to 1 µM TTX rapidly blocked conduction in all nerves. Together our results demonstrate that vagus and saphenous primary afferents reveal different activation and conductive properties, presumably correlating their particular physiological roles in transmitting sensory signals. © 2018 Wiley Periodicals, Inc.     

Evolution of motor and sensory deficits in amyotrophic lateral sclerosis estimated by neurophysiological techniques

Although amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motor neurons, there is evidence that the disease can affect other systems, including the sensory system. On the other hand, within the motor neuron pool there is possibly a predilection of the degenerative process for the motor neurons fibers with the fastest conduction velocity (MNFCV). We studied these two aspects of the disease in a group of 50 patients by prospectively assessing several sensory indices and by studying the selectivity of the spinal motor neuron loss. At baseline, nerve conduction studies and somatosensory evoked potentials showed abnormal slowing in the peripheral and central sensory pathways. Thermal thresholds for heating were elevated but were normal for cooling. In more than 60% of the patients at least one of the sensory tests studied was abnormal. However, except for a significant decrease in the amplitude of the sensory nerve action potentials of the sural nerves, these afferent dysfunctions were not progressive over the follow-up period of 6 months, in contrast to the marked deterioration in motor functions. Three different statistical models were applied to evaluate the presence of demyelination, selective loss of MNFCV, or the purely random degeneration of fast- and slow-conducting motor neurons. These data indicate a selective loss of the MNFCV and suggest that subclinical abnormalities of the sensory system in ALS are often present but almost nonprogressive. Furthermore, the amyotrophic lateral sclerosis disease process seems preferentially to affect MNFCV. Received: 22 December 1997 Received in revised form: 27 August 1998 Accepted: 26 October 1998     

Conduction velocity and temporal dispersion of the nerve volleys evoked by air-puff stimulation of the index finger and palm.

Air-puff stimuli were delivered to 5 successive sites (3 cm increments) over the index finger and palm to record propagating sensory nerve action potentials (SNAPs) from surface electrodes over the median nerve at the wrist. SNAPs consisted of a series of individual peaks (N1, P1, P2, N2 and P3) and the corresponding peaks in the records with stimulation at the various locations could be identified. The apparent conduction velocity of the first peak determined from the stimulation point at the finger tip to the wrist was 38 m/sec. With stimulation of the more proximal locations it became even slower. This paradoxical slowing is due to an increasing effect in the calculation of conduction velocity of the utilization time at the receptors for air-puff stimulation at progressively proximal sites. Segmental conduction velocity estimated between adjacent stimulus sites was 10-20 m/sec faster than the distal conduction velocity between the finger tip and the wrist. Within each segment, the conduction velocities of the individual peaks were not significantly different. These findings, together with invariant durations of the negative components (N1 and N2) in the propagating SNAPs along the ascending digital nerves, lead to the conclusion that the separate peaks are not the result of temporal dispersion due to differences in conduction velocity of skin afferents, but are primarily due to a more peripheral receptor mechanism involving variable delays in activation of different classes of mechanoreceptors.     

Motor and sensory conduction failure in overlap of Guillain-Barré and Miller Fisher syndrome: two simultaneous cases

We report 2 patients diagnosed simultaneously with an overlap of Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), who had anti-GT1a, anti-GQ1b, anti-GD1a and anti-GD1b antibodies. There was no identifiable specific preceding infection. Both patients presented with upper and lower limb paresthesias and severe weakness, bulbar and facial weakness, ophthalmoparesis and areflexia. In one, electrophysiology demonstrated multifocal conduction blocks (CBs) and mild motor conduction velocity slowing in intermediate segments and absent sensory nerve action potentials (SNAPs). The patient improved rapidly and fully recovered within 18 days from onset. CBs resolved, distal compound muscle action potential (CMAP) amplitudes increased and SNAPs normalized on subsequent testing. In the other patient, initial studies showed low/normal CMAPs, with absent SNAPs, without demyelinating features. This patient fully recovered within 21 days from onset. CMAPs markedly increased, SNAPs improved marginally. These 2 patients exhibited features indicative of the pathophysiological mechanism of conduction failure in motor and sensory fibers. This phenomenon relates to rapidly resolving CBs possibly induced by the transitory and limited attack of antiganglioside antibodies at the axolemma of the nodes of Ranvier not progressing to axonal degeneration. These cases widen the range of GBS subtypes in which reversible conduction failure has been described, to include overlap syndromes with MFS. The factors determining the electrophysiology, as well as the rate, degree and quality of recovery in GBS subtypes remain uncertain at the present time.     

Electrophysiological studies in five cases of abetalipoproteinemia

Auditory brainstem responses (ABRs), visual and somatosensory evoked responses (VEPs and SEPs) and nerve conduction studies were conducted in 5 patients with abetalipoproteinemia. The ABRs were normal in all cases. The VEPs were of normal amplitude but of increased latencies in two patients. The four eldest patients had delayed cortical SEPs but normal peripheral sensory nerve conduction studies. The peripheral motor conduction velocities were normal in all cases. The peripheral sensory studies showed normal velocity when a response was seen; however, the amplitude of the response was often reduced or it was absent. The electrophysiological studies reported here support a model of axonal loss of large myelinated fibres with secondary demyelination in abetalipoproteinemia.     

Use of somatosensory evoked potentials to evaluate the peripheral nervous system

Somatosensory evoked potentials (SEPs) are being used increasingly to evaluate peripheral somatosensory pathways. They have been used in patients with plexus lesions but may provide misleading information when multiple lesions are present, demonstrating only the electrophysiologic consequences of the most distal lesion that is present. Ulnar SEPs can be abnormal in neurogenic thoracic outlet syndrome, whereas they are normal in the nonneurogenic variety. SEPs to nerve trunk stimulation are generally not helpful in patients with isolated radiculopathies, and SEPs elicited by dermatomal or cutaneous nerve stimulation have provided conflicting results. SEPs may be important in evaluating conduction along inaccessible proximal segments of limb nerves. Their value in Guillain-Barré syndrome, in which pathology may be predominantly proximal, is unclear. In evaluating peripheral neuropathies, SEPs can sometimes be useful when peripheral sensory nerve action potentials are unobtainable; sometimes, however, SEPs provide misleading information concerning conduction velocity. The SEP findings should not be relied on to determine whether sensory loss is organic or nonorganic, although they are one factor to consider in making this determination.     

神经型布氏杆菌病周围神经损害的临床与电生理研究

目的研究神经型布氏杆菌病周围神经损害的临床特征,探讨电生理对其的诊断价值。方法对32例神经型布氏杆菌病周围神经损害患者(病例组)和32名性别及年龄与病例组匹配的正常对照组进行神经电生理检查,并对所得检查结果进行统计学分析。结果病例组与对照组在运动末梢潜伏期(distal motor latency,DML)、复合肌肉动作电位(compound motor active potentials,CMAP)波幅、运动神经传导速度(motor nerve conduction velocity,MCV)、感觉神经动作电位潜伏期(sensory nerve action potential latency,SL)、感觉神经动作电位(sensory nerve action potential,SNAP)波幅及感觉神经传导速度(sensory nerve conduction velocity,SCV)方面的比较,差异均有统计学意义(P0.05)。电生理检查提示上下肢周围神经损害,感觉神经及运动神经均受累,其中感觉神经占55.47%,运动神经占16.80%,上肢以正中神经(64条)最多见,下肢以腓肠神经(16条)最多见。四肢运动神经256条中43条传导速度减慢,占16.80%,四肢感觉神经256条中142条传导速度减慢,占55.47%,SCV较MCV改变明显,上肢病变重于下肢。结论神经电生理检查为神经型布氏杆菌病周围神经损害的临床诊断提供了客观依据。     

Conduction pathways of the solar plexus in dogs]

The conduction pathways of dog's solar plexus were studied, using the recording of action potentials of the plexus nerves. Greater splanchnic nerves consists of two groups of afferent A-fibres (conduction velocity of 12-15 and 25-56 m/s), afferent C-fibres (conduction velocity of 0.4-2.0 m/s) and preganglionic B- and C-fibres (conduction velocity of 1.0-12.0 m/s). Afferent A- and and C-fibres pass through the solar plexus ganglia to the dorsal roots; preganglionic fibres terminate synaptically on ganglionic neurons, their axons pass in the peripheral nerves to the viscera. Pathways between the peripheral nerves were found; probably they form peripheral reflex arcs.     

Slow motor conduction mainly limited to motor root in amyotrophic lateral sclerosis

Motor conduction velocity is expected to be normal or nearly normal in amyotrophic lateral sclerosis (ALS). Some studies have suggested that pathology may be present in the proximal axons. Indeed, some investigators have shown a decrease in the proximal conduction velocity in ALS by using motor conduction velocity measurements and H-reflex and F-response recordings, but they could not delineate the precise region of the conduction pathology. In this study, unlike the ones carried out previously, the most proximal segment has been studied in 11 patients with ALS, 13 normal controls, and 5 patients with sequel of poliomyelitis (SPM) by recording sensory and motor spinal root potentials. While no conduction pathology, H-reflex, or F-response abnormalities were found in ALS patients compared to normal subjects, it was shown that conduction velocity decreased in the proximal segment of the lower motor neuron of the ventral root. Despite motor neuron pathology in SPM, there was no proximal motor conduction slowing compared with that in normal subjects. © 1996 John Wiley & Sons, Inc.     

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.     

Peripheral neuropathy is linked to a severe form of myotonic dystrophy in transgenic mice

Myotonic dystrophy type 1 (DM1) is a multisystem disorder with a variable phenotype. The involvement of peripheral nerves in DM1 disease is controversial. The DM1 animal model DM300 transgenic mice that carry 350 to 500 CTG repeats express a mild DM1 phenotype but do not exhibit motor or sensory pathology. Here, we investigated the presence or absence of peripheral neuropathy in transgenic mice (DMSXL) that carry more than 1,300 CTG repeats and display a severe form of DM1. Electrophysiologic, histologic, and morphometric methods were used to investigate the structure and function of peripheral nerves. We observed lower compound muscle action potentials recorded from hind limb muscles and slowing of sciatic nerve conduction velocity in DMSXL versus control mice. Morphometric analyses showed an axonopathy and neuronopathy in the DMSXL mice characterized by a decrease in numbers of myelinated motor axons in sciatic nerve and in spinal cord motor neurons. Pathologic alterations in the structure of hind limb neuromuscular junctions were also detected in the DMSXL mice. These results suggest that peripheral neuropathy can be linked to a large CTG expansion and a severe form of DM1.     

Electroneurographic evidence of polyneuropathy in chronic liver disease.

An electroneurographic study performed on the peripheral nerves of 25 patients with severe cirrhosis following viral hepatitis showed slight slowing (P greater than 0.05) of motor conduction velocity (CV) and significant diminution (P less than 0.001) of sensory CV and mixed sensorimotor-evoked potentials, associated with a significant decrease in the amplitude of sensory evoked potentials. The slowing was about equal in the distal (digital) and in the proximal segments of the same nerve. A mixed axonal degeneration and segmental demyelination is presumed to explain these findings. The CV measurements proved helpful for an early diagnosis of hepatic polyneuropathy showing subjective symptoms in the subclinical stage.     

F response and somatosensory and brainstem auditory evoked potential studies in HMSN type I and II.

To evaluate conduction along the proximal and distal segments of motor and sensory long limb nerves, as well as along the very short acoustic nerve, F response and somatosensory and brainstem auditory evoked potential were studied in a series of patients with hereditary motor and sensory neuropathy (HMSN) types I and II. A diffuse and comparable slowing of conduction in proximal and distal nerve segments, as well as along the acoustic nerve, seems to favour a primary myelin defect in HMSN I. F response and motor conduction velocity showed a similar derangement in both proximal and distal motor segments. Latencies of somatosensory evoked potentials were symmetrically prolonged and correlated with motor nerve impairment. Central conduction times were normal. Studies of brainstem auditory evoked potentials showed a high incidence of acoustic nerve involvement, the most evident abnormality being a statistically significant increase in the latency of the I wave. Our data seem to support the presence of primary myelinopathic damage in HMSN I.     

Sensory conduction study in chronic sensory ataxic neuropathy.

Sensory conduction was studied in six patients with chronic sensory ataxic neuropathy of an idiopathic type and associated with Sjögren's syndrome. Motor nerve conduction velocities were normal in most cases, but sensory nerve potentials could not be evoked in a routine peripheral nerve conduction study. Cortical and cervical somatosensory evoked potentials (SEPs) and evoked potentials from Erb's point were barely recorded by median nerve stimulation at the wrist. When the median nerve was stimulated at more proximal points, clear potentials were recorded from Erb's point, but cortical SEPs were still hardly elicited. Thus the sensory nerves are centrally and peripherally involved in this condition, and the involvement is more prominent in the distal portion in the peripheral nerve. These findings suggest that central-peripheral distal axonopathy is a process involved in this illness and that the dorsal root ganglia may be primarily involved, in accord with previous pathological studies.