Syringomyelia-like manifestation of subacute combined degeneration.

A 32-year-old male presented with progressive weakness and numbness of both upper limbs of one-month duration. The patient had weakness and wasting of small muscles of both hands with weak grip. Sensory system revealed graded sensory loss to pain, temperature and touch in C5 to T1 distribution and vibration and joint position sense from C5 to C8 in the both upper limbs. There was areflexia in the upper limbs while there was no motor or sensory deficit in the lower limbs. The cortical potential on stimulation of posterior tibial nerve was prolonged on both sides. On MR imaging of the cervical spine there was iso to low intense lesion which was hyperintense on T2-weighted imaging along the dorsal aspect of the cord extending from C2 to C6 level. The axial images showed involvement of the posterior column. The serum vitamin B12 level was found to be low. The patient responded to parenteral cyanocobalamine therapy and the radiological lesion subsequently resolved.     

Sural nerve conduction velocity in peripheral neuropathies and subacute myelo-optico-neuropathies (SMON)

Sensory conduction velocity in the sural nerve (S-SCV) was measured in 10 cases of motor neuropathy, 35 cases of neuropathy with sensory symptoms and in 16 cases of subacute myelo-optico-neuropathy (SMON).In 2 cases of Friedreich's ataxis and 1 case of Charcot-Marie-Tooth disease, evoked sensory action potentials could not be recorded or S-SCV was reduced though sensation was normal; this finding suggests latent or subclinical involvement of the sensory nerves in these cases. In the other 7 cases of motor neuropathy, S-SCV was normal.In the cases of polyneuropathy with sensory symptoms, S-SCV was abnormal in 5 of 11 cases with subjective sensory complaints and in 6 of 10 cases with mild impairment of superficial sensation. No nerve potential could be evoked in 2 cases with severe impairment of superficial sensation, in 7 of 8 cases with mild impairment of deep sensation, and in 4 cases with severe impairment of deep sensation. These data suggest that S-SCV may be useful in confirming the extent of sensory nerve involvement in mildly-affected cases.In the case of SMON, though the S-SCVs could generally be correlated with the severity of the sensory symptoms, the degree of decrease in S-SCV was far less than in the cases of sensory neuropathy with similar symptoms. This discrepancy suggests that myelopathy in addition to peripheral neuropathy plays an important part in causing the sensory symptoms of SMON.     

Subacute combined degeneration of spinal cord. Significance of peripheral nerve involvement

A 36 year old woman was admitted to the hospital in November 1983 because of her inability to walk. For 3 months prior to admission, she took oral contraceptives (OCs) as a treatment for amenorrhea. 2 months prior to admission, she had general malaise, anorexia, and unsteady gait. 1 month before her admission, tingling and numbness began in the fingertips and spread up to the forearms, a tight feeling around the waist developed, and walking became ataxic. On admission to the hospital, she was thin and pale with greying hair. Her mind was clear and there were no abnormalities of the cranial nerves. Her extremities were hypotonic but not wasted. Slight muscle weakness of the hands and feet was noted. There was myokymia in both legs. Deep tendon reflexes of the extremities were absent. The plantar responses were extensor and lack of coordination in the extremities was noted. There was a definite glove and stocking type of hypesthesia to pinprick and cotton wool. Vibration sense was decreased below T11 and lost in both legs. There was a marked loss of position sense to passive movement in the legs and some impairment in the hands. Laboratory examination revealed mild magaloblastic anemia, elevated LDH, borderline low concentration of vitamin B12 in the serum, increased excretion of methylmalonate in the urine, achylia, positive antiparietal cell antibody and positive anti-intrinsic factor antibody. Cyanocobalamin absorption by the Schilling test was 5.6% after intrinsic factor, 11.3%. The diagnosis of pernicious anemia was made. Upper gastrointestinal studies showed typical carcinoid tumors of the stomach. Cerebrospinal fluid was normal. Peripheral nerve conduction studies demonstrated normal or slightly decreased motor conduction velocities and absent sensory action potential. Sural nerve biopsy was performed. Myelinated fibers were moderately decreased in number to 5554/mm squared and pronounced loss of large myelinated fibers was demonstrated in fiber histogram. Teased method of the single fiber showed mainly axonal degeneration. Anemia and neurologic function improved rapidly with parenteral hydroxocobalamin therapy and 1 month after treatment commenced, she was able to walk without assistance. The clinical significance of peripheral nerve involvement of subacute combined degeneration of the spinal cord was discussed, as the peripheral nerve affection is only poorly understood in contrast to the myelopathy. This was followed by discussion of the possible effect of the OCs and gastric carcinoid to neurological manifestation of pernicious anemia. (author's modified)     

中国亚急性联合变性诊治共识

亚急性联合变性由维生素B12缺乏导致,该病可以做到早期诊断和治疗,从而逆转临床症状。为了指导我国亚急性联合变性的规范性诊疗,在中华医学会神经病学分会的领导下,中华医学会神经病学分会周围神经病协作组、肌电图与临床神经电生理学组和神经肌肉病学组专家共同合作编写该共识。     

Acupuncture treatment improves nerve conduction in peripheral neuropathy

The etiology of peripheral neuropathy (PN) often remains elusive resulting in a lack of objective therapeutic strategies. We conducted a pilot study to evaluate the therapeutic effect of acupuncture on PN as measured by changes in nerve conduction and assessment of subjective symptoms. One hundred and ninety-two consecutive patients with PN as diagnosed by nerve conduction studies (NCS) were evaluated over a period of 1 year. Of 47 patients who met the criteria for PN of undefined etiology, 21 patients received acupuncture therapy according to classical Chinese Medicine as defined by the Heidelberg Model, while 26 patients received the best medical care but no specific treatment for PN. Sixteen patients (76%) in the acupuncture group improved symptomatically and objectively as measured by NCS, while only four patients in the control group (15%) did so. Three patients in the acupuncture group (14%) showed no change and two patients an aggravation (10%), whereas in the control group seven showed no change (27%) and 15 an aggravation (58%). Importantly, subjective improvement was fully correlated with improvement in NCS in both groups. The data suggest that there is a positive effect of acupuncture on PN of undefined etiology as measured by objective parameters.     

亚急性联合变性的神经电生理研究

目的:探讨神经电生理检查在亚急性联合变性(SCD)早期诊断及疾病预后判定中的意义.方法:选取35例SCD患者,分别进行脊髓MRI、胫后神经体感诱发电位(SEP)、正中神经SEP、视觉诱发电位(VEP)和神经传导速度(NCV)检查,比较上述检查阳性率的差异,探讨不同检查的诊断敏感性及其对应神经结构受累的时序差别.结果:本组30例SCD患者接受脊髓MRI检查,其中有12例(40％)发现异常,35例接受胫后神经SEP、正中神经SEP、VEP、NCV检查,分别有32例(91％)、23例(66％)、7例(20％)和15例(43％)发现异常.PT-SEP与脊髓MRI的阳性率存在显著差异(P＜0.05),PT-SEP、MN-SEP、VEP、NCV的阳性率也存在显著差异(P＜0.05).结论:①神经电生理检查在SCD的诊断过程中具有较高的敏感性,对SCD的早期诊断具有重要的临床意义;②神经电生理检查可以反映SCD神经结构受累的范围及时序,对SCD的疾病预后判定有一定帮助.     

A combined morphological and electrophysiological study of conduction block in peripheral nerve

The reliability of the electrophysiological criterion of conduction block in determining the presence of focal demyelination in a peripheral nerve has been studied in an animal model. Demyelination was produced in the rat tibial nerve by one or two closely spaced microinjections of lysophosphatidylcholine (LPC). Histological and electrophysiological data were obtained on the acute lesion (up to 6 days), and during recovery (up to 11 weeks). Single LPC injections produced a lesion of very variable severity. Double injections more reliably produced a severe lesion with marked conduction block. Slight axonal damage was occasionally seen in nerves showing severe demyelination. The ratio of amplitude of muscle action potentials evoked by stimuli proximal and distal to the sites of nerve injection was calculated to detect the development of conduction block. The post injection ratio was more than 2 standard deviations below the control mean in 86% of nerves showing signs of demyelination. No control saline injected nerves showed such evidence of conduction block. The severity of the electrophysiological abnormality did not prove a reliable indicator of the severity of the histological lesion, however. The possible reasons for this variability are discussed and it is argued that caution should be exercised when interpreting this particular electrophysiological finding in clinical practice.     

Ascorbic acid accelerates Wallerian degeneration after peripheral nerve injury

Wallerian degeneration occurs after peripheral nerve injury and provides a beneficial microenvironment for nerve regeneration. Our previous study demonstrated that ascorbic acid promotes peripheral nerve regeneration, possibly through promoting Schwann cell proliferation and phagocytosis and enhancing macrophage proliferation, migration, and phagocytosis. Because Schwann cells and macrophages are the main cells involved in Wallerian degeneration, we speculated that ascorbic acid may accelerate this degenerative process. To test this hypothesis, 400 mg/kg ascorbic acid was administered intragastrically immediately after sciatic nerve transection, and 200 mg/kg ascorbic acid was then administered intragastrically every day. In addition, rat sciatic nerve explants were treated with 200 μM ascorbic acid. Ascorbic acid significantly accelerated the degradation of myelin basic protein-positive myelin and neurofilament 200-positive axons in both the transected nerves and nerve explants. Furthermore, ascorbic acid inhibited myelin-associated glycoprotein expression, increased c-Jun expression in Schwann cells, and increased both the number of macrophages and the amount of myelin fragments in the macrophages. These findings suggest that ascorbic acid accelerates Wallerian degeneration by accelerating the degeneration of axons and myelin in the injured nerve, promoting the dedifferentiation of Schwann cells, and enhancing macrophage recruitment and phagocytosis. The study was approved by the Southern Medical University Animal Care and Use Committee(approval No. SMU-L2015081) on October 15, 2015.     

Wallerian degeneration of peripheral nerve

Summary The age-dependent loss of the major peripheral nerve lipids (cholesterol, phospholipid, and total galactolipid) was quantitated over a period of 9 weeks of Wallerian degeneration induced by surgical transection of rabbit sciatic nerves in animals of several ages. Proportionate losses of these lipids were determined by calculating the content of each lipid on a per nerve and on a per gram fresh weight basis remaining after a given period of Wallerian degeneration as a percent of original normal values at several times following surgery. The proportionate loss of each lipid from the distal stump was the most prompt and the most complete in nerves transected at 2 weeks of age, and the least in nerves transected at 20 weeks of age. The prompter clearance of these lipids from younger than older degenerating nerve gives convincing evidence that the suggestion from light-microscopic studies of faster clearance of neural debris in younger than in older animals is correct. A possible relationship between these biochemical findings and the phenomenon of greater functional recovery from peripheral nerve injury in younger than in older subjects is discussed.Supported by an N.I.H. grant (NS-10165)     

Role of microtubule dynamics in Wallerian degeneration and nerve regeneration after peripheral nerve injury

Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cytoskeletal reconstruction.However,it is unclear whether microtubule dynamics play a role in this process.To address this,we treated cultured sciatic nerve explants,an in vitro model of Wallerian degeneration,with the microtubule-targeting agents paclitaxel and nocodazole.We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation,whereas nocodazole-induced microtubule destabilization inhibited these processes.Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration,as well as functional recovery of nerve conduction and target muscle and motor behavior,respectively.These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration.This study was approved by the Animal Care and Use Committee of Southern Medical University,China(approval No.SMUL2015081) on October 15,2015.     

Central motor conduction time by magnetic stimulation of the cortex and peripheral nerve conduction follow-up studies in Friedreich's ataxia

A follow-up clinical study, peripheral motor and sensory nerve conduction velocities and central motor conduction by magnetic stimulation of the cortex were performed in 13 patients with classical Friedreich's ataxia (FA) phenotype, for a period of 9–12 years. Clinical worsening was unrelated to peripheral nerve abnormalities. The amplitude of the nerve action potentials and delayed conduction velocity remained unchanged for several years. Central motor conduction times were abnormal in all patients. Clinical conditions worsened significantly between successive examinations with significant increments in threshold and significant decrement of the amplitude of motor evoked potentials. The results are consistent with progressive pyramidal and cerebellar pathways involvement as the cause of clinical worsening in FA.     

Focal mucoid degeneration of peripheral nerve

Summary Focal mucoid degeneration was found in a N. suralis biopsy of a 8 year old child, diagnosed clinically and electrophysiologically as progressive muscular atrophy Charcot-Marie-Tooth.     

亚急性联合变性不典型性三例分析

目的探讨不典型亚急性联合变性患者临床与影像学表现,以及避免误诊的临床体会。方法分析3例不典型亚急性联合变性患者的临床表现和辅助检查资料,探讨其临床表现及早期误诊经过。结果3例患者不典型表现分别为治疗期间出现的激素副作用导致的"中心性浆液性脉络膜视网膜病变"、腰膨大病变与髓内病灶。结论不典型亚急性联合变性,临床表现多样,突出且持续的后索损害及症状体征的选择性、对称性是本病特点,对其认识不足是造成早期误诊原因。     

Lhermitte''s sign in subacute combined degeneration of the cord

Lhermitte's sign is a common early symptom of subacute combined degeneration of the cord occurring in 11 out of 44 patients admitted to the National Hospitals for Nervous Diseases during the decade 1962-71 with this diagnosis. Two patients, in both of whom it was the presenting complaint, are described in detail. It is concluded that, in these cases, Lhermitte's sign is due to stretching of demyelinated fibres in the posterior columns in the cervical cord, produced by neck flexion. The symptoms disappear after treatment with vitamin B₁₂. The clinical importance of this symptom is emphasized.     

Central and peripheral conduction times in multiple sclerosis

Somatosensory evoked potentials (SEPs) were recorded simultaneously from the cervical spine and scalp in 25 normal subjects and 105 patients with established or suspected multiple sclerosis (MS) using median nerve stimulation. The normal latency of the main peak of the cervical SEP (N14) following median nerve stimulation at the wrist was 13.7 +/- 0.8 msec. The peak latency of the first cortical event of the scalp SEP (N20) was 19.1 +/- 0.9 msec. The difference in these latencies (N20 -- N14) reflects a conduction time between the dorsal column nuclei and cortex. It measured 5.45 +/- 0.7 msec. The conduction times between the wrist and Erb's point and Erb's point and N14 measured 8.6 +/- 0.7 msec and 5.1 +/- 0.6 msec respectively. There was a 68.6% overall incidence of abnormalities of N14, N20 or (N20 -- N14) in the patients. This incidence was over 80% in definite and early probable or latent MS, 68.2% in progressive spinal MS and 40.0% in suspects. SEPs were also simultaneously recorded from the lower thoracic spine (T12) and scalp in a different group of 25 normal subjects using tibial nerve stimulation. The latency of the thoracic SEP (N21) was 21.4 +/- 1.5 msec and that of the first cortical event of the scalp SEP (P40) was 38.6 +/- 2.2 msec. The difference in these latencies (P40 -- N21) which reflects conduction between T12 and the cortex measured 17.2 +/- 1.7 msec. Conduction between the ankle and popliteal fossa was 7.0 +/- 0.65 msec and between the popliteal fossa and N21, it was 14.5 +/- 1.1 msec. All of a small group of MS suspects showed abnormality of P40 or (P40 -- N21).     

Central and peripheral motor conduction to cremasteric muscle

The few electrophysiologic studies of the cremasteric muscle (CM) have mainly been restricted to the cremaster reflex with no reference to central and peripheral nerve conduction to the muscle, probably for technical reasons.Twenty-six normal adult male volunteers were studied by transcranial magnetic cortical stimulation (TMS) and stimulation of thoracolumbar roots. The genitofemoral nerve (GFN) was stimulated electrically at the anterior superior iliac spine and a needle electrode was inserted into the CM for conduction studies. The motor latency to the CM from the cortical TMS ranged from 20 to 33 ms among the subjects (25.8 +/- 2.9 ms, mean +/- SD). Magnetic stimulation of the lumbar roots produced a motor response of the CM within 9.6 +/- 1.9 ms (range, 6-15). The central motor conduction time to the CM was 16.5 +/- 2.8 ms (range, 10-21). Stimulation of the GFN produced a compound muscle action potential with a mean value of 6.4 +/- 1.8 (range, 4-10) ms in 23 of the 26 cases. Thus, central motor nerve fibers to the CM motor neurons exist, and there may be a representation area for the CM in the cerebral cortex. The GFN motor conduction time to the CM may have clinical utility, such as in the evaluation of the groin pain due to surgical procedures in the lower abdomen.     

Acute vestibular dysfunction in childhood. Central vs. peripheral

Acute, vestibular symptoms in childhood are primarily caused by acute labyrinthitis (end organ dysfunction) or central nervous system diseases such as neoplasia involving the pons or cerebellar nuclei or infection manifested by pontine encephalitis. The evaluation, treatment, and prognosis of end organ versus central disease is so different that the ability to make a bedside, presumptive diagnosis provides an important advance. Both patients presented here had a central vestibulopathy. By paying particular attention to the character of the nystagmus and past pointing, the Romberg test, and the details of the vertiginous history, central disease was the presumptive diagnosis prior to invasive procedures. The neurophthalmological clues are reviewed to demonstrate their value in making more accurate diagnoses in children with acute vestibular dysfunction.