Activity-dependent conduction block in chronic inflammatory demyelinating polyneuropathy

Previous studies suggested that activity-dependent conduction block (CB) contributes to weakness in chronic inflammatory demyelinating polyneuropathy (CIDP). These studies, however, investigated only one nerve segment per patient, employed cervical magnetic stimulation which may be submaximal, included nerves with extremely low compound muscle action potentials (CMAPs) which precludes assessment of CB, and lacked predefined criteria for activity-dependent CB. Obtaining more robust evidence for activity-dependent CB is important because it may be treated pharmacologically. We investigated 22 nerve segments in each of 18 CIDP patients, employed supramaximal electrical stimulation, excluded nerves with markedly reduced CMAPs, and adopted criteria for activity-dependent CB. Each nerve was tested before and immediately after 60 s of maximal voluntary contraction (MVC) of the relevant muscle. Per nerve segment we calculated segmental area ratio: (area proximal CMAP)/(area distal CMAP). Per nerve we calculated total area ratio: (area CMAP evoked at Erb's point)/(area most distally evoked CMAP). MVC induced no change in mean area ratios and no activity-dependent CB according to our criteria, except for one segment. MVC induced increases in distal and proximal CMAP area and duration. In segments with demyelinative slowing, MVC induced an increase in CMAP duration prolongation. Thus, in CIDP, muscle activity induces virtually no CB, but it may increase temporal dispersion of nerve action potentials.     

Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of proximal upper limb motor nerve conduction study abnormalities in chronic inflammatory demyelinating polyneuropathy (CIDP), using standard percutaneous stimulations up to Erb's point. METHODS: Electrophysiologic data relating to proximal conductions of median and ulnar nerves of 22 patients with CIDP were retrospectively analyzed and compared to those of 22 controls with sensory neuropathy. Distal conduction results were also reviewed. RESULTS: The findings demonstrate independent high sensitivity of abnormal upper limb proximal nerve conduction studies in CIDP. Demonstration of conduction block of >20% and temporal dispersion of >15% had low specificity. However, conduction block was highly specific with cut-off values of >30% at axilla and >50% at Erb's point. Specificity was considerably improved using a cut-off value of >30% at proximal levels for temporal dispersion. Diagnostic sensitivity improved significantly with proximal studies with the criteria used in this population. No adverse effects had occurred as result of proximal stimulations. CONCLUSIONS: Proximal studies are safe, sensitive and reliable procedures in cases of suspected CIDP. Their use appears justified although adequate cut-off values are desirable to optimize their specificity. SIGNIFICANCE: This study indicates that proximal upper limb nerve conductions are appropriate in investigating suspected CIDP, as detailed in recently established electrophysiologic criteria. However, specificity is largely dependent on cut-off values for conduction block and temporal dispersion.     

Activity-dependent excitability changes in chronic inflammatory demyelinating polyneuropathy: A microneurographic study.

The purpose of this study was to investigate activity-dependent excitability changes in polyneuropathy and their correlation with symptomatology. First, we recorded sensory nerve action potentials (SNAPs) with an intraneural microelectrode during impulse trains in 11 patients with chronic inflammatory demyelinating polyneuropathy. When the stimulus frequency was increased to >/=20 Hz, all patients showed marked decreases in the amplitudes of averaged SNAPs (128 responses) associated with latency increases. The amplitude decreases were much greater than those in patients with axonal neuropathies. In single-unit recordings, responses showed latency increases, which were small but sufficient to cause decreases in the averaged responses. Clinical sensory impairment was correlated with the degree of preexisting conduction block or axonal loss, but not with the degree of rate-dependent amplitude decreases. Activity-dependent changes occur preferentially in demyelinating neuropathy and are a sensitive measure of demyelination. The mechanism responsible for the amplitude decreases could be conduction slowing or block caused by activity-dependent hyperpolarization.     

慢性炎症性脱髓鞘性多发性神经病多节段神经电生理研究

目的分析慢性炎症性脱髓鞘性多发性神经病(CIDP)节段性神经电生理表现。方法收集2013年1月~2014年8月于吉林大学第一医院神经内科就诊的22例CIDP患者,行正中神经及尺神经多节段神经电生理检测,正中神经刺激点包括:腕、肘、腋、Erb’s点;尺神经刺激点包括:腕、肘下、肘上、腋、Erb’s点。分析各节段神经电生理改变。结果 22例患者电生理各节段均出现明显的脱髓鞘改变,正中神经各节段(腕以下、腕-肘、肘-腋、腋-Erb’s点)运动传导时间较正常值延长分别为:125%、70%、122%、134%;尺神经各节段(腕以下、腕-肘下、肘下-肘上、肘上-腋、腋-Erb’s点)运动传导时间较正常值延长分别为84%、97%、140%、146%、149%。正中神经各刺激点(肘、腋、Erb’s点)传导阻滞(CB)例数分别为:2、6、14;尺神经各刺激点(肘下、肘上、腋、Erb’s点)CB例数分别为:5、4、10、16。结论 CIDP存在明显脱髓鞘的电生理改变,但在周围神经近端各节段脱髓鞘程度较远端重,CB以近端腋点、Erb’s点明显,多节段神经电生理检测更有利于协助CIDP的诊断并判断神经损害的严重程度。     

急、慢性炎症性脱髓鞘性多发性神经病神经电生理对比研究

目的 比较分析急性炎症性脱髓鞘性多发性神经病(AIDP)与慢性炎症性脱髓鞘性多发性神经病(CIDP)的电生理表现.方法 收集2011年1月～2013年1月在吉林大学白求恩第一医院神经内科就诊的19例AIDP患者及15例CIDP患者,分析上下肢周围神经传导检查各项指标.结果 AIDP与CIDP均表现为运动传导速度(MCV)减慢、远端潜伏期延长、波幅降低、传导阻滞、F波及H反射异常,但CIDP组MCV减慢明显,与AIDP组存在显著差异,且CIDP组感觉传导检测异常明显,AIDP组感觉神经传导异常少见.结论 AIDP患者主要以周围神经运动纤维受损为主,存在明显的脱髓鞘及轴索的损伤,但周围神经感觉纤维受损不明显.CIDP患者周围神经运动纤维及感觉纤维受损均非常明显,且脱髓鞘程度明显重于AIDP患者.     

Nerve conduction abnormalities in chronic inflammatory demyelinating polyneuropathy (CIDP)]

Changes in compound muscle action potentials (CMAPs) were evaluated in 13 cases with CIDP by using inching-stimulation technique. The presence of electrophysiological multifocal lesion distinguished CIDP from hereditary demyelinating neuropathy (HDN). The size of each CIDP lesion was sometimes as small as a few millimeters, showing a decrease in CMAP amplitude proximally. No HDN cases revealed such focal changes. It is thus important to demonstrate small lesions with CMAP changes of demyelination-type in diagnosis of CIDP. Decrease in amplitude of proximally-evoked CMAP is essential but sometimes inadequate to determine partial conduction block, because HDN may show decrease in CMAP amplitude, up to 45%, by elbow stimulation as compare to one by wrist stimulation in our series. In determining partial conduction block a standard two-point stimulation can cause an error, because that threshold is quite high over a demyelinated segment, and that a cross stimulation may occur when high voltage stimulation is applied. Multiple-sites stimulation is the most reliable technique to demonstrate convincing changes in CMAPs over small demyelinating lesions. Revival of blocked motor fibers introduces new units to CMAP. In most cases some increase in CMAP amplitude occur first, because remyelinated fibers are slowly-conducting. Some units with shorter latency occasionally revived first, which suggests a possibility of conduction block without morphological background.     

Motor-dominant chronic inflammatory demyelinating polyneuropathy

We reviewed the clinical, electrophysiological an laboratory findings, plus the therapeutics and evolution of patients with motor-dominant Chronic inflammatory demyelinating polyneuropathy (CIDP) and compared them with those of other CIDP patients. Among 12 consecutive CIDP patients, we identified five patients with motor-dominant CIDP. The five patients with motor-dominant CIDP initially presented with weakness of the upper limbs. Cervical magnetic resonance imaging (MRI) examinations of the patients with motor-dominant CIDP showed that the most affected lesions are the cervical nerve roots and brachial plexus. The clinical course of these patients was relapsing-remitting, and they improved markedly after treatment by intravenous immunoglobulin (IVIg) infusion or plasmapheresis. However, they did not improve in response to corticosteroid therapy during the acute phase of relapses. The relapses frequently occurred within 2 years, but rarely occurred after that. The score in the modified Rankin disability scale (mRDS) at the last follow-up period was statistically lower for the patients with motor-dominant CIDP than for the other CIDP patients (P < 0.002). The characteristic clinical features, responsiveness to treatment, and prognosis suggest that motor-dominant CIDP is a distinct subtype of CIDP, with a specific immunological background. Repeated IVIg therapy is required to maintain the motor functions of patients with motor-dominant CIDP. We consider that treatment for recurrence prevention as an alternative to IVIg therapy is very important for patients with motor-dominant CIDP.     

Immunoglobulins in chronic inflammatory demyelinating polyneuropathy

Neurological Sciences - This article reviews the efficacy and tolerability of intravenous immunoglobulins (IVIg) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), including those...     

Pure motor chronic inflammatory demyelinating polyneuropathy

We describe four patients affected by chronic inflammatory demyelinating polyneuropathy (CIDP) in a pure motor form. Selective involvement of motor fibers was suggested by the absence of sensory symptoms, normal sensation at neurological examination and normal findings on electrophysiological testing of sensory fibres and sural nerve biopsy. The onset of the disease occurred at a young age (3–29 years) and the clinical course was relapsing-remitting. Over a follow-up periode of 1.5–14 years, periodical clinical and electrophysiological examinations showed that selective involvement of motor fibers remained a constant feature. Electromyography and nerve conduction studies continued to show a purely demyelinating neuropathy without signs of axonal impairment. All patients were steroid-unresponsive, whereas they considerably improved after being treated with immunoglobulins. Two patients were treated with interferon alpha and showed a good response. In conclusion, the occurrence in our four patients of pure motor involvement over a long period of time during which several relapses occurred, suggests that pure motor CIDP may represent the result of a specific immunological process rather than of a random distribution of inflammation throughout peripheral nerves. Received: 21 December 2000 / Received in revised form: 2 February 2001 / Accepted: 10 March 2001     

Treatment of chronic inflammatory demyelinating polyneuropathy

The management of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the main topic of this review. A few comments will also be made about treatment of the demyelinating form of paraproteinaemic demyelinating polyneuropathy (PDN) and of multifocal motor neuropathy (MMN). The review briefly describes the main characteristics of these neuropathies, and examines case series and trials which evaluated the principal therapeutic strategies for CIDP, PDN and MMN, such as intravenous immunoglobulin (IVIg) therapy, steroid treatment, plasma exchange and immunosuppressor administration. Controlled trials demonstrated that IVIg, steroid treatment and plasma exchange are effective in CIDP. For PDN the therapeutic strategies are the same as for idiopathic CIDP, but usually the clinical response is poorer. For MMN, IVIg therapy is definitely the first choice treatment.

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Sommario Lo scopo principale di questa review è di esaminare le strategie terapeutiche nella neuropatia infiammatoria cronica demielineizzante (CIDP). Alcuni commenti vengono fatti anche riguardo il trattamento della forma demielinizzante della neuropatia demielinizzante paraproteinemica (PDN) e della neuropatia motoria multifocale (MMN). La review delinea le principali caratteristiche cliniche delle diverse forme di neuropatia demielinizzante ed esamina i principali studi clinici, controllati e non controllati, che hanno valutato il trattamento deila CIDP e della PDN e MMN con immunoglobuline endovena (IVIg), con la terapia steroidea, la plasmaferesi e farmaci immunosoppressori. Studi controllati hanno dimostrato che le IVIg, to steroide e la plasmaferesi sono efficaci nella CIDP. Per quanto riguarda la PDN le strategic terapeutiche sono analoghe a quelle adottate nella CIDP anche se la risposta clinica è solitamente meno evidente. Infine, nella MMN le IVIg sono sicuramente il trattamento di prima scelta.

     

Treatment of chronic inflammatory demyelinating polyneuropathy

PURPOSE OF REVIEW: Chronic inflammatory demyelinating poly(radiculo)neuropathy (CIDP) is a treatable disorder. There are three proven effective treatments available. Randomized controlled trials have only focused on short-term effects, but most patients need long-term therapy. The most up-to-date treatment options are discussed. Attention is also paid to the use of appropriate assessment scales and treatment of residual findings. RECENT FINDINGS: A Cochrane review is available indicating that intravenous immunoglobulin is an effective treatment. Equal efficacy of intravenous immunoglobulin and steroids was shown during a 6-week treatment period. New open studies indicated possible efficacy for mycophenolate, interferon-beta and etanercept. Combinations of treatment are scarcely studied yet. Some CIDP patients may have a more acute onset of disease since maximum severity is reached within 4-8 weeks, resulting in confusion about the diagnosis. It was shown that severe fatigue can be a major complaint in CIDP patients; a training regimen might partially resolve these problems. SUMMARY: CIDP is a treatable disorder, but most patients need long-term treatment. Intravenous immunoglobulin, steroids and plasma exchange are shown to be effective. It is suggested that other immunomodulatory agents can also be effective, but randomized trials are needed to confirm these benefits. General measures to rehabilitate patients and to manage symptoms like fatigue and other residual findings are important.     

Immunotherapy of chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated disease of the peripheral nervous system with an estimated prevalence of 1-2/100,000. The clinical presentation is heterogeneous, but the most common form causes symmetrical progressive or relapsing weakness affecting proximal and distal muscles. CIDP is among the most treatable peripheral nerve disorders and corticosteroids, plasmapheresis and intravenous immunoglobulin have been shown to be effective in short-term prospective, randomized controlled trials. Data however indicate that approximately one-third of patients do not respond to these treatment modalities, nor do they provide equivalent evidence for a durable clinical response. There is a lack of good quality controlled trials of any other immunosuppressive agent, but cyclophosphamide and cyclosporin may be of value in patients with poor response to first-line modalities. Alternatively, the use of combination therapy may increase the efficacy in unresponsive patients. This review highlights the current status of CIDP treatment trials and discusses the significance of any therapeutic option in terms of efficacy, tolerability and cost-effects.     

Atypical childhood chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon cause of progressive weakness in childhood. The diagnosis is easy when the clinical history and findings are supported by unequivocal electrophysiologic and laboratory evidence of demyelination, but it can be challenging if the criteria for demyelination are not met. We report a case of atypical childhood CIDP to highlight the diagnostic difficulties and the importance of recognizing this treatable condition. Muscle Nerve, 2010     

慢性炎症性脱髓鞘性多神经病的轴索损害

目的探讨慢性炎症性脱髓鞘性多神经病（CIDP）的轴索病理改变。方法对18例CIDP患者进行电生理和腓肠神经的病理检查，分析不同患者的腓肠神经病理改变特点，并对病理改变不同的两组进行临床、电生理及病理比较。结果5例以脱髓鞘改变为主者，主要出现薄髓鞘神经纤维和有髓神经纤维的洋葱球样结构，其中3例出现轴索损害。8例以轴索损害为主者，主要出现有髓神经纤维的Wallerian变性和再生簇结构。3例出现有髓神经纤维的髓鞘和轴索混合性损害。2例轻微病理改变。脱髓鞘损害为主者和轴索损害为主者的单核细胞浸润程度无明显差异，且两者可同时存在脱髓鞘和轴索损害的电生理改变特点。结论轴索损害是CIDP比较常见的病理改变，不应当作为该病的绝对排除标准。单核细胞的浸润是一种普遍改变。     

Evoked potentials in chronic inflammatory demyelinating polyneuropathy

Eighteen patients with chronic inflammatory demyelinating polyneuropathy were studied with evoked potentials to assess for evidence of central nervous system demyelination. Both visual and brain-stem auditory evoked responses were obtained, and the results were compared with magnetic resonance imaging (MRI). An evoked potential was abnormal in nine of 18 patients, five of whom had central nervous system evidence of demyelination by MRI. Evoked potentials identified four patients with probable anterior optic pathway involvement that was not demonstrable by MRI. These findings continue to support that chronic inflammatory demyelinating polyneuropathy is associated with a central demyelinating disorder and more importantly emphasize the possibility of a common pathogenic mechanism in central and peripheral nerve demyelination.