Unmyelinated fibers in sural nerve biopsies of chronic inflammatory demyelinating polyneuropathy

Summary Seven patients aged 29 to 76 years with various clinical subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated. Sural nerve biopsies were performed between 7 months and 19 years after onset of disease. Quantitative electron microscopy revealed involvement of primary unmyelinated fibers (UF) in all cases. When compared with age-matched controls from the literature and two controls of our own, there was an increase of degenerating primary UF in all cases, a definite decrease of density per mm² or number per nerve after subtraction of regenerates of myelinated and unmyelinated fibers in five cases, an increase of denervated Schwann cell complexes of the unmyelinated type in three cases, and an increased incidence of a high ratio (3) of primary UF per Schwann cell complex in five cases. Presumably due to the small number and heterogeneity of cases, the results did not correlate with type and duration of CIDP, but were obviously influenced by the degree of demyelination. The possible causes of UF damage in CIDP are discussed.     

Acute‐onset chronic inflammatory demyelinating polyneuropathy: An electrodiagnostic study

Introduction: Acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP) is an increasingly recognized CIDP subtype. Differentiating A‐CIDP from Guillain–Barré syndrome (GBS) is challenging but important, because there are different treatment outcomes. Methods: We report 3 patients with A‐CIDP who were initially diagnosed with severe GBS but were later confirmed to have CIDP based on their clinical course and electrodiagnostic (EDx) studies. We also report on the long‐term treatment of these patients and review the literature on EDx studies in this syndrome. Results: Three patients were initially diagnosed with GBS and responded to treatment. However, all 3 had arrest in improvement or deterioration during their rehabilitation phases. EDx studies showed prominent demyelinating changes many months after the initial presentation. All responded very well to immunotherapy. Conclusion: Although several features may suggest the diagnosis of A‐CIDP at initial presentation, close follow‐up of GBS patients during the recovery phase is also needed for accurate diagnosis. EDx studies may distinguish patients with A‐CIDP from GBS patients. Muscle Nerve 52 : 900–905, 2015     

Mandibular nerve involvement in diabetic polyneuropathy and chronic inflammatory demyelinating polyneuropathy

Sensory complaints in the area of the mandible and mouth often escape notice or remain undiagnosed. Using electromyographic recording of the trigeminal reflexes and motor responses, we sought trigeminal dysfunction in 50 patients with peripheral neuropathy, and tried to gain pathophysiological information on the mechanisms provoking trigeminal damage. Trigeminal reflex recordings (early and late blink reflex after supraorbital stimulation, early and late masseter inhibitory reflex after mental stimulation, and jaw jerk) disclosed abnormalities caused by sensory trigeminal neuropathy in 8 out of 15 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 out of 23 patients with severe diabetic polyneuropathy, and in none of 12 patients with mild diabetic polyneuropathy. Six patients had abnormal motor responses in facial or masseter muscles. The response affected most frequently was the masseter early inhibitory reflex (also called first silent period, SP1) after mental nerve stimulation, its latency being strongly delayed. We found these long delays not only in patients with CIDP, but also in diabetic patients with severe polyneuropathy. We conclude that peripheral polyneuropathies often cause subclinical damage to the trigeminal nerve, especially to its mandibular branch. We believe that the nerve fibers running along the alveolar–mandibular pathway are more exposed to damage because of their cramped anatomical route in the mandibular canal and below the internal pterygoid muscle and fascia. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1673–1679, 1998     

慢性炎性脱髓鞘性多发性神经病的治疗进展

慢性炎性脱髓鞘性多发性神经病（chronic inflammatory demyelinating polyradiculopathy,CIDP）是一种获得性的免疫介导的周围神经病.临床特征包括进展性或复发性的肢体无力、感觉缺失和腱反射消失等.     

儿童慢性炎症性脱鞘性多神经病的临床和病理改变特点

目的探讨儿童慢性炎症性脱鞘性多神经病(chronic inflammatory demyelinating polyneuropathy,CI-DP)的临床及病理改变特点。方法根据欧洲神经肌肉病中心修订的儿童CIDP诊断标准诊断的10例17岁以下患者,收集其临床资料,进行周围神经电生理以及腓肠神经的病理检查。结果所有患者主要表现为肢体无力,分别有4例和3例出现四肢感觉减退和颅神经损害。9例有脑脊液蛋白细胞分离现象。10例均出现运动或感觉神经传导速度减慢及远端潜伏期延长,9例患者的动作电位波幅降低。所有患者的有髓神经纤维出现轻-重度减少,其中3例患者的纤维脱失程度在不同束间存在差异,6例患者以脱髓鞘为主;3例以轴索损害为主。1例患者仅出现轻微改变。9例患者存在炎细胞浸润。结论儿童CIDP以肢体无力为主。部分患者以轴索损害为主,神经纤维脱失程度可以存在束间差异。     

The dropped head syndrome with chronic inflammatory demyelinating polyneuropathy

The dropped head syndrome occurs in a variety of neuromuscular disorders. We present a woman with chronic inflammatory demyelinating polyneuropathy who developed this syndrome, likely reflecting severe demyelination of nerves to cervical paraspinal muscles. © 1994 John Wiley & Sons, Inc.     

Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and of 12 age-matched normal controls. The numbers of unmyelinated axons, myelinated nerve fibers, denervated Schwann cell units and collagen pockets were quantified and related to the clinical and electrophysiological data of the patients with CIDP. In 4 patients with a rapid onset of the neuropathy and a highly elevated CSF protein, the numbers of both unmyelinated axons and myelinated nerve fibers were decreased equally. In 8 patients we found that the unmyelinated axons were relatively spared compared with the loss of myelinated nerve fibers. In these patients, however, the presence of denervated Schwann cell units and of collagen pockets was increased. We conclude that unmyelinated nerve fibers are affected in patients with CIDP.     

Anti‐ganglioside antibodies in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients

Introduction: In this study we investigated the relationships between anti‐ganglioside antibodies and Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. Results: In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti‐ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. Conclusions: These results suggest that IgG anti‐GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55 : 470–475, 2017     

Differences between acute‐onset chronic inflammatory demyelinating polyneuropathy and acute inflammatory demyelinating polyneuropathy in adult patients

Acute inflammatory demyelinating polyneuropathy (AIDP) and acute‐onset chronic inflammatory demyelinating polyneuropathy (A‐CIDP) are conditions presenting overlapping clinical features during early stages (first 4 weeks), although the latter may progress after 8 weeks. The aim of this study was to identify predictive factors contributing to their differential diagnosis. Clinical records of adult patients with AIDP or A‐CIDP diagnosed at our institution between January 2006 and July 2017 were retrospectively reviewed. Demographic characteristics, clinical manifestations, cerebrospinal‐fluid (CSF) findings, treatment and clinical evolution were analyzed. Nerve conduction studies were performed in all patients with at least 12 months follow‐up. A total of 91 patients were included (AIDP, n = 77; A‐CIDP, n = 14). The median age was 55.5 years in patients with A‐CIDP vs 43 years in AIDP (P = .07). The history of diabetes mellitus was more frequent in A‐CIDP (29% vs 8%, P = .04). No significant differences between groups were observed with respect to: human immunodeficiency virus (HIV) status, presence of auto‐immune disorder or oncologic disease. Cranial, motor and autonomic nerve involvement rates were similar in both groups. Patients in the A‐CIDP group showed higher frequency of proprioceptive disturbances (83% vs 28%; P < .001), sensory ataxia (46% vs 16%; P = .01), and the use of combined immunotherapy with corticoids (29% vs 3%; P = .005). There were no significant differences in CSF findings, intensive care unit (ICU) admission, or mortality rates. During the first 8 weeks both entities are practically indistinguishable. Alterations in proprioception could suggest A‐CIDP. Searching for markers that allow early differentiation could favor the onset of corticotherapy without delay.     

Pattern analysis of nerve enlargement using ultrasonography in chronic inflammatory demyelinating polyneuropathy

ObjectiveFocal nerve enlargement is a characteristic finding in chronic inflammatory demyelinating polyneuropathy (CIDP). We performed this study to assess the distribution of nerve enlargement through ultrasonographic examination of peripheral nerves and to correlate the ultrasonographic findings with clinical features.MethodsTo compare the ultrasonographic features of 10 subjects with CIDP with those of 18 healthy controls, we bilaterally measured the cross-sectional areas (CSA) of the vagus, brachial plexus, musculocutaneous, median, ulnar, radial, sciatic, tibial, common peroneal, and sural nerves. We also analyzed correlations between CSAs and various clinical and electrophysiological features.ResultsMean CSAs were significantly larger in CIDP patients than controls, especially at proximal and non-entrapment sites. CSAs were significantly correlated with muscle strength at initial presentation, but not at the time of ultrasonography. The CSAs of the median and ulnar nerves at the mid-forearm, tibial nerve at 7 cm proximal to the medial malleolus, and sural nerve correlated with the nerve conduction velocity of the corresponding region.ConclusionUltrasonography revealed widely distributed nerve enlargement, especially in proximal regions and non-entrapment sites, in patients with CIDP compared with healthy controls. Nerve enlargement correlated well with the electrophysiologic function of the nerve, but not current clinical status.SignificancePattern analysis of nerve enlargement using ultrasonography is a supportive tool in the diagnosis of CIDP.     

Focal cranial nerve involvement in chronic inflammatory demyelinating polyneuropathy: clinical and MRI evidence of peripheral and central lesions

Summary Five cases of chronic inflammatory demyelinating polyneuropathy are described in which cranial nerve involvement accompanied a more generalized neuropathy. Clinical, electrophysiological, radiological and nerve biopsy findings are presented. Cranial nerve lesions in this form of polyneuropathy may be related to lesions of the peripheral nerves or of the central nervous system, when they may be accompanied by MRI evidence of more widespread CNS demyelinating lesions. In cases of early onset, the occurrence of focal cranial nerve lesions may serve to distinguish chronic inflammatory from inherited demyelinating polyneuropathies.     

Acute‐onset chronic inflammatory demyelinating polyneuropathy with cranial nerve involvement,dysautonomia, respiratory failure,and autoantibodies

We examined a 27‐year‐old woman who developed rapidly progressive quadriplegia and acute respiratory failure that required mechanical ventilation in the intensive care unit. It was unclear whether this was a presentation of Guillain–Barré syndrome (GBS) or acute‐onset chronic inflammatory demyelinating polyradiculoneuropathy (A‐CIDP). Remarkable features included multiple cranial nerve involvement, respiratory failure, dysautonomia, and skin manifestations. Several autoantibodies were elevated, including antinuclear (ANA), anticardiolipin (aCL), thyroid, and calcium‐sensing receptor (CaSR) autoantibodies. The patient was initially diagnosed with GBS and treated with intravenous immunoglobulin (IVIg). After almost complete recovery, relapse with quadriplegia and respiratory failure was observed 12 weeks after motor symptom onset. She then received IVIg and steroid pulse therapy followed by maintenance oral methylprednisolone and plasma exchange. She recovered completely 4 months after the relapse. The further clinical and serological course was consistent with systemic lupus erythematosus (SLE)‐associated CIDP. Herein we evaluate the association between A‐CIDP and some biological markers of autoimmunity. Muscle Nerve, 2010     

Clinical and electrophysiological parameters distinguishing acute‐onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy

Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute‐onset CIDP (A‐CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A‐CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural‐sparing pattern, sensory ratio >1, nor the presence of A‐waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow‐up. Muscle Nerve, 2010     

Nerve ultrasound score in distinguishing chronic from acute inflammatory demyelinating polyneuropathy

ObjectiveAim of this study was to develop and evaluate the applicability of an ultrasound score (Bochum ultrasound score – BUS) in distinguishing chronic (CIDP) from acute inflammatory demyelinating polyneuropathy (AIDP).Methods

• •Step 1: For the development of BUS 75 healthy-controls, 20 CIDP, 20 AIDP patients underwent US 4.55 ± 3.5 and 3.4 ± 2.91 years, respectively after onset. After comparing the distribution pattern and frequency of pathological US changes between the two study groups, we developed BUS, summarizing the cross sectional area (CSA) of: (1) the ulnar nerve in Guyons’ canal, (2) the ulnar nerve in upper-arm, (3) the radial nerve in spiral groove, (4) the sural nerve between the gastrocnemius muscle.
• •Step 2: The BUS underwent blinded evaluation in further 10 CIDP, 21 AIDP patients 3.8 ± 2.7 and 2.3 ± 1.5 years, respectively after onset.
• •Step 3: The BUS underwent blinded, prospective evaluation in 8 patients with acute/subacute polyradiculoneuropathy (5 CIDP, 3 AIDP) 2.6 ± 1.8 weeks after onset.

ResultsThe BUS showed a sensitivity of 90% and specificity of 90.4% (positive predictive value, PPV = 81.8%; negative predictive value, NPV = 95%) in distinguishing CIDP from AIDP, when they showed no differences in disease duration (p = 0.0551).In addition, the BUS distinguished subacute-CIDP from AIDP with a sensitivity of 80%, specificity of 100% (PPV = 100%, NPV = 75%).ConclusionThe BUS seems to allow a reliable distinction of CIDP from AIDP.SignificanceThe BUS may be helpful in distinguishing subacute-CIDP from AIDP.     

Electrophysiological entrapment syndromes in chronic inflammatory demyelinating polyneuropathy

We do not know if peripheral nerves are more susceptible to entrapment syndromes in chronic inflammatory demyelinating polyneuropathy (CIDP). We studied 31 prospectively recruited patients with CIDP. We determined whether entrapment zones were more frequently affected by demyelination than adjacent segments. The median, ulnar, and fibular nerves were studied at the wrist, elbow, and fibular head bilaterally. Motor conduction velocity and motor conduction block were evaluated at entrapment sites and compared with contiguous segments. Demyelination was significantly more frequent for ulnar and fibular nerves away from entrapment sites. No significant difference was observed for median nerves. CIDP is not associated with increased frequency of demyelination at entrapment sites. The presence of diffuse entrapment neuropathies at compression sites does not favor a diagnosis of CIDP. Although electrophysiological study of entrapment sites is not diagnostically useful in CIDP, it may help distinguish it from other neuropathies and confirm clinically relevant, surgically treatable compressions.     

Subclinical electrophysiological alterations of phrenic nerve in chronic inflammatory demyelinating polyneuropathy

Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO₂ partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.     

High-dose intravenous gammaglobulin for chronic inflammatory demyelinating polyneuropathy

We report our preliminary experience of high-dose intravenous gammaglobulin in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) selected for inefficacy or severe side effects of steroid and immunosuppressive treatment. Our treatment proved safe and effective, reversing the disability of CIDP, the improvement being temporally related to the commencement of intravenous high-dose gammaglobulin. The possible mechanisms of action are discussed.

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Riassunto Gli AA. riportano i risultati emersi dal trattamento con gammaglobuline e.v. ad alte dosi in quattro pazienti affetti da polineuropatia cronica infiammatoria demielinizzante (CIDP), selezionati in base alla inefficacia o alla comparsa di gravi effetti collaterali da corticosteroidi e/o immunosoprressivi. Il trattamento fu prontamente seguito in ogni caso da sensibile miglioramento clinico, particolarmente vistoso in due pazienti; nessun effetto collaterale o complicanza risultò evidenziabile. I possibili meccanismi d'azione delle immunoglobuline intere e.v. ad alte dosi vengono discussi.

     

Restless legs syndrome in chronic inflammatory demyelinating polyneuropathy

The prevalence of restless legs syndrome (RLS) is unknown in chronic inflammatory demyelinating polyneuropathy (CIDP). We prospectively studied 28 patients with CIDP. Prevalence of RLS in CIDP was ascertained by face‐to‐face interview using validated criteria and compared with that in 28 age‐ and gender‐matched controls. Eleven (39.3%) CIDP patients were diagnosed with RLS, compared with 2 (7.1%) controls (P < 0.01). A significant correlation was ascertained between presence of RLS and lower limb weakness, functional disability, and summated compound muscle action potential (CMAP). The prevalence of RLS in CIDP was significantly higher than in controls in our study population, approaching 40%. Screening for RLS in CIDP patients may be appropriate, particularly in those with weakness, disability, and motor axonal loss in the lower limbs. Our findings may otherwise suggest the existence of peripheral components to the pathophysiology of RLS in patients with CIDP. Muscle Nerve, 2010     

慢性炎症性脱髓鞘性多发性神经病临床及神经电生理研究

目的 分析慢性炎症性脱髓鞘性多发性神经病(CIDP)的临床及神经电生理表现.方法 选取2010-07-2012-07我院7例CIDP患者,对其临床资料进行回顾性研究,分析临床表现、脑脊液及神经电生理检测结果.结果 7例CIDP患者均有四肢或双下肢肌力下降,腱反射减弱或消失,脑脊液蛋白升高,神经电生理异常.出院后3例恢复较良好,另外4例出现2～4次复发.结论 CIDP的诊断应结合临床表现、脑脊液检查和神经电生理检查,应依据具体情况采用免疫球蛋白和(或)皮质激素治疗.