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.     

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     

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     

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.     

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.     

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.     

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     

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.     

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.     

Autoantibodies to peripheral nerve glycosphingolipids SPG, SLPG, and SGPG in Guillain–Barré syndrome and chronic inflammatory demyelinating polyneuropathy

Unlike CNS myelin, human peripheral nerve myelin has the acidic glycosphingolipids sialosyl paragloboside (SPG), sialosyl lactosaminyl paragloboside (SLPG), and sulfated glucuronyl paragloboside(SGPG). To elucidate the pathogenesis of Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating neuropathy (CIDP), we investigated the autoantibodies to peripheral nerve molecules in patients with these diseases and compared the frequency of the autoantibodies with that of autoantibody to GM1 which is present in both the CNS and PNS. The report of Sheikh et al. (Ann. Neurol. 1995; 38: 350) that Campylobacter jejuni bears the SGPG epitope led us to study whether sera from patients with GBS subsequent to C. jejuni enteritis have anti-SGPG antibody; but, high anti-SGPG antibody titers were not found in the GBS patients from whom C. jejuni was isolated. Although the frequency of the anti-SPG, anti-SLPG, and anti-SGPG antibodies were lower than that of the anti-GM1 antibody in GBS, 5 patients with demyelinating GBS had high IgG anti-SPG antibody titers. IgG anti-SPG antibody may function in the development of demyelinating GBS. We found that 6 CIDP patients had elevated IgM anti-SGPG antibody titers. Immunoelectrophoresis failed to detect IgM M-protein in 3 of the patients. IgM anti-SGPG antibody could be a diagnostic marker for a subgroup of CIDP with or without paraprotein.     

T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barré syndrome

T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4⁺) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease to define circulating T cell populations. The proportion of T-helper cells (CD4⁺) was decreased (mean value 41±15%, P = 0.01) and the proportion of T cytotoxic/suppressor cells (CD8⁺) was increased (35±18%, P = 0.0006) as compared to the control group of healthy blood donors (47±8% and 26±7% respectively). The CD4⁺ population is divided into the helper/inducer (CD4⁺ CD29⁺) and suppressor/inducer (CD4⁺ CD45RA⁺) subsets. which normally are equally distributed (mean values in our control group were 45±15% and 44±15%, respectively). In patients with GBS, the helper/inducer (CD4⁺ CD29⁺) subset was increased (54±10%, P = 0.05) and the suppressor/inducer (CD4⁺ CD45RA⁺) subset was decreased (31±9, P = 0.005) compared to the controls. The proportion of activated HLA-DR-expressing T cells was increased (7±8%, P = 0.005) as compared to control (3±3%). The total proportions of T cells (CD2⁺), B cells (CD19⁺) and natural killer (NK) cells (CD56⁺) were similar in pateints and controls. The CD4⁺ and CD8⁺ populations, as well as the activated HLA-DR⁺ T cells, normalized during the disease course. The derivations within the CD4⁺ population also tended to normalize, but even at follow up after 6–33 (mean 23) months, some abnormalities remained. In conclusion, we confirm previous reports of T cell activation in peripheral blood from patients with GBS. A new finding is the derivation of T helper subpopulations with an increased helper/inducer (CD4⁺ CD29⁺) subset and a decreased suppressor/inducer (CD4⁺ CD45RA⁺) subset, which indicates a possible autoimmune character of GBS.     

Case of the month: Isaacs' syndrome associated with chronic inflammatory demyelinating polyneuropathy

We report the first case of Isaacs' syndrome in which an inflammatory demyelinating neuropathy was documented histologically. For 9 months, the patient developed slowly progressive weakness, muscle spasms and stiffness, fasciculations, and myokymia in the arms, which were unmodified by sleep. Nerve conduction studies showed multifocal motor conduction block, abnormal dispersion phenomenon, and abnormal sensory and mixed nerve conduction. Needle electromyogram showed continuous motor unit potentials at rest with bursts of rapid-firing discharges which were unaffected by spinal anesthesia but diminished by peripheral nerve block and completely abolished by local curarization. Sural nerve biopsy demonstrated an inflammatory demyelinating neuropathy. Muscle cramping, twitching, and stiffness responded to phenytoin. The patient's weakness gradually responded to prednisone and azathioprine. Over a 17-year period, the patient had three relapses which were well-controlled with prednisone and azathioprine. At this time, the patient is symptom-free without any medication. © 1996 John Wiley & Sons, Inc.     

Development of weakness in patients with chronic inflammatory demyelinating polyneuropathy and only sensory symptoms at presentation: A long-term follow-up study

This long-term follow-up study examined patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and only sensory symptoms at first presentation, with emphasis on the development of motor symptoms and long-term disability. From all CIDP patients referred to our Department between 1987 and 1995, seven had only sensory symptoms at first clinical presentation. These were investigated according to a standard protocol, including a quantified clinical neurological examination and nerve conduction studies. The mean duration of the disease before weakness developed was 3.1 years, but varied considerably (0.8–6.3 years). At follow-up, weakness developed in five patients and persisted in three of them. Five patients were not seriously incapacitated by their disease (Rankin 1 or 2), four of them being in remission now and one showing a very slow progression of disease. Two patients were moderately disabled (Rankin 3); one had severe persistent sensory ataxia and only weakness during relapses and one had stepwise progression and moderate weakness. Motor nerve conduction studies revealed that the most notable worsening in the entire group of patients was a decrease in distal compound muscle action potential amplitudes, indicating the development of distal conduction block or axonal degeneration. These findings show that CIDP with only sensory symptoms is a transient clinical stage that precedes the appearance of weakness in about 70% of patients. The long-term prognosis does not differ from that of patients with CIDP who have weakness at the beginning of the disease. Received: 3 December 1998 Received in revised form: 17 May 1999 Accepted: 2 July 1999     

Ophthalmoplegic and lower cranial nerve variants merge into each other and into classical Guillain-Barré syndrome

We delineated the place of cranial nerve variants within the concept of clinically defined Guillain-Barré syndrome (GBS). In the ophthalmoplegic variant (n = 7) the oculomotor nerves were early involved. In a lower cranial nerve variant (n = 9) the cranial nerves IX, X, and XI were early involved. During progression considerable overlap occurred between these two variants, but also with the classically ascending variant of clinically defined GBS. These findings indicate common immune mechanisms in all GBS variants. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 239–242, 1998     

Chronic inflammatory demyelinating polyneuropathy associated with dysglobulinemia: a peripheral nerve biopsy study in 18 cases

The possible occurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) in association with an identified dysglobulinemic status is recognized and a causal relationship between the two has been suggested. We had the opportunity to study 18 patients presenting with CIDP and dysglobulinemia. This was an IgG monoclonal gammopathy (IgG MG) in 8 cases, an IgM monoclonal gammopathy (IgM MG) in 8, an IgG-IgM biclonal gammopathy in 1 case and an IgM monoclonal cryoglobulinemia in another. A peripheral nerve biopsy specimen was available for all patients and the morphological findings in these specimens in the cases of CIDP with IgG MG or cryoglobulin did not differ from those without, whereas characteristic features were observed in the cases of CIDP with IgM MG and anti-myelin associated glycoprotein activity. Received: 7 April 1999 / Revised, accepted: 6 October 1999     

Spreading of autoimmunity from central to peripheral myelin: two cases of clinical association between multiple sclerosis and chronic inflammatory demyelinating polyneuropathy

Abstract Demyelinating inflammatory diseases of central and peripheral myelin share similar aetiopathogenesis but rarely occur simultaneously in the same individual. Here we report two clinical cases of temporal association between multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Our finding supports the hypothesis that clinically manifested central and peripheral demyelinating diseases could result from a common pathogenic event characterised by T-cell autoimmunity spreading from central to peripheral myelin.     

The expression of TNF-alpha receptors 1 and 2 on peripheral blood mononuclear cells in chronic inflammatory demyelinating polyneuropathy

The proportion of peripheral blood mononuclear cells (PBMCs) expressing TNF-alpha and its receptors (TNFR1, TNFR2) and the serum concentrations of its soluble forms were analyzed by FACS and ELISA in the patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and in controls. Elevated levels of TNFR2 were observed on blood T cells in CIDP and idiopathic polyneuropathy. Low levels of TNFR1 were detected on monocytes in the subgroup of patients with CIDP examined after treatment with intravenous immunoglobulin. However, the proliferative activity of PBMCs in CIDP was not influenced by soluble recombinant TNFR1. Our limited data suggested the exact role of TNF-alpha and its receptors need to study further in CIDP, as well as in idiopathic neuropathies.