Involvement of the central nervous system in chronic inflammatory demyelinating polyneuropathy: a clinical, electrophysiological and magnetic resonance imaging study.

In a consecutive series of 30 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) minor clinical evidence of CNS involvement was found in five. Cranial magnetic resonance imaging (MRI) was performed in 28 and revealed abnormalities consistent with demyelination in nine patients aged less than 50 years and abnormalities in five aged 50 years or over. Measurements of central motor conduction time (CMCT) were obtained in 18 and showed unilateral or bilateral abnormalities in six. It is concluded that subclinical evidence of central nervous system (CNS) involvement is common, at least in patients with CIDP in the United Kingdom, but that clinically evident signs of CNS disease are infrequent. The association of a multiple sclerosis-like syndrome with CIDP is rare.     

Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy

Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome.     

POEMS综合征六例临床特点分析

目的分析POEMS综合征的临床特点,提高临床医生对该病的认识。方法收集海军总医院2005-01—2015-05确诊的POEMS综合征6例,回顾分析其临床表现、实验室检查、治疗及预后等资料。结果男5例、女1例,发病年龄39~59岁;疾病初期临床表现可仅累及1个或2个系统,随着病情进展,临床表现为多发性周围神经病、皮肤改变及单克隆浆细胞异常增生6例,脏器及淋巴结肿大5例,内分泌异常5例,视乳头水肿4例,浆膜下积液3例,脑脊液蛋白细胞分离6例,血和脑脊液寡克隆区带阳性2例。行腓肠神经活检2例,病理学检查示活动性轴索病变伴髓鞘脱失。行发射型计算机断层(ECT)检查4例,结果显示骨髓增生性改变3例。行PET-CT检查2例,均显示硬化性骨病。误诊为慢性炎性脱髓鞘性多发性神经病(CIDP)4例,慢性周围神经病2例。结论 POEMS综合征常累及多个系统,常见的受累系统为周围神经系统和单克隆浆细胞异常增生的血液系统,早期易误诊为CIDP。血免疫固定电泳/PET-CT检查有助于早期发现该病。     

POEMS syndrome: follow-up study of a case.

We report here the case of a 20-year-old man with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M proteins, skin changes). This rare syndrome followed a 3-year history of a syndrome that mimics a chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with cyclophosphamide induced regression of the syndrome and improved peripheral nerve conduction.     

POEMS syndrome with plasmocytoma lytic bone lesion

INTRODUCTION: Crow-Fukase or Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes syndrome (POEMS) is a rare multisystemic affection with incompletely elucidated etiopathogenesis. CASE REPORT: We report a case of POEMS syndrome in a 48-year-old adult revealed four months before admission by areflexic flask tetraparesis prevalent on the lower limbs in connection with demyelinating and axonal CIDP "like" sensoriomotor neuropathy of the four limbs electroneuromyographically. The patient presented elevated protein level in the CSF with monoclonal standard IgG gammapathy associated with a narrow band lambda, suggesting POEMS syndrome. Further explorations revealed skin lesions with glomeruloid angiomas, edematous vasomotor disorders as well as erythrocyanose, hypogonadism, papillar edema and a lytic bone lesion of the left scapula. Radiotherapy was associated with corticosteroids and plasma exchanges. Outcome was good with resolution of the symptoms and stabilization of the neuropathy. DISCUSSION: POEMS syndrome is rare; the diagnosis is based on necessary criteria, the presence of a demyelinating and axonal polyneuropathy associated with an IgA or IgG monoclonal gammapathy, the light chain being almost entirely lambda, associated to other characteristic elements, in particular glomeruloid angiomas, endocrinopathy, sclerosing plasmocytoma which must be carefully required. Treatment is based on surgical cure or radiotherapy for bone lesion and non specific treatments such as corticosteroid therapy, plasma exchanges and IVIG.     

Optic atrophy and chronic acquired polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic, multifocal disorder usually defined as limited to the peripheral nervous system. Multifocal motor neuropathy, an acquired demyelinating neuropathy with conduction block affecting motor neurons only, may be a pathogenically distinct syndrome or a predominantly motor variant of chronic inflammatory demyelinating polyneuropathy. Central nervous system demyelination including optic neuropathy has been reported uncommonly previously in these entities. We report two cases and review the literature on the possible association of optic neuropathy and chronic acquired polyneuropathy.     

Blink R1 latency utility in diagnosis and treatment assessment of polyradiculoneuropathy‐organomegaly‐endocrinopathy‐monoclonal protein‐skin changes and chronic inflammatory demyelinating polyradiculoneuropathy

Introduction: In polyradiculoneuropathy‐organomegaly‐endocrinopathy‐monoclonal protein‐skin changes (POEMS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), limb nerve conduction studies (NCSs) are limited in identifying demyelination and in detecting treatment effects in severely affected patients. Blink R1 latency may improve these assessments. Methods: POEMS and CIDP patients who had undergone NCS and blink reflex were identified. Correlations among R1 latency, limb NCS, and neuropathy impairment scores (NIS) were compared. Results: Among 182 patients (124 POEMS, 58 CIDP) who were identified, R1 prolongation (>13 ms) occurred in 64.3% (65.3% POEMS, 62.1% CIDP). R1 prolongation correlated with more severely affected NCS in both POEMS (ulnar CMAP 2.6 mV vs. 4.5 mV, P = 0.001) and CIDP (2.0 mV vs. 6.1 mV, P < 0.001). In severely affected patients (ulnar CMAP ≤0.5 mV [10%:18/182]), R1 (>13 ms) helped establish demyelination. In 31 patients (16 POEMS, 15 CIDP), the R1 latency changes were concordant with NIS changes in 94% of patients with POEMS and 60% of patients with CIDP. Discussion: Blink R1 latencies are valuable in defining demyelination and detecting improvement in severely affected POEMS and CIDP patients. Muscle Nerve 57 : E8–E13, 2018     

Evidence for central nervous system demyelination in chronic inflammatory demyelinating polyradiculoneuropathy

It is unclear whether sporadic reports of concurrent multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent coincidence or whether these two demyelinating disorders are pathogenically related. We utilized the sensitivity of magnetic resonance imaging (MRI) in detecting central nervous system (CNS) lesions to investigate 16 patients with CIDP. Six of the 16 had periventricular, subcortical, and brainstem white matter lesions indistinguishable from those seen in MS. Three of these patients had definite clinical and laboratory evidence of MS; three others with abnormal MRIs had no findings indicative of CNS disease. Previous reports have indicated that a significant number of MS patients have peripheral nerve demyelination. Our study suggests that many CIDP patients have concurrent CNS demyelination. Taken together, these observations support the existence of a central-peripheral inflammatory demyelinating syndrome. Whether this combined demyelinating syndrome lies on a spectrum between MS and CIDP or is a separate pathogenic entity will require further investigation.     

Biomarkers of CIDP in patients with diabetes or CMT1

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease that targets the myelin sheaths in peripheral nerves. Primary demyelination can be detected by electrodiagnostic studies or nerve biopsy, but these do not distinguish between demyelination resulting from CIDP or from non-inflammatory causes such as diabetes or Charcot-Marie-Tooth type I. Consequently, the diagnosis of CIDP in such patients is often missed. Studies are needed to establish electrodiagnostic criteria for CIDP in patients with diabetes, and to identify biomarkers that distinguish between inflammatory and non-inflammatory causes of demyelinating neuropathy.     

Treatment of immune-mediated, dysimmune neuropathies

This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B-cell surface-membrane-marker CD20.     

Diagnostic value of myotactic reflexes in axonal and demyelinating polyneuropathy.

In 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 11 patients with chronic idiopathic axonal polyneuropathy (CIAP), absent myotatic reflexes were significantly associated more often with CIDP than with CIAP, an absent biceps-reflex having the highest sensitivity and specificity for the diagnosis of CIDP. In CIDP, the latencies of electromyographically recorded myotatic reflexes often indicated demyelination, notwithstanding normal clinically assessed myotatic reflexes. Myotatic reflexes may therefore be useful for the distinction between axonal and demyelinating polyneuropathy.     

Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord

CNS demyelinating lesions have been reported in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). There are no studies of cord atrophy in CIDP. Ten patients with CIDP underwent brain and spinal cord MRI to investigate CNS demyelination and cord atrophy. No CNS demyelination was found, but the mean cervical cord area was significantly smaller in CIDP patients vs control subjects. Spinal cord atrophy may be related to degeneration secondary to axonal loss.     

The spectrum of chronic inflammatory demyelinating polyneuropathy

Research criteria for the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) were proposed by an Ad Hoc Subcommittee of the American Academy of Neurology (AAN) in 1991, and since then these criteria have been widely used in clinical studies. We have been impressed by the frequent finding of electrophysiological changes of a demyelinating neuropathy in patients whose clinical presentation does not conform to the usually accepted clinical phenotype of CIDP. To determine the clinical spectrum of CIDP, we conducted a retrospective review of patients of the peripheral electrophysiology laboratory of the University of Miami-Jackson Memorial Medical Center. Diagnostic criteria for acquired demyelination of an individual nerve were adapted from the AAN research criteria for the diagnosis of CIDP (1991). Patients were accepted for inclusion when such evidence was demonstrated in at least one motor nerve or at least two sensory nerves. We then reviewed the clinical phenotype and the underlying etiology of the neuropathy in these cases. Eighty-seven patients, 63 male and 24 female, age of onset 4-84 (mean 49.3) years, met these inclusion criteria. Forty-seven patients (54%) had distinct features outside the usual clinical presentation of CIDP. Of these, 15 (17%) had predominantly distal features, 13 (15%) had exclusively sensory polyneuropathy; seven (8%) had markedly asymmetric disease, seven (8%) had associated CNS demyelination, four (5%) had predominant cranial nerve involvement, and one (1%) had only the restless legs syndrome. An associated medical condition that may have been responsible for the acquired demyelinating neuropathy was present in 60% of the patients. We conclude that spectrum of CIDP is broader than would be indicated by the strict application of the AAN research criteria, and that many of the cases meeting more liberal criteria frequently respond to immunosuppressive therapy.     

Fas-mediated T-cell apoptosis is impaired in patients with chronic inflammatory demyelinating polyneuropathy

The Fas death receptor is expressed by activated lymphocytes and is involved in switching-off the immune response. Its inherited defects cause auto-immune lymphoproliferative syndrome. Impaired Fas function may also play a role in other auto-immune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The aim of this work was to evaluate Fas function in T cells from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated Fas-induced apoptosis in T-cell lines from 27 patients with CIDP, 12 patients with acute inflammatory demyelinating polyneuropathy (AIDP), and 110 controls. CIDP patients displayed lower Fas function than both AIDP patients and controls, whereas no statistically significant difference was found between AIDP patients and controls. Moreover, Fas function was lower in CIDP patients with progressive course than in those with relapsing-remitting course and lower in CIDP patients with axonal damage than in those with pure demyelination. These data suggest that defective Fas function favours CIDP development and aggressive evolution.     

Chronic inflammatory demyelinating polyneuropathy

In 1975, clinical, electrodiagnostic, and pathologic features defined chronic inflammatory demyelinating polyneuropathy (CIDP). Subsequent reports have made it clear that demyelination is a cardinal feature of teh disorder. Over the past 30 years, variants have been described and associated systemic disorders identified. There continues to be discussion, however, as to how best to define CIDP and classify the disorders that are chronic, acquired, immune mediated, and demyelinating. Understanding the disorders allows clinicians to make appropriate treatment decisions. Some disorders originally considered as variants now are shown to have characteristic features that make them distinct from CIDP. It is imperative to recognize the differences between these disorders.     

Visual evoked potentials study in chronic idiopathic inflammatory demyelinating polyneuropathy.

BACKGROUND: The frequency of the association between chronic demyelinating inflammatory polyneuropathy (CIDP) and central nervous system (CNS) demyelinating lesions is probably underestimated. OBJECTIVE: To investigate the occurrence of combined central and peripheral demyelination in CIDP patients and to correlate visual evoked potential (VEP) abnormalities with CNS demyelinating lesions, observed on brain magnetic resonance imaging, and antibodies against glycolipids. METHODS: Nerve conduction studies, brain MRI and antibodies against glycolipids were prospectively studied in 17 patients who fulfilled the diagnostic criteria proposed for CIDP (Cornblath DR, Asbury AK, Albers JW, Feasby TE, Hahn AF, McLeod JG, Mendell JR, Parry GJ, Pollard JD, Thomas PK. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology, 1991;41:617-618). VEPs were performed in each case before and after 6 months treatment with either intravenous immunoglobulins (IVIG) or steroids. RESULTS: Eight patients (47%) had increased latencies in at least one eye or showed increased interocular latency difference. Four patients (23%) presented a significant high signal intensity on T2-weighted brain MRI images. Of these 4 patients, 3 had prolonged VEP latency. Two patients with delayed VEP latency had antibodies against GM1, and SGLPG and anti-sulfatides, respectively. One patient with normal VEPs also had antibodies to GM1. VEP results were not significantly modified after treatment, either with steroids or IVIG. CONCLUSION: This study confirmed the high frequency of abnormal VEPs in CIDP patients, and found that they are poorly correlated with CNS demyelinating lesions and antibodies against glycolipids. The VEP abnormalities of these patients may be explained by the susceptibility to immune-mediated damage of both the peripheral nervous system and the optic nerve.     

Motor and sensory demyelinating mononeuropathy multiplex (multifocal motor and sensory demyelinating neuropathy): a separate entity or a variant of chronic inflammatory demyelinating polyneuropathy?

We report 16 patients with motor and sensory demyelinating mononeuropathy multiplex (MSDMM) or multifocal motor and sensory demyelinating neuropathy (MMSDN). These patients had the clinical pattern of motor and sensory mononeuropathy multiplex, electrophysiological evidence of demyelination including conduction block, and segmental demyelination in the sural nerve biopsy. Sixty per cent of patients had high CSF protein. Eighty per cent of patients showed good responsiveness to steroid treatment. Unlike multifocal motor neuropathy (MMN), MSDMM is characterized by a shorter course, sensory deficits and sensory nerve conduction abnormalities, absence of GM1 antibody in most patients tested, and a good response to steroid therapy. We believe that MSDMM represents a variant of chronic inflammatory demyelinating polyneuropathy (CIDP) and an intermediate link between CIDP and MMN.     

Chronic acquired demyelinating symmetric polyneuropathy classified by pattern of weakness

OBJECTIVES: To study a representative group of patients with chronic acquired symmetric demyelinating polyneuropathies, and to evaluate classification by pattern of weakness and by presence of immunoglobulin monoclonal protein (M protein). METHODS: In Vest-Agder County, Norway, an unselected population of patients with chronic symmetric polyneuropathies who fulfill electrodiagnostic criteria for demyelination are registered in a database and followed up prospectively. Data were taken from the database on April 2, 2001. Patients with proximal as well as distal weakness were classified as having chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and patients with only distal symptoms as having distal acquired demyelinating symmetric polyneuropathy (DADS). RESULTS: A total of 29 patients had chronic acquired symmetric demyelinating polyneuropathy; 15 had CIDP and 14 had DADS. The 2 categories differed regarding spinal protein level (mean +/- SD, 0.102 +/- 0.060 g/dL in CIDP vs 0.065 +/- 0.029 g/dL in DADS; P =.05); clinical course (remitting in 6 of 13 patients with CIDP vs 0 of 14 with DADS; P =.02); disability score at diagnosis (mean +/- SD, 3.3 +/- 1.0 in CIDP vs 1.9 +/- 0.6 in DADS; P<.001) and at peak of symptoms (mean +/- SD, 3.6 +/- 1.1 in CIDP vs 2.3 +/- 0.6 in DADS; P<.001); and response to immunosuppressive treatment (11 of 12 patients with CIDP vs 2 of 7 with DADS; P =.01). An M protein was detected in 8 patients (3 with CIDP and 5 with DADS). Patients with polyneuropathy with and without M protein were similar in clinical features, course, disability, and treatment response. CONCLUSION: Classification by presence or absence of proximal weakness separates patients with chronic acquired symmetric demyelinating polyneuropathy into groups that are different in clinical course, disability, and treatment response.     

Dispersion of the distal compound muscle action potential in chronic inflammatory demyelinating polyneuropathy and carpal tunnel syndrome

Median neuropathy at the wrist can confound the electrodiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), since both conditions can prolong median distal motor latency. Dispersion of the distal CMAP (DCMAP) has recently emerged as a potentially useful adjunct in the electrodiagnosis of CIDP, with good specificity in distinguishing CIDP from certain axon-loss disorders. However, it is uncertain whether focal compression neuropathies produce dispersion of the DCMAP in a manner similar to CIDP. In this study we compared median DCMAP duration in 27 patients with CIDP and 86 with carpal tunnel syndrome, using 39 patients with non-neuropathic musculoskeletal pain syndromes as electrophysiologic controls. We found that, in contrast to CIDP, dispersion of the median DCMAP is uncommon, even in advanced carpal tunnel syndrome, being seen in only 8 of 103 (7.8%) hands. Although the pathophysiologic reasons for a differential effect of focal compression-mediated demyelination and multifocal immune-mediated demyelination (CIDP) on DCMAP duration are uncertain, our findings suggest that the presence of dispersion of the median DCMAP may prove useful in distinguishing immune-mediated demyelination from compression neuropathy alone.     

Threshold electrotonus in chronic inflammatory demyelinating polyneuropathy: correlation with clinical profiles

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by multifocal demyelination along the course of the nerves, and involvement of the intermediate segments may correlate with more severe demyelination associated with breakdown of the blood-nerve barrier. Threshold electrotonus was used to study whether altered membrane properties of the median nerve at the wrist (intermediate segment) are associated with clinical profiles in 21 CIDP patients. In response to hyperpolarizing conditioning stimuli, the threshold changes were significantly greater for CIDP patients than for normal controls (n = 49). The pattern was similar to that of 11 patients with Charcot-Marie-Tooth disease type 1a, who exhibited abnormally high thresholds to hyperpolarizing currents. The abnormal threshold electrotonus was present in 48% of the CIDP patients and was associated with longer disease duration, more severe disability, poorer response to immune treatments, and slower nerve conduction velocities. Threshold electrotonus can be used to detect demyelination at the tested sites and may provide new information about pathophysiology and distribution patterns of demyelination in CIDP.