Chronic inflammatory demyelinating polyneuropathy

In 12 cases of CIDP under surveillance for 14 years, the main nerve biopsy findings were endoneural oedema and demyelination of nerve fibres. IgM deposition was found in 1 patient and IgG deposits in another. Electron microscopy revealed proliferation of the Schwann cells and mononuclear cell infiltration. The diagnostic criteria and nerve biopsy findings in CIDP are listed in the tables.     

Chronic inflammatory demyelinating polyneuropathy: diagnosis and management

Over the course of 8 weeks, a 50-year-old man developed progressive bilateral leg and arm weakness, with numbness and tingling of the feet and hands. His symptoms persisted for 6 months, with impaired manual dexterity, arm weakness when brushing his teeth, tripping when walking, inability to climb stairs and gait imbalance. On examination, there is mild proximal and distal weakness of the upper and lower extremity muscles, length-dependent sensory loss of vibratory perception and joint position sense, areflexia, positive Romberg test and steppage gait with bilateral foot drop. Motor nerve conduction studies of the arms and legs show partial conduction blocks in several nerves with nonuniform slowing, and sensory responses are absent in the hands, however, normal sural responses are noted. Lumbar puncture reveals acellular cerebrospinal fluid with elevated protein. After 2 months following treatment, his strength and gait improved significantly, and his sensory symptoms resolved.     

Chronic inflammatory demyelinating polyneuropathy as first manifestation of human immunodeficiency virus infection

We studied three patients who were admitted to the hospital because of progressive weakness without other systemic signs or symptoms. All three cases were young males who had been intravenous drug user for many years. Electrophysiologic study showed prolonged distal latencies and marked slowing of motor and sensory conduction velocities, consistent with primary demyelination. Nerve biopsy also showed signs of demyelination. Antibodies against HIV in CSF and blood were detected during the diagnostic evaluation. Clinical and electrophysiological studies improved in two cases after prednisone administration. Patients with predominant motor demyelinating neuropathies and risk factors should be screen for HIV infection.     

Chronic inflammatory demyelinating polyneuropathy: immunopathological and ultrastructural study of peripheral nerve biopsy in 42 cases

The authors recently reexamined the peripheral nerve biopsies from 42 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). There were 27 males and 15 females, aged from 9 to 84 years, and 13 had relapses. No patient had vasculitis, monoclonal gammopathy, tumor, diabetes mellitus, Lyme disease, familial neuropathy, HIV, or any other immune deficiency. In the endoneurium, perivascular inflammatory cell infiltrates were present in only one case, but scattered histiocytes marked by KP1 on paraffin-embedded fragments were present in every case and there were no T-lymphocytes. At ultrastructural examination macrophage-associated demyelination was observed in 17 cases, of which 6 had relapses separated by intervals of several months or years. Axonal lesions without associated primary demyelination were observed in 4 cases and 3 of these had relapses. Thirty-two patients had mixed lesions of demyelination and axonal involvement. This study confirms other recent data indicating that in all cases of CIDP, macrophages are present in the endoneurium. Macrophage-associated demyelination is the characteristic feature of demyelinating forms. On the other hand, isolated primary axonal forms, which have been known since 1989, are relatively frequent and prone to relapses.     

Family with inflammatory demyelinating polyneuropathy and the HNPP 17p12 deletion

Hereditary neuropathy with liability to pressure palsies (HNPP), classically presenting as recurrent focal neuropathies precipitated by trauma or compression, is an autosomal dominant neuropathy due to a deletion at chromosomal locus 17p12. Inflammatory demyelinating polyneuropathy (IDP), a putative autoimmune disorder presenting in an acute (AIDP) or a chronic form (CIDP), has been rarely reported as familial. We present a father and two daughters of Jewish Kurdish origin who developed IDP within 10 years. The unusual familial history led us to reevaluate the diagnosis of IDP, and suggested an autosomal dominant pedigree. DNA analysis identified the deletion typical of HNPP on chromosome 17. Screening for the HNPP deletion in patients with atypical, recurrent, or familial IDP might be warranted.     

Chronic relapsing polyneuropathy associated with immunoblastic lymphadenopathy

Two episodes of severe, relapsing sensorimotor polyneuropathy closely paralleled the course of systemic illness in a patient with immunoblastic lymphadenopathy. A review of the literature shows three other cases, although none with documented pathologic changes in muscles and nerves. Based on the pathologic findings in this patient, the peripheral neuropathy associated with immunoblastic lymphadenopathy can be classified under the group of relapsing inflammatory polyneuropathies associated with systemic disorders. Whether prednisone therapy helped this condition is uncertain.     

CNS involvement in chronic inflammatory demyelinating polyneuropathy: an electrophysiological and MRI study

Eight consecutive patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated by visual evoked potential (VEP), brainstem auditory evoked response (BAER) and magnetic resonance imaging (MRI) to assess central nervous system (CNS) involvement. VEPs were abnormal in 6 patients and BAERs in 2. MRI showed changes suggestive of CNS demyelination in 2 cases. Our findings suggest the existence of a combined central and peripheral demyelinating syndrome and emphasize the possibility of a common pathogenetic mechanism for both.     

Lumbosacral acute demyelinating polyneuropathy following hepatitis B vaccination.

We report a patient who presented with an acute inflammatory demyelinating polyneuropathy, that followed the second injection of a hepatitis B vaccination, and characterized by motor and sensory deficit restricted to lower limbs and perineum, and persistent bladder dysfunction. The relationship between the preceding event and neurological disease is discussed.     

Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413–420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77–84, 2019. © 2019 Wiley Periodicals, Inc.     

慢性炎症性脱髓鞘性多发性神经病患儿的临床及神经电生理3例分析

目的:探讨儿童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变化.方法:回顾性分析3例CIDP的临床表现、脑脊液及神经电生理检测结果.结果:3例CIDP均有四肢肌力下降,腱反射减弱或消失,脑脊液蛋白升高,神经电生理异常(包括远端潜伏期延长、传导速度减慢、F波潜伏期延长).结论:对病程＞4周的肢体迟缓性麻痹患儿,应考虑到CIDP可能,及时进行脑脊液及神经电生理检测有助于诊断.     

Proteinases in inflammatory demyelinating disease

Conclusion Proteinases are likely to be involved in the generation of the immune response and the tissue injury found in inflammatory demyelination of the CNS and PNS. The mechanisms whereby proteinases effect changes in these disorders are imprecisely understood but may be important in terms of understanding susceptibility, the extent of tissue damage, and possibly as an avenue for therapeutically controlling the disease by inhibition of proteinases. Several recent observations on the role of proteinases in the immune response for antigen processing, B cell activation, production of selected peptides which may have autosensitization potential and in the cytotoxic damage of tissue indicate the importance which proteinases, acting alone, in sequence, or in combination, may have in inflammatory demyelination.     

Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy

Plasma exchange has been reported to be efficacious in chronic inflammatory demyelinating polyradiculoneuropathy. We performed a prospective double-blind trial in which patients with static or worsening disease were randomly assigned to plasma exchange (n = 15) or to sham exchange (n = 14) for three weeks. After three weeks, we observed statistically significant differences in combined measurements of nerve conduction (total, motor, proximal, velocity, and amplitude) favoring patients who had received plasma exchange. Improvement to a greater degree than for any patient receiving sham exchange was detected in the neurologic-disability score in five patients (P = 0.025) and in subset scores for weakness and reflex in four patients (P less than 0.057). We conclude that for some patients with chronic inflammatory demyelinating polyradiculoneuropathy, plasma exchange has an ameliorating effect on neurologic dysfunction and nerve conduction, but in others no improvement is observed. Because plasma was replaced with normal serum albumin, a humoral factor or factors may have a role in the neurologic deficit of this disorder.     

Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance.

BACKGROUND. Polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS) has been treated with plasma exchange, intravenous immune globulin, and chemotherapy, but the effectiveness of these treatments remains uncertain. METHODS. We randomly assigned 39 patients with stable or worsening neuropathy and MGUS of the IgG, IgA, or IgM type to receive either plasma exchange twice weekly for three weeks or sham plasma exchange, in a double-blind trial. The patients who initially underwent sham plasma exchange subsequently underwent plasma exchange in an open trial. RESULTS. In the double-blind trial, the average neuropathy disability score improved by 2 points from base line (from 62.5 to 60.5) in the sham-exchange group and by 12 points (from 58.3 to 46.3) in the plasma-exchange group (P = 0.06). A similar difference was observed in the weakness score, a component of the neuropathy disability score (improvement, 1 and 10 points, respectively; P = 0.07). After treatment the summed compound muscle action potentials of motor nerves were 1.2 mV lower (worse) than at base line in the sham-exchange group and 0.4 mV higher (better) in the plasma-exchange group (P = 0.07). The greater degree of improvement with plasma exchange was equal in magnitude to or greater than the difference between not being able to walk on the heels or toes and being able to perform these activities. Changes in the vibratory detection threshold, summed motor-nerve conduction velocity, and sensory-nerve action potentials did not differ significantly between the treatment groups. In the open trial, in which patients who initially underwent sham exchange were treated with plasma exchange, the neuropathy disability score (P = 0.04), weakness score (P = 0.07), and summed compound muscle action potentials (P = 0.07) improved more with plasma exchange than they had with sham exchange. In both the double-blind and the open trial, those with IgG or IgA gammopathy had a better response to plasma exchange than those with IgM gammopathy. CONCLUSIONS. Plasma exchange appears to be efficacious in neuropathy associated with MGUS, especially of the IgG or IgA type.     

Biological properties of a canine distemper virus isolate associated with demyelinating encephalomyelitis.

A canine distemper virus (CDV), DESIGNATED R252, originally recovered from a dog with demyelinating encephalomyelitis was shown to reproduce this disease in gnotobiotic dogs with a high incidence as compared to other CDV strains, which produced an acute fatal infection. In this investigation, R252 was propagated for the first time in Vero cells and compared to two known strains of CDV, Snyder-Hill (SH) and Onderstepoort (Ond). The results of this study revealed that intracellular R252 accumulated more slowly than either SH or Ond. There was extensive destruction of Vero monolayers infected with either R252 or SH. Each virus induced the formation of intracytoplasmic and intranuclear inclusions. Ond infection resulted in minimal cytopathic changes and intracytoplasmic inclusions. Immunofluorescence studies indicated that the spread of R252 infection within the monolayers was intermediate between the rapidly spreading SH and slowly spreading Ond. R252-infected cells developed characteristic immunofluorescent cytoplasmic inclusions. Initially, each stained homogeneously and later appeared as a non fluorescent body surrounded by a fluorescent ring. This characteristic pattern of fluorescence was observed only infrequently in thelate stage of SH infection and was absent in Ond-infected cultures. Reciprocal neutralization studies indicated that the three strains are of one serotype. These findings suggest that R252-CDV has biological properties which differ from two other strains of CDV and which may have bearing upon the in vivo capability of this virus to produce demyelinating encephalomyelitis.     

Systematic reviews of treatment for inflammatory demyelinating neuropathy

This review describes the progress made in preparing Cochrane systematic reviews of randomized controlled trials for Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and the demyelinating neuropathies associated with paraproteins. The discovery of antibodies against myelin and axolemmal glycolipids and proteins has not yet replaced the clinicopathological classification on which treatment trials have been based. Systematic reviews have endorsed the equivalence of plasma exchange (PE) and intravenous immunoglobulin (IVIg) and the lack of efficacy of steroids in GBS. Systematic reviews have also endorsed the value of steroids, PE and IVIg in CIDP but randomized controlled trials have only shown benefit from IVIg in MMN. There is a paucity of evidence concerning the efficacy of treatments in paraproteinaemic demyelinating neuropathy apartment from small trials showing short-term benefit from PE or IVIg. There is a lack of good quality controlled trials of immunosuppressive agents in any of these conditions. As the number of treatment trials increases, Cochrane systematic reviews will be an increasingly valuable resource for summarizing the evidence from randomised controlled trials on which to base clinical practice. They already demonstrate major deficiencies in the existing evidence base.     

The spectrum of post-vaccination inflammatory CNS demyelinating syndromes

A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases), meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases).In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO.Overal, the risk of a demyelinating CNS disease following vaccination, although non-negligible, is relatively low. The risk of onset or relapse of CNS demyelination following infections against which the vaccines are aimed to protect, is substantially higher and the benefits of vaccinations surpass the potential risks of CNS inflammation. This does not in any way exempt us from “learning” the lessons taught by the reported cases and searching new and safer ways to improve vaccination techniques and increase their safety profile.