Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system

During recent years, novel insights in basic immunology and advances in biotechnology have contributed to an increased understanding of the pathogenetic mechanisms of immune-mediated disorders of the peripheral nervous system. This increased knowledge has an impact on the management of patients with this class of disorders. Current advances are outlined and their implication for therapeutic approaches addressed. As a prototypic immune-mediated neuropathy, special emphasis is placed on the pathogenesis and treatment of the Guillain-Barré syndrome and its variants. Moreover, neuropathies of the chronic inflammatory demyelinating, multifocal motor, and nonsystemic vasculitic types are discussed. This review summarizes recent progress with currently available therapies and--on the basis of present immunopathogenetic concepts--outlines future treatment strategies.     

Monofocal motor neuropathy: Improvement with intravenous immunoglobulin

Multifocal motor neuropathy (MMN) is a chronic, immune-mediate, peripheral myelinopathy. Inherent in its name, MMN implies involvement of two or more motor nerves. We report three patients with weakness and partial motor conduction block restricted to a single nerve and localized to sites that are not at risk for entrapment or compression injury. None of the patients had sensory involvement and all showed a favorable response to intravenous immunoglobulin therapy. Based on these observations and reports of three additional patients, we believe that monofocal motor neuropathy is a partial form of MMN and should be treated as such.     

Multifocal sensory demyelinating neuropathy: Report of a case

Introduction: Multifocal sensory demyelinating neuropathy has not been adequately reported in the literature. Methods: A 42‐year‐old man with numbness of the left hand for 3 years and of the right hand for 6 months had a pure multifocal sensory neuropathy involving both hands, most prominently affecting 2‐point discrimination, number writing, and object recognition of the left hand. Near‐nerve needle sensory and mixed nerve conduction studies were performed on the left ulnar nerve. Results: Studies of the left ulnar nerve documented a demyelinating neuropathy characterized by temporal dispersion and marked decrease in the amplitudes of the sensory and mixed compound nerve potentials in the above‐elbow‐axilla segment. With intravenous immunoglobulin treatment, there was improvement in his neuropathic condition. Conclusion: In this study I describe a case of multifocal sensory demyelinating neuropathy as a counterpart of multifocal motor neuropathy. Muscle Nerve 56 : 825–828, 2017     

Nerve ultrasound protocol in differentiating chronic immune‐mediated neuropathies

Introduction: In this study we evaluated a new neuropathy ultrasound protocol (NUP) for differentiating chronic immune‐mediated neuropathies. Methods: The NUP was evaluated in 110 patients with clinical presentations of chronic immune‐mediated neuropathy. All patients were first evaluated clinically and electrophysiologically and divided into 4 polyneuropathy groups: (a) symmetric demyelinating; (b) symmetric axonal; (c) asymmetric demyelinating; and (d) asymmetric axonal. During step 2, the NUP was evaluated prospectively for all 4 study groups. Results: Overall, the NUP led to correct classification in 42 of 49 (85.7%) patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 13 of 15 (86.9%) with multifocal motor neuropathy (MMN), and 5 of 5 (100%) with multifocal‐acquired demyelinating sensory and motor neuropathy (MADSAM). The NUP had >80% sensitivity and specificity in distinguishing CIDP, MMN, and MADSAM in all 4 study groups. Conclusions: The NUP is a useful addition in the differential diagnosis of chronic immune‐mediated neuropathies in everyday practice. Muscle Nerve 54 : 864–871, 2016     

Sensory loss in multifocal motor neuropathy: A clinical and electrophysiological study

Some patients fulfilling the criteria for the diagnosis of multifocal motor neuropathy with conduction block (MMN‐CB) at the onset of disease may subsequently develop a sensory loss associated with electrophysiological sensory abnormalities. The latter could represent an overlap between MMN‐CB and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. The objective was to specify the features of MMN‐CB with sensory loss (MMN‐CB‐Se). Five patients in a series of 11 consecutive patients who fulfilled the criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine for MMN‐CB at the first examination and were treated periodically with intravenous immunoglobulin (IVIg) developed sensory loss in the course of the disease. In these five patients we compared the clinical, laboratory, and electrophysiological features found after the development of sensory loss with those at the first examination. The mean time to appearance of objective sensory signs was 7.2 years. In three of the five patients the sensory loss was preceded by intermittent paresthesias in the same nerve territories as the motor involvement. The most frequent electrophysiological abnormality was amplitude reduction of sensory nerve action potentials. There were no bilateral or symmetrical clinical and electrophysiological sensory abnormalities. Anti‐GM1 IgM antibodies were positive in four patients. MMN‐CB‐Se could be an overlap between MMN‐CB and MADSAM. It shares the distribution of the sensory disorders encountered in MADSAM, but it is closer to MMN‐CB on clinical and therapeutic levels. Study of more patients would be useful to classify this subgroup more accurately. Muscle Nerve, 2009     

Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

Objective – To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods – Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results – Two patients worsened gradually during the treatment and 1 remained unchanged. Conclusion – Rhesus anti-D immunoglobulin has no beneficial effect in patients with autoimmune neuropathy.     

Management challenges for chronic dysimmune neuropathies during the COVID-19 pandemic

Since March 2020, the COVID-19 pandemic has led to the need to re-think the delivery of services to patients with chronic dysimmune neuropathies. Telephone/video consultations have become widespread but have compounded concerns about objective evaluation. Therapeutic decisions need, more than ever before, to be considered in the best interests of both patients, and society, while not denying function-preserving/restoring treatment. Immunoglobulin therapy and plasma exchange, for those treated outside of the home, expose patients to the hazards of hospital or outpatient infusion centers. Steroid therapy initiation and continuation pose increased infectious risk. Immunosuppressant therapy similarly becomes highly problematic, with the risks of treatment continuation enhanced by uncertainties regarding duration of the pandemic. The required processes necessitate considerable time and effort especially as resources and staff are re-deployed to face the pandemic, but are essential for protecting this group of patients and as an integral part of wider public health actions.     

A prospective evaluation of phrenic nerve conduction in multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy

The purpose of the study was to evaluate electrophysiologically phrenic nerve involvement in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). The response latencies following phrenic nerve stimulation were increased in 11 of 14 (80%) patients in the CIDP group but in only 1 of 14 (8%) patients in the MMN group. The mean diaphragmatic compound muscle action potential (CMAP) was significantly lower in amplitude in the CIDP group compared to the MMN group and to a control group of 8 subjects (P < 0.001). There were no significant differences between the MMN and control groups. Only the reduction in CMAP amplitude correlated with the presence of restrictive lung function. Phrenic nerve conduction measurement should be performed more systematically, especially in CIDP and, when diaphragmatic CMAPs are reduced in amplitude, pulmonary function tests should be performed to look for a restrictive lung syndrome.     

Lewis–sumner syndrome of pure upper‐limb onset: Diagnostic,prognostic, and therapeutic features

We studied two 16‐year‐old males with juvenile muscular atrophy of the distal arm, “Hirayama disease,” resulting in asymmetric atrophy and weakness of the distal upper extremities. Pathogenic theories include a compressive myelopathy with or without ischemia, and occasional cases are accounted for by genetic mutations. To specifically address the ischemia hypothesis we performed spinal angiography and epidural venography. Neck flexion during spinal angiography showed a forward shift of a nonoccluded anterior spinal artery without impedance to blood flow. Epidural venography demonstrated engorgement of the posterior epidural venous plexus without obstruction to venous flow. The findings do not support large vessel obstruction as a contributory factor. The Hirayama hypothesis continues to best explain the disease pathogenesis: neck flexion causes tightening of the dura and intramedullary microcirculatory compromise with resultant nerve cell damage. The age‐related factor can most likely be accounted for by a growth imbalance between the vertebral column and the cord/dural elements. Resolution of progression is associated with cessation of body growth, after which the symptoms plateau or modestly improve. Muscle Nerve 40: 206–212, 2009     

Early neurophysiological evolution of chronic inflammatory demyelinating polyneuropathy in a patient with Hashimoto's thyroiditis

A patient with a known history of hypothyroidism due to Hashimoto's thyroiditis presented with a subacute, progressive sensorimotor deficit that affected the upper limbs predominantly. The electrophysiological findings progressively evolved from multifocal motor conduction block to multifocal demyelinating sensory and motor nerve involvement with conduction block, and finally to findings fulfilling the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy (CIDP). The patient did not respond adequately to intravenous immunoglobulin, whereas oral prednisone led to fast and complete recovery. This report discusses the evolution of early findings of CIDP, as well as its coexistence with Hashimoto's thyroiditis.     

Subcutaneous versus intravenous immunoglobulin for chronic autoimmune neuropathies: A meta‐analysis

Introduction: High‐dose intravenous immunoglobulin (IVIg) is an evidence‐based treatment for multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). Recently, subcutaneous immunoglobulin (SC‐Ig) has received increasing attention. Methods: We performed a meta‐analysis of reports of efficacy and safety of SC‐Ig versus IVIg for inflammatory demyelinating polyneuropathies. Results: A total of 8 studies comprising 138 patients (50 with MMN and 88 with chronic CIDP) were included in the meta‐analysis. There were no significant differences in muscle strength outcomes in MMN and CIDP with Sc‐Ig (MMN: effect size [ES] = 0.65, 95% confidence interval [CI] = ‐0.31‐1.61; CIDP: ES = 0.84, 95% CI = ‐0.01‐1.69). Additionally SC‐Ig had a 28% reduction in relative risk (RR) of moderate and/or systemic adverse effects (95% CI = 0.11‐0.76). Conclusions: The efficacy of SC‐Ig is similar to IVIg for CIDP and MMN and has a significant safety profile. Muscle Nerve 55 : 802–809, 2017