Immune-mediated diseases involving central and peripheral nervous systems.

BACKGROUND AND PURPOSE: In addition to combined central and peripheral demyelination, other immune diseases could involve both the central nervous system (CNS) and peripheral nervous system (PNS). METHODS: To identify immune-mediated diseases responsible for symptomatic combined central/peripheral nervous system involvement (ICCPs), we conducted a multicentric retrospective study and assessed clinical, electrophysiological, and radiological features of patients fulfilling our ICCP criteria. RESULTS: Thirty patients (20 males) were included and followed during a median of 79.5 months (interquartile range [IQR] = 43-145). The median age at onset was 51.5 years (IQR = 39-58). Patients were assigned to one of four groups: (i) monophasic disease with concomitant CNS/PNS involvement including anti-GQ1b syndrome (acute polyradiculoneuropathy + rhombencephalitis, n = 2), checkpoint inhibitor-related toxicities (acute polyradiculoneuropathy + encephalitis, n = 3), and anti-glial fibrillary acidic protein astrocytopathy (subacute polyradiculoneuropathy and meningoencephalomyelitis with linear gadolinium enhancements, n = 2); (ii) chronic course with concomitant CNS/PNS involvement including paraneoplastic syndromes (ganglionopathy/peripheral hyperexcitability + limbic encephalitis, n = 4); (iii) chronic course with sequential CNS/PNS involvement including POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome (polyradiculoneuropathy + strokes, n = 2), histiocytosis (polyradiculoneuropathy + lepto-/pachymeningitis, n = 1), and systemic vasculitis (multineuropathy + CNS vasculitis/pachymeningitis, n = 2); and (iv) chronic course with concomitant or sequential CNS/PNS involvement including combined central and peripheral demyelination (polyradiculoneuropathy + CNS demyelinating lesions, n = 10) and connective tissue diseases (ganglionopathy/radiculopathy/multineuropathy + limbic encephalitis/transverse myelitis/stroke, n = 4). CONCLUSIONS: We diagnosed nine ICCPs. The timing of central and peripheral manifestations and the disease course help determine the underlying immune disease. When antibody against neuroglial antigen is identified, CNS and PNS involvement is systematically concomitant, suggesting a common CNS/PNS antigen and a simultaneous disruption of blood-nerve and blood-brain barriers.

Temporal evolution of nerve conduction study abnormalities in anti-myelin-associated glycoprotein neuropathy.

BACKGROUND: A distal-predominant demyelinating symmetric pattern is most frequent in patients with neuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies. The literature however lacks longitudinal data to describe whether this is consistent over time. METHODS: From the Ottawa Neuromuscular Center database, we identified 23 patients with both immunoglobulin M gammopathy and anti-MAG antibodies. For median, ulnar and fibular motor conduction studies, we analyzed distal latency and amplitude, negative peak duration, terminal latency index (TLI), and conduction velocity. For median, ulnar, sural, and superficial fibular sensory conduction studies, we analyzed distal latency and amplitude. Results were compared for the earliest and the latest data sets. RESULTS: The mean time interval between the two assessment points was 6.5 years. Median and ulnar motor nerve conduction studies did not show a significant change for any of the parameters tested. There was disproportionate prolongation of median distal motor latency and reduction in TLI, compared to the ulnar nerve. Deep fibular motor conduction studies showed a marked reduction in amplitudes over time. Sensory potentials were recordable in the upper limb in less than 50% at the first study and less than 25% on the most recent study. There was an even larger attrition of recordable sural and superficial fibular sensory potentials. CONCLUSIONS: Our results highlight the stability of median and ulnar motor conduction study results over a mean observation period of 6.5 years. In contrast, lower limb motor and all sensory potentials show a marked trend toward becoming unrecordable.

Subacute demyelinating polyradiculoneuropathy complicating Epstein-Barr virus infection in GATA2 haploinsufficiency.

INTRODUCTION: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. METHODS: Herein we report on the clinical, serologic, electrophysiologic, and pathologic evaluations of a 29-year-old woman with GATA2 haploinsufficiency and active Epstein-Barr virus (EBV) infection complicated by subacute painful neuropathy. RESULTS: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy. Lumbar spine MRI showed thickening and enhancement of the cauda equina nerve roots. Serum and cerebrospinal fluid anti-IgG and IgM EBV capsid and nucleic acid antibodies were positive. Sural nerve biopsy showed microvasculitis and an increased frequency of fibers with segmental demyelination. Intravenous immunoglobulin and steroids improved the patient's neuropathy. CONCLUSION: GATA2 mutation-related immunodeficiency may predispose to EBV-associated subacute demyelinating polyradiculoneuropathy by both viral susceptibility and immune dysregulation. In patients who present in this manner, immunodeficiency syndromes should be considered when lymphomatous infiltration is excluded. Immunotherapy can be helpful. Muscle Nerve 57: 150-156, 2018.

DEVELOPMENT OF GANGLIONOPATHY AND TABETIC VISCERAL CRISES ON THE BACKGROUND OF POLYRADICULONEUROPATHY ASSOCIATED WITH MONOCLONAL GAMMOPATHY (CASE REPORT).

The article presents an analysis of the clinical occurrence of development of chronic polyradiculoneuropathy associated with monoclonal IgG/k (kappa) gammopathy of the undetermined significance. The peculiarity of this occurrence is the uniqueness of the development of the symptoms which are characteristic of tabes dorsalis in this pathology with episodic severe visceral crises and also with ganglionopathy. The example describes the clinical polymorphism of the course of visceral crises, the problems of their diagnosis and as a consequence of inadequate treatment with the development of severe social maladaptation. The importance of timely diagnosis and treatment of such conditions is discussed.

Immunotherapy-responsive allodynia due to distal acquired demyelinating symmetric (DADS) neuropathy.

INTRODUCTION: Distal acquired demyelinating symmetric (DADS) neuropathy is a distal variant of chronic inflammatory demyelinating polyradiculoneuropathy. It is characterized by chronic distal symmetric sensory or sensorimotor deficits. Sensory ataxia is a common clinical presentation. Nerve conduction studies typically show markedly prolonged distal motor latencies. METHODS: We report 2 patients with chronic progressive generalized pain and fatigue, with normal neurological examinations except for allodynia. RESULTS: Nerve conduction studies were typical of DADS neuropathy. Monoclonal protein studies were negative. Cerebrospinal fluid protein levels were elevated. Sural nerve biopsies revealed segmental demyelination and remyelination. One biopsy had marked endoneurial and epineurial lymphocytic infiltration. Immunomodulatory therapy alleviated the pain and fatigue and markedly improved distal motor latencies in both patients. CONCLUSIONS: DADS neuropathy can present with pain and a normal neurological examination apart from allodynia. Nerve conduction studies are necessary for diagnosis. These patients respond to immunotherapy better than typical DADS neuropathy patients with sensory ataxia. Muscle Nerve 54: 973-977, 2016.

Intracranial Hypertension Associated With Poly-Cranio-Radicular-Neuropathies: A Case Report and Review of the Literature.

INTRODUCTION: We present the case of a gentleman who developed rapidly progressive vision loss, ophthalmo-paresis, and flaccid quadriparesis in the context of severe intracranial hypertension. We reviewed the available cases in the literature to increase awareness of this rare clinical entity.Case Report:A 36-year-old man developed rapidly progressive vision loss, ophthalmo-paresis, and flaccid quadriparesis. He had an extensive workup, only notable for severe intracranial hypertension, >55 cm of H 2 O. No inflammatory features were present, and the patient responded to CSF diversion. Few similar cases are available in the literature, but all show markedly elevated intracranial pressure associated with extensive neuroaxis dysfunction. Similarly, these patients improved with CSF diversion but did not appear to respond to immune-based therapies. CONCLUSIONS: We term this extensive neuroaxis dysfunction intracranial hypertension associated with poly-cranio-radicular-neuropathy (IHP) and distinguish it from similar immune-mediated clinical presentations. Clinicians should be aware of the different etiologies of this potentially devastating clinical presentation to inform appropriate and timely treatment.

Repeated Acute Exacerbations of Chronic Inflammatory Demyelinating Polyradiculoneuropathy Accompanied by Pain and Swelling in Distal Extremities.

An 81-year-old man experienced acute progression of weakness in the extremities accompanied by a fever, tenderness, and swelling in distal parts of the extremities. He had flaccid tetraparesis with fasciculations and general hyporeflexia. Nerve conduction studies indicated demyelinating sensorimotor neuropathy. A cerebrospinal fluid examination revealed elevated proteins without pleocytosis. Immunological treatments were effective, but his symptoms exhibited repeated relapse and remission phases. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with an acute onset. The highlight of this case is pain with inflammatory reaction recognized as red flags of CIDP, with the clinical course and electrophysiological findings compatible with CIDP.

Coexistence of Charcot-Marie-Tooth disease type 1A and anti-MAG neuropathy.

At age 35, a man with a genetic diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) but no family history of neuropathy and no clinical symptoms developed rapidly progressive loss of balance, distal limb numbness, loss of manual dexterity, and hand tremor. Five years later, he walked with support and had mild pes cavus, marked sensory ataxia, severe leg and hand weakness, absent deep tendon reflexes (DTRs), severe sensory loss, and hand tremor. He had dramatically reduced motor nerve conduction velocity (MNCV), strikingly prolonged motor distal latencies, absent sensory action potentials and lower limb compound muscle action potentials. CMT1A duplication was reconfirmed but the dramatic change in his clinical course suggested a superimposed acquired neuropathy. An IgM-kappa monoclonal gammopathy of uncertain significance (MGUS) with high titer anti-myelin associated glycoprotein (anti-MAG) activity was found. Nerve biopsy showed severe loss of myelinated fibers with onion bulbs, no evidence of uncompacted myelin, and few IgM deposits. Rituximab was given and he improved. It is very likely that this is a chance association of two rare and slowly progressive neuropathies; rapidly worsening course may have been due to a "double hit". Interestingly, there are reports of possible superimposition of dysimmune neuropathies on hereditary ones, and the influence of the immune system on inherited neuropathies is matter for debate.

[2011: What's new in dysimmune neuropathies]. / Revue de la littérature 2011: neuropathies dysimmunitaires.

There are strong research activities in the field of dysimmune neuropathies. In Guillain-Barré syndrome, new pathophysiological mechanisms have been demonstrated with the potential development of new therapies, a clinical prediction model is applicable early in the course of disease, and under investigation are new treatment strategies with adapted intravenous Ig dosages. In chronic inflammatory demyelinating polyneuropathies, current diagnostic tests are discussed but biomarkers are needed, such as histological changes or differential gene expression in nerve or skin biopsies. The exploration of novel therapeutic approaches including monoclonal antibodies and oral immunosuppressants, known from multiple sclerosis studies, suggests new approaches to treatment. Changes of the peripheral nerves on MR imaging are better known and the usefulness of serum antibodies is reviewed.

European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision.

The aim of this guideline is to update the 2006 EFNS/PNS guideline on management of patients with a demyelinating neuropathy and a paraprotein (paraproteinemic demyelinating neuropathy [PDN]) by review of evidence and expert consensus. In the absence of adequate evidence, the panel agreed on good practice points: (1) patients with PDN should be investigated for a malignant plasma cell dyscrasia; (2) a monoclonal gammopathy of undetermined significance is more likely to be causing the neuropathy if it is immunoglobulin (Ig)M, anti-neural antibodies are present, and the clinical phenotype is chronic distal sensory neuropathy; (3) patients with IgM PDN usually have predominantly distal sensory impairment, prolonged distal motor latencies, and often anti-myelin-associated glycoprotein antibodies; (4) IgM PDN may respond to immunomodulatory therapies. Their potential benefit should be balanced against possible side effects and the usually slow disease progression; (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy; and (6) Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes syndrome is a multi-system malignant PDN.

[Cerebral venous thrombosis and acute polyradiculoneuritis revealing systemic lupus erythematosus]. / Thrombose veineuse cérébrale et polyradiculonévrite aiguë révélant un lupus érythémateux disséminé

INTRODUCTION: Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. In 40% of cases, lupus can be revealed by neurological symptoms. Cerebral nervous system complications predominate and can be a negative factor for prognosis. Peripheral features are rare and various and can compromise functional prognosis, sometimes with fatal outcome. CASE REPORT: We report the case of a 30-year-old woman who presented a cerebral venous thrombosis of the superior longitudinal sinus. Outcome was favorable with antibiotics and anticoagulants. Four months later, she developed an acute polyradiculoneuritis associated with an inflammatory syndrome and positive tests for antinuclear antibody and antinuclear anti-DNA. The diagnosis of neurolupus was retained on the basis of four criteria of the American college of Rheumatology. The patient was given steroid therapy associated with a course of intravenous immunoglobulin. She has fully recovered her deficit. CONCLUSION: Cerebral venous thrombosis and acute polyradiculonévrites are rare events in systemic lupus erythematosus. Early diagnosis and management are crucial.

MOG antibody-related disease with recurrent optic neuritis and sensory polyradiculoneuropathy: A case report.

Myelin oligodendrocyte glycoprotein (MOG) antibody-related diseases are inflammatory demyelinating conditions of the central nervous system (CNS) that induce a broad spectrum of symptoms. Since MOG is expressed exclusively in the CNS, the lesions are thought to be confined to the CNS. However, few cases of MOG antibody-related disease involve the peripheral nervous system (PNS); the mechanisms underlying such PNS involvement remain unclear. We herein present the case of a patient with MOG antibody-related disease with recurrent optic neuritis and sensory polyradiculoneuropathy unaccompanied by CNS lesions. Our report presents a novel phenotype of PNS involvement in MOG antibody-related disease.

Acute idiopathic polyradiculoneuritis with secondary arterial hypertension in a 5-year-old male Siberian Husky.

Acute canine idiopathic polyradiculoneuritis (ACIP) is one of the most common generalised neuromuscular diseases affecting dogs. In this report, we describe a 5-year-old, 25-kg, male, intact, Siberian Husky dog with ACIP with secondary induced arterial hypertension {systolic blood pressure [mean (m) ± standard deviation (sd)], 214 ± 19 mmHg; mean blood pressure (m ± sd), 164 ± 6.36 mmHg; and diastolic blood pressure (m ± sd), 137 ± 0.7 mmHg} and sinus tachycardia. Heart rate variability analysis indicated decreased vagal activity (low root-mean-square values of successive RR interval differences and percentages of the RR intervals differing by more than 50 ms in the entire recording) and predominance of sympathetic activity. Arterial hypertension was treated with amlodipine but remained greater than the upper limit for 51 days until the dog recovered ambulation. This is the first case report of ACIP and secondary arterial hypertension in a dog. Routine blood pressure measurements should be included in the monitoring of patients with ACIP if arterial hypertension might interfere with patient prognosis.

Campylobacter jejuni abscess, encephalomyelitis, and acute polyradiculoneuropathy.

We report an unusual case of spinal epidural Campylobacter jejuni abscess associated with acute polyradiculoneuropathy and parainfectious encephalomyelitis. Decompressive surgery, antibiotics, intravenous immunoglobulin (IVIg) therapy, and intravenous methylprednisolone resulted in rapid clinical improvement. C. jejuni infection can cause both an acute polyradiculoneuropathy as well as an encephalomyelitis, and a combined occurrence is possible.

[Varicella-zoster virus-associated polyradiculoneuritis with concomitant herpes zoster eruption: a case report].

A 76-year-old Japanese female who was treated with long-term use of prednisolone at 10 mg/day for interstitial pneumonia developed acute right-dominant lower limb paralysis and then upper limb paralysis with herpes zoster eruptions on the right C7-Th1 dermatomes. On admission, right predominant quadriplegia was observed with sensory symptoms; Hughes functional grade was level 4; the hand grip power was right, 0, and left, 7 kg, the deep tendon reflexes were abolished throughout without pathologic reflexes. Twenty days after the onset of the symptoms, the cerebrospinal fluid (CSF) revealed mild increases of lymphocytes (13 cells/µl) and protein content (73 mg/dl). Varicella-zoster virus (VZV) PCR was negative in the CSF, but an enzyme immunoassay for VZV was positive in her serum and CSF, and the high titers were prolonged. Peripheral nerve conduction and F wave studies suggested right-dominant demyelinating polyradiculoneuropathy. A T1-weighted MR contrast image exhibited right-dominant high-intensity lesions on the C7-Th1 spinal roots and similar lesions on the L4-5 spinal roots. We compared with several similar cases from the literature and proposed that VZV itself involves the pathogenesis of the polyradiculoneuritis in immunocompromised hosts.

Neuroinvasion by Mycoplasma pneumoniae in acute disseminated encephalomyelitis.

We report the autopsy findings for a 45-year-old man with polyradiculoneuropathy and fatal acute disseminated encephalomyelitis after having Mycoplasma pneumoniae pneumonia. M. pneumoniae antigens were demonstrated by immunohistochemical analysis of brain tissue, indicating neuroinvasion as an additional pathogenetic mechanism in central neurologic complications of M. pneumoniae infection.

Idiopathic polyradiculoneuropathy in a Bengal cat: electrophysiological findings and 1 year follow-up.

This report describes a rapidly progressive loss of motor function in a 16-month-old male neutered Bengal cat, beginning in the pelvic limbs and progressing to involve all limbs and rendering the cat non-ambulatory. The neurological examination revealed flaccid tetraparesis with decreased spinal reflexes but preserved conscious proprioception and skin sensation. Extensive electrophysiological tests were conducted including electromyography, motor and sensory peripheral nerves potential recordings and 'late' potentials, defining the electrodiagnostic characteristics of this disease. Based on the electrophysiological findings, a generalised proximal and predominantly axonal neuropathy affecting the ventral (motor) nerve roots was suspected. As no aetiology was identified, this disease was classified as idiopathic polyradiculoneuropathy. Over a year, the cat presented three separate episodes of tetraparesis, each with a spontaneous complete recovery, consistent with the reportedly good prognosis for this disease.