51-year old man with tingling, burning and progressive limb weakness

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

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Clinical Differential Diagnosis of Multifocal Motor Neuropathy

European Neurological Review ◽

10.17925/enr.2012.07.02.124 ◽

2012 ◽

Vol 7 (2) ◽

pp. 124 ◽

Cited By ~ 2

Author(s):

Jean-Marc Léger ◽

Eugen Gavriliuc ◽

◽

Keyword(s):

Differential Diagnosis ◽

Correct Diagnosis ◽

Rare Condition ◽

Multifocal Motor Neuropathy ◽

Motor Neuropathy ◽

Diagnostic Challenge ◽

Limb Weakness ◽

Progressive Muscle Weakness ◽

Immune Mediated ◽

Clinical Differential Diagnosis

Multifocal motor neuropathy (MMN) is a rare, clinically well-defined condition within the spectrum of chronic, immune-mediated neuropathies. A typical patient history involves slowly or stepwise progressive, predominantly distal, asymmetrical limb weakness and muscle wasting, most frequently in the arm, that may have developed over a period of years. As a rare condition, MMN may present a diagnostic challenge for non-specialists and some patients may wait years for a correct diagnosis. Timely and accurate diagnosis is essential for patients with MMN. Unlike some motor neuropathies, MMN is treatable with intravenous immunoglobulin and untreated patients are likely to experience progressive muscle weakness that may result in serious functional impairment and impaired quality of life. The aim of this article is therefore to provide a guide for non-specialist neurologists to the clinical recognition and differential diagnosis of MMN.

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Peripheral neuropathy in a cat with renal lymphoma

Journal of Feline Medicine and Surgery ◽

10.1016/j.jfms.2009.03.010 ◽

2009 ◽

Vol 11 (10) ◽

pp. 869-872 ◽

Cited By ~ 8

Author(s):

Paola Cavana ◽

Federica Sammartano ◽

Maria T. Capucchio ◽

Deborah Catalano ◽

Alberto Valazza ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Axonal Degeneration ◽

Malignant Tumour ◽

Lymphoproliferative Disorders ◽

Peripheral Neuropathies ◽

Muscle Denervation ◽

Limb Weakness ◽

Neoplastic Processes ◽

Renal Lymphoma ◽

Paraneoplastic Polyneuropathy

A 12-year-old male cat was referred for progressive limb weakness lasting 2 weeks. Physical examination detected muscle atrophy and bilateral renomegaly with distortion of the renal contours. The cat was ambulatory but tetraparetic. It showed a peculiar posture on forelimbs with bilateral flexion of the carpi and extrarotation of forearms. The cat was unable to go upstairs or jump. Neurological examination showed findings compatible with peripheral nervous system involvement. Histopathological findings revealed a high grade non-B, non-T cell renal lymphoma and peripheral neuropathy characterised by demyelination, axonal degeneration and muscle denervation. In the absence of congenital, metabolic and infectious diseases or exposure to toxins, a paraneoplastic peripheral neuropathy was hypothesised. In humans and dogs, paraneoplastic peripheral neuropathies have been documented with different neoplastic processes including lymphoproliferative disorders. To the authors' knowledge, this is the first report of suspected paraneoplastic polyneuropathy in a cat with malignant tumour.

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New Evidence for Secondary Axonal Degeneration in Demyelinating Neuropathies

Neuroscience Letters ◽

10.1016/j.neulet.2020.135595 ◽

2020 ◽

pp. 135595

Author(s):

Kathryn R. Moss ◽

Taylor S. Bopp ◽

Anna E. Johnson ◽

Ahmet Höke

Keyword(s):

Axonal Degeneration ◽

Demyelinating Neuropathies ◽

New Evidence

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Translational strategies in peripheral neuroinflammation and neurovascular repair

Translational Neuroscience ◽

10.2478/s13380-012-0039-4 ◽

2012 ◽

Vol 3 (4) ◽

Cited By ~ 5

Author(s):

Eroboghene Ubogu

Keyword(s):

Peripheral Nerve ◽

Nerve Regeneration ◽

Axonal Degeneration ◽

Peripheral Nerve Regeneration ◽

Treatment Strategies ◽

Normal Function ◽

New Drugs ◽

Immune Mediated ◽

Current Therapies

AbstractCurrent therapies for immune-mediated inflammatory disorders in peripheral nerves are non-specific, and partly efficacious. Peripheral nerve regeneration following axonal degeneration or injury is suboptimal, with current therapies focused on modulating the underlying etiology and treating the consequences, such as neuropathic pain and weakness. Despite significant advances in understanding mechanisms of peripheral nerve inflammation, as well as axonal degeneration and regeneration, there has been limited translation into effective new drugs for these disorders. A major limitation in the field has been the unavailability of reliable disease models or research tools that mimic some key essential features of these human conditions. A relatively overlooked aspect of peripheral nerve regeneration has been neurovascular repair required to restore the homeostatic microenvironment necessary for normal function. Using Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as examples of human acute and chronic immune-mediated peripheral neuroinflammatory disorders respectively, we have performed detailed studies in representative mouse models to demonstrate essential features of the human disorders. These models are important tools to develop and test treatment strategies using realistic outcomes measures applicable to affected patients. In vitro models of the human blood-nerve barrier using endothelial cells derived by endoneurial microvessels provide insights into pro-inflammatory leukocyte-endothelial cell interactions relevant to peripheral neuroinflammation, as well as potential mediators and signaling pathways required for vascular proliferation, angiogenesis, remodeling and tight junction specialization necessary to restore peripheral nerve function following injury. This review discusses some of the progress being made in translational peripheral neurobiology and some future

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Insulin-like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis

Multiple Sclerosis Journal ◽

10.1177/135245859500100102 ◽

1995 ◽

Vol 1 (1) ◽

pp. 2-9 ◽

Cited By ~ 71

Author(s):

X Liu ◽

D-L Yao ◽

Hde F. Webster

Keyword(s):

Spinal Cord ◽

Autoimmune Encephalomyelitis ◽

Limb Weakness ◽

Inflammatory Lesions ◽

Factor I ◽

Immune Mediated ◽

Igf I ◽

Blood Spinal Cord Barrier ◽

Clinical Deficits ◽

Experimental Autoimmune

Our goal was to test the effects of insulin-like growth factor I (IGF-I) treatment on clinical deficits, lesion number and lesion size in acute demyelinating experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats with an emulsion containing guinea pig spinal cord. In this EAE model, there is severe immune-mediated demyelination, which resembles that seen in actively demyelinating MS lesions. On day 12–13 after EAE induction, a total of 23 pairs of rats with the same mild degree of tail and hind limb weakness were given either intravenous IGF-I or placebo twice daily for 8 days. The daily IGF-I dose used in the first trial was 200 μg (about 0.6 mgkg-1) and in the second and third trials was 1 mg (about 3.0 mgkg-1). IGF-I treatment reduced permeability of the blood-spinal cord barrier to Evans blue-albumin. Maximum clinical deficit scores of IGF-I-treated rats were significantly lower and treated rats recovered faster than controls. IGF-I treatment produced significant reductions in weight loss and hind limb weakness. Treatment also improved treadmill walking, stride length and climbing performance. Morphometric analysis showed that spinal cord inflammatory lesions were significantly smaller and fewer in IGF-I-treated rots. The higher IGF-I dose produced a greater reduction in clinical and pathological deficits. We conclude that IGF-I treatment promotes clinical recovery by reducing EAE-induced blood-spinal cord barrier changes and the associated immune-mediated inflammatory lesions. Our results suggest that IGF-I may be useful in treating patients with multiple sclerosis and other demyelinating diseases.

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Anaphylaxis: how to recognise and manage in primary care

Practice Nursing ◽

10.12968/pnur.2021.32.6.232 ◽

2021 ◽

Vol 32 (6) ◽

pp. 232-236

Author(s):

Hannah Kramer ◽

Rebecca Batt

Keyword(s):

Primary Care ◽

Practice Nurse ◽

Correct Diagnosis ◽

Insect Sting ◽

Vulnerable Patients ◽

Immune Mediated ◽

Emergency Medication ◽

Life Threatening ◽

Systemic Hypersensitivity

Anaphylaxis is a life-threatening emergency. Hannah Kramer and Rebecca Batt explain how correct diagnosis, avoidance and patient education are fundamental in reducing risk Anaphylaxis is a serious systemic hypersensitivity reaction that is usually rapid in onset and can cause death. It is an immune-mediated reaction, which typically occurs when a person is exposed to a trigger, for example a food, drug, or insect sting. This article aims to assist with the recognition of symptoms and to guide management of anaphylaxis in primary care. Beyond the acute, the practice nurse can play a key role in helping patients to manage their allergies in the long-term, particularly for those who are most vulnerable. Patients should be supported in understanding how best to avoid their triggers, in managing their emergency medication, and in the importance of good asthma control.

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POEMS Syndrome

Hematology ◽

10.1182/asheducation-2005.1.360 ◽

2005 ◽

Vol 2005 (1) ◽

pp. 360-367 ◽

Cited By ~ 62

Author(s):

Angela Dispenzieri

Keyword(s):

Peripheral Neuropathy ◽

Chronic Inflammatory Demyelinating Polyneuropathy ◽

Early Recognition ◽

Correct Diagnosis ◽

Bone Lesion ◽

High Dose Chemotherapy ◽

Poems Syndrome ◽

Bone Lesions ◽

High Dose ◽

Sclerotic Bone

Abstract POEMS syndrome is defined by the presence of a peripheral neuropathy (P), a monoclonal plasma cell disorder (M), and other paraneoplastic features, the most common of which include organomegaly (O), endocrinopathy (E), skin changes (S), papilledema, edema, effusions, ascites, and thrombocytosis. Virtually all patients will have either sclerotic bone lesion(s) or co-existent Castleman’s disease. Not all features of the disease are required to make the diagnosis, and early recognition is important to reduce morbidity. Other names for the syndrome include osteosclerotic myeloma, Crow-Fukase syndrome, or Takatsuki syndrome. Because the peripheral neuropathy is frequently the overriding symptom and because the characteristics of the neuropathy are similar to that chronic inflammatory demyelinating polyneuropathy (CIDP), patients are frequently misdiagnosed with CIDP or monoclonal gammopathy of underdetermined significance (MGUS)-associated peripheral neuropathy. Not until additional features of the POEMS syndrome are recognized is the correct diagnosis made and effective therapies initiated. Clues to an early diagnosis include thrombocytosis and sclerotic bone lesions on plain skeletal radiographs. Therapies that may be effective in patients with CIDP and MGUS-associated peripheral neuropathy (intravenous gammaglobulin and plasmapheresis) are not effective in patients with POEMS. Instead, the mainstays of therapy for patients with POEMS include irradiation, corticosteroids, and alkylator-based therapy, including high-dose chemotherapy with peripheral blood stem cell transplantation.

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Neuropathy in Chronic Renal Failure

Bangladesh Journal of Neuroscience ◽

10.3329/bjn.v28i2.17183 ◽

2013 ◽

Vol 28 (2) ◽

pp. 116-127

Author(s):

Md Munzur Alahi ◽

Md Pervez Amin ◽

Md Ahmed Ali ◽

Md Kafiluddin ◽

Quamruddin Ahmad

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Peripheral Neuropathy ◽

Axonal Degeneration ◽

Muscle Wasting ◽

Autonomic Failure ◽

Neurological Complications ◽

Vibration Sense ◽

Pathologic Features ◽

Large Fiber

Peripheral neuropathy is common in chronic renal failure patients and its early detection and treatment reduces the sufferings of these patients. Studies of neuropathy in ESKD have demonstrated prevalence rates which vary from 60 to 100%. The striking pathologic features of peripheral neuropathy in patients of CRF are axonal degeneration in the most distal nerve trunks with secondary segmental demyelination. The most frequent clinical features are those of large-fiber involvement, with paresthesias, reduction in deep tendon reflexes, impaired vibration sense, weakness and muscle wasting. Patients of CRF may present with mononeuropathies or autonomic failure also. The exact cause of nerve involvement has not been identified but the middle molecule hypothesis is widely accepted. Dialysis in any form fails to improve the neuropathy but renal transplantation does improve the neurological complications. This review details the various features of neuropathy in patients of chronic renal failure. DOI: http://dx.doi.org/10.3329/bjn.v28i2.17183 Bangladesh Journal of Neuroscience 2012; Vol. 28 (2): 116-127

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Cisplatin induced neurotoxicity is mediated by Sarm1 and calpain activation

Scientific Reports ◽

10.1038/s41598-020-78896-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Aysel Cetinkaya-Fisgin ◽

Xinghua Luan ◽

Nicole Reed ◽

Ye Eun Jeong ◽

Byoung Chol Oh ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Side Effects ◽

Cancer Cells ◽

Wallerian Degeneration ◽

Axonal Degeneration ◽

Adduct Formation ◽

Calpain Activation ◽

Chemotherapy Agent ◽

Distal Axonal Degeneration ◽

Calpain Inhibitors

AbstractCisplatin is a commonly used chemotherapy agent with significant dose-limiting neurotoxicity resulting in peripheral neuropathy. Although it is postulated that formation of DNA-platinum adducts is responsible for both its cytotoxicity in cancer cells and side effects in neurons, downstream mechanisms that lead to distal axonal degeneration are unknown. Here we show that activation of calpains is required for both neurotoxicity and formation of DNA-platinum adduct formation in neurons but not in cancer cells. Furthermore, we show that neurotoxicity of cisplatin requires activation of Sarm1, a key regulator of Wallerian degeneration, as mice lacking the Sarm1 gene do not develop peripheral neuropathy as evaluated by both behavioral or pathological measures. These findings indicate that Sarm1 and/or specific calpain inhibitors could be developed to prevent cisplatin induced peripheral neuropathy.

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