Elsevier

Journal of the Neurological Sciences

Volume 367, 15 August 2016, Pages 184-202
Journal of the Neurological Sciences

Review article
Neuromuscular complications in cancer

https://doi.org/10.1016/j.jns.2016.06.002Get rights and content

Highlights

  • Neuromuscular complications in cancer are frequent.

  • Mechanisms comprise toxicity, neoplastic infiltration, paraneoplastic, metabolic and inflammatory causes.

  • Precise differential diagnosis is essential for treatment.

  • Drug toxicity can be a dose limiting factor of cancer therapy.

Abstract

Cancer is becoming a treatable and even often curable disease. The neuromuscular system can be affected by direct tumor invasion or metastasis, neuroendocrine, metabolic, dysimmune/inflammatory, infections and toxic as well as paraneoplastic conditions. Due to the nature of cancer treatment, which frequently is based on a DNA damaging mechanism, treatment related toxic side effects are frequent and the correct identification of the causative mechanism is necessary to initiate the proper treatment.

The peripheral nervous system is conventionally divided into nerve roots, the proximal nerves and plexus, the peripheral nerves (mono- and polyneuropathies), the site of neuromuscular transmission and muscle. This review is based on the anatomic distribution of the peripheral nervous system, divided into cranial nerves (CN), motor neuron (MND), nerve roots, plexus, peripheral nerve, the neuromuscular junction and muscle.

The various etiologies of neuromuscular complications – neoplastic, surgical and mechanic, toxic, metabolic, endocrine, and paraneoplastic/immune – are discussed separately for each part of the peripheral nervous system.

Introduction

Neuromuscular complications in cancer have different etiologies in different anatomical regions. Although metastases as the cause of a neuromuscular syndrome are often the primary concern, several other pathogenic causes exist.

CN lesions often have a neoplastic cause, in particular local metastases and meningeal infiltration. Nerve roots can be both damaged by mechanical and neoplastic causes, and the nerve plexi are predominantly affected by neoplastic lesions, and if radiated also radiation effects need to be considered.

Peripheral neuropathies can be caused by paraneoplastic etiologies, usually at the time of diagnosis, during the course of therapy by toxic drug effects and much rarer by infrequent causes such as neoplastic infiltration, metabolic or inflammatory causes.

The neuromuscular junction (NMJ) can be a site of paraneoplastic or dysimmune effects such as in myasthenia gravis, Lambert Eaton myasthenia syndrome (LEMS) or neuromyotonia.

In muscle paraneoplastic and inflammatory lesions dominate. Direct neoplastic involvement is rare. The most frequent type of muscle involvement is cachexia.

Neuromuscular complications can appear as the first sign of cancer, where often a tumor search is needed [1], or appear as a complication during the disease.

An important aspect affecting the impact of neuromuscular complications is associated with age. Pediatric cancer, adult cancer and increasingly geriatric aspects of cancer [2], [3] have a diverse spectrum of complications. This distinction can be based on several issues such as tolerance of treatment, development of persisting or late toxicity, and also the influence of other concomitant diseases.

Section snippets

Neoplastic

Different tumors have different propensities to metastasize at different time points and into different organs (organotropism). Cancer is usually classified into hematological and solid tumors. Both types have the ability to convert from a solid into a liquid state (meningeal carcinomatosis) and vice versa (chloroma or myelosarcoma). Other mechanisms are local compression, focal or diffuse invasion, and even rarer anterograde and retrograde spread along nerves and rarely local tumor or

CN

Anatomically, CN have a cerebral parenchymatous and an intracavitary part within the skull. They have a defined exit through the skull, followed by an extracranial course. The intracavitary part will not be considered here, with the exception of nerve infiltration or compression in leptomeningeal disease, as well as base of the skull tumors. Imaging is useful to demonstrate abnormalities of CNs [8].

Neoplastic lesions of CNs can be caused by a number of intracranial causes such as leptomeningeal

Bone marrow transplantation

BMT a treatment used for the hematological tumors and treatment and other cancers. Side effects from chemotherapy, RT, infections and immune dysregulations due to GVHD are observed. GVHD can be associated with several neuromuscular complications of muscle (myositis) [357], disordered neuromuscular transmission (MG) [358] and neuropathies such as GBS and CIDP [359]. In allogeneic transplantations these complications are more frequent.

Hematopoietic stem cell transplantation is used in the

Summary

Neurologists are important in the management and treatment of patients with systemic cancer. In the PNS a large number of differential diagnoses have to be evaluated, and treatment of neuromuscular symptoms and signs needs different approaches, depending on the etiology of the lesion. As the spectrum of tumor therapies broadens the pathogenetic mechanisms vary. The success of several tumor therapies has increased the number of long term survivors, who may also suffer from previously unknown

References (381)

  • C. Diard-Detoeuf et al.

    Association of a paraneoplastic motor neuron disease with anti-Ri antibodies and a novel SOD1 I18del mutation

    J. Neurol. Sci.

    (2014)
  • J. Kenda et al.

    Glycine receptor antibodies and progressive encephalomyelitis with rigidity and myoclonus with predominant motor neuron degeneration–expanding the clinical spectrum

    J. Neurol. Sci.

    (2015)
  • I. Cabrilo et al.

    Renal carcinoma relapse presenting as a peripheral nerve sheath tumor

    Neurochirurgie

    (2013)
  • K. Uchida et al.

    Metastatic involvement of sacral nerve roots from uterine carcinoma: a case report

    Spine J.

    (2008)
  • W. Grisold et al.

    Malignant cell infiltration in the peripheral nervous system

    Handb. Clin. Neurol.

    (2013)
  • A.W. Tarulli et al.

    Lumbosacral radiculopathy

    Neurol. Clin.

    (2007)
  • M. Bydon et al.

    The use of stereotactic radiosurgery for the treatment of spinal axis tumors: a review

    Clin. Neurol. Neurosurg.

    (2014)
  • P.F. Pradat et al.

    Late radiation injury to peripheral nerves

    Handb. Clin. Neurol.

    (2013)
  • M.J. Titulaer et al.

    Screening for tumours in paraneoplastic syndromes: report of an EFNS task force

    Eur. J. Neurol.

    (2011)
  • A. Hurria et al.

    Senior adult oncology

    J. Natl. Compr. Cancer Netw.

    (2012)
  • H.A. Burris et al.

    Radiation recall with anticancer agents

    Oncologist

    (2010)
  • L.J. Leandro-Garcia et al.

    Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy

    J. Med. Genet.

    (2013)
  • B. Giometto et al.

    Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers

    Arch. Neurol.

    (2010)
  • V. Chong

    Imaging the cranial nerves in cancer

    Cancer Imaging

    (2004)
  • H.S. Greenberg et al.

    Metastasis to the base of the skull: clinical findings in 43 patients

    Neurology

    (1981)
  • W. Grisold et al.

    Cancer around the brain

    Neurooncology Practice

    (2014)
  • A. Lee et al.

    Sixth cranial nerve palsy caused by gastric adenocarcinoma metastasis to the clivus

    Journal of Korean Neurosurgical Society

    (2015)
  • K. Marsot-Dupuch et al.

    Retrograde perineural extension of a metastatic recurrence of a frontal skin tumor

    Ann. Radiol.

    (1992)
  • G.C. Warner

    Diagnostic dilemma: slowly progressive cranial nerve palsies

    MJA

    (2006)
  • J. Viken et al.

    Facial pain and multiple cranial palsies in a patient with skin cancer

    Journal of Headache and Pain

    (2011)
  • S.R. Thada et al.

    Nerve afflictions of maxillofacial region: a report of two cases

    BMJ Case Reports

    (2013)
  • B.C. Leach et al.

    Cranial neuropathy as a presenting sign of recurrent aggressive skin cancer

    Dermatol. Surg.

    (2008)
  • V. Touitou et al.

    Primary CNS lymphoma

    Curr. Opin. Ophthalmol.

    (2015)
  • R. Weiss et al.

    Metastasis of solid tumors in extraocular muscles

    Acta Neuropathol.

    (1984)
  • J.P. O'Neill et al.

    Granulocytic sarcoma of the orbit presenting as a fulminant orbitopathy in an adult with acute myeloid leukemia

    Ophthal. Plast. Reconstr. Surg.

    (Apr 7 2015)
  • P.D. Thompson et al.

    Enophthalmos and metastatic carcinoma of the breast

    J. Neurol. Neurosurg. Psychiatry

    (1985)
  • K.S. Park

    Unilateral trigeminal mandibular motor neuropathy caused by tumor in the foramen ovale

    J. Clin. Neurol.

    (2006)
  • R.H. Boerman et al.

    Trigeminal neuropathy secondary to perineural invasion of head and neck carcinomas

    Neurology

    (1999)
  • M. Carbone et al.

    Numb chin syndrome as first symptom of diffuse large B-cell lymphoma

    Case Rep. Dent.

    (2014)
  • J.D. Breshears et al.

    Primary glioblastoma of the trigeminal nerve root entry zone: case report

    J. Neurosurg.

    (2015)
  • R. Sinha et al.

    Images in clinical medicine. Zosteriform metastases from malignant melanoma

    N. Engl. J. Med.

    (2014)
  • A.V. Evans et al.

    Lesson of the week zosteriform metastasis from melanoma

    BMJ

    (2003)
  • N. Sakai et al.

    Primary neurolymphomatosis of the lower cranial nerves presenting as dysphagia and hoarseness: a case report

    J. Neurol. Surg. Rep.

    (2014)
  • J.C. Li et al.

    Cranial nerve involvement in nasopharyngeal carcinoma: response to radiotherapy and its clinical impact

    Ann. Otol. Rhinol. Laryngol.

    (2006)
  • M: S. Iatrogene Nervenläsionen. Injektion, Operation, Lagerung, Strahlentherapie. Thieme 1996 PubMed Central ed 2...
  • J. Finsterer et al.

    Disorders of the lower cranial nerves

    J. Neurosci. Rural Pract.

    (2015)
  • A.K. Gupta et al.

    Preoperative embolization of hypervascular head and neck tumours

    Australas. Radiol.

    (2007)
  • P.J. Kelly et al.

    Unexpected late radiation neurotoxicity following bevacizumab use: a case series

    J. Neuro-Oncol.

    (2011)
  • S. Janssen et al.

    Radiation-induced lower cranial nerve palsy in patients with head and neck carcinoma

    Mol. Clin. Oncol.

    (2015)
  • P.S. Berger et al.

    Radiation-induced cranial nerve palsy

    Cancer

    (1977)
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