Painful Peripheral Neuropathy and Cancer
Painful Peripheral Neuropathy and Cancer
Panagiotis Zis . Giustino Varrassi 0 1 2
0 G. Varrassi University of L'Aquila , L'Aquila , Italy
1 P. Zis Department of Neurology, University of Sheffield , Sheffield , UK
2 P. Zis (&) Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield , UK
Peripheral neuropathy (PN) is very prevalent in cancer patients and a leading cause of pain related to cancer. However, the underlying pathophysiological mechanisms vary significantly. Peripheral neuropathy can be a direct or an indirect complication of cancer or cancer-related treatment, or a pre-existing comorbidity not related to cancer. PN might also occur as a paraneoplastic neurological syndrome. Such syndromes are immune-mediated manifestations that usually precede the diagnosis of cancer or cancer's relapse. Pain is very prevalent in paraneoplastic peripheral neuropathies and, therefore, merits attention.
The term peripheral neuropathy (PN) refers to
any disorder of the peripheral nervous system
including single and multiple (asymmetric)
mononeuropathies, symmetrical involvement
of many nerves (polyneuropathy) or sole
involvement of the dorsal root ganglia [
PN is very prevalent in cancer patients;
however the underlying pathophysiological
mechanisms vary significantly. PN can be a
direct or an indirect complication of cancer or
cancer-related treatment, or a pre-existing
comorbidity not related to cancer. Directly
cancer can cause single or multiple
mononeuropathies and plexopathy as a result of invasion
by cancer cells of the peripheral nerves and
plexus, respectively [
]. Indirectly, similar
pathologies might occur following iatrogenic
nerve and plexus injuries, either secondary to
radiotherapy or surgery [
PN also includes chemotherapy-induced PN,
which is probably the most common cause of
PN in cancer [
However, PN in cancer might occur as a
paraneoplastic neurological syndrome (PNS).
PNS are a heterogeneous group of neurological
disorders triggered by cancer. To be considered
as paraneoplastic, the neurological syndrome
should occur within 5 years of cancer diagnosis
], though there are many reports of possible
PNS that have exceeded this time-frame [
are caused by mechanisms other than
metastases, metabolic or nutritional deficits,
infections, coagulopathy, or side effects of
cancer treatment such as chemotherapy. The
discovery that many PNS are associated with
antibodies against neural antigens expressed by
the tumour (antineural antibodies) has
suggested that PNS are immune-mediated [
Paraneoplastic PN is one of the commonest PNS
and often is a cause of neuropathic cancer pain
This editorial is an introduction to an
up-to-date systematic review and meta-analysis
of all published case reports or case series of
patients with paraneoplastic PN (doi:10.1007/
s40122-017-0076-3). The systematic review and
meta-analysis shed light onto both the clinical
and neurophysiological aspects, with a
particular focus on pain as a manifestation of the
No funding or sponsorship was received for this
study or publication of this article. All named
authors meet the International Committee of
Medical Journal Editors (ICMJE) criteria for
authorship for this manuscript, take
responsibility for the integrity of the work as a whole,
and have given final approval for the version to
Disclosures. Panagiotis Zis and
Varrassi have nothing to disclose.
Compliance with Ethics Guidelines. This
article is based on previously conducted studies
and does not involve any new studies of human
or animal subjects performed by any of the
in any medium, provided you give appropriate
credit to the original author(s) and the source,
provide a link to the Creative Commons license,
and indicate if changes were made.
1. Martyn CN , Hughes RA . Epidemiology of peripheral neuropathy . J Neurol Neurosurg Psychiatry . 1997 ; 62 ( 4 ): 310 - 8 .
2. Zis P , Sarrigiannis PG , Rao DG , Hewamadduma C , Hadjivassiliou M. Chronic idiopathic axonal polyneuropathy: a systematic review . J Neurol . 2016 ; 263 ( 10 ): 1903 - 10 .
3. Marchettini P , Lacerenza M , Mauri E , Marangoni C . Painful peripheral neuropathies . Curr Neuropharmacol . 2006 ; 4 ( 3 ): 175 - 81 .
4. Marchettini P , Formaglio F , Lacerenza M. Iatrogenic painful neuropathic complications of surgery in cancer . Acta Anaesthesiol Scand . 2001 ; 45 ( 9 ): 1090 - 4 .
5. Hershman DL , Lacchetti C , Dworkin RH , Lavoie Smith EM , Bleeker J , Cavaletti G , Chauhan C , Gavin P , Lavino A , Lustberg MB , Paice J , Schneider B , Smith ML , Smith T , Terstriep S , Wagner-Johnston N , Bak K , Loprinzi CL , American Society of Clinical Oncology. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline . J Clin Oncol . 2014 ; 32 ( 18 ): 1941 - 67 .
6. Graus F , Delattre JY , Antoine JC , Dalmau J , Giometto B , Grisold W , Honnorat J , Smitt PS , Vedeler Ch, Verschuuren JJ , Vincent A , Voltz R . Recommended diagnostic criteria for paraneoplastic neurological syndromes . J Neurol Neurosurg Psychiatry . 2004 ; 75 ( 8 ): 1135 - 40 .
7. Zis P , Rao DG , Wagner BE , Nicholson-Goult L , Hoggard N , Hadjivassiliou M. Cerebellar ataxia and sensory ganglionopathy associated with light-chain myeloma . Cereb Ataxias . 2017 ; 4 ( 1 ): 1 .
8. Darnell RB , Posner JB . Paraneoplastic syndromes involving the nervous system . N Engl J Med . 2003 ; 349 ( 16 ): 1543 - 54 .
9. Vadalouca A , Raptis E , Moka E , Zis P , Sykioti P , Siafaka I. Pharmacological treatment of neuropathic cancer pain: a comprehensive review of the current literature . Pain Pract . 2012 ; 12 ( 3 ): 219 - 51 .