Topic 8.2. Pain related to neuropathy
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
8.1 Overview of pain in Friedreich ataxia
8.2 Pain related to neuropathy
8.2.1 Neuropathy in Friedreich ataxia
8.2.2 Management of painful neuropathy
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
8.2 Pain related to neuropathy
Theresa Zesiewicz, Sylvia Boesch and George Wilmot
The authors acknowledge Marios Hadjivassiliou for the use of some content from the previous version of the guidelines (2014).
8.2.1 Neuropathy in Friedreich ataxia
Peripheral neuropathy occurs in FRDA due to dysfunction in the central somatosensory pathways and dorsal root ganglia (7, 8). The exact incidence and prevalence of painful peripheral neuropathy in FRDA is unknown, but treatment of neuropathy-related pain appears to be an unmet need. In 2020, the Friedreich’s Ataxia Clinical Management Guideline Patient and Parent Advisory Panel was interviewed on the consequences, urgency and priority of neuropathic pain, among other disease symptoms. More than half the respondents thought that painful neuropathy in FRDA was, or probably was a serious issue in this population, and many respondents thought that treatment of painful neuropathy in FRDA was a ‘priority’.
8.2.2 Management of painful neuropathy
There is a lack of studies regarding treatment of painful peripheral neuropathy in FRDA. However, there is considerable published research related to the treatment of neuropathic pain in other conditions, including diabetic peripheral neuropathy, chemotherapy-induced peripheral neuropathy, and HIV-related neuropathy (9). Clinical guidelines based on randomized controlled trials (RCTs) in these conditions recommend several medications that could be considered to treat neuropathy related to FRDA, including pregabalin, venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids, and topical lidocaine and capsaicin (9). The use of these agents must be balanced against potential untoward side effects. Like all other aspects of FRDA, the neuropathy is best managed by a suitably trained health care professional who is familiar with the condition and the management of peripheral neuropathy (8).
Absence of distal sensation may make the individual more prone to the development of foot trauma leading to ulceration. The most common mechanism of injury is unperceived, excessive and repetitive pressure on plantar bony prominences. Foot deformities, which are very common in FRDA (10), may contribute to increased focal pressure, making ulceration more likely. Meticulous foot care is important and the input of a podiatrist may be required. This is even more important in those patients with FRDA who also have diabetes mellitus.
Neuropathic pain due to sensory neuropathy may be a significant feature in FRDA that can be treated in the same way as neuropathic pain due to any other cause. This includes the use of several antiepileptic drugs, such as gabapentin, pregabalin, and lamotrigine; tricyclic anti-depressant medication, such as amitriptyline; and the serotonin re-uptake inhibitor duloxetine (9, 11, 12)
Reduced mobility and weakness as well as the presence of a sensory neuropathy make FRDA patients more susceptible to focal neuropathies. If such mononeuropathies are clinically suspected, a neurophysiological assessment can help to confirm the diagnosis. If bothersome to the patient, such entrapment neuropathies can be alleviated by review of activities of daily living and wheelchair positioning, splinting or surgical release.
See Chapters 3.2 and 3.3 for further details on mobility issues.
See Chapter 9 for further details on surgical treatments.
Oral medication
QUESTION: Should oral medication versus none be used for painful neuropathy patients with Friedreich ataxia?
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RECOMMENDATION: We suggest the use of oral medication over no medication in individuals with Friedreich ataxia who have painful neuropathy.
JUSTIFICATION: There is good research on the treatment of neuropathic pain in other conditions, such as diabetic peripheral neuropathy, peripheral neuropathy from chemotherapy, and HIV-related neuropathy (9). Clinical guidelines based on randomized controlled trials (RCTs) in the above-mentioned conditions recommend medications that might help painful neuropathy, including pregabalin, venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids, and topical lidocaine and capsaicin (9).
SUBGROUP CONSIDERATION: When individuals with Friedreich ataxia and painful neuropathy are treated with medication, the risk of possible side effects that derive from other aspects of Friedreich ataxia, such as heart involvement, should be considered and monitoring for such side effects should be done.
Evidence to Recommendation Table PDFOral supplements
QUESTION: Should oral supplements versus none be used for peripheral neuropathy patients with Friedreich ataxia?
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RECOMMENDATION: We suggest that clinicians should not consider the use of oral supplements to manage neuropathic pain in individuals with Friedreich ataxia.
JUSTIFICATION: There is no evidence to support the use of oral supplements to manage neuropathic pain in individuals with Friedreich ataxia.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with peripheral neuropathy.
Evidence to Recommendation Table PDFTopical agents
QUESTION: Should topical agents versus none be used for peripheral neuropathy patients with Friedreich ataxia?
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RECOMMENDATION: We suggest the use of topical agents over no treatment in the management of neuropathic pain in Friedreich ataxia.
JUSTIFICATION: There is no evidence to support the use of topical agents in Friedreich ataxia; however, some studies in neuropathic pain related to other conditions indicate, on balance, small beneficial effects versus side effects (9). The cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. In the light of the necessity of treatment, topical treatments (such as lidocaine) may be used by individuals with Friedreich ataxia despite of lack of direct evidence.
SUBGROUP CONSIDERATION: Individuals with Friedreich ataxia with painful neuropathy may benefit from topical agents; however, based on clinical judgement, most of these patients would be managed with oral medicines instead. Topical agents might not be appropriate for patients with skin problems. On the other hand, topical agents might be useful in those who can’t tolerate oral medication.
Evidence to Recommendation Table PDFA detailed sensory assessment and examination by a clinician familiar with the peripheral neuropathy related to Friedreich ataxia will establish the extent of neuropathy.
Protective foot care is important.
Preventative measures such as review of daily activities, transfers and wheelchair positioning may reduce the incidence of focal neuropathies.
Lay summary of clinical recommendations for neuropathic pain in Friedreich ataxia
Peripheral neuropathy occurs in Friedreich ataxia due to damage in sensory pathways and nerves. It is not known how many individuals with Friedreich ataxia experience painful peripheral neuropathy, but treatment of pain related to neuropathy appears to be an unmet need, as indicated by patients and parents. The Friedreich’s ataxia Clinical Management Guideline Patient and Parent Advisory Panel was interviewed on the consequences, urgency and priority of neuropathic pain, among other disease symptoms in 2020. More than half the respondents thought that painful neuropathy in Friedreich ataxia was, or probably was a serious issue in this population, and many respondents thought that treatment of painful neuropathy in Friedreich ataxia was a priority.
Why these recommendations?
There is a lack of studies about treatment of painful peripheral neuropathy in Friedreich ataxia. However, there is good research about treatment of neuropathic pain in other conditions, including diabetic peripheral neuropathy, peripheral neuropathy from chemotherapy, and HIV-related neuropathy. Clinical guidelines from randomized controlled trials (RCTs) in these conditions recommend that several medications might help painful neuropathy, including pregabalin, venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids, and topical (applied to the skin) lidocaine and capsaicin. The use of these medicines must be balanced against potential side effects, and this should be discussed with your healthcare provider.
It is important that your healthcare provider takes a detailed history and carries out a clinical examination if you experience pain and numbness in the lower part of your limbs, particularly to rule out other causes of painful limbs or numbness that could be confused with painful neuropathy, such as a vascular condition, a metabolic condition, or an injury. It is important that you let your healthcare provider know how long you have experienced a painful neuropathy and if it affects your quality of life, such as sleeping or walking.
Peripheral neuropathy can be a consequence of Friedreich ataxia. However, there is as yet no published research or specific guidelines to help people with Friedreich ataxia manage painful peripheral neuropathy.
We suggest that you and your medical team explore management strategies to reduce painful neuropathy if it affects your quality of life.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It is important for you to speak with your Friedreich ataxia healthcare provider if you are experiencing painful neuropathy that adversely affects your quality of life.
Who is this recommendation specifically for?
People with Friedreich ataxia who are experiencing painful peripheral neuropathy.
Sylvia Boesch, MD, MSc
Head, Center for Rare Movement Disorders Innsbruck, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
Email: sylvia.boesch@i-med.ac.at
George Wilmot, MD, PhD
Associate Professor, Department of Neurology, Emory University, Atlanta, Georgia, USA
Email: gwilmot@emory.edu
Theresa Zesiewicz, MD
Professor, University of South Florida, Tampa, Florida, USA
Email: tzesiewi@usf.edu
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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.