Current issues in peripheral neuropathy

Journal of the Peripheral Nervous System 17(Supplement):1-3 (2012)
REVIEW
Current issues in peripheral neuropathy
Thomas H. Brannagan III
Columbia University, College of Physicians and Surgeons, New York, NY, USA
Abstract Twenty million people in the United States are estimated to have peripheral
neuropathy. However, many patients are not aware of their diagnosis, are not given the
diagnosis or being treated, or the diagnosis is delayed. Currently, the only treatments
available for neuropathy are aimed at treating the underlying medical conditions that cause
the neuropathy or treating symptoms such as pain. Neither treats the actual nerve fiber
dysfunction or fiber loss, or helps nerve fibers regenerate. Idiopathic neuropathy, that is
neuropathy for which a cause is not identified, is common, accounting in referral series for
25% in all neuropathy patients and 50% or more of patients with small fiber neuropathy.
Currently, there is only one FDA-approved medication for a specific neuropathy (chronic
inflammatory demylinating polyneuropathy) while there are two FDA approved medications
for diabetic neuropathy pain and four that are approved for post-herpetic neuralgia pain. For
many patients with painful neuropathy, these medications are ineffective or not tolerated.
Continued research into the underlying mechanisms of neuropathy and an increased
understanding of nerve regeneration and neuropathic pain are needed to address this
unmet medical need among patients with neuropathy.
Key
words:
chronic
inflammatory
demyelinating
polyradiculoneuropathy,
diabetic
neuropathy, nerve regeneration, neuropathic pain, peripheral neuropathy
Despite the enormous physical, emotional, and
conducted a national online poll of approximately 800
financial toll neuropathy takes on Americans' health
patients to determine how long after the onset of
and our health care system, neuropathy remains one
symptoms they were diagnosed. Less than 30% were
of the least recognized illnesses in the United States
given a diagnosis in 1 year and some patients had
today. In a survey of patients with diabetes melli-
symptoms for over 15 years before they were diag-
tus about symptoms of neuropathy, only one of four
nosed (Fig. 1).
patients with symptoms of neuropathy had been diag-
This supplement includes the proceedings of the
nosed with the disease. Fifty-six percent of those with
2010 Neuropathy Summit's Physicians Conference.
symptoms were unaware of the term diabetic neuropa-
The goal of the symposium was to discuss peripheral
thy. Over half believed their symptoms were related
neuropathy with a translational approach, including
to diabetes mellitus, but only 42% had been told by
laboratory advances in understanding the pathogene-
their doctor that diabetes was the cause. And one in
sis, clinical research, and clinical care. Topics included
seven said no cause was mentioned (American Dia-
diabetic neuropathy, inflammatory neuropathies, idio-
betes Association, 2005). The Neuropathy Association
pathic neuropathies, inherited neuropathies, nerve
regeneration, and neuropathic pain.
Diabetic neuropathy is now the most common
Address correspondence to: Thomas Brannagan, MD, Peripheral
cause of neuropathy worldwide according to the
Neuropathy Center, Neurological Institute, Columbia University,
World Health Organization (Martyn and Hughes, 1997).
College of Physicians and Surgeons, 710 W 168th Street, Box
163, New York, NY 10032, USA. Tel: +1 212-305-0405; Fax: +1
Therefore, the meeting began with the current under-
212-305-5396; E-mail: Tb2325@columbia.edu
standing of the pathogenesis of diabetic neuropathy
(c) 2012 Peripheral Nerve Society
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Brannagan
Journal of the Peripheral Nervous System 17(Supplement):1-3 (2012)
Table 2. Medications that were not better than placebo
in HIV neuropathy pain.
Amitriptyline - Kieburtz et al. (1998) and Shlay et al.
(1998)
Gabapentin - Hahn et al. (2004)
Pregabalin - Simpson et al. (2010)
Mexilitine - Kieburtz et al. (1998) and Kemper et al. (1998)
Evidence-based medicine and comparative effec-
tiveness research (CER) are being used increasingly in
discussions of changes that may occur in our health
Figure 1. Symptom onset to diagnosis.
care system. Kaufmann discussed the role of these
agencies in supporting CER and other research in
Table 1. Patients with idiopathic neuropathy, despite
intensive evaluation.
peripheral neuropathy. Another national poll conducted
by The Neuropathy Association noted that the major
Idiopathic or cryptogenic neuropathy
issue of concern to people responding was neuro-
25% - Dyck et al. (1981)
pathic pain. For this reason, neuropathic pain was a
23% - Barohn (1998)
major focus of this meeting. The initial goal in treat-
19% - Verghese et al. (2001)
ing patients with neuropathy is to treat the underlying
Percent idiopathic of small fiber neuropathy
90% - Periquet et al. (1999)
cause of the neuropathy. This is not always possible,
50% - Venkataramana et al. (2005)
but if patients have pain from neuropathy, this may
50% - De Sousa et al. (2006)
be treated. A commonly held belief is that neuropathic
pain treatment, directed at the mechanisms of pain or
(Hinder et al., 2012), the risks of impaired glucose tol-
plasticity in the nervous system, resulting from nerve
erance and the metabolic syndrome for neuropathy
damage, rather than the cause of the neuropathy or
(Smith, 2012) and a discussion of current and develop-
nerve damage, is appropriate. Two medications have
ing treatments for diabetic neuropathy (Bril, 2012).
been approved by the FDA for diabetic neuropathy
Soliven reviewed the role of animal models,
pain, duloxetine and pregabalin; however; these med-
specifically experimental allergic neuritis and the spon-
ications also work for neuropathy from other causes.
taneous autoimmune neuropathy in B7-2 knockout
In one form of neuropathy, however, HIV neuropathy,
non-obese diabetic mice, in increasing our understand-
several medications that have been shown to be effec-
ing of the pathogenesis of autoimmune neuropathies.
tive for diabetic neuropathy pain have been ineffective
Dalakas discussed currently available and emerging
in clinical trials for HIV neuropathy pain, including
treatments for autoimmune neuropathies.
amitriptyline, gabapentin, mexiletine, and pregabalin
Even after a thorough evaluation for causes of
(Kemper et al., 1998; Kieburtz et al., 1998; Shlay et al.,
neuropathy, most referral-based series have noted
1998; Hahn et al., 2004; Simpson et al., 2010) (Table 2).
that 20-25% of patients have no identified cause
Twenty million people are estimated to have
and are given a diagnosis of idiopathic or cryptogenic
peripheral neuropathy in the United States. Despite
neuropathy (Dyck et al., 1981; Barohn, 1998; Vergh-
the fact that it is one of the most common
ese et al., 2001). This is true to a greater degree in
chronic neurological disorders, public awareness of
patients with small fiber neuropathy where 50% or
this condition is inadequate. There are only limited
more of patients have idiopathic neuropathy (Periquet
treatments available for some types of neuropathy with
et al., 1999; Venkataramana et al., 2005; De Sousa
no treatment options for others. Continued research
et al., 2006) (Table 1). Singer et al. (2012) discussed
into the underlying mechanisms of neuropathy and
current research being done in idiopathic neuropathy.
an increased understanding of nerve regeneration and
The only treatment that we have for peripheral neu-
neuropathic pain are needed.
ropathy is when we can treat the identifiable cause.
But, for the large number of patients with idiopathic
neuropathy, we will only have a treatment for the
Disclosure
neuropathy available when we have the ability to
The author declares no conflict of interest.
regenerate nerves. Zochodne spoke on the advances
in nerve regeneration. Polydefkis discussed the use
of skin biopsies to assess epidermal nerve fibers as a
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