Presented by: WEBINAR: Well with Small Fiber Neuropathy “

11/12/2013
WEBINAR: “Understanding and Living
Well with Small Fiber Neuropathy”
”
Saturday, November 16th, 2013
2 - 3:15 pm ET
1 - 2:15 pm CT
12 - 1:15 pm MT
11 am - 12:15 pm PT
Presented by:
Shanna K. Patterson, MD
St. Luke’s - Roosevelt Hospital Center
Corey W. Hunter, MD
Ainsworth Institute of Pain Management
Brought to you by The Neuropathy Association and Transgenomic, Inc.
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Presentation Objectives
WHAT PARTICIPANTS CAN TAKE AWAY FROM THE WEBINAR:
Understand the relationship between small fiber neuropathy(SFN) and
peripheral neuropathy;
Recognize the symptoms and signs of small fiber neuropathy;
Understand the importance of getting an evaluation and accurate
diagnosis of small fiber neuropathy;
Appreciate the role of current and emerging (clinical research trials)
approaches for diagnosing and treating small fiber neuropathy; and,
Review the spectrum of pain management strategies.
SFN: Introduction
Two general categories of peripheral nerve fibers:
Large diameter
Myelinated
Sensory and motor function
Small diameter
Unmyelinated or thinly myelinated
Sensory function only
Located in the superficial layer of skin, known as the epidermis, as
well as in sweat glands in the skin
Also involved in innervation of the cardiovascular, genitourinary and
gastrointestinal systems
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SFN: Introduction
Small fiber neuropathy is a type of neuropathy where only small diameter
nerve fibers are affected.
A recent study showed that the prevalence of small fiber neuropathy in the
Southern Netherlands was approximately 53 cases per 100,000. The
incidence was higher in men than women, and in older individuals.
(Neurology 2013)
SFN: Sensory Symptoms
Symptoms are usually sensory in nature and include pain, numbness
or other uncomfortable sensations, such as tingling.
“Length dependent”: begins in the distal limbs, such as the feet
“Non-length dependent”: involves different locations on the body, may
occur in a multifocal, patchy distribution.
Symptoms of pain or tingling, or other uncomfortable sensations are
often more common than numbness in SFN. (Muscle Nerve 1992)
Because small diameter nerve fibers do not connect to muscles,
weakness will not be a symptom in this type of neuropathy.
Small fiber neuropathy may be a cause of muscle cramps.
In an evaluation of 12 consecutive patients with cramps but without
neuropathic complaints (pain, tingling, etc.) 60% had small fiber neuropathy,
as diagnosed with skin biopsy. (Muscle Nerve 2013)
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SFN: Autonomic Symptoms
Some (but not all) SFN patients may also develop symptoms of
autonomic neuropathy.
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Peripheral autonomic nerves control several vital body functions -- which we
do not consciously think about -- including blood pressure, heart rate,
digestion, dilation and constriction of the pupils of the eye, sexual function,
and bowel and bladder emptying.
- Gastrointestinal symptoms: constipation, diarrhea, early feelings of
satiety.
- Cardiovascular symptoms: blood pressure changes with position causing
dizziness when standing.
- Genitourinary symptoms: difficulty beginning to urinate, feeling of
incomplete bladder emptying, urinary incontinence, and sexual dysfunction.
- Other symptoms: abnormal sweating and increased sensitivity to warm and
cold temperatures.
SFN: Signs
Clinical signs on physical examination of a person with SFN can
include
Reduced temperature or pain (pin prick) sensation
Reduced light touch sensation
Increased sensitivity (hyperesthesia) to touch
Painful sensation to touch (allodynia)
However, in many cases the sensory examination may also be normal.
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SFN: Testing
Neuropathy involving large diameter nerves is detectable with nerve
conduction studies (NCS), but isolated small diameter nerve involvement is
not detectable using this test.
Testing for SFN is important:
It can lead to psychological validation for patients who previously did not
know the reason for their symptoms.
Objective diagnosis facilitates search for cause, as well as treatment.
SFN: Testing
Quantitative sensory testing:
An automated, standardized system that quantifies thresholds across
several sensory modalities. This allows for a more precise and sensitive
means of detecting abnormalities in sensation.
Skin punch biopsies:
The density of small diameter nerve fibers in a small (3mm) sample of
epidermal tissue (most superficial layer of skin) is measured. In SFN
there is a reduced number of nerve fibers (reduced epidermal nerve
fiber density).
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SFN: Causes
Many causes of SFN are similar to those of large fiber neuropathy.
Small fiber sensory neuropathy is a major manifestation in type 1
diabetes…and more prevalent than large fiber
neuropathy. (Diabetes Care)
If the cause of neuropathy is found, this can improve the chances of treating
the neuropathy.
In approximately half of cases no cause for SFN is found.
Ongoing research continues to search for additional causes.
SFN: Causes
Causes of SFN include:
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Metabolic conditions: diabetes, borderline diabetes
Toxic effects: alcohol abuse, heavy metals, certain medications
Deficiency or excess of vitamins
Infections: hepatitis C, Lyme disease, HIV, Leprosy
Auto-immune conditions: vasculitis, paraneoplastic conditions (autoimmune response to malignancy), Sjögren’s syndrome, Celiac disease
Hematologic conditions: malignancies, abnormal protein production
Hereditary neuropathies
Fabry disease: alpha-galactosidase A enzyme deficiency
Familial amyloidosis: transthyretin gene mutation
Voltage gated sodium channel mutations
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SFN: Relationship to sodium
channel mutations
In one study, 30% of patients with idiopathic SFN were found to have
SCN9A-gene mutations. (Clinical Genetics 2012)
This mutation produces abnormal increased function in nerve sodium
channels.
This type of sodium channel is more specific to small diameter
peripheral nerves. (This genetic cause may not be able to account for
an equally high percentage of idiopathic large diameter neuropathy
cases).
Treatment of pain symptoms for these patients may be best achieved by
using neuropathic pain medications that decrease sodium channel activity,
such as gabapentin or carbamazepine.
SFN: Evaluating for Causes
History
Detailed history to evaluate for possible exposures to certain
medications, toxins, etc.
Family history of certain conditions
Risk factors for certain conditions
Detailed medical history
Looking for certain physical examination features suggestive of other
potentially contributory causes.
Laboratory evaluation
May include genetic testing
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SFN: Treatment
If a reversible or treatable underlying cause is identified, this should be
addressed.
If blood sugar control is achieved and maintained, or a vitamin
deficiency is corrected, for example, over time the neuropathy may
improve.
It is difficult to precisely predict, as each patient’s clinical situation
and course is different.
In certain autoimmune-related types of SFN treatment with IVIG
(intravenous immunoglobulin) may be effective.
More information to come regarding symptomatic management of pain
with Dr. Corey Hunter…
SFN: Possible Relationship to
Fibromyalgia
Several recent studies have shown that a significant proportion of patients
with fibromyalgia have reduced epidermal nerve fiber density on punch skin
biopsies. (Brain 2013, Pain 2013)
Additional research is ongoing, but the cause of other painful conditions or
syndromes may in the end be related to small fiber neuropathy.
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Managing SFN: Overview
Small fiber neuropathy is frequently associated with neuropathic pain.
- A variety of medications for treatment of pain exist, and there are a number of
consensus guidelines that help clinicians in selecting appropriate treatment(s).
- Limited evidence for specific medications in the treatment of pain from small fiber
neuropathies.
How do clinicians partner with patients to select pain treatments?
- evidence of safety
- efficacy in other neuropathic conditions
- tolerability
- cost
- co-morbid conditions
- drug interactions
Partnering with a multi-disciplinary team of health care professionals
is important.
- neurologist specializing in neuromuscular diseases
- physical therapist
- pain medicine specialist
- immunologist
Managing SFN: Treating Underlying
Cause Is Key
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Treat the underlying cause of SFN (when possible) and the pain
Careful screening for reversible causes of small fiber neuropathy is critical.
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50% of SFN patients are given an “idiopathic” (or unknown cause)
diagnosis
Many patients with small fiber neuropathy are given an “idiopathic” diagnosis even
after comprehensive evaluation -- for these patients, pain management is critical.
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Evaluate and treat the autonomic symptoms
e.g., excessive sweating, gastroparesis, orthostatic hypotension
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Evaluate and treat the co-morbid symptoms
e.g., anxiety, depression, sleep disturbances
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Managing SFN:
Pharmacological Treatments
First-line treatments:
- Gabapentin (FDA-indicated for PHN)
- Gabapentin once-daily dose (FDA-indicated for PHN)
- Pregabalin (FDA-indicated for painful DPN, fibromyalgia, and PHN)
- Topical capsaicin (FDA-indicated for PHN)
- Topical lidocaine (FDA-indicated for PHN)
Second-line treatments:
- Duloxetine (FDA-indicated for painful DPN, fibromyalgia, chronic back pain)
- Tapentadol extended-release(FDA-indicated for painful DPN)
- Topical capsaicin (FDA-indicated for PHN)
- Topical lidocaine (FDA-indicated for PHN)
- Amytriptyline
- Nortriptyline
- Tramadol
- Venlafaxine
Third-line treatments:
- Tapentadol extended-release (FDA-indicated for painful DPN)
- Tramadol
Managing SFN:
Non-Pharmacological Treatments
According to the National Center for Complementary and Alternative
Medicine (NCCAM), nearly 40% of Americans use health care
approaches developed outside of mainstream Western -- or
conventional -- medicine for specific conditions or overall well-being.
- Dietary supplements
For more information about
- Mind and body practices
Complementary and Alternative
e.g., acupuncture, biofeedback, yoga,
Medicine, visit
meditation, tai chi, hypnotherapy
http://nccam.nih.gov/health/pain.
- Physical therapy
- Cool or warm soaks, soft socks, foot tents
It is critical that you inform your doctor(s) about any alternative /
complementary medicines you might be considering.
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Managing SFN:
Interventional Treatments
Infusion Therapy
Ketamine (requires in-patient hospital admission)
Lidocaine
Regional Nerve Blocks under Ultrasound
Sympathetic Blocks
Stellate Ganglion for the Upper Extremities
Lumbar Sympathetic Chain for the Lower Extremities
Spinal Cord Stimulators
Intrathecal Pumps
SFN Clinical Research Studies
A placebo-controlled, randomized, double
blind trial of milnacipran for the treatment
of idiopathic neuropathy pain
Safety and tolerability of lacosamide in
patients with gain-of-function Nav1.7
mutations-related small fiber neuropathy
Metanx effects on nerve fiber density in
neuropathic diabetics (SLHN2011-18)
Safety and efficacy of gabapentin for
neuropathic pain in Fabry disease
For a more comprehensive list
of neuropathy clinical trials
and to locate clinical trials in
your vicinity, visit
www.clinicaltrials.gov and
search using the words
“neuropathy” and the “name
of the city” you live in (e.g.,
neuropathy, NYC).
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Q and A
Provided by:
For more information about Transgenomic, Inc. and SCN9A
testing, visit www.transgenomic.com/labs/neurology.
For more information about peripheral neuropathy, small fiber
neuropathy, and The Neuropathy Association,
visit www.neuropathy.org.
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Testing for SCN9A Pain-related
Disorders
The SCN9A gene encodes the sodium channel protein Nav1.7 that is located in peripheral neurons.
SCN9A mutations may cause a loss- or gain-of-function of Nav1.7 whose primary function is mediating
pain sensations. Gain-of-function mutations result in hyper-excitability of pain signaling neurons causing
extreme sensitivity to pain, while loss-of-function mutations have the opposite effect on pain sensation.¹
Learn more about SCN9A testing and Transgenomic Labs:
www.transgenomic.com/labs/neurology
(P) 1.877.274.9432 / (F) 1.855.263.8668 / [email protected]
1. Drenth, JP, et al. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J. Clinical Investigation, 2017;117;3603-9.
2. Klein CJ, et al. Infrequent SCN9A mutations in congenital insensitivity to pain and erythromelalgia. J Neurol Neurosurg Psychiatry, November 2012.
3. Faber CG, et al. Gain of Function Nav1.7 Mutation in Idiopathic Small Fiber Neuropathy. Ann Neurol. 2012; 71:26-39.
4. Fertleman CR, et al. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes.Neuron. 2006;52:767-74.
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