pattismith
Senior Member
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Dr Levine refers to genetic EM with "mutation in SCN9A, a gene ... that encodes the alpha-subunit of Na(v)1.7 voltage-gated sodium channels.
Mutations in Na(v)1.7, expressed by neurons involved in nociception and sympathetic outflow, render the former hyperexcitable and the latter hypoexcitable, thus contributing to increased cutaneous blood flow resulting in pain, warmth, and erythema." (here)
Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning
"Abstract
Small fiber neuropathy (SFN) has a poorly understood pathology, but patients would benefit from determination of clinical phenotypes that allows for better diagnosis and treatment planning.
I propose that patients should be classified dependent on whether there is sodium channel dysfunction, classic neurologic symptoms only, widespread neuropathic pain, or autonomic symptoms.
Patients with SFN can then be considered in light of their clinical phenotype, allowing for focus on subsets of patients who might have diagnosable conditions or be more prone to responding to a particular type of therapy that may not be efficacious in the broader patient population with SFN.
There are several therapies currently available that can address the symptoms of SFN; however, to develop novel therapeutic strategies, it will be imperative to classify patients to understand and target the underlying pathology."
….
" I suggest using the term small fiber sodium channel dysfunction (SFSCD) as a way of referring to patients who have symptoms of paroxysmal neuropathic pain characteristic of mutations in sodium channel proteins such as NaV1.7, 1.8, or 1.9.
These patients may previously have been labeled as having erythromelalgia or other paroxysmal pain disorders.
These patients may differ from other patients with SFN as they may have genetically proven mutations in their sodium channels and physiologically proven nerve hyperexcitability without having a reduced intraepidermal nerve fiber density. While current sodium channel–blocking agents are not always effective, novel sodium channel blocking drugs could be revolutionary for this subset of patients, although not helpful to patients with other causes of painful SFN.7,8"
In addition to patients with sodium channel–mediated SFN are patients with SFN who have classic neuropathic symptoms such as burning, tingling, stabbing, and numbness.
These patients can be classified into the group small fiber–mediated painful neuropathy (SFMPN).
These patients will have reduced intraepidermal nerve fiber density on skin biopsy in addition to the classic neuropathic symptoms.
Another group of patients who have recently been shown to have objective evidence for damage to their small fibers are patients who have more widespread pain, experiencing muscle cramps and muscle pain, and in many cases, these patients have been confused as having fibromyalgia.
I propose labeling the group of these patients who have evidence for objective loss of small nerve fibers as having small fiber–mediated widespread pain (SFMWP).
These patients often have symptoms such as headache, fatigue, irritable bowel syndrome, cognitive dysfunction, and sleep disturbances.
In an extreme form of these disorders, patients have objective evidence for autonomic dysfunction: abnormal gastric emptying studies with nausea and vomiting, abnormal tilt table tests, and abnormal quantitative sudomotor autonomic reflex testing.
These patients should be labeled as having small fiber–mediated autonomic dysfunction (SFMAD), as their clinical phenotype is often overshadowed by gastrointestinal symptoms, heart rate dysregulation, temperature sensitivities, fatigue, and irritable bowel syndrome."....
Mutations in Na(v)1.7, expressed by neurons involved in nociception and sympathetic outflow, render the former hyperexcitable and the latter hypoexcitable, thus contributing to increased cutaneous blood flow resulting in pain, warmth, and erythema." (here)
Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning
"Abstract
Small fiber neuropathy (SFN) has a poorly understood pathology, but patients would benefit from determination of clinical phenotypes that allows for better diagnosis and treatment planning.
I propose that patients should be classified dependent on whether there is sodium channel dysfunction, classic neurologic symptoms only, widespread neuropathic pain, or autonomic symptoms.
Patients with SFN can then be considered in light of their clinical phenotype, allowing for focus on subsets of patients who might have diagnosable conditions or be more prone to responding to a particular type of therapy that may not be efficacious in the broader patient population with SFN.
There are several therapies currently available that can address the symptoms of SFN; however, to develop novel therapeutic strategies, it will be imperative to classify patients to understand and target the underlying pathology."
….
" I suggest using the term small fiber sodium channel dysfunction (SFSCD) as a way of referring to patients who have symptoms of paroxysmal neuropathic pain characteristic of mutations in sodium channel proteins such as NaV1.7, 1.8, or 1.9.
These patients may previously have been labeled as having erythromelalgia or other paroxysmal pain disorders.
These patients may differ from other patients with SFN as they may have genetically proven mutations in their sodium channels and physiologically proven nerve hyperexcitability without having a reduced intraepidermal nerve fiber density. While current sodium channel–blocking agents are not always effective, novel sodium channel blocking drugs could be revolutionary for this subset of patients, although not helpful to patients with other causes of painful SFN.7,8"
In addition to patients with sodium channel–mediated SFN are patients with SFN who have classic neuropathic symptoms such as burning, tingling, stabbing, and numbness.
These patients can be classified into the group small fiber–mediated painful neuropathy (SFMPN).
These patients will have reduced intraepidermal nerve fiber density on skin biopsy in addition to the classic neuropathic symptoms.
Another group of patients who have recently been shown to have objective evidence for damage to their small fibers are patients who have more widespread pain, experiencing muscle cramps and muscle pain, and in many cases, these patients have been confused as having fibromyalgia.
I propose labeling the group of these patients who have evidence for objective loss of small nerve fibers as having small fiber–mediated widespread pain (SFMWP).
These patients often have symptoms such as headache, fatigue, irritable bowel syndrome, cognitive dysfunction, and sleep disturbances.
In an extreme form of these disorders, patients have objective evidence for autonomic dysfunction: abnormal gastric emptying studies with nausea and vomiting, abnormal tilt table tests, and abnormal quantitative sudomotor autonomic reflex testing.
These patients should be labeled as having small fiber–mediated autonomic dysfunction (SFMAD), as their clinical phenotype is often overshadowed by gastrointestinal symptoms, heart rate dysregulation, temperature sensitivities, fatigue, and irritable bowel syndrome."....