CHRONIC, IDIOPATHIC, LENGTH-DEPENDENT SENSORY OR SENSORIMOTOR POLYNEUROPATHYIn our experience and others, a cause for neuropathy will not be found in as many as 50% of cases despite an extensive work-up.1–11 The chronic idiopathic polyneuropathies are likely a heterogeneous group of neuropathies. Most individuals have only sensory symptoms, but some may have mild weakness (e.g., toe extension) or slight abnormalities on motor conduction studies. The neuropathy may affect large- and/or small-diameter nerve fibers. As the etiology is unknown, only symptomatic management of the neuropathic pain is available.
CHRONIC, IDIOPATHIC, LENGTH-DEPENDENT SENSORY OR SENSORIMOTOR POLYNEUROPATHYMost individuals present with numbness, tingling, or pain (e.g., sharp stabbing paresthesias, burning, or deep aching sensation) in the feet between the ages of 45 and 70 years.1–11 This is a common problem occurring in approximately 3% of adults as they age. In a large series of 93 patients with idiopathic sensory polyneuropathy, 63% presented with numbness and paresthesia along with pain, 24% with numbness or paresthesia without pain, and 10% with pain alone.9 Eventually, 65–80% of affected individuals develop neuropathic pain.6,9–11 Sensory symptoms are first noted in the toes and slowly progress up the legs and later into the arms. The average time to involvement of the hands is approximately 5 years.6,9
Neurological examination reveals the typical length-dependent pattern of sensory loss.6,7,9,11 Vibratory perception is reduced in 80–100%, proprioception is impaired in 20–30%, pinprick sensation is diminished in 75–85%, and light touch is decreased in 54–92% of those with the neuropathy. Strength is usually normal, although mild distal weakness and atrophy involving toe muscles may be appreciated in 40–75% of cases, and rarely of ankle dorsiflexors and plantar flexors.6,9,11 However, upper limb strength, including the hand intrinsics, should be normal. Muscle stretch reflexes are usually absent at the ankle and diminished at the knees and arms. Generalized areflexia though is less common and would point to a hereditary or acquired demyelinating neuropathy.
Within the category of idiopathic sensory or sensorimotor polyneuropathies are people who have only a small fiber sensory neuropathy.2,3,7,9 By definition, these individuals should have normal nerve conduction studies (NCS), and nerve biopsies, if performed, demonstrate a relatively normal density of large myelinated nerve fibers. Most people with small fiber neuropathy (approximately 80%) complain of burning pain in the feet, while 40–60% describe sharp, lancinating pain; paresthesias; or just numbness. Symptoms may involve the distal upper extremities. Rarely, the neuropathy is restricted to the arms and face or involves the autonomic nervous system.2,3 Examination reveals reduced pinprick or temperature sensation in almost all patients, while vibratory perception is impaired in half. Muscle strength is preserved. Likewise, muscle stretch reflexes are also usually normal, but a few patients have reduced reflexes at the ankles.
The diagnosis of chronic idiopathic polyneuropathy is one of exclusion. Laboratory testing should include fasting blood glucose (FBS), hemoglobin A1 C (HgbA1 C), antinuclear antibody, anti-Ro and anti-La antibodies (SSA and SSB), erythrocyte sedimentation rate, B12, serum and urine immunoelectrophoresis/immunofixation, and thyroid, liver, and renal function tests.12,13 If the FBS and HgbA1 C are normal, we typically order an oral glucose tolerance test (GTT). The most common abnormality, when one is found, in patients with sensory neuropathy is diabetes or impaired glucose tolerance (IGT). IGT (defined as glucose of >140 and <200 mg/dL on 2-hour GGT) is seen in 17–61% and frank diabetes mellitus (DM) (defined as 2-hour glucose of >200 mg/dL on GGT or FBS of >126 mg/dL) in 20–31% of patients with sensory neuropathy (Table 22-1).14–18 In patients with painful sensory symptoms (not just numbness), the likelihood of IGT or DM is even higher. However, some authorities have not found increased risk of IGT in their patients with idiopathic neuropathy compared to age-matched controls.19 Thus, although the risk of both previously undetected DM and IGT may be increased in patients with sensory neuropathy, this is still controversial and a causal relationship has not been firmly established.20,21
TABLE 22-1. RESULTS OF GLUCOSE TOLERANCE TESTING IN OTHERWISE IDIOPATHIC POLYNEUROPATHY14–17
About 5% of patients with chronic idiopathic sensory or sensorimotor polyneuropathy have a monoclonal protein detected in the serum or urine, but this is not much higher than the age-matched normal controls. Furthermore, the relationship of these monoclonal proteins to the pathogenesis of most neuropathies is unclear. There is a strong pathogenic relationship established in people with demyelinating sensorimotor polyneuropathies with IgM monoclonal proteins, half of whom have myelin-associated glycoprotein (MAG) antibodies (discussed in Chapters 14 and 19). However, most individuals with chronic idiopathic sensory or sensorimotor polyneuropathy have axonal neuropathies both histologically and electrophysiologically. Amyloidosis is the other condition in which a pathogenic relationship between the neuropathy and the monoclonal protein is clear. Thus, amyloid neuropathy needs to be excluded in patients with a monoclonal gammopathy before concluding that the neuropathy is idiopathic in nature (see Chapter 16). This may require a fat pad, rectal, bone marrow, or nerve biopsy.
Although some studies have suggested that antisulfatide antibodies are common with painful small fiber neuropathy,22,23 subsequent reports suggest that these antibodies have a very low sensitivity and poor specificity.6,10 We never order them as we have found them to be of little use clinically, and a pathogenic relationship has never been demonstrated. That is, the presence of these antibodies does not imply that the patients have an immune-mediated neuropathy and that they may respond to treatment with immunotherapy. We also feel that there is no role for screening various antiganglioside and other antinerve antibodies (e.g., GM1 and Hu antibodies) in the workup of patients with chronic, indolent, sensory predominant, length-dependent polyneuropathies. CSF examination is usually normal and is also unwarranted.
In people with a large fiber neuropathy, the sensory NCS reveal either absent or reduced amplitudes that are worse in the legs.1,3,4,6–12 Sensory NCV are normal or only mildly slow. Quantitative sensory testing (QST) demonstrates abnormal thermal and vibratory perception in as many as 85% of patients.7,9 In addition, autonomic testing (e.g., quantitative sudomotor axon reflex and heart rate testing with deep breathing or Valsalva) is abnormal in some patients. Despite the fact that sensory symptoms predominate, motor NCS are often abnormal. Wolfe et al.9 reported that 60% of their patients with idiopathic polyneuropathy had abnormal motor NCS. The most common motor abnormalities are reduced peroneal and posterior tibialis compound muscle action potentials (CMAP) amplitudes, while distal latencies and conduction velocities of the peroneal and posterior tibial CMAPs are normal or only slightly impaired. Abnormalities of median and ulnar CMAPs are much less common. Fibrillation potentials and positive waves on needle EMG are also commonly found in intrinsic foot muscles as a further indicator of frequently subclinical motor involvement. In the authors’ experience, they may be the only indicator of motor involvement in what may otherwise appear to be a pure sensory neuropathy.
In patients with pure small fiber neuropathies, motor and sensory NCS are, by definition, normal. The peripheral autonomic nervous system is often affected in small fiber neuropathies; thus, autonomic testing can be useful.13,24–27 The quantitative sudomotor axon reflex test (QSART) can be performed in the distal and proximal aspects of the legs and arms (Fig. 22-1). Sweat glands are innervated by small nerve fibers, and impaired QSART is highly specific and sensitive for small fiber damage, with 59–80% of patients having an abnormal study (Table 22-2).24–27 Other autonomic tests [e.g., heart rate (HR) variability with deep breathing (DB) or Valsalva maneuver] may also be abnormal in affected individuals.7 In this regard, assessments include variability of HR to DB (Fig. 22-2) and response of the HR and blood pressure to Valsalva maneuvers and positional changes (e.g., response to tilt table or supine to standing position).
Figure 22-1. Quantitative sudomotor axon reflex test (QSART). Sudomotor function can be quantitated by measuring the amount of sweat produced in the distal and proximal aspects of the legs and arms. In (A), a normal response is seen (lower panel recorded from foot, middle panel for shin, and upper panel from thigh). Individuals with small fiber neuropathy may have reduced cumulative sweat. In length-dependent process, the QSART is worse distally (e.g., at the foot compared to more proximally (B), lower panel recorded from foot, middle panel for shin, and upper panel from thigh).
TABLE 22-2. COMPARISON OF DIAGNOSTIC TESTS IN PATIENTS WITH PREDOMINANTLY PAINFUL, SENSORY NEUROPATHY3,7,9,24–26,29–30,37
Figure 22-2. Heart rate variability. Normally, the heart rate varies with respiration (A). Some individuals with small fiber involvement have an autonomic neuropathy with cardiovagal abnormalities, as demonstrated by reduced heart rate variability with deep breathing (B).
Abnormal thermal and vibratory perception thresholds may be demonstrated using QST.28 Unlike NCS that only assess the physiology of large-diameter sensory fibers, QST of heat and cold perception can evaluate small fiber function. Abnormal QST has been reported in 60–85% of patients with predominantly painful sensory neuropathy (Table 22-2).9,25,29,30 However, QST depends on patient attention and cooperation; it cannot differentiate between simulated sensory loss and sensory neuropathy. Furthermore, the sensitivity and specificity of QST are lower than QSART and skin biopsies.31,32
Nerve biopsies in patients with chronic, sensory predominant, length-dependent neuropathies may reveal axonal degeneration, regenerating axonal sprouts, or axonal atrophy with or without secondary demyelination.5–7,9,33 Quantitative morphometry may reveal loss of large- and small-diameter myelinated fibers and small unmyelinated fibers. Occasionally, scattered perivascular and endoneurial lymphocytes may be seen on nerve biopsy,33,34 although necrotizing vasculitis is not a feature. A clonal restriction of the variable T-cell receptor γ-chain gene has been demonstrated by one group of researchers.35 Basal lamina area thickness, endoneurial cell area, and number of endothelial cell nuclei may be increased. However, the abnormalities on nerve biopsy are nonspecific and are generally not helpful in finding an etiology for the neuropathy. There, we do not routinely perform nerve biopsies on all patients with unexplained polyneuropathies. We consider doing a biopsy in people with autonomic sign or monoclonal gammopathies to assess for amyloidosis, those with multiple mononeuropathies, and in patients with underlying diseases associated with vasculitis (e.g., connective tissue disorders, cryoglobulinemia, and hepatitis B or C).
Nerve biopsies in individuals with small fiber neuropathies may show selective loss of small myelinated nerves and unmyelinated nerve fibers, but this requires quantitative analysis by electron microscopy (Fig. 22-3).13 A more sensitive and less invasive means of assessing these small fiber neuropathies histopathologically is by measuring intraepidermal nerve fiber (IENF) density on skin biopsies (Fig. 22-4).3,7,29,36,37,38–42 Assessment of IENF density also appears to be more sensitive in identifying patients with small fiber neuropathies than sural nerve biopsies, NCS, or QST (Table 22-2). Punch biopsy of the skin can be obtained at the foot, calf, or thigh, and immunohistochemistry using antibodies directed against protein gene product 9.5 (PGP 9.5) is used to stain small intraepidermal fibers. Intraepidermal nerve fibers arising entirely from the dorsal root ganglia represent the terminals of C and Aδ nociceptors. The density of these nerve fibers is reduced in patients with small fiber neuropathies, in which NCS, QST, and routine nerve biopsies are often normal. In at least a third of people with painful sensory neuropathies, IENF density on skin biopsies represents the only objective abnormality present following extensive evaluation.7
Figure 22-3. Specimen from a sural nerve biopsy. The nerve is morphologically normal on light microscopy (A). There is a focal perivascular lymphocytic infiltrate, and in one small perineurial vessel (arrow) the infiltrate extends through the wall (hematoxylin and eosin, ×125). There is no necrosis or other evidence of vasculitis or intraneural inflammation. An electron micrograph (B) shows empty Schwann-cell processes (arrows) that are consistent with the loss of small, unmyelinated fibers (×8,000). (Used with permission of Doctors Lawrence Hayward and Thomas Smith, University of Massachusetts Medical School, Worcester, MA.)
Figure 22-4. Specimens from skin-punch biopsies. A specimen obtained at the time of the patient’s first evaluation at this hospital (A) shows a focal perivascular lymphocytic infiltrate (hematoxylin and eosin, ×125). A section immunolabeled against protein gene product 9.5 to reveal neural processes or axons (thick arrows) (B) shows an epidermal neurite with axonal swellings, which are abnormal (thin arrow). The density of nerve fibers is greater than normal (immunoperoxidase, ×500). A specimen obtained 11 months later (C) shows marked reduction in neurite density and axonal swelling (arrow) in a remaining neurite (×300). (Reproduced with permission from Amato AA, Oaklander AL. Case 16–2004: A 76-year-old woman with numbness and pain in the feet and legs. N Engl J Med. 2004;350:2181–2189.)
As the name implies, the pathogenic basis of chronic, idiopathic, length-dependent sensory or sensorimotor polyneuropathy is unknown, but is likely multifactorial in etiology.19 Some may have genetic causes, while others may have a primary degenerative or immunological basis. Prediabetes is part of the metabolic syndrome, which also includes hypertension, hyperlipidemia, and obesity. Individual aspects of the metabolic syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy for those with both prediabetes and otherwise idiopathic neuropathy.54
Unfortunately, there is no treatment for slowing the progression or reversing the “numbness” or lack of sensation. Therapies are aimed at symptomatic management of neuropathic pain and reducing the risk of falling through the use of durable medical equipment.8,9,44–48 Most of the randomized controlled trials addressed patients with postherpetic neuralgia or painful neuropathy mainly caused by diabetes. A large number of such class I trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin, and opioids followed by topical lidocaine (in postherpetic neuralgia) and the newer antidepressants venlafaxine and duloxetine (in painful neuropathy).48
Our approach to treating the painful paresthesias and burning sensation associated with chronic idiopathic sensory neuropathy is uniform regardless of etiology (e.g., painful sensory neuropathies related to DM, HIV infection, and herpes zoster infection) (Table 22-3). We start off with Lidoderm 5% patches to the feet, as this treatment is associated with less systemic side effects.49 If this does not suffice (and it usually does not), our next step is to add an antiepileptic (e.g., gabapentin, pregabalin) or antidepressant (e.g., nortriptyline, duloxetine). We usually start at a low dose and gradually increase as necessary and as tolerated. A combination of an antiepileptic and antidepressant medication should be tried if monotherapy with either medication class fails. Tramadol is used to treat breakthrough pain.
TABLE 22-3. TREATMENT OF PAINFUL SENSORY NEUROPATHIES
IDIOPATHIC SENSORY NEURONOPATHY/GANGLIONOPATHYThis disorder is believed to be caused by an autoimmune attack directed against the dorsal root ganglia. The differential diagnosis of sensory neuronopathy includes a paraneoplastic syndrome, which is typically associated with anti-Hu antibodies, and a sensory ganglionitis related to Sjögren syndrome. Certain medications or toxins (e.g., various chemotherapies, vitamin B6), infectious agents (e.g., HIV), and other systemic disorders are also associated with a sensory neuronopathy. Despite extensive evaluation, many cases of sensory neuronopathy have no clear etiology, the so-called idiopathic sensory neuronopathy. The acute cases may represent a variant of GBS, although the onset can be insidiously in nature and slowly progressive.
Idiopathic sensory neuronopathy is a rare disorder that usually presents in adulthood (mean age of onset 49 years, with range 18–81 years) and has a slight female predominance.50–55 Symptoms can develop over a few hours or evolve more insidiously over several months or years, and the course can be monophasic with a stable or remitting deficit, chronic progressive, or chronic relapsing. Unlike typical GBS, only rare patients report a recent antecedent infection. The presenting complaint is numbness and tingling face, trunk, or limbs, which can be painful. Symptoms begin asymmetrically and in the upper limbs in nearly half of the patients, suggesting a ganglionopathy as opposed to a length-dependent process. Usually, the sensory symptoms become generalized, but they can remain asymmetric. Patients also describe clumsiness of the hands and gait instability. Severe autonomic symptoms develop in some.55
On examination, marked reduction in vibration and proprioception are found, while pain and temperature sensations are less affected. Manual muscle testing is usually normal. Some muscle groups may appear weak, but this is usually secondary to impaired modulation of motor activity due to the proprioceptive defect. Most patients have sensory ataxia, which can be readily demonstrated by having the patient perform the finger–nose–finger test with their eyes open and then closed. Patients may have only mild dysmetria with their eyes open, but when their eyes are closed, they consistently miss their nose and the examiner’s stationed finger. Pseudoathetoid movements of the extremities may also be appreciated. Patients exhibit a positive Romberg sign and, not surprisingly, describe more gait instability in the dark or with their eyes closed while in the shower. Muscle stretch reflexes are decreased or absent, while plantar reflexes are flexor.
A detailed history and examination are essential to exclude a toxic neuronopathy, paraneoplastic syndrome, or disorder related to a connective tissue disease (i.e., Sjögren syndrome). Importantly, the sensory neuronopathy can precede the onset of malignancy or SICCA symptoms (i.e., dry eyes and mouth); therefore, these disorders should always be kept in mind. Pertinent laboratory and malignancy workup should be ordered. A rose bengal stain or Schirmer’s test may be abnormal in patients with sicca symptoms. A lip or parotid gland biopsy likewise can be abnormal revealing inflammatory cell infiltration and destruction of the glands. Subacute sensory neuronopathy has also been associated with recent Epstein–Barr virus infection.56
The CSF protein is normal or only slightly elevated in most patients. However, the CSF protein can be markedly elevated (reportedly as high as 300 mg/dL) when examined within a few days in cases with a hyperacute onset. Only rare patients exhibit CSF pleocytosis. MRI scan can reveal gadolinium enhancement of the posterior spinal roots or increased signal abnormalities on T2-weighted images in the posterior columns of the spinal cord.55,57 Some patients have a monoclonal gammopathy (IgM, IgG, or IgA). Ganglioside antibodies, particularly GD1b antibodies, have been demonstrated in some cases of idiopathic sensory neuronopathy associated with IgM monoclonal gammopathy.58
Antineuronal nuclear antibodies (e.g., anti-Hu antibodies) should be assayed in all individuals with sensory neuronopathy to evaluate for a paraneoplastic syndrome. Likewise, antinuclear, SS-A, and SS-B antibodies should be ordered to look for evidence of Sjögren syndrome, which can also present with a sensory neuronopathy.
The characteristic NCS finding is low-amplitude or absent SNAPs in the arms, while the SNAPs in the legs may be normal,51,52,54,57 a pattern that can also be seen in sensory nerve conductions in acquired inflammatory demyelinating neuropathy. In the either case, this pattern indicates the non–length-dependent nature of these disorders. When SNAPs are obtainable, the distal sensory latencies and nerve conduction velocities are normal or only mildly abnormal. In contrast, motor NCS either are normal or reveal only mild abnormalities. In addition, H reflexes and blink reflexes are typically be unobtainable.59 An abnormal blink reflex favors a nonparaneoplastic etiology for a sensory neuronopathy but does not exclude an underlying malignancy.60 The masseter reflex or jaw jerk is abnormal in patients with sensory neuropathy but is usually preserved in patients with sensory neuronopathy.59 The masseter reflex is unique among the stretch reflexes in that the cell bodies of the afferent limb lie in the mesencephalic nucleus within the CNS. This differs from the sensory cell bodies innervating the limbs, which reside in the dorsal root ganglia of the PNS. The blink reflex can be impaired in sensory ganglionopathies, because the afferent cell bodies lie in the gasserian ganglia that are outside the CNS.
Sensory nerve biopsies may reveal a preferential loss of large myelinated or small unmyelinated fibers. Mild perivascular inflammation may be seen, but prominent endoneurial infiltrate is not appreciated. There is no evidence of segmental demyelination.
Autopsies performed in a couple of patients with acute idiopathic sensory neuronopathy have revealed widespread inflammation involving sensory and autonomic ganglia, with loss of associated neurons and wallerian degeneration of the posterior nerve roots and dorsal columns being evident in one.50 The motor neurons and roots were normal. Immunohistochemistry suggested a CD8+ T-cell mediated attach directed against sensory ganglia. In another autopsy, there was severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach’s plexus with well-preserved anterior horn cells.55 Myelinated fibers in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted.
In some cases, the sensory neuronopathies may be caused by an autoimmune attack directed against the dorsal root ganglia. Serum from affected patients immunostain dorsal root ganglia cells in culture and inhibits neurite formation.61 The neuronal epitope is unknown, but the ganglioside GD1b has been hypothesized to be the target antigen.58 GD1b localizes to neurons in the dorsal root ganglia, and antibodies directed against this ganglioside have been detected in some patients with idiopathic sensory neuronopathy.50 Furthermore, rabbits immunized with purified GD1b develop ataxic sensory neuropathy associated with loss of the cell bodies in the dorsal root ganglia and axonal degeneration of the dorsal column of the spinal cord but without demyelination or an inflammatory infiltrate.
Various modes of immunotherapy have been tried, including corticosteroids, PE, and IVIG.55,57 However, there have been no prospective, double-blind, placebo-controlled trials. Occasionally, patients appear to improve with therapy; however, some improve spontaneously and many stabilize without treatment. In our experience, most patients have not experienced a dramatic improvement following treatment. Perhaps, this is because once the cell body of the sensory neuron is destroyed, it will not regenerate. However, in patients seen in the acute setting or those who have a chronic progressive deficit, a trial of immunotherapy may be warranted.
IDIOPATHIC SMALL FIBER SENSORY NEURONOPATHYThis may represent a subtype of sensory neuropathy/ganglionopathy discussed in the preceding section but clinically only involved small fiber neurons.
Most patients with small fiber neuropathies typically present insidious with slowly progressive burning pain and paresthesia in a length-dependent fashion beginning in the feet. Most are idiopathic in nature, but DM, amyloidosis, Sjögren syndrome, and hereditary sensory and autonomic neuropathy need to be excluded. However, some individuals present with symptoms suggestive of a small fiber neuropathy that are not be length-dependent.62–64 Often the neuropathy begins acutely and an antecedent infection is common. Affected individuals often describe numbness, tingling, or burning pain in the face, trunk, or arms before or more severe than in the distal lower extremities. Patients with non–length-dependent small fiber neuronopathy may more often report an “itchy” quality and allodynia to light touch.64 Neurological examination discloses normal muscle strength and a non–length-dependent sensory loss for pain or temperature. Proprioception, vibratory perception, and reflexes are normal. The burning dysesthesia usually disappears within 4 months; however, the numbness and objective sensory loss tended to persist longer.
CSF examination may reveal albuminocytological dissociation. Motor and sensory conduction studies that primarily assess large fiber function are normal. Autonomic testing may be abnormal.
In an autopsy case, there was severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach’s plexus with well-preserved anterior horn cells.55 Myelinated fibers in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted. Skin biopsies in some patients have shown reduced nerve fiber density, which in most cases was worse in the thigh compared to calf.63
The acute clinical presentation often following an infection and CSF findings suggests that this is a rare variant of GBS.
A trial of IVIG would seem warranted in patients who present in the acute phase of the illness.
FACIAL ONSET SENSORY AND MOTOR NEURONOPATHYThis is a non–length-dependent neuronopathy/ganglionopathy that starts with loss of facial sensation and overtime also involves motor neurons.
Patients usually developed paraesthesia and numbness initially in a trigeminal nerve distribution that slowly progresses to involve sensory neurons innervating the scalp, neck, upper trunk, and upper limbs in a descending pattern.66–69 Over 5 to 10 years, dysphagia and dysarthria occur along with cramps, fasciculations and weakness, and atrophy in the arms due to slowly progressive lower motor neuron involvement. Ventilatory failure may also develop. Upper motor neuron signs do not typically appear.
NCS typically reveal reduced amplitudes or absent SNAPs in arms, while SNAPs are normal in the legs. Blink reflexes are abnormal. Subsequently, CMAP amplitudes may diminish and active denervation is apparent on EMG. MRI scans may demonstrate mild atrophy of the brainstem and spinal cord. Some patients have been reported with antisulfatide or GD1b antibodies.66
Autopsy in one patient disclosed loss of motor neurons in the hypoglossal nucleus and cervical anterior horns, along with loss of sensory neurons in the main trigeminal sensory nucleus and dorsal root ganglia.66
The pathogenic basis of facial onset sensory and motor neuronopathy (FOSMN) is unknown. The presence in some patients of autoantibodies has suggested a possible autoimmune basis. However, treatment with a variety of immunotherapies has not resulted in improvement or halt of progression, a finding which supports FOSMN being a primary neurodegenerative disorder.
Although a few patients have been reported with transient clinical benefit or subclinical improvement with immunotherapies, most continue to progress.
SUMMARYChronic idiopathic polyneuropathies are quite common in clinical practice despite extensive laboratory evaluation. A standard laboratory workup, including NCS, is important to perform before concluding that the neuropathy is idiopathic in nature. Many of the patients may have IGT, particularly those with a small fiber phenotype, if an oral GTT is performed, even if they have normal FBS and HgbA1C levels. Nerve biopsies are generally not indicated. Although skin biopsy may be informative by showing reduced epidermal nerve fibers when other studies (e.g., NCS, QST, and autonomic studies) are normal, they do not define etiology and often tell you nothing that you don’t already know based on the history and clinical examination. That is, persons with burning and tingling pain in their feet with normal reflexes and NCS probably have a small fiber neuropathy, regardless of what the skin biopsy shows. Patients need reassurance that it is not all that unusual for an etiology of neuropathy to be undetermined despite workup. Primary treatment is directed and symptomatic management of their pain.
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