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Background Multiple mononeuropathy is a rare presentation of primary (AL) amyloidosis and nerve biopsy is usually needed for diagnosis. Conventional imaging is useful to identify proximal nerve involvement but may be inadequate. We report a patient with multiple mononeuropathy whose presentation was suggestive of AL amyloid neuropathy and in whom repeated tissue biopsies were negative for amyloid (including two sensory nerves and one muscle). Methods The patient underwent magnetic resonance imaging (MRI) and whole body 18 F-florbetapir positron emission tomography (PET)/MRI. Results Whole body 18 F-florbetapir PET/MRI revealed abnormal low-level florbetapir uptake in the right proximal tibial and peroneal nerves, which provided a target for a sciatic bifurcation fascicular nerve biopsy that was diagnostic of AL amyloidosis. Conclusions 18 F-florbetapir PET/MRI imaging is a promising diagnostic tool for patients with suspected peripheral nerve amyloidosis (including multiple mononeuropathy) in whom conventional imaging and nerve and muscle biopsies miss the pathology.

ObjectiveTo define the clinicopathologic features of amphiphysin-immunoglobulin G (IgG)–mediated neuropathy.MethodsPatients examined at our institution from January 1, 1995, to September 30, 2018, with amphiphysin-IgG by indirect immunofluorescence and Western blot, were reviewed. Their phenotypes were compared to cases of coexisting collapsin response-mediator protein-5 (CRMP5)–IgG or anti-neuronal nuclear antibody type 1 (ANNA1-IgG) and CRMP5-IgG autoimmunity. Improvement in modified Rankin Scale (mRS) (≥1) on follow-up was considered a favorable outcome. Amphiphysin RNA expression was assessed in healthy nerves.ResultsFifty-three amphiphysin-IgG–positive cases were identified. Of 33 (60%) patients with neuropathy, 21 had amphiphysin-IgG alone, and 12 had coexisting autoantibodies (ANNA1-IgG, n = 8; CRMP5-IgG, n = 2; ANNA1-IgG and CRMP5-IgG, n = 2). The neuropathies in isolated amphiphysin-IgG autoimmunity included polyradiculoneuropathy (62%), diffuse sensory neuronopathy (35%), and facial neuropathy with gastroparesis (3%). Among these, pain (80%), breast cancer (63%), and CNS (57%) involvements commonly coexisted, and neuropathy frequently prompted breast cancer diagnosis (76%). Stiff-person spectrum disorder was the most common CNS accompaniment (45%). Nerve biopsies showed axonal loss (n = 6/6), subperineurial edema (n = 4/6), and CD4 predominant inflammation (n = 2/6). Median mRS score at last follow-up was 3.5; 58% of patients were immunotherapy-responsive. Patients with amphiphysin-IgG alone had more favorable immunotherapy response than patients with CRMP5-IgG polyneuropathy (n = 45) (44% vs 16%, p = 0.028, odds ratio 4.2, 95% confidence interval 1.1 to 15.5). Only 1/9 (11%) patients with amphiphysin-IgG with coexisting CRMP5-IgG or ANNA1-IgG had immunotherapy response. RNA amphiphysin expression occurred at low levels in nerve.ConclusionAmphiphysin-IgG autoimmune neuropathy has a recognizable phenotype, is frequently immune responsive, and can prompt early diagnosis of breast cancer.

We describe a 51-year-old woman who over 5 years had 9 painful monophasic attacks affecting the brachial plexus before a fascicular plexus biopsy diagnosed large B-cell lymphoma. The initial attacks were responsive to steroids with clinical resolution. At last attack, magnetic resonance imaging showed multifocal T2 hyperintensities and nodular gadolinium enhancement in the right brachial plexus not seen previously. Also seen were similar changes in the thoracic spinal cord, basal ganglia, cerebellum, and brainstem. Positron emission tomography revealed marked hypermetabolic activity of the plexus facilitating targeted fascicular brachial plexus biopsy, making the pathological diagnosis. Neurolymphomatosis affecting the peripheral nervous system typically presents with insidious painful progressive infiltration of nerves, roots, or plexi. Recurrent idiopathic brachial neuritis attacks (ie, Parsonage-Turner syndrome) in contrast most commonly are seen in persons with a family history and a discoverable genetic cause by SEPT9 mutations, which tested negative in this patient. This case illustrates how neurolymphomatosis, which represents a malignant transformation of B cells within peripheral nerves, can sometimes present with paraneoplastic immune-responsive neuritis mimicking Parsonage-Turner syndrome. Recurrence, an immune-refractory course or insidious progressive involvement of the nervous system, should raise suspicion of neurolymphomatosis.

Introduction: Voltage-gated Kv1 potassium channel-complex (VGKC) autoantibodies subtyped for leucine-rich-glioma-inactivated-1 (LGI1), contactin-associated-protein-like-2 (CASPR2), and Kv-IgGs have a spectrum of neurological presentations. Painful polyneuropathy is seen in some patients, but nerve pathology descriptions are lacking. Methods:Clinicopathologic features were studied in subtyped VGKC-autoantibody seropositive patients who had undergone nerve biopsies. Results:Five patients were identified, 1 LGI1-IgG-positive, 1 CASPR2-IgG-positive; all negative for Kv1.1,1.2,1.6 subtyped IgG-autoantibodies. Median symptom duration was 17 months. Pain was the predominant symptom; 3 had mild sensory loss and/or weakness. Histopathological abnormalities were limited to axonal loss in 3. None had mononuclear cellular infiltrates. Electron-micrographs revealed no interstitial abnormalities. Three patients reported marked improvement in pain with immunotherapy. Discussion:The nerve biopsy histopathology of patients subtyped for LGI1 and CASPR2-IgGs within the VGKC-complex spectrum disorders shows either normal density or axonal fiber loss without inflammatory infiltrates. A reversible neural hyperexcitabile mechanism is considered as a cause of this painful polyneuropathy. This article is protected by copyright. All rights reserved.

Introduction: Distal acquired demyelinating symmetric (DADS) neuropathy is a distal variant of chronic inflammatory demyelinating polyradiculoneuropathy. It is characterized by chronic distal symmetric sensory or sensorimotor deficits. Sensory ataxia is a common clinical presentation. Nerve conduction studies typically show markedly prolonged distal motor latencies. Methods: We report 2 patients with chronic progressive generalized pain and fatigue, with normal neurological examinations except for allodynia. Results: Nerve conduction studies were typical of DADS neuropathy. Monoclonal protein studies were negative. Cerebrospinal fluid protein levels were elevated. Sural nerve biopsies revealed segmental demyelination and remyelination. One biopsy had marked endoneurial and epineurial lymphocytic infiltration. Immunomodulatory therapy alleviated the pain and fatigue and markedly improved distal motor latencies in both patients. Conclusions: DADS neuropathy can present with pain and a normal neurological examination apart from allodynia. Nerve conduction studies are necessary for diagnosis. These patients respond to immunotherapy better than typical DADS neuropathy patients with sensory ataxia. Muscle Nerve 54: 973–977, 2016

ObjectiveTo describe an expanded teased nerve fibre classification in disease association.MethodsWe reviewed four newly proposed teased nerve fibre types (Types J–M): Type J, rope-like fibres; K, fibril-like clumps of osmium positivity; L, cellular debris along and within nerve fibres; M, circular axonal inclusions surrounded by thin myelin. Different clinical pathological entities were studied for these fibre types including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP: N=20); amyloid polyneuropathy (N=20); intraneural B-cell lymphoma (N=20) or adult-onset polyglucosan body disease (APBD: N=6) in comparison with 112 disease controls. Student’s t-test was used to test significance of association between the identified fibre types and the specific clinical diagnosis.ResultsEach fibre type significantly associated (pType J, 60% of CIDP cases; Type K, 75% of amyloid cases; Type L, 75% of intraneural lymphoma cases; Type M, 100% of APBD cases. Rarely were these fibres found in the other disease control cases ≤3% of cases. In three cases, the teased fibre findings were so striking additional paraffin nerve preparations were made to make the pathological diagnosis when initial paraffin sections were non-diagnostic.ConclusionsTeased nerve fibre Types J–M associate with commonly seen pathological diagnosis and are helpful in the consideration of specific neuropathy diagnoses.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a mutation in the alanine-glyoxalate aminotransferase (AGXT) gene which encodes the hepatic enzyme alanine-glyoxylate aminotransferase (AGT). AGT is responsible for converting glyoxylate into glycine. When the enzyme is deficient or defective, glyoxylate accumulates and is converted to oxalate. Oxalate cannot be metabolized and is excreted by the kidneys 4. In PH1, high urinary levels of oxalate lead to kidney stones and deposition of calcium oxalate crystals within the renal tubules and parenchyma, which results in progressive renal fibrosis. As kidney function declines, oxalate production increasingly exceeds renal oxalate clearance. Plasma oxalate levels rise, and insoluble calcium oxalate crystals are deposited in tissues throughout the body, including the kidney, heart, bone, blood vessels, retina, muscle, skin, and nerve. Hemodialysis is needed to remove oxalate from the body, but removal is incomplete, and even when it is intensive, dialysis is often insufficient to prevent progressive systemic oxalate deposition 5,6,7. Because oxalate removal with dialysis is incomplete, the treatment of choice for patients with PH1 and poor kidney function, is combined liver/ kidney transplantation. Liver transplantation is required in the majority of PH type 1 patients to restore the hepatic enzyme defect and protect the renal allograft from recurrent oxalate nephropathy. Significant neurologic improvement in patients with neuropathy has been noted following combined liver and kidney transplantation 8. Only a few case reports have described the nerve pathology associated with primary hyperoxaluria type 1. Demyelination (particularly at the internodes) and axonal degeneration have been reported,1 and some case reports describe crystals in nerve 1,3. The characterization and location of these crystals within nerve has not been well described, and their pathological significance has remained unclear 1,3. In each of these case reports, the patient had significant systemic oxalosis with deposition of oxalate into multiple tissues, whereas the patient we describe had oxalosis affecting peripheral nerve preferentially without other clinically discernible extrarenal manifestations. Approval by our Institutional Review Board and Biospecimens Committee was received for this study.

Importance Erythromelalgia is a clinical diagnosis based on intermittent warmth, erythema, and pain in the distal extremities. One problem facing physicians is how to objectively test for this disease. Given that other painful conditions of the distal extremities (ie, neuropathy related to human immunodeficiency virus, diabetes, or Fabry disease) can be evaluated with a skin biopsy to visualize pathologically decreased densities of the small nerve fibers that innervate the epidermis, one hypothesis is that erythromelalgia could similarly be associated with a loss of epidermal nerve fiber density (ENFD). Objectives To examine whether erythromelalgia is associated with a structural loss of small fibers using the ENFD technique and to compare this with functional studies of small nerve fibers. Design, Setting, and Participants In a retrospective study of 52 consecutive patients with erythromelalgia who were seen between September 1, 2010, and September 22, 2015, patients were interviewed and examined and their conditions clinically diagnosed by a board-certified dermatologist at a large tertiary referral center, where ENFD testing became a routine part of evaluating erythromelalgia in 2010. Thus, all 52 consecutive patients were included solely based on their clinical diagnosis of erythromelalgia. For quantification of ENFD, observers were masked to all patient information except for name and clinic number. Main Outcomes and Measures The hypothesis that patients with erythromelalgia would have decreased ENFD was formulated before data collection. Epidermal nerve fiber density, the primary outcome, is a measurement of the density of small nerve fibers within the epidermis. Secondary measures included functional small fiber evaluation, such as autonomic (heart rate, blood pressure, and sweat testing) and subjective testing of pain. Results In this cohort study, 52 consecutively seen patients were identified (female, 42 [80%]; median age, 44 years; age range, 13-82 years). Whereas only 5 of 52 patients (10%) had ENFD at or below the fifth percentile of healthy control individuals, most patients had functional abnormalities of these small fibers; 29 patients (60%) had abnormal sweat test results, 21 (42%) had abnormal pain thresholds, and 20 (38%) had abnormal blood pressure or heart rate control. Conclusions and Relevance Unlike other diseases of the small nerve fibers that cause acral pain syndromes, erythromelalgia is not characterized by loss of ENFD. However, most patients have impaired function of these small fibers. Physicians would benefit from performing functional rather than structural small fiber studies when evaluating erythromelalgia.

Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke).

We report a patient who developed subacute facial-predominant numbness and anhidrosis, oral incoordination, and esophageal achalasia with resultant cachexia. Great auricular nerve biopsy showed extensive epineurial perivascular inflammatory infiltrates. Sensation, sweating, and swallowing improved with pulse intravenous methylprednisolone given over 5 years. We suggest that the patient's deficits, including achalasia, were due to an immune-mediated sensory and autonomic neuropathy and that, in such cases, pathologic studies of the great auricular nerve may be diagnostically informative.

Provided is an overview of the pathology, clinically defining features, and subcategorization of peripheral nerve amyloidosis. This condition is pathologically hallmarked by infiltrative amyloid deposition in varied peripheral neural tissue localizations with associated clinical manifestations. Peripheral nerve involvement is a frequent presenting feature of systemic amyloidosis (Kyle et al., Peripheral Neuropathies, Saunders, Philadelphia, PA, 2,427–2,451, 2005). As with other organ systems, the diagnosis of amyloid involvement of peripheral nerve is often delayed because the clinical features may mimic many varieties of peripheral neuropathy. Therefore, pathologic discovery of unsuspected amyloidosis is common. The particular amyloid protein can determine the clinical course and preferred treatment modality, as well as potentially alert patients to familial predisposition. Advances in laboratory technology, including most notably mass spectrophotometric evaluation of nerve, continue to improve the accuracy and sensitivity of amyloid subtyping (Adams, J Neurol 248(8), 2001; Benson and Kincaid, Muscle Nerve 36(4), 2007; Klein et al. Arch Neurol 68(2), 2011). Appropriate directed peripheral neural biopsy can therefore be instrumental in identifying the diagnosis providing the specific amyloid type, informing prognosis, and directing care in each case.

In rats with streptozin-induced diabetes mellitus, the caliber of distal myelinated fiber (MF) axons in relation to the number of myelin lamellae is smaller than in controls. This finding usually has been attributed to axonal atrophy, but shrinkage or maldevelopment has also been considered. For human diabetic polyneuropathy (DP), axonal atrophy has been assumed by some investigators, but convincing evidence has not been demonstrated. We morphometrically evaluated transverse sections of 33 sural nerves from carefully evaluated diabetic patients > or = 30 years old without (8 patients) or with (25 patients) DP and compared them with 24 nerves from healthy subjects > or = 30 years old. Nerves from diabetic patients and controls were obtained under identical conditions and processed and evaluated in the same way, using an observer blind to the disease condition. Using computer digitization of electron micrographs, we evaluated the axonal area, perimeter, index of circularity, number of myelin lamellae, and frequency of adaxonal sequestration of 50.4 (mean) +/- 5.8 (SD) MF per sural nerve for healthy subjects and diabetic patients > or = 30 years old. The regression lines of the natural log (In) of axonal area on number of myelin lamellae of diabetic patients (with or without DP) were not significantly different from the regression lines of nerves of healthy subjects for large MFs-the most reliable group in which to recognize atrophy. Likewise, the regression lines of index of circularity (IC) (an index that is decreased with atrophy or shrinkage) on number of myelin lamellae for large fibers was not significantly different between the disease and control groups. The rate of adaxonal sequestration was not significantly higher in DP than in healthy subjects. These results do not support the hypothesis that axonal atrophy occurs in human DP. For small MF, or all MF, some significant differences in regression lines of In axonal area or IC on number of lamellae were found, but these changes are probably explained by events of remyelination and axonal regeneration, which can affect these relationships and are known to occur in DP.

We present the case of a 67-year-old man with a malignant peripheral nerve sheath tumor (MPNST) affecting the brachial plexus. He presented with progressive right upper extremity paresthesias, numbness, weakness, and severe pain. Nerve conduction studies/electromyography demonstrated a right lower and middle trunk predominant brachial plexopathy. Three-tesla magnetic resonance imaging of the brachial plexus showed a soft tissue mass with central necrosis and cystic changes and irregular contrast enhancement. Positron emission tomography showed increased fluorodeoxyglucose uptake within the mass. Targeted fascicular nerve biopsy revealed hypercellular tumor, featuring atypical cells with mitotic figures and limited immunoreactivity for S-100 protein. The findings were those of an MPNST. The effects on the variably involved fascicles were also seen in teased fiber preparations, paraffin sections, and through immunohistochemistry. This case illustrates the presentation of this rare type of tumor, and characteristic neuroimaging and pathologic features of MPNSTs.

Many varieties of neuropathy occur with diabetes mellitus (DM) from different underlying mechanisms, the most common being a symmetrical, length-dependent, sensorimotor polyneuropathy (DSPN). A less frequent diabetic neuropathy which can cause severe morbidity, diabetic lumbosacral radiculoplexus neuropathy (DLRPN), is a painful, rapidly evolving, asymmetric, lower-limb, paralytic neuropathy associated with weight loss1. The name DLRPN emphasizes the association of this syndrome with DM and its sites of involvement (roots, plexus and nerves). The natural history and underlying mechanisms of DLRPN have been debated with various names reflecting different views that include: diabetic myelopathy2, diabetic amyotrophy3, Bruns-Garland syndrome4, diabetic mononeuritis multiplex5, proximal diabetic neuropathy6, diabetic lumbosacral plexopathy7, diabetic polyradiculopathy8 and multifocal diabetic neuropathy9. Regardless, in most discussions of DLRPN, pain is usually present. In early clinical descriptions of DLRPN, Chokroverty and colleagues state that this syndrome can be symmetrical, slowly progressive and occasional painless10. They and others suggest that the pathological basis of DLPRN is probably metabolic derangement10–13. Others note that the disease is usually asymmetrical and painful, presenting as a “mononeuritis multiplex” due to ischemic injury5. Asbury incorporates both concepts proposing that the acute and asymmetrical cases are due to ischemic injury whereas the slower, more symmetrical cases result from metabolic derangement and that “proximal (motor) diabetic neuropathy” encompasses a spectrum of disorders6. Additional authors note that cases of purely proximal diabetic motor neuropathies exist, but are poorly defined14. Recent studies report ischemic injury from microvasculitis as the pathophysiological basis of typical, painful, DLPRN1, 15–19. In contrast, diabetic patients with lower limb motor syndromes without pain have received little attention. Amato and Barohn highlight that motor polyradiculoneuropathies without pain do occur in DM20. Although they consider this painless syndrome could be a type of DLRPN, they question whether such cases are chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) occurring in diabetic patients, an association also suggested by others21–24. Their discussion rekindles interest into how to best classify diabetic patients with a motor predominant painless neuropathy. However, there has been no systematic evaluation of the clinical, electrophysiological, and pathological features of this painless syndrome. Here, we study a cohort of diabetic patients with a lower limb and motor predominant neuropathy without pain and compare this group to a cohort of previously studied DLRPN patients1. In order to formally answer if painless diabetic motor neuropathy is a variant of DLPRN, diabetic CIDP, or another entity, we ask 1) What are the clinical features of this painless syndrome? 2) What are the laboratory and electrophysiological findings? 3) What are the pathological features? As we believe the classification should be primarily based on the underlying disease mechanism, we place the most emphasis on pathological findings in this group compared to nerve biopsies from DLRPN, DSPN and CIDP.

We present a case of a 60-year-old man with mild type 2 diabetes mellitus and step-wise progression of bilateral lower limb weakness, numbness, and pain over a 1-year period. At the time of evaluation, he used a walker. He had elevated cerebrospinal fluid protein, abnormal cooling and heat-pain thresholds on quantitative sensory testing, and nerve conduction studies/electromyography consistent with bilateral lumbosacral radiculoplexus neuropathies. Because it was not clear whether the disease was still active, a right superficial peroneal nerve biopsy was performed and showed evidence of active axonal degeneration, ischemic injury, and microvasculitis. On the basis of these results, the patient was diagnosed with diabetic lumbosacral radiculoplexus neuropathy and was treated with weekly intravenous methylprednisolone with marked improvement of neurologic symptoms and signs. This case illustrates the typical clinical, electrophysiologic, and pathologic features of diabetic lumbosacral radiculoplexus neuropathy and the utility of nerve biopsy to judge ongoing disease activity.

Whether compression nerve injury is due to ischemia, direct mechanical injury, or both remains unsettled. To assess structural changes of nerve during compression, peroneal nerves of rats were compressed at various pressures for different times, and the structural alterations were stopped by simultaneous in situ and perfusion fixation. The structural changes observed during a few minutes of compression cannot be explained by ischemic injury because the pathologic alterations characteristic of ischemia take many hours to develop and in any case are different from the ones found here. The pressure- and time-related structural changes observed in the present study under the cuff were (i) decrease in fascicular area and increase in fiber density due to expression of endoneurial fluid; (ii) compression and expression of axoplasm, sometimes to the point of fiber transection; (iii) lengthening of internodes; and (iv) obscuration of nodes of Ranvier due to cleavage and displacement of myelin and overlapping of nodes by displaced loops of myelin. At the edges of the cuff the changes were (i) increase of fascicular area probably from expressed endoneurial fluid; (ii) widening of nodal gaps, perhaps mainly from translocated axonal fluid; and (iii) disordered structure of axoplasm. We suggest that the process of paranodal demyelination and axonal transection are linked, occur during the act of compression, and are due to shear forces. The initial event is expression of endoneurial fluid, followed by compression and expression of axoplasm and cleavage and displacement of layers of myelin. Conceivably, with prolonged cuff compression ischemic injury might be found to be superimposed on mechanical injury.

Background: Chronic inflammatory neuropathies can present with a sensory ataxia due to involvement of dorsal root ganglia (DRG) or sensory nerves. Selective inflammatory involvement of sensory nerve roots proximal to the DRG has been postulated. Methods: The authors identified 15 patients with a sensory syndrome and normal nerve conduction studies. Sensory nerve root involvement was suggested by either somatosensory evoked potential (SSEP) or imaging abnormalities. CNS disease was excluded. Results: All patients had gait ataxia, large fiber sensory loss, and paresthesias, and nine had frequent falls. The disease course was chronic and progressive (median duration 5 years, range 3 months to 18 years). Sural sensory nerve action potential amplitudes were preserved and SSEP abnormalities were consistent with sensory nerve root involvement. Five patients had enlargement of lumbar nerve roots on MRI with enhancement in three. The CSF protein was elevated in 13 of 14 patients tested. Three patients had lumbar sensory rootlet biopsies that showed thickened rootlets, decreased density of large myelinated fibers, segmental demyelination, onion-bulb formation, and endoneurial inflammation. Six patients who required aids to walk were treated with immune modulating therapy and all had marked improvement with four returning to normal ambulation. Conclusion: Based on the described clinical features, normal nerve conduction studies, characteristic somatosensory evoked potential (SSEP) abnormality, enlarged nerve roots, elevated CSF protein, and inflammatory hypertrophic changes of sensory nerve rootlet tissue, we suggest the term chronic immune sensory polyradiculopathy (CISP) for this syndrome. This condition preferentially affects large myelinated fibers of the posterior roots, may respond favorably to treatment, and may be a restricted form of chronic inflammatory demyelinating polyradiculoneuropathy.

To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament.