Changes In Sural Nerve Research Articles

Phosphorylated α-synuclein and phosphorylated tau-protein in sural nerves may contribute to differentiate Parkinson’s disease from multiple system atrophy and progressive supranuclear paralysis

Differential diagnosis of Parkinson’s disease (PD), multiple system atrophy (MSA) and progressive supranuclear paralysis (PSP) is challenging. This study aimed to investigate the expression of phosphorylated α-synuclein (p-α-syn) and phosphorylated tau-protein (p-tau) in sural nerves from patients with PD, MSA and PSP to find biomarkers for differential diagnosis. Clinical evaluations and sural nerve biopsies were performed on 8 PD patients, 8 MSA patients, 6 PSP patients and 8 controls (CTRs). Toluidine blue staining was used to observe morphological changes in sural nerves. The deposition of p-α-syn and p-tau was detected by immunohistochemistry with semiquantitative evaluation. Locations of p-α-syn and p-tau were identified by double immunofluorescent staining. In case groups, the density of nerve fibres decreased with swollen or fragmented Schwann cells (SCs). All cases (22/22) but no CTRs (0/8) presented p-α-syn immunoreactivity with gradually decreasing semiquantitative levels among the PD (6.00 ± 2.07), MSA (5.00 ± 2.33) and PSP (3.50 ± 1.52) groups. p-tau aggregates were found in 7/8 MSA (1.88 ± 1.46) and 6/6 PSP (1.67 ± 0.52) patients but not in PD patients or CTRs. There were different expression patterns of p-α-syn and p-tau in PD, MSA and PSP patients. These findings suggest that peripheral sensory nerve injury exists in PD, MSA and PSP patients. With a different expression pattern and level, p-α-syn and p-tau in sural nerves may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP.

Macroscopic changes in sural nerve after gastrocnemius recession: a cadaver study

BackgroundGastrocnemius recession is a common foot and ankle procedure and various techniques that have been utilized are mainly delineated by the anatomic position of the gastrocnemius transection; the 2 common ones are the Baumann and Strayer procedure. Both can adversely affect the sural nerve. The objective of this study was to evaluate the macroscopic changes in the sural nerve following gastrocnemius recession, and to compare the efficacy of the two procedures, regarding the improvement of maximal ankle dorsiflexion. MethodsTen fresh-frozen, above knee cadaveric legs were assigned to one of two gastrocnemius recession techniques: Baumann (n = 5) or Strayer (n = 5). A goniometer was used to measure degree of ankle dorsiflexion before and after the surgery. The sural nerve was meticulously dissected and marked with two suture knots, 2 cm apart. The ankle was passively dorsiflexed from 90° to maximal dorsiflexion in 5° degree increments, and the distance between two suture knots was measured at each increment. The distance between the two cut ends of gastrocnemius muscle was measured with the ankle at 90° and at maximal dorsiflexion. ResultsOverall, a mean increase in length between the suture knots on the sural nerve was 0.2 cm, from 90° to maximum ankle dorsiflexion (130°); both the Baumann and Strayer techniques resulted in 0.2 cm increase. The mean improvement in maximal ankle dorsiflexion in the Baumann and Strayer group was 22.6° and 22°, respectively. The mean change in distance between the two cut ends of the gastrocnemius muscle in the Baumann and Strayer group was 1.0 cm and 0.9 cm, respectively. ConclusionIncreased dorsiflexion of the ankle following Strayer or Baumann gastrocnemius recession resulted in similar macroscopic change in the sural nerve, which may contribute to the development of sural neuritis. Further clinical studies are warranted to assess clinical implications of these findings.

Activated Schwann cells and increased inflammatory cytokines IL-1β, IL-6, and TNF-α in patients' sural nerve are lack of tight relationship with specific sensory disturbances in Parkinson's disease.

AimsNeuroinflammation is one of the most important processes in the pathogenesis of Parkinson's disease (PD). Sensory disturbances are common in patients with PD, but the underlying pathophysiological mechanisms remain unknown. This study aimed to characterize the activation of Schwann cells (SCs) and the increase of expression of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α in the sural nerve of PD, and further explore whether peripheral nerve inflammation is the cause of PD sensory disturbances.MethodsA total of 14 patients with PD (including 5 with sensory disturbances and 9 without sensory disturbances) and 6 controls were included. The excitation and conduction function of sural nerve was detected by sural nerve electrophysiological examination. With sural nerve biopsy samples, ultrastructural changes of sural nerve were observed by electron microscopy; Schwann cell biomarker glial fibrillary acid protein (GFAP) and inflammatory cytokines including interleukin‐1beta (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) were detected by immunohistochemistry, and the outcome of immunostaining slice was semiquantitatively counted; double immunofluorescence was used to identify the locus immunoreactive for inflammatory cytokines.ResultsCompared with healthy controls, nerve conduction velocity (NCV) slowed down and sensory nerve action potential (SNAP) amplitude decreased in PD patients, accompanied by axonal degeneration and demyelinating lesions, and expression of GFAP and inflammatory cytokines was increased. Inflammatory cytokines were significantly colocalized with GFAP and slightly colocalized with NF. These indicators did not differ significantly between PD patients with and without sensory disturbances.ConclusionOur study results suggest that peripheral sensory nerve injury exists in PD patients, accompanied by Schwann cell activation and inflammation, thus demonstrate peripheral nerve inflammation participates in the pathophysiological process of PD but it is not necessarily related to the patient's sensory disturbance.

NOX, NOX, Are You Here? The Emerging Role of NOX5 in Diabetic Neuropathy

Diabetic neuropathy (DN) is one of the most common complications of diabetes worldwide, affecting up to 60% of all diabetic patients. Although the pathogenesis of DN is poorly understood, it is widely accepted that reactive oxygen species (ROS) mediate in part the cellular and molecular injury observed in DN. NADPH oxidase (Nox) enzymes generate ROS and of the 7 isoforms, NOX5 is present only in man. In this study, we aimed to investigate a role for NOX5 in DN by identifying the cellular localization, methylation status and expression levels of NOX5 in cutaneous nerve fibers and sural nerve biopsies of diabetic patients. Cellular localization of NOX5, myelin basic protein (MBP) and protein gene product (PGP) 9.5 were determined in cutaneous nerve fibers of controls and subjects with DN. NOX5 methylation status and protein levels were assessed in subjects with DN that were divided into two groups based on changes in sural nerve myelinated fiber density: regenerators (showing significant nerve regeneration) and degenerators (showing significant nerve degeneration). NOX5 expression was present in deep myelinated cutaneous fibers. Bisulfite sequencing revealed that the NOX5 promoter, enriched with CpG sites, is hypomethylated in sural nerve biopsies of the degenerator cohort compared to the regenerator. The increase in NOX5 expression in degenerator sural nerves was accompanied with a decrease in MBP levels relative to the regenerator group. Our results highlight that in subjects with DN with sural nerve degeneration, there is hypomethylation of the NOX5 promoter associated with an increase in its protein expression, suggesting a potential epigenetic and mechanistic role of NOX5 in DN. Disclosure S. Eid: None. J.M. Hayes: None. K. Guo: None. C. Pacut: None. F. Mendelson: None. J. Hur: None. E.L. Feldman: None.

T30. Sural nerve conduction studies in differentiation of hereditary and inflammatory demyelinating polyneuropathies

Introduction Nerve Conduction Studies (NCS) are invaluable tools for diagnosis and classification of polyneuropathies. However, differentiation of different types of demyelinating polyneuropathies may sometimes be difficult. Detection of demyelination and differentiation of inflammatory and hereditary polyneuropathies are mainly based on motor NCS. We aimed in this study to examine the role of sural nerve sensory NCS in differentiation of inflammatory and hereditary polyneuropathies. Methods Nineteen patients with chronic demyelinating polyneuropathy (CIDP), 16 patients with Guillain Barre syndrome (GBS) and 23 patients with hereditary motor sensory neuropathy with PMP22 duplication were included. In all patients, sural nerve was examined unilaterally or bilaterally with surface electrodes (13 patients) or near nerve technique (45 patients). In case of bilaterally examined sural nerves, right side was chosen for analysis. Results were compared to laboratory controls. The pathophysiological state of sural nerve was classified as normal, axonal loss or demyelinating according to ESTEEM criteria (Tankisi et al., 2005). Results The mean conduction velocity (CV) was higher in CIDP (42.6 ± 5.6) and GBS (46.5 ± 8.1) than patients with PMP22 duplication (22.5 ± 5.3) (p 35 m/s). Sural NCS showed demyelination in all patients with PMP22 duplication and in 2 GBS whereas none of the CIDP patients had demyelination of the sural nerve. Normal sural nerve was seen in 10 GBS and in 5 CIDP patients whereas sural NCS showed axonal loss in 4 GBS and in 14 CIDP. Conclusion Sural NCS may help in differentiation of inflammatory and hereditary demyelination polyneuropathies. Demyelinating changes in sural nerve are characteristic for PMP22 duplication whereas axonal loss is mostly seen in CIDP and normal sural nerve NCS in GBS.

Preliminary study of hyperfrequency ultrasound in patients with the diabetic cutaneous nerve neuropathy

Objective To evaluate the morphological changes of sural nerve in patients with type 2 diabetes mellitus by hyperfrequency ultrasound.Methods Fifty-six sural nerves of symptomatic group,64 sural nerves of asymptomatic group,and 60 sural nerves of control group were identified by 22 MHz Ultrasound.The thickness/width (T/W) ratio,cross-sectional areas (CSA) and the maximum thickness of neuronal fascicles (MT) of the sural nerve were calculated in transverse sonograms.Results ①Ultrasound can clearly show these structures of sural nerve such as epineurium,perineurium and nerve bundles and so on.②In symptomatic group,asymptomatic group and control group,T/W ratio and MT were gradually increased,and the differences among the three groups were statistically significant (P＜0.05).Whereas,there were no statistically significant differences in CSA among the three groups (P=0.257).Conclusions22 MHz ultrasound may be a valuable tool in evaluating the diabetic cutaneous nerve neuropathy Key words: Ultrasonography; Diabetes mellitus; Sural nerve

Long-Term Treatment With Ranirestat (AS-3201), a Potent Aldose Reductase Inhibitor, Suppresses Diabetic Neuropathy and Cataract Formation in Rats

We investigated the chronic functional and histopathological changes in the sciatic nerve and lens of streptozotocin (STZ)-diabetic rats and evaluated the preventive effects of ranirestat (AS-3201), a potent aldose reductase inhibitor, on these changes. Sorbitol levels in the sciatic nerve and lens, motor nerve conduction velocity (MNCV), and development of cataracts were measured in STZ-diabetic rats given a ranirestat-admixed diet (0.0005%) for 35 weeks. Ranirestat reduced sorbitol accumulation in the sciatic nerve and improved the decrease in MNCV of STZ-diabetic rats. Morphological and morphometric examination of changes in sural nerve revealed that treatment with ranirestat prevented both the deformity of myelinated fibers and the decrease in their axonal and myelin areas (atrophy). Ranirestat also averted the changes in the size frequency histogram of myelinated fibers. Finally, STZ-diabetic rats developed early lens opacities 8 weeks after STZ injection and had cataract by the end of the experimental period. However, in the ranirestat-treated diabetic rats, no lens opacity was observed in any rat throughout the entire experimental period. This study suggests that the polyol pathway plays an important role in the progress of diabetic neuropathy and cataract formation in STZ-diabetic rats. Ranirestat should be a promising agent for the treatment of complications associated with diabetes, especially neuropathy.

A clinical, electrophysiological, and pathological study of neuropathy in rheumatoid arthritis

Neuropathy in rheumatoid arthritis (RA) may result secondary to entrapment, vasculitis, and drug toxicity. We aimed to study clinical and electrophysiological neuropathy and pathological changes in sural nerve in patients with RA. One hundred eight patients of RA, fulfilling American College of Rheumatology 1987 criteria (mean age, 45.83 years; M/F 1:3, 80.3% seropositive) were examined clinically and electrophysiologically for evidence of peripheral neuropathy. Sural nerve biopsies were performed in the involved cases. In all RA patient medications, disease activity, results of blood tests, and X-rays of affected joints were recorded. Twenty-three patients complained of paresthesias in the extremities. Vibration sensations were decreased in 9, and tendon reflexes were decreased or absent in 28 patients. Sixty-two (57.4%) patients had electrophysiologic evidence of neuropathy. Of these 53 (85.5%) patients had pure sensory or sensory motor axonal neuropathy (mononeuritis multiplex, n = 7), while 9 (14.5%) had demyelinating neuropathy (chronic inflammatory demyelinating polyneuropathy, n = 1). Carpal tunnel syndrome was seen in 11 (10.1%) patients (associated with neuropathy in 6). Of 23 sural nerve biopsies available, perineurial thickening (n = 5, amyloid deposits n = 4), perivascular lymphomononuclear cell infiltrate (n = 4), loss of myelin fibers (n = 2), and necrotizing vasculitis (n = 1) were found. Clinically, however, seven patients had evidence of cutaneous vasculitis. Comparing the clinical characteristics of the patients with or without electrophysiological neuropathy, absence of deep tendon jerks (p < 0.005) and presence of extra articular manifestations (p < 0.01) were conspicuous in the neuropathic group. There was no relation of neuropathy with the duration of RA, seropositivity, joint erosions, joint deformities, prior disease-modifying anti-rheumatic drugs or glucocorticoid intake, and 28-joint disease activity score. Neuropathy in RA was mostly subclinical and predominantly axonal. Pathologically, neuropathy secondary to amyloid infiltration was second only to vasculitic neuropathy. Absence of deep tendon jerks and presence of vasculitis were more commonly observed in patients with neuropathy.

Expression of capsaicin receptor immunoreactivity in human peripheral nervous system and in painful neuropathies

We describe the expression of the capsaicin receptor (TRPV1) in human peripheral nervous system (PNS) and its changes in sural nerve and skin nerve fibers of patients with painful neuropathy. Dorsal root ganglion (DRG), root, and spinal cord autopsy specimens from subjects without PNS diseases were immunoassayed with anti-TRPV1 antibodies. Bright-field and confocal microscope studies using anti-TRPV1, protein gene product 9.5 (PGP 9.5), and unique-beta-tubulin (TuJ1) antibodies were performed in skin biopsies from 15 healthy subjects and 10 painful neuropathies. The density of intraepidermal nerve fiber (IENF) labeled by each antibody was quantified. Sural nerve biopsies from three patients with painful, one patient with nonpainful diabetic neuropathy, and two patients with multifocal motor neuropathy used as controls were immunoassayed with anti-TRPV1 antibodies and investigated by immunoelectron microscopy. TRPV1 strongly labeled laminae I and II of dorsal horns, most small-size and some medium-size DRG neurons, and small-diameter axons of dorsal roots. In sural nerve, TRPV1 was expressed within the cytoplasm of most unmyelinated and some small myelinated axons, in the muscular lamina of epineural vessels, and in the endothelium of endoneurial vessels. The density of IENF labeled by TRPV1, PGP 9.5, and TuJ1 did not differ. TRPV1 colocalized with TuJ1 in all IENF and dermal nerve bundles. Painful neuropathies showed a diffuse loss of TRPV1-positive axons both in the sural nerve and in the skin. Our findings demonstrated that TRPV1 is normally expressed throughout the nociceptive pathway of PNS and that TRPV1-positive peripheral nerve fibers degenerate in painful neuropathies.

Sensory-predominant, painful, idiopathic neuropathy: inflammatory changes in sural nerves.

Sensory-predominant, painful, idiopathic neuropathies are a common clinical problem. In this retrospective study of 11 patients with such a neuropathy, we found axonal loss in 9, with multifocal axonal loss in 4 patients; there were large perivascular mononuclear inflammatory infiltrates (>50 cells) in 4 and smaller infiltrates (10-20 cells) in 4. These findings suggest that some cases of this neuropathy may be due to autoimmune vasculopathy and therefore may respond to immunotherapy.