Peripheral Nerves In Patients Research Articles

Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRβ clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

Three-dimensional magnetic resonance neurography aids in detection of brachial plexus nerve root signal and size alterations in patients with amyotrophic lateral sclerosis: a case-control study.

Since previous histopathological studies have shown a distal to proximal gradient of axonal damage in peripheral nerves of patients with amyotrophic lateral sclerosis (ALS), it would be worthwhile to evaluate consequence of such changes on magnetic resonance imaging (MRI). The aim of this study was to assess proximal-distal longitudinal signal and size alterations of brachial plexus nerve roots in ALS patients using 3-dimensional (3D) magnetic resonance neurography (MRN). A total of 21 ALS patients and 19 controls were evaluated. The diameters and signal-to-noise (SNR) ratio values of C5-C8 roots were measured at five points from proximal to distal sites. Student's t-test was performed to compare the differences at each point between two groups. Linear regression was performed for each nerve root, and the differences in linear regression slopes between two groups were analyzed. Receiver operating characteristic (ROC) analysis was performed for the diameter and SNR value ratio of the distal to the proximal points. Interobserver agreement was excellent [intraclass correlation coefficient (ICC): 0.802-0.913]. The diameters and SNR values of C5-C8 roots showed a significant decrease (P<0.05) from proximal to distal except SNR value of C5 root in controls. The slope values of diameters in ALS were -0.01924 for C5, -0.04404 for C6, -0.06228 for C7, and -0.06464 for C8. The slope values of SNR values in ALS were -10.14 for C5, -12.86 for C6, -15.99 for C7, and -19.06 for C8. The slope of nerve diameters and SNR values for ALS patients were more negatively sloped than controls (P<0.05) except SNR values of C5 and C7 roots. The ROC analysis confirmed that the diameter and SNR value ratio could differentiate ALS patients from controls with high accuracy. The cutoff values of diameter ratio were 0.7418 for C5, 0.6952 for C6, 0.6431 for C7, and 0.7147 for C8. The cutoff values of SNR value ratio were 0.5989 for C5, 0.6516 for C6, 0.6065 for C7, and 0.6758 for C8. Proximal-distal longitudinal diameters and SNR values decreased significantly for brachial plexus nerve roots in ALS patients with larger differences in slopes compared to controls. These results reflect pathophysiological changes of ALS and may be helpful in improving the diagnosis of ALS.

Association of Small Fiber Function with Microvascular Perfusion of Peripheral Nerves in Patients with Type 2 Diabetes

Introduction/aimsDiabetic small fiber neuropathy (SFN) is caused by damage to thinly myelinated A‑fibers (δ) and unmyelinated C‑fibers. This study aimed to assess associations between quantitative sensory testing (QST) and parameters of peripheral nerve perfusion obtained from dynamic contrast enhanced (DCE) magnetic resonance neurography (MRN) in type 2 diabetes patients with and without SFN.MethodsA total of 18 patients with type 2 diabetes (T2D, 8 with SFN, 10 without SFN) and 10 healthy controls (HC) took part in this cross-sectional single-center study and underwent QST of the right leg and DCE-MRN of the right thigh with subsequent calculation of the sciatic nerve constant of capillary permeability (Ktrans), extravascular extracellular volume fraction (Ve), and plasma volume fraction (Vp).ResultsThe Ktrans (HC 0.031 min−1 ± 0.009, T2D 0.043 min−1 ± 0.015; p = 0.033) and Ve (HC 1.2% ± 1.5, T2D: 4.1% ± 5.1; p = 0.027) were lower in T2D patients compared to controls. In T2D patients, compound z‑scores of thermal and mechanical detection correlated with Ktrans (r = 0.73; p = 0.001, and r = 0.57; p = 0.018, respectively) and Ve (r = 0.67; p = 0.002, and r = 0.69; p = 0.003, respectively). Compound z‑scores of thermal pain and Vp (r = −0.57; p = 0.015) correlated negatively.DiscussionThe findings suggest that parameters of peripheral nerve microcirculation are related to different symptoms in SFN: A reduced capillary permeability may result in a loss of function related to insufficient nutritional supply, whereas increased capillary permeability may be accompanied by painful symptoms related to a gain of function.

Detectıon of vısual-audıtory reactıon rates ın ındıvıduals wıth type 2 dıabetes mellıtus

AIM: The primary purpose of our study was to understand the damage in the peripheral nerves of patients with diabetes and to determine the change in patients’ reaction rates and perceptions by the age groups, duration of diabetes, fasting plasma glucose and HbA1c values, and compare these with those of the healthy individuals.METHODS: This study was carried out at the Baskent University Hospital Endocrinology and Metabolic Diseases Outpatient Clinic. A total of 64 patients diagnosed with type 2 diabetes and 64 healthy controls were included in the study. Finger tapping, visual, and auditory reaction time tests were performed on the subjects, respectively. The subjects’ fasting plasma glucose and HbA1c levels, and the duration of their diabetes were recorded. Analyses were performed using the SPSS version 25. Differences were considered statistically significant when the p-value is &lt;0.05.RESULTS: It was observed that the participants in the control group between the ages of 18-34 showed a faster reaction in all tests (p=0.01), but the difference in reaction rates in both groups decreased as the age increased. There were positive correlations between the duration of type 2 diabetes and the visual and auditory examination results (r= 0.69, p&lt;0.05, r=0.52, p&lt;0.05, respectively). There was also a positive correlation between the HbA1c (%) and the visual (r=0.97, p&lt;0.05) examination results.CONCLUSIONS: As the patients’ HbA1c levels and the time spent with type 2 diabetes increased, their reaction rate and perception skills decreased. Especially in the early stages of the disease, cognitive decline was observed to be rapid. It is thought that early diabetic control is significant.

Evaluation of the median nerve by shear wave elastography in patients with Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is characterized by enlargement and stiffness of peripheral nerves due to edema with large numbers of "onion bulbs" in the endoneurium. Ultrasound elastography seems to be an ideal method to detect this condition. The aim of this study was to analyze the shear wave elastography (SWE) features of peripheral nerves in patients with CMT1A. We included 24 CMT1A patients with a mean age of 28 years, along with 24 age- and gender-matched controls. All patients presented with mutations of the PMP22 gene and showed length-dependent polyneuropathy. The motor nerve conduction velocity (MNCV) of the median nerve ranged from 5.2 to 37.4 m/s. SWE and cross-sectional area (CSA) were used to evaluate the bilateral median nerves at predefined sites in both patients and con-trols. The average elastography value (EV) of the median nerve was 73.5±11.7 kPa in patients with CMT1A and 37.5±6.1 kPa in control subjects. The difference between the two groups was statistically significant (P<0.05). In CMT1A pa-tients, the average EV at the proximal and distal parts of the median nerve were 81.4±9.4 kPa and 65.2±8.1 kPa, respectively. The average CSAs at the proximal and distal parts of the median nerve were 0.29±0.06 cm2 and 0.20±0.05 cm2, respectively. The EV on SWE was positively correlated with CSA (p< 0.01) and negatively correlated with MNCV in the median nerve (p< 0.01). Peripheral nerve stiffness dramatically increases in CMT1A and is correlated with the severity of nerve involvement.

The cross-sectional area of peripheral nerve in amyotrophic lateral sclerosis: A case-control study

ObjectiveA growing body of literature recognises the importance of peripheral nerve ultrasound in neuromuscular disorders. Several attempts have been made to differentiate amyotrophic lateral sclerosis (ALS) from multifocal motor neuropathy (MMN) using peripheral nerve ultrasound. A much-debated question is whether the cross-sectional area (CSA) of peripheral nerve in ALS patients is significantly smaller compared to healthy controls. This study aims to determine the CSA of peripheral nerves in patients with ALS. MethodsOne hundred and thirty-nine patients with ALS and 75 healthy controls were recruited. Ultrasound of the median, ulnar, and trunks of the brachial plexus and cervical nerve roots was undertaken in ALS patients and controls. ResultsCompared to controls, ALS patients had mild reductions of the median nerve, most sites of the ulnar nerve, trunks of the brachial plexus and cervical nerve roots. Another important finding of this study is that the median nerve tends to have a more significant reduction than the ulnar nerve in ALS patients, especially at the proximal. ConclusionsUltrasound could be sensitive to nerve motor fibre loss in patients with ALS. CSA at the proximal Median nerve may be a promising biomarker in patients with ALS.

Nerve Ultrasound of Peripheral Nerves in Patients Treated with Immune Checkpoint Inhibitors.

Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60-77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1-2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0-2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8-13, p < 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.

Surgical Release of Ulnar and Median Nerves in CMT1A: Prevention and Treatment of a Second Hit (P14-8.013)

<h3>Objective:</h3> To evaluate outcomes of carpal tunnel (CT, CTS), cubital tunnel (CuT, CuTS), and Guyon’s Canal (GC, GCS) release in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). <h3>Background:</h3> Peripheral nerves in patients with CMT1A are diffusely enlarged and areas of potential compression at the CT, CuT, and GC can be released to reduce the risk of a “second hit” (nerve injury due to compression) in the setting of their genetic, progressive neuropathy, however there is little data on the efficacy and timing of surgical nerve decompression. <h3>Design/Methods:</h3> Genetically diagnosed and suspected CMT1A patients that reported hand symptoms seen in clinic in 2021–2022 with electrophysiologic data who were evaluated by neurosurgery for surgical decompression for CTS, CuTS, and GCS were reviewed. <h3>Results:</h3> All patients had severe slowing of motor nerve conduction velocities and absent sensory responses on NCS consistent with CMT1A. Electrographic CTS occurred bilaterally in 83%(5/6). Electrographic bilateral GCS and unilateral CuTS were observed in 33%(2/6) of patients. Three patients with sonographic data all demonstrated diffuse enlargement of the ulnar and median nerves at the forearm (mean cross-sectional area, CSA=20 mm2 and 26 mm2). Focal narrowing occurred at the CT in two patients (mean CSA=11.2 mm2 vs 37 mm2 at the forearm). One patient underwent unilateral and one patient underwent bilateral decompression at the CT, CuT, and GC with a follow-up time of 8 months and 2 months. Both patients endorsed significant improvement of gross grip strength in at least one hand and resolution of median sensory abnormalities in territories of released nerves. <h3>Conclusions:</h3> Although altered due to the nature of CMT1A, electrophysiologic and sonographic data provided focal findings in our patients with hand symptoms. Patients who underwent surgical decompression had symptomatic benefits. These releases can reduce the risk of a “second hit” of neurologic injury due to compression. <b>Disclosure:</b> Dr. McKeen has nothing to disclose. Dr. Katyal has nothing to disclose. Dr. Sakamuri has received personal compensation in the range of $0-$499 for serving as a Conference Faculty with AANEM. Dr. Wilson has nothing to disclose. Dr. Greene has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Dysimmune Diseases Foundation .

Multiparametric Quantitative MRI of Peripheral Nerves to Differentiate Axonal from Demyelinating Neuropathies (P11-8.002)

<h3>Objective:</h3> To develop a multiparametric quantitative MRI (qMRI) method to track pathological changes of peripheral nerves in patients with peripheral neuropathies. <h3>Background:</h3> Irrespective of the causes or types of polyneuropathies, peripheral nerves are mainly afflicted by two kinds of pathologies – axonal loss and demyelination. It is critical to differentiate the two as treatments are different for the two conditions. While nerve conduction studies (NCS) have been used to differentiate the two pathologies in the distal nerves, there are no tools to probe the pathologies in the proximal peripheral nerves. This is particularly needed when distal nerves become non-responsive in NCS. <h3>Design/Methods:</h3> We have developed a multiparametric qMRI method that quantifies the sciatic and tibial nerves with 10 parameters that are sensitive to different aspects of myelin and axonal pathologies: magnetization transfer ratio (MTR), magnetization transfer saturation index (MTsat), longitudinal relaxation time (T1), proton density (PD), effective transverse relaxation time (T2*), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and nerve fascicular volume (fVol). In this pilot study, we studied 4 patients with Charcot-Marie-Tooth type-1A (CMT1A), 2 patients with CMT type-2S (CMT2S), and 17 healthy controls. <h3>Results:</h3> Compared with healthy controls, patients with CMT2S (reportedly as axonal type) had comparable MTR, MTsat, T1, PD and fVol, but reduced T2*. While patients with CMT1A (dysmyelinating type) had reduced MTR and MTsat, increased fVol, T1 and PD, and comparable T2*. All the 6 patients shared changes of reduced FA which was driven by a reduced AD and an increased RD. <h3>Conclusions:</h3> The data show different qMRI patterns between axonal and demyelinating neuropathies. The differential changes will be further verified in a larger cohort of patients with peripheral neuropathies. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Mr. Baraz has nothing to disclose. Ms. Xuan has nothing to disclose. Sadaf Saba has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Castoro has nothing to disclose. Yang Xuan has nothing to disclose. Dr. Roth has nothing to disclose. The institution of Dr. Dortch has received research support from NIH. The institution of Dr. Dortch has received research support from DOD. Dr. Li has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Board of Directors with ANA that is relevant to AAN interests or activities.

Features of damage to the conductive structures of the nervous system in patients with vibration disease, burdened with diabetes mellitus and metabolic syndrome

Introduction. Of interest are the processes developing in vibration disease (VD) in combination with metabolic syndrome (MS) or diabetes mellitus (DM), combined forms of diseases worsen their course and prognosis.&#x0D; The study aims to assess the features of the state of central afferent conductive structures and peripheral nerves in patients with vibration disease, burdened with diabetes mellitus or metabolic syndrome.&#x0D; Materials and methods. The scientists have examined 155 workers with VD — group one with an established diagnosis of VD (86 people); group two — with VD combined with DM (30 people); group three — with VD burdened with MS (39 people). The authors have conducted the electroneuromyographic examination and registration of somatosensory evoked potentials, with stimulation of the median nerve in the wrist. Abduction points — Erb point, cervical spinal cord, from the scalp of the projection area of the precentral gyrus. The researchers have applied multivariate discriminant analysis from the STATISTICA — version 6 application software package of StatSoft Inc (USA).&#x0D; Results. With VD complicated by MS, changes were in the distal part of the motor axons, with VD burdened with DM, the amplitude of the motor component of the median and tibial nerves decreased, the speed of the pulse in the proximal part of the median nerve. Somatosensory evoked potentials in VD in combination with MS revealed an increase in latency of N13 and N20. The duration of N13-N18, N13-N20, latency N18, N20, N30 increased in the case of WB, burdened with DM.&#x0D; Limitations. The limitation of the study is the use of unrelated samples for statistical analysis. The study of the state of central and peripheral conductive structures in connected samples should be considered evidence-based: metabolic syndrome and further — diabetes mellitus.&#x0D; Conclusion. The patterns of peripheral nerve damage in VD associated with exposure to general and local vibration, burdened with DM or MS, were disorders of afferent axons of the upper and lower extremities, as well as changes in the distal parts of the motor component of the tibial and median nerves. The features of the peripheral nerve states in VD, burdened with DM, were the complex involvement of the motor component in the pathological process, characterized by changes in the amplitude, pulse transit time at the level of the terminal unmyelinated fibers of the median and tibial nerves and changes in the proximal part of the median nerve. In VD complicated by MS, pathological changes were characteristic of the distal part of the motor axons. The patterns of afferent conductive structures lesion in VD, burdened with DM or MS, consisted in a violation of the activity of neurons of the cervical spinal cord and the somatosensory cortex. The peculiarity of the state of the central afferent conducting structures in VD, burdened with DM, was the slowing down of the afferent excitation wave in the area of thalamic structures to the somatosensory zone of the cortex, a violation of the conduction from the trunk to the cortical projections of the somatosensory zone. In case of VD, complicated by MS — the time of the afferent excitation wave at the level of the cervical spine and the somatosensory cortex.&#x0D; Ethics. Conclusion of the MEC of the Federal State Budgetary Scientific Institution "East Siberian Institute of Medical and Environmental Research" No. 32 dated 09.10.2019.

Chronic Hypoxemia Triggers a Neuropathic Process in Chronic Obstructive Pulmonary Disease: Insight From In Vivo Neurophysiological Assessments.

Peripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength-duration time constant, threshold electrotonus (TE), current-threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40-60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+-K+-ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

A mechanistic understanding of the relationship between skin innervation and chemotherapy-induced neuropathic pain.

Neuropathic pain is a frequent complication of chemotherapy-induced peripheral neurotoxicity (CIPN). Chemotherapy-induced peripheral neuropathies may serve as a model to study mechanisms of neuropathic pain, since several other common causes of peripheral neuropathy like painful diabetic neuropathy may be due to both neuropathic and non-neuropathic pain mechanisms like ischemia and inflammation. Experimental studies are ideally suited to study changes in morphology, phenotype and electrophysiologic characteristics of primary afferent neurons that are affected by chemotherapy and to correlate these changes to behaviors reflective of evoked pain, mainly hyperalgesia and allodynia. However, hyperalgesia and allodynia may only represent one aspect of human pain, i.e., the sensory-discriminative component, while patients with CIPN often describe their pain using words like annoying, tiring and dreadful, which are affective-emotional descriptors that cannot be tested in experimental animals. To understand why some patients with CIPN develop neuropathic pain and others not, and which are the components of neuropathic pain that they are experiencing, experimental and clinical pain research should be combined. Emerging evidence suggests that changes in subsets of primary afferent nerve fibers may contribute to specific aspects of neuropathic pain in both preclinical models and in patients with CIPN. In addition, the role of cutaneous neuroimmune interactions is considered. Since obtaining dorsal root ganglia and peripheral nerves in patients is problematic, analyses performed on skin biopsies from preclinical models as well as patients provide an opportunity to study changes in primary afferent nerve fibers and to associate these changes to human pain. In addition, other biomarkers of small fiber damage in CIPN, like corneal confocal microscope and quantitative sensory testing, may be considered.

Diametrical Effects of Glucose Levels on Microvascular Permeability of Peripheral Nerves in Patients With Type 2 Diabetes With and Without Diabetic Neuropathy.

Clinical studies investigating the benefit of glucose control on the progression of diabetic neuropathy (DN) have come to controversial results in patients with type 2 diabetes (T2D). This study aimed to assess associations of HbA1c levels with parameters of nerve perfusion in patients with T2D with and without DN using dynamic contrast-enhanced magnetic resonance neurography (DCE-MRN) at 3 Tesla. A total of 58 patients with T2D (20 with DN and 38 without DN) took part in this cross-sectional single-center study. Groups were matched for age, BMI, HbA1c, duration of T2D, and renal function. All patients underwent DCE-MRN with subsequent electrophysiologic and serologic testing. The extended Tofts model was used to quantify the sciatic nerve's microvascular permeability (Ktrans), volume fraction of the extracapillary extracellular space, and volume fraction of the plasma space. As a main result, we found that Ktrans correlated positively with HbA1c in patients with DN, while a negative correlation between the two parameters was found in patients without DN. Our results indicate that the effect of glucose control on the capillary permeability of peripheral nerves differs between patients with T2D with and without DN.

Lower Extremity Nerve Decompression for Diabetic Peripheral Neuropathy: A Systematic Review and Meta-analysis.

Background:Diabetic peripheral neuropathy (DPN) is a leading cause of morbidity. This systematic review and meta-analysis evaluate the efficacy of lower extremity nerve decompression in reducing DPN symptoms and complications.Methods:A database search was performed using Medline, Embase, Google Scholar, and Cochrane Central Register of Controlled Trials. Articles addressing surgical decompression of lower limb peripheral nerves in patients with diabetes were screened for inclusion. Two independent reviewers undertook the assessment. Methodological quality measures were the Cochrane risk of bias and Newcastle-Ottawa scale.Results:The pooled sample size from 21 studies was 2169 patients. Meta-analysis of 16 observational studies showed significant improvement in the visual analog scale (VAS) (P < 0.00001) and two-point discrimination (P = 0.003), with strong reliability. Decompression of the tarsal tunnel region had the highest improvement in VAS [MD, 6.50 (95% CI, 3.56–9.44)]. A significant low-risk ratio (RR) of ulcer development and lower limb amputation was detected (P < 0.00001). Lowest RR of ulcer development was detected with tarsal tunnel release [RR, 0.04 (95% CI, 0.00–0.48)]. Improvements in VAS, two-point discrimination, and nerve conduction velocity were nonsignificant in the meta-analysis of five randomized controlled trials (RCTs). The RCT analysis was limited to only two studies for each outcome.Conclusions:Meta-analysis of observational studies highlights the efficacy of lower extremity nerve decompression in reducing DPN symptoms, ulcerations, and amputations. Releasing the tibial nerve in the tarsal tunnel region was the most effective observed procedure. Nevertheless, high-quality RCTs are required to support the utility of this intervention in DPN.

Association between probable REM sleep behavior disorder and increased dermal alpha-synuclein deposition in Parkinson's disease

IntroductionMany patients with Parkinson's disease suffer from REM sleep behavior disorder, potentially preceding the onset of motor symptoms. Phospho-alpha-synuclein is detectable in skin biopsies of patients with isolated REM sleep behavior disorder several years prior to the onset of manifest PD, but information on the association between dermal phospho-alpha-synuclein deposition and REM sleep behavior disorder in patients with manifest PD is limited. We therefore aimed to investigate the alpha-synuclein burden in dermal peripheral nerve fibers in patients with Parkinson's disease with and without REM sleep behavior disorder. MethodsPatients with Parkinson's disease (n = 43) who had undergone skin biopsy for the immunohistochemical detection of phosphorylated alpha-synuclein were screened for REM sleep behavior disorder using RBDSQ and Mayo Sleep Questionnaire. Skin biopsies from 43 patients with isolated polysomnography-confirmed REM sleep behavior disorder were used as comparators. ResultsDermal alpha-synuclein deposition was more frequently found (81.8% vs. 52.4%, p = 0.05) and was more abundant (p = 0.01) in patients with Parkinson's disease suffering from probable REM sleep behavior disorder compared to patients without REM sleep behavior disorder and was similar to patients with isolated REM sleep behavior disorder (79.1%). ConclusionThe phenotype of REM sleep behavior disorder is associated with high amounts of dermal alpha-synuclein deposition, demonstrating a strong involvement of peripheral nerves in patients with this non-motor symptom and may argue in favor of REM sleep behavior disorder as an indicator of a “body-predominant” subtype of Parkinson's disease.

P 78 Sonographic and electrophysiological characterization of peripheral nerves in patients with diabetes type 2

Introduction: Diabetic polyneuropathy is a significant complication of diabetes mellitus, occurring in approximately 20-30% of diabetic patients. Our objective is to characterize the peripheral nerves of patients with type two diabetes especially with nerve ultrasound because there have been inconsistent results regarding nerve enlargement in the past years. Methods: 75 patients with diabetes type 2 (with and without polyneuropathy) underwent clinical, sonographic (using the UPS Score), and electrophysiological evaluation. Results: Nerve ultrasound showed only few sites with nerve enlargement at non-compression sites. Our results confirmed increased cross-sectional areas (CSA) in peripheral nerves at compression sites as it was shown before by Pitarokoili and colleagues. First one-year follow-up examinations revealed an improvement of nerve enlargement after dietary change, weight reduction and change of diabetes medication. Conclusion: Diabetic polyneuropathy cannot be detected reliably by using the UPS Score, but the score is useful to exclude competing inflammatory demyelinating causes of neuropathy. CSA improvement after one year with dietary change, weight reduction and change of diabetes medication indicates that the result of these metabolic changes might be directly visible using nerve ultrasound. Further longitudinal studies are required to confirm our results.

Ultrasonographic evaluation reveals thinning of cervical nerve roots and peripheral nerves in spinal and bulbar muscular atrophy.

Ultrasonography (US) is a noninvasive and patient-friendly tool for the evaluation of peripheral nerves. In motor neuron diseases, amyotrophic lateral sclerosis (ALS) has been reported to show the atrophy of peripheral nerves on US. However, the US findings are still unclear in spinal and bulbar muscular atrophy (SBMA), an adult-onset lower motor neuron disease caused by an abnormal CAG repeat expansion in the androgen receptor gene. We prospectively recruited and evaluated 11 patients with genetically confirmed SBMA and 9 patients with ALS diagnosed according to the revised El Escorial ALS criteria or the Awaji electrodiagnostic criteria. The C5-C7 cervical nerve roots and the median and ulnar nerves were evaluated ultrasonographically. The cross-sectional areas (CSAs) of the C6 and C7 nerve roots, the median nerve in the upper arm and forearm, and the ulnar nerve in the upper arm were smaller in patients with SBMA than those in patients with ALS (p < 0.05), whereas the CSAs of the C5 nerve root and the ulnar nerve in the forearm were not smaller. US showed that the peripheral nerves in patients with SBMA were thinner than those in patients with ALS despite similar degrees of weakness and motor neuron loss. Possible causes include additional sensory nerve involvement and longer disease duration in patients with SBMA than those in patients with ALS.

Advances in Interventional Therapies for Painful Diabetic Neuropathy: A Systematic Review.

Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice. We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN. We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+). Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.

Evaluation of peripheral amyloid neuropathy

Symptoms of peripheral nervous system (PNS) damage are common clinical manifestations of systemic amyloidosis. Peripheral amyloid neuropathy is characterized by a progressive course, leading to the disability of patients; however, the current possibilities of pathogenetic therapy make the early diagnosis of amyloid neuropathy particularly urgent.Objective: to evaluate the informative value of laser confocal microscopy (LCM) of the cornea in diagnosing small fiber neuropathy of peripheral nerves in patients with systemic amyloidosis.Patients and methods. The study included nine patients (three men and six women) with morphologically confirmed primary amyloidosis (ALamyloidosis) and 12 patients (three men and nine women) with hereditary transthyretin amyloidosis (TTR-amyloidosis) verified by genetic and morphological methods. At baseline, the mean age of patients with AL-amyloidosis was 60.6±10.7 years, with hereditary TTR-amyloidosis – 57.1±13.1 years. According to the history of the disease in AL-amyloidosis, the mean duration of clinical symptoms was 2.7±1.4 years, with TTR-amyloidosis – 5.5±3.6 years. 20 age- and sex-adjusted healthy volunteers were included in the control group. All patients underwent a clinical neurological examination with an assessment of the severity of neuropathy according to the Neuropathy Impairment Score (NIS); 21 patients with systemic amyloidosis and all volunteers of the control group underwent LCM of the corneal nerve fibers (CNF). The coefficients of anisotropy (КΔL) and orientation symmetry (Ksym) of the CNF were calculated to assess the severity of damage to the corneal nerves.Results and discussion. Clinical neurological examination in patients with AL-amyloidosis revealed polyneuropathic syndrome (45%), tunnel syndrome (22%), their combination (22%), and autonomic dysfunction in the form of orthostatic hypotension and impaired motility of the gastrointestinal tract (GI tract; 56%). Symptoms in patients with TTR-amyloidosis were characterized by a combination of tunnel neuropathy and sensory-motor polyneuropathy (50%), distal symmetric polyneuropathy (42%). Frequent symptoms of PNS damage in systemic amyloidosis include autonomic neuropathy (56% – in AL-amyloidosis, 92% – in TTR-amyloidosis) presenting with orthostatic hypotension, impaired gastrointestinal motility, hypohidrosis, and dysuria. The mean NIS score, which characterizes the severity of somatic neuropathy, was significantly higher in patients with TTR-amyloidosis than AL-amyloidosis (p&lt;0.02). LCM of the cornea showed disturbances in the course and structure of the corneal nerve fibers in all examined patients with systemic amyloidosis. The mean anisotropy coefficient values were lower in patients with systemic amyloidosis than in the control group. There were no significant differences in the AL- and TTR-amyloidosis groups. An inverse correlation of average strength between the values of the anisotropy coefficient and NIS was revealed (r=-0.6; p=0.04) in the group of patients with TTR-amyloidosis.Conclusion. Clinical polymorphism of peripheral somatic and autonomic nervous systems lesions is typical for patients with systemic amyloidosis. LCM of the cornea is informative in the diagnosis of small fibers neuropathy of peripheral nerves in systemic amyloidosis; however, it cannot establish the nosology of neuropathy.

Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type\xa02

PurposeTo examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology.MethodsIn this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3–S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14–100 months. In one patient, imaging findings were further correlated to histology.ResultsFollow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified.ConclusionPeripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.