Idiopathic Peripheral Neuropathy Research Articles

Plasma proteomic analysis on neuropathic pain in idiopathic peripheral neuropathy patients.

Why only half of the idiopathic peripheral neuropathy (IPN) patients develop neuropathic pain remains unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain. We conducted unbiased mass-spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein-protein interactions associated with neuropathic pain. Univariate modeling was done with linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modeling was performed using elastic net analysis and validated with internal cross-validation and bootstrapping. In the univariate analysis, 73 proteins showed a p-value <.05 and 12 proteins showed a p-value <.01. None were significant after Benjamini-Hochberg adjustment for multiple testing. Elastic net analysis created a model containing 12 proteins with reasonable discriminatory power to differentiate between painful and painless IPN (false-negative rate 0.10, false-positive rate 0.18, and an area under the curve 0.75). Eight of these 12 proteins were clustered into one interaction network, significantly enriched for the complement and coagulation pathway (Benjamini-Hochberg adjusted p-value = .0057), with complement component 3 (C3) as the central node. Bootstrap validation identified insulin-like growth factor-binding protein 2 (IGFBP2), complement factor H-related protein 4 (CFHR4), and ferritin light chain (FTL), as the most discriminatory proteins of the original 12 identified. This proteomics analysis suggests a role for the complement system in neuropathic pain in IPN.

Evidence of Oligoclonal Bands Does Not Exclude Non-Inflammatory Neurological Diseases.

Cerebrospinal fluid analysis is an essential part of the diagnostic workup in various neurological disorders. Evidence of an intrathecal immunoglobulin synthesis, as demonstrated by Reiber’s diagram or the more sensitive oligoclonal bands (OCB), are typical for neuroinflammatory diseases, and normally not expected in non-inflammatory neurological diseases. Therefore, patients with non-inflammatory neurological diseases are often used in control groups in studies investigating autoimmune diseases of the central nervous system. However, data about the frequency of intrathecal immunoglobulin synthesis in non-inflammatory neurological disease are scarce. The cerebrospinal fluid (CSF) records of a total of 3622 patients were screened and 2114 patients included with presumably non-inflammatory neurological diseases like dementia, idiopathic peripheral neuropathy, motoneuron disease, stroke, and epileptic seizures. Evidence of an intrathecal immunoglobulin synthesis can be found with low frequency also in non-inflammatory neurological diseases. A much higher rate of patients showed intrathecal immunoglobulin synthesis as demonstrated by OCB than by Reiber’s diagram. In patients with disorders of the peripheral nervous system the frequency of OCB was much lower than in patients presenting with central nervous system manifestations. Evidence of an intrathecal immunoglobulin synthesis should not automatically lead to exclusion of non-inflammatory neurological diseases but should rather prompt the way to investigate for the origin of the intrathecal immunoglobulin synthesis.

Risk of idiopathic peripheral neuropathy in end-stage renal disease: A population-based cohort study.

Whether patients with end-stage renal disease (ESRD) have a higher risk of idiopathic polyneuropathy (IPN) than those without ESRD remains unclear. We hypothesised that carpal tunnel syndrome (CTS) is a prodrome of IPN in patients with ESRD. Data were collected from the Taiwan National Health Insurance research database (NHIRD) for the 2000-2011 period. Two matching strategies, age- and sex-matching and propensity matching, were used, which yielded 2596 age- and sex-matched patients with ESRD and 2210 propensity-matched patients with ESRD. The comparison cohort was chosen in a 1:4 ratio for the age- and sex-matched method and in a 1:1 ratio for the propensity-matching method. The primary outcome was the incidence of IPN. Cox proportional hazards modelling was used. In the age- and sex-matched cohort, the IPN incidence was 7.64 and 2.88 per 1000 person-years for the ESRD and controls cohorts, respectively. After we adjusted for age, sex, comorbidities and medications relative to controls, having ESRD was significantly associated with increased risk of IPN (hazard ratio [HR]=2.45, 95% confidence interval [CI]=1.76-3.41). Competing risk of death as sensitivity analysis revealed that having ESRD with CTS was still associated with higher risk of IPN than having CTS without ESRD (HR=2.85, 95% CI=1.87-4.34). Patients with ESRD with CTS had higher incidences of idiopathic peripheral neuropathy than those without ESRD with CTS.

A Case of Idiopathic Peripheral Neuropathy Improved by Combined with Electroacupuncture and Bee Venom Acupuncture

A Case of Idiopathic Peripheral Neuropathy Improved by Combined with Electroacupuncture and Bee Venom Acupuncture

Ultrasound-guided injections of amniotic membrane/umbilical cord particulate for painful neuropathy of the lower extremity

Treatment of peripheral neuropathy remains a challenge. It has been shown clinically that cryopreserved human amniotic membrane (AM) and umbilical cord (UC) reduce pain, and they may serve as a beneficial treatment option for peripheral neuropathy. Here, we report findings from a single-center, retrospective review of peripheral neuropathy patients treated with AM/UC particulate. Seventeen patients with recalcitrant diabetic (n = 8), idiopathic (n = 7), or chemotherapy-induced peripheral neuropathy (n = 2) were included in the study. At presentation, all 17 patients complained of pain, along with numbness (n = 10), paresthesia (n = 8), poor balance (n = 9), poor range of motion (n = 5), or weakness (n = 7). After an average of 2.7 injections of AM/UC particulate per extremity, symptoms improved by 30.0 ± 24.5% at 1 week, 46.6 ± 29.9% at 1 month (P < .005), 70.7 ± 14.3% at 2 months (P < .001), 72.3 ± 16.9% at 3 months (P < .001), and 61.0 ± 34.4% at 5–6 months (P < .01). No complications or adverse events related to AM/UC injection were observed. These results suggest local perineural injection of AM/UC particulate may reduce pain and alleviate symptoms in patients suffering from painful peripheral neuropathy of the lower extremities.

Charcot neuroarthropathy of the knee due to idiopathic sensory peripheral neuropathy

BackgroundCharcot neuroarthropathy is a systemic disease that generates pathological changes in the musculoskeletal system, causing instability, dislocations, and deformities. Charcot neuroarthropathy of the knee, due to either diabetes mellitus or syringomyelia, is anecdotally reported with the epidemic of the diseases. However, idiopathic sensory peripheral neuropathy can inflict osteoarticular structures directly, inducing a dysfunctional Charcot neuroarthropathy. An early diagnosis and effective relief of the symptomatic deformity is essential for the treatment.Case presentationWe report the case of a patient with idiopathic sensory peripheral neuropathy who presented with a swelling right knee, as well as distorted and painless gait disorder, diagnosed as Charcot neuroarthropathy of the knee. Partial weight bearing with a hinged knee brace was used to correct the abnormal alignment and gait posture, and bisphosphonates were prescribed to decrease pathological bone resorption. Although the alignment and Knee Society Score got a gradual deterioration, the combination of orthosis and pharmacy could alleviate the symptom to a certain extent.ConclusionThe diagnosis of Charcot neuroarthropathy of the knee is rare that requiring early diagnosis. The presence of features, including painlessness, numbness, and deformed arthropathy following chronic-onset algesthesia loss should be taken carefully.

Peripheral Neuropathy Research Registry: A prospective cohort.

The Peripheral Neuropathy Research Registry (PNRR) is a prospective cohort of peripheral neuropathy (PN) patients focused on idiopathic axonal peripheral neuropathy. Patients with diabetic, human immunodeficiency virus-, and chemotherapy-induced peripheral neuropathies are enrolled as comparison groups. The PNRR is a multi-center collaboration initiated and funded by the Foundation for Peripheral Neuropathy (FPN) with the objective to recruit a well characterized cohort of patients with different phenotypes and symptoms in each diagnostic category, and to advance research through development of biomarkers and identification of previously unknown causes of PN. The overall goal of the initiative is to find disease-altering treatments and better symptom relief for patients. We present the study design, types of data collected, and characteristics of the first 1150 patients enrolled. We also discuss ongoing analyses on this dataset, including untargeted-omics methodologies.

Quality of Life in Patients with Gluten Neuropathy: A Case-Controlled Study

Background: Gluten neuropathy (GN) is defined as an otherwise idiopathic peripheral neuropathy in the presence of serological evidence of gluten sensitivity (positive native gliadin antibodies and/or transglutaminase or endomysium antibodies). We aimed to compare the quality of life (QoL) of GN patients with that of control subjects and to investigate the effects of a gluten-free diet (GFD) on the QoL. Methods: All consecutive patients with GN attending a specialist neuropathy clinic were invited to participate. The Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of the neuropathy. The 36-Item Short Form Survey (SF-36) questionnaire was used to measure participants’ QoL. A strict GFD was defined as effectively being able to eliminate all circulating gluten sensitivity-related antibodies. Results: Fifty-three patients with GN and 53 age- and gender-matched controls were recruited. Compared to controls, GN patients showed significantly worse scores in the physical functioning, role limitations due to physical health, energy/fatigue, and general health subdomains of the SF-36. After adjusting for age, gender, and disease severity, being on a strict GFD correlated with better SF-36 scores in the pain domain of the SF-36 (beta 0.317, p = 0.019) and in the overall health change domain of the SF-36 (beta 0.306, p = 0.017). Conclusion: In GN patients, physical dysfunctioning is the major determinant of poor QoL compared to controls. Routine checking of the elimination of gluten sensitivity-related antibodies that results from a strict GFD should be encouraged, as such elimination ameliorates the overall pain and health scores, indicating a better QoL.

Reduction in Idiopathic Peripheral Neuropathy Diagnoses Using a Comprehensive EMR-based Laboratory Order Set (P2.442)

Reduction in Idiopathic Peripheral Neuropathy Diagnoses Using a Comprehensive EMR-based Laboratory Order Set (P2.442)

Ultrasound analysis of a novel therapeutic intervention for neuropathy: intraneural facilitation acute effects on idiopathic and chemotherapy induced peripheral neuropathy

Intraneural Facilitation (INF) is a novel therapy for the treatment of various neuropathic pathologies. INF is an evidence‐based approach which utilizes physical‐therapy‐based “holds” to stretch and relax peripheral associated nerve areas and thus potentially allows for re‐establishment of blood supply (oxygen and nutrients) to damaged nerves.The acute efficacy of INF therapy to treat idiopathic or chemotherapy‐induced neuropathy remains undetermined. Therefore, in a pilot feasibility study, we examined the effects of acute changes by ultrasound assessment of the arterial pulsatility index and volume flow with pre‐ and post‐Intraneural Facilitation Treatment in patients with chemotherapy‐induced neuropathy and idiopathic peripheral neuropathy.PurposeTo determine the acute effect of a novel therapeutic intervention called intraneural facilitation on patients with idiopathic (IPN) and chemotherapy‐induced (CIN) peripheral neuropathies.MethodsThis is a prospective pre‐ and posttest, single group clinical pilot study in an outpatient physical therapy clinic. Participants are patients with peripheral idiopathic or chemotherapy‐induced neuropathy. Outcome measures were assessed with ultrasound measures 1) pulsatility index (PI), which is a measure of the variability of blood velocity in a vessel, equal to the difference between the peak systolic and minimum diastolic velocities divided by the mean velocity during the cardiac cycle, and 2) volume flow (VF), a measure of a cross‐sectional blood vessel area in a time‐averaged velocity.ResultsThere were 38 arterial ultrasound measurements in 13 patients diagnosed with either CIN or IDN for this pilot study. The PI showed significant improvement from pre‐ to post‐treatment in both neuropathy categories, CIN and IDN respectively (p &lt; 0.05). The average total percent change in the 38 arterial measurements of PI was +1.32% and VF was −2.59%. The percent change in PI and VF in patients with IDN was +1.25% and −8.26% and CIN was +1.36% and +0.12%, respectively. Ultrasound measurements of the left radial artery showed a treatment efficacy with a significant change in PI (p = 0.0463).ConclusionThese preliminary pilot outcome results, using ultrasound assessment parameters PI and VF are clinically promising. Intraneural facilitation treatment improves objective PI and VF “markers” in patients with CIN and IDN. Overall, the average percent change of PI showed that there was a significant acute improvement in patients with both CIN and IDN. Greater frequency and chronicity of INF treatment is suggestive to be potentially efficacious in the resolution of the respective neuropathies. These promising pilot patient data suggests the need for further expansive prospective studies to expand a more comprehensive clinical understanding of this new novel treatment called, Intraneural Facilitation Treatment. These studies are currently in progress.Support or Funding InformationDepartmentalThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The effects of dry needling and neurodynamic exercise on idiopathic peripheral neuropathy: A case report

A single patient (male, 67) with a medical diagnosis of idiopathic peripheral neuropathy (G60.9) was referred to physical therapy. The patient presented with signs and symptoms consistent with peripheral neuropathy, including bilateral single leg balance deficits, sensation impairments, and antalgic gait. Treatment consisted of dry needling (DN) with electrical stimulation and a home exercise program involving a neurodynamic exercise to be performed daily. Dry needling included the use of thin filiform needles to stimulate the underlying structures directed at eliciting a change within the tissues. The needles were left in situ and connected to an electrical stimulation unit. The neurodynamic exercise used in this case study was designed to target the distal branches of the sciatic nerve. The patient was directed to complete 3 sets of 10 repetitions in the slumped position and moving between ankle plantar flexion and dorsiflexion. The patient was treated for a total of 4 visits over a 5-week period. The Foot and Ankle Ability Measure (FAAM), Numeric Pain Rating Scale (NPRS), Romberg Test, and sensation testing were collected at baseline and then again after the 4th treatment. A Global Rating of Change (GROC) score was obtained at the end of treatment. After the 4th visit, functional self-report scores were not improved (93.75%–86.9% at completion), while NPRS decreased to 2 from a baseline rating of 4. The eyes closed portion of the Rhomberg balance test improved from 5 s on the right limb to 15 s and from 8 s to 20 s on the left limb. Sharp/dull sensation testing of the L4 dermatome also improved from 2 out of 5 correctly selected on the left lower limb to 5 out of 5. At the S1 level, sensation improved on the left lower limb from 2 out of 5 to 4 out of 5 and from 2 out of 5 on the right lower limb to 5 out of 5. The patient's GROC score was rated as quite a bit better (+5). The outcomes of this case study suggest that clinicians may consider the addition of DN with electrical stimulation and neurodynamic exercises to the treatment of this patient population given the sizeable and rapid improvements in pain, balance, and sensation testing following only 4 treatments.

A Case of Idiopathic Peripheral Neuropathy Related to a Running Injury Treated Successfully with Acupuncture

Idiopathic peripheral neuropathy lacks a specific cause. The risk of developing this condition increases with age and can seriously affect a patient’s quality of life. Symptoms relate to whichever nerves are damaged and may progress slowly or remain unchanged after onset. No cure exists. Notably, acupuncture has proven efficacy in nerve regeneration and nerve function improvement. This case presentation describes a 60-year-old male regular runner who developed right-sided drop foot after completing a marathon in June 2016. He was subsequently diagnosed as having a deep fibular nerve injury. After two months of physical rehabilitation, the right ankle remained dropped, with accompanying weakness and tightness in the anterior part of the right leg. In August 2016, the man commenced four months of electroacupuncture, three times a week. He experienced an obvious improvement in the velocity of motor nerve transduction and in F-wave testing. Moreover, there were marked improvements for the right ankle dorsiflexion range of motion in the supine (120o to 100o ) and seated (15o to 30o ) positions. The man resumed jogging in March 2017. Acupuncture may facilitate functional recovery after peripheral nerve injury.

NaV channel variants in patients with painful and nonpainful peripheral neuropathy.

Objective:To examine the incidence of nonsynonymous missense variants in SCN9A (NaV1.7), SCN10A (NaV1.8), and SCN11A (NaV1.9) in patients with painful and nonpainful peripheral neuropathy.Methods:Next-generation sequencing was performed on 457 patient DNA samples provided by the Peripheral Neuropathy Research Registry (PNRR). The patient diagnosis was as follows: 278 idiopathic peripheral neuropathy (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy (77% painful and 23% nonpainful).Results:We identified 36 (SCN9A), 31 (SCN10A), and 15 (SCN11A) nonsynonymous missense variants, with 47.7% of patients carrying a low-frequency (minor allele frequency <5%) missense variant in at least 1 gene. The incidence of previously reported gain-of-function missense variants was low (≤3%), and these were detected in patients with and without pain. There were no significant differences in missense variant allele frequencies of any gene, or SCN9A haplotype frequencies, between PNRR patients with painful or nonpainful peripheral neuropathy. PNRR patient SCN9A and SCN11A missense variant allele frequencies were not significantly different from the Exome Variant Server, European American (EVS-EA) reference population. For SCN10A, there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations.Conclusions:These results suggest that identification of a genetically defined subpopulation for testing of NaV1.7 inhibitors in patients with peripheral neuropathy is unlikely and that additional factors, beyond expression of previously reported disease “mutations,” are more important for the development of painful neuropathy than previously discussed.

Transglutaminase 6 antibodies in gluten neuropathy

BackgroundTG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies). MethodsThis was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy. ResultsTwenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy. ConclusionsWe found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.

Clinical Characteristics, Electrophysiology, and Skin Biopsy of 38 Peripheral Neuropathy Cases with Small Fiber Involvement of Various Etiologies.

Background:In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN.Methods:Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test.Results:Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) (r = 0.372, P = 0.025), and proximal (r = 0.383, P = 0.021) and distal (r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve (r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups (χ2 = 9.901, P = 0.007). IENFD was significantly decreased (χ2 = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups (χ2 = 8.172, P < 0.017). The proximal (F = 4.336, P = 0.021) and distal (F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups.Conclusions:IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.

Effects of foot and ankle devices on balance, gait and falls in adults with sensory perception loss: a systematic review.

EXECUTIVE SUMMARYBackgroundFoot and ankle devices are being developed as a method of preventing people with sensory perception loss sustaining a fall. Such devices are believed to work by reducing the likelihood of a fall by improving the balance and gait of the user.ObjectivesThe objective of the review was to evaluate the effectiveness of foot and ankle devices for the prevention of falls and the improvement of balance and gait in adults with sensory perception loss.Inclusion criteria Types of participantsParticipants were community-dwelling adults with bilateral pathological sensory perception loss.Types of intervention(s)/phenomena of interestThe current review evaluated any foot or ankle device, including but not restricted to, all types of footwear (therapeutic and retail), insoles (customized and prefabricated) and ankle-foot orthoses (AFOs).Types of studiesIn the absence of randomized controlled trials (RCT), the review considered experimental and epidemiological study designs, except case series, individual case reports and descriptive cross-sectional studies.OutcomesThe primary outcome was number of falls. Secondary outcome measures were clinical or laboratory measures of balance or gait.Search strategyA search for published and unpublished literature from inception to March 2015 written in the English language was conducted across a number of major electronic databases. A three-step search strategy was developed using MeSH terminology and keywords to ensure all that relevant materials are captured.Methodological qualityMethodological quality of included studies was assessed by two reviewers, who appraised each study independently, using standardized Joanna Briggs Institute (JBI) critical appraisal tools.Data extractionQuantitative data were extracted from the studies that were identified as meeting the criteria for methodological quality using the standardized JBI data extraction tools.Data synthesisDue to the heterogeneity of populations, interventions and outcome measures, meta-analyses were not possible and results are presented in narrative form.ResultsNine trials (from 10 papers) involving 238 participants, (14 with multiple sclerosis and 16 with idiopathic peripheral neuropathy, 150 with diabetic neuropathy) and 58 controls were included in the review. No study reported falls as an outcome measure. The results of the included studies found that in people with sensory perception loss, postural sway improved with vibrating insoles and AFO, altering the softness and texture of the top cover had no effect on postural sway, wearing footwear over long distances or AFOs improved step-to-step consistency, and no foot and ankle device was reported to have a negative effect on the balance or gait of people with sensory perception loss. The methodological quality of the included studies was poor. No study used a randomized controlled trial (RCT) methodology. No study incorporated a follow-up period or tested the intervention within the context of the intended clinical environment.ConclusionThere is limited evidence to suggest that footwear and insole devices can artificially alter postural stability and may reduce the step-to-step variability in adults with sensory perception loss. Varying the material properties of an insole does not notably affect static balance or gait.

Novel clinical and therapeutic aspects in autoimmunity.

The Autoimmunity Congress has become a tradition and an important biannual event in the world of autoimmunity. The following issue of Immunological Research is dedicated to the important contributions that were presented during the recent Autoimmunity Congress that was held in Leipzig, Germany, on April 6–10, 2016, attended by 2210 participants. We will go through the essentials of these publications referring to novel clinical and therapeutic aspects in the following report. One-third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. These antibodies are associated with reduced drug levels, loss of drug efficacy, clinical non-responsiveness and an increased risk of adverse effects. Monitoring drug and anti-drug antibody levels appears to be a putative strategy for optimal and cost-effective intervention [1, 2]. Ogric et al. [3] reviewed the progress and the pitfalls of modern bioassays detecting anti-adalimumab antibodies. It is evident that successful detection of anti-ADL antibodies depends on selection of a proper assay, its capacity to break down potential immune complexes and to detect anti-ADL antibodies. This review presents the diverse methodologies available nowadays with their advantages and drawbacks. Henoch–Schonlein purpura (HSP) or immunoglobulin A (IgA) vasculitis is an immune complex vasculitis affecting small vessels with dominant IgA deposits [4]. It is characterized by a tetrad of palpable purpuric rash, arthralgia/arthritis, gastrointestinal symptoms (i.e., abdominal pain, gastrointestinal bleeding) and renal disease. Fenoglio et al. [5] summarized their clinical experience with rituximab therapy for HSP. There is evidence that glucocorticoids may reduce the severity and enhance resolution of extrarenal symptoms, especially arthritis, abdominal pain and swelling, yet we do not have solid data regarding glucocorticoid efficacy in patients with nephritis. The authors describe their promising experience with rituximab in a small series of adult HSP with biopsy-proven aggressive glomerulonephritis. All patients achieved a complete renal remission. Concurrent association of idiopathic thrombocytopenic purpura (ITP) and peripheral neuropathy is a rare condition. There are only a few case reports published concerning peripheral neuropathy with ITP. In their report Katchan et al. [6] describe a case study of a 47-year-old woman who was diagnosed with a two-year history of idiopathic thrombocytopenic purpura and who later developed a chronic combined inflammatory demyelinating polyneuropathy. While high-dose corticosteroid therapy yielded no benefit, the patient showed a significant improvement of platelet count and of the neuropathic symptoms following therapy intravenous immunoglobulin. Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. It is characterized by abundant autoantibodies that form immune complex with autoantigens and deposit in organs and cause tissue damage by inducing inflammation. The pathogenesis of SLE has been intensively studied but remains unclear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials and various genetic and epigenetic factors are believed to contribute to the initiation and development of SLE [7]. & Howard Amital howard.amital@sheba.health.gov.il

Evaluation of Peripheral Neuropathy of Unknown Origin in an Outpatient Foot and Ankle Practice.

The foot and ankle surgeon can see peripheral neuropathy in the treatment of foot and ankle conditions. The purpose of this study was (1) to evaluate the demographics and presenting complaints of patients diagnosed with idiopathic peripheral neuropathy during an examination by a foot and ankle surgeon and (2) to identify the type and frequency of subsequent diagnosis of medical causes of neuropathy. This was a retrospective study of patients diagnosed with idiopathic peripheral neuropathy in our practice between January 1997 and December 2008. Ninety-five patients were identified, and demographic data, presenting complaints, and medical comorbidities were extracted from the medical record. Examination findings of decreased sensation to Semmes Weinstein 5.07 monofilament testing were documented, and electromyogram and nerve conduction study results were reviewed when available. Laboratory values were noted, as were neurologic evaluations performed to diagnose medical conditions associated with peripheral neuropathy. The most common presentation was foot pain, in 36 patients (38%). Ninety-one patients had Semmes Weinstein 5.07 monofilament testing, with loss of protective sensation reported in 75 of the 91 tested (82%). Only 30 of the 95 patients had electromyogram and nerve conduction study results available, with a test positive for peripheral neuropathy in 20 of the 30 tested. Thirty-two patients were evaluated by a neurologist. A specific cause was identified in 12 of the 32 seen by a neurologist. Of the total group of 95 patients, 31 patients (33%) were diagnosed with a condition that may be associated with peripheral neuropathy. Thirty-three percent of the patients presenting to our clinic and given a diagnosis of idiopathic peripheral neuropathy were ultimately diagnosed with a medical cause of neuropathy-most commonly, diabetes. For those patients with idiopathic neuropathy, a spectrum of disease was encountered, including pain, ulcer, infection, and Charcot neuroarthropathy. Level IV, retrospective case series.

Case Report: Senile‐Onset Amyloidosis Presenting with Painful Lower Extremity Neuropathy

Case Report: Senile‐Onset Amyloidosis Presenting with Painful Lower Extremity Neuropathy

Charcot arthropathy of the foot and ankle in patients with idiopathic neuropathy.

Charcot neuroarthropathy in the developed countries is primarily associated with diabetic neuropathy. This study investigated a series of patients with Charcot arthropathy associated with idiopathic peripheral neuropathy to evaluate the natural history in these patients and to evaluate the efficacy of a treatment protocol used for diabetic Charcot joints. The records and radiographs of patients with Charcot arthropathy of the foot and ankle treated between 1986 and 2009 were retrospectively reviewed. Patients with known causes of or risk factors for peripheral neuropathy were excluded, identifying 82 feet in 59 patients with idiopathic neuropathy. Twenty-three (39%) were bilateral. The average age was 76 years and the average follow-up was 60 months. Data were analyzed for medical history and diagnoses, medications, anatomic classification of Charcot arthropathy, history of ulcerations, ambulatory status, shoe wear and bracing, and operative interventions. Patient care was based on previous published treatment algorithms, based on conservative management with operative intervention reserved for nonhealing ulcers, infection, and/or nonplantigrade, unbraceable feet. Therapeutic success was a plantigrade foot with healed soft tissue envelope that allowed weight-bearing. In all, 55% involved the midfoot (type 1), 34% the hindfoot (type 2), and 11% the ankle, (type 3A). Seventy-one of 82 feet were successfully treated at the time of last follow-up. Thirty-six feet (43%) were treated nonoperatively with success in 33 (92%). Forty-six of 82 feet required operative intervention, with success at last follow-up in 38 (83%). There were 8 operative failures resulting in 2 transtibial amputations and 6 feet with persistent ulceration. This series of patients with Charcot arthropathy associated with idiopathic neuropathy demonstrated a wider spectrum of Charcot arthropathy of the foot and ankle than has been previously recognized or documented. At the present time, heightened awareness is needed to promote accurate diagnosis and appropriate treatment in nondiabetic patients with Charcot arthropathy. Level IV, retrospective case series.