Course Of Peripheral Neuropathy Research Articles

Периферійна нейропатія при хламідійному реактивному артриті

Актуальність: периферійна нейропатія (ПНП) при реактивному хламідійному урогенітальному артриті (РХА) описується у вигляді поодиноких спостережень, і багато клініко-патогенетичних аспектів такого ураження нервової системи залишаються нез’ясованими. Мета дослідження: оцінити частоту й характер перебігу ПНП при РХА, взаємозв’язок нервових та суглобових ушкоджень, вивчити питання патогенетичних побудов цієї нейропатії, виділити чинники ризику. Матеріал і методи. Під наглядом перебував 101 хворий на РХА, середній вік яких становив 32 роки, тривалість захворювання — 4 роки, а співвідношення чоловіків і жінок — 1 : 1. У 90 % спостережень РХА виявлено Chlamydia trochamatis у секреті передміхурової залози, зіскобах з уретри, шийки матки, стінок піхви, у 83 % — позитивні серологічні тести на хламідійну інфекцію. Результати. При РХА ознаки ПНП мають місце в 19 % хворих у співвідношенні мононейропатія/полінейропатія як 1 : 1, із моторними, сенсорними і змішаними розладами в пропорції 1 : 3 : 6, наявністю вегетативних змін у кожного другого пацієнта та частішою дистальною локалізацією процесу в руках, на що впливають тяжкість перебігу суглобового синдрому, високі рівні протихламідійних антитіл у крові, а на аксональні й демієлінізуючі показники електронейроміографії — вираженість уражень урогеніталій і наявність синдрому Гійена — Барре. Високий показник темпів прогресування артриту є прогнознегативною ознакою перебігу ПНП у хворих на РХА. У патогенетичних побудовах ПНП беруть участь запальні імунні білки, порушення ендотеліальної функції судин та фізико-хімічні поверхневі реологічні властивості сироватки. Висновок. ПНП має місце в кожного п’ятого пацієнта з РХА, взаємопов’язана з клініко-лабораторними ознаками уражень суглобів, а в майбутньому буде корисним активне виявлення такої патології нервової системи для подальших своєчасних реабілітаційних заходів, причому серопозитивність РХА за антитілами до циклічного цитрулінового пептиду є чинником ризику такої ПНП.

Predictive Assay for Chemotherapy-Induced Peripheral Neuropathy Associated with Vinca Alkaloids in Lymphoid Malignancies

Introduction: Vinca alkaloids, such as vincristine, are important anticancer agents mainly employed in the treatment of hematological cancers. The principal mechanism for the antineoplastic activity is microtubule disruption. However, these agents also cause damage to mitochondria which leads to oxidative stress and production of reactive oxygen species (ROS). Other chemotherapeutic drugs that are suggested to cause peripheral neuropathy by this mechanism, i.e., increased oxidative stress, include taxanes and platinum compounds. Oxidative damage to peripheral neurons can cause damage to myelin sheath, mitochondrial proteins, and other antioxidant enzymes, resulting in hyperexcitability of peripheral neurons. This nerve damage results in the commonly seen dose-limiting neurological side effect chemotherapy-induced peripheral neuropathy (CIPN). Hence, assessment of biomarkers for peroxidation, myelin repair/maintenance, and red-ox balance (glutathione recycling) can be helpful in monitoring the on-set and course of peripheral neuropathy. We hypothesize that chemotherapeutic agents with similar effects on mitochondria (vinca alkaloids, taxanes and platinum compounds) will produce a specific pattern of glutathione recycling in patients prone to CIPN.Methods: Patients who had given written consent to participate in this exploratory single-centered, prospective IRB approved study contributed a blood sample prior to each treatment cycle. At each visit, the Rotterdam Symptoms Check-List (RSCL) was filled out and reported symptoms confirmed by comparison to notes in medical records.Whole blood was analyzed for glutathione recycling capacity using the bioactive probe hydroxyethyldisulfide (HEDS) and incubated at room temperature for 2 hours with gentle mixing. Prior to spectrophotometric determination, blood cells and proteinaceous thiols will be removed from the sample by acid precipitation and centrifugation. The final spectrophotometric reading will be converted into ME produced using the conversion factor provided in the assay kit Rockland Inc). Recycling capacity was compared to self-reported grade of CIPN.Results: Thus far we have enrolled 276 patients with an average age of 63.69 years (±12.85 STDEV; Range; 25-91). Patients are predominantly of Caucasian heritage (80.8%) along with 18.1 % African American and 1.1% Asian heritage. Females constitute 53.26 % of the cohort. To date we have 150 patients with more than 24 months of follow-up and among these patients, 5.5% had no reported symptoms of CIPN. Of those with severe CIPN (NCCN grade 3) neuropathy, 71% had a reduction in GSH recycling of greater than or equal to 40% from pre-treatment level. The reduced glutathione recycling capacity preceded on-set of symptoms by approximately 4 weeks. The majority of patients demonstrating this pattern of glutathione recycling had persistence CIPN that lasted for 6-18 months before an improvement was noted in medical records. We are currently assessing the value of adding biomarkers for lipid peroxidation and/or myelin formation/maintenance to further improve the likelihood ratio and AUROC values for the test.Conclusions: This data suggests the importance of GSH recycling in the ability to predict risk of CIPIN. Patients whose pre-treatment baseline was less than 1 or progressively dropped by at least 40%, seem to be at most risk for CIPN. Further, this may predict persistence of CIPN even after cessation of chemotherapy. Most patients in this cohort received taxanes or platinum therapy. However, given the similarity in mechanism and results from an early assessment of lymphoma patients treated with vinca alkaloids that resulted in similar outcomes with reduced glutathione recycling capacity suggest the possible use of this test to predict CIPN among lymphoma patients. DisclosuresNo relevant conflicts of interest to declare.

The course of peripheral neuropathy and its association with health-related quality of life among colorectal cancer patients

PurposeTo gain more insight into the course of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on health-related quality of life (HRQoL) in a population-based sample of colorectal cancer (CRC) patients up to 2 years after diagnosis.MethodsAll newly diagnosed CRC patients from four hospitals in the Netherlands were eligible for participation in an ongoing prospective cohort study. Patients (n = 340) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30) before initial treatment (baseline) and 1 and 2 years after diagnosis.ResultsAmong chemotherapy-treated patients (n = 105), a high sensory peripheral neuropathy (SPN) level was reported by 57% of patients at 1 year, and 47% at 2-year follow-up, whereas a high motor peripheral neuropathy (MPN) level was reported by 47% and 28%, at years 1 and 2, respectively. Linear mixed model analyses showed that SPN and MPN symptoms significantly increased from baseline to 1-year follow-up and did not return to baseline level after 2 years. Patients with a high SPN or MPN level reported a worse global quality of life and a worse physical, role, emotional, cognitive, and social functioning compared with those with a low SPN or MPN level.ConclusionsFuture studies should focus on understanding the mechanisms underlying CIPN so targeted interventions can be developed to reduce the impact of CIPN on patient’s lives.Implications for cancer survivorsPatients need to be informed of both CIPN and the impact on HRQoL.

Delayed recovery and increased severity of Paclitaxel-induced peripheral neuropathy in patients with diabetes.

Although diabetes mellitus (DM) is recognized as a risk factor for chemotherapy-induced neurotoxicity, its true impact on intensity and time course of peripheral neuropathy is still unclear. The goal was to analyze the relevance of preexisting DM to weekly paclitaxel-induced peripheral neuropathy (PIPN). We performed a retrospective case-control study (1:2) including a total of 129 patients with breast cancer (43 with DM and 86 controls) treated with single-agent weekly paclitaxel (wP). Compared with controls, patients with DM treated with wP experienced PIPN more frequently (74.4% vs 58.4%; P=.016) and with higher severity (grade 2-3: 51.2% vs 27.7%; P=.014). A significant delay in PIPN resolution was observed in women with DM (P=.001) and, in a multivariate analysis, DM was the only independent predictor for delayed recovery (hazard ratio [HR], 0.16; 95% CI, 0.05-0.55; P=.003). After 2 years, 68.7% of patients with DM (vs 29.2% of women without DM) still experienced PIPN, which was functionally significant (grade 2-3) in 18.2%. Significantly more dose delays and reductions because of PIPN occurred in patients with DM. Preexisting DM associates with long-lasting significant PIPN in patients treated with wP. Benefits and risks of long-term significant PIPN should be carefully balanced in patients with DM before starting wP chemotherapy.

Clinico-electrophysiological and pathological characteristics of neuropathy in Sjögren's syndrome: a report of 5 cases

To summarize the clinical features, electrophysiological and neuropathological characteristics of peripheral nerves in patients with primary Sjögren's syndrome (SS). We retrospectively analyzed the clinical, electrophysiological and neuropathological characteristics of 5 female SS patients with neuropathy complications undergoing electrophysiology and sural nerve biopsy at our department from January 2011 to June 2013. They had an age range of 20-75 years. The course of peripheral neuropathy ranged 0.5-60 months and the whole course 12-240 months. pSS-associated neuropathy included multiple mononeuropathy (n = 1), symmetrical axonal sensorimotor polyneuropathy (n = 1) and sensory ganglioneuronopathy (n = 3). All biopsies showed varying degrees of myelinated fiber loss. Three biopsies had axonal degeneration associated with demyelination. However, there was no formation of onion bulb regeneration or plexus. Necrotizing vasculitis was diagnosed in 2 cases. The manifestations of peripheral nerve n pSS include multiple mononeuropathy, axonal symmetric sensorimotor polyneuropathy and sensory gangioneuronopathy. Sural biopsy shows typical necrotizing vasculitis in some cases and myelinated fiber loss and axonal degeneration in others. The pathogenic mechanisms of neurological involvement in pSS remain unknown. However, vasculitis, ischemic and immunological insults resulting in sensory gangioneuronopathy have been described.

Lenalidomide Therapy Is Associated with Improvement of Peripheral Neuropathy in Patient with Relapsed/Refractory Multiple Myeloma: Preliminary Results From a Single-Centre Prospective Non Interventional Study.

Abstract 4949In recent years, proteasome inhibitors and immunomodulatory drugs (IMIDs) have provided invaluable advantage in the therapy of multiple myeloma (MM) in terms of disease free survival and often overall survival. However the benefits have sometimes been blunted by the occurrence of adverse effects which strongly impact quality of life. Among them, peripheral neuropathy (PN) represents one of the most disabling and often dose-limiting side effect. Lenalidomide, a second generation IMID and a structural analogue of thalidomide, has been claimed to have low toxicity on peripheral nervous system. In a single-centre prospective study we evaluated the natural history of chemotherapy-induced PN in consecutive patients previously treated with bortezomib and/or thalidomide, who shifted to lenalidomide for relapsed or refractory MM. The aim was to evaluate the clinical course of PN during lenalidomide therapy. Patients and methods34 consecutive patients previously treated with bortezomib and/or thalidomide were treated with lenalidomide (25 mg daily for 21 day cycle) alone or associated with low dose dexametasone for relapsed/refractory MM. Patients previously treated with bortezomib and/or thalidomide, who developed a chemotherapy-induced PN and whose MM was still in remission, were used as control. Neurological evaluation was planned at baseline, after 6 and 12 months from the beginning of lenalidomide therapy. Patients were assessed with the Total Neuropathy Score clinical version (TNSc), which has been previously validated against the most common neurotoxicity scales used by oncologists (NCI-CTC 2.0, ECOG); pain was assessed with the visual analogue score (VAS). The Eastern Cooperative Oncology Group (ECOG) performance status was also assessed. Nerve conduction studies were performed at the beginning of the treatment and regularly during follow up. Lack of chemotherapy-induced PN at baseline was not an exclusion criteria, as well as progression of myeloma during lenalidomide treatment. ResultsOf the 34 patient in lenalidomide therapy, sixteen (mean age 66 yrs ± 8) were available for evaluation with at least six months follow up. Fourteen patients presented chemotherapy-induced PN at baseline, confirmed also by neurophysiological studies. Two patients had no PN at baseline (TNSc: 0) despite previous exposure to bortezomib in one case, and bortezomib and thalidomide in the other case. The majority of evaluable patients (75%) had a TNSc >2 at baseline (median = 6.7, SD ±3.6, range 3-15). Two patients had a baseline TNSc ' 2 (median 1,5). After 6 months of follow up, hematological response was documented in 14 patients (4 patients were in VGPR, 10 in PR) whereas 2 patients were in progression after initial response. Neurological evaluation after 6 months revealed improvement or stability of symptoms and neurological scale in 12 out of 14 patients (TNSc 5.5, SD ±3.9 at baseline vs 3.8, SD ±2.2 post 6 months therapy, respectively). The improvement of symptoms was generally more evident in those patients with the highest baseline TNSc. One patient with bortezomib and thalidomide-induced PN, while presenting a subjective and neurophysiologic improvement, had a worse TNSc score due only to a worse vibration sensibility score alone. However, this patient was also on antituberculosis treatment with isoniazid, which is known to be neurotoxic. Two patients without PN at baseline, still remained with score 0 at 6 months follow up. As expected, clinical improvement not always correlated with electrophysiological improvement. In two cases evaluation at one year was possible, and data showed a continuous improvement of PN. ConclusionsUsing validated clinical and instrumental tools, the preliminary results of our prospective study suggest that during lenalidomide therapy PN improves, regardless of myeloma response. Updated results of the study will be presented at the meeting. The results of the on-going follow up study on a wider population of patients will help confirm these data and define appropriate timing for the detection of electrophysiological improvement. DisclosuresNo relevant conflicts of interest to declare.

Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy

The current prospective study sought to trace the incidence and severity of cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its clinical and electrophysiological pattern. Furthermore, it was attempted to describe its evolution by following up the course of peripheral neuropathy (PN) during chemotherapy as well as 3 months after its discontinuation. Thirteen adult patients scheduled to be treated with six courses of cumulative DDP+P-based regimens for a non-myeloid malignancy participated in this study. These patients were clinically and electrophysiologically monitored at baseline, during chemotherapy and 3 months after its discontinuation. The severity of PN was summarized by means of a modified PN score. Evidence of PN was disclosed in nine of the 13 patients (69.2%). The mean PN score for patients that manifested some grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons concerning the motor conduction velocities (MCV) variables failed to reach significance. By contrast, comparisons of the mean changes at baseline and each of the follow-up studies revealed a significant decrease in all sensory action potentials examined. The follow-up evaluation performed 3 months after the discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists and progresses over time. Our results indicate that the majority of patients treated with a DDP+P-based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity, which would persist for several months after the discontinuation of chemotherapy.

Peripheral neuropathy in Krabbe disease

Hematopoietic stem cell transplantation (HSCT) may slow the progression of Krabbe disease (KD) if performed early in the disease. The authors' studies indicate that more than 90% of patients with KD have severe abnormalities in peripheral nerve conduction. To assess the effect of HSCT on nerve conduction in patients with KD. The authors performed serial nerve conduction studies (NCS) in 12 patients with KD after HSCT. The average follow-up was 18 months (6 months to 3 years) after HSCT. Pretransplant NCS were not available in two patients; all others (10 of 12) had significant pretransplant abnormalities. After HSCT, previously absent F-waves (1 patient) and sural sensory responses (SNR) (3 patients) were found recordable. All patients continued to have recordable SNR after HSCT, and these became normal in 7 of 12 patients. Distal motor nerve latency became normal in 6 of 17 and motor nerve conduction velocity (CV) in 2 of 17 nerves; F-wave latencies (FWL) improved in 6 of 17 nerves, but did not become normal in any. There was greater improvement in nerve conduction abnormalities if the transplant was performed earlier in life. After an initial improvement, there was subsequent worsening of motor latencies (2 of 12), motor CV (2 of 12), FWL (3 of 12), and SSR (1 of 12), indicating that benefit from HSCT may be temporary. Serial nerve conduction studies are useful in following the course of peripheral neuropathy in Krabbe disease. Hematopoietic stem cell transplantation is followed by improvement in peripheral nerve conduction abnormalities in these patients, suggesting remyelination of the nerves.

Green tea pain modulating effect in sciatic nerve chronic constriction injury rat model

We investigated the effect of green tea (GT) in unilateral chronic constriction injury (CCI) to the rat scaitic nerve. Five groups ( n = 6 rats/group) sham group: rats which underwent operation but with no ligation to the scaitic nerve, and received tap water for two weeks before and for five weeks after the surgery. Four experimental groups underwent CCI to the right sciatic nerve, divided randomly as follows: group E were given tap water throughout the study. Group B received GT before and after CCI. Group C was given GT following CCI. Group D received GT for two weeks prior to CCI. Groups which consumed GT showed significant improvement in the toe spread ( P Consumption of GT improves both reflexes and sensation which are often affected in the course of peripheral neuropathy.

Incidence and Clinical Course of Peripheral Neuropathy in Patients Receiving Thalidomide for the Treatment of Multiple Myeloma.

Background: Although thalidomide induced neuropathy has been described for decades, many features such as incidence, risk factors, severity and character of the neuropathy are not well defined. We retrospectively reviewed the incidence and clinical course of peripheral neuropathy in patients treated with thalidomide or thalidomide/dexamethasone (Thal/Dex) on a Phase II Mayo Clinic trial.Methods: Patients who participated in a Mayo Clinic Phase II trial of thalidomide in myeloma were studied. In this trial, patients with SMM and RMM received thalidomide 200 mg per day escalated as tolerated to a maximum of 800 mg/day. Patients with NMM received thalidomide 200 mg/day plus dexamethasone 40 mg/day orally on days 1–4, 9–12, 17–20 (odd cycles) and 40 mg/day days 1–4 (even cycles) repeated monthly. The incidence and clinical course of neuropathy was assessed by chart review. The study was approved by the Mayo Clinic Institutional Review Board.Results: All 113 patients (70 male, 43 female) treated on trial were studied; 31 patients with smoldering/indolent myeloma (SMM), 32 patients with relapsed/refractory myeloma (RMM) and 50 patients with newly diagnosed myeloma (NMM). Patients were accrued to the parent protocol from April 1999 through March 2002. The median age was 62 years (range, 36–78). The median duration of thalidomide therapy on protocol was 15 months in SMM, 6 months in RMM and 4 months in NMM. Overall, 63 patients (56 %) developed symptoms of peripheral neuropathy. The incidence of neuropathy was 77%, 50%, and 46% in patients with SMM, RMM, and NMM, respectively. Neuropathy worsened during the treatment phase with/without dose reduction or after cessation in 15%, remained stable in 52%, and improved in 27%. Overall grade of neuropathy was grade 1 in most pts; 11% of all patients had grade 2 neuropathy and 2% had grade 3 neuropathy. Predominant symptoms of neuropathy were tingling and numbness involving both upper limb and lower limbs. Small subsets of patients complained of hearing loss 6 patients), and erectile dysfunction (4 patients). Electromyographic studies and nerve conduction studies were performed in 11 patients; the most common finding was a length dependent axonal neuropathy.Conclusion: Peripheral neuropathy is an important and common adverse event with thalidomide therapy that often limits the dose and duration of treatment. Its incidence and severity are likely related to dose and duration of therapy.

What Is the Course of Peripheral Neuropathy in Lupus

Peripheral neuropathy occurs in as many as one third of patients with systemic lupus erythematosus (SLE) and typically manifests as a mild, distal