Mild Peripheral Neuropathy Research Articles

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% (20/23) in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Incidence and Clinical Presentation of Severe Neurotoxicity from Nelarabine in Patients with T-Cell Acute Lymphoblastic Leukemia

BackgroundNelarabine is a purine analog with demonstrated efficacy in the treatment of T-cell Lymphoblastic Leukemia and Lymphoma (T-ALL/LBL). Despite its efficacy and excellent blood-brain barrier penetration, it has a significant side effect profile which is namely concerning for neurotoxicity. Reported neurotoxicity has varied from mild peripheral neuropathy to debilitating grade 4 neurologic complications including Guillain-Barre like syndrome and myelopathy. Patients and MethodsWe conducted a single centered, retrospective case series to study patients who developed severe neurotoxicity after receiving nelarabine as part of T-ALL treatment. One hundred thirty-five patients were identified. Thirteen patients were reviewed for severe neurotoxicity (defined as ≥grade 3), and of those five patients were deemed to have neurotoxicity secondary to nelarabine exposure. ResultsFive patients (4%) developed severe neurotoxicity as manifested by Guillain-Barre like syndrome or myelopathy within a timeframe of eight to fifty-eight days from last nelarabine dose. Upon diagnosis, patients received formal neurologic evaluation by our neuro-oncology specialists including imaging, cerebrospinal fluid testing, and electromyography. Patients were treated with IVIG, and steroids upon diagnosis, but the majority of neuro-deficits were irreversible. ConclusionOur study shows that nelarabine is generally well-tolerated, and the incidence of severe neurotoxicity is rare. Given the potential risk of severe neurotoxicity, we propose capped dose of nelarabine 1000 mg/day, neurological assessment before subsequent dosing, and avoidance of simultaneous IT therapy during nelarabine administration.

Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A (α-Gal). Loss of α-Gal activity leads to progressive lysosomal accumulation of α-Gal substrate, predominately globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). FD manifestations include early onset neuropathic pain, gastrointestinal symptoms, and later onset life-threatening renal, cardiovascular and cerebrovascular disorders. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing cardiac efficacy of new drugs. Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. Reports of minor cardiac function abnormalities in GlaKO model are inconsistent between different studies. Recently, G3Stg/GlaKO was generated by crossbreeding GlaKO with transgenic mice expressing human Gb3 synthase. G3Stg/GlaKO demonstrate higher tissue substrate accumulation and develop cellular and tissue pathologies. Functional renal pathology analogous to that found in early stages of FD has also been described in this model. The objective of this study is to characterize cardiac phenotype in GlaKO and G3Stg/GlaKO mice using echocardiography. Longitudinal assessments of cardiac wall thickness, mass and function were performed in GlaKO and wild-type (WT) littermate controls from 5-13 months of age. G3Stg/GlaKO and WT mice were assessed between 27-28 weeks of age due to their shortened lifespan. Several cardiomyopathy characteristics of early Fabry pathology were found in GlaKO mice, including mild cardiomegaly [up-to-25% increase in left ventricular (LV mass)] with no significant LV wall thickening. The LV internal diameter was significantly wider (up-to-24% increase at 9-months), when compared to the age-matched WT. In addition, there were significant increases in the end-systolic, end-diastolic volumes and stroke volume, suggesting volume overload. Significant reduction in Global longitudinal strain (GLS) measuring local myofiber contractility of the LV was also detected at 13-months. Similar GLS reduction was also reported in FD patients. Parameters such as ejection fraction, fractional shortening and cardiac output were either only slightly affected or were not different from controls. On the other hand, some of the cardiac findings in G3Stg/GlaKO mice were inconsistent with Fabry cardiomyopathy seen in FD patients. This could be potentially an artifact of the Gb3 synthase overexpression under a strong ubiquitous promoter. In conclusion, GlaKO mouse model presents mild cardiomegaly, mild cardiac dysfunction, but significant cardiac volume overload and functional changes in GLS that can be used as translational biomarkers to determine cardiac efficacy of novel treatment modalities. The level of tissue Gb3 accumulation in G3Stg/GlaKO mouse more closely recapitulates the level of substrate accumulation in FD patients and may provide better translatability of the efficacy of new therapeutics in clearing pathological substrates from cardiac tissues. But interpretation of the effect of treatment on cardiac structure and function in this model should be approached with caution.

Prevalence and disease burden of peripheral neuropathy in the general population in Mexico city: a cross-sectional epidemiological study

Objective Peripheral neuropathy (PN) is one of the most common diseases of the peripheral nervous system. Symptoms range from mild sensory signs to severe neuropathic pain. Untreated PN is progressive and can lead to complications and impair quality of life (QoL). However, PN prevalence is underestimated in the general population and affected individuals often remain undiagnosed. This study aimed to contribute to the global generation of prevalence data and determine sociodemographic and disease-related characteristics of PN sufferers. Methods This cross-sectional study collected information on PN prevalence and associated factors in the adult population (40–65 years) of the Mexico City area. Participants were recruited in public places and screened for PN using the Michigan Neuropathy Screening Instrument (MNSI). Subjects with PN answered the Neuropathy Total Symptom Score-6 (NTSS-6), the Short Form-36 Health Survey (SF-36), and the QoL Pharmacoeconomic Questionnaire. Statistical analysis included descriptive methods and calculation of PN prevalence with 95% confidence intervals. Results Of 3066 participants, 448 had PN based on the MNSI physical examination. The overall PN prevalence was 14.6%, with the highest (18.9%) seen in subjects aged 61–65 years. PN was undiagnosed in 82.6%, and 62.9% had never heard of PN. Although half of all subjects had only mild PN symptoms, QoL was impacted in 91.8%. Conclusions The results confirm that PN prevalence in the general population is high. Despite the disease burden, most affected persons are undiagnosed and unaware of the disease. Almost all felt their QoL was impacted. The data highlight the need to raise awareness and identify undiagnosed individuals to prevent complications.

Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

To investigate the etiology of cerebellar ataxia in an adult male patient. We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities. The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms. Nerve conduction studies showed mild peripheral sensory neuropathy and normal motor nerve conduction velocities. Brain imaging showed progressive cerebellar atrophy and gliosis of the olivopontocerebellar fibers, characterized by T2 hyperintensity within the pons. Genetic testing revealed a likely pathogenic germline variant in MFN2 (NM_014874: c.[838C>T];[=], p.(R280C)) in the GTPase domain (G) interface; pathogenic variants of MFN2 typically cause hereditary sensory and motor neuropathy VI or Charcot-Marie-Tooth disease 2A. The presence of progressive ataxia, "hot cross bun" sign, and dysautonomia has been associated with multiple system atrophy, cerebellar type (MSA-C). We describe progressive cerebellar ataxia in an individual with a deleterious variant in MFN2. Our findings suggest that pathogenic variants in MFN2 can result in a spectrum of phenotypes including cerebellar ataxia with cerebellar-pontine atrophy in the absence of significant neuropathy and in a manner closely resembling MSA-C.

Heterozygous variants in TBCK cause a mild neurologic syndrome in humans and mice.

TBCK-related encephalopathy is a rare pediatric neurodegenerative disorder caused by biallelic loss-of-function variants in the TBCK gene. After receiving anecdotal reports of neurologic phenotypes in both human and mouse TBCK heterozygotes, we quantified if TBCK haploinsufficiency causes a phenotype in mice and humans. Using the tbck+/- mouse model, we performed a battery of behavioral assays and mTOR pathway analysis to investigate potential alterations in neurophysiology. We conducted as well a phenome-wide association study (PheWAS) analysis in a large adult biobank to determine the presence of potential phenotypes associated to this variant. The tbck+/- mouse model demonstrates a reduction of exploratory behavior in animals with significant sex and genotype interactions. The concurrent PheWAS analysis of 10,900 unrelated individuals showed that patients with one copy of a TBCK loss-of-function allele had a significantly higher rate of acquired toe and foot deformities, likely indicative of a mild peripheral neuropathy phenotype. This study presents an example of what may be the underappreciated occurrence of mild neurogenic symptoms in heterozygote individuals of recessive neurogenetic syndromes.

A Geriatrician’s Perspective on an Aging Joe Biden

A Geriatrician’s Perspective on an Aging Joe Biden

The Association between Waist Hip Ratio and Severity of Diabetic Peripheral Neuropaty in Diabetes Melitus Type 2 by Using Toronto Clinical Scoring System

Introduction: Diabetic neuropathy is a common and progressive microvascular complication of diabetes, so early detection and prevention is very important. Other modifiable risk factors such as hypertension, dyslipidemia, or central obesity can be managed. Central obesity with insulin resistance is a key pathophysiological factor in the metabolic syndrome. Waist hip ratio (WHR) has been proposed as a tool for detecting central obesity. Toronto Clinical Scoring System (TCSS) is a diabetic neuropathy scoring system that has high sensitivity and specificity. The aim of this study was to determine the relationship between waist hip ratio and the severity of peripheral diabetic neuropathy in type 2 Diabetes Melitus (DM) according to the Toronto Clinical Scoring System (TCSS). Method: This study used a cross-sectional design. Sampling was conducted at the Endocrinology Polyclinic and Neurology Polyclinic Hospital H. Adam Malik Medan. The research sample was taken as many as 45 subjects consecutively. TCSS examination is performed to diagnose and determine the severity of diabetic neuropathy Therefore, waist hip ratio was calculated to assess central obesity. Data analysis using Chi Square test. Results: On the demographic characteristics of the research subjects were male, age range 51-60 years, high school education level, not working, history of DM 5-10 years. The mean value of WHR is 0.87±0.051. Median TCSS Score 10 (6-16). The majority of subjects had mild diabetic peripheral neuropathy. Patients with central obesity had a grading of neuropathy that was classified as severe as many as 13 people (56.5%), moderate as many as 7 people (30.4%), and mild as many as 3 people (13.0%). While patients who are not obese have a grading of neuropathy that is classified as severe as many as 1 person (4.5%), moderate as many as 5 people (22.7%), mild as many as 16 people (72.7%). Based on the Chi Square test, it was found that there was a significant association between the waist hip ratio and the severity of diabetic peripheral neuropathy in type 2 DM patients with p<0.01. Conclusion: There is a statistically significant association between waist hip ratio and the severity of diabetic neuropathy in type 2 DM with p < 0.01.

Amyloid Myopathy as Initial Manifestation of ATTRwt: A Rare Phenomenon (P9-8.007)

<h3>Objective:</h3> To describe a rare presentation of amyloid myopathy. <h3>Background:</h3> Wild-type transthyretin amyloidosis (ATTRwt) is an age-related progressive disease with limited treatment options. Cardiomyopathy and peripheral neuropathy are well-recognized manifestations of transthyretin (ATTRwt) amyloidosis but myopathy is rarely the initial presentation. <h3>Design/Methods:</h3> NA <h3>Results:</h3> An 80-year-old man presented with slowly progressive bilateral lower limb weakness for over 5 years making him bedridden for one year. He denied any oculo-bulbar, sensory, or autonomic symptoms and reported no family history of neuromuscular disease. Physical examination revealed severe symmetric weakness of hip flexors and quadriceps and mild weakness of proximal arms bilaterally. Laboratory workup showed normal CK and no myositis antibodies were detected. Screen for monoclonal protein was negative. EMG performed was consistent with an irritable chronic myopathic process predominantly affecting the proximal leg muscles, along with a mild length-dependent peripheral neuropathy. Right quadriceps biopsy revealed fairly diffuse atrophic changes associated with focal amyloid deposition within adipose tissue and the blood vessel wall without any inflammation. Mass spectrometry suggested ATTR type amyloid and TTR genetic testing was negative confirming diagnosis of ATTRwt amyloid myopathy. A cardiac PYP scan showed diffusely increased myocardial uptake of the radiotracer. Patient was started on Tafamidis by cardiologist to slow disease progression. <h3>Conclusions:</h3> Neurological manifestations of ATTRwt are being increasingly recognized but myopathy is rarely reported as an initial presentation. The clinical presentation of myopathy can mimic other relatively common neuromuscular disorders and hence a high index of suspicion and through workup is needed to confirm diagnosis. Patients can have concomitant cardiomyopathy, which is potentially treatable, and therefore increased awareness is required. Supportive therapy remains the mainstay of therapy for neurological involvement, but future studies can pave the way for targeted treatments. <b>Disclosure:</b> Dr. Bovino has nothing to disclose. Dr. Young has nothing to disclose. Peter Pytel has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Colianni&amp;Colianni. Peter Pytel has received publishing royalties from a publication relating to health care. Dr. Nadkarni has nothing to disclose. Dr. Paul has nothing to disclose.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

Thiamine-responsive pyruvate dehydrogenase complex deficiency presenting as recurrent muscle weakness: Identification of a novel mutation (p.T111I) in the PDHA1 gene.

How T118M peripheral myelin protein 22 predisposes humans to Charcot–Marie–Tooth disease

Data from gnomAD indicates that a missense mutation encoding the T118M variation in human peripheral myelin protein 22 (PMP22) is found in roughly 1 of every 75 genomes of western European lineage (1:120 in the overall human population). It is unusual among PMP22 variants that cause Charcot-Marie-Tooth disease (CMT) in that it is not 100%-penetrant. Here, we conducted cellular and biophysical studies to determine why T118M PMP22 predisposes humans to CMT, but with only incomplete penetrance. We found that T118M PMP22 is prone to mistraffic, but differs even from the WT protein in that increased expression levels do not result in a reduction in trafficking efficiency. Moreover, the T118M mutant exhibits a reduced tendency to form large intracellular aggregates relative to other disease mutants and even WT PMP22. NMR spectroscopy revealed that the structure and dynamics of T118M PMP22 resembled those of WT. These results show that the main consequence of T118M PMP22 in WT/T118M heterozygous individuals is a reduction in surface-trafficked PMP22, unaccompanied by formation of toxic intracellular aggregates. This explains the incomplete disease penetrance and the mild peripheral neuropathy observed for WT/T118M CMT cases. We also analyzed BioVU, a large biobank linked to de-identified electronic medical records, and found a statistically robust association of the T118M mutation with the occurrence of long and/or repeated episodes of carpal tunnel syndrome. Collectively, our results both illuminate the cellular effects of the T118M PMP22 variation leading to CMT disease and indicate a second disorder for which it is a risk factor.

Neurochondrin Autoimmunity With Slow Saccades: A Case Report

Objective N/A. Background Neurochondrin is a cytoplasmic neuronal antigen that can be targeted by specific antibodies, resulting in an antigen-specific T-cell response and autoimmune cerebellar and brain stem degeneration.1 Previously reported cases of neurochondrin antibody positivity have been predominantly associated with rapidly-progressive rhombencephalitis, but various other neurological symptoms and signs may be present.1,2 Design/Methods N/A. Results 34-year-old woman presented with 2 years of constant numbness in her toes, gradually worsening to involve the entire lower and upper extremities. She also reported dysarthria, imbalance, and leg spasticity. Neurological examination showed a slow, wide-based gait, brisk reflexes bilaterally, and bilateral extensor plantar responses. MRI brain was normal and CSF analysis showed 7 oligoclonal bands. The patient was diagnosed with probable multiple sclerosis and steroids were initiated but resulted in no improvement of symptoms. Plasmapheresis was also ineffective. 3 months later, MRI showed subtly increased T2 signal of the central cord mainly involving the gray matter at the level of C5 and C6. CSF analysis showed 15 oligoclonal bands and an elevated IgG index of 1.39. VDRL was nonreactive. HTLV, ANCA, AQP4, CSF VZ PCR, HSV PCR, and HHV6 PCR were all negative. EMG showed mild length-dependent axonal sensory motor peripheral neuropathy. On neuro-ophthalmic examination, the patient showed slowed saccades with some preservation of optokinetic nystagmus (OKN) fast phases. Repeat MR showed abnormal T2 hyperintensity in the anterior horns of the gray matter from C1-2 to T1. Serum testing at that time showed a positive neurochondrin antibody. She was then started on cyclophosphamide and mycophenolate mofetil. 6 months after initiation of cyclophosphamide, dysarthria and upper limb mobility improved, and she had no further neurological deterioration at that time. Conclusions Neurochondrin IgG-related autoimmunity is rare and can result in a wide variety of neurological signs and symptoms. Ocular dysmotility, including slowed saccades, may be present.

The predictive value of fibrinogen in the occurrence of mild cognitive impairment events in patients with diabetic peripheral neuropathy

BackgroundResearch suggests that fibrinogen (Fib) is related to mild cognitive impairment (MCI) and diabetic peripheral neuropathy (DPN) and the risk of MCI in patients with DPN is greatly increased, although no studies have evaluated the predictive value of Fib for the risk of MCI in patients with DPN.MethodsThis prospective observational clinical study enrolled 207 type 2 diabetes mellitus (T2DM) patients, who were divided into diabetes with no neuropathy (102 cases) and diabetes with neuropathy (105 cases) groups. Meanwhile, 90 healthy unrelated subjects were recruited as controls. The incidence of MCI in the DPN patients was followed up for 2 years. Divide patients in the DPN group into subgroups according to whether MCI occur, use multivariate logistic regression to analyze independent factors of MCIs in DPN patients within 2 years, and use ROC curve to analyze the predictive value of Fib for MCI in DPN patients.ResultsFib levels were significantly higher in diabetic subjects with neuropathy compared with those without (P < 0.001). In further subgroup analysis of DPN patients who were divided according to the occurrence of MCI, baseline data of the MCI subgroup showed Fib levels were higher than that in the non-MCI group while education levels declined (P < 0.001). The education level and increased Fib levels were independent factors for the occurrence of MCI within 2 years after the onset of DPN (OR = 0.769, 95% CI: 0.605 ~ 0.968, P = 0.037; OR = 2.674, 95% CI: 1.094 ~ 3.168, P = 0.002). The ROC curve indicated that the predictive value of Fib was (AUC = 0.764, 95% CI: 0.671 ~ 0.842, P < 0.001).ConclusionsFib may function as a predictor for assessing the risk of MCI in DPN patients.

Second report of SHMT2 related neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities

Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities (NEDCASB; MIM# 619121) is a recently described metabolic disorder with characteristic features of mild dysmorphism, intellectual disability, spasticity, peripheral neuropathy, cardiomyopathy, and thin corpus callosum. Biallelic variants in SHMT2 (MIM 138450), encoding mitochondrial serine hydroxymethyltransferase enzyme, have been recently linked to this disorder. Till now, a total of seven variants including six missense and one deletion-insertion has been reported in SHMT2. We hereby report an additional individual with novel homozygous missense variant c.1133A > G in SHMT2 (NM_005412.6) identified by exome sequencing and review the phenotype and genotype of the previously reported individuals with NEDCASB.

OCULAR MANIFESTATIONS OF ASP38ALA AND THR59LYS FAMILIAL TRANSTHYRETIN AMYLOIDOSIS.

To describe the ophthalmic manifestations of familial transthyretin amyloidosis (FTA) mutations, including Asp38Ala and Thr59Lys, which have not been previously reported to have ocular involvement. This is an observational case series of prospectively collected data of 16 patients with FTA who were taking tafamidis for mild peripheral neuropathy and underwent a comprehensive ophthalmic examination at a single tertiary center, between January 2013 and March 2020. The ocular involvement of each FTA mutation type and the specific manifestations were the main outcome measures. Six of 16 patients with FTA manifested ocular involvement. Ocular involvement was noted in two of three patients with Glu89Lys mutations having retinal deposits, retinal hemorrhages, and corneal opacity. Three of nine patients with Asp38Ala mutations and one of two patients with Thr59Lys mutations showed ocular involvement that had not been previously described. The ophthalmic findings included glaucoma, anterior lens capsule opacity, vitreous opacity, and retinal deposits. The decrease in vascular flow due to perivascular cuffing of the amyloid deposits was detected by optical coherence tomography angiography. The current study newly described that two transthyretin mutation types of FTA, Asp38Ala and Thr59Lys, may manifest with ocular findings such as anterior lens capsule opacity and retinal deposits.

Alterations in plantar vessel blood flow in patients with mild diabetic peripheral neuropathy

IntroductionEarly identification and treatment of diabetic peripheral neuropathy (DPN) are crucial. Presently, the mechanism of DPN is not very clear, and there are inconclusive conclusions about the influencing factors of...

Induction Therapy With Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) For Primary Plasma Cell Leukemia (pPCL)

IntroductionPrimary plasma cell leukemia (pPCL) is an uncommon, highly aggressive plasma cell dyscrasia with a poor prognosis. A limited number of small retrospective studies have reported promising results in treating PCL using the novel agent bortezomib (btz). We therefore undertook a retrospective study of our cohort of patients (pts) with newly diagnosed pPCL treated with cyclophosphamide, btz, and dexamethasone (CyBorD) as front-line therapy. MethodsBetween August 2008 and June 2013, 10 newly diagnosed pts with pPCL (≥20% PCs in peripheral blood and/or absolute PCs ≥ 2.0x109/L) were referred to Princess Margaret Cancer Centre. Pts received a median of 4 (range 4-8) 28-day cycles of CyBorD induction consisting of weekly cyclophosphamide 300 mg/m2po, weekly btz 1.5 mg/m2IV or SQ, and dexamethasone in pulse fashion for cycles 1 and 2 and then weekly as well. Hematologic responses were assessed using IMWG consensus criteria for serological, and, if available, bone marrow, criteria. Survival times were measured from the time of first treatment. ResultsThe median age was 54 yrs (range 45-68); 6 were male. Median (range) hemoglobin was 85 g/L (27-135), creatinine 212 umol/L (57-404), albumin 37g/L (25-47), LDH 215 U/L (163-537) and β2-microglobulin 441 nmol/L (295-1136); median WBC was 10.6 (4.8-32.2), ANC 2.0 (1.4-3.3), and platelet count 94 (36-159) x 109/L. Abnormal cytogenetics were common; of 9 pts with FISH results available, 4 pts had deletion 13q (44.4%), 3 had deletion 17p (33.3%), 3 had t(14;16) (33.3%), 4 had t(11;14) (44.4%) and 2 had other changes (22.2%). The overall response rate (ORR defined as ≥ PR) after CyBorD induction was 100% and included PR in 3 pts (33.3%), VGPR in 5 pts (50%), and CR in 2 pt (20%). Nine pts underwent successful stem cell (SC) mobilization with cyclophosphamide + G-CSF (median CD 34+ cells 3.42 x 106/kg [range 2.16-7.31]); 1 pt, who has been given 8 cycles to date, is awaiting a second attempt at SC collection. Two other patients relapsed after completion of planned induction while awaiting transplant; these required additional therapy to control the disease before ASCT. In total, 9 pts have undergone subsequent ASCT, including tandem ASCT in 4 pts. After ASCT, 1 pt received maintenance therapy with thalidomide, while 6 more recently treated pts were given lenalidomide maintenance. Best responses post-ASCT were as follows: ≥ PR in all 9 pts (100%, specifically PR in 1 (11.1%), VGPR in 4 (44.4%), and CR in 4 (44.4%, including 1 pt with nonsecretory disease in documented CR pre-ASCT who was not formally reassessed but clinically remained in CR after ASCT). Five patients have relapsed post-ASCT with time to relapse from ASCT of 13.5 mos (range 3-38), including both pts who had progressed and required additional therapy before ASCT (time to relapse 3 and 4 months). The median PFS for all pts from the start of therapy was 18 mos (range 4-44 mos).Currently, 7 pts (70%) are alive after a median follow-up of 25 mos (range 8-58); 5 of these pts are alive without relapse after a median of 25 mos (range 8-28) while 2 pts (20%) are alive after ≥ 1 relapse at a median of 49 mos (range 39-58). Three pts (30%) have died from disease a median of 20 mos (range 7-24) after commencing therapy.During CyBorD induction, 5 pts required hospitalization for a median of 10 days (range 6-53); heme toxicity was generally mild, with only 1 grade 4 neutropenia and no grade 3 or 4 thrombocytopenia. Other toxicities included: mild peripheral neuropathy in 5 pts (50%) (grade 1 in 4; grade 2 in 1) in addition to grade 1 shingles (10%), grade 2 drug fever attributed to btz (10%), and anemia requiring transfusion (10%). ConclusionsAlthough compromised by the small sample size, our study suggests that induction with CyBorD for pts with pPCL produces a high initial ORR with a favorable toxicity profile. However, disease progression is common in this entity and can occur early, while waiting for ASCT; these pts have a particularly poor outcome even after reinduction and subsequent ASCT. Although CyBorD is an effective initial regimen for patients with pPCL, innovative therapies will be needed to maintain long-term disease control. Disclosures:Reece:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Millennium Pharmaceuticals: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; BMS: Research Funding; Otsuka: Honoraria, Research Funding; Onyx: Consultancy. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Trudel:Sanofi: Honoraria; GSK: Research Funding; Celgene: Honoraria.

Pedobarographic Statistical Parametric Mapping may identify specific plantar pressure patterns in patients with diabetes mellitus among different degrees of peripheral neuropathy: A pilot study.

Peripheral neuropathy (PN) in patients with diabetes can lead to changes in the distribution of plantar pressure during walking, which can be recorded with pedobarography. Compared to traditional spatial data reduction analysis, the pedobarographic Statistical Parametric Mapping (pSPM) allows comparison of the footprints with the advantage that sub-regions do not need to be defined a priori. Aim of the study was to test the potential of pSPM in identifying specific distribution of spatial pressure in different stages of PN. PN was defined according to usual tools (i.e., tendon reflexes and sensory tests). Four groups were compared: patients with diabetes without PN (n=24; 239 steps); with signs of mild PN (n=12; 117 steps); with signs of severe PN (n=6; 52 steps) and a control group without diabetes (n=12; 124 steps). Traditional spatial data reduction and pSPM were performed to compare plantar pressures in the different groups. In patients with PN, traditional spatial data reduction analysis showed lower plantar pressures with PN severity. pSPM analysis is able to better define the initial changes: mild PN patients presents higher pressures on the anterior side of the metatarsal heads compared to patients without neuropathy. Patients with severe PN are characterised by higher pressures under the medial foot arch compared to other groups. pSPM may identify specific features of plantar pressure distribution during walking in patients with mild PN and may become a useful screening tool for a timely identification of this complication.

Early diagnosis of diabetic peripheral neuropathy based on infrared thermal imaging technology.

The purpose of this study was to detect and compare the surface temperature of plantar vessels in mild diabetic peripheral neuropathy (DPN) patients and healthy controls, to explore a simple, convenient and reliable method for early diagnosis of DPN, and to explore the influence of sex and age on vascular surface temperature. In this study, 60 mild DPN patients (30 males and 30 females) and 60 healthy volunteers were randomly recruited according to their age and sex. Intra-class correlation coefficient was used to evaluate the repeatability of skin temperature measurement in the vascular area. A general linear model was used to analyse the difference of skin temperature between mild DPN patients and healthy controls. The infrared detection results of skin temperature corresponding to blood vessels showed excellent test-retest reliability. There was no significant difference in skin temperature between sex and age. But there were significant differences in skin temperature between mild DPN patients and healthy controls, except for the posterior tibial artery. For mild DNP patients, in case of no obvious abnormality in the infrared detection of lower extremity arterial surface temperature, the small vessels have shown early abnormal body surface temperature, that is, the surface temperature of related vessels increased. The research conclusions of this article not only enable us to better understand the correlation between body surface temperature and hemodynamic parameters, but also provide an in vivo, non-invasive, and convenient way of thinking and methods for early diagnosis of DPN.

Peripheral neuropathy in the COVID-19 era

The term peripheral neuropathy refers to disorders of the peripheral nervous system (PNS) including single and multiple (asymmetric) mononeuropathies, and symmetrical involvement of many nerves (polyneuropathy). Further classification depends on a mixture of phenomenological, neurophysiological, pathological and aetiological parameters. The temporal evolution of symptoms divides polyneuropathy (PN) into acute or chronic. Acute PN e.g. Guillain-Barré syndrome (GBS) is rare but an important entity to recognise because whilst at times severe, it is treatable. Most PN are chronic and usually develop over several months. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by SARS-CoV-2. Symptoms of COVID-19 are variable, but often include fever, cough, headache, fatigue, breathing difficulties, and loss of smell or taste. Neurological complications have been reported in the context of COVID-19 infection both in the acute and subacute phase, as part of the post-COVID syndrome or as a result of the vaccination against SARS-CoV-2. In the acute phase, it has been reported that GBS prevalence is 15 cases per 100,000 SARS-CoV-2 infections. Demyelinating GBSs variant in particular is the most prevalent. Although not necessarily directly caused by SARS-CoV-2, prolonged stay in ICUs is associated with increased risk of ICU related neuro-myopathy. In the chronic phase, preliminary results of ongoing prospective observational studies suggest that patients suffered from COVID-19 have increased risk of developing mild axonal peripheral neuropathy that shows evidence of length dependency. Interestingly, it has been reported that – even in the absence of electrophysiologically confirmed PN – 1 in 5 patients reported deterioration of pre-existing neuropathic symptoms or development of new neuropathic symptoms, particularly pain, after COVID-19. Such symptoms tend to persist for months. Further studies are needed to describe the natural history of the PNS involvement during and after COVID-19 infection.