Manifestations Of Peripheral Neuropathy Research Articles

Retrospective analysis of peripheral neuropathy in blood cancer survivors evaluated for cellular therapy.

12087 Background: Blood cancer survivors (BCS) sustain peripheral neuromotor decline from toxic therapies but also aging, diabetes and cancer. Peripheral neuropathy (PN) threatens balance and quality of life, and pre-existing nerve deficits raise future PN risk. The evaluation for cellular therapies is an opportunity to identify functional deficits and optimize their management before additional toxic exposures or disease progression. PN is often diagnosed by paresthesias, but toe strength and sensory deficits also impact balance. We aim to quantify the prevalence of these 3 PN manifestations and walking difficulty in BCS evaluated at our center for possible cellular therapies and compare BCS with and without paresthesias. Methods: We retrospectively analyzed clinical data from 5 years of physical therapy (PT) evaluations during the medical assessment for cellular therapy. As count (%) or mean ± SD we described foot paresthesias [Functional Assessment of Cancer Therapy (FACT) Item NTX2], hallux extension weakness (Medical Research Council Grade ≤4 either side), hallux vibration deficit (biothesiometer ≥24.7 V), and reported trouble walking (FACT An6). We then dichotomized the cohort by NTX2 and compared groups with Chi-square, Fisher’s exact or Wilcoxon rank sum tests. Results: 598 (87.6%) of 683 BCS evaluated by PT had FACT data (79.1% White, 5.5% Latinos); 1 in 2 BCS reported paresthesias, 71.2% as moderate-severe. See table for group comparisons. Race (p=.654) & ethnicity (p=.608) were n.s. 506 BCS with FACT (84.6%) had both strength and sensory data; we found ≥ 1 hallux deficit in 396 (78.3%), more commonly with paresthesias (86.3% vs. 69.5%, p<.001). Conclusions: At cellular therapy evaluation, 1 in 2 BCS reported foot paresthesias, and 3 in 4 had strength or sensory hallux deficit. Regardless of the cause, these deficits could contribute to the trouble walking reported by 44%. BCS with paresthesias were older and had more myeloma, diabetes, chemotherapy, hallux deficits, and trouble walking. But trouble walking and hallux deficits were also common without paresthesias. Research is needed to quantify hallux-gait relationships in BCS, and to establish the highest-value rehabilitative approaches to improve strength and walking before further toxic exposures. [Table: see text]

Charcot Neuro-Osteoarthropathy With Superimposed Osteomyelitis in a Nondiabetic Patient, as a Consequence of Cancer Chemotherapy: A MR-Monitored Case Report.

Charcot neuro-osteoarthropathy (CNO) is a manifestation of peripheral neuropathy as a chronic complication of diabetes mellitus but, less frequently, can be associated to other conditions such as alcoholism or neurotoxic therapies. An increasingly emerging cause of CNO is the use of oncological drugs which can cause neuropathic damage. The use of these therapies dramatically increased in recent years. CNO leads to a progressive degeneration of the foot's joints and to bone destruction and resorption which ends in deformities. These alterations in the foot's anatomy determine a high risk of ulceration, infection, and osteomyelitis. The superimposition of osteomyelitis on CNO increases the risk of major amputation, already high in patients suffering either from only CNO or osteomyelitis alone. We report the case of a 61-year old nondiabetic woman affected by CNO as a consequence of antiblastic therapy for breast cancer and the subsequent overlap of osteomyelitis, confirmed by magnetic resonance imaging. This case underlines how it is necessary to consider CNO as a possible complication of antiblastic therapy in the view of the severe consequences of missing its diagnosis.

Drug utilization patterns for peripheral neuropathy in a neurology outpatient department at a tertiary care center: A cross-sectional observational study

Background: Peripheral neuropathy is a broad term encompassing any condition that impacts the peripheral nerves. It encompasses a wide range of conditions, presenting with a variety of abnormalities that affect different aspects of both the voluntary (somatic) and involuntary nervous systems (autonomic nervous system). The manifestations of peripheral neuropathy can vary significantly based on the specific nerves affected. This disorder can induce numbness, tingling, or pins and needles sensations along with sharp and pulsating pain. Commonly employed medications for treating peripheral neuropathy encompass analgesics such as opioids and over-the-counter pain relievers, as well as anti-epileptic drugs such as topiramate, gabapentin, and pregabalin. For enhancing the management of peripheral neuropathy, it is imperative to gather data regarding the prevailing utilization trends of medications prescribed for neuropathic pain. Drug utilization studies constitute continuous activity for evidence based therapeutic practices; it implies rational therapy with focus on the prime parameters. This study aims to assess the drug utilization pattern for peripheral neuropathy under various prescriptions which provides the scope for various etiologies and severity requiring judicious choice of drug use. Aims and Objectives: The objective of the study was to assess the pattern of medications dispensed to patients diagnosed with various types of peripheral neuropathy at a tertiary care center and to evaluate the drug regimen given for particular type of peripheral neuropathy. Materials and Methods: It is a cross-sectional observational study conducted at a neurology outpatient department at a tertiary care center. Patients diagnosed with peripheral neuropathy due to various disease conditions were included in the study. Patients were selected through convenient sampling. Prescriptions were reviewed to evaluate the medication profile, comprehensiveness, and concordance with the diagnosed condition. Drug details were analyzed utilizing the descriptive statistics within Statistical Package for the Social Sciences software version 29.0. Results: Our study included a cohort of 110 patients diagnosed with peripheral neuropathy due to various disease conditions. The mean age of the study participants were 43.4 years, 58 were males, and 52 were females. Out of 110 patients 58 (52.7%) patients were prescribed pregabalin + methylcobalamin, 38 (34.5%) patients received methylcobalamin alone, 8 (7.2%) patients received duloxetine, 5 (4.5%) patients received the combination of pregabalin and amitriptyline, and 1 patient with peripheral neuropathy due to hypothyroidism received levothyroxine. Conclusion: In our study, the predominant medication utilized for peripheral neuropathy treatment is the combination of pregabalin and methylcobalamin, with methylcobalamin monotherapy being the subsequent choice.

Prevention of vincristine-induced peripheral neuropathy by protecting the endothelial glycocalyx shedding

Vincristine-induced peripheral neuropathy (VIPN) adversely affects the quality of life and treatment continuity of patients. The endothelial glycocalyx (eGCX) protects nerves from harmful substances released from the capillary vessels, but its role in peripheral neuropathy remains unclear. We investigated the impact of eGCX protection on VIPN. Using a murine model of VIPN, we administered nafamostat mesylate to protect the eGCX shedding, and analyzed the eGCX integrity and manifestation of peripheral neuropathy. Nafamostat treatment suppressed allodynia associated with neuropathy. Additionally, nafamostat administration resulted in the suppression of increased vascular permeability in capillaries of peripheral nerves, further indicating its positive influence on eGCX in VIPN model mice. This study provided the importance of eGCX in VIPN. With the potential for rapid clinical translation through drug repositioning, nafamostat may be a new promising treatment for the prevention of VIPN.

Alpha lipoic acid and diabetes mellitus: potential effects on peripheral neuropathy and different metabolic parameters

ABSTRACT Introduction: Alpha lipoic acid (ALA) is an antioxidant used in the treatment of neuro-inflammation, diabetes and diabetic nephropathy. The current study aiming to gauge the effect of oral ALA on diabetic peripheral neuropathy, glycemic control, LDL-C, and HDL-C. Methods: This is a prospective, interventional study carried out on patients with type 2 diabetes mellitus (DM) who were following at the outpatient internal medicine & diabetes clinics at Benha University Hospital. Treatment with ALA for 3 months was given to patient with diabetic peripheral neuropathy. Data in the form of age, sex, body mass index (BMI), duration & treatment of DM, manifestations of peripheral neuropathy were collected. LDL-C, HDL-C, HbA1c, TSH, ALT, AST were measured before and after intervention. Peripheral neuropathy symptoms, nerve conduction velocities, cardiovascular (CV) tests of autonomic neuropathy, and cross-section area of the posterior tibial nerve were performed before and after treatment intervention. Results: 90 adult diabetic patients were recruited in the study, 42.2% were females and 57.8% were males with a median age of 50–60.3 years (IQR = 52). A statistically significant improvements of neuropathic symptoms, nerve conduction velocity, and cardiovascular autonomic neuropathy were noted after 3 months of administration of ALA (p ˂0.001). However, the cross-section area of the posterior tibial nerve at baseline and after treatment did not change significantly (p value of 0.84). There was a significant improvement in the BMI, HDL-C, LDL-C, HbA1c (p ˂ 0.001). Conclusion: Oral treatment with ALA might cause ameliorations of peripheral neuropathy, HbA1c, and LDL-C & HDL-C levels in diabetic patients. Our result failed to proof effect of ALA on nerve cross-section area. The global data encourage further studies with this medication as an ancillary treatment of DM2. Clinical trial registration: It was registered in clinical trial website; ClinicalTrials.gov Identifier (NCT number): NCT04322240.

DIAGNOSIS OF THE CARDIAC AUTONOMIC NEUROPATHY IN DIABETIC PATIENT

Cardiac autonomic neuropathy (CAN) is a very common diabetes-related complication that has a major effect on CVD, mortality and morbidity in patients with DM. Careful and timely testing of CAN with easy standard bedside tests in patients with DM 1 and 2 is critically important for early diagnoses and prophylaxes of further CV complications. Aim of the study was to evaluate the CAN characteristics in DM 1 versus DM 2 patients and to identify the relationship between CAN and typical diabetic complications. Materials and methods. A descriptive and comparative cross-sectional study was developed with 75 patients with Diabetes Mellitus (DM 1 — 30 patients, DM 2 — 45 patients) who were hospitalized to the endocrinology department for treatment. All patients were investigated routinely – complains, anamnestic data, objective examination, lab and instrumental examination. For defining of CAN next five classical tests were done (cardiac autonomic reflex testing (CART)): Evaluating of the Resting tachycardia; Heart rate response to deep breathing; Valsalva maneuver; Systolic blood pressure response to standing; Diastolic blood pressure response to sustained handgrip. Results and discussions. Absence of CAN, according to proposed score, was defined in those patients without clinical features of CVD. 46.8% of all patients presented with early and definitive CAN, while the higher prevalence of definitive CAN was diagnosed in DM 2 patients. Severe CAN was confirmed more often in DM 2 patients also. Coexistence of CAN and peripheral neuropathy was higher in patients with DM 1 than in DM 2 patients. Among DM 1 patients with CAN only 11.8% persons had not sensory peripheral neuropathy, while 29.7% DM 2 patients with CAN, were free of sensory peripheral neuropathy. Positive correlations were found between the duration of the DM and manifestations of CAN in patients with DM II, the development of sensory polyneuropathy, retinopathy and CAN in patients with DM I, and this diabetic complication preceded the clinical manifestations of peripheral neuropathy. Thus, the proposed set of diagnostic measures should be obviously and easily used for the timely diagnosis of CAN in diabetic patients, especially in asymptomatic cases, and objectively assessing the effectiveness of the therapy.

Otorrinolaringological manifestations of granulomatosis with multiple Mononeuropathy and Poliangeiacute;tis: A diagnostic challenge

Granulomatosis with Polyangiitis (GPA), previously known as Wegener's Granulomatosis, is an entity with great potential to trigger multiple manifestations in the head and neck region. The initial presentation form and its non-specific characteristics is usually misdiagnosed and confused with different entities. Within the manifestations of peripheral neuropathy, multiple mononeuritis is more common, while central nervous system involvement is more rare. We address an interesting case of granulomatosis with polyangiitis that manifested itself with multiple cranial nerve involvement mononeuritis.

Monocular Oculomotor Nerve Disorder Manifesting as Cranial Neuropathy in Systemic Lupus Erythematosus

We herein report the case of a patient who developed peripheral neuropathy of the bilateral lower legs that later became complicated with isolated oculomotor nerve disorder and was finally diagnosed as systemic lupus erythematosus (SLE). Based on the findings for oculomotor nerve paralysis and contrast-enhanced magnetic resonance imaging findings for the oculomotor nerve in the prepontine cistern, the isolated oculomotor nerve disorder was considered to be a manifestation of peripheral neuropathy. This oculomotor nerve disorder may contribute to the diagnosis of SLE and can be effectively treated with steroid pulse therapy. Reports of SLE manifesting as isolated oculomotor nerve paralysis are rare.

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

AbstractBackground:Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3′,4′-dimethoxy flavonol, 6,3′-dimethoxy flavonol, 7,2′-dimethoxy flavonol and 7,3′-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice.Methods:A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitablein vitroassays.Results:A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner.Conclusions:These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

Neuroelectrophysiological characteristics of peripheral neuropathy in primary Sjögren's syndrome: study protocol for a prospective case series and pre-preliminary results

Background and objectives: Sjogren's syndrome (SS) is a chronic progressive autoimmune disease. The incidence of peripheral nervous system damage in patients with primary SS (pSS) is 10–30%. Previous studies have shown that there are multiple electrophysiological manifestations in pSS patients presenting with peripheral neuropathy. However, there is no consensus on its neuroelectrophysiological manifestations. Peripheral neuropathy associated with pSS is easily confused with peripheral neuropathy of other etiologies. We hope to observe the neuroelectrophysiological manifestations of peripheral neuropathy associated with pSS to assist in the diagnosis of the disease. Design: A prospective case series. Methods: A total of 100 pSS patients with peripheral neuropathy receiving treatment in the Department of Neurology, First Affiliated Hospital of Kunming Medical University, China will be included in this study. Fifty-two patients presenting with peripheral neuropathy associated with pSS have been included in a preliminary investigation. Outcome measures and preliminary results: The primary outcome measure is the incidence of abnormal motor nerve conduction velocity in these patients. The secondary outcome measures are the incidences of abnormalities in terminal motor latencies, compound muscle action potential amplitudes, sensory nerve conduction velocities, sensory nerve action potential amplitudes, F waves, and sympathetic skin responses. The results of 52 patients included in the preliminary study showed that the incidences of each electrophysiological index was similar between the upper and lower extremities. Abnormal motor nerve conduction velocity occurred more frequently than abnormal compound muscle action potential amplitude. Abnormal sensory nerve conduction velocity was observed significantly more often than abnormal sensory nerve action potential amplitude. Abnormal motor nerve conduction velocity had a similar incidence to abnormal sensory nerve conduction velocity. Abnormal compound muscle action potential amplitude had a similar incidence to abnormal sensory nerve action potential amplitude. Abnormal F waves were observed significantly less frequently than abnormal motor nerve conduction study. Abnormal sympathetic skin response was seen with a similar incidence to abnormal motor nerve conduction study. Discussion: The results of this study, as indicated by the preliminary investigation, will reveal the neuroelectrophysiological abnormalities in peripheral neuropathy associated with pSS, which will aid diagnosis of the disease. Ethics and dissemination: This study was approved by Medical Ethics Committee of Kunming Medical University of China on October 14 th , 2005 (approval No. 20051014). The study protocol was designed in September 2016 and registered in April 2018. The study protocol received ethics approval from Medical Ethics Committee of Kunming Medical University of China on October 14 th , 2016 (approval No. 2016101411). Patient recuritment for the preliminary study was performed during January to October 2017. Patient recuritment for this study will begin in June 2018. Data collection will end in December 2020. The current study will be performed from June 2018 to December 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Anonymized trial data will be published at www.figshare.com . Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800015669).

Safety of BTZ retreatment for patients with low-grade peripheral neuropathy during the initial treatment

Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment. Charts were reviewed from 93 patients who were retreated with a BTZ-containing regimen after previously being treated with this drug. Among the patients who developed PN, most patients in the study had low-grade neuropathy during the initial BTZ treatment (n=52, 68%). The results showed no evidence of cumulative toxicity, and there was no significant difference in the incidence and severity of PN upon retreatment. Factors such as the presence of baseline PN, number of prior treatments, dose of BTZ, and comorbidities did not increase the severity of PN upon retreatment. The lapse of time between the two regimens also did not affect the severity of PN. The results suggest that retreatment with BTZ may be a feasible option, without additional risks of PN, for MM patients even with peripheral neuropathy during their initial treatment with this drug.

Course of Atypical Manifestations of a Case of Charcot-Marie-Tooth Disease over 35 Years of Clinical Observation

Introduction: Atypical manifestations of peripheral neuropathy are not rare, challenging the differential diagnosis. In the past, the diagnosis of hereditary neuropathy was mainly based on the clinical and electromyographic (EMG) findings and, occasionally, biopsy. Nowadays, the genetic tests allow us to identify more than 40 different genes/loci associated with Charcot-Marie-Tooth (CMT) disease, although some subtypes are clinically indistinguishable. We have followed a patient with a clinical diagnosis of apparent sporadic and atypical CMT and recently diagnosed genetically as distal hereditary motor neuropathy, type V (dHMN-V). Case Report: Thirty-five years ago, a 16 years old patient complained muscular weakness and wasting at the hands small muscles. Sporadic fasciculations were observed whereas deep tendon reflexes and sensation were normal. EMG examination revealed neurogenic muscular denervation in the distribution of C7, C8 and T1 segments bilaterally. Muscular biopsy of the left Biceps Brachii showed rare atrophic fibers and some cellular atypia. The disease has undergone a clinical and EMG progression and diffusion over the years, involving the lower limbs and leading to a bilateral steppage. A more slight diffuse axonal motor neuropathy was also identified in the proband’s son and second cousin. The genetic study found a known missense mutation in BSCL2 gene related to a dHMN-V. Interestingly, there was a remarkable intra-familiar phenotypic variability, especially in the clinical onset and severity. Discussion: Atypical manifestations of hereditary neuropathies often overlap with other conditions. The present case highlights how a comprehensive clinical evaluation and a careful follow-up have led to a correct diagnosis even 35 years later and have allowed to identify other affected family members. The apparent lack of familiarity was probably due to the very soft presentation in the proband’s relatives. Although the genetic study was not available at that time, the first clinical diagnosis was not disavowed. The main differential diagnoses and a brief review of similar reported cases are discussed.

Neuroanatomical Basis of Acupuncture Treatment for Some Common Illnesses

Dr Cheng is to be commended for his article on the neuroanatomical basis of acupuncture.1 However, Cheng has based his conclusions on the analysis of acupuncture formulae for common illnesses, as prescribed by five acupuncture academies. This approach, using consensus acupoints, is unfortunately vague, since they are surface markings intended as guides for acupuncturists, whereas target receptors are often deeply situated and can vary from person to person. Furthermore, the diagnoses are also vague: for example, “low back pain” is a common unspecific complaint that can be derived from many different causes; likewise, sciatica. In commenting on the Gunn model for pain of radiculopathic origin, he referred to muscle shortening, but neglected the other segmental manifestations of peripheral neuropathy. ‘Neuropathy’ (ie, altered function in the …

Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

Fabry disease is an X-linked inherited lysosomal disorder with dysfunction of the lysosomal enzyme α-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system. Pain and somatosensory disturbances are prominent manifestations of this disease. Until recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation between pain VAS score, quantitative sensory testing and intraepidermal nerve fiber density. Our study demonstrates that careful evaluation of symptoms in female Fabry patients is important as small fiber disease manifestations are present, which in some cases is only detected by skin biopsy.

Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy.

Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses.

Diabetic Keratopathy as a Manifestation of Peripheral Neuropathy

In a study of 102 patients (64 women and 38 men; 63 whites and 39 nonwhites; 77 with adult-onset disease and 25 with juvenile-onset disease), the data, after being adjusted for age, showed that diabetic peripheral neuropathy was associated with diabetic keratopathy. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than .01); the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were reduced tear break-up time (P less than .03), the type of diabetes (P less than .01), and metabolic status, shown by fasting C-peptide levels (P less than .01). No significant relationships were found between keratopathy and tear glucose levels, endothelial cell densities, corneal thickness, or duration of disease.