Fiber Neuropathy In Patients Research Articles

Small fibre neuropathy frequently underlies the painful long-COVID syndrome

Abstract Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case–control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post–COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post–COVID-19 controls. This case–control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post–COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.

Investigation of small fiber neuropathy in patients with diabetes mellitus by corneal confocal microscopy

ObjectivesCorneal confocal microscopy (CCM) is a non-invasive technique that examines the corneal cellular structure. Its use in the detection of small fiber neuropathy is being researched. In our study, we examined the role of CCM in the detection of small fiber neuropathy in diabetic patients, as well as the differences between CCM findings in diabetic patients with and without overt polyneuropathy with neuropathic symptoms. Methods56 Diabetes Mellitus (DM) patients and 18 healthy controls were included in the study. The individuals included in the study were divided into three groups. Patients with diabetes who were found to have polyneuropathy according to electrophysiological diagnostic criteria were classified as Group 1, patients with diabetes and neuropathic symptoms without overt polyneuropathy according to electrophysiological diagnostic criteria were classified as Group 2, and healthy individuals were classified as Group 3. Electrophysiological examination and corneal imaging with CCM were performed in all groups. ResultsThe CNFD and CNFL values of individuals in the diabetic group were discovered to be lower. CNFD values differ statistically between the groups (p = 0.047). Group 1-Group 3 differs from Group 2-Group 3 (respectively; p = 0.018, p = 0.048). ConclusionOur study demonstrates that CCM can be used in patients with neuropathic symptoms and no polyneuropathy detected in EMG and thought to have small fiber neuropathy. CCM provides an opportunity for early diagnosis in small fiber neuropathy.

Small fiber neuropathy in irritable bowel syndrome.

In this study, we intend to evaluate the occurrence of small fiber neuropathy in patients with irritable bowel syndrome (IBS). Small fiber neuropathy (SFN) is a sensory neuropathy that results from the degeneration of small Aδ and unmyelinated C fibers. SFN manifests positive symptoms, such as tingling, burning, prickling, and aching, and negative symptoms, including numbness, tightness, and coldness. The SFN coexistence with other comorbidities (e.g., fibromyalgia, inflammatory bowel disease, celiac disease) has been reported in previous studies. We conducted a cross-sectional study to assess the coexistence of SFN and IBS. Forty-two IBS patients and forty-three healthy individuals were asked to complete the Michigan Neuropathy Screening Instrument (MNSI) questionnaire. Results greater than three (>3) were considered positive. Participants with positive MNSI questionnaire results were examined for any neuropathy signs according to the Utah Early Neuropathy Scale (UENS) examination. The participants with positive results for the questionnaire and examination were checked for the sural and the superficial peroneal nerve conduction study (NCS). Normal NCS represented intact large fibers and the diagnosis of SFN. Ten participants, 7 (16.7 %) in the IBS group and 3 (6.9 %) in the healthy group, had positive results for the questionnaire. Four participants were positive for the examination, with normal NCS, and were classified as SFN-positive. All four SFN diagnoses were from the IBS group. No one in the healthy group was diagnosed with SFN. We could find a significant statistical difference (p<0.05) between the IBS and healthy groups regarding the prevalence of SFN diagnosis. The co-occurrence of SFN and IBS suggests the possibility of a generalized neuropathy syndrome characterized by widespread neuronal impairment. Thus, any peripheral neuropathy symptom in IBS patients (and potentially other chronic pain disorders) should be evaluated for SFN since timely diagnosis and proper treatment result in a better quality of life for the patients.

Guía de Práctica Clínica para el diagnóstico de compromiso orgánico en amiloidosis: Parte 3/3 Año 2020

Method: Use the PICO format to generate a series of questions, focusing on the specificity and sensitivity of the amyloidosis diagnostic test. PubMed searches were conducted in English and Spanish from July to August 2019. The level of evidence and recommendation are based on the GRADE system (http://www.gradeworkinggroup.org/index.htm). The recommendations are graded according to their direction (for or against) and strength (strong and weak). Finally, it is recommended to use GLIA tools to evaluate the obstacles and facilitators in implementation. Suggested explanation A strong suggestion indicates a high degree of trust in support or opposition to the intervention. When defining a strong recommendation, this guide uses the "recommended" language. The weaker recommendations indicate that the outcome of the intervention (favorable or unfavorable) is doubtful. In this case, if a weak recommendation is defined, the "recommendation" language is used. How to use these guidelines: Recommendations must be explained within the scope of special care in validated diagnostic studies conducted by specially trained doctors. It is not assumed to change the coexistence conditions of the disease process. Presumably, the attending physician has a high degree of suspicion of amyloidosis. It assumes that diagnostic research is conducted by well-trained doctors using a validated standardized method. This guide is intended for health care professionals and those involved in health care policies to help ensure that the necessary agreements have been reached to provide appropriate care. Summary of recommendations For patients with suspected amyloidosis, it is recommended: Measured value of creatinine be used as a preliminary assessment for the diagnosis of renal involvement in patients with suspected renal amyloidosis. 24-hour proteinuria be measured and characterized to diagnose renal involvement in patients with suspected renal amyloidosis. Immunohistochemical staining of skin biopsy for patients genetically diagnosed with ATTR, for early diagnosis of neuropathy. The signs or symptoms of these patients suggest the presence of fine fiber neuropathy. Skin biopsy and immunohistochemical staining for early diagnosis of neuropathy. These patients show signs or symptoms suggesting fine fiber neuropathy. Conduct nerve conduction studies on motor and sensory fibers to diagnose total fiber neuropathy in patients who are diagnosed or suspected of having amyloidosis. Test (Sudoscan) is recommended for the early diagnosis of peripheral autonomic neuropathy (even in asymptomatic patients) in patients with suspected autonomic neuropathy due to amyloidosis. Ewing's standard to measure heart rate variability to diagnose autonomic hypofunction in patients with autonomic neuropathy suspected of having amyloidosis. Measure orthostatic hypotension to diagnose early autonomic hypotension for patients with amyloidosis or systemic amyloidosis suspected of autonomic neuropathy. It is suggested: QST test to diagnose neuropathy early for patients genetically diagnosed with ATTR, if they show signs or symptoms suggesting fine fiber neuropathy Measure alkaline phosphatase to initially assess liver involvement in patients with amyloidosis.

Corneal confocal microscopy detects small-fiber neuropathy in patients with amyotrophic lateral sclerosis

Objective: To investigate small fiber neuropathy in patients with amyotrophic lateral sclerosis (ALS) by corneal confocal microscopy. Methods: A total of 57 ALS patients were consecutively enrolled in Department of Neurology between June 2015 and February 2016, including 37 men and 20 women with mean age 24-80 (52±11) years. There were 30 controls including 21 men and 9 women with mean age 23-76 (55±13) years. All subjects underwent corneal confocal microscopy (CCM), contact heat evoked potential (CHEP) and skin sympathetic reflection (SSR) to quantify small nerve fiber pathology. Four parameters, such as nerve fiber length (NFL), nerve branch density (NBD), nerve fiber density (NFD) and nerve fiber tortuosity (NFT) were assessed by corneal confocal microscopy. All statistical calculations were conducted using SPSS version 12.0. Results: Compared with control group, corneal nerve fiber length (NFL),nerve fiber density (NFD) were significantly decreased [(12.2±4.4)mm/mm2 vs.(15.1±4.5) mm/mm2,P=0.028;(50.8±24.0)/mm2 vs. (68.3±16.4)/mm2,P=0.002],and nerve fiber tortuosity (NFT) were significantly increased [(2.6±1.0)level vs.(1.0±0.5)level, P<0.01)] in SFN group, while nerve branch density (NBD) were comparable (P=0.700).The course of disease is correlated with NFT (r=0.25,P=0.030). Conclusions: CCM is a new sensitive noninvasive clinical technique that detects early small fiber nerve damage in patients with ALS.

Modified collision study to isolate and study small fibre neuropathy in patients with Type 2 diabetes.

Introduction:Diabetic distal symmetrical polyneuropathy (DSPN) can be categorized as small fibre, large fibre, and mixed neuropathy. Even though small fibre neuropathy is the most prevalent, unfortunately it is usually not recognized by routine electrophysiologic studies. In this study, we intend to examine the slow velocity small fibres responsible for small fibre DSPN, by isolating them using collision technique principle in patients with diabetes.Methods:This is an observational case-control study designed to compare nerve conduction values with application of collision technique in 60 patients with T2D and in 60 age and sex matched controls.Results:The collision study in patients with Type 2 Diabetes showed mean Latency of 10.5 ± 1.7 ms and mean Amplitude of 3.4 ± 2.3 mV on the right side and mean Latency of 10.5 ± 1.7 ms and the mean Amplitude of 3.5 ± 2.2 mV on the left side. There was a statistically significant difference (P value < 0.001) in the amplitute and latency of CNAPs of small fibres in median nerve innervated APBs of both arms between those with T2D and controls.Discussion and Conclusion:Collision study helps to examine the slower conducting fibres of the larger nerves. Our study suggests that the Collision Technique can be used to identify early peripheral neuropathy regardless of the diabetes status, thus making it more practically feasible and cost-effective.

Small Fiber Neuropathy in Patients with Chronic Pain and a Previous Diagnosis of Multiple Chemical Sensitivity Syndrome.

Small fiber neuropathy (SFN) is characterized by the involvement of Aδ and C fibers leading to sensory, mainly pain, and/or autonomic symptoms. Multiple chemical sensitivity syndrome (MCS) is an incompletely defined condition characterized by the onset of various symptoms in patients after exposure to several chemical substances. Pain is a common symptom in these patients. In this study, we report the histological and clinical data of a cohort of 21 patients who had been diagnosed as having MCS and who were referred to us with the suspicion of SFN because of chronic pain. All patients underwent neurological clinical examination, (including scales for pain and autonomic disorders), and a skin biopsy. Age-matched healthy subjects were used as controls for the skin biopsies. Nerve conduction studies and serum screening to exclude possible causes of peripheral neuropathy were also performed. Skin biopsies disclosed a somatic SFN in all patients. Although the majority (18 out of 21) of patients also had autonomic symptoms. we found sparing of autonomic innervation in the biopsies. These observations suggest that chronic pain in MCS could be secondary to the presence of somatic SFN, although more data are needed to confirm these observations.

No evidence of improvement in neuropathy after renal transplantation in patients with end stage kidney disease.

To assess the impact of renal transplantation on peripheral nerve damage in patients with chronic kidney disease (CKD). Fifteen patients with CKD (eGFR <15 mL/min/1.73 m2 ) underwent longitudinal assessment after renal transplantation (age: 56.88 ± 2.53 years, eGFR: 46.82 ± 4.86) and were compared with 15 age-matched controls (age: 58.25 ± 2.18 years, eGFR: 86.0 ± 2.0). The neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration perception threshold (VPT), cold and warm sensation threshold (CST and WST), cold and heat induced pain (CIP and HIP), deep breathing heart rate variability (DB-HRV), nerve conduction studies and corneal confocal microscopy (CCM) to quantify small nerve fibre pathology, were undertaken within 1-month of renal transplantation (baseline) and at 6, 12 and 24 months of follow up. There was no significant difference in NSP (P=.1), NDS (P=.3), VPT (P=.6), CST (P=.2), CIP (P=.08), HIP (P=.1), DB-HRV (P=.9) and sural (P=.4) and peroneal (P=.1) nerve amplitude between patients with CKD and controls at baseline. However, sural (P=.04), peroneal (P=.002) and tibial (P=.007) nerve conduction velocity and tibial nerve amplitude (P=.03) were significantly lower, WST (P=.02) was significantly higher and corneal nerve fibre density (P=.004) was significantly lower in patients with CKD compared with controls. There was no significant change in NSP, NDS, quantitative sensory testing, DB-HRV, nerve conduction or CCM parameters 24 months after renal transplantation. There is evidence of small and large fibre neuropathy in patients with CKD, but no change up to 24 months after successful renal transplantation.

A reappraisal of the presence of small or large fiber neuropathy in patients with erythromelalgia

ObjectiveTo assess the contribution of large and small nerve fiber alteration in erythromelalgia (EM). MethodsThirty-three EM patients were included and underwent clinical evaluation based on EM severity score, DN4, and Utah Early Neuropathy Scale (UENS) score. Neurophysiological evaluation consisted in nerve conduction studies (NCS) for large nerve fibers and specific tests for small nerve fibers: electrochemical skin conductance, cold and warm detection thresholds, and laser evoked potentials. Finally, the evaluation of vascular changes was based on the presence of clinical feature of microvascular disorders and the measurement of the Toe Pressure Index (TPI). ResultsWhile 28 patients (85%) had vascular alteration on TPI or clinical features, 23 patients (70%) had small-fiber neuropathy on neurophysiological tests, and only 10 patients (30%) had large fiber neuropathy on NCS. Regarding clinical scores, there was no difference between groups (presence or absence of large- or small-fiber neuropathy or microvascular disorder) except for a higher UENS score in patients with large fiber neuropathy. ConclusionPeripheral neuropathy, mostly involving small nerve fibers, is almost as common as microvascular changes in EM, but remains inconstant and not related to a specific neuropathic pattern or higher clinical severity. SignificanceThe association of neuropathic and vascular factors is not systematic in EM, this syndrome being characterized by different pathophysiological mechanisms leading to a common clinical phenotype.

Small Fibre Neuropathy Is Associated With Impaired Vascular Endothelial Function in Patients With Type 2 Diabetes.

Diabetic polyneuropathy (DPN) and endothelial dysfunction are prevalent complications of diabetes mellitus. Currently, there are two non-invasive markers for endothelial dysfunction: flow-mediated dilation and reactive hyperaemia peripheral arterial tonometry (RH-PAT). However, the relationship between diabetic small fibre neuropathy and macroangiopathy remains obscure thus far. Corneal confocal microscopy (CCM) has emerged as a new diagnostic modality to assess DPN, especially of small fibre. To clarify the relationship between diabetic small fibre neuropathy and vascular dysfunction, we aimed to determine the functions of peripheral nerves and blood vessels through clinical tests such as nerve conduction study, coefficient of variation in the R-R interval, CCM, and RH-PAT in 82 patients with type 2 diabetes. Forty healthy control subjects were also included to study corneal nerve parameters. Correlational and multiple linear regression analyses were performed to determine the associations between neuropathy indices and markers for vascular functions. The results revealed that patients with type 2 diabetes had significantly lower values for most variables of CCM than healthy control subjects. RH-PAT solely remained as an explanatory variable significant in multiple regression analysis for several CCM parameters and vice versa. Other vascular markers had no significant multiple regression with any CCM parameters. In conclusion, endothelial dysfunction as revealed by impaired RH-PAT was significantly associated with CCM parameters in patients with type 2 diabetes. This association may indicate that small fibre neuropathy results from impaired endothelial dysfunction in type 2 diabetes. CCM parameters may be considered surrogate markers of autonomic nerve damage, which is related to diabetic endothelial dysfunction. This study is the first to report the relationship between corneal nerve parameter as small fibre neuropathy in patients with type 2 diabetes and RH-PAT as a marker of endothelial dysfunction.

Assessment of small fiber neuropathy in patients carrying the non-classical Fabry variant p.D313Y.

The pathophysiological significance of the Fabry-related, non-classical variant p.D313Y still remains to be solved. This study assesses the involvement of the peripheral nervous system with respect to small fiber neuropathy and neuropathic pain in female patients carrying p.D313Y. This study examined nine females carrying the Fabry-related p.D313Y variant by obtaining skin punch biopsies above the right lateral malleolus. Intraepidermal nerve fiber density was determined for each patient and compared to reference values matched for the patient's decade of life and sex. Moreover, each patient was characterized by a detailed neurological examination and by pain assessment via questionnaire. Compared to sex-matched lower fifth percentile reference values per decade, intraepidermal nerve fiber density was decreased in seven out of nine patients. Four patients reported acral paresthesias and neuropathic pain with an average visual analogue scale score of 7 out of 10 points. Two patients experienced acute pain crises. Six out of seven patients diagnosed with small fiber neuropathy had a their medical history of hypo- and/or hyperhidrosis. The diagnosis of small fiber neuropathy was made in seven out of nine females carrying the non-classical variant p.D313Y. Moreover, neuropathic pain and symptoms indicative of autonomic nervous system dysfunction seem to be common findings that may be of clinical significance and may warrant therapeutic intervention.

Correlation Between Corneal Nerve Density and Symptoms of Small Fiber Neuropathy in Patients With Fibromyalgia: The Confounding Role of Severe Anxiety or Depression.

A consistent line of investigation proposes fibromyalgia as a dysautonomia-associated neuropathic pain syndrome. Comorbid anxiety or depression amplifies fibromyalgia symptoms. The recent recognition of small fiber neuropathy in fibromyalgia patients supports the neuropathic nature of the illness. Corneal confocal microscopy accurately identifies small nerve fiber pathology. The newly developed Small-Fiber Symptom Survey captures the spectrum of small fiber neuropathy symptoms. We aimed to correlate corneal nerve density with different fibromyalgia disease severity questionnaires including the Small-Fiber Symptom Survey. We defined the possible confounding role of comorbid anxiety or depression severity in the clinical-pathological association. This is a case series of 28 women with fibromyalgia. A single ophthalmologist quantified corneal subbasal plexus nerve density. Corneal innervation was correlated (Spearman ρ) with the following clinical questionnaires scores: Small-Fiber Symptom Survey, Revised Fibromyalgia Impact Questionnaire, and COMPASS-31 (Composite Autonomic Symptom Survey 31-Item Score). Validated inquiry forms assessed the comorbid anxiety and/or depression severity. There were no clinical-pathological correlations in the group as a whole. In the subgroup of fibromyalgia women without severe anxiety or depression (n = 13), there was a strong negative correlation between corneal nerve density with the Small-Fiber Symptom Survey score (ρ = -0.771, p = 0.002) and COMPASS-31 score (ρ = -0.648, p = 0.017). Patients with profound anxiety or depression (n = 15) had more intense symptoms but had not clinical-pathological correlations. Small fiber neuropathy and dysautonomia symptoms correlate with corneal denervation in women with fibromyalgia without severe anxiety or depression. This clinical-pathological association reinforces fibromyalgia as a dysautonomia-related neuropathic pain syndrome. Severe anxiety or depression distorts fibromyalgia symptoms. Corneal confocal microscopy may become a useful procedure to study fibromyalgia patients.

Unclear etiology and current hypotheses of the pathogenesis of fibromyalgia

Introduction and purpose: Fibromyalgia is a chronic condition affecting almost 2% of the general population, mostly women. The main symptoms are chronic diffuse musculoskeletal pain or stiffness, tiredness, nonrestorative sleep, anxiety, depression and cognitive dysfunction. The etiology of fibromyalgia remains unclear and has been the subject of debate and scientific investigation. The aim of this article was to collect and analyse current and new information on the etiology of fibromyalgia and present the most popular hypotheses.Brief description of the state of knowledge: Pathogenesis of fibromyalgia is multifactorial. Genetic factors, in addition to environmental factors, such as psychical stress and various types of infection, are considered to be the triggers of the disease. Central sensitization became a commonly accepted hypothesis of the fibromyalgia’s pathogenesis. However, the newest finding of small fiber neuropathy in patients with fibromyalgia supports another hypothesis, in which the disease is presented as stress-related dysautonomia with neuropathic pain features.Conclusions: Understanding the pathogenesis of fibromyalgia is essential to provide the best care to the patients with fibromyalgia. Although there are multiple evidence for central sensitization hypothesis, new findings continue to emerge and question commonly accepted paradigm. Despite numerous findings on etiology of fibromyalgia, more studies are needed.

Associations of Small Fiber Neuropathy with Geriatric Nutritional Risk Index and Arterial Stiffness in Hemodialysis.

Background Peripheral neuropathy is a common neurological complication in uremic patients, and quantitative sensory testing (QST) is effective for diagnosis of small fiber neuropathy. Malnutrition and arterial stiffness are prevalent in patients undergoing hemodialysis (HD). The associations of small fiber neuropathy with nutritional status and arterial stiffness remain uncertain in maintenance HD patients. Methods A total of 152 HD patients were included. Geriatric nutritional risk index (GNRI), an indicator of nutritional status, was calculated by serum albumin and actual and ideal body weight. Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) > 1400 cm/s. Small fiber neuropathy was assessed by an abnormal QST threshold of cold and warm sensation in patients' hands or feet. Multivariate forward logistic regression analysis was performed to examine the associations among abnormal QST threshold, GNRI, and arterial stiffness. Results baPWV and prevalence of abnormal QST threshold were significantly higher in diabetic patients. Multivariate logistic analyses revealed that older age (OR, 1.081; 95% CI, 1.026–1.139, p = 0.003) and male gender (OR, 4.450; 95% CI, 1.250–15.836, p = 0.021) were associated with abnormal warm threshold of hands. Furthermore, diabetes (OR, 3.966; 95% CI, 1.351–11.819, p = 0.012) and lower GNRI (per 1 unit increase, OR, 0.935, 95% CI, 0.887–0.985, p = 0.012) were associated with abnormal cold threshold of feet. Arterial stiffness (OR, 5.479, 95% CI, 1.132–22.870, p = 0.020) and higher calcium-phosphorus product (OR, 1.071, 95% CI, 1.013–1.132, p = 0.015) were associated with abnormal warm threshold of feet. Conclusions Lower GNRI and arterial stiffness were significantly associated with small fiber neuropathy in patients undergoing HD. Malnutrition risk and vascular factors might play important roles in small fiber neuropathy among patients undergoing HD.

Fibromyalgia: is it a neuropathic pain?

Fibromyalgia is a chronic pain syndrome of unclear pathophysiology. It is believed to be a dysfunction of the CNS, but no definite structural lesion has been identified so far. Despite a number of changes in the diagnostic criteria, diagnosis remains a clinical one. Since the 2011 revision of the IASP definition of neuropathic pain, fibromyalgia has been excluded from the diagnosis of neuropathic pain. More recent studies however found newer evidences of pathophysiology including small fiber neuropathy in patients with fibromyalgia. This may challenge the existing consensus and have implications on future diagnosis and management of this condition.

0668 Small Fiber Neuropathy in Patients with Refractory RLS: A Case Series

0668 Small Fiber Neuropathy in Patients with Refractory RLS: A Case Series

The histopathological evaluation of small fiber neuropathy in patients with vitamin B12 deficiency.

Small fiber neuropathy (SFN), due to loss of A-delta and unmyelinated C fibers, is a cause of neuropathic pain. Although the patients with vitamin B12 deficiency are included in SFN studies in the literature, there is no histopathological study investigating the small fiber loss solely in patients with vitamin B12 deficiency. In this pilot study, we aim to demonstrate the intraepidermal nerve fiber density (IENFD) in skin punch biopsy of patients with vitamin B12 deficiency. Ten patients with vitamin B12 deficiency suffering from neuropathic pain and as control group ten patients with vitamin B12 deficiency without neuropathic pain were included. Neurological examination, electrophysiological evaluation, and DN4 questionnaire were performed. Subsequently, skin punch biopsy 10cm above the lateral malleolus was done. The biopsy samples were stained with PGP9.5 antibody, and IENFD was determined. IENFD was low in two groups compared to their age normative values. The median of IENFD was 3.345 (1.12-5.32) in patients with neuropathic pain and 6. 20 (4.6-9.8) in controls (p<0.001). Our pilot study showed that vitamin B12 deficiency causes symptomatic as well as asymptomatic small fiber loss like diabetes mellitus.

Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain

Dear Editor, In the United States, approximately 800,000 strokes occur annually, with 11%-55% of stroke survivors experiencing post-stroke pain [1–5]. Central post-stroke pain (CPSP) is recognized as a neuropathic condition often defined as being of thalamic origin, although extra-thalamic stroke can also result in CPSP [3,5–7]. The reported prevalence of CPSP is between 1% and 12% following all stroke, and up to 18% when sensory deficits are present [3,6,7]. Although the pathophysiology of CPSP remains incompletely understood, as the name implies, CPSP is most often associated with “central,” not peripheral nervous system abnormalities. Here we report four consecutive patients without prior evidence of a peripheral neuropathy, who developed CPSP following a stroke and in who further evaluation led to the documentation of skin biopsy findings consistent with small fiber neuropathy (SFN). Decreased peripheral intraepidermal nerve fiber density (IENF) is observed in many painful conditions associated with SFN including complex regional pain syndrome, diabetic neuropathy, chemotherapy-induced neuropathy, and hypothyroidism [8–15]. Similar skin biopsy findings have been recently reported in some, but not all, fibromyalgia patients leading some clinicians to consider the diagnosis of SFN in certain fibromyalgia patients. Although the precise role that the loss of small caliber (presumptive nociceptor) IENF plays in clinical pain symptoms is still unclear, their normal physiologic role in acute pain mechanisms is well-defined. Since the anatomy of the nociceptive/pain pathways (matrix) approximates a closed-loop system, coupled with the recognition that …

Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.