Early Detection Of Peripheral Neuropathy Research Articles

Effect of high-fat diet on peripheral neuropathy in C57BL/6 mice.

Objective. Dyslipidemia may contribute to the development of peripheral neuropathy, even in prediabetics; however, few studies have evaluated vascular dysfunction and oxidative stress in patients with peripheral neuropathy. Methods. Using high-fat diet- (HFD-) induced prediabetic C57BL/6 mice, we assessed motor and sensory nerve conduction velocity (NCV) using a BIOPAC System and thermal algesia with a Plantar Test (Hargreaves' method) Analgesia Meter. Intraepidermal nerve fiber density and mean dendrite length were tested following standard protocols. Vascular endothelial growth factor-A (VEGF-A) and 12/15-lipoxygenase (12/15-LOX) were evaluated by immunohistochemistry and Western blot, respectively. Results. HFD-fed mice showed deficits in motor and sensory NCV, thermal hyperalgesia, reduced mean dendrite length, and VEGF-A expression in the plantar skin and increased 12/15-LOX in the sciatic nerve (P < 0.05 compared with controls). Conclusion. HFD may cause large myelinated nerve and small sensory nerve fiber damage, thus leading to neuropathy. The mean dendrite length may be a more sensitive marker for early detection of peripheral neuropathy. Reduced blood supply to the nerves and increased oxidative stress may contribute to the development and severity of peripheral neuropathy.

Subclinical Peripheral Neuropathy Is a Common Finding in Colorectal Cancer Patients Prior to Chemotherapy

Of the numerous complications associated with cancer and cancer treatment, peripheral neuropathy is a deleterious and persistent patient complaint commonly attributed to chemotherapy. The present study investigated the occurrence of subclinical peripheral neuropathy in patients with colorectal cancer before the initiation of chemotherapy. Fifty-two patients underwent extensive quantitative sensory testing (QST) before receiving chemotherapy. Changes in multiple functions of primary afferent fibers were assessed and compared with a group of healthy control subjects. Skin temperature, sensorimotor function, sharpness detection, and thermal detection were measured, as was touch detection, using both conventional (von Frey monofilaments) and novel (Bumps detection test) methodology. Patients had subclinical deficits, especially in sensorimotor function, detection of thermal stimuli, and touch detection that were present before the initiation of chemotherapy. The measured impairment in touch sensation was especially pronounced when using the Bumps detection test. The patients with colorectal cancer in this study exhibited deficits in sensory function before undergoing chemotherapy treatment, implicating the disease itself as a contributing factor in chemotherapy-induced peripheral neuropathy. The widespread nature of the observed deficits further indicated that cancer is affecting multiple primary afferent subtypes. Specific to the finding of impaired touch sensation, results from this study highlight the use of newly used methodology, the Bumps detection test, as a sensitive and useful tool in the early detection of peripheral neuropathy.

The implications of statin induced peripheral neuropathy

Peripheral neuropathy is a neurological condition that commonly presents to the practicing podiatrist. Traditionally when sensory neuropathy is present one assumes diabetes mellitus to be the contributing aetiology. However, this is not always the case. Other common causes such as spinal damage, alcoholism, and vitamin B12 deficiency can be precipitating aetiologies that the clinician would be aware. 26% of individuals over 65 years of age (without a predisposing disease known to cause neuropathy) will develop peripheral neuropathy at some point in life. What does the clinician do when none of the common causes are present? One clinical presentation tested this predicament. A female patient presented with diagnosed statin induced sensory peripheral neuropathy. This uncommon aetiology lead to a literature search relating to the less common causes of peripheral neuropathy. There are reported cases of statin induced peripheral neuropathy, which in the initial stages can be reversible. Accumulating this research is difficult due to the wide variances in results and study methods; proving further independent research is needed. The reported incidence rate of peripheral neuropathy ranges between 4-14 times more likely for those on statins compared to control groups. This case study will help to raise the profile of this aetiology with the aim to preventing misdiagnosis. Interestingly, the quality of life and political implications of statin induced peripheral neuropathy are an aspect not commonly considered. What was the eventual outcome and how was the patient's quality of life affected? The patient now suffers from an irreversible peripheral neuropathy. Thus, the patient is now exposed to the complications of peripheral neuropathy, including shoe wear and hosiery changes, daily foot checks, pressure area development, and possibility of future neuropathic ulceration. Could the outcome of peripheral neuropathy have been changed if podiatry was involved earlier in the patient's management? The early detection of peripheral neuropathy may have lead to a change in specific medication to a statin that is not associated with peripheral neuropathy, therefore preventing the irreversible damage. It should be asked was this patient managed appropriately? Without the statins the patient would be at risk of hypercholesterolemia, therefore increasing cardiovascular risks such as acute myocardial infarction. Diet and exercise modifications can have great effect with lowering serum cholesterol. Such modifications should be the initial treatment, or should be utilised in conjunction with pharmacological intervention. Statins should be used to lower serum cholesterol levels when unable to do so with dietary modifications. However, there are alternative statins available which do not contain the same side effects (peripheral neuropathy) as others within the class. So the drug of choice should be made critically. Often medication is the first line treatment option due to patient compliance and ease of medical practitioner review. But it needs to be asked, who would be liable if the patient was to ulcerate and progressed to amputation? The patient, medical practitioner, or podiatrist?

Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations

In multiple myeloma, peripheral neuropathy has for a long time been considered as mainly secondary to the plasma cell dyscrasia itself. With the advent of new targeted drugs such as thalidomide and bortezomib, the iatrogenic neurotoxicity has become the leading cause of peripheral neuropathy. This review discusses the pathogenesis, incidence, risk factors, diagnosis, characteristics, and management of peripheral neuropathy related to new multiple myeloma drugs, mainly bortezomib and thalidomide. The current knowledge of the pathophysiology of the new forms of peripheral neuropathy is still limited. The mechanisms involved depend on the agents used, patient's medical history, and duration of exposure and/or treatment doses or sequence. Diagnosis of such peripheral neuropathy is often easier than treatment. A full anamnesis and regular clinical evaluation are necessary. Electrophysiological assessments may support the diagnosis, although their contribution remains insufficient. Complex clinical features may require a specialized neurological assessment within the context of a multi-disciplinary approach. Finally, early detection of peripheral neuropathy and the use of dose adjustment algorithms as in the case of bortezomib, should help reduce the side effects while maintaining anti-tumor efficacy.

Comparable morphometric data of pathological nerve obtained using the three‐window sampling method and total fiber quantification

Morphometric analysis of nerve biopsy provides data of structural changes that are essential for early detection of peripheral neuropathy. Because of the laborious work associated with the total fiber quantification, various sampling methods have been introduced with controversial accuracy. Three-window sampling technique has been recently proposed to provide the accurate morphometric data of normal human sural nerve. However, its application in the diseased nerve has not been validated. This study, therefore, compared the morphometric data of nerve biopsies from 12 patients with various neuropathies obtained using this sampling method and those obtained by total fiber analysis. Total number, density, and diameter of myelinated fibers including myelin thickness and g ratio were analyzed. Intraclass correlation coefficients ranging from 0.95 to 0.99 indicate the high agreement between the data derived from the two methods in these parameters. This finding suggests the accuracy of the three-window sampling technique in the morphometric study of nerve with pathological alterations.

Cutaneous Thermal Sensitivity in Diabetic Neuropathy

The goal of this investigation was to determine if cutaneous thermal sensitivity could be used as a discriminator of peripheral neuropathy in diabetic subjects who were sensate to the Semmes-Weinstein 5.07 monofilament. Sixty adult subjects were separated into two groups. The control group (A) was composed of 30 young healthy individuals without a history of diabetes. The focus group (B) was composed of 26 individuals with adult onset diabetes and four with juvenile onset. All of the subjects underwent thermal sensitivity testing in peripheral nerve root dermatomes of their hands and feet. Testing was performed with custom devices fabricated from materials with different thermal conduction capacities (copper, steel, glass, and plastic). Similar tests were performed with glass tubes containing heated or cooled water to develop a range of thermal sensitivity for the subjects. There was a strong relationship between cold perception and stimulation with the copper probe in dermatomes of the radial nerve of the upper limb and the superficial peroneal dermatome of the lower limb. Thermal sensitivity to copper and cold stimulation may be more discriminative and have a higher threshold than sensitivity to the Semmes-Weinstein monofilament. This simple method may have a role in the early detection of peripheral neuropathy in adult-onset diabetes mellitus.

0366 Quantitative sensory testing with the method-of-limits enables early detection of peripheral neuropathy in genetically verified FAP without electrophysiological abnormalities

0366 Quantitative sensory testing with the method-of-limits enables early detection of peripheral neuropathy in genetically verified FAP without electrophysiological abnormalities

Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration.

To evaluate the sensitivity and specificity of 3 sensory perception testing instruments to screen for risk of diabetic foot ulceration. This case-control study prospectively measured the degree of peripheral sensory neuropathy in diabetic patients with and without foot ulcers. We enrolled 115 age-matched diabetic patients (40% male) with a case-control ratio of approximately 1:3 (30 cases and 85 controls) from a tertiary care diabetic foot specialty clinic. Cases were defined as individuals who had an existing foot ulceration or a history of a recently (< 4 weeks) healed foot ulceration. Controls were defined as subjects with no foot ulceration history. Using receiver operating characteristic analysis, we evaluated the sensitivity and specificity of 2 commonly used nephropathy assessment tools (vibration perception threshold testing and the Semmes-Weinstein 10-g monofilament wire system) and a 4-question verbal neuropathy score to evaluate for presence of foot ulceration. A vibration perception threshold testing using 25 V and lack of perception at 4 or more sites using the Semmes-Weinstein 10-g monofilament wire system had a significantly higher specificity than neuropathy score used. The neuropathy score was most sensitive when 1 or more answers were affirmative. When modalities were combined, particularly the monofilament wire system plus vibration perception threshold testing and the neuropathy score plus the monofilament wire system, there was a substantial increase in specificity with little or no diminution in sensitivity. The early detection of peripheral neuropathy or loss of "protective sensation" is paramount to instituting a structured treatment plan to prevent lower extremity amputation. The results of our study suggest that all 3 sensory perception testing instruments are sensitive in identifying patients at risk for ulceration. Combining modalities appears to increase specificity with very little or no diminution in sensitivity.

Cockayne syndrome: MRI correlates of hypomyelination

Two siblings with Cockayne syndrome are reported who had most of the stigmata characteristic of the syndrome as it was initially described in 1936. Unusual findings are emphasized, such as the early onset of cataracts and the early detection of peripheral neuropathy. The previously reported autopsy abnormalities in this condition are correlated with the present magnetic resonance imaging findings of mild ventricular enlargement and delay in myelination of the cerebrum and cerebellum. Properly myelinated structures included the basal ganglia, thalamus, internal capsule, splenium, and genu of the corpus callosum.