Clinical Peripheral Neuropathy Research Articles

The importance of medial plantar nerve conduction study in detectıon of polyneuropathy in inflammatory bowel disease

Background & Objective: Peripheral neuropathy is the most frequent neurologic complication of inflammatory bowel disease (IBD). We aimed to evaluate the clinical utility of medial plantar nerve conduction study (NCS) in the detection of distal sensory polyneuropathy in IBD patients. Methods: The study was performed with 21 Crohn’s disease (Group 1) patients, 24 Ulcerative Colitis (Group 2) patients without clinical peripheral neuropathy and 28 healthy participants (Group 3). Each patient group underwent electrophysiological conduction studies. The findings were analyzed statistically. Results: Abnormal medial plantar nerve conduction was present on both sides in 11 (24.4 %) patients with IBD; 5 (11.1 %) patients had low sural nerve amplitude, and 5 (11.1 %) had low superficial peroneal nerve amplitude bilaterally. There were significant differences between the IBD groups (Group 1 and 2) and Group 3 in the mean sensory nerve action potential amplitude of the right medial plantar nerve (p<0.024), and in the mean sensory nerve action potential amplitude of the left medial plantar nerve (p<0.025). The polyneuropathy pattern was mostly of the sensory axonal type in patients with IBD. Conclusions: These electrophysiologic findings indicate that peripheral neuropathy is more prevalent in IBD. In IBD patients the amplitudes of the medial plantar nerve were abnormal more than in the sural and superficial peroneal nerves.

Should we follow the guidelines on vitamin B12 deficiency and diabetes? A retrospective analysis of data from middle eastern population

ABSTRACT Background Vitamin B12 is a micronutrient required for hematopoietic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been recognized in patients with type 2 diabetes mellitus. One of the adverse effects of long-term metformin use is vitamin B12 malabsorption. Aim of the study was to assess the state of vitamin B12 deficiency in people with type 2 diabetes and to ascertain the relationship between vitamin B12 status, metformin use and peripheral neuropathy. It is a retrospective study that was conducted on 8040 subjects included 2126 type 2 diabetic patients, and 5914 nondiabetic individuals. Personal information, medical history, including metformin and multivitamin therapy use as well as the existence of clinical peripheral neuropathy, were all included data. For the purpose of measuring the amount of vitamin B12, blood samples were taken. Serum B12 levels <200 pg/ml was defined as B12 deficiency. Results Vitamin B12 deficiency was detected in 12.9% of diabetic group and 19.9% of control group. The mean value of vitamin B12 level between diabetic (563 ± 470.6 pg/ml) and non-diabetic (429.7 ± 310.9 pg/ml) showed a high significant difference, p value <0.001. The vitamin B12 levels were higher in people with diabetes. Vitamin B12 deficiency was not associated with metformin intake or diabetic neuropathy. Conclusions Vitamin B12 level was significantly higher in diabetic compared to nondiabetic individuals. Neither peripheral neuropathy, anemia nor metformin therapy was associated with vitamin B12 deficiency. Vitamin B12 supplementation is not recommended as a routine practice in people with diabetes. This is contrary to the common practice that is sometimes done. The cost of supplementation can be used to provide more beneficial services and drugs for these people.

Corneal Nerve Changes Observed by In Vivo Confocal Microscopy in Patients Receiving Oxaliplatin for Colorectal Cancer: The COCO Study.

An objective method of early identification of people at risk of chemotherapy-induced peripheral neuropathy is needed to minimize long-term toxicity and maximize dose intensity. The aims of the study were to observe corneal nerve microstructure and corneal sensitivity changes and peripheral neuropathy in patients receiving oxaliplatin, and to determine its association with corneal parameters at different stages of treatment and assess utility as non-invasive markers to detect and monitor peripheral neuropathy. Twenty-three patients scheduled to receive oxaliplatin chemotherapy with intravenous 5-FU for gastro-intestinal cancer were recruited and followed up with for 12 months. Ocular examinations including corneal and retinal evaluations, alongside peripheral neuropathy assessment, were performed. The corneal nerve density did not show significant change after chemotherapy when measured with a widely used semi-automated program or an automated analysis technique. Macula and optic nerve function did not change during or after oxaliplatin chemotherapy. However, the corneal nerve density modestly correlated with clinical peripheral neuropathy after 20 weeks of chemotherapy (r = 0.61, p = 0.01) when peripheral neuropathy is typical most profound, and corneal nerve sensitivity correlated with neuropathy at 12 (r = 0.55, p = 0.01) and 20 weeks (r = 0.64, p = 0.006). In conclusion, corneal changes detected on confocal microscopy show moderate association with peripheral neuropathy, indicating their potential to identify the development of oxaliplatin-induced peripheral neuropathy. However, further studies are required to confirm these findings.

Neurophysiological evaluation of juvenile systemic lupus erythematosus

BackgroundPeripheral nervous system and the central nervous system involvement in systemic lupus erythematosus (SLE) patients are one of the major causes of morbidity and mortality. The aim of this work was to study the nervous system clinically and electrophysiologically in children with systemic lupus erythematosus.ResultsThe study was carried out on thirty-eight children with SLE. Their age ranged from 5 to 16 years. The most encountered neurologic manifestations were tremors. It was observed in 47.4% of children, followed by headache in 39.5%, sensory manifestation as numbness in 23.7%, cerebrovascular stroke in 5.3%, and chorea in 2.6%, which was unilateral mostly in the upper limb, tics, and convulsion had the same percentage. Around 16% of children had positive findings in MRI, such as cerebrovascular disease, minimal hematoma, pseudotumorcerebri, vasculitis, and ectatic ventricles. Subclinical peripheral neuropathy was reported in nearly 52.6% of children, and clinical peripheral neuropathy was reported in 23.6%. Pure sensory subclinical peripheral neuropathy was detected in 13.1% of children, but mixed subclinical peripheral neuropathy was detected in 39.4%. Nearly 53% of studied children had an abnormal somatosensory-evoked potential study of posterior tibial and median nerves.ConclusionThe current study reported that the clinical neurological manifestations in juvenile SLE is common. Peripheral neuropathy is commonly detected, which could be either clinical or sub-clinical. Somatosensory evoked potential study is of value for early detection of central affection.So, we recommend more studies to determine the guidelines when to order these informative investigations for children with JSLE.

Frequency Of Peripheral Neuropathy in Chronic Hepatitis C Patients Presenting at Liaquat University Hospital, Hyderabad

Hepatitis C virus (HCV) and its infective pathogenic role leads to the psychiatric and neurological signs and symptoms. Therefore, close monitoring and regular follow-up is warranted. Objective: To find out the frequency of peripheral neuropathy among patients presenting at Liaquat University Hospital, Hyderabad, having Chronic Hepatitis C. Methods: The cross-sectional study included 359 patients with chronic HCV, aged 20 to 70 years, who presented to the Liaquat University Hospital's Hepatitis Clinic and Outpatient Department of General Medicine and Neurology. Non-probability - sequential sampling was used to choose patients. Patients were asked about demographic information and the duration of chronic HCV after giving informed written consent. The clinical examination was performed to see if there were any reduced tendon reflexes in all of the patient's extremities. To diagnose peripheral neuropathy based on nerve conduction velocity, all patients had an electrophysiological test using a simplified nerve conduction study (NCS) methodology (NCV). The research lasted six months, from June 2021 to December 2021. The information was examined via SPSS version 25.0. Results: There were 219 Men (61%) And 140 Females (39%) among the 359 Patients. The average age (SD) of the participants was 42.3 (8.7) years (range 22–70). HCV infection lasted 36 months on average (range 1–156). Out of 359 patients, 61 had clinical peripheral neuropathy (PN) (17%). Electrophysiological evidence of PN was present in all of these patients, electrophysiological investigation revealed subclinical PN in 19 more patients (5.3%). Conclusion: On the basis of the findings from this study, it can be concluded that a high prevalence of peripheral neuropathy is present among the patients with HCV in our locality. However, an electrophysiological examination should always be done to avoid underestimating PN, particularly in older HCV patients.

Association between vitamin B12 level and clinical peripheral neuropathy in type 2 diabetic patients on metformin therapy

BackgroundVitamin B12 malabsorption is one of the side effects of long-term metformin intake. Prolonged vitamin B12 deficiency can lead to irreversible nervous system damage. So, the current study aimed to determine the association between serum vitamin B12 level and clinical peripheral neuropathy among type 2 DM patients who are on metformin in comparison to those not taking it. It is a cross-sectional study that was conducted in Egypt and recruited 100 type 2 diabetic patients who were divided into 2 groups: metformin treated, and non-metformin treated (50 subjects per group). The collected data included personal history, medical history, dietetic history that included frequency of eating food rich in vitamin B12 and clinical peripheral neuropathy assessment by Toronto Clinical Scoring System (TCSS). Blood samples were collected for assessment of HbA1c and vitamin B12 level.ResultsVitamin B12 deficiency was present in 4% of metformin group and 2% of non-metformin group. The mean value of vitamin B12 between metformin users (624.3 ± 364.1 pg/ml) and non-metformin users (991.0 ± 489.9 pg/ml) showed a high significant difference, p value < 0.001. There was a significant difference between study groups regarding HbA1c level (p value = 0.03). Peripheral neuropathy was significantly associated with HbA1c (p value = 0.04) and female gender (p value = 0.001).ConclusionsVitamin B12 level was lower in type 2 diabetic patients on metformin compared to those on other oral anti-diabetic drugs, but without significant deficiency. Peripheral neuropathy was significantly associated with poor glycemic control and female gender, but was not associated with vitamin B12 deficiency.

Systemic lupus erythematosus may have an early effect on peripheral nerve function in patients without clinical or electrophysiological neuropathy: comparison with age- and gender-matched controls.

Asymptomatic electrophysiological peripheral neuropathy is described in systemic lupus erythematosus (SLE) patients. To determine if SLE could have an even earlier effect on peripheral nerve function even before the development of electrophysiological abnormalities, we compared nerve conduction studies (NCS)of SLE patients without electrophysiological or clinical peripheral neuropathy with healthy controls. Consecutive SLE patients without clinical neuropathy (or other known causes of neuropathy) underwent sensory and motor NCS of all four limbs. Results of 61 patients without electrophysiological criteria of neuropathy were compared with age- and gender-matched controls. Although still within the laboratory's range of normal values, significant differences were found in several NCS parameters between patients and controls. SLE patients had lower amplitudes for ulnar, fibular, and tibial compound muscle action potentials (CMAP) and sural sensory nerve action potentials (SNAP); slower conduction velocities for median, ulnar, and fibular motor nerves, and median, ulnar and sural sensory nerves. SLE patients also had longer minimum F-wave latencies for median, ulnar, fibular, and tibial nerves. H reflexes were more often absent in patients. Correlations were found between the number of disease relapses and motor conduction velocities of the fibular and tibial nerves. SLE may have early effect on peripheral nerve function in patients even before they develop electrophysiological or clinical neuropathy.

In vivo and in situ real-time fluorescence imaging of peripheral nerves in the NIR-II window

The peripheral nervous system (PNS) is essential for performing and maintaining various motor and sensory functions. Abnormalities can lead to a series of peripheral neurological conditions, such as paraesthesia, pain, or spasms, which are debilitating and lowering the quality of life. The current guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction, which occur already at an advanced stage. There are currently no effective methods that visually reflect the extent of peripheral neuropathy. In our study, we present a novel in vivo and in situ real-time imaging of peripheral nerves based on the second near-infrared window (NIR-II) fluorescence. In NIR-II system, PbS Qds with NIR-II fluorescence specifically bound to motor neuron-specific protein agrin, acting as image contrast. In mice model, peripheral nerves were visible as soon as after 2 h post injection. We provide evidence for the efficacy of this approach, which allows to directly demonstrate peripheral nerves, their structure, and potential damage sites and degree. Furthermore, our products were of good biocompatibility, while the neural fluorescence signal was solid, bright and stable for 4 h in vivo. Thus, overall, our results suggest that NIR-II is an effective new method for direct imaging of peripheral nerves in vivo, opening new horizons on early, improved and more precise, targeted diagnosis. A resulting more rapid installation of personalized therapy facilitates a better prognosis of clinical peripheral neuropathy.

Ixazomib in the treatment of relapsed multiple myeloma

Ixazomib (NINLARO, Takeda Pharmaceutical Company Limited) is the first oral proteasome inhibitor which approved in combination with lenalidomide and dexamethasone (IRd) for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is a boron-containing selective and reversible proteasome inhibitor that have high antitumor activity with excellent safety. This combination was approved based on the results from the phase 3, double-blind, placebo-controlled TOURMALINE-MM1 study, which demonstrated a 35% improvement in progression-free survival (PFS) for IRd versus placebo-Rd: median: 20.6 vs 14.7 months; hazard ratio (HR): 0.74, P = 0.012. PFS was improved in both high-and standard-risk cytogenetics subgroups with median PFS in high-risk patients 21.4 vs 9.7 months (HR 0.54; P = 0.021) and in standard-risk patients 20.6 vs15.6 months (HR 0.64; P = 0.007). The addition of ixazomib to Rd regimen was associated with minimal additional toxicity. Common grade ≥3 adverse events with ixazomib include gastrointestinal adverse events, rash, and thrombocytopenia. No significant inhibition of neuronal cell survival protease HtrA2/Omi was noted in response on ixazomib treatment in vitro that explains its minimal clinical peripheral neuropathy. The present review addresses the current knowledge regarding the clinical use of ixazomib in relapsed myeloma patient and the prospects for further expansion of therapeutic indications.

Comparative Study of Nerve Conduction Velocity Studies in Type II Diabetes Mellitus with &amp; Without Features of Clinical Peripheral Neuropathy

Comparative Study of Nerve Conduction Velocity Studies in Type II Diabetes Mellitus with &amp; Without Features of Clinical Peripheral Neuropathy

Neurophysiologic evaluation of peripheral nerve function in uremic Egyptian children

Information concerning clinical and sub-clinical peripheral neuropathy in uremic children is still scarce. We aimed to evaluate role of neurophysiologic testing for detection of peripheral nerve dysfunction in asymptomatic uremic Egyptian children. A cohort of 81 uremic children was enrolled from Pediatric Nephrology Unit in Mansoura University Children's Hospital. It comprised 39 cases on conservative therapy; conservative group (CG) (27 males and 12 females, with mean age 9.8 ± 3.3 years) and 42 cases under regular hemodialysis for at least 6 months; hemodialysis group (HG) (27 males and 15 females, with mean age 11.8 ± 1.6 years). A third group of twenty healthy children was taken as control (12 males, and eight females, with mean age 9.9 ± 2.4 years). Nerve conduction studies including motor and sensory functions were done successfully in most cases; data were analyzed using SPSS version 10.0. Different proportions of abnormal motor and sensory conduction studies were reported in both patients' groups with reference to pediatric ranges built-in Sierra II software. Comparing these observations to controls, motor peroneal and median conduction velocities as well as sensory ulnar conduction velocity were significantly delayed in HG (38.46 ± 4.49 vs. 48.33 ± 3.35 for peroneal, 50.68 ± 10.87 vs. 57.22 ± 7.13 for median and 32.82 ± 9.8 vs. 52.08 ± 20.12 for ulnar nerve). However, in CG antidromic sensory median conduction was the only significant abnormality detected (41.13 ± 9.63 vs. 53.89 ± 12.32). F wave latencies in CG were almost normal but in HG they were moderately affected compared to controls. We can conclude that sensory dysfunction could be early detected in asymptomatic uremic children by neurophysiologic testing. Further prospective studies should be warranted to evaluate sequential electrophysiological changes in response to hemodialysis.

Neuropatia da Doença de Hansen: Um Diagnóstico a Considerar na Investigação da Neuropatia Periférica

Leprosy is still one of the most frequent causes of peripheral neuropathy. Although regarded as eradicated in Portugal, is still documented in neuropathological study of patients with clinical peripheral neuropathy without proper diagnosis. Review of the cases of Hansen disease neuropathy diagnosed in Neuropathology Unit of Centro Hospitalar do Porto between 1978 and 2013, atending to gender, age, clinical manifestations and neuropathological findings. Twenty one patients were identified with neuropathological diagnosis of Hansenâs disease neuropathy, predominantly male. The mean age at diagnosis was 52 years, and sensory symptoms predominate as neurological manifestation of disease. Interval between symptoms and diagnosis was 1-38 years. In most nerve samples tuberculoid type of disease was identified. Bacilli were detected in skin and nerve in 44% of cases. Mononeuritis is the most common presentation of leprosy but other clinical manifestations are possible, including skin lesions. Infection with M. leprae injures myelinated and unmyelinated fibres, with replacement of nerve tissue by collagen fibrosis. The diagnosis of leprosy is only achieved by neuropathological study of skin lesions and / or peripheral nerve, supported by the identification of the bacillus. Hansen disease remains a public health problem in tropical areas and, although rare, still described in Western countries reason why should still be considered as a diagnostic possibility in the investigation of peripheral neuropathy.

Use and Utility of Ankle Brachial Index in Patients with Diabetes

Ankle brachial index (ABI) is a simple method to screen peripheral arterial disease (PAD) and to evaluate cardiovascular (CV) prognosis in the general population. Measuring it requires a hand-held Doppler probe but it can be done also with an automatic device. ABI is an effective tool for clinical practice or clinical studies. However, in diabetic patients, it has some specific caveats. Sensitivity of the standard threshold of 0.9 appears to be lower in diabetic patients with complications. Moreover, highly frequent arterial medial calcifications in diabetes increase ABI. It has been demonstrated that measurements >1.3 are well correlated with both an increased prevalence of PAD and CV risk. Therefore, ABI thresholds of less than 0.9 and more than 1.3 are highly suspicious for PAD and high CV risk in diabetic patients. However, when there is concomitant clinical peripheral neuropathy or high risk of arterial calcification, the efficiency of ABI seems to be limited. In this case, other methods should be applied, toe pressure, in particular. Thus, the ABI could be used in patients with diabetes, but values should be interpreted with precision, according to the clinical situation.

Foot Muscle Energy Reserves in Diabetic Patients Without and With Clinical Peripheral Neuropathy

OBJECTIVETo investigate changes in the foot muscle energy reserves in diabetic non-neuropathic and neuropathic patients.RESEARCH DESIGN AND METHODSWe measured the phosphocreatinine (PCr)/inorganic phosphate (Pi) ratio, total 31P concentration, and the lipid/water ratio in the muscles in the metatarsal head region using MRI spectroscopy in healthy control subjects and non-neuropathic and neuropathic diabetic patients.RESULTSThe PCr/Pi ratio was higher in the control subjects (3.23 ± 0.43) followed by the non-neuropathic group (2.61 ± 0.36), whereas it was lowest in the neuropathic group (0.60 ± 1.02) (P < 0.0001). There were no differences in total 31P concentration and lipid/water ratio between the control and non-neuropathic groups, but both measurements were different in the neuropathic group (P < 0.0001).CONCLUSIONSResting foot muscle energy reserves are affected before the development of peripheral diabetic neuropathy and are associated with the endothelial dysfunction and inflammation.

Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

OBJECTIVE—Alström syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alström syndrome and matched young-onset type 2 diabetic subjects was therefore undertaken.RESEARCH DESIGN AND METHODS—Fifty-eight subjects with Alström syndrome (18 insulin-resistant nondiabetic and 40 diabetic; aged 8–43 years) and 30 young-onset diabetic subjects (aged 13–35 years) were studied. Neuropathy symptom questionnaires were administered. Graded monofilament and 128-MHz tuning fork vibration perception were assessed in both feet.RESULTS—Neuropathic symptoms, loss of monofilament, and/or vibration perception were reported by 12 of the 30 young-onset type 2 diabetic subjects (6 had neuropathic ulceration) but none of the subjects with Alström syndrome.CONCLUSIONS—The striking preservation of protective foot sensation in Alström syndrome may provide a clue to the causes of differential susceptibility to neuropathy in the wider diabetic population.

Neurology of Fabry disease

Fabry disease has diverse neurological manifestations, many of which influence morbidity and quality of life. The aim of the study was to document the clinical and subclinical neurological manifestations in a cohort of Australian patients with Fabry disease, using multiple clinical tools and a multidisciplinary approach. Participants completed focused questionnaires and underwent clinical neurological examination, Neurocognitive testing using Mini Mental State Examination and Neuropsychiatry Unit Cognitive Screen, Quantitative Sensory Testing (QST), autonomic assessment using RR interval variation, intracranial magnetic resonance imaging (MRI) and audiology. In subsets of patients who had previously undergone QST and/or prospective serial quality-of-life assessments over the previous 5 years, results before and after enzyme replacement therapy were compared. Twenty hemizygotes and two heterozygotes were recruited. The age (mean +/- standard deviation (SD)) of male participants was 40.4 +/- 11.9 years (range 20-62 years); the women were aged between 20 and 56 years. Increasing age was strongly associated with increasing neurological disability. Clinical peripheral neuropathy predominantly affected thermal sensation in all patients, with variable involvement of pinprick and light touch. QST confirmed these findings. Clinical cerebellar tests were commonly abnormal: this has not been previously reported in the absence of symptomatic cerebrovascular disease. There was hearing loss was in 90% of patients and no patient older than 44 years had normal hearing. MRI lesion prevalence increased with age. Despite neurological complications being common, formal cognitive testing was basically normal. QST thresholds for pain showed a significant change after enzyme replacement therapy. Neurological complications in Fabry disease are common, complex and may be devastating. All patients studied had neurological involvement, with protean and diverse manifestations.

Foot Small Muscle Atrophy Is Present Before the Detection of Clinical Neuropathy

To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ((31)P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). We studied 12 control subjects, 9 non-neuropathic diabetic patients, and 12 neuropathic diabetic patients using (31)P RARE and proton ((1)H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial (1)H and (31)P images. The average (31)P concentration across the metatarsal head region was measured from the (31)P images. The muscle area-to-total area ratio differed among all three groups (means +/- SD): 0.55 +/- 0.04 vs. 0.44 +/- 0.05 vs. 0.06 +/- 0.06 for control, non-neuropathic, and neuropathic subjects, respectively (P < 0.0001). The average (31)P concentration also differed among all groups: 27.7 +/- 3.8 vs. 21.7 +/- 4.8 vs. 7.9 +/- 8.8 mmol/l for control, non-neuropathic, and neuropathic subjects (P < 0.0001). The muscle area-to-total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = -0.83, P < 0.0001; vibration perception threshold, r = -0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = -0.87, P < 0.0001. Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The (31)P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.

Aldose reductase gene polymorphisms and peripheral nerve function in patients with type 2 diabetes.

We screened the human aldose reductase (ALR) gene for DNA sequence variants in type 2 diabetic and nondiabetic subjects and investigated whether the previously reported and novel polymorphisms were associated with neurophysiologic deterioration and clinical peripheral neuropathy. The study population included 85 Finnish type 2 diabetic and 126 nondiabetic subjects. The genetic analyses were performed using the PCR, single-strand conformation polymorphism, restriction fragment-length polymorphism, and automated laser fluorescence scanning analyses. A detailed neurologic examination and neurophysiologic analyses were performed at the time of diagnosis and at the 10-year examination. The genetic screening identified four polymorphisms: C-106T, C-11G, A11370G, and C19739A. The C and Z-2 alleles of the C-106T polymorphism and the previously reported (CA)(n) repeat marker were more frequent in type 2 diabetic subjects than in nondiabetic subjects. At baseline, the diabetic subjects with the T allele of the C-106T polymorphism had lower sensory response amplitude values in the peroneal (P = 0.025), sural (P = 0.007), and radial (P = 0.057) nerves and, during follow-up, a greater decrease in the conduction velocity of the motor peroneal nerve than those with the C-106C genotype. No associations were found between the polymorphisms examined and clinical polyneuropathy. The C-106T polymorphism of the ALR gene may contribute to an early development of neurophysiologic deterioration in type 2 diabetic patients.

Thalidomide‐associated neuropathy in multiple myeloma

Thalidomide is a neurotoxic immunomodulating agent currently used in Multiple Myeloma (MM). We prospectively evaluated the frequency and characteristics of peripheral neuropathy in a continuous series of 25 patients (13 M, 12 F; age 38–60, median 55 yrs) treated with thalidomide for MM. Patients underwent a neurological and neurophysiological evaluation before starting thalidomide therapy and monthly throughout duration of treatment. Sixteen patients (5 M, 11 F) developed neurophysiological characteristics of axonal sensitive damage and/or clinical peripheral neuropathy with distal sensory symptoms; treatment duration ranged between 95 and 572 days (median 298) in patients with neuropathy, and 49–264 days (median 162) in patients without neuropathy; the total amount of thalidomide taken ranged between 26 and 169 g (median 83 g) for patients with neuropathy and 13–170 g (median 51 g) for those without. In four patients, ENG alterations appeared before clinical symptoms, while in two patients they were not followed by clinical symptoms. In the remaining three patients, clinical symptoms preceded neurophysiological alterations. Age at onset of MM, disease duration before thalidomide therapy was started, total dose, duration of therapy and previous treatments were not correlated with neuropathy (multivariate logistic regression analysis). Female gender was a risk factor for developing neuropathy (OR 7.7).

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes–Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. (≈10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. (≈246 mN) and averaged 4.97 a.u. (≈92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.