Peripheral Polyneuropathy Research Articles

Poster 197: Inflammatory Myopathy in a Diabetic Presenting With Foot Drop: A Case Report

Setting: Outpatient clinic. Patient: A 29-year-old man referred for electrodiagnostics with 1 year complaint of progressive foot drop and ataxia. Case Description: Patient has medical history of poorly controlled diabetes type 1 (diagnosed 14 years prior), hyperlipidemia (with current statin use), hypertension, and depression. History of present illness revealed proximal and distal weakness in upper and lower extremities and numbness in stocking and glove distribution. Lumbar magnetic resonance imaging showed disk herniations with no stenosis. The patient denied back pain, radicular pain, muscle aches, or family history of neurologic conditions. Physical exam revealed diffuse atrophy, proximal and distal weakness with trace bilateral ankle dorsiflexion, absent reflexes, and normal muscle tone. Electrodiagnostics revealed a sensorimotor peripheral polyneuropathy with neuropathic findings on electromyography (EMG) without specific myopathic features. Lab studies revealed CPK greater than 1000, elevated aldolase, ESR greater than 100, and a negative rheumatologic panel. Muscle biopsy was suggestive of a chronic myopathy, possibly inflammatory, with features of neurogenic atrophy. Assessment/Results: This patient's clinical picture and diagnostics are suggestive of multifactorial weakness—due to a chronic inflammatory myopathy—polymyositis versus statin-induced myopathy, with a superimposed diabetic neuropathy. The patient has been discontinued from statins, started on corticosteroids and azathioprine, fitted with bilateral ankle foot orthoses, and treated with physical therapy. His functional status remains stable with ongoing treatment. Conclusions: Correlation of thorough history, physical exam, and diagnostics is essential for appropriate diagnosis and treatment. EMG findings for this patient were suggestive of a neuropathic process, while physical exam also suggested a myopathic process. Through laboratory and histologic studies a more complete pathophysiology and treatment plan was formed. It is important to remember that weakness can be multifactorial. Complex cases where history and physical do not correlate with findings necessitate further diagnostic investigation, consideration, and cross-specialty physician collaboration to achieve the best patient outcomes.

Deficiência de tiamina como causa de cor pulmonale reversível

Thiamine deficiency may present four classic clinical forms: peripheral polyneuropathy, anorexia and muscular weakness (dry beriberi); high output heart failure with signs of congestion (wet beriberi); beriberi associated with shock (Shoshin beriberi) and Wernicke's encephalopathy. In this report we describe a picture that is suggestive of severe pulmonary hypertension and cor pulmonale, with jugular stasis, congestive hepatitis and generalized edema that reversed completely after the administration of thiamine.

Pharmacokinetics of Acetyl-L-Carnitine Given in Single or Multiple Doses to HIV-1 Infected Patients with Toxic Peripheral Polyneuropathy

The use of nucleoside reverse transcriptase inhibitors in the treatment of HIV infection is associated with antiretroviral toxic polyneuropathy (ATN). Previous studies suggest that long term treatment with Acetyl-L-carnitine (ALCAR) 1.5 gram twice daily improves symptoms and promotes nerve regeneration. It is unknown whether the drug’s pharmacokinetic profile would allow for a once daily administration. Twenty three HIV-1 infected subjects taking ALCAR for ATN were enrolled in a cross over trial and switched from twice to once daily dosing. Their regimen was changed from 1.5g twice daily to 1g (4 patients), 2g (7), and 3g (12) once daily, respectively. Twelve healthy volunteers served as control. Plasma levels of ALCAR and its metabolite L-carnitine were measured. Patients receiving ALCAR had higher pre-dose levels than control subjects. Post dose levels were not significantly higher than pre dose levels in any treatment group. The pre / post dose ALCAR concentrations were 7.6 / 7.7, 7.1 / 6.8, 7.7 / 6.8, and 7.1 / 7.5 µmol/l for 1.5g twice daily, 1g once daily, 2g once daily, and 3g once daily, respectively. All values were significantly higher than the mean concentration in the control group (4.3 µmol/l). For ALCAR and L-carnitine, measurements for once daily regimens did not differ from the twice daily regimen. Once daily dosing of ALCAR can achieve similar plasma levels as twice daily dosing but intra-mitochondrial levels remain unknown. The pharmacokinetic profile of orally administered ALCAR is complex and likely to be highly affected by endogenous concentrations.

P151 Association of inflammatory bowel diseases and peripheral polyneuropathy

P151 Association of inflammatory bowel diseases and peripheral polyneuropathy

Acute effect of metoclopramide on esophagus motility in diabetes mellitus

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

Childhood Thalidomide Neuropathy: A Clinical and Neurophysiologic Study

Thalidomide was recently reintroduced to treat several immune-mediated pathologies. Peripheral neuropathy is a significant side effect limiting its clinical use. Our aims include: (1) describing and identifying the incidence of clinical or electrophysiologic peripheral neuropathy in children, (2) determining whether peripheral neuropathy correlates with cumulative dose of thalidomide and with age, and (3) defining its reversibility rate. We studied 13 children manifesting immune-mediated pathologies treated with thalidomide at doses ranging from 25-100 mg/day. Clinical and neurophysiologic evaluation was performed before and after starting treatment. Seven children (53.8%) showed neurophysiologic signs of sensory peripheral axonal polyneuropathy. Five presented associated clinical symptoms, while the other two only presented subclinical, neurophysiologic signs of peripheral neuropathy. We found a significant correlation between the incidence of peripheral neuropathy and thalidomide cumulative dose (P = 0.02). We observed a lower incidence of peripheral neuropathy at a cumulative dose <20 gm, and a correlation with age (P < 0.01). The clinical and electrophysiologic recovery rate was 40%, and clinical improvement alone was observed in another 40%. Thalidomide induces dose-dependent and age-dependent peripheral neuropathy at a significant frequency in childhood (53.8%). In our experience a cumulative dosage at >20 gm and long-term administration for >10 months seem to increase the risk of peripheral neuropathy. We propose clinical and neurophysiologic follow-up every 3 months to identify and monitor possible side effects.

Cerebrospinal Fluid Neopterin in Patients with Tumors and other Disorders

Abstract Increased urinary or serum concentrations of neopterin have been reported in cancer patients, but less is known about neopterin concentrations in cerebrospinal fluid (CSF). CSF neopterin was determined with radioimmunoassay in 64 patients. CSF neopterin concentrations in patients with tumors were significantly higher compared to patients with predominantly peripheral infections (Lyme borreliosis and herpes simplex infection) and no infectious, inflammatory or neoplastic disorder, and significantly lower compared to patients with meningitis or encephalitis. Among patients with tumors, CSF neopterin was significantly higher in patients with non- Hodgkin lymphoma (NHL) compared to other tumors. The difference between patients with tumors other than NHL and predominantly peripheral infections was of borderline significance, and a significant difference was observed between patients with tumors other than NHL and no disorder. CSF neopterin was significantly higher in patients with NHL compared to patients with predominantly peripheral infections, multiple sclerosis or polyneuropathy and no disorder, and no difference was evident compared to patients with meningitis or encephalitis. In conclusion, among patients with tumors, high CSF neopterin may suggest the diagnosis of NHL.

High-Tone External Muscle Stimulation in End-Stage Renal Disease: Effects on Symptomatic Diabetic and Uremic Peripheral Neuropathy

Pain and peripheral neuropathy are frequent complications of end-stage renal disease (ESRD). Because drug treatment is associated with numerous side effects and is largely ineffective in many maintenance hemodialysis (MHD) patients, nonpharmacologic strategies such as electrotherapy are a potential recourse. Among various forms of electrostimulation, high-tone external muscle stimulation (HTEMS) is a promising alternative treatment for symptomatic diabetic peripheral polyneuropathy (PPN), as demonstrated in a short-term study. Based on these novel findings, we performed a prospective, nonrandomized, pilot trial in MHD patients to determine (1) whether HTEMS is also effective in treating diabetic PPN in the uremic state, and (2) whether uremic PPN is similarly modulated. In total, 40 MHD patients diagnosed with symptomatic PPN (25 with diabetic and 15 with uremic PPN) were enrolled. Both lower extremities were treated intradialytically with HTEMS for 1 hour, three times a week. Initially, a subgroup of 12 patients was followed for 4 weeks, and a further 28 patients for 12 weeks. The patients' degree of neuropathy was graded at baseline before HTEMS and after 1 and 3 months, respectively. Five neuropathic symptoms (tingling, burning, pain, numbness, and numbness in painful areas) as well as sleep disturbances were measured, using the 10-point Neuropathic Pain Scale of Galer and Jensen (Neurology 48:332-338, 1997). A positive response was defined as the improvement of one symptom or more, by at least 3 points. Other parameters included blood pressure, heart rate, dry body weight, and a routine laboratory investigation. The HTEMS led to a significant improvement in all five neuropathic symptoms, and to a significant reduction in sleep disturbances for both diabetic and uremic PPN. The response was independent of the patient's age, with a responder rate of 73%. The improvement of neuropathy was time-dependent, with the best results achieved after 3 months of treatment. The HTEMS was well-tolerated by nearly all patients. This pilot study shows for the first time that HTEMS can ameliorate the discomfort and pain associated with both diabetic and uremic PPN in MHD patients, and could be a valuable supplement in the treatment of pain and neuropathic discomfort in patients who do not respond to, or are unable to participate in, exercise programs during hemodialysis treatment.

PROSPECTIVE FOLLOW-UP OF PATIENTS WITH EWING SARCOMA WITHIN THE LATE EFFECTS SURVEILLANCE SYSTEM

INTRODUCTION: It is known that antineoplastic treatment may induce early and late organ toxicities depending on treatment modalities and intensity. OBJECTIVE: The aim of this study was to determine the cumulative incidence of sequelae within our cohort of patients treated within the EICESS-92 (European Intergroup Cooperative Ewing's Sarcoma Study, 1992) treatment trial. METHODS: Since 1998, the Late Effects Surveillance System (LESS) of the German Society for Pediatric Oncology and Hematology has prospectively registered late effects in patients of all ages with relapse-free bone and soft tissue sarcoma in Austria, Germany, and Switzerland. The follow-up is conducted locally in accordance with LESS guidelines. Data are reported to the LESS center for collation and analysis. RESULTS: There were 67 patients available for analysis (42 male, 25 female) with a median age at diagnosis of 13 years and a median follow-up of 3.5 years. Registration had to be terminated for 17 patients as a result of relapse. In total, 43.3% (29 of 67) of the patients were reported to have at least 1 sequelae of treatment. Sixteen patients suffered toxicity in 1 organ system, 9 patients developed toxicity in 2 organ systems, and there were 3 organ systems affected in 4 patients. Nephrotoxicity was reported in 10.4% (7 of 67), cardiotoxicity in 8.9% (6 of 67), peripheral polyneuropathy in 5.9% (4 of 67), and other toxicities in 34.3% (23 of 67) of the patients. CONCLUSIONS: Sequelae of treatment for Ewing sarcoma within this cohort of the EICESS-92 study were not more frequent than reported previously. Patients are at risk for the development of several toxicities after treatment for Ewing sarcoma, and they should receive adequate medical follow-up.

Autonomic dysfunction in cirrhosis and portal hypertension

Liver cirrhosis and portal hypertension are frequently associated with signs of circulatory dysfunction and peripheral polyneuropathy, which includes defects of the autonomic nervous system. Autonomic dysfunction, which is seen in both alcoholic and non‐alcoholic liver cirrhosis and increases with severity and duration of the liver disease, is associated with a significant increase in mortality. The lack of total resolution after liver transplantation indicates that the autonomic neuropathy is not exclusively functional. This article highlights some aspects of the autonomic dysfunction in chronic liver disease. A description is given of its aetiology and the typical circulatory dysfunction with characteristic hyperdynamic and hyporeactive circulation and heart failure, and the most important tests of the autonomic nervous system.

A message in a bottle: a case report

In intensive care medicine, correctly identifying the underlying cause of illness in patients presenting to critical care units is often the key to applying a successful therapeutic regimen. We report on a patient in whom, despite anamnestic hints, the correct diagnosis was obscured by misleading laboratory results. A previously healthy male physician aged 36 years presented to the emergency room because of balance disturbances and gait problems. These symptoms began a few hours after ingestion of remarkably bitter tasting mineral water in the office of the research laboratory. Soon after admission, the patient became progressively confused and reported visual hallucinations; his neurological symptoms rapidly worsened. The findings of initial diagnostic tests, including blood tests, microbiological and toxicological screening, cranial computed tomography scanning and magnetic resonance imaging, were unremarkable. Nevertheless, the patient soon had to be sedated and intubated to prevent aspiration. Within the next 24 hours the patient developed multiple organ failure with renal, liver, respiratory and circulatory failure, and signs of disseminated intravascular coagulation and rhabdo-myolysis. Severe sepsis of unknown cause was presumed, and empirical treatment with antibiotics and a course of activated protein C was initiated; clinical management required high amounts of fluids and catecholamines. Extensive microbiological tests, including repeated blood and sputum cultures, serology for leptospira and borrelia, and polymerase chain reaction for herpes simplex virus DNA, were unfruitful. On day 3 after admission repeated toxicological examination of blood samples and the mineral water revealed contamination with acrylamide at high concentrations. Treatment with antibiotics and activated protein C was immediately terminated, and therapy with high doses of N-acetylcysteine was initiated to replenish hepatic glutathione stores. Between days 4 and 8 cardiac function gradually returned to normal, and platelet count, coagulation parameters and renal function also improved. On day 6 the patient was extubated; he exhibited signs of severe peripheral polyneuropathy with initial tetraplegia, bilateral affection of the vagal nerve and resulting laryngoplegia. When he was transferred for further neurological rehabilitation after 21 days of intensive care, the patient was still suffering from occasional confusion and hallucinations and was unable to walk. Acute acrylamide intoxication in humans is a rare event that has been reported only once in the literature [1]. The diagnosis should be considered in individuals with access to acrylamide (for instance, those working in molecular laboratories) who develop symptoms of central nervous system disturbances followed by cardiovascular, respiratory and other organ manifestations [2]. Gas chromatographic tandem mass spectrometry has been proven to be a sensitive method for the detection of acrylamide [3]. The clinical picture of acrylamide intoxication might suggest severe sepsis with acute onset, but this diagnosis should be challenged as long as it remains a working hypothesis.

Thalidomide in consecutive multiple myeloma patients: single‐center analysis on practical aspects, efficacy, side effects and prognostic factors with lower thalidomide doses

In this single-center analysis, we assessed whether lower thalidomide doses are feasible and result in favourable treatment response in multiple myeloma (MM) patients. Between May 2001 and October 2006, 38 consecutive MM patients received thalidomide. Their median age was 62.4 yr, all had stage II/III MM and 31.6% had deletion 13q14 (del13q14). Prior to thalidomide, patients had received a median of two treatment lines. The median thalidomide dose was 100 mg/d (range 50-800) and the median treatment duration was 34 wk. The median cumulative thalidomide dose was 24 g. Sixteen patients received thalidomide as a single agent and 22 in combination (+dexamethasone n = 18; others n = 4). The median time-to-treatment failure (TTF) after thalidomide initiation was 30.4 wk. Analysis of prognostic factors showed a significantly prolonged TTF without del13q14 (38.1 vs. 8.9 wk with del13q14; P = 0.006). Our analysis of TTF between thalidomide given alone vs. in combinations showed a better TTF for the combination (23.6 vs. 30.6 wk), albeit not reaching significance (P = 0.20). Other parameters, such as age, stage, and prior SCT showed no difference in TTF. Peripheral polyneuropathy (PNP) frequencies were increased with longer (>28 wk) and increased cumulative thalidomide doses (>40 g), which emphasizes (a) the need to carefully escalate thalidomide from 50 to 200 mg/d, thereby reducing side effects and increasing patient compliance, and (b) that PNP occurs more frequently with longer and higher thalidomide doses. The strategy to lower thalidomide doses seems a feasible and attractive approach in MM patients, this being currently tested in prospective randomized trials.

DOOR syndrome: Clinical report, literature review and discussion of natural history

DOOR syndrome (deafness, onychodystrophy, osteodystrophy, and mental retardation) is a rarely described disorder with less than 35 reports in the literature. The hallmarks of the syndrome, represented in the DOOR acronym, include sensorineural hearing loss, hypoplastic or absent nails on the hands and feet, small or absent distal phalanges of the hands and feet, and mental retardation. The purpose of our communication is to report on an additional patient with DOOR syndrome, delineate common as well as less frequent manifestations of DOOR syndrome, bring attention to the under appreciated facial features in DOOR syndrome, document the natural history of this disorder, and propose a suggested workup of those suspected of DOOR syndrome. DOOR syndrome is associated with characteristic, coarse facial features with large nose with wide nasal bridge, bulbous tip and anteverted nares, a long prominent philtrum and downturned corners of the mouth. The natural history is one of a deteriorative course, with progressive neurological manifestations including sensorineural deafness, seizures from infancy, optic atrophy, and a peripheral polyneuropathy. The majority of patients with DOOR syndrome have elevated levels of 2-oxoglutarate in the urine and plasma. In this report, we present a newborn with manifestations consistent with DOOR syndrome and a progressive clinical course. A comprehensive literature review reveals 32 patients with DOOR syndrome. In conclusion, DOOR syndrome is a neurometabolic disorder with recognizable facial features and a progressive natural history.

Usefulness of a new indicator test for the diagnosis of peripheral and autonomic neuropathy in patients with diabetes mellitus

The aim of the present study was to assess the performance of a new indicator test (NIT), based on the measurement of sweat production after exposure to dermal foot perspiration, in the diagnosis of both peripheral sensorimotor polyneuropathy (PSN) and autonomic neuropathy in patients with diabetes. One hundred and seventeen diabetic patients were examined. PSN was assessed using the neuropathy symptoms score, the neuropathy disability score and the vibration perception threshold. Cardiac autonomic neuropathy (CAN) was assessed using the battery of the four classical standardized tests proposed by Ewing et al., Diabetes Care 1985; 8: 491-498. Sudomotor dysfunction was assessed using the NIT. Fifty patients (42.7%) had PSN and 44 patients (37.6%) had CAN. Of the 50 patients with PSN, 43 had a positive NIT (sensitivity 86%) and, out of the 67 patients without PSN, a negative NIT was obtained in 45 patients (specificity 67%). The positive and the negative predictive value of the NIT in detecting PSN were 66.2 and 86.5%, respectively. The sensitivity and specificity of NIT in detecting CAN was 59.1 and 46.5%, respectively. In the case of severe CAN, the sensitivity was increased to 80.9% and the specificity to 50%. The NIT has good sensitivity and negative predictive value for diagnosis of PSN and can be used as a screening method for detection of this complication in patients with diabetes. In addition, the test has a low sensitivity for detection of autonomic neuropathy in patients with milder forms of CAN.

A Case of Peripheral Neuropathy Combined with Leukoencephalopathy after Injection with Intrathecal Methotrexate and Vincristine.

Vincristine and methotrexate are the anchor drugs in the treatment of acute lymphocytic leukemia. The neurological complications caused by either vincristine or methotrexate have been well documented. A 10 year-old girl diagnosed acute lymphocytic leukemia without central nervous involvement and treated with CCG 1882 based therapy. She suffered from ascending paralysis from lower extremities without seizure or mental change three days after the fifth dose of vincristine and the fifth dose of intrathecal methotrexate during consolidation chemotherapy composed of 3-drug(vincristine, methotrexate, and L-asparaginase). Two days later, she developed dysarthria and respiratory discomfort. Her neurological examination showed a symmetric, flaccid, quadriparesis with loss of deep tendon reflex. But, she did not have sensory loss. We thought Guillain-Barre syndrome as first impression and carried out diagnostic evaluation. Viral study revealed no abnormality and cerebrospinal fluid study was not consistent with Guillain-Barre syndrome or infectious disease. Diffusion weighted magnetic resonance imaging showed a well-demarcated area of moderately high signal intensity in the white mater of the both parietal lobes. Neuromuscular conduction test revealed severe amplitude reduction in motor nerve action potential meaning on peripheral polyneuropathy. These findings were corresponded with drug-induced peripheral neuropathy and chemotherapy-related leukoencephalopathy that was detected incidentally. She did not receive further doses of vincristine and intrathecal methotrexate during the consolidation phase. There was gradual improvement of the weakness in the both lower and upper limbs for 3 months. She was recovery to walk with minimal support. We report peripheral neuropathy combined with subclinical leukoencephalopahty after injection with intrathecal methotrexate and vincristine.

Acute Inflammatory Demyelinating Polyneuropathy and a Unilateral Babinski/Plantar Reflex

Acquired acute demyelinating peripheral polyneuropathy (AADP) is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS). GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus) or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae). A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign). A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

Trasplante autólogo de progenitores hematopoyéticos en el síndrome de POEMS: resultados en 4 casos

POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome is a rare disorder characterized by a clonal plasma cell proliferation with a monoclonal protein typically small and lambda restricted. Clinically, this syndrome is a multisystemic disease whose major clinical feature is a peripheral polyneuropathy. A specific treatment for this disease does not exist. We report 4 patients with POEMS syndrome treated with an autologous haematopoietic stem cell transplantation in our centre. All patients had an improvement in neurologic symptoms and other manifestations of the syndrome. The monoclonal component and bone lesions decreased or disappeared. In conclusion, autologous haematopoietic stem cell transplantation is an effective therapy in patients with POEMS syndrome.

Subclinical Neurological Abnormalities in Children With Celiac Disease Receiving a Gluten‐free Diet

Because clinically evident manifestations are frequent in adults with celiac disease (CD), we aimed to investigate whether early neurological abnormalities may be detected in children with CD. Electroencephalography, electromyography, and somatosensory evoked potentials were performed in children with CD receiving a gluten-free diet. The neurophysiological tests revealed subclinical neurological abnormalities associated with CD in 3 (11%) of 27 children: 2 had peripheral polyneuropathy documented with electromyography, and 1 had prolonged latencies in somatosensory evoked potential. Magnetic resonance imaging showed abnormalities in 2 (7.4%) of children: pontine demyelinization in 1 and cortical atrophy in the other. Because the rate of neurological problems is increased in children with CD, neurological abnormalities should be carefully investigated early after the diagnosis of CD is made.

Repair Capacity for Platinum-DNA Adducts Determines the Severity of Cisplatin-Induced Peripheral Neuropathy

The pronounced neurotoxicity of the potent antitumor drug cisplatin frequently results in the onset of peripheral polyneuropathy (PNP), which is assumed to be initially triggered by platination products in the nuclear DNA of affected tissues. To further elucidate the molecular mechanisms, we analyzed in a mouse model the formation and processing of the main cisplatin-induced DNA adduct (guanine-guanine intrastrand cross-link) in distinct neuronal cell types by adduct-specific monoclonal antibodies. Comparison of the adduct kinetics in cisplatin-injected mice either proficient or deficient for nucleotide excision repair (NER) functions revealed the essential role of this DNA repair pathway in protecting differentiated cells of the nervous system from excessive formation of such lesions. Hence, chronic exposure to cisplatin resulted in an accelerated accumulation of unrepaired intrastrand cross-links in neuronal cells of mice with dysfunctional NER. The augmented adduct levels in dorsal root ganglion (DRG) cells of those animals coincided with an earlier onset of PNP-like functional disturbance of their sensory nervous system. Independently from the respective repair phenotype, the amount of persisting DNA cross-links in DRG neurons at a given cumulative dose was significantly correlated to the degree of sensory impairment as measured by electroneurography. Collectively, these findings suggest a new model for the processing of cisplatin adducts in primary neuronal cells and accentuate the crucial role of effectual DNA repair capacity in the target cells for the individual risk of therapy-induced PNP.

(633): Alterations in forebrain activation patterns associated with neuropathic pain in Zucker type 2 diabetic rats

A significant percentage of patients with type 2 diabetes mellitus develop peripheral polyneuropathy and experience severe and unremitting chronic neuropathic pain. This condition is among the most difficult to manage and often resists effective treatment altogether. This pain can be debilitating, frequently leads to physical impairments and functional limitations and can significantly impact on the quality of life. The pathophysiology of the diabetic neuropathy and its painful variant remain poorly understood.