Nutritional peripheral neuropathies.

Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B1, B2, B6, B9 and B12). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B2 and B9).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.

New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment.

BACKGROUND: Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far. We describe four patients with MFN due to a novel DHH likely pathogenic homozygous variant and the results of nerve ultrasound assessment. METHODS: This retrospective observational study included 4 individuals from 2 unrelated Brazilian families evaluated for severe peripheral neuropathy. Genetic diagnosis was performed with a peripheral neuropathy next-generation sequencing (NGS) panel based on whole exome sequencing focused analysis that included a control SRY probe to confirm genetic sex. Clinical characterization, nerve conduction velocity studies, and high-resolution ultrasound nerve evaluation were performed in all subjects. RESULTS: Molecular analysis disclosed in all subjects the homozygous DHH variant p.(Leu335Pro). Patients had a striking phenotype, with marked trophic changes of extremities, sensory ataxia, and distal anesthesia due to a sensory-motor demyelinating polyneuropathy. One 46, XY phenotypically female individual had gonadal dysgenesis. High-resolution nerve ultrasound showed typical minifascicular formation and increased nerve area in at least one of the nerves assessed in all patients. CONCLUSION: Gonadal dysgenesis with minifascicular neuropathy is a severe autosomal recessive neuropathy characterized by trophic alterations in limbs, sensory ataxia, and distal anesthesia. Nerve ultrasound studies are very suggestive of this condition and may help to avoid invasive nerve biopsies.

The association of peripheral neuropathy detected by monofilament testing with risk of falls and fractures in older adults.

BACKGROUND: In persons with diabetes, annual screening for peripheral neuropathy (PN) using monofilament testing is the standard of care. However, PN detected by monofilament testing is common in older adults, even in the absence of diabetes. We aimed to assess the association of PN with risk of falls and fractures in older adults. METHODS: We included participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent monofilament testing at visit 6 (2016-2017). Incident falls and fractures were identified based on ICD-9 and ICD-10 codes from active surveillance of all hospitalizations and linkage to Medicare claims. We used Cox models to assess the association of PN with falls and fractures (combined and as separate outcomes) after adjusting for demographics and risk factors for falls. RESULTS: There were 3617 ARIC participants (mean age 79.4 [SD 4.7] years, 40.8% male, and 21.4% Black adults), of whom 1242 (34.3%) had PN based on monofilament testing. During a median follow-up of 2.5 years, 371 participants had a documented fall, and 475 participants had a documented fracture. The incidence rate (per 1000 person-years) for falls or fractures for participants with PN versus those without PN was 111.1 versus 74.3 (p < 0.001). The age-, sex-, and race-adjusted 3-year cumulative incidence of incident fall or fracture was significantly higher for participants with PN versus those without PN (26.5% vs. 18.4%, p < 0.001). After adjusting for demographics, PN remained independently associated with falls and fractures (HR 1.48, 95% CI 1.26, 1.74). Results were similar for models including traditional risk factors for falls, when falls and fractures were analyzed as separate outcomes, and after adjustment for competing risk of death. CONCLUSIONS: PN, as measured by monofilament testing, is common in older adults and associated with risk of falls and fracture. Screening with monofilament testing may be warranted to identify older adults at high risk for falls.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

Importance: In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. Objective: To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. Design, Setting, and Participants: In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Exposures: Chemotherapy agents known to be toxic to peripheral nerves. Main Outcomes and Measures: The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Results: Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 µV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Conclusions and Relevance: Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

Peripheral neuropathy in Tangier disease: A literature review and assessment.

Tangier disease (TD) (OMIM#205400) is a rare cause of inherited metabolic neuropathies characterized by marked deficiency of high-density lipoproteins and accumulation of cholesterol esters in various tissue resulting from reverse cholesterol transport deficiency. We report a case of a patient with TD with multifocal demyelinating neuropathy with conduction block who presents with winging scapula, tongue, and asymmetric extremity weakness. We also present a review of all studies published from 1960 to 2017 regarding peripheral neuropathy in TD. Our search identified 54 patients with TD with peripheral neuropathy. Syringomyelia-like neuropathy subtype (52.4%) was more frequent than multifocal sensorial and motor neuropathy subtype (26.2%), focal neuropathy subtype (19.1%), and distal symmetric polyneuropathy subtype (2.4%). Splenomegaly was the most common (40.7%) clinical manifestation in these patients. The pattern of electrodiagnostic abnormalities are: (1) demyelinating abnormalities were more predominant in the upper extremities than in the lower extremities and (2) slowing of motor nerve conduction was more prominent in the intermediate segment than in distal nerve segments. The sural-sparing pattern was present in 34.6% and conduction block was present in 11.5% of the patients. Our literature review and our case showed the clinical spectrum of TD neuropathy is quite wide and that it should be considered in the differential diagnosis of non-uniform demyelinating neuropathies.

Impact of chemotherapy-induced neurotoxicities on adult cancer survivors' symptom burden and quality of life.

PURPOSE: Limited information is available on the impact of chemotherapy (CTX)-induced neurotoxicity on adult survivors' symptom experience and quality of life (QOL). Purposes were to describe occurrence of hearing loss and tinnitus and evaluate for differences in phenotypic characteristics and measures of sensation, balance, perceived stress, symptom burden, and QOL between survivors who received neurotoxic CTX and did (i.e., neurotoxicity group) and did not (i.e., no neurotoxicity group) develop neurotoxicity. Neurotoxicity was defined as the presence of chemotherapy-induced neuropathy (CIN), hearing loss, and tinnitus. Survivors in the no neurotoxicity group had none of these conditions. METHODS: Survivors (n = 609) completed questionnaires that evaluated hearing loss, tinnitus, stress, symptoms, and QOL. Objective measures of sensation and balance were evaluated. RESULTS: Of the 609 survivors evaluated, 68.6% did and 31.4% did not have CIN. Of the survivors without CIN, 42.4% reported either hearing loss and/or tinnitus and 48.1% of the survivors with CIN reported some form of ototoxicity. Compared to the no neurotoxicity group (n = 110), survivors in the neurotoxicity group (n = 85) were older, were less likely to be employed, had a higher comorbidity burden, and a higher symptom burden, higher levels of perceived stress, and poorer QOL (all p < .05). CONCLUSIONS: Findings suggest that CIN, hearing loss, and tinnitus are relatively common conditions in survivors who received neurotoxic CTX. IMPLICATIONS FOR CANCER SURVIVORS: Survivors need to be evaluated for these neurotoxicities and receive appropriate interventions. Referrals to audiologists and physical therapists are warranted to improve survivors' hearing ability, functional status, and QOL.

Improvement in Neuropathy Specific Quality of Life in Patients with Diabetes after Vitamin D Supplementation.

OBJECTIVE: To assess the effect of vitamin D supplementation on neuropathy specific quality of life (NeuroQoL) in patients with painful diabetic neuropathy. METHODS: This prospective, open label study was conducted between June 2012 and April 2013. Patients with symptomatic diabetic neuropathy were given a single dose of 600,000 IU intramuscular vitamin D, and NeuroQol was assessed at baseline and at five follow-up visits every 4 weeks. RESULTS: Of 143 participants, 41.3% were vitamin D deficient (vitamin D < 20 ng/ml). Treatment with vitamin D resulted in a significant increase in 25(OH)D (P < 0.0001) and a significant improvement in the NeuroQoL subscale score for emotional distress (P = 0.04), with no significant change in the other NeuroQoL domains of painful symptoms and paresthesia, loss of temperature and touch sensation, unsteadiness, limitation in daily activities, and interpersonal problems. There was a significant reduction in patient perception about foot problems on QoL of "quite a lot" (P < 0.05) and "very much" (P < 0.0001) with a significant reduction in the baseline response of having a "poor" QoL from 5.2% to 0.7% (P < 0.0001) and an increase in the response of an "excellent QoL" from 1.5% to 7.4% (P < 0.0001). CONCLUSION: Vitamin D is effective in improving quality of life in patients with painful diabetic neuropathy.

Complication assessment and prevention strategies using midfoot fusion bolt for medial column stabilization in Charcot's osteoarthropathy.

In Charcot's osteoarthropathy stabilization of the medial column of the foot was introduced in order to establish a stable foot and reduce the risk for amputation. This study was performed to analyze postoperative complications, define risk factors for those and develop strategies for prevention. Since bolt dislocation takes place frequently, it was aimed to predict an appropriate time point for bolt removal under the condition that osseous healing has occurred. Fourteen consecutive patients with neuroosteoarthropathy of the foot and arch collapse were treated with open reduction and stabilization using midfoot fusion bolt and lateral lag screws. Age, gender, presence of preoperative osteomyelitis or ulcer, number of complications and operative revisions, Hba1c value, consolidation of arthrodesis, presence of a load-bearing foot and period to bolt dislocation was assessed. The mean follow-up was 21.4±14.6 (mean±SDM) months, 64% of patients suffered from diabetes with a preoperative Hba1c of 8.5±2.4. The mean number of revisions per foot was 3.6±4.1. Bolt dislocation was seen in 57% of the patients following 11.3±8.5 months; in 75% of these patients bony healing occurred before dislocation. There was a significant association between preoperative increased Hba1c value, presence of preoperative ulcer and wound infection. Healing of arthrodesis was demonstrated in 57% and a permanent weight-bearing foot without recurrent ulcer was achieved in 79%. The early and late postoperative complications could be controlled in general. A fully load-bearing and stable foot was obtained, despite osseous consolidation was not detected in all of these cases. Once a stable foot has established early removal of fusion bolt should be considered. To decrease the risk of infection Hba1c should be adjusted and ulcers should be treated before the operation.

Relationship of urologic complications with health-related quality of life and perceived value of health in men and women with type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) cohort.

OBJECTIVE: Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R). RESULTS: In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90-4.75) times greater with erectile dysfunction and 2.65 (1.68-4.18) times greater with LUTS and in women, 2.04 (1.25-3.35) times greater with sexual dysfunction and 2.71 (1.72-4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures. CONCLUSIONS: Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.

Chemotherapy-induced peripheral neurotoxicity (CIPN): what we need and what we know.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent and severe long-term side effects of cancer chemotherapy. Preclinical and clinical studies have extensively investigated CIPN searching for effective strategies to limit its severity or to treat CIPN-related impairment, but the results have been disappointing. Among the reasons for this failure are methodological flaws in both preclinical and clinical investigations. Their successful resolution might provide a brighter perspective for future studies. Among the several neurotoxic chemotherapy drugs, oxaliplatin may offer a clear example of a methodological approach eventually leading to successful clinical trials. However, the same considerations apply to the other neurotoxic agents and, although frequently neglected, also to the new "targeted" agents.

Vibration perception threshold in relation to postural control and fall risk assessment in elderly.

PURPOSE: This study investigates (i) the potential discriminative role of a clinical measure of peripheral neuropathy (PN) in assessing postural performance and fall risk and (ii) whether the integration of a simple screening vibration perception threshold (VPT) for PN in any physical (fall risk) assessment among elderly should be recommended, even if they do not suffer from DM. METHOD: One hundred and ninety-five elderly were entered in a four-group model: DM with PN (D+; n = 75), DM without PN (D-; n = 28), non-diabetic elderly with idiopathic PN (C+; n = 31) and non-diabetic elderly without PN (C-; n = 61). Posturographic sway parameters were captured during different static balance conditions (AMTI AccuGait, Watertown, MA). VPT, fall data, Mini-Mental State Examination and Clock Drawing Test were registered. Two-factor repeated-measures ANOVA was used to compare between groups and across balance conditions. RESULTS: The groups with PN demonstrated a strikingly comparable, though bigger sway, and a higher prospective fall incidence than their peers without PN. CONCLUSIONS: The indication of PN, irrespective of its cause, interferes with postural control and fall incidence. The integration of a simple screening for PN (like bio-thesiometry) in any fall risk assessment among elderly is highly recommended. Implications for Rehabilitation The indication of peripheral neuropathy (PN), irrespective of its cause, interferes with postural control and fall incidence. Therefore, the integration of a simple screening for PN (like bio-thesiometry) in any fall risk assessment among elderly is highly recommended. It might be useful to integrate somatosensory stimulation in rehabilitation programs designed for fall prevention.

Myelin protein zero Arg36Gly mutation with very late onset and rapidly progressive painful neuropathy.

Mutations in myelin protein zero (MPZ) protein result in a wide spectrum of peripheral neuropathies, from congenital hypomyelinating to late onset sensory and motor axonal forms. In some patients, neuropathic pain can be a prominent symptom, making the diagnosis challenging mainly in those with other risk factors for neuropathy. We describe a 77-year-old woman with impaired glucose tolerance presenting with rapidly progressive axonal neuropathy leading to excruciating pain and severe weakness of lower limbs within 2 years from the onset. Her son abruptly complained of similar painful symptoms at the age of 47 years. Molecular analysis revealed a novel heterozygous missense mutation (c.106A>G) in MPZ exon 2, causing the substitution of arginine-36 with glycine in the extracellular domain. Our observation suggests that MPZ-related neuropathy should be considered in the diagnostic work up of patients with painful axonal neuropathy even presenting with rapid progression and at a very late age of onset.

Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice.

BACKGROUND: A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice RESULTS: We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. CONCLUSIONS: Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

The prevalence, clinical features and management of periphral neuropathy among diabetic patients in Tikur Anbessa and St. Paul's Specialized University Hospitals, Addis Ababa, Ethiopia.

BACKGROUND: Neuropathy is one of the common chronic complications of diabetes. There are many forms of diabetic neuropathy, one of which is distal symmetric polyneuropathy (DSP). There are only few data on diabetic neuropathy in Ethiopia. OBJECTIVE: The objectives of this study were to determine the prevalence of peripheral neuropathy, describe the clinical features, identify risk factors and treatment of neuropathy among diabetic patients. METHODS: A cross-sectional study was conducted at Tikur-Anbessa (TASH) and St. Paul's Specialized (SPH) University Hospitals in Addis Ababa. A total of 384 diabetic patients were selected using systematic random sampling method taking every third patients from clinics attendees from December 2009 to February 2010. Data were collected using structured questionnaires containing sociodemographic data, risk factors and UK neuropathy screening test score, Neurological examination for pain, Achilles tendon reflex, Vibration, and temperature. RESULTS: A total of 176 males and 208 females were included, 27% were type 1 and 73% were type 2 diabetic patients. The overall prevalence of distal symmetrical polyneuropathy (DSP) was 48.2% (53.6% in type 2 and 33.3% in type 1 diabetic patients). DSP was present in 37% of patient with duration of diabetes < 5yrs and 53% of those with diabetic duration > 10yrs. Autonomic neuropathy was identified in 30% of patients. Out of 185 patients with peripheral Neuropathy 136 (77%) had moderate and severe symptom scores; while 101 (58%) had moderate and severe sign scores. Type of Diabetes, duration of diabetes, systolic hypertension, and age were significantly associated with DSP (p < 0.05). Amitriptylline in 14 (28.6%), Carbamazepine in 4 (8.2%), and other NSAIDs 7 (12.2%) were used for treatment of painful neuropathy. CONCLUSIONS: Distal symmetrical polyneuropathy is common. The commonest presenting features are pain and loss of sensation. Duration of diabetes 10yrs, type 2 D, old age and hypertension were the major risk factors for DSP. Treatment of painful diabetic neuropathy was not optimal. RECOMMENDATIONSs: We recommend strengthening of routine screening for neuropathy, to emphasis on foot ulcer risk reduction, management of co-morbidities like hypertension and dyslipidemia, to optimize treatment of painful neuropathy.

[Medical and economic reflections on Restore and Itrel neurostimulation systems for neuropathic pain treatment]. / Réflexion sur l'intérêt médicoéconomique des boîtiers de neurostimulation Restore et Itrel dans le traitement des douleurs neuropathiques chroniques.

In 2007, four patients where implanted with the Restore neurostimulation system for intractable chronic leg pain at the Poitiers Hospital. The potential for improving the patients' quality of life and medical-economic concerns motivated this choice for these highly selected patients. In this paper, we propose brief clinical case reports and discuss the reasons for choosing this new rechargeable system, even though it was initially more expensive than the standard neurostimulation system (Itrel 3). All patients receiving implants declared that they were very satisfied with the quality of stimulation provided by Restore and noted a significant improvement in their quality of life. If this solution becomes advantageous from an economic point of view, clinical data should lend support to the utility of this technological innovation for patients who have hitherto been in treatment failure.

A cost-utility analysis of pregabalin in the management of peripheral neuropathic pain.

OBJECTIVES: To assess the cost per QALY (quality-adjusted life years) of pregabalin in the management of peripheral neuropathic pain. METHODS: We compared pregabalin on top of "usual care" with "usual care" alone. In this study, usual care was defined as a mix of drug therapies, excluding anti-epileptic drugs (AEDs), because the latter represented only 9% of current use, and clinical evidence of pregabalin was demonstrated versus usual care without anti-epileptic drugs. A Markov model was developed to simulate the evolution of a patient cohort over 1 year, and applied cycles of 4 weeks. During each cycle, patients remained in 1 out of 4 possible states: severe, moderate or mild pain, and therapy withdrawal. The health care payers perspective was taken into account. Clinical data were obtained from a trial comparing usual care plus placebo to usual care plus pregabalin, at either 150, 300, or 300/600 mg/day (the latter depending on clearance of creatinin). Resulting effects on pain were transformed into transition-probabilities between different pain levels. Cost and SF36 utility data of pain levels were obtained from a 1-month observational study in 88 patients. RESULTS: Usual care resulted in a yearly cost of Euros 6,200 compared to Euros 5,984 for an all dose pregabalin-mix, meaning a cost saving of Euros 216 per patient. Utility increase was 0.01 for the pregabalin-mix (QALY 0.510 usual care; 0.520 pregabalin-mix). Monte Carlo analysis showed cost savings were not significant. However, the utility gain, albeit small, was statistically significant. CONCLUSIONS: Based on this analysis, it may be concluded, that in the considered patient population, at the specialist level, pregabalin is at least cost neutral to current usual care (without AEDs) and offers a slight but significant increase in quality of life.

The health consequences of peripheral neurological deficits in an elderly cohort: an Oklahoma Physicians Resource/Research Network Study.

OBJECTIVES: To determine whether the belief that loss of deep tendon reflexes and vibratory sensation in the ankles in older patients is of no great consequence is valid. DESIGN: Four-year longitudinal cohort study. SETTING: Primary care practice-based research network. PARTICIPANTS: Six hundred four noninstitutionalized individuals aged 65 and older with no self-reported medical conditions known to cause peripheral neuropathy (PN), recruited from the practices of 23 primary care physicians in central Oklahoma. MEASUREMENTS: Annual standardized peripheral neurological examination performed by two research nurses plus a questionnaire that included self-reported measures of health, health-related quality of life (HRQoL Quality of Well-Being--Self Administered (QWB-SA) and Health Utilities Index-3 (HUI-3), physical functioning--(Medical Outcomes Study 36-item Short Form Survey (SF-36)), falls, and use of healthcare services. Deaths were determined from participant contacts, primary care physicians, and the Social Security death index. RESULTS: One hundred sixty of 604 participants had symmetrical peripheral neurological deficits (SPNDs). After controlling for age, sex, race, education, income, body mass index, HRQoL, physical functioning, self-rated health, cognitive test score, and a variety of medical conditions, SPNDs were associated with earlier hospitalization (P=.03); greater mortality (P<.001); and declines in HRQoL (QWB-SA, P<.001), self-rated health (P=.02) physical functioning (SF-36, P=.005), and bodily pain (SF-36, P=.001). CONCLUSION: SPNDs of undetermined cause, found in older patients on physical examination, appear to be associated with greater morbidity and mortality.

[Assessment of neuropathic pain]. / Utredning av nevropatisk smerte.

Neuropathic pain is underdiagnosed and, in consequence, not properly treated. Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. The term dysfunction is not clearly defined and is suggested not used. The prevalence of neuropathic pain is unknown, but a few detailed studies show that neuropathic pain is more common than previously assumed. Some common causes of neuropathic pain are entrapment/injuries to peripheral nerves, painful neuropathies, infections in the nervous system (i.e. postherpetic neuralgia), spinal cord injuries, multiple sclerosis and cerebral infarcts. Evaluation of neuropathic pain is performed on the basis of a thorough clinical examination which includes detailed questioning of different types of pain. Both spontaneous (ongoing and paroxysmal) as well as evoked pain may occur. The ongoing pain may be described by a large number of adjectives such as burning, aching, throbbing, sore, cutting, but there is no pain descriptor which is diagnostic for neuropathic pain. Pain may usually be evoked by lightly touching the skin or by exposure to cold. A clinical neurological examination is necessary in the evaluation of the level of injury, possibly also electromyography/neurography in case of peripheral nerve lesions or CT/MR in case of central lesions. Neuropathic pain is almost always characterised by changes in sensibility, usually involving the thin-fibre system (peripheral nerve fibres or central projections). Special emphasis is put on the examination of sensory dysfunction.

Spinal cord stimulation: a seven-year audit.

OBJECTIVE: To evaluate the outcome and complications of spinal cord stimulation (SCS) for chronic neuropathic pain in an Australian population. MATERIALS AND METHODS: An independent researcher retrospectively examined the records of 138 patients trialing SCS between 1995 and 2002 at our institution. Information collected included pain relief, ability to perform activities of daily living (ADLs), return to work and reduction in opiate analgesia. Clinical, psychological, demographic and financial data were also collected. RESULTS: Of 138 patients who trialed SCS, 103 (74.7%) achieved a greater than 50% reduction in their pain and proceeded to permanent implantation. At 1 year following permanent implantation, 84.4% of these still had a reduction in their pain by greater than 50%. The majority of patients, 59.1%, stated that their analgesia was good (50-74% pain reduction). All patients required opiate analgesics prior to SCS implantation, but this fell to 54.6% after SCS implantation. Additionally, 73.6% had a significant improvement in their ability to perform ADLs and 24% of patients were able to return to work. CONCLUSION: SCS is an effective treatment in the control of chronic neuropathic pain, particularly in combination with comprehensive medical management within a multidisciplinary pain management centre.