[Idiopathic inflammatory myopathies. A review]. / Miopatías inflamatorias idiopáticas: una mirada actualizada al diagnóstico y el manejo.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired immune-mediated diseases, which typically involve the striated muscle with a variable involvement of the skin and other organs. Clinically, they are characterized by proximal muscle weakness, elevation of muscle enzymes, myopathic changes on electromyography and an abnormal muscle biopsy. The different IIM have been classified according to their distinctive histopathologic features in dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Several myositis-specific antibodies are associated with the different phenotypes, as well as with different risk of neoplastic disease and systemic complications. The basis for the treatment of DM, PM, and IMNM is immunosuppression. For IBM there are only symptomatic treatments. Steroids, associated or not with other immunosuppressant drugs, are the first line of treatment. Biologic drugs will allow future individualized therapies. The 10-year survival of DM, PM and IMNM is 62 to 90%. The leading causes of death are neoplastic, lung and cardiac complications. IBM does not impair survival, although it affects the quality of life.

[Neuropathy and Fabry's disease. Report of five cases]. / Compromiso neuropático y autonómico en Enfermedad de Fabry: presentación de casos clínicos.

Fabry's disease is an X-linked multisistemic lisosomal storage disorder caused by deficiency or absence in α-Galatosidase A. Symptoms develop early in childhood with small fiber neuropathy, autonomic disorders and skin lesions (angiokeratomas). More severe in males, patients develop over years heart disease (hypertrophic cardiomyopathy, bradycardia), proteinuria, renal failure, transient ischemic attacks and stroke, associated with decreased life expectancy. We report five patients with Fabry's disease aged between 21 to 56 years and with family history. Neuropathic symptoms are described and neurophysiological testing findings of nerve conduction studies, quantitative sensory testing, autonomic testing and sympathetic skin response are presented.

[Acute polyradiculoneuropathy associated with human Herpes Virus 7 in an immunocompetent patient. Case report]. / Polirradiculoneuritis aguda asociada a infección por Virus Herpes Humano 7 en un paciente adulto inmunocompetente.

Human herpes virus 7 (HHV-7) is a cause of encephalitis, meningitis and myeloradiculoneuropathy in adults who are immunocompetent or with immunosuppression. The involvement of the peripheral nervous system is always associated with myelitis. We report a case of acute polyradiculoneuropathy due to HHV-7, without involvement of central nervous system, in an immunocompetent patient. A 35-years-old man complained of lumbar pain radiating to both buttocks. On examination muscle strength and tendon reflexes were normal. He had asymmetric pinprick and light touch saddle hypoesthesia and also in the perineal region, dorsum and lateral aspect of the left foot. Magnetic resonance imaging showed mild thickening and contrast enhancement of cauda equina nerve roots. Polymerase chain reaction performed on cerebrospinal fluid was positive for HVV-7. Other inflammatory, infectious and neoplastic etiologies were ruled out. Lumbar pain and hypoesthesia improved progressively and neurological examination was normal after one month. He did not receive antiviral therapy.

Vitamin B12 status does not influence central motor conduction time in asymptomatic elderly people: a transcranial magnetic stimulation study.

INTRODUCTION: Vitamin B12 deficiency causes neurologic and psychiatric disease, especially in older adults. Subacute combined degeneration is characterized by damage to the posterior and lateral spinal cord affecting the corticospinal tract. OBJECTIVE: To test corticospinal tract projections using motor evoked potentials (MEPs) by transcranial magnetic stimulation (TMS) in asymptomatic older adults with low vitamin B12 (B12) levels. METHODS: Cross-sectional study of 53 healthy older adults (>70 years). MEPs were recorded in the abductor pollicis brevis and tibialis anterior muscles, at rest and during slight tonic contraction. Central motor conduction time (CMCT) was derived from the latency of MEPs and peripheral motor conduction time (PMCT). Neurophysiological variables were analyzed statistically according to B12 status. RESULTS: Median age was 74.3 ± 3.6 years (58.5% women). Twenty-six out of the 53 subjects had low vitamin B12 levels (B12 < 221 pmol/l). MEPs were recorded for all subjects in upper and lower extremities. There were no significant differences in either latency or amplitude of MEPs and CMCT between low and normal B12 groups. There was a significant PMCT delay in the lower extremities in the low B12 group (p = 0.014). CONCLUSIONS: No subclinical abnormality of the corticospinal tract is detected in asymptomatic B12-deficient older adults. The peripheral nervous system appears to be more vulnerable to damage attributable to this vitamin deficit. The neurophysiological evaluation of asymptomatic older adults with lower B12 levels should be focused mainly in peripheral nervous system evaluation.

[Overlapping features of frontotemporal dementia and amyotrophic lateral sclerosis]. / Manifestaciones neuropsiquiátricas y cognitivas en demencia frontotemporal y esclerosis lateral amiotrófica: dos polos de una entidad común.

Recent genetic and neuropathologic advances support the concept that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are overlapping multisystem disorders. While 10-15% of ALS patients fulfil criteria for FTD, features of motor neuron disease appear in approximately 15% of FTD patients, during the evolution of the disease. This overlap has been reinforced by the discovery of Transactive Response DNA Binding Protein 43 kDa (TDP43) inclusions as the main neuropathologic finding in the majority of ALS cases and almost a half of FTD cases. Also, an expansion in the intron of C9ORF72 (chromosome 9p21) has been identified in families affected by ALS, ALS-FTD and FTD. This review provides an update on the recent genetic and neuropathologic findings of ALS and FTD and a characterization of their clinical presentation forms, based on the current diagnostic criteria. Finally it underscores the importance of having a national registry of patients with ALS and FTD, to provide an earlier diagnosis and a multidisciplinary care.

Motor evoked potentials by transcranial magnetic stimulation in healthy elderly people.

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a non-invasive, safe, and painless method for evaluating the corticospinal pathway. The population of older adults is growing, along with the prevalence of neurological diseases common to this group. Latency and amplitude of motor evoked potentials (MEPs) vary among healthy subjects and no reference normal values for MEPs in healthy older adults are available. OBJECTIVE: To create a reference value for MEPs by TMS for healthy older adults. METHODS: Descriptive study in 36 healthy 70-year-old and older subjects. A 90-mm circular coil Magstim® magnetic stimulator was applied over Cz and Fz. Recording was done in the abductor pollicis brevis and tibialis anterior muscles, at rest and during sustained tonic contraction. Central motor conduction time (CMCT) was derived from MEP latency and peripheral motor conduction time (PMCT). Values were related to age, gender, standing height, and knee height. RESULTS: Mean age was 73.3 ± 2.4 years (58% female). In the upper extremity, average MEP latency was 23.3 ± 1.9 ms at rest and 19.9 ± 1.9 ms during tonic contraction. In the lower extremity, average MEP latency was 30.6 ± 2.5 ms at rest and 27.2 ± 2.3 ms during tonic contraction. There was a significant correlation between MEP latency and standing height, greater in the lower extremities. Female gender appeared as an independent factor determining lower MEP latency, but not CMCT, in upper and lower extremities. CONCLUSION: We have provided clinically useful reference values for MEPs by TMS in healthy adults older than 70 years of age. As in the younger population, standing height is important in defining normal MEPs. The difference between genders might be due to the lower height of women.

Thymectomy for non-thymomatous myasthenia gravis.

BACKGROUND: Treatments currently used for patients with myasthenia gravis (MG) include steroids, non-steroid immune suppressive agents, plasma exchange, intravenous immunoglobulin and thymectomy. Data from randomized controlled trials (RCTs) support the use of some of these therapeutic modalities and the evidence for non-surgical therapies are the subject of other Cochrane reviews. Significant uncertainty and variation persist in clinical practice regarding the potential role of thymectomy in the treatment of people with MG. OBJECTIVES: To assess the efficacy and safety of thymectomy in the management of people with non-thymomatous MG. SEARCH METHODS: On 31 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 3), MEDLINE (January 1966 to March 2013), EMBASE (January 1980 to March 2013) and LILACS (January 1992 to March 2013) for RCTs. Two authors (RS and GC) read all retrieved abstracts and reviewed the full texts of potentially relevant articles. These two authors checked references of all manuscripts identified in the review to identify additional articles that were of relevance and contacted experts in the field to identify additional published and unpublished data. Where necessary, authors were contacted for further information. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of thymectomy against no treatment or any medical treatment, and thymectomy plus medical treatment against medical treatment alone, in people with non-thymomatous MG.We did not use measured outcomes as criteria for study selection. DATA COLLECTION AND ANALYSIS: We planned that two authors would independently extract data onto a specially designed data extraction form and assess risk of bias; however, there were no included studies in the review. We would have identified any adverse effects of thymectomy from the included trials. MAIN RESULTS: We did not identify any RCTs testing the efficacy of thymectomy in the treatment of MG. In the absence of data from RCTs, we were unable to do any further analysis. AUTHORS' CONCLUSIONS: There is no randomized controlled trial literature that allows meaningful conclusions about the efficacy of thymectomy on MG. Data from several class III observational studies suggest that thymectomy could be beneficial in MG. An RCT is needed to elucidate if thymectomy is useful, and to what extent, in MG.

Delayed recurrent stroke in a young patient with acute posterior multifocal placoid pigment epitheliopathy.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a chorioretinal disease that causes acute binocular visual disturbance with characteristic funduscopic lesions at the level of the retinal pigment epithelium. APMPPE has been associated with multiple neurologic complications, including cerebrovascular diseases. We report a 15-year-old patient who had bilateral APMPPE, which was successfully treated with corticosteroids. One year later he presented with transient dysarthria and right hemiparesis. Brain magnetic resonance imaging (MRI) showed bilateral ischemic lesions in both lenticular nuclei and corona radiata. Brain MRI performed 3 months later revealed a new asymptomatic ischemic lesion. Cerebral angiography showed diffuse multifocal segmental vessel narrowing. The cerebrospinal fluid showed mononuclear pleocytosis in keeping with vasculitis. We started corticosteroid treatment, which lasted 10 months. Currently, after 2 years of clinical and neuroradiologic follow-up, the patient is asymptomatic and shows no worsening of the cerebrovascular lesions.

Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background.

Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol [ISRCTN 02694183].

BACKGROUND: Older people have a high risk of vitamin B12 deficiency; this can lead to varying degrees of cognitive and neurological impairment. CBL deficiency may present as macrocytic anemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. Less is known about subclinical vitamin B12 deficiency and concurrent neuroconduction and cognitive impairment. A Programme of Complementary Feeding for the Older Population (PACAM) in Chile delivers 2 complementary fortified foods that provide approximately 1.4 µg/day of vitamin B12 (2.4 µg/day elderly RDA). The aim of the present study is to assess whether supplementation with vitamin B12 will improve neuroconduction and cognitive function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of clinical deficiency. METHODS: We designed a cluster double-blind placebo-controlled trial involving community dwelling people aged 70-79 living in Santiago, Chile. We randomized 15 clusters (health centers) involving 300 people (20 per cluster). Each cluster will be randomly assigned to one of three arms: a) a 1 mg vitamin B12 pill taken daily and a routine PACAM food; b) a placebo pill and the milk-PACAM food fortified to provide 1 mg of vitamin B12; c) the routine PACAM food and a placebo pill.The study has been designed as an 18 month follow up period. The primary outcomes assessed at baseline, 4, 9 and 18 months will be: serum levels of vitamin B12, neuroconduction and cognitive function. CONCLUSIONS: In view of the high prevalence of vitamin B12 deficiency in later life, the present study has potential public health interest because since it will measure the impact of the existing program of complementary feeding as compared to two options that provide higher vitamin B12 intakes that might potentially may contribute in preserving neurophysiologic and cognitive function and thus improve quality of life for older people in Chile. TRIAL REGISTRATION: ISRCTN: ISRCTN02694183.

Neuropathic pain syndrome displayed by malingerers.

Among 237 patients communicating chronic pain, associated with sensory-motor and "autonomic" displays, qualifying taxonomically for neuropathic pain, there were 16 shown through surveillance to be malingerers. When analyzed through neurological methods, their profile was characteristically atypical. There were no objective equivalents of peripheral or central processes impairing nerve impulse transmission. In absence of medical explanation, all 16 had been adjudicated, by default, the label complex regional pain syndrome (CRPS). The authors emphasize that CRPS patients may not only harbor unrecognized pathology ("lesion") of the nervous system (CRPS II), hypothetical central neuronal "dysfunction" (CRPS I), or conversion disorder, but may display a recognizable simulated illness without neuropsychiatric pathology.

Surgical versus non-surgical treatment for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome results from entrapment of the median nerve in the wrist. Common symptoms are tingling, numbness, and pain in the hand that may radiate to the forearm or shoulder. Most symptomatic cases are treated non-surgically. OBJECTIVES: The objective is to compare the efficacy of surgical treatment of carpal tunnel syndrome with non-surgical treatment. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (January 2008), MEDLINE (January 1966 to January 2008), EMBASE (January 1980 to January 2008) and LILACS (January 1982 to January 2008). We checked bibliographies in papers and contacted authors for information about other published or unpublished studies. SELECTION CRITERIA: We included all randomised and quasi-randomised controlled trials comparing any surgical and any non-surgical therapies. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility of the trials. MAIN RESULTS: In this update we found four randomised controlled trials involving 317 participants in total. Three of them including 295 participants, 148 allocated to surgery and 147 to non-surgical treatment reported information on our primary outcome (improvement at three months of follow-up). The pooled estimate favoured surgery (RR 1.23, 95% CI 1.04 to 1.46). Two trials including 245 participants described outcome at six month follow-up, also favouring surgery (RR 1.19, 95% CI 1.02 to 1.39).Two trials reported clinical improvement at one year follow-up. They included 198 patients favouring surgery (RR 1.27, 95% CI 1.05 to 1.53). The only trial describing changes in neurophysiological parameters in both groups also favoured surgery (RR 1.44, 95% CI 1.05 to 1.97). Two trials described need for surgery during follow-up, including 198 patients. The pooled estimate for this outcome indicates that a significant proportion of people treated medically will require surgery while the risk of re-operation in surgically treated people is low (RR 0.04 favouring surgery, 95% CI 0.01 to 0.17). Complications of surgery and medical treatment were described by two trials with 226 participants. Although the incidence of complications was high in both groups, they were significantly more common in the surgical arm (RR 1.38, 95% CI 1.08 to 1.76). AUTHORS' CONCLUSIONS: Surgical treatment of carpal tunnel syndrome relieves symptoms significantly better than splinting. Further research is needed to discover whether this conclusion applies to people with mild symptoms and whether surgical treatment is better than steroid injection.

Genome-wide circulating microRNA expression profiling reveals potential biomarkers for amyotrophic lateral sclerosis.

The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA levels. miRNAs are present in different biological fluids and have been proposed as potential biomarkers. Here we used next-generation sequencing to perform a comparative analysis of the expression profile of circulating miRNAs in the serum of 2 mutant superoxide dismutase 1 transgenic mice. Top hit candidates were then validated using quantitative real-time polymerase chain reaction, confirming significant changes for 6 miRNAs. In addition, one of these miRNAs was also altered in mutant TDP-43 mice. Then, we tested this set of miRNAs in the serum from sporadic ALS patients, observing a significant deregulation of hsa-miR-142-3p and hsa-miR-1249-3p. A negative correlation between the revised ALS functional rating scale and hsa-miR-142-3p levels was found. Bioinformatics analysis of the regulatory network governed by hsa-miR-142-3p identified TDP-43 and C9orf72 as possible targets, suggesting a connection with ALS pathogenesis. This study identifies miRNAs that are altered in ALS that may serve as potentials biomarkers.

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status.

BACKGROUND: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. OBJECTIVE: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid. DESIGN: A pretreatment and posttreatment study was conducted in 51 participants (median ± SD age: 73 ± 3 y; women: 47%) with serum vitamin B-12 concentrations <120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by measuring cB-12 and neurophysiologic variables at baseline and 4 mo after treatment. RESULTS: Treatment increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001) and reduced plasma tHcy and serum MMA (P < 0.001). Treatment produced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of both the left and right sural nerves improved on the basis of faster median conduction times of 3.1 and 3.0 ms and 3.3 and 3.4 ms, respectively (P < 0.0001). A total of 10 sensory potentials were newly observed in sural nerves after treatment. Participants with high serum folate at baseline (above the median, ≥33.9 nmol/L) had less improvement in cB-12 (P < 0.001) than did individuals whose serum folate was less than the median concentration (i.e., with a concentration <33.9 nmol/L). CONCLUSION: Asymptomatic Chilean elderly with poor vitamin B-12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatment and an interaction with folate status, which was detected only with the use of cB-12. This trial was registered at www.controlled-trials.com as ISRCTN02694183.