Sympathetic and electrochemical skin responses in the assessment of sudomotor function: a comparative study.

OBJECTIVES: The sympathetic skin response (SSR) is a well-established test, whereas the electrochemical skin conductance (ESC) is still under evaluation. Our aim was therefore to assess the diagnostic accuracy of ESC to detect abnormal sudomotor function, using SSR as a reference test. METHODS: A cross sectional observational study was performed of 61 neurological patients assessed for possible sudomotor dysfunction and 50 age-matched healthy controls (HC). Patients with diagnoses of vasovagal syncope (VVS, n=25), Parkinson's disease (PD, n=15), multiple system atrophy (MSA, n=11) and peripheral neuropathies (PN, n=10) were included. Sudomotor function was assessed with SSR and ESC tests in all participants. The absence of SSR in the palms or soles indicates abnormal sudomotor function. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of the ESC. Cardiovascular autonomic (CV-Aut) function was evaluated through the Ewing score, based on the following tests: Heart rate change with deep breathing, Valsalva ratio, 30:15 ratio, blood pressure changes on standing and during isometric exercise. A Ewing score ≥ 2 indicates the presence of CV-Aut dysfunction. RESULTS: Mean SSR amplitudes and ESC values showed differences between HC and patients with MSA or PN (p < 0.05), but not in patients with VVS or PD. Absence of SSR was associated with abnormal ESC (p < 0.05). Patients with abnormal CV-Aut dysfunction had lower ESC (p< 0.05). Palm ESC (P-ESC) and sole ESC (S-ESC) assessment had a sensitivity of 0.91 and 0.95 to predict sudomotor dysfunction, with a specificity of 0.78 and 0.85, respectively. The area under ROC curve was 0.905 and 0.98, respectively. CONCLUSIONS: ESC in palms and soles has a high diagnostic accuracy for sudomotor dysfunction as detected by absent SSR in patients with MSA and PN.

Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature.

Small fiber neuropathy usually presents with gradual and progressive chronic length-dependent pain. Acute small fiber neuropathy is rarely reported. Three patients with acute onset neuropathic pain after Oxford-AstraZeneca ChAdOx1-S vaccination are described. Two patients were identified at the Oxford University NHS Foundation Trust, Oxford, UK and one patient in Red de Salud UC Christus, Santiago, Chile. All patients underwent a clinical assessment that included a detailed neurological examination, laboratory investigations, nerve conduction studies, thermal threshold testing, and skin biopsy for intra-epidermal nerve fiber density. Patients seen in Oxford underwent MRI of the brain and spinal cord. Cerebrospinal analysis was not performed. Neuropathic symptoms (burning pain, dysaesthesias) developed in the hands and feet within 2 weeks of vaccination. On clinical examination, there was pinprick and thermal hyposensitivity in the area of neuropathic pain. Laboratory investigation, nerve conduction tests, sympathetic skin responses, and MRI showed no relevant abnormalities. Thermal thresholds were abnormal and intra-epidermal nerve fiber density in the lower leg was reduced. In two cases symptoms persist after several months. Three cases of definite acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination are described. At follow up, neuropathic pain was present in two of the patients.

Clinical Subtypes of Medication Overuse Headache - Findings From a Large Cohort.

BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2  = 10.953, P = .027 and χ2  = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.

Economic benefits of treating medication-overuse headache - results from the multicenter COMOESTAS project.

BACKGROUND: Medication-overuse headache is a costly disease for individuals and society. OBJECTIVE: To estimate the impact of medication-overuse headache treatment on direct and indirect headache-related health care costs. METHODS: This prospective longitudinal study was part of the COMOESTAS project (COntinuous MOnitoring of Medication Overuse Headache in Europe and Latin America: development and STAndardization of an Alert and decision support System). Patients with medication-overuse headache were included from four European and two Latin American headache centers. Costs of acute medication, costs of health care services, and measurements of productivity were calculated at baseline and at 6-month follow-up Treatment consisted of overused drug withdrawal with optional preventive medication. RESULTS: A total of 475 patients (71%) completed treatment and were followed up for 6 months. Direct health care costs were on average reduced significantly by 52% ( p < 0.001) for the total study population. Significant reductions were seen in both number of consumed tablets (-71%, p < 0.001) and number of visits to physicians (-43%, p < 0.001). Fifty percent of patients reduced their number of consumed tablets ≥ 80%. Headache-related productivity loss, calculated either as absence from work or ≥ 50% reduction of productivity during the workday, were reduced by 21% and 34%, respectively ( p < 0.001). CONCLUSION: Standardized treatment of medication-overuse headache in six countries significantly reduced direct health care costs and increased productivity. This emphasizes the importance of increasing awareness of the value of treating medication-overuse headache. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (no. NCT02435056).

Psychological, clinical, and therapeutic predictors of the outcome of detoxification in a large clinical population of medication-overuse headache: A six-month follow-up of the COMOESTAS Project.

AIM: To identify factors that may be predictors of the outcome of a detoxification treatment in medication-overuse headache. METHODS: Consecutive patients entering a detoxification program in six centres in Europe and Latin America were evaluated and followed up for 6 months. We evaluated anxious and depressive symptomatology (though patients with severe psychiatric comorbidity were excluded), quality of life, headache-related disability, headache characteristics, and prophylaxis upon discharge. RESULTS: Of the 492 patients who completed the six-month follow up, 407 ceased overuse following the detoxification (non overusers), another 23 ceased overuse following detoxification but relapsed during the follow-up. In the 407 non-overusers, headache acquired an episodic pattern in 287 subjects (responders). At the multivariate analyses, lower depression scores (odds ratio = 0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis - migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the preventive treatment with flunarizine (compared to no such treatment) (odds ratio = 0.891; p = 0.001) predicted being a responder. A longer duration of chronic headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality of life and disability were not associated with any of the outcomes. CONCLUSIONS: Though exploratory in nature, these findings point to specific factors that are associated with a positive outcome of medication-overuse headache management, while identifying others that may be associated with a negative outcome. Evaluation of the presence/absence of these factors may help to optimize the management of this challenging groups of chronic headache sufferers.

Changes in anxiety and depression symptoms associated to the outcome of MOH: A post-hoc analysis of the Comoestas Project.

Aims To evaluate the impact of treatment success on depression and anxiety symptoms in medication-overuse headache (MOH) and whether depression and anxiety can be predictors of treatment outcome. Methods All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion over a six-month period. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Results A total of 663 MOH patients were evaluated, and 492 completed the entire protocol. Of these, 287 ceased overuse and reverted to an episodic pattern (responders) and 23 relapsed into overuse. At the final evaluation, the number of patients with depressive symptoms was reduced by 63.2% among responders ( p < 0.001) and did not change in relapsers ( p = 0.13). Anxious symptomatology was reduced by 43.1% in responders ( ps < 0.001) and did not change in relapsers ( p = 0.69). At the multivariate analysis, intake of a prophylactic drug and absence of symptoms of depression at six months emerged as prognostic factors for being a responder (OR 2.406; p = 0.002 and OR 1.989; p = 0.019 respectively), while lack of antidepressant drugs and presence of symptoms of depression at six months were prognostic factors for relapse into overuse (OR 3.745; p = 0.004 and OR 3.439; p = 0.031 respectively). Conclusions Symptomatology referred to affective state and anxiety can be significantly reduced by the treatment of MOH. Baseline levels of depression and anxiety do not generally predict the outcome at six months. Their persistence may represent a trait of patients with a negative outcome, rather than the consequence of a treatment failure.

The added value of an electronic monitoring and alerting system in the management of medication-overuse headache: A controlled multicentre study.

Background Medication-overuse headache (MOH) is a chronic disabling condition associated with a high rate of relapse. Methods We evaluated whether the adoption of electronic-assisted monitoring, advice and communication would improve the outcome over a follow-up of 6 months in a controlled, multicentre, multinational study conducted in six headache centres located in Europe and Latin America. A total of 663 MOH subjects were enrolled and divided into two groups: the Comoestas group was monitored with an electronic diary associated with an alert system and a facilitated communication option, and the Classic group with a paper headache diary. Results We observed a significantly higher percentage of overuse-free subjects in the Comoestas group compared with the Classic group: 73.1 vs 64.1% (odds ratio 1.45, 95% confidence interval 1.07-2.09, p = 0.046). The Comoestas group performed better also regarding the number of days/month with intake of acute drugs and the level of disability [Migraine Disability Assessment Score: Comoestas group - 42.5 ± 53.6 (35.5-49.3) and Classic group - 27.5 ± 56.1 (20.6-34.3) ( p < 0.003)]. Conclusion The adoption of the electronic tool improved the outcome of patients suffering from MOH after withdrawal from overused drugs. Information and communication technology represents a valid aid for optimizing the management of chronic conditions at risk of worsening or of relapsing. Trial registration The trial was registered at ClinicalTrials.gov (no. NCT02435056).

Clinical and Demographical Characteristics of Patients with Medication Overuse Headache in Argentina and Chile: Analysis of the Latin American Section of COMOESTAS Project.

BACKGROUND: Data on the characteristics of Medication Overuse Headache (MOH) in Latin American (LA) are scarce. Here we report the demographic and clinical features of the MOH patients from Argentina and Chile enrolled in the multinational COMOESTAS project in the period 2008-2010. METHODS: The LA population was formed by 240 MOH subjects, 110 from Chile and 130 from Argentina, consecutively attending the local headache centres. In each centre, specifically trained neurologist interviewed and confirmed the diagnosis according to the ICHD-II criteria. A detailed history was collected on an electronic patient record form. RESULTS: The mean patient age was 38.6 years, with a female/male ratio of 8:2. The mean time since onset of the primary headache was 21 years, whereas duration of MOH was 3.9 years. The primary headache was migraine without aura in 77.5 % and migraine with aura in 18.8 %. Forty two % of the patients self-reported emotional stress associated with the chronification of headache; 43.8 % reported insomnia. The most overused medications were acute drug combinations containing ergotamine (70 %), NSAIDs (33.8 %) and triptans (5.4 %). CONCLUSION: Though little described, MOH is present also in LA, where it affects mostly women, in the most active decades of life. Some differences emerge as regards the demographic and clinical characteristics of MOH in this population as compared to Europe or Northern America. What seems more worrying about MOH in Argentina and Chile is that most patients overuse ergotamine, a drug that may cause serious adverse events when used chronically. These findings once more underscore the importance of properly diagnose and treat MOH.

Medication overuse headache in Europe and Latin America: general demographic and clinical characteristics, referral pathways and national distribution of painkillers in a descriptive, multinational, multicenter study.

BACKGROUND: Medication overuse headache (MOH) is a very disabling and costly disorder due to indirect costs, medication and healthcare utilization. The aim of the study was to describe general demographic and clinical characteristics of MOH, along with the national referral pathways and national painkillers distribution in several European and Latin American (LA) Countries. METHODS: This descriptive cross-sectional observational study included 669 patients with MOH referred to headache-centers in Europe and LA as a part of the COMOESTAS project. Information about acute medication and healthcare utilization were collected by extensive questionnaires, supplemented with structured patient interviews. RESULTS: Triptans were overused by 31 % European patients and by 6 % in LA (p < 0.001), whereas ergotamines were overused by 4 % in Europe and 72 % in LA (p < 0.001). Simple analgesics were overused by 54 % in Europe and by 33 % in LA (p < 0.001), while combination-analgesics were more equally overused (24 % in Europe and 29 % in LA). More European patients (57 %) compared with LA patients (27 %) visited general practitioners (p < 0.001), and 83 % of European patients compared to 38 % in LA consulted headache specialists (p < 0.001). A total of 20 % in Europe and 30 % in LA visited emergency rooms (p = 0.007). CONCLUSION: There are marked variations between LA and Europe in healthcare pathways and in acute medication overuse regarding patients with MOH. This should be considered when planning prevention campaigns against MOH.

Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis.

BACKGROUND: Duchenne muscular dystrophy (DMD) is characterized by the absence of the cytoskeletal protein dystrophin, muscle wasting, increased transforming growth factor type beta (TGF-ß) signaling, and fibrosis. At the present time, the only clinically validated treatments for DMD are glucocorticoids. These drugs prolong muscle strength and ambulation of patients for a short term only and have severe adverse effects. Andrographolide, a bicyclic diterpenoid lactone, has traditionally been used for the treatment of colds, fever, laryngitis, and other infections with no or minimal side effects. We determined whether andrographolide treatment of mdx mice, an animal model for DMD, affects muscle damage, physiology, fibrosis, and efficiency of cell therapy. METHODS: mdx mice were treated with andrographolide for three months and skeletal muscle histology, creatine kinase activity, and permeability of muscle fibers were evaluated. Fibrosis and TGF-ß signaling were evaluated by indirect immunofluorescence and Western blot analyses. Muscle strength was determined in isolated skeletal muscles and by a running test. Efficiency of cell therapy was determined by grafting isolated skeletal muscle satellite cells onto the tibialis anterior of mdx mice. RESULTS: mdx mice treated with andrographolide exhibited less severe muscular dystrophy than untreated dystrophic mice. They performed better in an exercise endurance test and had improved muscle strength in isolated muscles, reduced skeletal muscle impairment, diminished fibrosis and a significant reduction in TGF-ß signaling. Moreover, andrographolide treatment of mdx mice improved grafting efficiency upon intramuscular injection of dystrophin-positive satellite cells. CONCLUSIONS: These results suggest that andrographolide could be used to improve quality of life in individuals with DMD.

[Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness]. / Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna.

Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion of mutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification of MIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. We estimated the degree of heteroplasmy of the mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a femóle adult patient. For this purpose, PCR producís were inserted in a vector creating plasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Pure autonomic failure with cold induced sweating.

Pure autonomic failure (PAF) is a progressive autonomic neurodegenerative disorder. Cold induced sweating occurred in syndromes with mutations in CRLF1 and CLCF1 genes and in a case of cervical dissection. A patient with PAF developed sweating induced by cool ambient temperatures. He had severe orthostatic hypotension, abnormal cardiovagal reflexes, and paradoxical sweating in the upper trunk at a room temperature of 18°C. Skin biopsy showed involvement of somatic epidermal unmyelinated nerve fibers. Quantitative sensory testing showed abnormal thresholds to all thermal modalities. Possible mechanisms include cold induced noradrenaline release in remaining autonomic innervation and a supersensitive sudomotor response.

Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna / Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness

Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion ofmutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification ofMIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. We estimated the degree of heteroplasmy ofthe mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a femóle adult patient. For this purpose, PCR producís were inserted in a vector creatingplasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Cervical disc herniation producing acute Brown-Sequard syndrome: dynamic changes documented by intraoperative neuromonitoring.

INTRODUCTION: Brown-Sequard syndrome is an incomplete spinal cord lesion characterized by ipsilateral loss of motor function and contralateral loss of pain and temperature sensitivity, reflecting a hemi-compression or hemi-section of the spinal cord. Cervical disc herniation is an exceptional cause of this syndrome. MATERIAL AND METHODS: We report a case of cervical disc herniation causing Brown-Sequard syndrome in a patient with an unusually rapid neurological deterioration associated to cervical extension, which was documented by neuromonitoring. CONCLUSION: A prompt diagnosis, followed by spinal cord decompression should be warranted. Intraoperative neuromonitoring is a useful tool in preservation of neurologic function in these cases.

[Stem cells therapy in amyotrophic lateral sclerosis treatment. A critical view]. / Trasplante de células troncales como terapia para la esclerosis lateral amiotrófica. Una mirada crítica.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. At present, there are not curative therapies for ALS. Pathogenic and progression mechanisms suggest the existence of oxidative stress, abnormal intracellular protein aggregation, mitochondrial dysfunction, axonal transport impairment, impairment of trophic support, altered glial cell function, and glutamate excitoxicity. AIM: To evaluate therapeutic results with adult stem cell for ALS treatment. DEVELOPMENT: Stem cells represent a potential therapeutic strategy, because their biological mechanisms could act on several of the pathogenic mechanisms proposed for ALS. Bone marrow mesenchymal stem cells are especially interesting among adult stem cells. Mesenchymal stem cells can differentiate in all central nervous system cells and potentially replace them. Furthermore, they have immunomodulatory effects, secreting, especially in neuroinflammatory environments, neurotrophic and antiinflammatory factors. Studies in murine models of ALS show decrease of inflammation and disease progression, and increase on animal highly heterogeneous, suggest that mesenchymal stem cells transplant in ALS appears to be safe. However, they fail showing clinical improvement of patients. CONCLUSION: Additional preclinical studies are necessary to refine this therapeutic approach, to assess long term survival and differentiation of mesenchymal stem cells, dosing, biological activity and safety should be conducted before any planning further human testing occurs.

Transient orthostatic hypertension after partial cerebellar resection.

An effective baroreflex and autonomic pathways normally ensure that blood pressure (BP) is satisfactorily maintained, despite various stimuli in daily life that include postural changes. We describe a 20-year-old man with a cerebellar hematoma and acute hydrocephalus, who had a vermian and partial right cerebellar hemisphere resection followed by orthostatic hypertension (OHT) and mutism. On standing his systolic BP rose over 60 mmHg with a fivefold increase in plasma noradrenaline. After a period of 8 weeks, postural BP regulation improved along with his ability to communicate. We conclude that transient impairment of cerebellar autonomic modulation or dysfunction of the baroreflex medullary circuit, may have resulted in OHT.

Temblor ortostático como causa de inestabilidad postural en enfermedad de Parkinson: Caso clínico / Orthostatic tremor causing postural instability in Parkinson disease: Report of one case

Parkinson disease (PD) is a movement disorder characterized clinically by the variable combination of rigidity, bradykinesia, rest tremor and postural instability. Usually postural instability is a late-onset manifestation and is frequently associated with axial manifestations and with a poor prognosis. We report a 67-year-old female with orthostatic tremor as the etiology of her postural instability. The patient was treated with increasing doses of clonazepam, reaching 2 mg/day, and levodopa. There was an improvement of postural instability with a good response of parkinsonian symptoms.

Resección de lesiones cerebrales con asistencia de mapeo cortical intraoperatorio / Intraoperative cortical mapping in surgery for brain lesions

Introducción: Se ha demostrado que la resección extensa de tumores intracraneanos intra-axiales malignos mejora la sobrevida. Esto no siempre es posible dada la eventual ubicación de estos tumores en o cercanos a áreas elocuentes, como corteza motora primaria o de lenguaje. En estas circunstancias, el desafío es evitar secuelas neurológicas. Uno de los métodos para disminuir dicho riesgo es el mapeo cortical intraoperatorio (MCI). El presente trabajo describe la técnica de mapeo cortical intraoperatorio de áreas elocuentes, al igual que su factibilidad y complementariedad con otras técnicas de localización tumoral. Método: Se analizan 7 pacientes operados, portadores de lesiones cercanas a áreas elocuentes. Se utilizó neuronavegación y MCI (estimulación directa de corteza y registro de potenciales evocados somatosensoriales). Se analizó la localización, tamaño y tipo de la lesión, grado de resección y estado neurológico pre y postoperatorio. Resultados: En todos los pacientes el MCI fue efectivo en localizar corteza motora primaria. Hubo 6 pacientes en los que se pudo resecar el área tumoral no asociada a funcionalidad, logrando en 5 de ellos resección completa o superior al 90 por ciento. En un paciente la lesión correspondió a una malformación arteriovenosa profunda ubicada en corteza motora primaria en que el MCI permitió una vía de abordaje por corteza no elocuente para su resección completa. No hubo déficit neurológico agregado postoperatorio con seguimiento de 12 meses. Conclusión: El MCI es útil y localiza en forma efectiva, simple y reproducible áreas de corteza funcional, haciendo posible realizar resecciones extensas de tumores en áreas elocuentes. Esta técnica es complementaria a otros métodos de ubicación anatómica y fisiológica pudiendo contribuir a una cirugía más segura y efectiva.

Introduction: Extensive resection for malignant intraaxial intracranial tumors has been demonstrated to improve survival. This is not always possible due to potential tumor location in or next to eloquent brain regions, like primary motor cortex or speech areas. In this case, avoiding neurological deficits is challenging. One of the tools for minimizing that risk is intraoperative cortical mapping (ICM). This report describes the ICM technique of eloquent brain regions, feasibility and complementariness with other methods for tumor localization. Methods: Seven patients with brain lesions near eloquent regions operated on were analyzed. Frameless stereotaxis (neuronavigation) and intraoperative cortical mapping (direct cortical stimulation and monitoring of somatosensory evoked potentials) were used. The location, size, type of lesion, amount of resection, pre and postoperative neurological status were studied. Results: ICM was effective in localizing primary motor cortex in all patients. In 6 patients the tumor area without functionality was removed, achieving complete or greater than 90 percent resection in 5 of them. In one patient the lesion was a deep arteriovenous malformation located below the primary motor cortex. In this case ICM made feasible an approach from non-eloquent cortex to achieve total resection. No new postoperative deficit was found in a 12 month follow-up period. Conclusion: ICM is useful and localize functional cortical regions effectively, simply and reliably, making possible to perform extensive tumor resections in eloquent regions. This technique is complementary to other tools for anatomical or physiological localization and could contribute to a safer and more effective surgery.

[Orthostatic tremor causing postural instability in Parkinson disease: report of one case]. / Temblor ortostático como causa de inestabilidad postural en enfermedad de Parkinson: Caso clínico.

Parkinson disease (PD) is a movement disorder characterized clinically by the variable combination of rigidity, bradykinesia, rest tremor and postural instability. Usually postural instability is a late-onset manifestation and is frequently associated with axial manifestations and with a poor prognosis. We report a 67-year-old female with orthostatic tremor as the etiology of her postural instability. The patient was treated with increasing doses of clonazepam, reaching 2 mg/day, and levodopa. There was an improvement of postural instability with a good response of parkinsonian symptoms.

Intracellular amyloid formation in muscle cells of Abeta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification.

BACKGROUND: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine Abeta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that Abeta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that Abeta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. RESULTS: In the present work, we found that intracellular Abeta aggregation in muscle cells of Caenorhabditis elegans overexpressing Abeta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type Abeta. We show that intracellular amyloid aggregation of wild type Abeta is accelerated by Cu2+ and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that Abeta-transgenic worms display a higher tolerance to Cu2+ toxic effects and that this resistance may be linked to the formation of amyloid aggregates. CONCLUSION: Our data show that intracellular Abeta amyloid aggregates may trap excess of free Cu2+ buffering its cytotoxic effects and that accelerated intracellular Abeta aggregation may be part of a cell protective mechanism.