Extensive pharmacokinetic variability of Levetiracetam. ¿Are doctors aware?

INTRODUCTION: Levetiracetam was presented as a drug with linear pharmacokinetics. There is currently evidence on its extensive pharmacokinetic variability in real clinical practice. OBJECTIVE: To describe levetiracetam pharmacokinetic variability in patients with epilepsy in real clinical practice. To evaluate the effect on levetiracetam levels of gender, age, renal function, and polytherapy. To describe how clinicians prescribe based on age and co-medication. METHODS: Retrospective analysis of epilepsy patients treated with levetiracetam for whom plasma levels were available. RESULTS: 151 patients. Median levetiracetam level of 17.75 mg/L, median dose of 2000 mg/day. There was a significant correlation between daily dose and serum levels (p < 0.01). There was a 18.1% increase in levetiracetam concentration/dose ratio in patients over 65 years of age (p < 0.05) that also correlated with decreased glomerular filtration (p < 0.01). Clinicians corrected doses so patients over 65 years had similar levels than younger patients. There was a 30.1% decrease of concentration/dose ratio in patients on polytherapy with potent enzyme inducer antiseizure medication (p < 0.05), and a 46.3% decrease for carbamazepine (p < 0.01). Clinicians did not correct doses, so patients treated with levetiracetam and carbamazepine had 27.5% lower levels than patients taking other polytherapy. CONCLUSION: The pharmacokinetic variability of levetiracetam is wider than originally thought. Age and co-medication with strong enzyme-inducing drugs, especially carbamazepine, significantly influence levetiracetam levels. Clinicians at our center did not consider this interaction and prescribed similar doses of levetiracetam when it was used in combination with these drugs or with others, so they probably were not aware of this interaction.

[Response to perampanel in a patient with chronic post-hypoxic myoclonus]. / Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.

INTRODUCTION: Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response. CASE REPORT: We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits. CONCLUSIONS: Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.

TITLE: Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Usefulness of multiparametric computerized tomography findings in the differential diagnosis of stroke mimics of epileptic origin: A preliminary study. / Utilidad de la tomografía computarizada cerebral multiparamétrica en el diagnóstico diferencial de patología comicial en el código ictus. Estudio preliminar.

OBJECTIVE: Thirty percent of the patients for whom code stroke is activated have stroke mimics, the most common being epilepsy. Our purpose was to evaluate the usefulness of multiparametric CT for differentiating between seizure-related symptoms and vascular events. MATERIAL AND METHODS: We conducted a retrospective observational study; data were gathered prospectively during one year. We studied multiparametric CT images of patients admitted following code stroke activation and finally diagnosed with epilepsy. RESULTS: The study included a total of 11 patients; 36% were men and mean age was 74.5 years. Three patients had right hemisphere syndrome, 4 displayed left hemisphere syndrome, and the remaining 4 had isolated aphasia. Maximum time from symptom onset to multiparametric CT study was 8.16hours. Perfusion CT results were normal in 2 patients. Nine patients showed longer or shorter times to peak (Tmax); cerebral blood volume (CBV) and cerebral blood flow (CBF) maps varied. EEG was performed a maximum of 47.6hours after symptom onset. Four patients showed findings compatible with status epilepticus, 2 displayed focal epileptiform activity, and 5 showed post-ictal slowing ipsilateral to perfusion CT abnormalities. CONCLUSION: The most sensitive parameter for differentiating between stroke and epilepsy in our series was increased time to peak in multilobar cortical locations in the absence of large-vessel occlusion and basal ganglia involvement. Multiparametric CT is a fast, readily available, and useful tool for the differential diagnosis of acute-onset neurological signs of epileptic origin in patients initially attended after code stroke activation.

Life history of Neoseiulus californicus (McGregor, 1954) (Acari: Phytoseiidae) fed with castor bean (Ricinus communis L.) pollen in laboratory conditions.

The predatory mite, Neoseiulus californicus (McGregor, 1954) (Acari: Phytoseiidae) is one of the principal natural enemies of tetranychid mites in several countries, promoting efficient control of those mites in several food and ornamental crops. Pest attacks such as that of the spider mite, Tetranychus urticae Koch, 1836 (Acari: Tetranychidae), is one of the problems faced by farmers, especially in the greenhouse, due to the difficulty of its control with the use of chemicals because of the development of fast resistance making it hard to control it. The objective of this work was to study the life history of the predatory mite N. californicus as a contribution to its mass laboratory rearing, having castor bean plant [Ricinus communis L. (Euphorbiaceae)] pollen as food, for its subsequent use as a natural enemy of T. urticae on a cultivation of greenhouse rosebushes. The studies were carried out in the laboratory, at 25 ± 2°C of temperature, 70 ± 10% RH and a 14 hour photophase. The biological aspects and the fertility life table were appraised. Longevity of 32.9 days was verified for adult females and 40.4 days for males. The intrinsic rate of increase (rm) was 0.2 and the mean generation time (T) was 17.2 days. The population doubled every 4.1 days. The results obtained were similar to those in which the predatory mite N. californicus fed on T. urticae.

Development of a non-viral gene delivery vector based on the dynein light chain Rp3 and the TAT peptide.

Gene therapy and DNA vaccination trials are limited by the lack of gene delivery vectors that combine efficiency and safety. Hence, the development of modular recombinant proteins able to mimic mechanisms used by viruses for intracellular trafficking and nuclear delivery is an important strategy. We designed a modular protein (named T-Rp3) composed of the recombinant human dynein light chain Rp3 fused to an N-terminal DNA-binding domain and a C-terminal membrane active peptide, TAT. The T-Rp3 protein was successfully expressed in Escherichia coli and interacted with the dynein intermediate chain in vitro. It was also proven to efficiently interact and condense plasmid DNA, forming a stable, small (∼100nm) and positively charged (+28.6mV) complex. Transfection of HeLa cells using T-Rp3 revealed that the vector is highly dependent on microtubule polarization, being 400 times more efficient than protamine, and only 13 times less efficient than Lipofectamine 2000™, but with a lower cytotoxicity. Confocal laser scanning microcopy studies revealed perinuclear accumulation of the vector, most likely as a result of transport via microtubules. This study contributes to the development of more efficient and less cytotoxic proteins for non-viral gene delivery.

Predatory potential of Euseius alatus (Phytoseiidae) on different life stages of Oligonychus ilicis (Tetranychidae) on coffee leaves under laboratory conditions.

This study evaluated the predatory capacity of Euseius alatus (DeLeon) as a biological control agent of the pest mite Oligonychus ilicis (McGregor) on coffee leaves under laboratory conditions, using arenas containing 25 O. ilicis per coffee (Coffea arabica) leaf to one specimen of each stage of the predator mite. The functional response and oviposition rate of adult females of E. alatus were evaluated on coffee leaf arenas and offered from 1 to 125 immature stages of O. ilicis per arena. The number of preys killed and the number of eggs laid by the predator were evaluated every 24 h during 8 days. The preys consumed were daily replaced. Male and female adults of E. alatus were the most efficient in killing all developmental stages of O. ilicis. Larvae and nymphs of O. ilicis were the most consumed by all stages of the predatory mite. The functional response and oviposition rates of E. alatus increased as the prey density increased, with a positive and highly significant correlation. Regression analysis suggested a type II functional response, with a maximum predation of 22 O. ilicis/arena and a maximum oviposition rate of 1.7 eggs/day at a density of 70 O. ilicis/arena.

Overexpression and purification of PWL2D, a mutant of the effector protein PWL2 from Magnaporthe grisea.

The rice blast disease caused by the ascomycete Magnaporthe grisea continues to cause a tremendous impact in rice (Oryza sativa) cultures around the world. Elucidating the molecular basis of the fungus interactions with its host might help increase the general understanding of the pathogen-host relationship. At the moment of invasion, the fungus secretes effectors that modify host defenses and cellular processes as they successively invade living rice cells. PWL2, an effector protein, is a known AVR (avirulence) gene product. The PWL2 gene prevents the fungus from infecting weeping lovegrass (Eragrostis curvula). In this study, we identified a PWL2 allele gene (which we termed PWL2D) in a strain of M. grisea. The sequence of PWL2D has only two bases different from that of PWL2, producing alterations in residue 90 and residue 142. However, the alteration of residue 90 (from D(90) to N(90)) is critical to gene function. Here, we cloned the gene PWL2D in a pET System vector, expressed the gene product in Escherichia coli and evaluated by spectroscopic techniques some aspects of the PWL2D structure. While TRX-tagged PWL2D is prone to aggregation, the solubility of PWL2D is improved when it is overexpressed without its original signal peptide. Expression and purification procedures for these constructs are described. Finally, we found out that the protein seems to be an intrinsically disordered protein. Results from these studies will facilitate structural analysis of PWL2D and might contribute to understanding the gene's function and of fungal/plant interactions.

Consistency of clinical diagnosis of dementia in NEDICES: A population-based longitudinal study in Spain.

BACKGROUND: Few longitudinal studies have verified the clinical diagnosis of dementia based on clinical examinations. We evaluated the consistency of the clinical diagnosis of dementia over a period of 3 years of follow-up in a population-based, cohort study of older people in central Spain. METHODS: Individuals (N = 5278) were evaluated at baseline (1994-1995) and at follow-up (1997-1998). The evaluation included a screening questionnaire for dementia and a neurological assessment. RESULTS: Dementia screening consisted of a 37-item version of the Mini-Mental State Examination (MMSE) and the Pfeffer Functional Activities Questionnaire (FAQ). Study neurologists investigated those participants who screened positively (N = 713) as well as 843 who had screened negatively to test the sensitivity of the screening instruments or because they had a positive screening for other chronic neurological diseases. We detected 295 patients among those who screened positive and 13 among those who screened negatively. Three years follow-up evaluation demonstrated 14 diagnostic errors at baseline (4.5%) leading to a final number of 306 patients with dementia. The corrected prevalence of dementia was 5.8% (95% confidence interval [CI] 5.2-6.5). CONCLUSIONS: The diagnosis of dementia was highly accurate in this population-based, Spanish cohort study, and our prevalence figures agree with other European surveys. Given the high cost and difficulties of population rescreening and its relatively low yield, we conclude that a single 2-phase investigation (screening followed by clinical examination) provides accurate information for most population-based prevalence studies of dementia.

[Lymphomatosis cerebri as the cause of leukoencephalopathy]. / Linfomatosis cerebral como causa de leucoencefalopatía.

INTRODUCTION: Lymphomatosis cerebri (LC) is an infrequent type of primary lymphoma of the central nervous system that is characterised by diffuse, infiltrating involvement of the white matter of the brain without the formation of a mass. AIM: To report the case of a patient with LC in order to draw attention to this disease, which is rarely diagnosed, and to its initial presentation in magnetic resonance imaging (MRI) as leukoencephalopathy. CASE REPORT: Our patient was a 56-year-old female who had clinical signs and symptoms of sub-acute dementia. Computerised axial tomography and MRI of the head revealed extensive, diffuse and bilateral involvement of the white matter, basal nuclei, mesencephalon and pons, with no mass effect or contrast enhancement. A stereotactic biopsy of the white matter (which was not conclusive) showed a perivascular mixed mononuclear-cell inflammatory infiltrate of B and T cells. No cytologic atypia was observed. Treatment was established with corticoids, which produced a clinical and radiological improvement in the first two months. During the next month the patient underwent rapid clinical deterioration with sleepiness and a worsening of the ability to walk. In an MRI scan the lesion had a more heterogeneous appearance with mass effect on adjacent structures and patchy contrast enhancement. A wedge biopsy of brain tissue led to a diagnosis of high-grade B-cell lymphoma. CONCLUSIONS: The imaging and histological appearance of LC may not be the one typically found in primary lymphomas of the central nervous system, and its clinical presentation may be similar to that of other diffuse processes involving compromise of the white matter (cerebral gliomatosis, inflammatory diseases of the white matter, such as Behçet's disease, Sjögren's disease or systemic lupus erythematosus).

[Inflammation and Alzheimer's disease]. / Inflamación y enfermedad de Alzheimer.

INTRODUCTION: Although Alzheimer's disease (AD) has not been traditionally regarded as an inflammatory process, there is an innate chronic inflammatory reaction in the affected tissues. The most important elements of this reaction are the activation of the phagocytic cells (microglia) with the production of cytokines and toxic substances, and the activation of the complement system. DEVELOPMENT: Inflammation is considered an important, although secondary, element in the pathogenesis of AD. It has been observed in epidemiological studies and in laboratory that treatment with anti-inflammatory drugs delays the appearance of AD. There are still no studies in humans that recommend the use of these drugs on a generalized way. CONCLUSIONS: The therapeutic targets given by the study of the inflammatory system in the brain are under investigation to obtain new drugs with less adverse effects. Those drugs could be used as primary and secondary prevention of AD.

[Transient cerebral oedema associated to hypoglycaemia]. / Edema cerebral transitorio asociado a hipoglucemia.

INTRODUCTION: In the adult, hypoglycaemia is documented as a consequence of overdose of insulin or oral hypoglycaemic agents. Neonatal hypoglycaemia is common but rarely symptomatic due to protective mechanisms. Very few reports on hypoglycaemic injury are available in adults and most of them in patients with poor outcome. CASE REPORT: Woman, 45 years old. She is referred to emergency room due to insulin overdose and coma of unknown duration. Glucose level was 15 mg% without other metabolic anomalies. Computerized tomography revealed brain oedema most obvious in the parieto-occipital lobes. Therapy with manitol and glucose was started with total functional recovery. CONCLUSIONS: Brain imaging in neonatal hypoglycaemia shows similar findings. In the acute phase oedema in the parieto-occipital cortex and underlying white matter and atrophy or malacic cysts in the chronic phase have been described. Chronic changes are related to long-term sequelae that vary from development delay and epilepsy to persistent vegetative state. In adults lesions involve hippocampus and basal ganglia. The reasons of different sensitivity of these regions are not fully clear. Differences in regional blood flow autoregulation or in excitotoxins receptors of aspartate have been postulated. Hypoglycaemia may induce blood-brain-barrier permeability and subsequently brain oedema.

[The importance of neurological examinations in the age of the technological revolution]. / Importancia de la exploración neurológica en la era de la revolución tecnológica.

INTRODUCTION: Neurologic practice and care have been modified in many important ways during the past ten years, to adapt to the explosion of new information and new technology. Students, residents and practicing physicians have been continuing programs to a model that focuses almost exclusively on the applications to neurologic disorders of the new knowledge obtained from biomedical research. On the other hand high demand for outpatient neurologic care prevents adequate patient's evaluation. CASE REPORTS: Case 1: 65 years old female. Occipital headache diagnosed of tensional origin (normal computerized tomography). Two months later is re-evaluated due to intractable pain and hypoglossal lesion. An amplified computerized tomography revealed a occipital condyle metastasis. Case 2: 21 years old female. Clinical suspicion of demyelinating disease due to repeated facial paresis and sensitive disorder. General exploration and computerized tomography revealed temporo-mandibular joint. Case 3: 60 years old female. Valuation of anticoagulant therapy due to repeated transient ischemic attacks. She suffered from peripheral facial palsy related to auditory cholesteatoma. CONCLUSIONS: Neurologic education is nowadays orientated to new technologies. On the other hand, excessive demand prevents adequate valuation and a minute exploration is substituted by complementary evaluations. These situations generate diagnostic mistakes or iatrogenic. It would be important a consideration of the neurologic education profiles and fulfillment of consultations time recommendations for outpatients care.

[Orthostatic tremor induced by pharmaceuticals]. / Temblor ortostático inducido por fármacos.

INTRODUCTION: Dopamine blocking agents can induce gravel types of 'tardive syndromes' (buccolinguomasticatory syndrome, dystonia, akathisia, and less frequently tremor, tourettism, and myoclonus). To our knowledge, orthostatic tremor has not been previously described as a complication of exposure to these drugs. CASE REPORTS: We report four patients who developed orthostatic tremor after exposure to dopamine blocking drugs. Two of them had orthostatic tremor as the predominant but not exclusive type of tremor, and the other two had 'pure' high-frequency orthostatic tremor. Tremor disappeared completely in 3 patients and improved markedly in the other one after gradual withdrawal of the offending drugs (metoclopramide in case 1, sulpiride and thyethylperazine in case 2, and sulpiride in cases 3 and 4). CONCLUSIONS: We propose that this 'tardive orthostatic tremor' could be considered into the spectrum of drug-induced movement disorders.

[Behavioural disorders in Alzheimer's disease. Data from a populational study]. / Alteraciones del comportamiento en la enfermedad de Alzheimer. Datos de un estudio poblacional.

AIMS: The purpose of this work was to study the characteristics of the behavioural disorders (non-cognitive or neuropsychiatric symptoms) presented by subjects with Alzheimer's disease from a sample of the population together with their relation to the cognitive and functional impairment suffered by these patients. PATIENTS AND METHODS: NEDICES is a longitudinal populational study based on the census of neurological diseases in subjects above the age of 64. In 2001, a study was conducted of the situation of 83 subjects who had started suffering from Alzheimer's disease between 1994 and 1997. Due to death and a number of other reasons, only 32 of them could be examined. Patients were administered a structured interview with scales referring to the cognitive state, functional capacity, severity of the dementia and the presence and severity of neuropsychiatric disorders. RESULTS: All the patients studied presented some non-cognitive symptom. Apathy was the most frequent (93.8%), followed by irritability (81.1%), anxiety (75.0%), dysphoria (71.8%) and agitation-aggressiveness (56.2%). The least frequent were deliria (50.2%), altered nocturnal behaviour and aberrant motor activity (37.6%), altered appetite and eating, and hallucinations (24.9%), disinhibition (21.8%) and euphoria (21.6%). The degree of cognitive impairment and the presence of non-cognitive symptoms exerted a similar and independent effect on functional capacity. Only 56.3% of the patients were treated with some kind of anticholinesterase or psychotropic medication. CONCLUSIONS: Our census-based populational study confirmed the high prevalence rate of non-cognitive symptoms in patients with Alzheimer's disease. These data confirm the notion that these symptoms are intrinsic manifestations of the disease.

[Bilateral thalamic gliomas: report of a case with cognitive impairment]. / Glioma talámico bilateral: presentación de un caso con deterioro cognitivo.

INTRODUCTION: Bilateral thalamic tumours are very rare and have been recently identified as a subgroup of thalamic neoplasms due to their characteristic clinical presentation, with behavioural and memory disorders and without sensory or motor changes. We describe a patient who presented with mood and behaviour changes due to a bilateral thalamic glioma, discuss the literature related to these rare neoplasms and review the anatomical bases of their particular clinical presentation. CASE REPORT: A 67-year-old woman consulted because of behavioural changes and frequent forgetfulness. Neurological examination was normal except from a deficit in the retention of words and numbers. MR images revealed bilateral thalamic swelling by a isointense in T1, hyperintense in T2 and protonic density mass that did not enhance. The tumour was diagnosed as an astrocytoma by stereotactic biopsy. She continued to deteriorate and a year after diagnosis she was bedridden and with a severe dementia. CONCLUSION: Bithalamic tumors, as other lesions that affect the thalamus bilaterally, characteristically present with mood and behaviour changes and memory impairment.

Acute myocardial infarction with cardiogenic shock: treatment with mechanical circulatory assistance and heart transplantation.

UNLABELLED: The mortality of cardiogenic shock (CS) after an acute myocardial infarction (AMI) still remains high. Thrombolysis, PTCA or CABG, when possible, can improve the results, but when all the treatments fail death is almost certain. OBJECTIVE: We investigate the use of the mechanical circulatory assistance (MCA) and heart transplantation (HT) to improve the adverse results in this irreversible situation. METHODS: Among 11 patients with irreversible CS after an AMI we used a MCA (Abiomed BVS-5000). After improvement and hemodynamic stabilization, we performed heart transplantation in 7 patients of mean age 52 years (35-60) including two women. The MCA was univentricular in 7 patients and biventricular in 4. Mean duration of the MCA was 5 days (1-12). RESULTS: Three patients died during the MCA: two due to cerebrovascular accidents and one multiorgan failure. Weaning was possible in one patient. Among Seven transplanted patients one died due to sepsis. Seven (64%) patients are long-term survivors. CONCLUSION: When all the treatments have failed for CS after an AMI, MCA may be used as a bridge to heart transplantation in a select group of patients where the procedure is not contraindicated. The long-term results of 64% survivors in our experience is satisfactory.

[Olanzapine improves chorea in patients with Huntington's disease]. / La olanzapina mejora el corea en pacientes con enfermedad de Huntington.

INTRODUCTION: The main treatment for choreatic movements associated to Huntington s disease are the neuroleptic drugs, however, its use causes long term troubles. CASE REPORTS: We describe two patients with a predominantly choreic Huntington s disease, who experience improvement of choreatic movements after introduction of olanzapine to their treatment, being this drug well tolerated. CONCLUSIONS: The improvement of chorea suggests that olanzapine has a dopaminergic D2 receptors blocking action.

[Multiple latency test in a patient with episodes of sleep induced by pergolide]. / Test de latencias múltiples en un paciente con episodios de sueño inducidos por pergolida.

OBJECTIVE: Recently, there have been report sleep attacks in parkinsonian patients as a side effect of pramipexole and ropinirole. We report a patient with similar episodes related with pergolide. CASE REPORT: A 64 year old man with rigid akinetic parkinsonism, treated with carbidopa/levodopa and pergolide, developed sudden, irresistible sleep episodes after increasing the dose of pergolide to 2.25 mg/day because of bad control of parkinsonian symptoms. These episodes started 30 minutes after each dose of pergolide and lasted 2 hours. Following reduction of the dose of pergolide to 1.5 mg/day the sleep episodes disappeared. Two double blind multiple sleep latency tests were performed, one after intaking pergolide and other after intaking placebo. RESULTS: The latencies to sleep onset were lower with pergolide than with placebo, but the differences did not reach statistical significance. There was no premature REM sleep onset. CONCLUSION: Sleep episodes are likely a not specific effect of dopamine agonists

The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2-1p36.3.

Guanine nucleotide exchange factors from the Dbl family are proto-oncogenic proteins that activate small GTPases of the Rho family. Here we report the characterization of GEF720, a novel Dbl-like protein related to p115Rho-GEF. GEF720 activated RhoA both in our recently developed Yeast Exchange Assay and in biochemical in vitro exchange assays. GEF720 induced RhoA dependent assembly of actin stress fibers in REF52 fibroblastic cells. In NIH3T3 cells this Dbl-like protein elicited formation of transformation foci with a morphology similar to RhoA-V14 induced foci. In the PC12 neuron-like cell line, expression of GEF720, whose mRNA is brain specific, inhibited NGF-induced neurite outgrowth. Finally, GEF720 gene is located on human chromosome 1 on band 1p36, between Tumor Protein 73 and Tumor Necrosis Factor Receptor 12, two genes rearranged in many neuroblastoma cell lines. Together, these results show that this new Dbl related protein, GEF720, is an exchange factor that can directly activate RhoA in vivo and is potentially involved in the control of neuronal cell differentiation. GEF720 is also a new candidate gene involved in the progression of neuroblastoma and developmental abnormalities associated with rearrangements in the 1p36 chromosomal region.

[MELAS syndrome masquerading as herpes encephalitis: genetic diagnosis]. / Síndrome MELAS que asemeja una encefalitis por virus herpes: diagnóstico genético.

INTRODUCTION: MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes) is a mitochondrial disease related to the mitochondrial DNA mutation. The tRNALeu(UUR) mutation at the base pair 3234 is associated to 80% of cases of MELAS syndrome. The onset with the stroke like episodes is often before the age 40. Herpes simplex encephalitis (HSE) presents as acute episodes of focal neurologic deficit that are often related to the temporal lobe. Occasionally MELAS syndrome and HSE may have a similar clinical presentation. CLINICAL CASE: A 33-year-old woman presented with seizures and a right parietotemporal syndrome of acute onset. The differential diagnosis between HSE and MELAS syndrome was established. MELAS syndrome was suspected based on her phenotype. The diagnosis of MELAS syndrome was confirmed by the presence of the mitochondrial tRNALeu(UUR) mutation at the base pair 3243. CONCLUSION: The clinical presentation of the MELAS syndrome may mimic that of the HSE, and antiviral treatment should be given until the diagnosis of MELAS syndrome is definitive. The study of the mitochondrial DNA helps diagnosing in a non invasive way many patients with MELAS syndrome.