Delayed hypersensitivity reaction to oral dimethyl fumarate

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Histamine-N-methyl transferase polymorphism and risk for multiple sclerosis.

BACKGROUND: Histamine N-methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis-MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. METHODS: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR-RLFP method. RESULTS: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. CONCLUSION: The HNMT polymorphism is not related with the risk for MS.

[The neurochemistry and neuropharmacology of diffuse Lewy body disease]. / Neuroquímica y neurofarmacología de la enfermedad difusa de cuerpos de Lewy.

INTRODUCTION AND DEVELOPMENT: The main neurochemical alteration in diffuse Lewy body disease (DLBD) is the cholinergic deficit in the cerebral cortex, which involves mainly cholin-acetyl-transferase. There have been also described dopamine deficiency and alterations affecting other neurotransmitters and neuromodulators, such as serotonin, noradrenaline, neuropeptides, etc. Cerebral perfusion and glucose metabolism studies usually show diffuse hypoperfusion or hypometabolism, with higher alteration of associative cortex, including occipital involvement. Several studies have shown increased markers of oxidative stress in brain and other tissues, suggesting its possible role in the pathogenesis of DLBD. CONCLUSIONS: Acetylcholinesterase inhibitors seem to improve cognitive and conductual symptoms, although their usefulness according evidence-based medicine criteria is weak. Some patients need atypical neuroleptics at low doses to get the symptomatic control of conductual alterations.

[The neurochemistry and neuropharmacology of frontotemporal dementia]. / Neuroquimica y neurofarmacologia de la demencia frontotemporal.

AIM: To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). DEVELOPMENT: The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and diffuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonin reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. CONCLUSIONS: The main neurochemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems.

Neuroquímica y neurofarmacología de la enfermedad difusa de cuerpos de Lewy / The neurochemistry and neuropharmacology of diffuse Lewy body disease

Introducción y desarrollo. La principal alteración neuroquímica en la enfermedad difusa de cuerpos de Lewy (EDCL) es el déficit colinérgico cortical, que afecta especialmente a la colinacetil transferasa. También se ha descrito un déficit dopaminérgico y alteraciones de otros neurotransmisores y neuromoduladores, como la serotonina, noradrenalina, neuropéptidos, etc. Los estudios de perfusión cerebral y de metabolismo cerebral de glucosa suelen mostrarhipoperfusión o hipometabolismo difuso con una mayor afectación de la corteza asociativa que incluye la afectación occipital. Algunos estudios han mostrado un aumento de diversos marcadores de estrésoxidativo en cerebro y en otros tejidos, por lo que se ha sugerido el posible papel patogénico de este último en la EDCL. Conclusiones. Los anticolinesterásicos parecen mejorar los síntomas cognitivos y conductuales, aunque su utilidad de acuerdo con los criterios de la medicina basada en la evidencia es débil. Algunos pacientes precisan neurolépticos atípicos en dosis bajas para el control sintomático de las alteraciones de conducta (AU)

Introduction and development. The main neurochemical alteration in diffuse Lewy body disease (DLBD) is the cholinergic deficit in the cerebral cortex, which involves mainly cholin-acetyl-transferase. There have been also described dopamine deficiency and alterations affecting other neurotransmitters and neuromodulators, such as serotonin, noradrenaline, neuropeptides, etc. Cerebral perfusion and glucose metabolism studies usually show diffuse hypoperfusion orhypometabolism, with higher alteration of associative cortex, including occipital involvement. Several studies have shown increased markers of oxidative stress in brain and other tissues, suggesting its possible role in the pathogenesis of DLBD. Conclusions. Acetylcholinesterase inhibitors seem to improve cognitive and conductual symptoms, although their usefulness according evidence-based medicine criteria is weak. Some patients need atypical neuroleptics at low doses to get the symptomatic control of conductual alterations (AU)

Neuroquímica y neurofarmacología de la demencia frontotemporal / The neurochemistry and neuropharmacology of frontotemporal dementia

Objetivo. Se revisan las alteraciones neuroquímicas y las opciones terapéuticas de la demencia frontotemporal (DFT). Desarrollo. Las principales alteraciones neuroquímicas en la DFT son el déficit serotoninérgico y dopaminérgico, sin que se hayan encontrado, al contrario de lo que sucede en la enfermedad de Alzheimer yen la enfermedad difusa de cuerpos de Lewy, alteraciones significativas del sistema colinérgico. Los estudios de perfusión cerebral y de metabolismo cerebral de glucosa suelen mostrar hipoperfusión o hipometabolismo, que afectan predominantemente al córtex temporaly frontal. Se han descrito algunas alteraciones relacionadas con el estrés oxidativo y la apoptosis, aunque su posible papel patogénico en la DFT no es bien conocido. Existen muy pocos estudios sobre la eficacia de diversos fármacos en la DFT. Los fármacos más estudiados son los inhibidores de recaptación de serotonina, pero, a pesar del déficit serotoninérgico descrito en la DFT, los resultados obtenidos son poco concluyentes. Conclusiones. Las principales alteraciones neuroquímicas de la DFT son el déficit serotoninérgico y dopaminérgico. El tratamiento no está bien establecido, si bien teóricamente sería ideal utilizar los fármacos que modulan estos sistemas neurotransmisores (AU)

Aim. To review the neurochemical features and therapeutic options for frontotemporal dementia (FTD). Development. The main neurochemical alterations in FTD are the serotoninergic and dopamine depletion. In contrast with Alzheimer's and difuse Lewy bodies disease, there are not significant alterations of the cholinergic system. Cerebral perfusion and glucose metabolism studies usually show hypoperfusion or hypometabolism, with predominant involvement of temporal and frontal cortices. There have been described some alterations related with oxidative stress and apoptosis, although its pathogenetic role in FTD is not well known. Treatment of FTD is not well established, because there are only a few studies with some drugs. The most studied drugs are serotonine reuptake inhibitors, however, despite the well-known serotoninergic deficiency described in FTD, the results are not conclusive. Conclusions. The main neuchemical alterations of FTD are serotoninergic and dopaminergic deficiencies. The treatment is not well established, although it should be theoretically ideal to use drugs which modulate these neurotransmitter systems (AU)

[Oxidative stress and Alzheimer's disease]. / Estrés oxidativo y enfermedad de Alzheimer.

INTRODUCTION: According to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free radicals, transition metals), the deficiency of antioxidant defensive mechanisms, or both. Oxidative stress has been implicated in the pathogenesis of aging of the brain and several neurological diseases, including Alzheimer's disease (AD). DEVELOPMENT: In recent years there are many data suggesting a possible role of oxidative stress in the pathogenesis of AD. These include the demonstration of increased oxidation of lipids, proteins and deoxyribonucleic acid, alterations in mitochondrial function and the possible role of amyloid beta and its precursor protein in the oxidative reactions in experimental models (cortical neuronal cultures and transgenic animals). CONCLUSIONS: Many studies show increased oxidative stress in the brain of patients with AD, although its possible role con the pathogenesis of this disease are controversial.

Estrés oxidativo y enfermedad de Alzheimer / Oxidative stress and alzheimer’s disease

Introducción. Según la hipótesis del estrés oxidativo, la patogenia de algunas enfermedades se relacionaría con el exceso de producción de sustancias prooxidantes (radicales libres, metales de transición), el déficit de mecanismos de defensa contra la oxidación, o ambos factores. El estrés oxidativo se ha implicado enla patogenia del envejecimiento cerebral y de algunas enfermedades neurológicas, incluida la enfermedad de Alzheimer (EA). Desarrollo.E n los últimos años se han presentado numerosos datos que parecen sugerir un posible papel del estrés oxidativo en la patogenia de la EA. Éstos incluyen la demostración de un aumento de los procesos oxidativos de lípidos, proteínas y ácido desoxirribonucleico, alteraciones en las concentraciones de algunos factores prooxidantes y antioxidantes en el cerebro y en otros tejidos, alteraciones de la función mitocondrial y del papel del amiloide y su proteína precursora en los procesos oxidativos en modelos experimentales(cultivos de neuronas corticales y animales transgénicos).Conclusiones. Existen muchos estudios que muestran un aumentodel estrés oxidativo en el cerebro de los pacientes con EA, si bien su posible papel en los procesos patogénicos de la misma es controvertido (AU)

Introduction. According to the oxidative stress hypothesis, the pathogenesis of several diseases should be related with an excessive production of prooxidant substances (free radicals, transition metals), the deficiency of antioxidant defensive mechanisms, or both. Oxidative stress has been implicated in the pathogenesis of aging of the brain and several neurological diseases, including Alzheimer’s disease (AD). Development. In recent years there are many data suggesting a possible role of oxidative stress in the pathogenesis of AD. These include the demonstration of increased oxidation of lipids, proteins and deoxyribonucleic acid, alterations in mitochondrial function and the possible role of amyloid beta and its precursor protein in the oxidative reactions in experimental models (cortical neuronal cultures and transgenic animals).Conclusions. Many studies show increased oxidative stress in the brain of patients with AD, although its possible role con the pathogenesis of this disease are controversial (AU)

Tau protein concentrations in cerebrospinal fluid of patients with multiple sclerosis.

UNLABELLED: FUNDAMENTALS AND OBJECTIVE: Multiple sclerosis (MS) is the prototype of demyelinating disease, but recently, it has been shown that the existence of axonal lesions contribute to irreversible central nervous system damage in this disease. Tau proteins are considered to be important for maintaining the stability of axonal microtubules involved in the mediation of fast axonal transport of synaptic constituents. There have been reports of increased cerebrospinal fluid (CSF) tau concentrations in patients with MS, and it has been suggested that this could be a marker of axonal damage. The objective of the present study was to elucidate whether CSF tau levels could be a marker of MS activity. PATIENT AND METHODS: We measured tau concentrations in the CSF of 20 patients with MS (nine in the first, seven in the second, one in the fourth exacerbation, and three patients with chronic progressive course) and 32 age- and sex-matched controls, using a specific enzyme-linked immunosorbent assay method. RESULTS: The CSF tau concentrations of patients with MS did not differ from those of controls, and they were not correlated with age at onset and duration of the disease. CONCLUSION: CSF tau concentrations are not a marker of MS activity.

[Symptomatic treatment of multiple sclerosis]. / Tratamiento sintomático de la esclerosis múltiple.

INTRODUCTION: Multiple sclerosis is a chronic neurological disorder which affects middle aged adults. It usually means serious physical, psychological, social and employment problems for the patients concerned. METHOD: From the anatomo pathological point of view, it is characterized by demyelination and axon damage in the central nervous system. The clinical features are variable, depending on the course of the disease, its clinical form and the sites of the lesions. Symptoms may appear in bouts, as relapses of the disorder or as a result of incomplete recovery from these episodes and cause severe disability. CONCLUSION: We review the physiopathology and most widely used treatment for management of the commonest symptoms of multiple sclerosis.

Tratamiento sintomático de la esclerosis múltiple / Symptomatic treatment of multiple sclerosis

Introducción. La esclerosis múltiple es una enfermedad neurológica crónica que afecta a los adultos en la edad media de la vida y que supone, por lo general, un importante efecto físico, psicológico y sociolaboral a los individuos que la padecen. Desarrollo. Desde el punto de vista anatomopatológico, se caracteriza por desmielinización y daño axonal en el sistema nervioso central. Sus manifestaciones clínicas son variables y derivan del momento evolutivo de la enfermedad, de su forma clínica y de la topografía de las lesiones. Por otra parte, la aparición de síntomas puede estar en relación con brotes o reagudizaciones de la enfermedad, o con recuperación incompleta de los mismos, produciendo una grave discapacidad. Conclusión. Revisamos la fisiopatología y los tratamientos más empleados en el manejo de los síntomas más comunes de la esclerosis múltiple (AU)

Cerebral lymphoma presenting as a leukoencephalopathy.

Cerebral lymphoma is infrequent in immunocompetent patients. This tumour usually appears on CT and MRI as a single lesion or as multiple lesions with mass effect and homogeneous enhancement after contrast administration. A patient is described with a cerebral lymphoma, confirmed by histopathological examination, who presented as a progressive leukoencephalopathy.

[Respiratory form of onset of motor neuron disease]. / Forma de comienzo respiratorio de la enfermedad de motoneurona.

OBJECTIVE: To present a case of respiratory failure as the form of onset of amyotrophic lateral sclerosis, to review the main clinical findings, data of the investigations done which suggest the presence of this disorder and describe its therapeutic management. CLINICAL CASE: A 68 year old man presented with a subacute illness characterized by a sleep disorder with sleep fragmentation, snoring of increasing intensity, without clear pauses of apnea, progressive diurnal hypersomnia accompanied by progressive dyspnea followed by respiratory failure with respiratory acidosis and difficulty in manipulating things with his hands. Diagnostic investigations showed a restrictive pattern without pulmonary fibrosis, due to paralysis of the diaphragm, and the presence of electromyographic signs compatible with motorneuron disease. The patient was treated with riluzole 100 mg/day and non-invasive mechanical ventilation and maintained an acceptable quality of life. CONCLUSIONS: Motorneuron disease may start with acute or progressive respiratory failure without a clear etiological cause and may appear to be similar to obstructive sleep apnea syndrome. The treatment of choice for this respiratory problem is non-invasive mechanical ventilation. Absence of symptoms of bulbar involvement is essential for a favourable prognosis.

Forma de comienzo respiratorio de la enfermedad de motoneurona / Respiratory form of onset of motorneuron disease

Objetivo. Presentar un caso de insuficiencia como forma de comienzo de la esclerosis lateral amiotrófica, así como revisar sus manifestaciones clínicas principales, los datos de pruebas diagnósticas sugestivos de esta enfermedad y su manejo terapéutico. Caso clínico. Varón de 68 años que presentó cuadro subagudo caracterizado por la aparición de trastorno del sueño con fragmentaciones del mismo y ronquidos crecientes en intensidad, sin claras pausa de apnea, junto con hipersomnia diurna progresiva, acompañado de disnea progresiva y posterior fallo respiratorio con acidosis respiratoria y de dificultad manipulatoria en manos. Los tests diagnósticos objetivaron un patrón restrictivo sin la presencia de fibrosis pulmonar debido a parálisis diafragmática y a la presencia de signos electromiográficos compatibles con enfermedad de motoneurona. El paciente recibió tratamiento con riluzole 100 mg/día y ventilación mecánica no invasiva manteniendo una calidad de vida aceptable. Conclusiones. La enfermedad de motoneurona puede comenzar como un cuadro de insuficiencia respiratoria aguda o progresiva sin una causa etiológica clara, pudiendo simular un síndrome de apnea obstructiva del sueño. El tratamiento de elección para su problema respiratorio sería la ventilación mecánica no invasiva, siendo fundamental para un pronóstico más favorable la ausencia de síntomas de afectación bulbar (AU)

[Do antioxidants in the diet affect the risk of developing Parkinson disease?]. / Influyen los antioxidantes de la dieta en el riesgo para desarrollar enfermedad de Parkinson?

OBJECTIVE: A number of studies suggest the existence of 'oxidative stress' in the substantia nigra from parkinsonian patients. If 'oxidative stress' should be relevant in the pathogenesis of Parkinson's disease (PD), the consumption of antioxidant or prooxidant substances in the diet could theoretically influence the risk for this disease. DEVELOPMENT: A critical up to date review of the literature regarding premorbid consumption of antioxidants or prooxidants by PD patients and controls has been done. Most studies have been retrospective, they have been performed following different designs, and disclosed contradictory results. CONCLUSION: From the current literature, it is unlikely that dietetic consumption of prooxidants and antioxidant, specially vitamin E (the most frequently studied antioxidant) have any influence on the risk for PD.