RESUMEN
Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management.
Asunto(s)
Administración Intravenosa , Administración Oral , Inmunosupresores , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Crotonatos , Dimetilfumarato , Progresión de la Enfermedad , Esquema de Medicación , Clorhidrato de Fingolimod , Fumaratos , Humanos , Hidroxibutiratos , Inmunosupresores/administración & dosificación , Mitoxantrona , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Natalizumab , Nitrilos , Glicoles de Propileno , Medición de Riesgo , Esfingosina/análogos & derivados , ToluidinasRESUMEN
This case series identified drug causes of seizures in patients with depressive disorders. Three patients with seizures were admitted for video-electroencephalography (EEG) monitoring in the context of high-dose antidepressants and sodium valproate. Very high-dose antidepressants caused complex partial seizures with secondary generalisation that gave characteristic EEG discharges. This is the first reported series to capture the ictal EEG features associated with antidepressants.
Asunto(s)
Antidepresivos/efectos adversos , Electroencefalografía/métodos , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Grabación en Video/métodos , Adulto , Antidepresivos/administración & dosificación , Femenino , Humanos , Convulsiones/diagnóstico , Adulto JovenRESUMEN
We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.
Asunto(s)
Antiinflamatorios/uso terapéutico , Corteza Cerebral/efectos de los fármacos , Metilprednisolona/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Estudios Prospectivos , Factores de TiempoRESUMEN
Clusterin is a serum glycoprotein which is an inhibitor of complement and is expressed in many tissues in cell injury and death. It has been identified normal and pathological brain tissue and is a component of normal human cerebrospinal fluid (CSF). We have measured the clusterin concentration of 115 abnormal and normal human CSF samples and related these data to the patient's clinical diagnoses. CSF clusterin levels in patients with neurodegenerative and meningeal disease were within the normal range. Twelve of 15 patients with demyelination, however, had significant elevation of CSF clusterin concentration. This was not a specific finding for multiple sclerosis as elevated clusterin levels were also seen in patients with other acute neuropathology. Determination of CSF clusterin concentration may be of clinical value in neurological diagnosis.
Asunto(s)
Glicoproteínas/líquido cefalorraquídeo , Chaperonas Moleculares , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedad Aguda , Anestesia Raquidea , Western Blotting , Proteínas del Líquido Cefalorraquídeo/análisis , Clusterina , Complemento C9/líquido cefalorraquídeo , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Humanos , Concentración Osmolar , Enfermedades del Sistema Nervioso Periférico/líquido cefalorraquídeo , Valores de ReferenciaRESUMEN
The reliability of the electrophysiological criterion of conduction block in determining the presence of focal demyelination in a peripheral nerve has been studied in an animal model. Demyelination was produced in the rat tibial nerve by one or two closely spaced microinjections of lysophosphatidylcholine (LPC). Histological and electrophysiological data were obtained on the acute lesion (up to 6 days), and during recovery (up to 11 weeks). Single LPC injections produced a lesion of very variable severity. Double injections more reliably produced a severe lesion with marked conduction block. Slight axonal damage was occasionally seen in nerves showing severe demyelination. The ratio of amplitude of muscle action potentials evoked by stimuli proximal and distal to the sites of nerve injection was calculated to detect the development of conduction block. The post injection ratio was more than 2 standard deviations below the control mean in 86% of nerves showing signs of demyelination. No control saline injected nerves showed such evidence of conduction block. The severity of the electrophysiological abnormality did not prove a reliable indicator of the severity of the histological lesion, however. The possible reasons for this variability are discussed and it is argued that caution should be exercised when interpreting this particular electrophysiological finding in clinical practice.
Asunto(s)
Enfermedades Desmielinizantes/fisiopatología , Conducción Nerviosa , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Animales , Enfermedades Desmielinizantes/patología , Modelos Animales de Enfermedad , Lisofosfatidilcolinas , Músculos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/patología , RatasRESUMEN
Family physicians generally find the neurological examination a problem because of its perceived length and complexity. But the neurological examination can be made both shorter and more informative by seeing it as commencing from the moment of first meeting the patient and continuing through the history taking and combining this with a focusing of the formal examination of relevant areas.
Asunto(s)
Enfermedades del Sistema Nervioso/fisiopatología , Examen Neurológico , Medicina Familiar y Comunitaria , Humanos , Anamnesis , Enfermedades del Sistema Nervioso/diagnósticoRESUMEN
Three middle-aged men with risk factors for vascular disease developed brief, stereotyped hemi-sensory symptoms on sitting or standing. These symptoms occurred in the absence of postural hypotension. On clinical criteria, these episodes were indicative of small vessel (perforator) ischaemia, rather than large vessel disease. This was supported by the absence of any stenosis on duplex scanning of the neck vessels. Two of the patients progressed to develop a fixed deficit. In all 3 patients the outcome was benign, with minimal residual disability.
Asunto(s)
Isquemia Encefálica/etiología , Postura , Anciano , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/diagnóstico por imagen , Humanos , Hipotensión Ortostática/complicaciones , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
A family is described in which 5 (4 female and 1 male) of 8 siblings from one marriage developed a late onset cerebellar degeneration. Four of the 5 affected persons presented separately to different neurologists. Because the original enquiries into family history were negative, and because of the exclusion of other recognised causes for the clinical picture, a diagnosis of idiopathic chronic cerebellar degeneration was made for the individual patients. All patients experienced their first symptoms between the ages of 48 and 55 years, with a gradual unremitting deterioration from the onset. Cerebellar atrophy was confirmed on CT head scan in all cases. Clinically, apart from the cerebellar ataxia, there were no consistent signs of degeneration of any other central or peripheral nervous system pathway. Geographical factors severely limited family contact, and consequently none of those afflicted was aware of similarly affected relatives. Hence, this particular family illustrates the great importance of obtaining a detailed, accurate family history and of assiduous follow-up of the entire family. Only after many years did it become obvious that multiple members of the family were affected by a similar neurological problem.
Asunto(s)
Enfermedades Cerebelosas/genética , Anciano , Atrofia , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Patients with mild multiple sclerosis (MS) regularly report subjective complaints characterized by generalized cognitive inefficiency. A feature of these complaints is reduced verbal fluency, for example, losing the thread of conversation. Mild MS patients and controls were compared on subjective complaints, verbal fluency, and working memory, and the possible role of working memory was investigated. As predicted, subjective difficulties and verbalfluency each correlated with working memory. Subjective difficulties and verbal fluency were also related. Within the control group, the subjective difficulties were associated only with depression. On the other hand, in the MS group, subjective difficulties were unrelated to affective state but were correlated with working memory. For the patients, partialing out depression and anxiety did not influence any of the correlations involving subjective difficulties, verbal fluency, or working memory. These findings support the proposal that working memory impairment underlies subjective complaints of mild MS patients and that verbal dysfluency is part and parcel of this phenomenon.
Asunto(s)
Memoria a Corto Plazo/fisiología , Esclerosis Múltiple/psicología , Conducta Verbal/fisiología , Adulto , Ansiedad/etiología , Ansiedad/psicología , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Masculino , Esclerosis Múltiple/complicaciones , Pruebas Neuropsicológicas , Calidad de Vida/psicología , Encuestas y Cuestionarios , Escalas de WechslerRESUMEN
Electrophysiological studies were performed on median and ulnar nerves in 234 cases of carpal tunnel syndrome. Abnormalities of the ulnar nerve sensory action potential were found in 39·3% of cases. The amplitude of the ulnar nerve sensory action potential was related to the amplitude of the median nerve sensory action potential, and to the median nerve motor conduction velocity in the forearm. The findings suggest that in a significant proportion of patients with carpal tunnel syndrome, a more generalized subclinical neuropathy may be present.
Asunto(s)
Síndrome del Túnel Carpiano/fisiopatología , Nervio Mediano/fisiopatología , Nervio Cubital/fisiopatología , Potenciales de Acción , Adulto , Anciano , Estimulación Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras , Conducción NerviosaRESUMEN
The efficacy of lysophosphatidyl choline (LPC) type I and type IV in producing demyelination was assessed in rat tibial and sural nerve. By light and electron microscopy, a greater myelinolytic activity was demonstrated with type I, and concomitantly electrophysiology showed a more severe conduction block. In teased nerve preparations and 1-microns thin sections, demyelinated fibres were more frequent with LPC type I. At 1 h after injection, electron microscopy showed much more extensive myelin lysis in the form of fine vesicular debris. By 6 days, completely demyelinated fibres were much more common and associated Schwann cells contained either small quantities or no myelin debris. With type IV LPC, cytopathological changes were more extensive at 1 h. A minority of Schwann cells showed swollen hydropic cytoplasm and degradation of organelles. Axonal retraction from the myelin sheath occurred in occasional fibres, and in a few unmyelinated fibres axoplasm showed organelle depletion and increased granularity. By 6 days, Schwann cells still contained large quantities of gross myelin debris and had often retracted to expose extensive areas of axolemma. The findings suggest that the two types of LPC have different myelinolytic actions, which may be related to their different fatty acid content. A possible role for the two types of LPC in 'bystander demyelination' is considered.
Asunto(s)
Ácidos Grasos/farmacología , Lisofosfatidilcolinas/farmacología , Vaina de Mielina/efectos de los fármacos , Nervio Sural/efectos de los fármacos , Nervio Tibial/efectos de los fármacos , Animales , Ácidos Grasos/análisis , Lisofosfatidilcolinas/análisis , Lisofosfatidilcolinas/clasificación , Masculino , Microscopía Electrónica , Degeneración Nerviosa/efectos de los fármacos , Ratas , Ratas Endogámicas , Relación Estructura-ActividadRESUMEN
The no-reflow phenomenon has been produced in the cerebral hemispheres of the gerbil by 30 minutes of bilateral carotid artery occlusion. The no-reflow phenomenon was found to develop in relation to the fall in blood pressure which occurred on release of bilateral carotid clips. Metaraminol tartrate intravenously prevented the fall of blood pressure and significantly reduced the occurrence of the no-reflow phenomenon. Metaraminol tartrate, however, did not alter the morbidity or mortality of carotid artery occlusion for 30 minutes. There is thus no support from these experiments for the view that the no-relow phenomenon plays an important functional role in the reversibility of the effects of severe cerebral ischaemia.
Asunto(s)
Circulación Cerebrovascular , Trastornos Cerebrovasculares/fisiopatología , Modelos Animales de Enfermedad , Animales , Trastornos Cerebrovasculares/tratamiento farmacológico , Trastornos Cerebrovasculares/mortalidad , Hipotensión/etiología , Metaraminol/uso terapéuticoRESUMEN
Ligation of the common carotid artery in the gerbil was found to be associated with an increase in wet weight, volume, and area of the ipsilateral cerebral hemisphere. True swelling and oedema of the hemisphere occurs. This evidence suggests that it is reasonable to continue to use the gerbil as an animal model of the oedema that many accompany cerebral infarction.
Asunto(s)
Edema Encefálico/etiología , Trastornos Cerebrovasculares/complicaciones , Modelos Animales de Enfermedad , Animales , Tamaño de los ÓrganosRESUMEN
Patients with reflex epilepsies may provide insights into cerebral pathophysiology. We report a patient with an unusual form of reflex epilepsy in whom seizures are induced by tooth brushing. Magnetic resonance imaging (MRI) demonstrated a right posterior frontal low-grade tumor predominantly involving the precentral gyrus. Video-telemetry demonstrated right-sided epileptiform activity during a typical induced complex partial seizure. An ictal single photon emission computed tomography (SPECT) scan showed an area of hyperfusion that corresponded to the MRI lesion on coregistration with a surface-matching technique. A subsequent coregistered interictal SPECT scan demonstrated hypoperfusion in the same region. Ours is the first report to demonstrate a structural focus in this unusual form of reflex epilepsy. Possible mechanisms to explain the induction of the seizures are discussed.
Asunto(s)
Epilepsia/etiología , Lóbulo Frontal/fisiopatología , Cepillado Dental/efectos adversos , Adulto , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagen , Electroencefalografía , Epilepsia/diagnóstico , Epilepsia/fisiopatología , Epilepsia Parcial Compleja/diagnóstico por imagen , Epilepsia Parcial Compleja/etiología , Epilepsia Parcial Compleja/fisiopatología , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos XRESUMEN
A patient who developed an acute brainstem syndrome following Mycoplasma pneumoniae respiratory infection is reported. MRI showed changes consistent with brainstem demyelination. Clinical features and laboratory investigations support an immune mediated mechanism with no evidence of direction CNS invasion. On the basis of this case and a review of the literature, we postulate two mechanisms for the development of M. pneumoniae associated CNS disease: direct CNS invasion causing meningitis and an immune-mediated acute disseminated encephalomyelitis (ADEM). This has obvious therapeutic implications.
Asunto(s)
Tronco Encefálico/patología , Enfermedades Desmielinizantes/diagnóstico , Encefalomielitis Aguda Diseminada/diagnóstico , Imagen por Resonancia Magnética , Meningitis Bacterianas/diagnóstico , Neumonía por Mycoplasma/diagnóstico , Adulto , Anticuerpos Antibacterianos/líquido cefalorraquídeo , Tronco Encefálico/inmunología , Enfermedades Desmielinizantes/inmunología , Encefalomielitis Aguda Diseminada/inmunología , Humanos , Masculino , Meningitis Bacterianas/inmunología , Mycoplasma pneumoniae/inmunología , Neumonía por Mycoplasma/inmunologíaRESUMEN
We report the case of a 49-year-old woman suffering combined central and peripheral demyelination, with serial magnetic resonance images scans illustrating the development of central demyelination in a patient with established chronic inflammatory demyelinating polyneuropathy. This is the sixth patient with this rare overlap syndrome reported to date. We review the available literature and argue that an inherited predisposition to both diseases is the most likely explanation for its occurrence. Copyright 1999 Harcourt Publishers Ltd.