RESUMEN
We investigated the role of the intrinsic mevalonate cascade in the neuronal cell death (NCD) induced by the inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in rat primary cortical neurons cultured from the brains of 17-d-old fetal SD rats. HMG-CoA reductase inhibitors induced NCD [HMG-CoA reductase inhibitor-induced NCD (H-NCD)] in time- and dose-dependent manners. The apoptotic characteristics were revealed by the formation of the DNA ladder and by the electron microscopical observation. During the progression of H-NCD, p53 was induced followed by the expression of Bax. Although the mevalonate completely inhibited H-NCD, the cholesterol did not. Thus, we examined two major metabolites of mevalonate, geranylgeranyl-pyrophosphate (GGPP) and farnesyl-pyrophosphate (FPP), using a novel liposome system for uptake into the cells. GGPP, not FPP, prohibited H-NCD with inhibition of the induction of p53 and Bax. The inhibition of HMG-CoA reductase decreased the amount of membrane-associated Rho small GTPase families, but not Ras small GTPase, and GGPP restored the blockage by HMG-CoA reductase inhibitor in the translocation or redistribution of Rho small GTPase families to membrane. These data indicated that (1) the inhibition of the intrinsic mevalonate cascade induces the apoptotic NCD with the induction of p53 followed by that of Bax, (2) the inhibition of HMG-CoA reductase concomitantly causes blockage of the translocation or redistribution of Rho small GTPase families, not Ras small GTPase, to membrane, and (3) GGPP, not FPP, is one of the essential metabolites in the mevalonate cascade for protecting neurons from H-NCD.
Asunto(s)
Muerte Celular/efectos de los fármacos , Hidroximetilglutaril-CoA Reductasas/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Ácido Mevalónico/farmacología , Neuronas/efectos de los fármacos , Fosfatos de Poliisoprenilo/farmacología , Animales , Recuento de Células/efectos de los fármacos , Muerte Celular/fisiología , Células Cultivadas , Fragmentación del ADN , Femenino , Feto , Hidroximetilglutaril-CoA Reductasas/metabolismo , Ácido Mevalónico/metabolismo , Neuronas/fisiología , Embarazo , Prosencéfalo , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Sesquiterpenos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Factores de Tiempo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Melanotransferrin (MTf), also known as p97, has been localized in capillary endothelial cells of human brain. In Alzheimer's-diseased (AD) brain tissues, reactive microglial cells located in senile plaques exhibit elevated levels of MTf. The localization of the p97 protein may reflect its site of synthesis or could reflect a paracrine site of action. We examined the expression of MTf mRNA by in situ hybridization histochemistry using AD and healthy brain tissues. We also examined normal liver tissues by immunohistochemistry and in situ hybridization. In all the brain tissues examined, capillaries had positive signals for MTf mRNA. In AD tissues, expression of MTf mRNA appeared in reactive microglial cells in the grey matter specifically associated with dense plaques. In liver tissues, immunohistochemistry using anti-p97 antibody demonstrated that sinusoids were positively stained. In addition, in situ hybridization histochemistry revealed that hepatocytes had positive signals. These results suggest that p97 expression in reactive microglial cells are closely related to AD pathology. These results also support the notion that p97, which appears elevated in the cerebral spinal fluid and serum of AD patients, originates in the reactive microglia associated with dense senile plaques. Thus, p97 is a unique cellular hallmark of AD and further suggests that metal transport mechanisms play a role in this disease.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Microglía/patología , Proteínas de Neoplasias/genética , Placa Amiloide/patología , Anciano , Anciano de 80 o más Años , Animales , Antígenos de Neoplasias , Células CHO , Membrana Celular/química , Membrana Celular/ultraestructura , Cricetinae , Femenino , Expresión Génica/fisiología , Humanos , Hibridación in Situ , Hígado/metabolismo , Masculino , Antígenos Específicos del Melanoma , Microglía/química , Microglía/ultraestructura , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , ARN Mensajero/análisisRESUMEN
Astrocytes, a subtype of glial cells, have been demonstrated to have an abundant number of receptors for pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide of the VIP/secretin family which stimulates cAMP accumulation 1000 times more potent than VIP in astrocytes. PACAP is reported to stimulate the proliferation of astrocytes at low concentrations at which it does not yet stimulate the cAMP accumulation. In the present study, we examined the effect of PACAP on the activation of mitogen-activated protein kinase (MAPK), one of the important intracellular signals for the proliferation, and compared it with that of epidermal growth factor (EGF). To investigate the activation of MAPK, we focused on ERK2, one of MAPK, in cultured rat astrocytes. The activation of ERK2 was determined by immunoblotting and measurement of the activity in terms of the phosphorylating activity of immunoprecipitates with MAPK antibody on myelin basic protein. One pM of PACAP38 temporarily activated ERK2 at 10 min. In contrast, EGF activated ERK2 from 10 min to 60 min continuously. As for the dose-response effect, PACAP stimulated ERK2 at as low a concentration as 10-14 M and peaked at 10-12 M. Thereafter, its activating effect gradually decreased at 10-10 M and returned to the basal level at 10-8 M, forming a bell-shaped dose-dependency. Neither an inhibitor of PKA (H89) nor inhibitors of PKC (staurosporine and calphostin C) had any effect on the ERK2 activation induced by 1 pM PACAP38. Dibutyryl cAMP suppressed ERK2 activity in a dose-dependent manner. These data clearly demonstrated that PACAP stimulates MAPK in both a PKA- and a PKC-independent manner in cultured rat astrocytes.
Asunto(s)
Astrocitos/efectos de los fármacos , Astrocitos/enzimología , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Quinasas Activadas por Mitógenos , Neuropéptidos/farmacología , Neurotransmisores/farmacología , Sulfonamidas , Animales , Astrocitos/citología , Bucladesina/farmacología , Células Cultivadas , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Isoquinolinas/farmacología , MAP Quinasa Quinasa 4 , Proteína Quinasa 1 Activada por Mitógenos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Embarazo , Proteína Quinasa C/metabolismo , Proteínas Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Quinasas p38 Activadas por MitógenosAsunto(s)
Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Lóbulo Parietal/patología , Postura , Temblor/etiología , Brazo/inervación , Brazo/fisiopatología , Electromiografía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/inervación , Músculo Esquelético/fisiopatología , Grabación de Cinta de VideoRESUMEN
A previous study showed a lower incidence of ischemic stroke in patients with Parkinson's disease (PD) than in controls. It has been speculated that this may be related to less severe atherosclerosis in PD. In this study we examined the magnetic resonance imaging (MRI) and blood chemistry in 106 parkinsonian patients and compared the data with those from control cases. Abnormal MRI findings (état criblé, lacunar infarctions or periventricular hyperintensity) were found in 55.7% of cases. No case of cortical artery infarction was found. In comparison with a control population, the PD group showed a lower frequency of hypercholesterolemia, a higher frequency of low HDL cholesterol and a lower frequency of obesity. These results suggest that patients with PD have a reduction in risk factors for cortical artery infarction.
RESUMEN
We studied the effect of double filtration and immunoadsorption plasmapheresis in Guillain-Barré syndrome retrospectively in 70 patients. Thirty three patients had plasmapheresis, of whom 23 had double filtration and 10 immunoadsorption. The rest of 37 patients consisted of a control group. Clinical disability was evaluated using the functional grading scale by Hughes. In patients having a maximum disability of grade 4 and 5, the double filtration plasmapheresis group showed statistically significant improvement at 3 months after the treatment. There was no significant difference in prognoses between the immunoadsorption plasmapheresis and control groups. In mildly-illed patients having grade 2 and 3, the prognoses were not different between the three groups. In Guillain-Barré syndrome, double filtration plasmapheresis, as well as well-established plasma exchange, had benefit for severely-illed patients.
Asunto(s)
Filtración , Técnicas de Inmunoadsorción , Plasmaféresis/métodos , Polirradiculoneuropatía/terapia , Adulto , Femenino , Humanos , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Neurotrophic effects resulting from the insulin/insulin receptor system have been recognized as important in determining the etiological basis of neurodegenerative disorders. In Parkinson's disease, selective neuronal loss in the substantia nigra is accompanied by decreased immunoreactivity of the insulin receptor as determined using immunohistochemical studies. We performed semiquantitative mRNA analysis by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers for human insulin receptor exon 22, which encodes a region of the beta subunit of the receptor serving as a tyrosine kinase domain. The relative levels of mRNA in the substantia nigra from Parkinson's brain tissues showed a marked depression compared with those of normal controls. Further investigations are needed to decide whether this is a primary, disease-specific alteration of gene expression or merely a secondary process.
Asunto(s)
Enfermedad de Parkinson/genética , Receptor de Insulina/genética , Sustancia Negra/fisiología , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN/genética , Humanos , Datos de Secuencia Molecular , Enfermedad de Parkinson/metabolismo , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Sustancia Negra/químicaRESUMEN
The localization of the glucose transporter 3 (GLUT3) was examined immunohistochemically, using a newly developed polyclonal antibody, in human brainstem and cerebellar tissues from neurologically normal, lacunar stroke and Alzheimer disease cases. In the brainstem, GLUT3 immunoreactivity was limited to the melanized neurons of the paranigral nucleus and substantia nigra, and to neurons in dorsal nucleus of the vagus nerve, and in the oculomotor, pontine, ambigius and hypoglossal nuclei. In the cerebellum, only the dentate nucleus had positive immunoreactivity. Glial cells and endothelial cells were not immunopositive. The results suggest a preferential expression of GLUT3 in particular neurons with a differential glucose need.
Asunto(s)
Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas del Tejido Nervioso , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Anticuerpos Monoclonales , Femenino , Transportador de Glucosa de Tipo 3 , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Transporte de Monosacáridos/química , Proteínas de Transporte de Monosacáridos/inmunología , Neuronas/metabolismoRESUMEN
The localization of alpha-interferon (alpha-IFN) and its induced protein, MxA, was examined in human brain tissues from neurologically normal, Alzheimer's disease (AD) and Parkinson's disease (PD) cases. In all cases, a few neurons in the superficial cortical layers and microglial cells in the white matter were stained with the antibody to alpha-IFN. In AD brains, white matter microglia were intensely labeled for alpha-IFN and reactive microglia, such as those on senile plaques, were strongly positive for MxA protein. In PD, Lewy bodies in the substantia nigra were positive for MxA, but there was no staining for alpha-IFN in that region. These results suggest that increased expression of alpha-IFN in the white matter microglia and appearance of MxA protein in reactive microglia contribute to Alzheimer pathology. The staining of some Lewy bodies for MxA may be indicative of a viral infection or other unknown factor.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Proteínas de Unión al GTP , Interferón-alfa/metabolismo , Enfermedad de Parkinson/metabolismo , Proteínas/metabolismo , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales , Humanos , Inmunohistoquímica , Microglía/metabolismo , Proteínas de Resistencia a Mixovirus , Neuronas/metabolismo , Valores de ReferenciaRESUMEN
Human liver carboxylesterase (CE) is an enzyme capable of metabolizing drugs, and may also function as a regulator of lipid metabolism. We examined one isoform of CE by immunohistochemistry in the brains of neurologically normal, Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS) and cerebral infarction cases. In all but the infarcted brains, the anti-CE antibody stained only capillary endothelial cells in the brain and spinal cord tissues. In infarct brain areas, intense immunoreactivity of the macrophages was seen. In contrast, the macrophages in the ALS lateral columns and the reactive microglia located in the center of classical senile plaques in AD, as well as other reactive microglial cells in the grey matter, showed no immunoreactivity. In the central nervous system, CE may function as a protective factor against foreign chemicals in capillary endothelial cells, and the antibody to CE may serve as a marker for invading macrophages from the systemic circulation.
Asunto(s)
Encéfalo/enzimología , Hidrolasas de Éster Carboxílico/análisis , Endotelio Vascular/enzimología , Hígado/enzimología , Macrófagos/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/enzimología , Esclerosis Amiotrófica Lateral/enzimología , Especificidad de Anticuerpos , Western Blotting , Carboxilesterasa , Infarto Cerebral/enzimología , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
We described two types of involuntary movement accompanied with a well-located thalmaic lesion shown by MR imaging in five patients. All patients had the involuntary movements of an upper limb contralateral to the thalamic lesion. Two patients (1 and 2) had choreoathetosis that became most prominent when their index finger approached their nose, where irregular and dysynchronous oscillation occasionally superimposed. This choreoathetosis was differentiated from pseudoathetosis caused by disturbance of proprioceptive sensations. The MRI lesion was located at the middle level of thalamus including nucleus centromedianus. The other three patients (3, 4 and 5) had a regular and rhythmic oscillation in their forearm. The oscillation began to appear after their index finger reached their nose on finger-to-nose test. We considered the oscillation as a postural tremor based on its rhythmicity and regularity. Patient 4 had additional tremor in movement. Their postural tremor continued while the arm kept the position. Surface electromyogram showed the reciprocal discharges between the forearm extensor and flexor muscles with a frequency of 3 to 4 Hz. This tremor was not accentuated during limb movement toward the nose nor was coarse, and was distinguished from intention tremor described by Charcot and Dejerine. This tremor was also different from hyperkinesis volitionnelle and movement oppositionist. The "rubral tremor" differed from the tremor shown in our cases for a lack of resting tremor. The responsible lesion shown by MRI located at caudal posterior thalamus including pulvinar in patient 3, or located at the upper level of thalamus in patient 4 and case 5 that was more rostral than the lesion of the choreoathetosis cases. In cases of cerebrovascular accidents, both types of involuntary movement appeared after several months from the stroke. This delayed appearance suggests that these involuntary movements were the result not only of functional disturbance of thalamus, but of secondary repairing mechanism occurring at the lesion.
Asunto(s)
Trastornos del Movimiento/etiología , Enfermedades Talámicas/complicaciones , Adulto , Anciano , Hemorragia Cerebral/complicaciones , Infarto Cerebral/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Immunohistochemistry using both a newly developed polyclonal, and a commercially available monoclonal, anti-insulin receptor antibody was done on the midbrain from cases of idiopathic Parkinson's disease (PD), Alzheimer's disease, amyotrophic lateral sclerosis, vascular parkinsonism and non-neurological controls. Both antibodies gave identical patterns of neuronal staining. The neurons of the oculomotor nucleus were immunopositive in all the brains. However, the neurons in the pars compacta of the substantia nigra, paranigral nucleus, parabrachial pigmental nucleus, tegmental pedunculopontine nucleus, supratrocheal nucleus, cuneiform nucleus, subcuneiform nucleus and lemniscus medialis, which were positive in other diseases and in non-neurological controls, were not stained by these antibodies in PD brains. These results suggest that, in PD, a dysfunction of the insulin/insulin receptor system may precede death of the dopaminergic neurons.
Asunto(s)
Neuronas/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Receptor de Insulina/metabolismo , Sustancia Negra/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Anticuerpos Monoclonales , Humanos , Immunoblotting , Inmunohistoquímica , Valores de Referencia , Sustancia Negra/patologíaRESUMEN
Plasma and CSF levels of C4d and the circulating immune complex (CIC) to C1q were measured in 27 patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD) and cervical spondylosis (CS). There was no significant difference among groups in plasma C4d or in plasma or CSF CIC to C1q. However, the PSP group had significantly higher CSF levels of C4d than the PD and CS groups. Higher CSF C4d index in the PSP group was also shown compared with PD and CS groups. These results suggest that augmented complement activation in the wide areas of the central nervous system occurs in PSP. CSF levels of C4d or C4d index may serve as a basis for differentiating PSP from PD.
Asunto(s)
Complemento C4/líquido cefalorraquídeo , Complemento C4b , Fragmentos de Péptidos/líquido cefalorraquídeo , Parálisis Supranuclear Progresiva/inmunología , Anciano , Encéfalo/inmunología , Vértebras Cervicales , Vía Clásica del Complemento/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/inmunología , Valores de Referencia , Osteofitosis Vertebral/diagnóstico , Osteofitosis Vertebral/inmunología , Parálisis Supranuclear Progresiva/diagnósticoRESUMEN
The distributions of androgen receptor (AR) like protein were studied immunohistochemically in the central nervous system of rat and human medulla and spinal cord. Six male rats, weighing 160-180 g and medulla and spinal cord from three non-neurological human cases were used. The rats were perfused through the heart and fixed with 4% paraformaldehyde. Small blocks of the medulla and spinal cord from the human samples were also fixed with the same manner. Tissue sections of 20 microns were incubated with primary antibody (NH27; anti-human androgen receptor) and processed by the peroxidase-avidin-biotin complex methods. The specificity of this antibody was analyzed by Western blotting. A band of approximately 95 kDa which corresponds to AR and other several bands which may be degradating products were seen. Immunohistochemical examination of the rat brain and spinal cord revealed that positive neurons were localized in the amygdala, hypothalamus, motor nuclei of cranial nerves in brainstem, reticular formation of pons and medulla, Purkinje cells and anterior horn cells. The localizations of the immunoreactivity were chiefly in the cytoplasm as well as the processes. In the non-neurological human tissues, hypoglossal nucleus and anterior horn cells had positive immunoreactivity for AR like protein. They were localized in the cytoplasm and their processes. The abnormality of CAG repeat site of gene which code the androgen receptor has been recognized in X-linked spinal and bulbar muscular atrophy (Kennedy-Alter-Sung syndrome; KAS).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Bulbo Raquídeo/metabolismo , Receptores Androgénicos/metabolismo , Médula Espinal/metabolismo , Anciano , Animales , Cerebelo/metabolismo , Diencéfalo/metabolismo , Humanos , Inmunohistoquímica , Masculino , Enfermedad de la Neurona Motora/metabolismo , Neuronas Motoras/metabolismo , Puente/metabolismo , Ratas , Ratas WistarRESUMEN
We reported a case of 89-year-old woman showing rhythmic skeletal myoclonus mainly on the right upper limb. This myoclonus appeared five days after the cerebral infarction. It was seen constantly both at rest and in posture, and decreased during voluntary movement. When the patient was under emotional stress, it spread to the submandibular, neck and trunks of upper limb. During sleep, this movement completely disappeared. There was no myoclonus in palato-pharyngo-laryngo-oculo-diaphragmatic muscle group. In the examination of the surface electromyography, the movement was not reciprocal between extensor and flexor muscles, and its cycle was about 3.5 Hz. It was different from the intention tremor because it did not increase during the movement phase on the finger nose test. The examination of MRI revealed a small infarction including right dentate nucleus and right superior cerebellar peduncle, and from which an infarction of the superior cerebellar artery territory was considered. Only a few cases of rhythmic skeletal myoclonus without palatal myoclonus have been reported in the literature. All of these cases had small infarction of the same region as the above case. Their myoclonus began 5 to 15 days after the onset of cerebral infarction. These periods were markedly shorter than that of intention tremor and palatal myoclonus. This fact suggest that the rhythmic skeletal myoclonus has a different mechanism from that of the palatal myoclonus.
Asunto(s)
Mioclonía/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , HumanosRESUMEN
We reported two patients with neurocutaneous angiomatosis. Patient 1, a 36-year-old woman of Cobb syndrome had cutaneous portwine angiomas in the high back and spinal arteriovenous malformations at the level of Th4-11. She had also atrophy and livedo reticularis presenting during standing position in the left lower extremity. Patient 2, a 47-year-old man of Klippel-Trenaunay-Weber syndrome had varices in the bilateral lower extremities, cutaneous portwine angiomas in the high back and bilateral lower extremities, and hypertrophy of the bilateral legs. Neuroradiological examination revealed abnormal vessels in the spinal canal at the level of C5 and Th4. These syndromes may have no essential difference because of the presence of neural and cutaneous angiomas at the corresponding level, venous system disorders and trophic changes (hypertrophy/atrophy).
Asunto(s)
Hemangioma/diagnóstico , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias de la Médula Espinal/diagnóstico , Adulto , Angiografía de Substracción Digital , Malformaciones Arteriovenosas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nevo/patología , Piel/patología , Médula Espinal/irrigación sanguínea , SíndromeRESUMEN
Two sibling cases of cerebrotendinous xanthomatosis with parkinsonism were reported. One was a woman of 39 years old, and another was her sister of 36 years old. In both cases, febrile convulsion appeared on 1.5 year old, and mental deterioration, ataxic -spastic gait, cataract and swelling of Achilles tendons developed in order since entrance into elementary school. Five years ago, while they were in hospital at the first time, they were diagnosed as cerebrotendinous xanthomatosis by mental disturbance, cerebellar ataxia, pyramidal tract sign, histologically xanthomatous granuloma of Achilles tendons and hypercholestanolemia and family history of autosomal recessive trait. After the second admission, parkinsonism was noticed in addition to those findings above. Parkinsonism consisted of the following: Resting tremor of parkinsonian type, mild muscle rigidity of forearm and intrinsic-plus hand were observed in the elder sister, and generalized severe rigidity and bradykinesia in the younger sister. In both cases, brain CT showed the pontocerebellar atrophy, and the bilateral low density area in corona radiata, posterior portion of internal capsule, cerebral peduncle, tegmentum of midbrain and deep matter of cerebellum. Brain MRI also showed abnormal intensity in the same regions as on the brain CT. Administration of anti-parkinsonian drugs was challenged for the parkinsonism. Oral L-dopa test (500 mg) moderately improved parkinsonism in both cases. Therapy of diphenylpyraline hydrochloride (10 mg/day) entirely inhibited parkinsonian tremor and mild rigidity in the elder sister but was less effective for severe rigidity in the younger sister than administration of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Encefalopatías/genética , Enfermedad de Parkinson/genética , Xantomatosis/genética , Tendón Calcáneo/patología , Adulto , Encefalopatías/complicaciones , Encefalopatías/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiología , Piperidinas/administración & dosificación , Tomografía Computarizada por Rayos X , Xantomatosis/complicaciones , Xantomatosis/diagnósticoRESUMEN
A 12-year-old boy developed occasional attacks of oculogyric crisis after physical exercises or when tired. Following the initial symptom, progressive Parkinsonian features such as bradykinesia, muscular rigidity, hand tremors in posture, mild dysarthria and disorder of postural reflexes developed. There was no marked diurnal fluctuation o symptoms. Serum ceruloplasmin, copper levels, cranial X-ray CT scan and MRI were normal. Measurement of the plasma levels of L-dopa after single oral administration (300 mg) were normal. The treatment with L-dopa improved the Parkinsonian features excluding the attacks of oculogyric crisis in a few weeks. This case is not identical with juvenile Parkinsonism proposed by Yokochi et al for lack of both crural or truncal dystonia and remarkable response to L-dopa. Oculogyric crisis is known in several patients with severe generalized dystonia, and seldom in patients with Parkinson disease or juvenile Parkinsonism. Oculogyric crisis may be one of focal dystonias confined to extraocular muscles.