RESUMEN
Deep brain stimulation (DBS) represents an established treatment option in a growing number of movement disorders. Recent case reports suggest beneficial effect of globus pallidus internus (GPi)-DBS in selected patients suffering from Huntington's disease with marked disabling chorea. We present a 41-year-old man with genetically confirmed HD following quadruple GPi- and subthalamic nucleus (STN)-DBS. Motor function was assessed by Abnormal Involuntary Movement Scale (AIMS) and by Unified Huntington Disease Rating Scale (UHDRS) presurgery and postsurgery for up to 4 years. Furthermore, cognitive, neuropsychiatric state and quality of life (QoL) including life satisfaction (QLS) were annually evaluated. Chorea assessed by AIMS and UHDRS subscores improved by 52 and 55 %, 45 and 60 %, 35 and 45 % and 55-66 % at 1-4 years, respectively, compared to presurgical state following GPi-STN-DBS. During these time periods bradykinesia did not increase following separate STN- and combined GPi-STN-DBS compared to presurgical state. Mood, QoL and QLS were ameliorated. However, dysexecutive symptoms increased at 4 years postsurgery. The present case report suggests that bilateral GPi- and STN-DBS may represent a new treatment avenue in selected HD patients. Clinically, GPi-DBS attenuated chorea and was associated with a larger effect-adverse effect window compared to STN-DBS. However, GPi-DBS-induced bradykinesia may emerge as one main limitation of GPi-DBS in HD. Thus, quadruple GPi-STN-DBS may be indicated, if separate GPi-DBS does not result in sufficient control of motor symptoms. Future controlled studies need to confirm if the present anecdotal observation of additive beneficial effects of GPi- and STN-DBS in a HD patient with severe generalized chorea and relatively intact cognitive and affective functions indeed represents a new therapeutic option.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Globo Pálido/fisiopatología , Enfermedad de Huntington/fisiopatología , Enfermedad de Huntington/terapia , Núcleo Subtalámico/fisiopatología , Adulto , Estimulación Encefálica Profunda/efectos adversos , Globo Pálido/patología , Humanos , Enfermedad de Huntington/patología , Enfermedad de Huntington/psicología , Imagen por Resonancia Magnética , Masculino , Actividad Motora/fisiología , Núcleo Subtalámico/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: High-frequency stimulation of the globus pallidus internus (GPi) is a highly effective therapy in primary dystonia. Recent reports have also demonstrated almost immediate improvement of motor symptoms in patients with tardive dystonia after pallidal deep brain stimulation (DBS). Here, we show the long-term effect of continuous bilateral GPi DBS in tardive dystonia on motor function, quality of life (QoL), and mood. METHODS: Nine consecutive patients undergoing DBS for tardive dystonia were assessed during continuous DBS at 3 time points: 1 week, 3 to 6 months, and last follow-up at the mean of 41 (range 18-80) months after surgery using established and validated movement disorder and neuropsychological scales. Clinical assessment was performed by a neurologist not blinded to the stimulation settings. RESULTS: One week and 3 to 6 months after pallidal DBS, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor scores were ameliorated by 56.4 +/- 26.7% and 74.1 +/- 15.8%, BFMDRS disability scores by 62.5 +/- 21.0% and 88.9 +/- 10.3%, and Abnormal Involuntary Movement Scale (AIMS) scores by 52.3 +/- 24.1% and 69.5 +/- 27.6%, respectively. At last follow-up, this improvement compared with the presurgical assessment was maintained as reflected by a reduction of BFMDRS motor scores by 83.0 +/- 12.2%, BFMDRS disability scores by 67.7 +/- 28.0%, and AIMS scores by 78.7 +/- 19.9%. QoL improved significantly in physical components, and there was a significant improvement in affective state. Furthermore, cognitive functions remained unchanged compared with presurgical status in the long-term follow-up. No permanent adverse effects were observed. CONCLUSION: Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.
Asunto(s)
Estimulación Encefálica Profunda/métodos , Trastornos Distónicos/terapia , Globo Pálido/fisiología , Adulto , Afecto/fisiología , Anciano , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/terapia , Estimulación Encefálica Profunda/estadística & datos numéricos , Evaluación de la Discapacidad , Trastornos Distónicos/fisiopatología , Trastornos Distónicos/psicología , Femenino , Globo Pálido/anatomía & histología , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/etiología , Trastornos del Humor/fisiopatología , Trastornos del Humor/terapia , Movimiento/fisiología , Satisfacción del Paciente , Calidad de Vida/psicología , Recuperación de la Función/fisiología , Índice de Severidad de la Enfermedad , Tiempo , Resultado del TratamientoRESUMEN
The role of nuclear medicine imaging in the diagnosis of vascular parkinsonism (VP) has been addressed by only few studies up to now. Most previous reports suggest no or only mild impairment of DAT and D2 receptors in VP. In contrast, in four patients with VP, reported here, the combined DAT and D2 receptor SPECT showed highly unusual changes in the pre- and/or postsynaptic dopaminergic system. The possible value of combined DAT/D2 receptor SPECT imaging should be investigated by future prospective studies.
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/metabolismo , Receptores de Dopamina D2/metabolismo , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Anciano de 80 o más Años , Benzamidas , Radioisótopos de Carbono , Circulación Cerebrovascular , Demencia Vascular/diagnóstico por imagen , Demencia Vascular/metabolismo , Antagonistas de Dopamina , Femenino , Humanos , Radioisótopos de Yodo , Masculino , Pirrolidinas , TropanosRESUMEN
AIM: Cerebral ultrasound perfusion examinations have been focused on the diencephalic plane. We describe perfusion abnormalities in the mesencephalon. METHOD: Phase-Inversion-Harmonic-Imaging (PIHI, Siemens Sonoline Elegra) was performed in a patient with ponto-mesencephalic cysts, that was defined by MRI. The signal increase (bolus kinetics, SonoVue) was quantified for peak-signal-increase (PSI) and time-to-peak (TTP). RESULTS: PSI and TTP could be quantified for the ipsi- and contralateral posterior cerebral arteries, the ipsilateral middle cerebral artery, the mesencephalon and the ipsilateral temporal lobe. The contrast agent influx was diminished or extinct in the area of the cysts. PSI and TTP delineated the area of the cystic structure well. CONCLUSION: PIHI in the mesencephalic plane is feasible and allows identification of pathological structures within the mesencephalon.
Asunto(s)
Encefalopatías/diagnóstico por imagen , Medios de Contraste , Quistes/diagnóstico por imagen , Mesencéfalo/diagnóstico por imagen , Femenino , Lateralidad Funcional , Humanos , Aumento de la Imagen , UltrasonografíaRESUMEN
PURPOSE: Comparison of extracellular K+ regulation in sclerotic and nonsclerotic epileptic hippocampus. METHODS: Measurements of K+ signals with double-barreled K+-selective reference microelectrodes in area CAI of slices from human and rat hippocampus, induction of increases in extracellular potassium concentration by repetitive alvear stimulation or iontophoresis. and block of inward-rectifying and background K+ channels in astrocytes by barium. RESULTS: In the CA1 pyramidal layer from normal rat hippocampus, barium augmented extracellular K+ accumulation induced by iontophoresis or antidromic stimulation in a dose-dependent manner. Similarly, barium augmented stimulus-induced K+ signals from nonsclerotic hippocampi (human mesial temporal lobe epilepsy). In contrast, barium failed to do so in sclerotic hippocampi (human mesial temporal lobe epilepsy, rat pilocarpine model). CONCLUSIONS: Our findings suggest that in areas of reduced neuronal density (hippocampal sclerosis), glial cells adapt to permit rather large increases in extracellular potassium accumulation. Such increases might be involved in the transmission of activity through the sclerotic area.
Asunto(s)
Epilepsia del Lóbulo Temporal/fisiopatología , Hipocampo/fisiopatología , Neuroglía/fisiología , Potasio/fisiología , Animales , Bario/farmacología , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/patología , Espacio Extracelular/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Técnicas In Vitro , Neuroglía/efectos de los fármacos , Neuroglía/patología , Pilocarpina/farmacología , Potasio/metabolismo , Células Piramidales/efectos de los fármacos , Células Piramidales/fisiología , Células Piramidales/fisiopatología , Ratas , EsclerosisRESUMEN
PURPOSE: Neuronal network reorganization might be involved in epileptogenesis in human and rat limbic epilepsy. Apart from aberrant mossy fiber sprouting, a more widespread fiber rearrangement in the hippocampal formation might occur. Therefore, we studied sprouting in area CA1 because this region is most affected in human temporal lobe epilepsy. METHODS: In slices from hippocampi of patients operated on for temporal lobe epilepsy (n = 134), from pilocarpine-treated rats (n = 74), and from control rats (n = 15), viable neurons were labeled with fluorescent dextran amines. RESULTS: In human hippocampi as well as in pilocarpine-treated rats, the degree of nerve cell loss varied. In 67 of 134 slices from human specimens with distinct Ammon's horn sclerosis and in 23 of 74 slices from pilocarpine-treated rats, a severe shrunken area CA1 presented with a similar picture: few damaged neurons were labeled, and aberrant fiber connections were not visible. This was in contrast to human resected hippocampi and hippocampi from pilocarpine-treated rats with no or moderate loss of neurons. In these cases, pyramidal cells remote from the injection site were labeled (human tissue, n = 59 of 134; pilocarpine-treated rats, n = 39 of 74). In human resected hippocampi without obvious pathology and in control animals, no pyramidal neurons were labeled apart from the injection site. CONCLUSIONS: Axon collaterals of CA1 pyramidal cells are increased in human temporal lobe epilepsy and in pilocarpine-treated rats. Adjacent CA1 pyramidal cells project via aberrant collaterals to the stratum pyramidale and the stratum radiatum of area CA1. This network reorganization can contribute to hyperexcitability via increased backward excitation.
Asunto(s)
Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Vías Nerviosas/patología , Plasticidad Neuronal , Animales , Modelos Animales de Enfermedad , Epilepsia del Lóbulo Temporal/inducido químicamente , Colorantes Fluorescentes , Hipocampo/citología , Humanos , Pilocarpina/farmacología , Células Piramidales/patología , RatasRESUMEN
In the hippocampus of patients with therapy-refractory temporal lobe epilepsy, glial cells of area CA1 might be less able to take up potassium ions via barium-sensitive inwardly rectifying and voltage-independent potassium channels. Using ion-selective microelectrodes we investigated the effects of barium on rises in [K+]o induced by repetitive alvear stimulation in slices from surgically removed hippocampi with and without Ammon's horn sclerosis (AHS and non-AHS). In non-AHS tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of recovery by 90%. The barium effect was reversible, concentration dependent, and persisted in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid [GABA(A)] receptor antagonists. In AHS tissue, barium caused a decrease in the baseline level of [K+]o. In contrast to non-AHS slices, in AHS slices with intact synaptic transmission, barium had no effect on the stimulus-induced rises of [K+]o, and the half time of recovery from the rise was less prolonged (by 57%). Under conditions of blocked synaptic transmission, barium augmented stimulus-induced rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced negative slow-field potentials following repetitive stimulation but did not alter the mean population spike amplitude. The findings suggest a significant contribution of glial barium-sensitive K+-channels to K+-buffering in non-AHS tissue and an impairment of glial barium-sensitive K+-uptake in AHS tissue.
Asunto(s)
Compuestos de Bario/farmacología , Cloruros/farmacología , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Potasio/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , Adulto , Bicuculina/farmacología , Tampones (Química) , Estimulación Eléctrica , Electrofisiología , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/fisiopatología , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas del GABA/farmacología , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Técnicas In Vitro , Quinoxalinas/farmacología , Esclerosis , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
Upon perfusion with Mg2+-free artificial cerebrospinal fluid (ACSF) organotypic hippocampal slice cultures develop seizure-like events and tonic recurrent discharges in which areas CA3 and CA1 and, in contrast to acute slices, also the dentate gyrus (DG) participate. Using the fluorescent dye propidium iodide (PI) we show that sustained epileptic activity causes cell death in the DG and pyramidal cell layer particularly evident in the granule cell layer of the DG. This correlates with the decrease of the electrophysiological responses to hilar stimulation. Interestingly, perfusion with carbogenated serum-free ACSF also induces some cell death which is, however, mild compared with low magnesium treated slice cultures.
Asunto(s)
Epilepsia/etiología , Epilepsia/fisiopatología , Hipocampo/patología , Hipocampo/fisiopatología , Magnesio/administración & dosificación , Animales , Muerte Celular/fisiología , Técnicas de Cultivo , Giro Dentado/patología , Giro Dentado/fisiopatología , Estimulación Eléctrica , Electrofisiología , Epilepsia/patología , Colorantes Fluorescentes , Propidio , Células Piramidales/patología , Células Piramidales/fisiología , Ratas , Factores de TiempoRESUMEN
Immature glia may not be able to buffer K+ ions released during neuronal activity. Therefore, we investigated entorhinal-hippocampal slices of juvenile rats (ages P15-18 and P22-26) using a perfusion medium containing 2 mM BaCl2 in order to block glial inward rectifying and leak potassium channels. In contrast to adult animals, rises in [K+]o in slices from juvenile animals elicited by repetitive alvear stimulation were not augmented by Ba2+. Ba2+ effects on fast field potentials, slow field potentials and the applied current sink source distribution were roughly similar as in adult rats. We conclude that the capacity to buffer large quantities of K+ ions by mechanisms involving Ba2+-sensitive K+ channels has not yet developed in juveniles.
Asunto(s)
Bario/farmacología , Hipocampo/metabolismo , Potasio/metabolismo , Animales , Estimulación Eléctrica , Hipocampo/citología , Hipocampo/efectos de los fármacos , Técnicas In Vitro , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Ratas , Ratas WistarRESUMEN
The effects of barium on stimulus-induced rises in [K+]o were studied in the dentate gyrus (DG) and area CA1 of human hippocampal slices. Rises in [K+]o elicited by repetitive stimulation of the hilus, stratum moleculare, alveus, or stratum radiatum were dependent on stimulus intensity and frequency. Barium augmented rises in [K+]o in the DG by about 120% but failed to do so in area CA1. In both DG and area CA1 barium had no effects on population spikes whereas stimulus-induced slow field potentials were reduced. Since barium interferes with K+ uptake and redistribution by blocking leak conductances and inwardly-rectifying currents in astrocytes, our findings suggest that glial cells in the sclerotic hippocampal area CA1 may contribute less to K+ regulation.
Asunto(s)
Bario/farmacología , Giro Dentado/metabolismo , Epilepsia/metabolismo , Hipocampo/metabolismo , Potasio/metabolismo , Adulto , Giro Dentado/efectos de los fármacos , Electrofisiología , Hipocampo/efectos de los fármacos , Humanos , Técnicas In VitroRESUMEN
Laminar profiles of rises in [K+]o and slow field potentials induced by alvear stimulation were recorded in area CA1 of hippocampal slices from control and pilocarpine-treated rats in absence and presence of Ba2+. In control animals, Ba2+ augmented rises in [K+]o in stratum pyramidale (SP) as well as in stratum radiatum (SR). In pilocarpine-treated animals an augmentation of rises in [K+]o was restricted to SP and its immediate vicinity. Moreover, the effect of Ba2+ in SP was small or missing in eight out of 15 slices of pilocarpine-treated animals. In these slices laminar profiles of rises in [K+]o were not affected by Ba2+. It is suggested that spatial K+-buffering is reduced in area CA1 of epileptic animals.