RESUMEN
OBJECTIVES: To elucidate the pathophysiology of urinary dysfunction in idiopathic normal-pressure hydrocephalus (iNPH) by single-photon emission computed tomography (SPECT) and statistical brain mapping. METHODS: Urinary symptoms were observed and N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-SPECT imaging was performed in 97 patients with clinico-radiologically definite iNPH. The patients included 56 men and 41 women; mean age, 74 years. The statistical difference in normalized mean tracer counts was calculated and visualized between patients with urinary dysfunction of severer degrees (>grade 2/4) and milder degrees (Asunto(s)
Lóbulo Frontal/irrigación sanguínea
, Lóbulo Frontal/diagnóstico por imagen
, Hidrocéfalo Normotenso/complicaciones
, Flujo Sanguíneo Regional/fisiología
, Incontinencia Urinaria/epidemiología
, Trastornos Urinarios/epidemiología
, Anciano
, Anciano de 80 o más Años
, Mapeo Encefálico
, Trastornos del Conocimiento/fisiopatología
, Femenino
, Lóbulo Frontal/fisiopatología
, Trastornos Neurológicos de la Marcha/fisiopatología
, Humanos
, Hidrocéfalo Normotenso/fisiopatología
, Radioisótopos de Yodo
, Masculino
, Persona de Mediana Edad
, Estudios Retrospectivos
, Índice de Severidad de la Enfermedad
, Tomografía Computarizada de Emisión de Fotón Único
, Incontinencia Urinaria/fisiopatología
, Trastornos Urinarios/fisiopatología
RESUMEN
BACKGROUND: Lithium is the first-line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3ß and brain-derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium. METHOD: Fifty patients with BDs and 50 healthy subjects (mean age 55.0 ± 15.0 years; M/F 19/31) participated. We examined structural variation of the GSK3ß and BDNF genes by real-time PCR. We examined the influence of structural variation of these genes on the therapeutic responses to lithium and the occurrence of antidepressant-emergent affective switch (AEAS). The efficacy of lithium was assessed using the Alda scale, and AEAS was evaluated using Young Mania Rating Scale. RESULTS: Although we examined structural variations within intron II and VII of the GSK3® gene and from the end of exon IV to intron IV and within exon IX of the BDNF gene, no structural variation was found in BDs. Whereas 5 of 50 patients exhibited three copies of the genomic region within exon IV of the BDNF gene, all healthy subjects had two copies. No difference in the therapeutic efficacy of lithium was found between patients with three and two copies. No difference in the occurrence of AEAS was found between the two groups. CONCLUSION: The amplification of the BDNF gene influenced neither the therapeutic responses to lithium nor the occurrence of AEAS.
Asunto(s)
Antimaníacos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Proteínas del Citoesqueleto/genética , Compuestos de Litio/farmacología , Proteínas Nucleares/genética , Adulto , Anciano , Factor Neurotrófico Derivado del Encéfalo/química , Proteínas del Citoesqueleto/química , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Proteínas Nucleares/química , Pruebas de FarmacogenómicaRESUMEN
In patients with Alzheimer's disease (AD), it is sometimes challenging to identify typical findings in electroencephalography (EEG) or magnetoencephalography (MEG) such as a slowing of the posterior dominant activity or an increase in slow activity. In this MEG study, we evaluated the event-related synchronization (ERS) of alpha activity after eye closing in patients with early AD and mild cognitive impairment (MCI) who presented no slow MEG pattern. Thirteen patients with probable AD and thirteen patients with MCI, who met NINCDS-ADRDA and Petersen's diagnostic criteria, respectively, were enrolled. We also selected fourteen age-matched normal control subjects. MEG activity was acquired during eye-open and eye-closed states. The ERS after eye closing within 8-15Hz frequency band was calculated and its cortical source was superimposed on the individual's MRI by using the beamformer implemented in Brain Electrical Source Analysis (BESA). The Source image was converted into a standardized image, and group comparisons across patients with AD, MCI and controls were performed using BrainVoyager QX. The averaged ERS was observed dominantly in posterior regions in all three groups. Significant difference in ERS was observed only for the comparison between AD patients and controls, with AD patients showing increased ERS in frontal regions. Frontal shift of posterior alpha activity was observed clearly in AD patients using the combination of beamformer and group comparison.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Trastornos del Conocimiento/diagnóstico , Sincronización Cortical , Magnetoencefalografía , Anciano , Enfermedad de Alzheimer/fisiopatología , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , MasculinoRESUMEN
AIMS OF STUDY: It is reported that severe bladder disorder in idiopathic normal-pressure hydrocephalus (iNPH) is predicted by right frontal hypoperfusion. However, it is not known whether bladder recovery is predicted by brain perfusion change after shunt surgery. To address this issue, we compared bladder and brain function before and after shunt surgery in iNPH. METHODS: We enrolled 75 patients in the study. Before and 12 months after shunt surgery, we analyzed brain perfusion by SPECT and bladder disorder by a specialized grading scale. The scale consisted of grade 0, none; grade 1, urinary urgency and frequency; grade 2, urinary incontinence 1-3 times a week; grade 3, urinary incontinence >daily; and grade 4, loss of bladder control. More than one grade improvement is defined as improvement, and more than one grade decrement as worsening; otherwise no changes. RESULTS: Comparing before and after surgery, in the bladder-no-change group (32 cases) there was an increase in blood flow which is regarded as reversal of enlargement in the Sylvian fissure and lateral ventricles (served as control). In contrast, in the bladder-improved group (32 cases) there was an increase in bilateral mid-cingulate, parietal, and left frontal blood flow (p < 0.05). In the bladder-worsened group (11 cases) no significant blood flow change was observed. CONCLUSION: The present study showed that after shunt surgery, bladder recovery is related with mid-cingulate perfusion increase in patients with iNPH. The underlying mechanism might be functional restoration of the mid-cingulate that normally inhibits the micturition reflex.
Asunto(s)
Encéfalo/diagnóstico por imagen , Hidrocefalia/cirugía , Presión Intracraneal/fisiología , Recuperación de la Función , Tomografía Computarizada de Emisión de Fotón Único/métodos , Vejiga Urinaria/fisiopatología , Incontinencia Urinaria/fisiopatología , Micción/fisiología , Anciano , Anciano de 80 o más Años , Encéfalo/fisiopatología , Derivaciones del Líquido Cefalorraquídeo/métodos , Femenino , Estudios de Seguimiento , Humanos , Hidrocefalia/complicaciones , Hidrocefalia/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Factores de Tiempo , Incontinencia Urinaria/etiologíaRESUMEN
Semantic dementia (SD) is a neurodegenerative disease characterized by atrophy of the anterior temporal regions and progressive loss of semantic memory. SD has recently been reported to be associated with a pathologic diagnosis of frontotemporal lobar degeneration (FTLD) with Tar DNA-binding protein of 43 kDa (TDP-43) immunoreactive inclusions (FTLD-TDP) type 2 by Mackenzie. In the first several years of the disease, SD patients, especially those with left hemisphere-dominant temporal atrophy, present with primary progressive aphasia, in which language deterioration is obvious; however, they do not have other cognitive and behavioral impairments. The language impairment in SD is termed as word meaning aphasia, in which patients experience both word finding difficulties and word recognizing difficulties (two-way anomia). Phonemic cues are not effective in improving anomia. In addition, SD patients do not experience a sense of familiarity with words that they cannot find or recognize. While reading and writing Japanese words, SD patients, except those who also have motor neuron disease, exhibit well-preserved kana (phonogram) processing. However, in the case of kanji, they often exhibit surface dyslexia while reading and also exhibit phonetic miswriting. In the aphasic stage, SD patients can explain what the objects are and can use them appropriately; however, they cannot find or recognize the names of the objects. On progressing to the semantic memory impairment stage, the patients do not exhibit any familiarity with the objects whose names they cannot find or recognize and are unable to appropriately use these objects. Semantic memory impairment in SD is attributed to damage of gray matter and of superior and inferior white matter connections in the anterior temporal lobe.