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1.
Neurobiol Dis ; 199: 106589, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38969232

RESUMEN

BACKGROUND: Despite the large body of work on local field potentials (LFPs), a measure of oscillatory activity in patients with Parkinson's disease (PD), the longitudinal evolution of LFPs is less explored. OBJECTIVE: To determine LFP fluctuations collected in clinical settings in patients with PD and STN deep brain stimulation (DBS). METHODS: Twenty-two STN-DBS patients (age: 67.6 ± 8.3 years; 9 females; disease duration: 10.3 ± 4.5 years) completed bilateral LFP recordings over three visits in the OFF-stimulation setting. Peak and band power measures were calculated from each recording. RESULTS: After bilateral LFP recordings, at least one peak was detected in 18 (81.8%), 20 (90.9%), and 22 (100%) patients at visit 1, 2, and 3, respectively. No significant differences were seen in primary peak amplitude (F = 2.91, p = 0.060) over time. Amplitude of the second largest peak (F = 5.49, p = 0.006) and low-beta (F = 6.89, p = 0.002), high-beta (F = 13.23, p < 0.001), and gamma (F = 12.71, p < 0.001) band power demonstrated a significant effect of time. Post hoc comparisons determined low-beta power (Visit 1-Visit 2: t = 3.59, p = 0.002; Visit 1-Visit 3: t = 2.61, p = 0.031), high-beta (Visit 1-Visit 2: t = 4.64, p < 0.001; Visit 1-Visit 3: t = 4.23, p < 0.001) and gamma band power (Visit 1-Visit 2: t = 4.65, p < 0.001; Visit 1-Visit 3: t = 4.00, p < 0.001) were significantly increased from visit 1 recordings to both follow-up visits. CONCLUSION: Our results provide substantial evidence that LFP can reliably be detected across multiple real-world clinical visits in patients with STN-DBS for PD. Moreover, it provides insights on the evolution of these LFPs.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Femenino , Masculino , Núcleo Subtalámico/fisiopatología , Anciano , Estimulación Encefálica Profunda/métodos , Persona de Mediana Edad
3.
Sci Rep ; 13(1): 11003, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37420081

RESUMEN

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.


Asunto(s)
Estimulación Encefálica Profunda , Distonía , Trastornos Distónicos , Hematoma Subdural Crónico , Enfermedad de Parkinson , Humanos , Distonía/diagnóstico por imagen , Distonía/terapia , Enfermedad de Parkinson/diagnóstico por imagen , Resultado del Tratamiento , Estimulación Encefálica Profunda/métodos , Trastornos Distónicos/diagnóstico por imagen , Trastornos Distónicos/terapia , Cráneo/diagnóstico por imagen , Globo Pálido
4.
Brain Nerve ; 75(1): 5-14, 2023 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-36574968

RESUMEN

Dystonia is a movement disorder characterized by sustained muscle contractions that result in abnormal "patterned" movements and/or postural abnormalities. Based on the accompanying symptoms, dystonia can be classified as isolated (i.e., with dystonia only), combined (i.e., with other movement disorders such as myoclonus), or complex (i.e., with symptoms other than movement disorders such as mental retardation). Moreover, dystonia may affect single or multiple parts of the body and accordingly be classified as focal, segmental, multifocal, hemi, or generalized. The most common type of dystonia is isolated focal dystonia, often accompanied with a specific action (task-specific action). The "task-specificity" uniquely illustrates the nature of dystonia, and this phenomenon is most clearly observed in occupation-related dystonias that include musician's and athlete's dystonia. In this article, we first elucidate the general issues of common focal dystonia (cervical dystonia, blepharospasm, and focal hand dystonia) and then present several educational cases of occupational (task-specific) dystonia with some clinical pearls for practical management.


Asunto(s)
Distonía , Trastornos Distónicos , Trastornos del Movimiento , Humanos , Distonía/diagnóstico , Trastornos Distónicos/diagnóstico , Movimiento
5.
Sci Rep ; 12(1): 20350, 2022 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-36437372

RESUMEN

We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ρ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.


Asunto(s)
Distonía , Trastornos Distónicos , Trastornos Heredodegenerativos del Sistema Nervioso , Humanos , Estudios Retrospectivos
6.
J Med Invest ; 68(3.4): 400-403, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34759169

RESUMEN

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.


Asunto(s)
Hermanos , Deficiencia de Vitamina E , Ataxia/genética , Humanos , Filipinas , Deficiencia de Vitamina E/complicaciones , Deficiencia de Vitamina E/diagnóstico , Deficiencia de Vitamina E/genética
7.
Life (Basel) ; 11(6)2021 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-34074009

RESUMEN

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% (p < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.

8.
J Med Invest ; 67(3.4): 222-228, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33148892

RESUMEN

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.


Asunto(s)
Malformaciones Arteriovenosas Intracraneales/cirugía , Humanos , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/patología
9.
Brain Sci ; 10(9)2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32942724

RESUMEN

The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.

10.
Stereotact Funct Neurosurg ; 98(6): 399-403, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32894852

RESUMEN

BACKGROUND: The Lance-Adams syndrome (LAS) is a myoclonus syndrome caused by hypoxic-ischemic encephalopathy. LAS cases could be refractory to first-line medications, and the neuronal mechanism underlying LAS pathology remains unknown. OBJECTIVES: To describe a patient with LAS who underwent bilateral globus pallidus internus (GPi) stimulation and discuss the pathophysiology of LAS with intraoperative electrophysiological findings. PATIENTS: A 79-year-old woman presented with a history of cardiopulmonary arrest due to internal carotid artery rupture following carotid endarterectomy after successful cardiopulmonary resuscitation. However, within 1 month, the patient developed sensory stimulation-induced myoclonus in her face and extremities. Because her myoclonic symptoms were refractory to pharmacotherapy, deep brain stimulation of the GPi was performed 1 year after the hypoxic attack. RESULTS: Continuous bilateral GPi stimulation with optimal parameter settings remarkably improved the patient's myoclonic symptoms. At the 2-year follow-up, her Unified Myoclonus Rating Scale score decreased from 90 to 24. In addition, we observed burst firing and interburst pause patterns on intraoperative microelectrode recordings of the bilateral GPi and stimulated this area as the therapeutic target. CONCLUSION: Our results show that impairment in the basal ganglion circuitry might be involved in the pathogenesis of myoclonus in patients with LAS.


Asunto(s)
Estimulación Encefálica Profunda/métodos , Globo Pálido/fisiología , Hipoxia-Isquemia Encefálica/terapia , Monitorización Neurofisiológica Intraoperatoria/métodos , Mioclonía/terapia , Anciano , Femenino , Globo Pálido/diagnóstico por imagen , Humanos , Hipoxia-Isquemia Encefálica/complicaciones , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Microelectrodos , Mioclonía/diagnóstico por imagen , Mioclonía/etiología , Resultado del Tratamiento
11.
Intern Med ; 59(14): 1749-1753, 2020 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-32238726

RESUMEN

A 65-year-old woman with spinocerebellar ataxia presented with generalized seizures due to subcortical hemorrhaging. Magnetic resonance imaging (MRI) revealed obstruction of the superior sagittal sinus. Despite treatment, she became comatose. MRI newly revealed subdural fluid collection and descent of the brainstem. Her history indicated a recent fall, prompting additional studies, which revealed lumbar fracture and cerebrospinal fluid (CSF) leaks. We performed an epidural blood patch, and her consciousness was fully restored in one month. This is the first report of cerebral venous thrombosis with CSF leaks in the lumbar region due to a fall injury.


Asunto(s)
Accidentes por Caídas , Parche de Sangre Epidural/métodos , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/terapia , Traumatismos Vertebrales/complicaciones , Ataxias Espinocerebelosas/complicaciones , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Anciano , Femenino , Humanos , Resultado del Tratamiento
12.
World Neurosurg ; 137: 393-397, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32068175

RESUMEN

BACKGROUND: Bow hunter's syndrome (BHS) is caused by posterior circulation insufficiency that results from the occlusion or compression of the vertebral artery (VA) during neck rotation. Owing to its rarity, there is no guideline to support the decision of selecting a conservative or a surgical approach. Management of BHS is dependent on each patient. CASE DESCRIPTION: A 13-year-old girl presented with transient visual disturbance, hypoesthesia, and paralysis of the left side of the body. Magnetic resonance imaging revealed an acute cerebral infarction in the right thalamus, and magnetic resonance angiography demonstrated occlusion of the right posterior cerebral artery and dilation of V3 of the left VA. Digital subtraction angiography revealed a left VA dissecting aneurysm at V3 and left VA occlusion at the level of C1-C2 during neck rotation to the right. A dynamic x-ray suggested atlantoaxial joint instability, and three-dimensional computed tomography revealed aplasia of C1 lamina and atlantoaxial rotatory dislocation. BHS with left VA dissecting aneurysm caused by atlantoaxial rotatory dislocation was diagnosed. We performed C1-C2 posterior fusion by the Goel-Harms technique. Stroke did not recur, and computed tomography angiography obtained 8 months postoperatively demonstrated a decrease in the dissecting aneurysm. CONCLUSIONS: To our knowledge, this is the first case of BHS with VA dissecting aneurysm and aplasia of C1 lamina. Based on this case, we suggest that C1-C2 posterior fusion is effective for BHS with VA dissecting aneurysm.


Asunto(s)
Disección Aórtica/etiología , Articulación Atlantoaxoidea/cirugía , Infarto de la Arteria Cerebral Posterior/etiología , Luxaciones Articulares/complicaciones , Disección de la Arteria Vertebral/etiología , Insuficiencia Vertebrobasilar/etiología , Adolescente , Disección Aórtica/diagnóstico por imagen , Articulación Atlantoaxoidea/anomalías , Articulación Atlantoaxoidea/diagnóstico por imagen , Atlas Cervical/anomalías , Atlas Cervical/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Femenino , Humanos , Imagenología Tridimensional , Infarto de la Arteria Cerebral Posterior/diagnóstico por imagen , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Angiografía por Resonancia Magnética , Rotación , Fusión Vertebral , Disección de la Arteria Vertebral/diagnóstico por imagen , Insuficiencia Vertebrobasilar/diagnóstico por imagen
13.
J Med Invest ; 66(3.4): 314-318, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31656296

RESUMEN

Objective : One major complication associated with STB is intratumoral hematoma, which is also the most common cause of morbidity related to permanent paralysis and mortality in STB. The risk of perioperative hemorrhage is generally between 1% and 10%, but this could be an underestimation since it is not common for many neurosurgeons to perform CT scans after uncomplicated STBs. In this study, we describe the incidence of cerebral hemorrhage, including asymptomatic cerebral hemorrhage. Methods : We recently reviewed data on the diagnosis rate and occurrence of complications, including symptomatic and asymptomatic cerebral hemorrhage, in 80 patients who underwent STB at our facility between 2005 and 2014. Results : Histological diagnosis was established for 75 cases (93.8%), glioma was the most frequently encountered tumor. Symptomatic hemorrhage was observed in two cases (2.6%), with the symptoms subsiding within two days. The morbidity and mortality rate was 0%. However, asymptomatic hemorrhages were observed in 23 cases (28.8%). Conclusion : Stereotactic biopsy is a less invasive procedure for obtaining samples of brain tumors for diagnosis. The bleeding of the tissue-resection cavity that includes asymptomatic hemorrhage occurs at a constant rate. It is important to reduce the symptomatic bleeding associated with stereotactic biopsy. J. Med. Invest. 66 : 314-318, August, 2019.


Asunto(s)
Biopsia/efectos adversos , Neoplasias Encefálicas/diagnóstico , Encéfalo/patología , Hemorragia Cerebral/etiología , Técnicas Estereotáxicas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
14.
J Clin Neurosci ; 60: 79-83, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30318398

RESUMEN

The observation of walking improves gait ability in chronic stroke survivors. It has also been suggested that activation of the mirror neuron system contributes to this effect. However, activation of the mirror neuron system during gait observation has not yet been assessed in sub-acute stroke patients. The objective of this study was to clarify the activation of mirror neuron system during gait observation in sub-acute stroke patients and healthy persons. In this study, we sequentially enrolled five sub-acute stroke patients who had undergone gait training and nine healthy persons. We used fMRI to detect neuronal activation during gait observation. During the observation period in the stroke group, neural activity in the left inferior parietal lobule, right and left inferior frontal gyrus was significantly higher than during the rest period. In the healthy group, neural activity in the left inferior parietal lobule, left inferior frontal gyrus, left middle frontal gyrus, left superior temporal lobule and right and left middle temporal gyrus was significantly higher than during the rest period. The results indicate that the mirror neuron system was activated during gait observation in sub-acute stroke patients who had undergone gait training and also in healthy persons. Our findings suggest that gait observation treatment may provide a promising therapeutic strategy in sub-acute stroke patients who have experienced gait training.


Asunto(s)
Encéfalo/fisiología , Marcha , Neuronas Espejo/fisiología , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/fisiopatología , Adulto , Terapia por Ejercicio , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
15.
Neurol Med Chir (Tokyo) ; 58(11): 468-476, 2018 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-30298831

RESUMEN

This study was to assess the efficacy of microdiscectomy, cage fixation, and right tranuncal foramintomy for the patients suffering from right radiulo-myelopathy. Anterior cervical foraminotomy was reported to be an effective option for the treatment of cervical degenerative radiculopathy but with the problem of recurrence. Since Hakuba reported the method of trans-unco-discal approach in 1976, it was designed as keyhole foraminotomy which was called transuncal approach, transpedicular approach or transvertebral approach. In the anterior approach, we usually use the right-sided approach because most of us are right-handed surgeons. We retrospectively investigated our patients who had the right foraminal stenosis causing radiculopathy and were treated with microdiscectomy, cage fixation, and right keyhole transuncal foraminotomy. Since 2011, 23 patients were treated with the manner. All of the 23 patients who had central canal stenosis and among the 23 patients, 8 patients showed only right radiculopathy and 15 patients showed radiculo-myelopathy. In all patients, the radiculopathy disappeared or significantly improved without any complications postoperatively. The average of VAS scores was 7.6 ± 2.2 in preoperative state, 2.8 ± 2.2 at discharge, and 1.1 ± 1.6 in 1 month after surgery. The average of follow-up time was 38.3 months and they had no recurrence of radiculopathy. We showed that this manner is effective and one option for the combined disease of right foraminal and canal stenosis and we believe that this manner is not complex and safe if we can understand the anatomy.


Asunto(s)
Discectomía , Foraminotomía , Radiculopatía/cirugía , Enfermedades de la Médula Espinal/cirugía , Estenosis Espinal/cirugía , Espondilosis/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiculopatía/etiología , Estudios Retrospectivos , Enfermedades de la Médula Espinal/etiología , Estenosis Espinal/complicaciones , Espondilosis/complicaciones , Resultado del Tratamiento
16.
J Neurooncol ; 139(2): 323-332, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29779087

RESUMEN

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. METHODS: GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. RESULTS: Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. CONCLUSIONS: Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.


Asunto(s)
Antineoplásicos Alquilantes/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Temozolomida/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Distribución Aleatoria , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
17.
World Neurosurg ; 116: 50-55, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29777885

RESUMEN

BACKGROUND: Spontaneous intracranial hypotension (SIH) has been increasingly recognized as a phenomenon caused by cerebrospinal fluid (CSF) leaks; however, its pathogenesis remains unclear. CASE DESCRIPTION: We report 2 cases of SIH resulting from CSF leak from a meningeal diverticulum at the C2 nerve root sleeve. The first case is that of a 46-year-old man who experienced orthostatic headache after a bicycle accident at age 45. Computed tomography (CT) myelography revealed CSF leaks at the C1-2 level. He underwent epidural blood patch therapy, but it was unsuccessful. Next, we performed direct surgery and found a meningeal diverticulum originating from the left C2 nerve root; therefore, we ligated the diverticulum. His symptoms and image findings strikingly improved after surgery. The second case is that of a 45-year-old man who experienced orthostatic headache 1 month after jumping into a river. Magnetic resonance imaging of the head showed bilateral subdural hematoma. CT myelography revealed CSF leaks at the C1-2 level and multiple cyst formations at the cervical and thoracic nerve root sleeves. epidural blood patch was performed, and his symptoms immediately improved. CONCLUSIONS: Recent studies have reported that meningeal diverticulum is involved in various cases of CSF leaks. The 2 cases indicate that traumatic accidents, such as back-and-forth neck movement or falls, presumably induce an increase in CSF pressure, followed by the rupture of an existing meningeal diverticulum, leading to CSF leak.


Asunto(s)
Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Pérdida de Líquido Cefalorraquídeo/diagnóstico por imagen , Vértebras Cervicales/diagnóstico por imagen , Divertículo/diagnóstico por imagen , Meninges/diagnóstico por imagen , Parche de Sangre Epidural/estadística & datos numéricos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/terapia , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/terapia , Divertículo/etiología , Divertículo/terapia , Humanos , Masculino , Persona de Mediana Edad
18.
J Stroke Cerebrovasc Dis ; 27(8): 2134-2140, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29622372

RESUMEN

BACKGROUND: Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. METHODS: Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. RESULTS: Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. CONCLUSION: Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed.


Asunto(s)
Aneurisma Intracraneal/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Espironolactona/análogos & derivados , Anciano , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/prevención & control , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Eplerenona , Femenino , Estudios de Seguimiento , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Masculino , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Fármacos Neuroprotectores/efectos adversos , Proyectos Piloto , Espironolactona/efectos adversos , Espironolactona/uso terapéutico , Resultado del Tratamiento
19.
Parkinsonism Relat Disord ; 52: 55-61, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29653907

RESUMEN

BACKGROUND: Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with complex early-onset dystonia. Almost all reported KMT2B mutations occurred de novo in the paternal germline or in the early development of the patient. We describe clinico-genetic features on four Japanese patients with novel de novo mutations and demonstrate the phenotypic spectrum of KMT2B mutations. METHODS: We performed genetic studies, including trio-based whole exome sequencing (WES), in a cohort of Japanese patients with a seemingly sporadic early-onset generalized combined dystonia. Potential effects by the identified nucleotide variations were evaluated biologically. Genotype-phenotype correlations were also investigated. RESULTS: Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC, c.3325_3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed a reduced expression of mutant transcript frame. All patients presented with motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset generalized dystonia and superimposed choreoathetosis or myoclonus. One patient cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three patients had bilateral globus pallidal deep brain stimulation (DBS) with excellent or partial response. CONCLUSIONS: We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.


Asunto(s)
Discapacidades del Desarrollo/genética , Enanismo/genética , Trastornos Distónicos/genética , Haploinsuficiencia/genética , N-Metiltransferasa de Histona-Lisina/genética , Microcefalia/genética , Mioclonía/genética , Adolescente , Adulto , Estudios de Cohortes , Femenino , Mutación del Sistema de Lectura , Humanos , Masculino , Fenotipo , ARN Mensajero , Secuenciación del Exoma , Adulto Joven
20.
Neuroradiology ; 59(6): 587-595, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28397019

RESUMEN

PURPOSE: Arterial spin labeling (ASL) involves perfusion imaging using the inverted magnetization of arterial water. If the arterial arrival times are longer than the post-labeling delay, labeled spins are visible on ASL images as bright, high intra-arterial signals (IASs); such signals were found within occluded vessels of patients with acute ischemic stroke. The identification of the occluded segment in the internal carotid artery (ICA) is crucial for endovascular treatment. We tested our hypothesis that high IASs on ASL images can predict the occluded segment. METHODS: Our study included 13 patients with acute ICA occlusion who had undergone angiographic and ASL studies within 48 h of onset. We retrospectively identified the high IAS on ASL images and angiograms and recorded the occluded segment and the number of high IAS-positive slices on ASL images. The ICA segments were classified as cervical (C1), petrous (C2), cavernous (C3), and supraclinoid (C4). RESULTS: Of seven patients with intracranial ICA occlusion, five demonstrated high IASs at C1-C2, suggesting that high IASs could identify stagnant flow proximal to the occluded segment. Among six patients with extracranial ICA occlusion, five presented with high IASs at C3-C4, suggesting that signals could identify the collateral flow via the ophthalmic artery. None had high IASs at C1-C2. The mean number of high IAS-positive slices was significantly higher in patients with intra- than extracranial ICA occlusion. CONCLUSION: High IASs on ASL images can identify slow stagnant and collateral flow through the ophthalmic artery in patients with acute ICA occlusion and help to predict the occlusion site.


Asunto(s)
Estenosis Carotídea/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Marcadores de Spin , Anciano , Anciano de 80 o más Años , Angiografía Cerebral , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Valor Predictivo de las Pruebas , Estudios Retrospectivos
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