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1.
Intern Med ; 58(21): 3077-3082, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243232

RESUMO

Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM. Methods Eleven consecutive HIV-negative patients with CM who presented at one of three emergency hospitals in Japan from April 2001 to March 2018 were enrolled. For all patients, we retrospectively assessed the relationships between clinical and laboratory information and the presence of WMLs. Results At presentation, 6 patients had WMLs on magnetic resonance imaging (MRI). The cerebrospinal fluid immunoglobulin G (CSF IgG) index was significantly higher in the patients with WMLs than in those without WMLs (mean, 1.34 vs. 0.70, p=0.017). The time from the symptom onset to initial neuroimaging was also significantly longer in the patients with WMLs than in those without WMLs (median, 31.5 vs. 7.0 days; p=0.008). The clinical outcome was comparable among the patients with and without WMLs. Conclusion In HIV-negative patients with CM, a persistent, aberrant immune response to Cryptococcus, such as intrathecal IgG synthesis, may induce WML formation.

2.
Am J Hum Genet ; 104(5): 925-935, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-30982609

RESUMO

Colony stimulating factor 1 receptor (CSF1R) plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts. Mono-allelic mutations of CSF1R are known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an adult-onset progressive neurodegenerative disorder. Here, we report seven affected individuals from three unrelated families who had bi-allelic CSF1R mutations. In addition to early-onset HDLS-like neurological disorders, they had brain malformations and skeletal dysplasia compatible to dysosteosclerosis (DOS) or Pyle disease. We identified five CSF1R mutations that were homozygous or compound heterozygous in these affected individuals. Two of them were deep intronic mutations resulting in abnormal inclusion of intron sequences in the mRNA. Compared with Csf1r-null mice, the skeletal and neural phenotypes of the affected individuals appeared milder and variable, suggesting that at least one of the mutations in each affected individual is hypomorphic. Our results characterized a unique human skeletal phenotype caused by CSF1R deficiency and implied that bi-allelic CSF1R mutations cause a spectrum of neurological and skeletal disorders, probably depending on the residual CSF1R function.

3.
J Clin Neurosci ; 62: 226-228, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612916

RESUMO

Progressive multifocal leukoencephalopathy (PML) is caused by John Cunningham (JC) virus in immunocompromized patients such as those with human immunodeficiency virus (HIV) infection, hematological malignancy, autoimmune disorder, and immunodeficiency disorder as well as those undergoing chemotherapy or immunosuppressive therapy. No effective treatments have been established for PML, which commonly causes severe neurological sequelae. We describe the first case of PML in a patient without HIV infection who exhibited remarkable improvement following acute pyelonephritis with Escherichia coli bacteremia.


Assuntos
Hospedeiro Imunocomprometido , Leucoencefalopatia Multifocal Progressiva/imunologia , Pielonefrite/complicações , Adulto , Anemia Hemolítica Autoimune/complicações , Bacteriemia/complicações , Feminino , Humanos , Neoplasias Pulmonares/complicações , Linfoma de Zona Marginal Tipo Células B/complicações
4.
J Clin Monit Comput ; 33(6): 987-998, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30610516

RESUMO

Many neuroendovascular treatments are supported by real-time anatomical and visual hemodynamic assessments through digital subtraction angiography (DSA). Here we used DSA in a single-center prospective randomized crossover study to assess the intracranial hemodynamics of patients undergoing coiling for cerebral aneurysm (n = 15) during sevoflurane- and propofol-based anesthesia. Color-coded DSA was used to define time to peak density of contrast medium (TTP) at several intravascular regions of interest (ROIs). Travel time at a particular ROI was defined as the TTP at the selected ROI minus TTP at baseline position on the internal carotid artery (ICA). Travel time at the jugular bulb on the anterior-posterior view was defined as the cerebral circulation time (CCT), which was divided into four segmental circulation times: ICA, middle cerebral artery (MCA), microvessel, and sinus. When bispectral index values were kept between 40 and 60, CCT (median [interquartile range]) was 10.91 (9.65-11.98) s under propofol-based anesthesia compared with 8.78 (8.32-9.45) s under sevoflurane-based anesthesia (P < 0.001). Circulation times for the ICA, MCA, and microvessel segments were longer under propofol-based anesthesia than under sevoflurane-based anesthesia (P < 0.05 for all). Our results suggest that, relative to sevoflurane, propofol decreases overall cerebral perfusion.

6.
Intern Med ; 57(23): 3451-3458, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29984771

RESUMO

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is an autoimmune disorder involving the brainstem and spinal cord and is sometimes associated with thymoma. We encountered a 75-year-old woman with typical PERM features, glycine receptor antibody, and thymoma. Her neurologic symptoms improved after thymectomy, but she unexpectedly developed anasarca with massive pleural effusions and hypoalbuminemia and finally succumbed to death. The autopsy showed edema and mononuclear infiltration in the pleura but no neuropathological findings typical of PERM. Effective treatment of PERM can reverse the neuropathological signs of encephalomyelitis. The autoimmune nature of anasarca is possible but not proven.

7.
Phys Med ; 49: 19-27, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29866338

RESUMO

PURPOSE: As there have been few reports on quantitative analysis of inter-institutional results for independent monitor unit (MU) verification, we performed a multi-institutional study of verification to show the feasibility of applying the 3-5% action levels used in the U.S. and Europe, and also to show the results of inter-institutional comparisons. METHODS: A total of 5936 fields were collected from 12 institutions. We used commercial software employing the Clarkson algorithm for verification after a validation study of measurement and software comparisons was performed. The doses generated by the treatment planning systems (TPSs) were retrospectively analyzed using the verification software. RESULTS: Mean ±â€¯two standard deviations of all locations were 1.0 ±â€¯3.6%. There were larger differences for breast (4.0 ±â€¯4.0%) and for lung (2.5 ±â€¯5.8%). A total of 80% of the fields with differences over 5% of the action level involved breast and lung targets, with 7.2 ±â€¯5.4%. Inter-institutional comparisons showed various systematic differences for field shape for breast and differences in the fields were attributable to differences in reference point placement for lung. The large differences for breast and lung are partially attributable to differences in the methods used to correct for heterogeneity. CONCLUSIONS: The 5% action level may be feasible for verification; however, an understanding of larger differences in breast and lung plans is important in clinical practice. Based on the inter-institutional comparisons, care must be taken when determining an institution-specific action level from plans with different field shape settings and incorrectly placed reference points.


Assuntos
Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Humanos , Aceleradores de Partículas , Controle de Qualidade , Dosagem Radioterapêutica , Estudos Retrospectivos , Software
8.
J Radiat Res ; 59(4): 490-500, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29790997

RESUMO

In inhomogeneous media, there is often a large systematic difference in the dose between the conventional Clarkson algorithm (C-Clarkson) for independent calculation verification and the superposition-based algorithms of treatment planning systems (TPSs). These treatment site-dependent differences increase the complexity of the radiotherapy planning secondary check. We developed a simple and effective method of heterogeneity correction integrated with the Clarkson algorithm (L-Clarkson) to account for the effects of heterogeneity in the lateral dimension, and performed a multi-institutional study to evaluate the effectiveness of the method. In the method, a 2D image reconstructed from computed tomography (CT) images is divided according to lines extending from the reference point to the edge of the multileaf collimator (MLC) or jaw collimator for each pie sector, and the radiological path length (RPL) of each line is calculated on the 2D image to obtain a tissue maximum ratio and phantom scatter factor, allowing the dose to be calculated. A total of 261 plans (1237 beams) for conventional breast and lung treatments and lung stereotactic body radiotherapy were collected from four institutions. Disagreements in dose between the on-site TPSs and a verification program using the C-Clarkson and L-Clarkson algorithms were compared. Systematic differences with the L-Clarkson method were within 1% for all sites, while the C-Clarkson method resulted in systematic differences of 1-5%. The L-Clarkson method showed smaller variations. This heterogeneity correction integrated with the Clarkson algorithm would provide a simple evaluation within the range of -5% to +5% for a radiotherapy plan secondary check.


Assuntos
Algoritmos , Tomografia Computadorizada por Raios X , Mama/diagnóstico por imagem , Mama/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Imagens de Fantasmas , Radiocirurgia , Reprodutibilidade dos Testes
9.
Medicine (Baltimore) ; 97(10): e0082, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29517672

RESUMO

RATIONALE: OSAM is a rare ventriculoperitoneal (VP) shunt complication where cervical spinal cord compression by epidural venous plexus engorgement is caused by cerebrospinal fluid (CSF) overdrainage. Symmetrically indented deformity of the upper cervical spinal cord and surrounding epidural venous engorgement are characteristic radiological findings. Both of them are typically detected on magnetic resonance imaging (MRI) and enhanced computed tomography (CT). PATIENT CONCERNS: The 77-year-old man who underwent the placement of a VP shunt without an antisiphon device to treat post-subarachnoid hemorrhage (SAH) hydrocephalus presented with progressive quadriplegia 10 years postoperatively. DIAGNOSIS: MRI revealed a symmetrically indented spinal cord from the craniocervical junction (CCJ) to the C2 level and enhanced CT showed the epidural venous engorgement, which were characteristic radiological findings of overshunting-associated myelopathy (OSAM). However, MRI atypically failed to detect the engorged epidural vein and showed no compressive lesion around the spinal cord. INTERVENTION: In order to reveal how the cervical spinal cord was deformed and compressed by engorged epidural vein, CT myelography was performed. OUTCOMES: CT myelography proved that the epidural vein dynamically engorged and compressed the cervical spinal cord immediately after rotation and extension of the neck. LESSONS: CT myelography combined with neck rotation and extension revealed the dynamic change of the epidural venous engorgement, and is useful for evaluation and diagnosis of OSAM especially when epidural venous engorgement was not detectable on MRI.


Assuntos
Mielografia/métodos , Compressão da Medula Espinal/etiologia , Doenças da Medula Espinal/complicações , Tomografia Computadorizada por Raios X/métodos , Derivação Ventriculoperitoneal/efeitos adversos , Idoso , Medula Cervical/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Compressão da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/diagnóstico por imagem
10.
J Stroke Cerebrovasc Dis ; 27(5): 1237-1251, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29337049

RESUMO

BACKGROUND: Development of collateral circulation after acute ischemic stroke is triggered by shear stress that occurs in pre-existing arterioles. Recently, sphingosine-1-phosphate receptor 1 (S1P1) on endothelial cells was reported to sense shear stress and transduce its signaling pathways. METHODS: BALB/c mice (n = 118) were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham operation. We investigated the effect of an S1P1-selective agonist SEW2871 on leptomeningeal collateral arteries and neurological outcome after pMCAO. RESULTS: Immunohistochemistry showed that without treatment, the expression of S1P1 on endothelial cells of leptomeningeal arteries and capillaries increased early after pMCAO, peaking at 6 hours, whereas a significant increase in the expression of S1P1 in neurons was seen from 24 hours later. After intraperitoneal administration of SEW2871 for 7 days after pMCAO, the number of leptomeningeal collateral arteries was significantly increased, cerebral blood flow improved, infarct volume was decreased, and neurological outcome improved compared with the controls. Significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS) as early as 6 hours after pMCAO and higher expression of tight junction proteins at postoperative day 3 were observed with SEW2871 treatment as assessed by Western blot. Daily administration of SEW2871 also increased capillary density in peri-infarct regions and promoted monocyte/macrophage mobilization to the surface of ischemic cortex at 7 days after pMCAO. CONCLUSIONS: An S1P1-selective agonist enhanced leptomeningeal collateral circulation via eNOS phosphorylation and promoted postischemic angiogenesis with reinforced blood-brain barrier integrity in a mouse model of acute ischemic stroke, leading to smaller infarct volume and better neurological outcome.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Circulação Colateral/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Meninges/irrigação sanguínea , Meninges/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Oxidiazóis/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Tiofenos/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Meninges/metabolismo , Meninges/patologia , Camundongos Endogâmicos BALB C , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Receptores de Lisoesfingolipídeo/metabolismo , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo , Fatores de Tempo
11.
Intern Med ; 57(4): 601-604, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29269644

RESUMO

Myasthenia gravis (MG), a neuromuscular junction autoimmune disease, sometimes complicates second malignancies; however, T-cell lymphoproliferative disorders have rarely been reported. A 55-year-old man, who received oral tacrolimus and prednisolone for MG for 16 years after thymectomy, presented with left abdominal pain, lymphadenopathy, and splenomegaly. A lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is the first report of oral tacrolimus leading to a T-cell lymphoproliferative disorder in patient without a history of transplantation. Physicians should be aware of the possibility of rare T-cell lymphoproliferative disorders, such as PTCL-NOS, occurring as complications in MG patients on immunosuppressive regimens after thymectomy.


Assuntos
Imunossupressores/efeitos adversos , Linfoma de Células T Periférico/induzido quimicamente , Linfoma de Células T Periférico/diagnóstico , Miastenia Gravis/tratamento farmacológico , Tacrolimo/efeitos adversos , Timectomia , Terapia Combinada , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Miastenia Gravis/cirurgia , Tacrolimo/uso terapêutico
12.
Ann Neurol ; 82(5): 841-849, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29083502

RESUMO

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease mostly caused by autoantibodies against acetylcholine receptor associated with thymus abnormalities. Thymectomy has been proven to be an efficacious treatment for patients with MG, but postoperative myasthenic crisis often occurs and is a major complication. We aimed to develop and validate a simple scoring system based on clinical characteristics in the preoperative status to predict the risk of postoperative myasthenic crisis. METHODS: We studied 393 patients with MG who underwent thymectomy at 6 tertiary centers in Japan (275 patients for derivation and 118 for validation). Clinical characteristics, such as gender, age at onset and operation, body mass index, disease duration, MG subtype, severity, symptoms, preoperative therapy, operative data, and laboratory data, were reviewed retrospectively. A multivariate logistic regression with LASSO penalties was used to determine the factors associated with postoperative myasthenic crisis, and a score was assigned. Finally, the predictive score was evaluated using bootstrapping technique in the derivation and validation groups. RESULTS: Multivariate logistic regression identified 3 clinical factors for predicting postoperative myasthenic crisis risk: (1) vital capacity < 80%, (2) disease duration < 3 months, and (3) bulbar symptoms immediately before thymectomy. The postoperative myasthenic crisis predictive score, ranging from 0 to 6 points, had areas under the curve of 0.84 (0.66-0.96) in the derivation group and 0.80 (0.62-0.95) in the validation group. INTERPRETATION: A simple scoring system based on 3 preoperative clinical characteristics can predict the possibility of postoperative myasthenic crisis. Ann Neurol 2017;82:841-849.


Assuntos
Miastenia Gravis/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/cirurgia , Estudos Retrospectivos , Fatores de Risco , Timectomia/efeitos adversos
14.
Igaku Butsuri ; 36(4): 188-196, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28701660

RESUMO

It is essential for quality assurance to verify the safety of each individual patient's plan in radiation therapy. The tolerance level for independent verification of monitor unit calculations for non-IMRT clinical radiotherapy has been shown in the AAPM TG114. Thus, we investigated the precision of independent MU (dose) verification considering a wedge off-axis calculation and we conducted a study at twelve institutes for independent verification with the wedge off-axis calculation. The results obtained with the wedge off-axis calculation showed better agreement with the treatment planning system calculation results than those without the former calculation in a phantom study and in the patient retrospective study. The confidence limits with the wedge off-axis calculation were 2.2±3.4% and 2.0±4.3% for the plans with a physical wedge and a non-physical wedge in the patient study, respectively. However, the confidence limits were over 5% without the off-axis calculation. From our multi-institutional study, the results suggested that the tolerance level for the wedge off-axis plan would be 5% when considering the wedge off-axis calculation and the level was similar to that of the treatment planning system using other conventional irradiation techniques.


Assuntos
Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Imagens de Fantasmas , Software
15.
Igaku Butsuri ; 36(4): 197-206, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28701661

RESUMO

PURPOSE: A multi-institutional study was performed to identify the impact of different independent dose verification programs on independent dose verification software program. METHODS: Data for 1,543 treatment fields were collected in three institutions. RADCALC and Simple MU Analysis (Simple MU) using the Clarkson-based algorithm were used. RADCALC needs the input of radiological path length (RPL) from radiotherapy treatment planning systems (RTPSs) (Eclipse or Pinnacle3). The Simple MU computes the RPL using CT images independently from the RTPSs. Ion-chamber measurements were performed for commissioning the two programs and the RTPSs. Next, the results of the two programs were compared to the RTPSs obtained in the clinically-approved plans in all three institutions. RESULTS: The commissioning results showed ±1.5% variation in the ion-chamber measurements and there was slight difference between the institutions. The RADCALC (0.9±2.2%) and the Simple MU (1.7±2.1%) results showed a slight systematic difference. Pinnacle3 computed longer RPLs because it used CT-physical density tables. Thus, there was an impact on the accuracy in the treatment plans involving bone and other high-density materials. CONCLUSION: Dose calculation algorithms in different dose verification programs provided similar results. However, care must be taken because different RPL calculation methods in the RTPSs may affect dose difference between different independent dose verification programs by 1%.


Assuntos
Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Software , Humanos , Tomografia Computadorizada por Raios X
17.
Phys Med ; 38: 98-104, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28610704

RESUMO

PURPOSE: The aim of the present investigation was to evaluate the dosimetric variation regarding the analytical anisotropic algorithm (AAA) relative to other algorithms in lung stereotactic body radiation therapy (SBRT). We conducted a multi-institutional study involving six institutions using a secondary check program and compared the AAA to the Acuros XB (AXB) in two institutions. METHODS: All lung SBRT plans (128 patients) were generated using the AAA, pencil beam convolution with the Batho (PBC-B) and adaptive convolve (AC). All institutions used the same secondary check program (simple MU analysis [SMU]) implemented by a Clarkson-based dose calculation algorithm. Measurement was performed in a heterogeneous phantom to compare doses using the three different algorithms and the SMU for the measurements. A retrospective analysis was performed to compute the confidence limit (CL; mean±2SD) for the dose deviation between the AAA, PBC, AC and SMU. The variations between the AAA and AXB were evaluated in two institutions, then the CL was acquired. RESULTS: In comparing the measurements, the AAA showed the largest systematic dose error (3%). In calculation comparisons, the CLs of the dose deviation were 8.7±9.9% (AAA), 4.2±3.9% (PBC-B) and 5.7±4.9% (AC). The CLs of the dose deviation between the AXB and the AAA were 1.8±1.5% and -0.1±4.4%, respectively, in the two institutions. CONCLUSIONS: The CL of the AAA showed much larger variation than the other algorithms. Relative to the AXB, larger systematic and random deviations still appeared. Thus, care should be taken in the use of AAA for lung SBRT.


Assuntos
Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Algoritmos , Anisotropia , Humanos , Neoplasias Pulmonares , Imagens de Fantasmas , Estudos Retrospectivos
18.
Radiol Phys Technol ; 10(3): 286-293, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28425084

RESUMO

An add-on micro multi-leaf collimator (mMLC) is used for stereotactic radiosurgery (SRS) and brain stereotactic radiotherapy (SRT), in which rotational radiotherapy may make more complex and time-consuming. We performed a retrospective study of an independent dose calculation verification for brain SRS and SRT in two institutions to show the accuracy of the verification system and propose a tolerance value for the verification. Several comparisons of static plans and patients' plans were conducted using a phantom measurement, and patients' plans using the patients' own computed tomography image. We evaluated the accuracy of the Clarkson-based dose calculation based on either the equivalent square field formed by the mMLC or by the collimator jaws to determine the collimator scatter factor (S c). The results for the static plans showed good agreement (<1%), except when we used a 1 cm2 field size (<4%). The phantom measurements for the patients' plans showed deviations of 0.1 ± 2.3 and 1.2 ± 1.6% (2 SD) for the treatment planning system and the verification system, respectively. The patients' plans showed a deviation of 2.0 ± 2.1% (2 SD). Depending on the mMLC system, the S c was calculated using the equivalent field size formed by the mMLC. In this study, we suggest a tolerance level for the brain SRS and SRT of 2-3.5%. However, beam modeling in the treatment planning system would affect the deviation. The S c should be computed according to the size of the collimator fitted to the MLC.


Assuntos
Encéfalo/efeitos da radiação , Doses de Radiação , Radiocirurgia/métodos , Humanos , Aceleradores de Partículas , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Rotação
19.
J Affect Disord ; 213: 191-198, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28278447

RESUMO

BACKGROUND: Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. METHODS: We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Åsberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei-damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. RESULTS: Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. LIMITATIONS: We did not assess the damage to the ascending projection fibers from the raphe nuclei. CONCLUSIONS: Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.


Assuntos
Infartos do Tronco Encefálico/patologia , Infartos do Tronco Encefálico/psicologia , Transtorno Depressivo/patologia , Núcleos da Rafe/patologia , Idoso , Estudos Transversais , Transtorno Depressivo/diagnóstico , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos
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