Machine Learning to Predict Three Types of Outcomes After Traumatic Brain Injury Using Data at Admission: A Multi-Center Study for Development and Validation.

The difficulty of accurately identifying patients who would benefit from promising treatments makes it challenging to prove the efficacy of novel treatments for traumatic brain injury (TBI). Although machine learning is being increasingly applied to this task, existing binary outcome prediction models are insufficient for the effective stratification of TBI patients. The aim of this study was to develop an accurate 3-class outcome prediction model to enable appropriate patient stratification. To this end, retrospective balanced data of 1200 blunt TBI patients admitted to six Japanese hospitals from January 2018 onwards (200 consecutive cases at each institution) were used for model training and validation. We incorporated 21 predictors obtained in the emergency department, including age, sex, six clinical findings, four laboratory parameters, eight computed tomography findings, and an emergency craniotomy. We developed two machine learning models (XGBoost and dense neural network) and logistic regression models to predict 3-class outcomes based on the Glasgow Outcome Scale-Extended (GOSE) at discharge. The prediction models were developed using a training dataset with n = 1000, and their prediction performances were evaluated over two validation rounds on a validation dataset (n = 80) and a test dataset (n = 120) using the bootstrap method. Of the 1200 patients in aggregate, the median patient age was 71 years, 199 (16.7%) exhibited severe TBI, and emergency craniotomy was performed on 104 patients (8.7%). The median length of stay was 13.0 days. The 3-class outcomes were good recovery/moderate disability for 709 patients (59.1%), severe disability/vegetative state in 416 patients (34.7%), and death in 75 patients (6.2%). XGBoost model performed well with 69.5% sensitivity, 82.5% accuracy, and an area under the receiver operating characteristic curve of 0.901 in the final validation. In terms of the receiver operating characteristic curve analysis, the XGBoost outperformed the neural network-based and logistic regression models slightly. In particular, XGBoost outperformed the logistic regression model significantly in predicting severe disability/vegetative state. Although each model predicted favorable outcomes accurately, they tended to miss the mortality prediction. The proposed machine learning model was demonstrated to be capable of accurate prediction of in-hospital outcomes following TBI, even with the three GOSE-based categories. As a result, it is expected to be more impactful in the development of appropriate patient stratification methods in future TBI studies than conventional binary prognostic models. Further, outcomes were predicted based on only clinical data obtained from the emergency department. However, developing a robust model with consistent performance in diverse scenarios remains challenging, and further efforts are needed to improve generalization performance.

Current Status of Treatment for Acute Large Vessel Occlusion Stroke in Awaji Island Area after the Introduction of Endovascular Treatment.

Objective: We retrospectively analyzed the current status of treatment for anterior circulation large vessel occlusion (LVO) in island areas with a high population aging rate. Methods: We investigated 62 consecutive patients with ischemic stroke due to acute anterior circulation LVO between October 1, 2017 and June 30, 2019. Results: In all, 26 (41.1%) patients underwent endovascular treatment (EVT). The successful recanalization rate of EVT was 88.5% (23/26). There was a significant difference in the age (median, 75.5 years vs. 81 years, respectively, P = 0.0411) and the rate of intravenous tissue plasminogen activator (tPA) therapy (53.5% vs. 11.1%, respectively, P <0.001) between the EVT group and the non-EVT group. Patients in the EVT group achieved a favorable outcome more frequently than those in the non-EVT group (50% vs. 11.1%, respectively, P = 0.0012). In the analysis based on the place of onset among the three cities comprising Awaji Island and the four groups with in-hospital onset, there was no significant difference in the rate of EVT, and the outcome of the in-hospital onset group was poor. Among the EVT group, there was a significant difference in the pre-treatment National Institutes of Health Stroke Scale score (median, 15 vs. 19, respectively, P = 0.0237) and time from onset to recanalization (O2R; median, 240 min vs. 323 min, respectively, P = 0.0128) between the favorable outcome group and the unfavorable outcome group. Conclusion: Even in an island area, it is possible to complete the treatment of ischemic stroke due to LVO within the regional medical area.

[A Case of Multiple Brain Lesions Associated with Hydrophilic Polymer Allergy after Coil Embolization that Showed Repeated Progression and Regression].

A 41-year-old woman underwent coil embolization for subarachnoid hemorrhage associated with a ruptured anterior cerebral artery(A1)aneurysm. Approximately 3 weeks later, MRI revealed right cerebral white matter changes with extensive edema and enhancement lesions. Even though she was asymptomatic, we suspected an allergic reaction to the hydrophilic coating polymer and initiated steroid treatment. After tapering and discontinuing the steroid treatment, follow-up MRI revealed development of white matter lesions;thus, steroid treatment was reinitiated. Progression and regression of the lesions occurred repeatedly, and she was radiologically stable at almost 1 year after coiling. We speculated that these white matter lesions were foreign body granulomas that reacted to the hydrophilic coating of the endovascular device. Overall, an allergic reaction to hydrophilic coating polymer could occur as a delayed complication after coil embolization and that progression and regression of the lesions could repeatedly occur in rare cases.

[A Case of Aplastic or Twig-like Middle Cerebral Artery with a Ruptured Aneurysm at an Anomalous Collateral Artery].

A 69-year-old man presented with sudden loss of consciousness and was admitted to our hospital. Computed tomography revealed diffuse subarachnoid hemorrhage. Digital subtraction angiography revealed occlusion of the left M1 segment, collateral arteries from the left A1 to the left M2 via twig-like networks, and a 6-mm aneurysm in the collateral arteries. Clipping surgery was performed on the 3rd hospital day. Vascular abnormalities of the middle cerebral artery with twig-like networks have been reported with an incidence of 0.11-0.17%. In addition, aneurysms are reported as complications in 40% of cases, suggesting hemodynamic stress and structural vulnerability. (Received January 16, 2018; Accepted June 21, 2018; Published September 1, 2018).

[A Case of Transoral Penetrating Head Injury from a Crossbow-Fired Arrow].

Penetrating head injuries are extremely rare in Japan. The authors describe a case involving a penetrating head injury from an arrow fired from a crossbow. A 52-year-old man who had shot himself transorally in a suicide attempt was admitted to the authors' hospital. On admission, he was conscious and exhibited no neurological deficits. The end of the arrow was visible inside his oral cavity. Computed tomography revealed the arrow had penetrated the right cerebellum and occipital lobe, resulting in a very small hematoma. Digital subtraction angiography revealed no significant vascular injuries. After considering these findings and the nature of the object, the authors decided to remove the arrow from the cranium by pulling it from the patient's oral cavity. To remove the arrow, surgery was performed with several devices, including intraoperative X-ray, endoscopy, and intraoperative angiography. The authors were able to completely remove the arrow, and the patient experienced no new deficits, except mild ataxia and mild dysphasia, and no signs of cerebral infection or cerebrospinal fluid leakage after the surgery. Although most cases of penetrating head injuries require craniotomies, the authors were able to safely remove the foreign object in this case without performing a craniotomy. Because guidelines for the treatment of penetrating head injuries have not been established, the treatment of each case must be modified according to the nature of the foreign object and the findings of preoperative imaging techniques.

[A case of possible immunoglobulin G4-related disease (IgG4-RD) with retroperitoneal fibrosis and central diabetes insipidus due to infundibulohypophysitis].

We report a case of possible immunoglobulin G4-related disease(IgG4-RD)that resulted in complications such as retroperitoneal fibrosis and infundibulohypophysitis. The patient was a 72-year-old male who presented with polyuria and polydipsia. Magnetic resonance imaging(MRI)revealed a thickened pituitary stalk and contrast enhancement with gadolinium. T1-weighted imaging revealed that the posterior pituitary high-signal zone had disappeared. Central diabetes insipidus was diagnosed on the basis of results of the hypertonic saline test. In addition, pressure due to retroperitoneal fibrosis resulted in hydronephrosis and elevated serum IgG4 levels. Because it was determined that the patient could have IgG4-RD, he was administered prednisolone, following which a decrease in the size of the pituitary stalk and retroperitoneal fibrosis was observed. IgG4-RD is characterized by elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into various organs, including the central nervous system. Recently, IgG4-RD research teams organized by the Ministry of Health, Labour and Welfare established guidelines for the diagnosis of IgG4-RD. According to these guidelines, this case would fall under the category of "possible IgG4-RD." This case suggested that when infundibulohypophysitis is detected by neuroradiology, further investigation into the possibility of IgG4-RD should be recommended.

Xanthogranuloma of the sellar region--case report.

A 55-year-old woman presented with a rare xanthogranuloma of the sellar region after complaining of severe headache and visual disturbance 3 months previously. Clinical examination showed she was alert with early signs of bitemporal hemianopsia. Endocrinological examination revealed hypopituitarism. Magnetic resonance imaging showed an intrasellar mass extending into the suprasellar region and compressing the optic chiasma, which appeared homogeneously hyperintense on T(1)-weighted images. Endonasal transsphenoidal resection of the tumor was performed. Histological examination disclosed granulomatous tissue with cholesterol clefts, hemosiderin deposits, fibrous tissues, and macrophages containing rich fat. The histological diagnosis was xanthogranuloma of the sellar region. Her visual symptoms recovered postoperatively although the hypopituitarism remained. Xanthogranuloma of the sellar region is rare, but must be considered in the differential diagnosis of tumors of the sellar region.

Rosette-forming glioneuronal tumor of the fourth ventricle--case report.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare tumor included as a novel glioneuronal neoplasm in the 2007 World Health Organization classification of brain tumors. A 15-year-old female patient presented with RGNT of the fourth ventricle manifesting as headache persisting for one month. Magnetic resonance imaging disclosed a nonenhanced solid mass in the fourth ventricle and vermis. The tumor was gross totally resected. Histological examination revealed biphasic neurocytic and glial architecture. The neurocytic component consisted of uniform neurocytes forming neurocytic rosettes and perivascular pseudorosettes. Only 31 cases of RGNT have been reported. RGNT of the fourth ventricle should be considered in the differential diagnosis of infratentorial lesions in young adults. The prognosis is benign, but relatively aggressive behaviors such as tumor growth, recurrence, and acute deterioration due to intratumoral hemorrhaging can occur. Surgical resection requires care to prevent major surgical morbidities associated with lesions invading the cerebellum or brainstem.

Glioblastoma multiforme associated with klinefelter syndrome.

A 54-year-old man with Klinefelter syndrome presented with glioblastoma multiforme manifesting as a 2-week history of motor weakness of the bilateral extremities. Magnetic resonance imaging showed multiple heterogeneously enhanced tumors in the bilateral frontal lobes. Angiography showed no tumor stain or arteriovenous shunt. The tumor was partially removed through a right craniotomy. The histological diagnosis was glioblastoma. Immunohistochemical examination showed no O(6)-methylguanine-deoxyribonucleic acid methyltransferase protein expression. Postoperative local radiotherapy (60 Gy/30 fractions) combined with temozolomide (75 mg/m(2) x 42 days) and interferon-beta (3,000,000 U, 3 times/week) was performed. The patient's clinical status rapidly deteriorated during chemoradiotherapy, and he died of tumor progression 3.5 months after the surgery. Postmortem examination revealed widespread glioblastoma infiltrating the basal ganglia and thalamus. Klinefelter syndrome is associated with increased cancer predisposition, especially for male breast cancer and germ cell tumors, but glioma is extremely rare. The abnormal genetic constitution of this patient may have been directly responsible for the poor outcome.

Rapid regrowth of an atypical choroid plexus papilloma located in the cerebellopontine angle.

Choroid plexus papilloma usually occurs in the lateral or the fourth ventricle. Primary choroid plexus papilloma of the cerebellopontine angle, as described here, is an uncommon lesion. A 42-year-old man presented with a 1-month history of dysphagia and gait unsteadiness. CT scans and MRI showed a large extra-axial tumor in the right cerebellopontine angle. Pathological study revealed that the lesion was choroid plexus papilloma. Repeat imaging conducted 1 year after the operation showed that the tumor had recurred with distinct cystic features. Pathological examination again revealed increased mitotic activity and supported a diagnosis of atypical choroid plexus papilloma.

Multiple cavernous angiomas of the cauda equina. Case report.

An 18-year-old male presented with multiple cavernous angiomas of the cauda equina manifesting as acute onset of severe low back pain radiating into the bilateral legs. Magnetic resonance imaging revealed a 20 mm by 15 mm nonenhanced, heterogeneous intensity intradural mass at the L-1 level, which had completely obliterated the spinal canal. After laminectomy at T12-L1 and dural incision, a 20 mm dark-bluish, mulberry-like tumor was seen, displacing the cauda equina circumferentially. After total removal of this tumor, four more small tumors were found adhering to different nerve roots, which were not resected. Histological examination revealed cavernous angioma. Although the postoperative course was uneventful, close observation of the residual tumors is required.

Cloning of a protein binding to the most proximal Pit-1 binding element of prolactin gene from human pituitary cDNA library.

A human pituitary cDNA library was screened using a yeast one-hybrid system to find a factor binding Pit-1 binding elements in the PRL gene other than Pit-1. Beside colonies containing Pit-1 or Oct-1 cDNA, three colonies contained mPOU cDNA, a member of the POU protein family. Immunohistochemical analysis showed mPOU-like immunoreactivity was present in human PRL-producing pituitary tumors but not in non-functioning pituitary tumors. Mobility shift analysis revealed that mPOU bound to Pit-1 binding elements of the PRL gene, 1P and 3P. mPOU activated the expression of 0.6 k PRL and 7x1P reporter genes in the presence of Pit-1 and cAMP, although it did not enhance Pit-1-induced expression of 7x3P reporter gene. These findings suggest that mPOU is involved in the activation of the PRL gene by cAMP through 1P in the presence of Pit-1.

Panhypopituitarism induced by cholesterol granuloma in the sellar region--case report.

A 67-year-old man with generalized fatigue and weight loss developed hyponatremia. Endocrinologic examination demonstrated panhypopituitarism. Magnetic resonance imaging showed a pituitary mass extending slightly to the suprasellar region. Transsphenoidal resection of the tumor was performed. Histological examination found exclusively granulomatous tissue with cholesterol clefts, and no epithelial component. This cholesterol granuloma may be classified as xanthogranuloma of the sellar region.

Expression of mPOU protein in the human pituitary adenomas.

OBJECTIVE: mPOU is a POU protein classified as class VI. It is present in the pituitary gland as well as the brain, heart muscle, skeletal muscle, lung, and lymphocytes. In our previous investigation, mPOU bound to the Pit-1-binding DNA elements of the rat PRL gene, and promoted transcription of the GH and PRL genes. In this study, we immunohistologically investigated the expression of mPOU in pituitary adenomas. METHODS: 17 patients with pituitary adenoma underwent tumor excision by transsphenoidal approach at our hospital (PRL: 5, GH: 4, FSH: 1, non-functioning: 7). The expression in the tissue sections was investigated using immunostaining (ABC method). RESULTS: In all GH-producing and PRL-producing adenomas, mPOU protein was specifically expressed, particularly in the nuclei. DISCUSSION: Pit-1 has been considered to be a factor determining the expression of GH and PRL genes, but mPOU may also be involved in the expression.