Clinical narratives as a predictor for prognosticating functional outcomes after intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke type that causes high mortality rates and severe disability among survivors. Many prognostic models are available for prognosticating patients with ICH. This study aimed to investigate whether clinical narratives can improve the performance for predicting functional outcomes after ICH. METHODS: This study used data from the hospital stroke registry and electronic health records. The study population (n = 1363) was randomly divided into a training set (75%, n = 1023) and a holdout test set (25%, n = 340). Five risk scores for ICH were used as baseline prognostic models. Using natural language processing (NLP), text-based markers were generated from the clinical narratives of the training set through machine learning (ML) and deep learning (DL) approaches. The primary outcome was a poor functional outcome (modified Rankin Scale score of 3 to 6) at hospital discharge. The predictive performance was compared between the baseline models and models enhanced by incorporating the text-based markers using the holdout test set. RESULTS: The enhanced prognostic models outperformed the baseline models, regardless of whether ML or DL approaches were used. The areas under the receiver operating characteristic curve (AUCs) of the baseline models were between 0.760 and 0.892. Adding the text-based marker to the baseline models significantly increased the model discrimination, with AUCs ranging from 0.861 to 0.914. The net reclassification improvement and integrated discrimination improvement indices also showed significant improvements. CONCLUSIONS: Using NLP to extract textual information from clinical narratives could improve the predictive performance of all baseline prognostic models for ICH.

Aging-Associated Thyroid Dysfunction Contributes to Oxidative Stress and Worsened Functional Outcomes Following Traumatic Brain Injury.

The incidence of traumatic brain injury (TBI) increases dramatically with advanced age and accumulating evidence indicates that age is one of the important predictors of an unfavorable prognosis after brain trauma. Unfortunately, thus far, evidence-based effective therapeutics for geriatric TBI is limited. By using middle-aged animals, we first confirm that there is an age-related change in TBI susceptibility manifested by increased inflammatory events, neuronal death and impaired functional outcomes in motor and cognitive behaviors. Since thyroid hormones function as endogenous regulators of oxidative stress, we postulate that age-related thyroid dysfunction could be a crucial pathology in the increased TBI severity. By surgically removing the thyroid glands, which recapitulates the age-related increase in TBI-susceptible phenotypes, we provide direct evidence showing that endogenous thyroid hormone-dependent compensatory regulation of antioxidant events modulates individual TBI susceptibility, which is abolished in aged or thyroidectomized individuals. The antioxidant capacity of melatonin is well-known, and we found acute melatonin treatment but not liothyronine (T3) supplementation improved the TBI-susceptible phenotypes of oxidative stress, excitotoxic neuronal loss and promotes functional recovery in the aged individuals with thyroid dysfunction. Our study suggests that monitoring thyroid function and acute administration of melatonin could be feasible therapeutics in the management of geriatric-TBI in clinic.

Brain abscess caused by Parvimonas micra: A rare case report and literature review.

Brain abscesses mostly develop due to direct infection caused by a nearby infectious lesion or hematogenous spread and are rarely caused by an odontogenic infection. We report a 47-year-old woman who presented with high fever, disturbed consciousness, headache, and neck pain. Imaging studies revealed a ring-shaped enhanced mass in the left frontal lobe causing a mass effect and midline shift. Magnetic resonance spectroscopy revealed a peak alanine concentration of 1.5 ppm. Supraorbital keyhole surgery with abscess removal was performed, and a bacterial culture confirmed a diagnosis of Parvimonas micra infection. After undergoing 6-week antibiotic treatment, the patient's symptoms resolved completely. No recurrence of abscess was observed during the follow-up period. Although brain abscess caused by P. micra has rarely been reported, an odontogenic origin should be investigated, especially when a patient has a history of periodontal infection or tooth extraction.

Cryptotanshinone protects against oxidative stress in the paraquat-induced Parkinson's disease model.

Parkinson's disease (PD) is a common neurodegenerative disorder associated with striatal dopaminergic neuronal loss in the Substantia nigra. Oxidative stress plays a significant role in several neurodegenerative diseases. Paraquat (PQ) is considered a potential neurotoxin that affects the brain leading to the death of dopaminergic neurons mimicking the PD phenotype. Various scientific reports have proven that cryptotanshinone possesses antioxidant and anti-inflammatory properties. We hypothesized that cryptotanshinone could extend its neuroprotective activity by exerting antioxidant effects. This study was designed to evaluate the effects of cryptotanshinone in both cellular and animal models of PQ-induced PD. Annexin V-PI double staining and immunoblotting were used to detect apoptosis and oxidative stress proteins, respectively. Reactive oxygen species kits were used to evaluate oxidative stress in cells. For in vivo studies, 18 B6 mice were divided into three groups. The rotarod data revealed the motor function and immunostaining showed the survival of TH+ neurons in SNpc region. Our study showed that cryptotanshinone attenuated paraquat-induced oxidative stress by upregulating anti-oxidant markers in vitro, and restored behavioral deficits and survival of dopaminergic neurons in vivo, demonstrating its therapeutic potential.

Pneumatosis intestinalis after systemic chemotherapy for colorectal cancer: A case report.

BACKGROUND: Pneumatosis intestinalis (PI), also known as intramural gas in the small intestine, is a rare condition encountered by patients with cancer after receiving chemotherapy. CASE SUMMARY: A 78-year-old man with a history of colorectal cancer developed epigastric pain and diarrhea after receiving combination chemotherapy of fluorouracil, leucovorin, irinotecan, and cetuximab. Abdomen radiography revealed intramural air in the small intestinal wall. A computed tomography scan of the abdomen revealed the features of PI with air expanding into the mesentery. After surgery, the patient remained symptom-free throughout a 9 mo follow-up period during which he received chemotherapy of fluorouracil, leucovorin, and irinotecan. CONCLUSION: Although chemotherapy-induced PI is rare among patients with cancer, the differential diagnosis of PI and fulminant complications (such as ischemia, infarction, and perforation of the gastrointestinal tract) should be conducted, in which case an urgent surgical intervention is required.

Advances in Antibody-Based Therapeutics for Cerebral Ischemia.

Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood-brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice.

Cervical myeloradiculopathy as an initial presentation of pseudogout.

Pseudogout, also known as calcium pyrophosphate deposition disease, is an inflammatory arthropathy that primarily occurs in the peripheral joints, such as the knee or elbow. Spinal pseudogout is uncommon, and neck pain is its most common clinical manifestation. However, cervical myeloradiculopathy as an initial presentation of pseudogout attack of the ligamentum flavum has rarely been reported in the literature. We report a case of a 65-year-old woman who presented with neck pain, bilateral finger numbness, and left-sided upper extremity weakness. Magnetic resonance images showed an epidural mass at the C4-5 level, compressing the spinal cord. Following laminectomy with removal of the calcified mass, the profound neurologic deficits gradually recovered. A pathological examination confirmed the diagnosis of cervical pseudogout.

Extrahepatic pseudocyst in an adult.

Ventriculoperitoneal (VP) shunts are commonly used in neurosurgical procedures to treat hydrocephalus. Although shunt-associated abdominal complications are well documented, extrahepatic pseudocysts are a rare shunt complication in adult patients. Therefore, we herein report the case of a 54-year-old male patient who presented with a bulging mass around the previous surgical site at the right upper quadrant of the abdomen. He had a 4-year history of VP shunt surgery for posthemorrhagic hydrocephalus. A computed tomographic scan revealed a large extrahepatic pseudocsyt. Our case represented a rare entity of extrahepatic pseudocyst in adult patients underwent VP shunt surgery. The clinical presentation, diagnostic tools, and treatment methods were discussed.

Acute hemiparesis. A rare presentation of spontaneous spinal epidural hematoma mimicking acute stroke.

Acute hemiparesis is an extremely rare presentation of spontaneous spinal epidural hematoma, which may be misdiagnosed as acute ischemic stroke and improperly treated with an intravenous thrombolytic agent. Here, we report a case of a 54-year-old woman who presented with acute neck pain and right-sided weakness. She was initially suspected of having ischemic stroke and therefore treated with an intravenous thrombolytic agent. However, she developed progressive tetraparesis, and subsequent magnetic resonance images confirmed cervical spontaneous spinal epidural hematoma.

Association between cranial asymmetry severity and chronic subdural hematoma laterality.

OBJECTIVE: To analyze the association between cranial asymmetry severity and chronic subdural hematoma (CSDH) laterality. METHODS: We retrospectively assessed 120 patients with surgically treated unilateral CSDH from January 2009 to December 2018. Preoperative computed tomography images were used to determine occipital vault angles, bilateral cranium areas, and cranial index of symmetry (CIS) ratios. RESULTS: The male sex (70%) was the predominant factor promoting CSDH pathogenesis. In the overall study population (mean age, 71.3 years; left-sided CSDH, 58/120 [48%] patients; right-sided CSDH due to right-sided flat cranium, 38 patients; left-sided CSDH due to right-sided flat cranium, 37 patients). Flat cranial asymmetry was nonsignificantly associated with CSDH laterality (p-value=.689). However, most CSDH patients (86.7% of 120 patients) presented dominant-sided nonoverlapping areas on the left side. Thirteen (81.3%) patients presenting right-dominant nonoverlapping areas had right-sided CSDH, and 55 (52.9%) patients had left-dominant nonoverlapping area had left-sided CSDH (p-value=0.01). The CIS ratio was significantly higher in patients with right-dominant nonoverlapping areas than in those with left-dominant nonoverlapping areas (97.2% vs 95.9%, p-value<0.0001). CONCLUSION: Left-sided hematoma predominance is not associated with a flat cranium and laterality of unilateral CSDH. Moreover, more asymmetric crania with lower CIS ratios may predict left-sided CSDHs, whereas the right-sided CSDHs may be more common in symmetric crania with higher CIS ratios. The CSDH laterality is potentially attributable to cranial asymmetry severity.

The impact of time from injury to surgery in functional recovery of traumatic acute subdural hematoma.

BACKGROUND: The time from injury to surgery (TIS) is critical in the functional recovery of individuals with traumatic acute subdural hematoma (TASDH). However, only few studies have confirmed such notion. METHODS: The data of TASDH patients who were surgically treated in Chia-Yi Christian Hospital between January 2008 and December 2015 were collected. The significance of variables, including age, sex, traumatic mechanism, coma scale, midline shift on brain computed tomography (CT) scan, and TIS, in functional recovery was assessed using the student's t-test, Mann-Whitney U test, chi-square test, univariate and multivariate models, and receiver operating characteristic (ROC) curve. RESULTS: A total of 37 patients achieved functional recovery (outcome scale score of 4 or 5) and 33 patients had poor recovery (outcome scale score of 1-3) after at least 1 year of follow-up. No significant difference was observed in terms of age, sex, coma scale score, traumatic mechanism, or midline shift on brain CT scan between the functional and poor recovery groups. TIS was found to be significantly shorter in the functional recovery group than in the poor recovery group (145.5 ± 27.0 vs. 181.9 ± 54.5 min, P-value = 0.002). TIS was a significant factor for functional outcomes in the univariate and multivariate regression models. The analysis of TIS with the ROC curve between these two groups showed that the threshold time for functional recovery in comatose patients and those with TASDH who were surgically treated was 2 h and 57.5 min. CONCLUSIONS: TIS is an important factor l for the functional recovery of comatose TASDH patients who underwent surgery.

Gastric perforation by a ventriculoperitoneal shunt in an adult.

Ventriculoperitoneal (VP) shunt operation is a common neurosurgical procedure applied for managing intracranial hydrocephalus. Migration of a distal catheter is an uncommon complication, and related gastric perforation is rarely reported. Herein, we report the case of gastric perforation in a patient with VP shunt who presented with fever. The distal catheter within the stomach was confirmed by preoperative computed tomographic scan of abdomen and gastric endoscopy. Surgical intervention and appropriate antibiotics management enabled patient recovery. This case emphasizes the importance of early recognition and surgical intervention in this rare complication related to the shunt procedure.

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials.

Transorbital penetrating brain injury by branchlet: a rare case.

Penetrating injury of the brain and skull is uncommon, representing about 0.4% of head injuries. With advances in radiological techniques such as high-resolution and reconstruction computed tomography (CT), assessment of injuries is more accurate and easier. In this article, we report the case of a 46-year-old man presenting with head injury after a branchlet had penetrated through the right orbit into the brain. CT scan of the brain revealed diffuse subarachnoid hemorrhage, intraventricular hemorrhage, and mild obstructive hydrocephalus. CT scan of the brain with reconstruction revealed that the branchlet tip penetrated through the medial aspect of the right orbit to the parasellar region. CT scan of the brain with contrast showed gradual tapering of the right proximal internal carotid artery with total occlusion after the carotid bulb. Advance radiological examinations, such as three-dimensional CT, are required to obtain the correct emergent diagnosis and treatment of such injuries.

A pitfall in neck pain: occult odontoid fracture.

Type III odontoid fractures of the axis are the second most common injuries of the cervical spine. Most of these result from motor vehicle accidents and falls. Occult odontoid fractures without preceding trauma are rarely reported in the literature and may be difficult to diagnose. We report the case of a healthy patient who had no history of trauma, but sustained sudden pain in the neck and guarding during head movement after sleep. Initial radiographs of the cervical spine including open-mouth, anterior-posterior, and lateral views did not reveal any obvious fractures. Type III odontoid fracture was uneventfully diagnosed via high-quality three-dimensional reconstruction of computed tomography. The possible mechanism was hyperextension of the neck during the change from the supine to the sitting position. Type III odontoid fractures can occur in the absence of major trauma. The usefulness of computed tomography is emphasized and the literature is also reviewed.

Problem of dural tail sign in glioblastoma multiforme?

A dural tail, which is a linear enhancement along the dura mater on contrast T1-weighted resonance images, is considered as a common and useful sign for distinguishing meningioma from other intracranial lesions. However, the specific nature of dura tail signs is still controversial. To the best of our knowledge, only seven cases of glioblastoma multiforme have been described with dural tail signs. Here, we report a case of glioblastoma multiforme with a dural tail sign and cerebrospinal fluid cleft sign and review the relevant literature.

Delayed traumatic thoracic spinal epidural hematoma: a case report and literature review.

Spinal epidural hematoma is a relatively uncommon disease, but an important cause leading to cord compression. Posttraumatic spinal epidural hematoma is a rare entity and remains a challenge for clinical physicians. Magnetic resonance imaging is the best choice for early diagnosis, and urgent surgical decompression with evacuation of hematoma could improve some neurologic deficits, especially vital cord functions. We presented a 77-year-old woman who sustained back pain after a fall 1 month before admission, complaining of progressive weakness and sensory loss in bilateral lower extremities since 2 weeks before admission. Radiography of the thoracic spine revealed decreased body height at T10 and compression fracture. Magnetic resonance imaging of the thoracic spine revealed epidural hematomas at the level of T11 to T12. An urgent decompressive laminectomy with evacuation of hematoma was performed immediately. Postoperatively, her previous neurologic deficits improved except for an underactive neurogenic bladder and fecal incontinence.