Evaluating the Utility of Repeat Computed Tomography Scans in Patients with Isolated Mild Traumatic Subarachnoid Hemorrhage.

BACKGROUND: Traumatic subarachnoid hemorrhage (tSAH) is a common consequence of head trauma. Treatment of patients with tSAH commonly involves serial computed tomography (CT) scans to assess for expansile hemorrhage. However, growing evidence suggests that these patients rarely deteriorate or require neurosurgical intervention. We assessed the utility of repeat CT scans in adult patients with isolated tSAH and an intact initial neurological examination. METHODS: Patients presenting to Mass General Brigham hospitals with tSAH between 2000 and 2021 were eligible for inclusion in this retrospective cohort study. Patients were excluded if subarachnoid hemorrhage was nontraumatic, they experienced another form of intracerebral hemorrhage, or they had a documented Glasgow Coma Scale score of ≤12 and/or poor presenting neurological examination. Univariate and multivariate regression models were used for statistical analysis. RESULTS: Overall, 405 patients were included (191 male). The most common mechanism of trauma was fall from standing (58%). The mean number of total CT scans for all patients was 2.3, with 329 patients (80%) receiving ≥2 scans. In 309 patients, no significant neurological symptoms were present. No patients developed acute neurological deterioration or required neurosurgical intervention related to their bleed, although 5 patients had mild hemorrhagic expansion on follow-up imaging. CONCLUSIONS: In this study, repeat imaging rarely demonstrated meaningful hemorrhagic expansion in this cohort of neurologically intact patients with isolated tSAH. In these patients with mild traumatic brain injury, excessive CT scans are perhaps unlikely to affect patient management and may present unnecessary burden to patients and hospital systems.

Spinal Metastases from Colorectal Cancer at Mass General Brigham: A Twenty-Year Case Series With Literature Review.

OBJECTIVE: We present an institutional case series of patients treated for colorectal carcinoma (CRC) spinal metastases to investigate the outcomes between no treatment, radiation, surgery, and surgery/radiation. METHODS: A retrospective cohort of patients with CRC spinal metastases presenting to affiliated institutions between 2001 and 2021 wereidentified. Information related to patient demographics, treatment modality, treatment outcomes, symptom improvement, and survival was collected by chart review. Overall survival (OS) was compared between treatments by log-rank significance testing. A literature review was conducted to identify other cases series of CRC patients with spinal metastases. RESULTS: Eighty-nine patients (mean age 58.5) with CRC spinal metastases across a mean of 3.3 levels met inclusion criteria: 14 (15.7%) received no treatment, 11 (12.4%) received surgery alone, 37 (41.6%) received radiation alone, and 27 (30.3%) received both radiation and surgery. Patients treated with combination therapy had the longest median OS of 24.7 months (range 0.6-85.9), which did not significantly differ from the median OS of 8.9 months (range 0.2-42.6) observed in patients who received no treatment (P = 0.075). Combination therapy provided objectively longer survival time in comparison to other treatment modalities but failed to reach statistical significance. The majority of patients that received treatment (n = 51/75, 68.0%) experienced some degree of symptomatic or functional improvement. CONCLUSIONS: Therapeutic intervention has the potential to improve the quality of life in patients with CRC spinal metastases. We demonstrate that surgery and radiation are useful options for these patients, despite their lack of objective improvement in OS.

Delirium and Previous Psychiatric History Independently Predict Poststroke Posttraumatic Stress Disorder.

OBJECTIVES: Delirium is an acute brain dysfunction that has been correlated with adverse mental health outcomes, such as depression and posttraumatic stress disorder (PTSD). However, delirium has not been studied in relation to mental health outcomes after cerebrovascular events. This study aimed to examine the incidence of PTSD after nontraumatic intracerebral hemorrhage (ICH) and identify new predictors of poststroke PTSD symptoms. METHODS: Clinical data were collected from 205 patients diagnosed with nontraumatic ICH. Demographics and hospital course data were examined. Univariate and multivariable correlational analyses were performed to determine predictors of PTSD symptoms. PTSD symptoms were assessed using PTSD checklist-civilian version (PCL-C) scores. RESULTS: Diagnostic criteria for a positive PTSD screen (PCL-C score ≥44) were met by 13.7%, 20.2%, and 11.6% of nontraumatic patients with ICH at 3, 6, and 12 months, respectively. On univariate analysis, younger age, female sex, unemployed, and in-hospital delirium were correlated with higher PCL-C scores. In multivariable models, younger age, female sex, unemployed, in-hospital delirium, and a previous anxiety or depression diagnosis were associated with higher PCL-C scores at different follow-up times. Modified Rankin Scale scores were also positively correlated with PCL-C scores at each time point. CONCLUSIONS: Delirium, previous psychiatric history, younger age, female sex, and unemployment status were found to be associated with a greater degree of posthemorrhagic stroke PTSD symptoms. More significant PTSD symptoms were also correlated with greater functional impairment. A better understanding of patient susceptibility to PTSD symptoms may help providers coordinate earlier interventions.

Neural Bypasses: Literature Review and Future Directions in Developing Artificial Neural Connections.

Reported neuro-modulation schemes in the literature are typically classified as closed-loop or open-loop. A novel group of recently developed neuro-modulation devices may be better described as a neural bypass, which attempts to transmit neural data from one location of the nervous system to another. The most common form of neural bypasses in the literature utilize EEG recordings of cortical information paired with functional electrical stimulation for effector muscle output, most commonly for assistive applications and rehabilitation in spinal cord injury or stroke. Other neural bypass locations that have also been described, or may soon be in development, include cortical-spinal bypasses, cortical-cortical bypasses, autonomic bypasses, peripheral-central bypasses, and inter-subject bypasses. The most common recording devices include EEG, ECoG, and microelectrode arrays, while stimulation devices include both invasive and noninvasive electrodes. Several devices are in development to improve the temporal and spatial resolution and biocompatibility for neuronal recording and stimulation. A major barrier to entry includes neuroplasticity and current decoding mechanisms that regularly require retraining. Neural bypasses are a unique class of neuro-modulation. Continued advancement of neural recording and stimulating devices with high spatial and temporal resolution, combined with decoding mechanisms uninhibited by neuroplasticity, can expand the therapeutic capability of neural bypassing. Overall, neural bypasses are a promising modality to improve the treatment of common neurologic disorders, including stroke, spinal cord injury, peripheral nerve injury, brain injury and more.

Transcranial Doppler and computed tomography angiography for detecting cerebral vasospasm post-aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is a life-threatening complication following aneurysmal subarachnoid hemorrhage (aSAH). While digital subtraction angiography (DSA) is the current gold standard for detection, the diagnostic performance of computed tomography angiography (CTA) and transcranial Doppler (TCD) remains controversial. We aimed to summarize the available evidence and provide recommendations for their use based on GRADE criteria. A literature search was conducted for studies comparing CTA or TCD to DSA for adults ≥ 18 years with aSAH for radiographic vasospasm detection. The DerSimonian-Laird random-effects model was used to pool sensitivity and specificity and their 95% confidence intervals (CI) and derive positive and negative pooled likelihood ratios (LR + /LR -). Out of 2070 studies, seven studies (1646 arterial segments) met inclusion criteria and were meta-analyzed. Compared to the gold standard (DSA), CTA had a pooled sensitivity of 82% (95%CI, 68-91%) and a specificity of 97% (95%CI, 93-98%), while TCD had lower sensitivity 38% (95%CI, 19-62%) and specificity of 91% (95%CI, 87-94%). Only the LR + for CTA (27.3) reached clinical significance to rule in diagnosis. LR - for CTA (0.19) and TCD (0.68) approached clinical significance (< 0.1) to rule out diagnosis. CTA showed higher LR + and lower LR - than TCD for diagnosing radiographic vasospasm, thereby achieving a strong recommendation for its use in ruling in or out vasospasm, based on the high quality of evidence. TCDs had very low LR + and a reasonably low LR - , thereby achieving a weak recommendation against its use in ruling in vasospasm and weak recommendation for its use in ruling out vasospasm.

Predicting leptomeningeal disease spread after resection of brain metastases using machine learning.

OBJECTIVE: The incidence of leptomeningeal disease (LMD) has increased as treatments for brain metastases (BMs) have improved and patients with metastatic disease are living longer. Sample sizes of individual studies investigating LMD after surgery for BMs and its risk factors have been limited, ranging from 200 to 400 patients at risk for LMD, which only allows the use of conventional biostatistics. Here, the authors used machine learning techniques to enhance LMD prediction in a cohort of surgically treated BMs. METHODS: A conditional survival forest, a Cox proportional hazards model, an extreme gradient boosting (XGBoost) classifier, an extra trees classifier, and logistic regression were trained. A synthetic minority oversampling technique (SMOTE) was used to train the models and handle the inherent class imbalance. Patients were divided into an 80:20 training and test set. Fivefold cross-validation was used on the training set for hyperparameter optimization. Patients eligible for study inclusion were adults who had consecutively undergone neurosurgical BM treatment, had been admitted to Brigham and Women's Hospital from January 2007 through December 2019, and had a minimum of 1 month of follow-up after neurosurgical treatment. RESULTS: A total of 1054 surgically treated BM patients were included in this analysis. LMD occurred in 168 patients (15.9%) at a median of 7.05 months after BM diagnosis. The discrimination of LMD occurrence was optimal using an XGboost algorithm (area under the curve = 0.83), and the time to LMD was prognosticated evenly by the random forest algorithm and the Cox proportional hazards model (C-index = 0.76). The most important feature for both LMD classification and regression was the BM proximity to the CSF space, followed by a cerebellar BM location. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest risk factors for both LMD occurrence and time to LMD. CONCLUSIONS: The outcomes of LMD patients in the BM population are predictable using SMOTE and machine learning. Lymph node metastasis of the primary tumor at BM diagnosis and a cerebellar BM location were the strongest LMD risk factors.

The low utility of routine cranial imaging after pediatric shunt revision.

OBJECTIVE: Postoperative routine imaging is common after pediatric ventricular shunt revision, but the benefit of scanning in the absence of symptoms is questionable. In this study, the authors aimed to assess how often routine scanning results in a change in clinical management after shunt revision. METHODS: The records of a large, tertiary pediatric hospital were retrospectively reviewed for all consecutive cases of pediatric shunt revision between July 2013 and July 2018. Postoperative imaging was classified as routine (i.e., in the absence of symptoms, complications, or other direct indications) or nonroutine. Reinterventions within 30 days were assessed in these groups. RESULTS: Of 387 included shunt revisions performed in 232 patients, postoperative imaging was performed in 297 (77%), which was routine in 244 (63%) and nonroutine in 53 (14%). Ninety revisions (23%) underwent any shunt-related procedure after postoperative imaging, including shunt reprogramming (n = 35, 9%), shunt tap (n = 10, 3%), and a return to the operating room (OR; n = 58, 15%). Of the 244 cases receiving routine imaging, 241 did not undergo a change in clinical management solely based on routine imaging findings. The remaining 3 cases returned to the OR, accounting for 0.8% (95% CI 0.0%-1.7%) of all cases or 1.2% (95% CI 0.0%-2.6%) of cases that received routine imaging. Furthermore, 27 of 244 patients in this group returned to the OR for other reasons, namely complications (n = 12) or recurrent symptoms (n = 15); all arose after initial routine imaging. CONCLUSIONS: The authors found a low yield to routine imaging after pediatric shunt revision, with only 0.8% of cases undergoing a change in management based on routine imaging findings without corresponding clinical findings. Moreover, routine imaging without abnormal findings was no guarantee of an uneventful postoperative course. Clinical monitoring can be considered as an alternative in asymptomatic, uncomplicated patients.

Classification of glioblastoma versus primary central nervous system lymphoma using convolutional neural networks.

A subset of primary central nervous system lymphomas (PCNSL) are difficult to distinguish from glioblastoma multiforme (GBM) on magnetic resonance imaging (MRI). We developed a convolutional neural network (CNN) to distinguish these tumors on contrast-enhanced T1-weighted images. Preoperative brain tumor MRIs were retrospectively collected among 320 patients with either GBM (n = 160) and PCNSL (n = 160) from two academic institutions. The individual images from these MRIs consisted of a training set (n = 1894 GBM and 1245 PCNSL), a validation set (n = 339 GBM; 202 PCNSL), and a testing set (99 GBM and 108 PCNSL). Three CNNs using the EfficientNetB4 architecture were evaluated. To increase the size of the training set and minimize overfitting, random flips and changes to color were performed on the training set. Our transfer learning approach (with image augmentation and 292 epochs) yielded an AUC of 0.94 (95% CI: 0.91-0.97) for GBM and an AUC of 0.95 (95% CI: 0.92-0.98) for PCNL. In the second case (not augmented and 137 epochs), the images were augmented prior to training. The area under the curve for GBM was 0.92 (95% CI: 0.88-0.96) for GBM and an AUC of 0.94 (95% CI: 0.91-0.97) for PCNSL. For the last case (augmented, Gaussian noise and 238 epochs) the AUC for GBM was 0.93 (95% CI: 0.89-0.96) and an AUC 0.93 (95% CI = 0.89-0.96) for PCNSL. Even with a relatively small dataset, our transfer learning approach demonstrated CNNs may provide accurate diagnostic information to assist radiologists in distinguishing PCNSL and GBM.

Compounded oral ketamine.

The nonnarcotic nonaddictive neuropathic pain reliever ketamine, which was synthesized in the early 1960s by Parke-Davis, was first administered to human patients in 1965. Used by the U. S. military as a field anesthetic during the Vietnam War, it slowly became popular as both an induction and maintenance agent for the general anesthesia required during brief surgical procedures. The use of ketamine in the past has been limited primarily to intravenous administration in hospitalized patients. Very recently, several published reports have described the use of low-dose ketamine for the relief of pain, refractory depression, and anxiety in patients with or without cancer. Because chronic pain, depression, and anxiety often occur in hospice patients with or without cancer and in palliative care patients who are not eligible for hospice, the discovery of new and effective uses for an established drug to treat those conditions has excited interest in the palliative care community. We support that interest with this case report, which describes our experience in treating a 44-year-old male hospice patient with severe constant anxiety, fear, and depression in addition to multiple near-terminal comorbid physical conditions that produce chronic pain. Prior treatments prescribed to resolve this patient's pain, anxiety, and depression had proven ineffective. However, a single low-dose (0.5 mg/kg) subcutaneous test injection of ketamine provided dramatic relief from those symptoms for 80 hours, although the anesthetic effects of that drug are not of long duration. This good outcome has been sustained to date by daily treatment with a compounded flavored oral ketamine solution (40 mg/5 mL) that is not commercially available. Flavoring the solution masks the bitter taste of ketamine and renders the treatment palatable. We found ketamine to be a well-tolerated and effective treatment for the triad of severe anxiety, chronic pain, and severe depression in a hospice patient with multiple comorbid conditions. To our knowledge, this report chronicles the first use of compounded oral ketamine for home-based palliative or hospice care in Louisiana. A formulation for a flavored oral ketamine solution is provided for easy reference.

Update on manging neuropathic pain.

Severe chronic neuropathic pain, which can profoundly and negatively affect quality of life, is usually caused by damage to peripheral nerve tissue from various physical, thermal, or chemical agents and is difficult to relieve. Commonly used opioids are quite effective in relieving nociceptive pain, but nerves that are damaged send pain-sensing fibers into an area of the spinal cord in which there are no mu or kappa receptors to receive opioids or the endogenous endorphins that relieve pain. Clinicians who treat neuropathic pain face daunting therapeutic challenges, but specific analgesic agents have proven effective in relieving that excruciating discomfort. In this article, drugs that target neuropathic pain are discussed, and case reports of patients who have overcome nerve-related pain are presented. Formulations for effective analgesic preparations useful in treating neuropathic pain are included.

Can levorphanol be used like methadone for intractable refractory pain?

BACKGROUND: Levorphanol has been reported to provide analgesia at doses that suggest it does not act like other pure agonist opioids. A dual effect of action on both opioid receptors and n-methyl, d-aspartate (NMDA) receptors has been proposed to be responsible for this effect. METHOD: Case series of patients treated with levorphanol when pain did not respond adequately to other opioids, including methadone. RESULTS: During a 5-year period in a single palliative medicine practice, 20 of 244 patients with chronic nonmalignant pain in a palliative care clinic and 11 of 1508 terminally ill patients enrolled in hospice care whose severe chronic pain was not relieved by treatment with other opioids were treated with oral levorphanol. Of those 31 patients, 16 (52%) reported excellent relief of pain and 7 (22%) reported fair relief for a total response rate of 74%. DISCUSSION: These results suggest that levorphanol has a role in the treatment of pain syndromes that are refractory to other opioids. The pattern of relief seen in this case series is similar to that reported for methadone. Could it be that levorphanol may have a role like methadone for pain that is poorly controlled with other pure agonist opioids? We summarize what is known about levorphanol and provide a table for converting other opioids to levorphanol that was used for this case series.

Levorphanol for excruciating pain from oral cancer: a case report.

In the United States the most common cancers of the head and neck are those of the oral cavity and pharynx. In 2007, oral cancer will be diganosed in more than 37,000 Americans and will claim more than 7,500 lives. The report presented here describes a case of extrarodinary pain in a woman with metastatic adenocarcinoma of the hard palate. At the time of her referral for hospice care, she was experiencing excruciating, unremitting, chronic pain graded 10 of 10 on a standard pain scale. Her analgesic treatment consisted of opioids prescribed in increasingly higher doses until they were ineffective, the effects of treatment could not be tolerated, or she could not swallow the quantity or oral medication needed to provide relief. Only the opioid levorphanol has provided effective analgesia with few adverse effects, and the patient's malignant pain is manageable with far fewer doses of oral medication. Comments from the patient's physician, the pain management specialist who provided the successful conversion between analgesic therapies, the patient's husband, and the compounding pharmacist who used his own funds to pay in advance for treatment are provided. Formulations of compounded levorphanol are also featured, and the patient described in this report kindly discusses the results of her treatment.

Levorphanol for the treatment of severe chronic pain.

The search for an effective and affordable treatment for severe chronic pain, particularly neuropathic pain, has been elusive. The reluctance of many physicians to prescribe strong opioids for pain when other modalities have failed has resulted in the undertreatment of many patients. Levorphanol is 1 of 2 opioids that block N-methyl-D-aspartate receptors. In this article, the mechanism of N-methyl-D-aspartate receptor activation is described, the efficacy of levorphanol in the treatment of severe chronic pain is examined, and the properties and clinical applications of that agent are reviewed. Other N-methyl-D-aspartate receptor antagonists are commented upon, and the outcome of treatment with levorphanol in chronic-pain patients is described in detail.

Biotechnology: impact on biological warfare and biodefense.

Advances in biological research likely will permit development of a new class of advanced biological warfare (ABW) agents engineered to elicit novel effects. In addition, biotechnology will have applications supporting ABW weaponization, dissemination, and delivery. Such new agents and delivery systems would provide a variety of new use options, expanding the BW paradigm. Although ABW agents will not replace threats posed by traditional biological agents such as Bacillus anthracis (anthrax) and Variola (smallpox), they will necessitate novel approaches to counterproliferation, detection, medical countermeasures, and attribution.