High-salt diet induces microbiome dysregulation, neuroinflammation and anxiety in the chronic period after mild repetitive closed head injury in adolescent mice.

The associations between human concussions and subsequent sequelae of chronic neuropsychiatric and cardiovascular diseases such as hypertension have been reported; however, little is known about the underlying biological processes. We hypothesized that dietary changes, including a high-salt diet, disrupt the bidirectional gut-brain axis, resulting in worsening neuroinflammation and emergence of cardiovascular and behavioural phenotypes in the chronic period after repetitive closed head injury in adolescent mice. Adolescent mice were subjected to three daily closed head injuries, recovered for 12 weeks and then maintained on a high-salt diet or a normal diet for an additional 12 weeks. Experimental endpoints were haemodynamics, behaviour, microglial gene expression (bulk RNA sequencing), brain inflammation (brain tissue quantitative PCR) and microbiome diversity (16S RNA sequencing). High-salt diet did not affect systemic blood pressure or heart rate in sham or injured mice. High-salt diet increased anxiety-like behaviour in injured mice compared to sham mice fed with high-salt diet and injured mice fed with normal diet. Increased anxiety in injured mice that received a high-salt diet was associated with microgliosis and a proinflammatory microglial transcriptomic signature, including upregulation in interferon-gamma, interferon-beta and oxidative stress-related pathways. Accordingly, we found upregulation of tumour necrosis factor-alpha and interferon-gamma mRNA in the brain tissue of high salt diet-fed injured mice. High-salt diet had a larger effect on the gut microbiome composition than repetitive closed head injury. Increases in gut microbes in the families Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae were positively correlated with anxiety-like behaviours. In contrast, Muribaculaceae, Acholeplasmataceae and Lactobacillaceae were negatively correlated with anxiety in injured mice that received a high-salt diet, a time-dependent effect. The findings suggest that high-salt diet, administered after a recovery period, may affect neurologic outcomes following mild repetitive head injury, including the development of anxiety. This effect was linked to microbiome dysregulation and an exacerbation of microglial inflammation, which may be physiological targets to prevent behavioural sequelae in the chronic period after mild repetitive head injury. The data suggest an important contribution of diet in determining long-term outcomes after mild repetitive head injury.

Traumatic Spinal Cord Injury.

OBJECTIVE: This article provides a review of the initial clinical and radiologic evaluation and treatment of patients with traumatic spinal cord injuries. It specifically highlights essential knowledge for neurologists who encounter patients with these complex injuries. LATEST DEVELOPMENTS: There has been improvement in the care of patients with traumatic spinal cord injuries, particularly in the prehospital evaluation, approach for immediate immobilization, standardized spinal clearance, efficient triage, and transportation of appropriate patients to traumatic spinal cord injury specialized centers. Advancements in spinal instrumentation have improved the surgical management of spinal fractures and the ability to manage patients with spinal mechanical instability. The clinical evidence favors performing early surgical decompression and spine stabilization within 24 hours of traumatic spinal cord injuries, regardless of the severity or location of the injury. There is no evidence that supports the use of neuroprotective treatments to improve outcomes in patients with traumatic spinal cord injuries. The administration of high-dose methylprednisolone, which is associated with significant systemic adverse effects, is strongly discouraged. Early and delayed mortality rates continue to be high in patients with traumatic spinal cord injuries, and survivors often confront substantial long-term physical and functional impairments. Whereas the exploration of neuroregenerative approaches, such as stem cell transplantation, is underway, these methods remain largely investigational. Further research is still necessary to advance the functional recovery of patients with traumatic spinal cord injuries. ESSENTIAL POINTS: Traumatic spinal cord injury is a complex and devastating condition that leads to long-term neurologic deficits with profound physical, social, and vocational implications, resulting in a diminished quality of life, particularly for severely affected patients. The initial management of traumatic spinal cord injuries demands comprehensive interdisciplinary care to address the potentially catastrophic multisystem effects. Ongoing endeavors are focused on optimizing and customizing initial management approaches and developing effective therapies for neuroprotection and neuroregeneration to enhance long-term functional recovery.

Neuroendovascular Surgery Applications in Craniocervical Trauma.

Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions.

Rash, Facial Droop, and Multifocal Intracranial Stenosis Due to Varicella Zoster Virus Vasculitis.

Background: This is a case of multifocal intracranial stenosis in a 74 year old male ultimately discovered to be due to Varicella Zoster Virus infection. Purpose: We highlight the importance of a broad differential diagnosis, even when the most likely etiology of intracranial stenosis is atherosclerosis. Our paper reviews the differential diagnosis as well as "red flags" for intracranial vasculopathy. Even though intracranial atherosclerotic disease is the most common cause of vasculopathy, infectious or inflammatory vasculitis should be considered on the differential. Conclusions: Before considering bypass surgery or other invasive neurosurgical procedures, ensure reversible causes of vasculopathy have been ruled out. The presence of cranial neuropathies, rash, and/or elevated inflammatory markers should be red flags for vasculitis in patients presenting with stroke.

Surgical Management in Herpes Simplex Encephalitis: Illustrative Case Report and Systematic Review of the Literature.

BACKGROUND: Herpes simplex virus (HSV) is a common cause of viral encephalitis and can result in refractory seizures. Although HSV encephalitis (HSVE) is treated primarily with acyclovir, surgery can play a role in medically intractable cases. OBJECTIVE: To systematically review cases describing surgery for the treatment of severe HSVE. We also present an illustrative case of anterior temporal lobectomy (ATL) for refractory status epilepticus in a patient with unilateral HSVE. This case demonstrates one clinical context in which surgery can be a useful adjunct. METHODS: We performed a systematic review using PubMed and Google Scholar, including case reports and series describing surgical interventions for HSVE. Clinical data were extracted from 54 publications that incorporated 67 patient cases. RESULTS: Surgical decompression occurred at a wide range of times after the onset of illness, although most patients were operated on 4 or more days after HSVE symptoms began. Numerous reports indicated that decompressive craniectomy, temporal lobectomy, and hematoma removal could treat intractably elevated intracranial pressure because of HSVE with favorable long-term outcomes. We describe an additional case in which a 52-year-old woman with HSVE developed refractory right temporal lobe seizures. After ATL, the seizures resolved with significant clinical improvement. CONCLUSION: Surgical treatment can be a useful adjunct for treatment of HSVE. There is substantial variability in the timing of surgical decompression in patients with HSVE, which can be necessary up to approximately 3 weeks after illness onset. ATL should be considered for refractory status epilepticus in HSVE with a unilateral seizure focus.

Disparities in Decompressive Cranial Surgery Utilization in Severe Traumatic Brain Injury Patients without a Primary Extra-Axial Hematoma: A U.S. Nationwide Study.

OBJECTIVE: Decompressive craniectomy is recommended to reduce mortality in severe traumatic brain injury (TBI). Disparities exist in TBI treatment outcomes; however, data on disparities pertaining to decompressive craniectomy utilization is lacking. We investigated these disparities, focusing on race, insurance, sex, and age. METHODS: Hospitalizations (2004-2014) were retrospectively extracted from the Nationwide Inpatient Sample. The criteria included are as follows: age ≥18 years and indicators of severe TBI diagnosis. Poor outcomes were defined as discharge to institutional care and death. Multivariable logistic regression models were used to assess the effects of race, insurance, age, and sex, on craniectomy utilization and outcomes. RESULTS: Of 349,164 hospitalized patients, 6.8% (n = 23,743) underwent craniectomy. White (odds ratio [OR] = 0.50, 95% confidence interval [CI] = 0.44-0.57; P < 0.001) and Black (OR = 0.45, 95% CI = 0.32-0.64; P = 0.003) Medicare beneficiaries were less likely to undergo craniectomy. Medicare (P < 0.0001) and Medicaid beneficiaries (P < 0.0001) of all race categories had poorer outcomes than privately insured White patients. Black (OR = 1.2, 95% CI = 1.08-2.34; P = 0.001) patients with private insurance and Black (OR = 1.39, 95% CI = 1.22-1.58; P < 0.0001) Medicaid beneficiaries had poorer outcomes than privately insured White patients (P < 0.0001). Older patients (OR = 0.74, 95%, CI = 0.71-0.76; P < 0.001) were less likely to undergo craniectomy and were more likely to have poorer outcomes. Females (OR = 0.82, 95% CI = 0.76-0.88; P < 0.001) were less likely to undergo craniectomy. CONCLUSIONS: There are disparities in race, insurance status, sex, and age in craniectomy utilization and outcome. This data highlights the necessity to appropriately address these disparities, especially race and sex, and actively incorporate these factors in clinical trial design and enrollment.

Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study.

BACKGROUND: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. METHODS: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. RESULTS: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. CONCLUSIONS: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.

Extra-Axial Fluid Collections After Decompressive Craniectomy: Management, Outcomes, and Treatment Algorithm.

BACKGROUND: Extra-axial fluid collections (EACs) frequently develop after decompressive craniectomy. Management of EACs remains poorly understood, and information on how to predict their clinical course is inadequate. We aimed to better characterize EACs, understand predictors of their resolution, and delineate the best treatment paradigm for patients. METHODS: We reviewed patients who developed EACs after undergoing decompressive craniectomy for treatment of refractory intracranial pressure elevations. We excluded patients who had an ischemic stroke, as EACs in these patients have a different clinical course. We performed univariate analysis and multiple linear regression to find variables associated with earlier resolution of EACs and stratified our analyses by EAC phenotype (complicated vs. uncomplicated). We conducted a systematic review to compare our findings with the literature. RESULTS: Of 96 included patients, 73% were male, and median age was 42.5 years. EACs resolved after a median of 60 days. Complicated EACs were common (62.5%) and required multiple drainage methods before cranioplasty. These were not associated with a protracted course or increased risk of death (P > 0.05). Early bone flap restoration with simultaneous drainage was independently associated with earlier resolution of EACs (ß = 0.56, P < 0.001). Systematic review confirmed lack of standardized direction with respect to EAC management. CONCLUSIONS: Our analyses reveal 2 clinically relevant phenotypes of EAC: complicated and uncomplicated. Our proposed treatment algorithm involves replacing the bone flap as soon as it is safe to do so and draining refractory EACs aggressively. Further studies to assess long-term clinical outcomes of EACs are warranted.

Endovascular treatment of a ruptured posterior fossa pure arterial malformation: illustrative case.

BACKGROUND: Pure arterial malformations (PAMs) are rare vascular anomalies that are commonly mistaken for other vascular malformations. Because of their purported benign natural history, PAMs are often conservatively managed. The authors report the case of a ruptured PAM leading to subarachnoid hemorrhage (SAH) with intraventricular extension that was treated endovascularly. OBSERVATIONS: A 38-year-old man presented with a 1-day history of headaches and nausea. A computed tomography scan demonstrated diffuse SAH with intraventricular extension, and angiography revealed a right posterior inferior cerebellar artery-associated PAM. The PAM was treated with endovascular Onyx embolization. LESSONS: To the authors' knowledge, only 2 other cases of SAH associated with PAM have been reported. In those 2 cases, surgical clipping was pursued for definitive treatment. Here, the authors report the first case of a ruptured PAM treated using an endovascular approach, showing its feasibility as a treatment option particularly in patients in whom open surgery is too high a risk.

Spontaneous hemorrhage after external ventricular drain placement in the setting of low factor VII secondary to liver cirrhosis.

BACKGROUND: Alterations in normal coagulation and hemostasis are critical issues that require special attention in the neurosurgical patient. These disorders pose unique challenges in the management of these patients who often have concurrent acute ischemic and hemorrhagic injuries. Although neurosurgical intervention in such cases may be unavoidable and potentially life-saving, these patients should be closely observed after instrumentation. CASE DESCRIPTION: A 57-year-old male with liver cirrhosis secondary to amyloid light-chain amyloidosis was admitted to the intensive care unit for the management of delayed hydrocephalus. An external ventricular drain (EVD) was placed for the treatment and monitoring of hydrocephalus. Five days after EVD placement, a head computed tomography scan revealed a tract hemorrhage. However, on repeated imaging, the size of the hemorrhage continued to increase despite aggressive blood pressure control and several doses of phytonadione. Extensive coagulopathy workup was remarkable for low factor VII levels. In that setting, recombinant activated factor VII was administered to normalize factor VII levels, and the tract hemorrhage stabilized. CONCLUSION: To the best of our knowledge, this is the first case of spontaneous hemorrhage after EVD placement in the setting of liver cirrhosis-associated factor VII deficiency. Our case highlights the importance of identifying coagulation disorders in neurosurgical patients at high risk for coagulopathy and closely monitoring them postoperatively.

Neurological toxicities associated with chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor T cell therapy has become an important tool in the treatment of relapsed and refractory malignancy; however, it is associated with significant neurological toxicity. We characterized the neurological toxicity associated with chimeric antigen receptor T-cell therapy in a consecutive series of 100 patients up to 2 months post transfusion, 28 of whom were obtained from chart review and the others by prospective observation. The underlying neoplasms were lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 64.5 years old and 39% of patients were female. The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%). Focal neurological deficits are frequently observed after chimeric antigen receptor T-cell therapy and are associated with regional EEG abnormalities, FDG-PET hypometabolism, and elevated velocities on transcranial Doppler ultrasound. In contrast, structural imaging was typically normal. As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population.

Clinical Problem-Solving: Lethargy and Fever in an Immunocompromised Patient.

We present the case of a 63-year-old woman with a glioblastoma multiforme on immunosuppressive steroid doses who developed lethargy and fever. We review the differential diagnosis and emphasize the importance of reframing the case when the clinical course differs from expectation. Once the diagnosis is evident, we discuss the incidence and clinical course in different patient populations.

Anterior Temporal Lobectomy for Refractory Status Epilepticus in Herpes Simplex Encephalitis.

BACKGROUND: Herpes simplex virus (HSV) is a common cause of viral encephalitis that can lead to refractory seizures. The primary treatment of HSV encephalitis is with acyclovir; however, surgery sometimes plays a role in obtaining tissue diagnosis or decompression in cases with severe mass effect. We report a unique case in which anterior temporal lobectomy was successfully used to treat refractory status epilepticus in HSV encephalitis. METHODS: Case report and review of the literature. RESULTS: We report a case of a 60-year-old man with HSV encephalitis, who presented with seizures originating from the right temporal lobe refractory to maximal medical management. Right anterior temporal lobectomy was performed for the purpose of treatment of refractory status epilepticus and obtaining tissue diagnosis, with ultimate resolution of seizures and excellent functional outcome. CONCLUSIONS: We suggest that anterior temporal lobectomy should be considered in cases of HSV encephalitis with refractory status epilepticus with clear unilateral origin.

Drug-induced thrombocytopenia secondary to natalizumab treatment.

A 52-year-old woman with a 10-year history of relapsing-remitting multiple sclerosis (RRMS) was started on natalizumab after she developed side effects for interferon ß-1a and glatiramer acetate. The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura. Laboratory testing revealed progressive worsening thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet antibodies to platelet-specific antigen as well as antibodies against natalizumab were positive. Bone marrow biopsy was negative. The patient was diagnosed with drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side effect which was treated with intravenous methylprednisolone followed by rituximab with successful resolution of thrombocytopenia. The patient had a stable course of RRMS with no relapses and no brain MRI changes at 2 years after initiation of rituximab.