Pearls & Oy-sters: Status Epilepticus and Cerebral Edema From Hyperammonemia Due to Disseminated Ureaplasma and Mycoplasma Species.

Nonhepatic hyperammonemia syndrome is a rare cause of neurologic dysfunction and cerebral edema and has most commonly been reported in posttransplant patients. Only recently has opportunistic infection with Ureaplasma species and Mycoplasma hominis been found to be key to the pathogenesis. We describe the cases of 3 immunosuppressed patients who developed hyperammonemia syndrome with new-onset refractory status epilepticus and diffuse cerebral edema. PCR was positive for M hominis in 1 patient and Ureaplasma parvum in the other 2. Despite early diagnostic suspicion and aggressive management with empirical antibiotics, seizure control, hypertonic saline, and ammonia elimination, none of our patients survived this life-threatening infection. Nonhepatic hyperammonemia and new-onset seizures can be presenting features of disseminated Ureaplasma species and M hominis infections in posttransplant patients. Immunosuppression in the absence of organ transplantation is likely sufficient to trigger this entity, as was the case in our third patient. When suspected, empiric combination antibiotics should be used due to high likelihood of resistance. The diagnostic test of choice is PCR. Patients with hyperammonemia syndrome associated with these infections typically have a poor prognosis. Early recognition and aggressive multimodal interventions may be key to ameliorating the high mortality and severe neurologic sequelae from this entity.

Intrathecal Methotrexate Toxicity Resulting in Brain Death due to Generalized Cerebral Edema Case Report.

Intrathecal methotrexate (IT MTX) resulting in severe adverse events including life-threatening cerebral edema is not well described. We report a rare case of death in a 37-year-old BRCA1+ woman with metastatic triple-negative breast cancer status post mastectomy following administration of IT MTX for leptomeningeal carcinomatosis. Within the 24 hours after intraoperative IT MTX delivery, she developed neurologically devastating diffuse cerebral edema leading to uncal and cerebellar tonsillar herniation. This case report highlights a rare but devastating side effect of IT MTX.

IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury.

Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 is upregulated in mechanical ventilation-induced lung injury (VILI) and may contribute to delirium, it is not known whether the inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model, VILI was simulated in anesthetized adult mice using a 35 cc/kg tidal volume mechanical ventilation model. There were two control groups, as follow: 1) spontaneously breathing or 2) anesthetized and mechanically ventilated with 10 cc/kg tidal volume to distinguish effects of anesthesia from VILI. Two hours before inducing VILI, mice were treated with either anti-IL-6 antibody, anti-IL-6 receptor antibody, or saline. Neuronal injury, stress, and inflammation were assessed using immunohistochemistry. CC3 (cleaved caspase-3), a neuronal apoptosis marker, was significantly increased in the frontal (P < 0.001) and hippocampal (P < 0.0001) brain regions and accompanied by significant increases in c-Fos and heat shock protein-90 in the frontal cortices of VILI mice compared with control mice (P < 0.001). These findings were not related to cerebral hypoxia, and there was no evidence of irreversible neuronal death. Frontal and hippocampal neuronal CC3 were significantly reduced with anti-IL-6 antibody (P < 0.01 and P < 0.0001, respectively) and anti-IL-6 receptor antibody (P < 0.05 and P < 0.0001, respectively) compared with saline VILI mice. In summary, VILI induces potentially reversible neuronal injury and inflammation in the frontal cortex and hippocampus, which is mitigated with systemic IL-6 inhibition. These data suggest a potentially novel neuroprotective role of systemic IL-6 inhibition that justifies further investigation.

Self-perceptions on cognitive versus motor disability among neurologists.

OBJECTIVE: The modified Rankin Scale is a functional outcome measure that disproportionately represents motor deficits. We hypothesize that among physicians who most commonly use the modified Rankin Scale to counsel patients on neurological treatment options, personal perception of acceptable or optimal outcome may be discordant with those described in clinical trials. METHODS: A three-question anonymous voluntary survey was emailed to academic and community practicing neurologists and board-eligible or board-certified neurology fellows inquiring about their personal perception of a better quality of life between two choices featuring clinical scenarios that would qualify as modified Rankin Scale 2 and 4 disability outcome scores. RESULTS: Sixty-nine percent of participants were 30-45 years old, 24% were 45-60 years old, and 7% were over 60 years old. Most responders were general neurologists (31.3%). The remaining responders represented multiple subspecialties including neurocritical care, vascular neurology, neurohospitalist medicine, neuromuscular neurology, neurophysiology, child neurology, neuro-oncology, headache, neuroimmunology, movement disorders, and palliative care medicine. Forty-four of 45 neurologists (97.7%) stated they would choose needing a wheelchair if still able to function at their cognitive baseline at work (p < 0.000001). One responder preferred to get around without assistance, despite new cognitive symptoms that would preclude them from working as a physician. CONCLUSIONS: The modified Rankin Scale may not adequately represent preferred outcomes among neurology specialists, particularly with respect to cognitive symptoms. Future studies are needed to characterize long-term cognitive outcomes in patients with acute stroke-related conditions.

Intracerebral Hemorrhage in Women: A Review with Special Attention to Pregnancy and the Post-Partum Period.

Non-traumatic intracranial hemorrhage includes subarachnoid hemorrhage, subdural hemorrhage, and intracerebral hemorrhage (ICH), which can be classified as primary or secondary. Primary ICH is due to arterial hypertension or cerebral amyloid angiopathy, and secondary ICH is due to cerebral vascular malformations, coagulopathies, infectious complications, brain tumors, and illicit stimulant drug use. This review explores the epidemiology and management of non-traumatic ICH in women, with a focus on pregnancy and the post-partum period, defined as 6 weeks post-delivery.

Differential effects of hypothermia on neurovascular unit determine protective or toxic results: Toward optimized therapeutic hypothermia.

Therapeutic hypothermia (TH) benefits survivors of cardiac arrest and neonatal hypoxic-ischemic injury and may benefit stroke patients. Large TH clinical trials, however, have shown mixed results. Given the substantial pre-clinical literature supporting TH, we explored possible mechanisms for clinical trial variability. Using a standard rodent stroke model (n = 20 per group), we found smaller infarctions after 2 h pre- or post-reperfusion TH compared to 4 h. To explore the mechanism of this discrepancy, we used primary cell cultures of rodent neurons, astrocytes, or endothelial cells subjected to oxygen-glucose deprivation (OGD). Then, cells were randomly assigned to 33℃, 35℃ or 37℃ for varying durations after varying delay times. Both 33 and 35℃ TH effectively preserved all cell types, although 33℃ was superior. Longer cooling durations overcame moderate delays to cooling initiation. In contrast, TH interfered with astrocyte paracrine protection of neurons in a temperature-dependent manner. These findings suggest that longer TH is needed to overcome delays to TH onset, but shorter TH durations may be superior to longer, perhaps due to suppression of astrocytic paracrine support of neurons during injury. We propose a scheme for optimizing TH after cerebral injury to stimulate further studies of cardiac arrest and stroke.

Visualizing wall enhancement over time in unruptured intracranial aneurysms using 3D vessel wall imaging.

BACKGROUND: Few studies directed at assessing the visualization of the walls of unruptured aneurysms have used higher-resolution 3D MRI vessel wall imaging. Prospective longitudinal studies are also needed to screen vessel wall changes in unruptured aneurysms. PURPOSE: To compare the aneurysm wall visualization on pre- and post-3D isotropic T1 -weighted Sampling Perfection with Application-optimized Contrasts by using different flip angle Evolutions (SPACE) images and to explore whether there is a change in wall enhancement at follow up. STUDY TYPE: Prospective. POPULATION: Twenty-nine patients with a total of 35 unruptured intracranial aneurysms. SEQUENCE: 3D T1 -weighted pre- and postcontrast SPACE (0.5 mm isotropic) at 3.0T. ASSESSMENT: The aneurysm wall visibility (0-5 scale) between pre- and postcontrast images as well as the wall enhancement (0-5 scale) between follow-up and baseline studies (6-30 months, average 12.7 months) were compared. Differences in wall visibility and enhancement were also investigated as a function of aneurysm diameter and location. STATISTICAL TEST: The Wilcoxon signed rank paired test was used to compare the wall visibility score between pre- and postcontrast SPACE images, as well as wall enhancement between follow-up and baseline. The Mann-Whitney and Kruskal-Wallis tests were used to investigate the enhancement difference between different diameters and locations. RESULTS: Postcontrast images had significantly higher wall visibility (P = 0.01). A wall enhancement score ≥2 was found in 71% of the aneurysms. Changes in levels of wall enhancement were found in 17% of the aneurysms at follow-up studies, but those changes were small. Wall visibility and enhancement scores of large aneurysms were significantly higher than small ones (P < 0.001). DATA CONCLUSION: 3D T1 -weighted higher resolution SPACE can be used to assess changes in enhancement at follow-up studies. Contrast SPACE image provides better aneurysm wall visibility and improves visualization of the aneurysm wall. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:193-200.

A Simple Infection Control Protocol Durably Reduces External Ventricular Drain Infections to Near-Zero Levels.

OBJECTIVE: External ventricular drains (EVDs) historically have a high rate of infection, and EVD infections are a cause of significant morbidity and mortality. We have shown previously that a simple infection control protocol reduced the rate of EVD infections during a 3-year period, and the present study examines whether infection rates were durably reduced over an additional 4 years. METHODS: Retrospective analysis of EVDs placed in the intensive care unit of a tertiary neurosurgical center over an additional 4 year follow-up period. RESULTS: In the 4-year follow-up period, 189 EVDs were placed in 173 patients. The previously observed decrease in cerebrospinal fluid culture positivity from 9.8% in the baseline period to 0.8% in the first 3 years of the protocol period continued in the 4-year follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P < 0.001 compared with baseline). The previously observed decrease in the rate of ventriculitis from 6.3% to 0.8% also continued in the follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P < 0.001 compared with baseline). Over the total 7 years of protocol use, the rate of culture positivity was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days) and the rate of ventriculitis was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days). The only observed infection over 7 years occurred in a patient who removed their own EVD. CONCLUSIONS: A straightforward EVD infection control protocol substantially and durably reduces EVD infections to a near-zero rate.

Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine.

Although traditional hallucinogenic drugs such as marijuana and lysergic acid diethylamide (LSD) are not typically associated with seizures, newer synthetic hallucinogenic drugs can provoke seizures. Here, we report the unexpected consequences of taking a street-bought hallucinogenic drug thought to be LSD. Our patient presented with hallucinations and agitation progressing to status epilepticus with a urine toxicology screen positive only for cannabinoids and opioids. Using liquid chromatography high-resolution mass spectrometry, an additional drug was found: an amphetamine-derived phenylethylamine called 2,5-dimethoxy-4-chloroamphetamine. We bring this to the attention of the neurologic community as there are a growing number of hallucinogenic street drugs that are negative on standard urine toxicology and cause effects that are unexpected for both the patient and the neurologist, including seizures.

CNS intravascular large cell lymphoma in a patient with autoimmune hemolytic anemia.

Intravascular large cell lymphoma (IVLCL) is a rare disease characterized by proliferation of malignant lymphocytes within the small blood vessel lumens. The association of IVLCL with autoimmune hemolytic anemia (AIHA) has been described in a single case report, but the true prevalence of this co-occurrence is not known because of declining autopsy rates. Here, we report a case of a 41-year-old woman who carried a diagnosis of AIHA for 2 years, with repeated hemolytic episodes that were initially well controlled with immunomodulatory treatment. At her last presentation, the patient developed rapidly progressive neurologic symptoms and leukoencephalopathy on MRI; she died 4 weeks later with a clinical impression of thrombotic microangiopathy, a known complication of AIHA. At autopsy, the brain showed widespread platelet thrombi and intraparenchymal hemorrhages characteristic of this disorder. In addition, there was evidence of a clinically unsuspected IVLCL, most likely of B-cell lineage. This case illustrates a potential association between IVLCL and AIHA, highlights the need for broad differential diagnosis in cases with atypical disease presentation or progression, and underlines the importance of autopsy in establishing the full cause of morbidity and mortality.

Utility of MRI in spinal arteriovenous fistula.

OBJECTIVE AND BACKGROUND: Spinal arteriovenous fistula (SAVF) is a rare but treatable cause of myelopathy. The diagnostic accuracy of MRI for detecting SAVF is unknown. Our objective was to determine the sensitivity and specificity of MRI in the diagnosis SAVF and characterize its radiographic features. METHODS: We conducted a retrospective case-control study of all SAVF treated at our institution from 1995 to 2010, including patients who presented with myelopathy, had MRIs available for review, and underwent either spinal angiogram or had another diagnosis confirming test. Two blinded board-certified radiologists reviewed a series of MRIs and listed the most likely diagnoses, radiologic findings, and recommended follow-up. Sensitivities and specificities of MRI compared to spinal angiogram were calculated. We additionally conducted a literature review of cases describing MRI findings in spinal dural and perimedullary arteriovenous fistula. RESULTS: We identified 36 cases of SAVF (median age 56, 67% male) and 32 controls (median age 54, 44% male). MRI was sensitive in identifying SAVF as the primary diagnosis in 94% (radiologist A, 95% confidence interval [CI] 0.87-1.02) and 89% (radiologist B, 95% CI 0.79-0.99) of cases. The sensitivity of spinal cord T2 hyperintensity or flow voids was 100% and the specificity of T2 hyperintensity and flow voids was 97%. CONCLUSIONS: Among patients with myelopathy, spinal angiography is mandatory in the presence of both T2 hyperintensity and flow voids but may be unnecessary if both of these findings are absent.

Organ donation after cardiac death in amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis (ALS) are often told that solid organ donation is not possible following death, although the reasons for exclusion are not evidence based. Because ALS patients typically remain sentient until death, organs may be procured under donation after cardiac death protocols. Anticipating this need, our institution created a process for organ donation in ventilator-dependent ALS patients that was subsequently implemented. To our knowledge, this is the first report of organ donation in a patient with rapidly progressive ventilator-dependent ALS.

Neurovascular complications of cocaine use at a tertiary stroke center.

OBJECTIVE: An association between cocaine use and stroke has been reported, but few studies have examined cocaine-related neurovascular disease using modern stroke diagnostic techniques. We describe a large cohort of patients with cocaine-related stroke to define the pathophysiology and manifestations of cocaine-related neurovascular disease. METHODS: All adult admissions to a tertiary neurovascular service from July 1, 1998 to July 1, 2008 were screened for evidence of current or previous cocaine use. Patients included underwent thorough review of medical records including diagnostic procedure, laboratory, and imaging results. RESULTS: A total of 5,142 records were screened and 96 patients were identified; 45 (47%) were given the diagnosis of ischemic stroke/transient ischemic attack (TIA), 26 (27%) with intracerebral hemorrhage (ICH), and 25 (26%) with subarachnoid hemorrhage. In all, 61 (63.5%) patients were categorized as active and 35 (36.5%) as previous cocaine users. Stroke type differed significantly between active and prior users (P=.004), with active users more likely to have ICH compared with previous users (37.7% v 8.6%) and less likely to have ischemic stroke or TIA (36.1% v 65.7%). The most common stroke/TIA cause was large artery atherosclerosis in 20 (44%) patients. Of the 25 subarachnoid hemorrhage cases, 22 (88%) were aneurysmal. CONCLUSION: Ischemic stroke/TIA is a common neurovascular presentation in patients with a remote history of cocaine use, often as a result of atherosclerotic disease; neither vasculitis nor vasospasm was a common cause of stroke in this cohort. ICH is more common in those currently using cocaine perhaps because of acute spikes in blood pressure. Further prospective trials are needed to confirm these results.