Ayush Batra

Antagonism of peripheral inflammation reduces the severity of status epilepticus

Status epilepticus (SE) is one of the most serious manifestations of epilepsy. Systemic inflammation and damage of blood-brain barrier (BBB) are etiologic cofactors in the pathogenesis of pilocarpine SE while acute osmotic disruption of the BBB is sufficient to elicit seizures. Whether an inflammatory-vascular-BBB mechanism could apply to the lithium-pilocarpine model is unknown. LiCl facilitated seizures induced by low-dose pilocarpine by activation of circulating T-lymphocytes and mononuclear cells. Serum IL-1beta levels increased and BBB damage occurred concurrently to increased theta EEG activity. These events occurred prior to SE induced by cholinergic exposure. SE was elicited by lithium and pilocarpine irrespective of their sequence of administration supporting a common pathogenetic mechanism. Since IL-1beta is an etiologic trigger for BBB breakdown and its serum elevation occurs before onset of SE early after LiCl and pilocarpine injections, we tested the hypothesis that intravenous administration of IL-1 receptor antagonists (IL-1ra) may prevent pilocarpine-induced seizures. Animals pre-treated with IL-1ra exhibited significant reduction of SE onset and of BBB damage. Our data support the concept of targeting systemic inflammation and BBB for the prevention of status epilepticus.

In Vivo and In Vitro Effects of Pilocarpine: Relevance to Ictogenesis

Objectives: A common experimental model of status epilepticus (SE) utilizes intraperitoneal administration of the cholinergic agonist pilocarpine preceded by methyl‐scopolamine treatment. Currently, activation of cholinergic neurons is recognized as the only factor triggering pilocarpine SE. However, cholinergic receptors are also widely distributed systemically and pretreatment with methyl‐scopolamine may not be sufficient to counteract the effects of systemically injected pilocarpine. The extent of such peripheral events and the contribution to SE are unknown and the possibility that pilocarpine also induces SE by peripheral actions is yet untested.

An Analysis of Inflation Times During Balloon-Assisted Aneurysm Coil Embolization and Ischemic Complications

Background and Purpose— The introduction of balloon remodeling has revolutionized the approach to coiling of wide-neck aneurysms. We studied the effects of balloon inflation during coil embolization on ischemic complications. Methods— A retrospective review was undertaken of the most recent 147 patients undergoing balloon remodeling for unruptured intracranial aneurysm coil embolization at a single institution (81 balloon, 66 unassisted). All underwent postprocedural MRI. Results— Among patients in the “balloon” group, the mean total inflation time was 18 minutes (range, 1–43), a mean number of inflations of 4 (range, 1–9), a mean maximum single inflation time of 7 minutes (range, 1–19), a mean reperfusion time of 2.2 minutes between inflations, and an average procedure time of 2 hours and 10 minutes. Asymptomatic diffusion-weighted imaging abnormalities were detected on postprocedural MRI in 21.5% of patients and symptomatic lesions were identified in 3.8%. Both silent and symptomatic ischemic rates were similar in the internal control group. Patients with ischemic findings were older and more likely have diabetes; no differences were found with respect to total balloon inflation time, number of inflations, maximum inflation time, or reperfusion times. Conclusions— We found no significant relationship between balloon inflation practices and ischemic events. Older and diabetic patients were more likely to have ischemic events develop.

Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke.

In this study, we examined the relationship between tissue and blood levels of matrix metalloproteinase (MMP)-2 and MMP-9 through gelatin zymography at multiple time points after experimental stroke. We additionally investigated the association between these levels and the evidence of blood–cerebrospinal fluid (CSF) barrier (BCSFB) and blood–brain barrier (BBB) disruption on post-contrast fluid-attenuated inversion-recovery (FLAIR) imaging. Increased plasma MMP-9 was associated with BCSFB disruption at 1h post-reperfusion. Ventricular enhancement ipsilateral to the stroke was 500±100%, significantly higher than sham, 24, and 48 h groups. Increased tissue MMP-2 and MMP-9 were associated with BBB disruption at 48 h post-reperfusion. Parenchymal enhancement was 60±20% for a volume equivalent to 260±80 mm3. Although the percent enhancement was comparable across groups, the volume of enhancing lesion was significantly higher at 48 h (260±80 mm3, 100%) in comparison to 1 h (8±3 mm3, 3%) and 24 h (51 mm3, 18%). These findings support the use of imaging markers of BCSFB and BBB status as indirect measures of MMP regulation in the blood and brain tissue. The methods presented herein should be useful in understanding the link between MMPs, barrier integrity, and subsequent hemorrhagic transformation.

Cerebrovascular complications of pregnancy and the postpartum period.

Cerebrovascular complications of pregnancy, though uncommon, threaten women with severe morbidity or death, and they are the main causes of major long-term disability associated with pregnancy. In this review, we discuss the epidemiology, pathophysiology, presentation and diagnosis, and management and outcomes of ischemic and hemorrhagic stroke and cerebral venous thrombosis. We also discuss the posterior reversible encephalopathy syndrome, the reversible cerebral vasoconstriction syndrome including postpartum cerebral angiopathy, and their relationship as overlapping manifestations of pre-eclampsia-eclampsia.

Meningioangiomatosis associated with focal cortical dysplasia and neurofibrillary tangles.

Meningioangiomatosis is a rare developmental lesion of probable hamartomatous origin. It is marked by a proliferation of blood vessels and meningothelial cells and is associated with chronic epilepsy. We report a case of a 23-year-old male with no evidence of Neurofibromatosis Type II who presented with meningioangiomatosis. Intracytoplasmic neurofibrillary tangles within dysplastic neurons were present throughout the lesion. Cortical tissue adjacen to the lesion demonstrated cytoarchitectural disorganization with an absence of cortical Layer II, malpositioning of cortical neurons and dysmorphic neurons consistent with a Palmini et al. focal cortical dysplasia type IIA, ILAE focal cortical dysplasia Type IIIc. The presence of coexistent focal cortical dysplasia supports a developmental nature of the meningioangiomatosis and has potential implications regardg the epileptogenicity of the lesion.

Review of Critical Illness Myopathy and Neuropathy

Critical illness myopathy (CIM) and neuropathy are underdiagnosed conditions within the intensive care setting and contribute to prolonged mechanical ventilation and ventilator wean failure and ultimately lead to significant morbidity and mortality. These conditions are often further subdivided into CIM, critical illness polyneuropathy (CIP), or the combination—critical illness polyneuromyopathy (CIPNM). In this review, we discuss the epidemiology and pathophysiology of CIM, CIP, and CIPNM, along with diagnostic considerations such as detailed clinical examination, electrophysiological studies, and histopathological review of muscle biopsy specimens. We also review current available treatments and prognosis. Increased awareness and early recognition of CIM, CIP, and CIPNM in the intensive care unit setting may lead to earlier treatments and rehabilitation, improving patient outcomes.

Soluble ST2 predicts outcome and hemorrhagic transformation after acute stroke

ST2 is a member of the toll‐like receptor superfamily that can alter inflammatory signaling of helper T‐cells. We investigated whether soluble ST2 (sST2) could independently predict outcome and hemorrhagic transformation (HT) in the setting of stroke.

An Isolated Trigeminal Sensory Neuropathy

A 60-year-old woman with no significant medical history presented to her neurologist with decreased sensation of the left cheek. Magnetic resonance imaging (MRI) with gadolinium contrast of the head, including the brain and cranial nerves, and magnetic resonance angiography of the head and neck were interpreted as normal. After a 2-year period of clinical stability, the sensory deficit gradually progressed to involve the entire left lower half of her face followed by the emergence of lancinating pain and allodynia over the same region. Neurologic examination confirmed a mild sensory deficit to light touch, temperature, and pin prick in the entire distribution of the second (V2) and third (V3) divisions of the left trigeminal nerve. She was started on carbamazepine with no relief. Subsequent MRIs of the head demonstrated abnormal thickening and enhancement throughout the entire left V2 nerve segment extending through Meckel cave and involving the cisternal portion of the left trigeminal nerve. In retrospect, the initial MRI demonstrated a small enhancing focus in the same region. The patient was referred to our facility for trigeminal nerve biopsy and concomitant microvascular decompression for symptomatic relief. Collected specimens demonstrated chronic inflammation without evidence of malignancy. A prednisone taper was started with good response. One month later, an incomitant left hypertropia with vertical diplopia (worse on right and downward gaze), along with poor activation of the left masseter and temporalis muscles, was noted on examination. The course of prednisone was extended. Three months later, the patient was readmitted in the setting of a massive pulmonary embolism. Neurologic examination demonstrated persistent left facial numbness with a new left esotropia and left lateral rectus palsy as well as downbeating nystagmus in primary gaze.

Medication History versus Point-of-Care Platelet Activity Testing in Patients with Intracerebral Hemorrhage

OBJECTIVE We evaluated whether reduced platelet activity detected by point-of-care (POC) testing is a better predictor of hematoma expansion and poor functional outcomes in patients with intracerebral hemorrhage (ICH) than a history of antiplatelet medication exposure. METHODS Patients presenting with spontaneous ICH were enrolled in a prospective observational cohort study that collected demographic, clinical, laboratory, and radiographic data. We measured platelet activity using the PFA-100 (Siemens AG, Germany) and VerifyNow-ASA (Accumetrics, CA) systems on admission. We performed univariate and adjusted multivariate analyses to assess the strength of association between those measures and (1) hematoma growth at 24 hours and (2) functional outcomes measured by the modified Rankin Scale (mRS) at 3 months. RESULTS We identified 278 patients for analysis (mean age 65 ± 15, median ICH score 1 [interquartile range 0-2]), among whom 164 underwent initial neuroimaging within 6 hours of symptom onset. Univariate association with hematoma growth was stronger for antiplatelet medication history than POC measures, which was confirmed in multivariable models (β 3.64 [95% confidence interval [CI] 1.02-6.26], P = .007), with a larger effect size measured in the under 6-hour subgroup (β 7.20 [95% CI 3.35-11.1], P < .001). Moreover, antiplatelet medication history, but not POC measures of platelet activity, was independently associated with poor outcome at 3 months (mRS 4-6) in the under 6-hour subgroup (adjusted OR 3.6 [95% CI 1.2-11], P = .023). CONCLUSION A history of antiplatelet medication use better identifies patients at risk for hematoma growth and poor functional outcomes than POC measures of platelet activity after spontaneous ICH.