Patients with Low National Institutes of Health Stroke Scale Scores Have Longer Door-to-Needle Times: Analysis of a Telestroke Network.

BACKGROUND: The benefits of intravenous tissue-type plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) are time dependent. Because emergency rooms quickly initiate a stroke alert with more severe symptoms, we hypothesized that patients with lower National Institutes of Health Stroke Scale (NIHSS) scores, indicating a less severe stroke, would have longer door-to-needle (DTN) times compared to patients with higher NIHSS scores. METHODS: Data obtained from the 19-hospital Providence Stroke Registry were used to identify AIS patients who received IV-tPA within 4.5 hours of last-known-well. NIHSS scores were obtained prior to tPA administration at the time of emergency department presentation and categorized as low-NIHSS (score = 0-5) or high-NIHSS (score = 6-42) strokes. Median DTN times were collected for both groups as the primary outcome variable. Linear mixed-effects regression models were used to assess the effect of NIHSS scores on DTN and its 2 components: door-to-CT (DCT) and CT-to-needle (CTN) times. RESULTS: We identified 692 AIS patients who received IV-tPA within 4.5 hours of last-known-well, with 198 patients presenting with low-NIHSS strokes and 494 patients with high-NIHSS strokes. In multivariable analysis, median DTN time was estimated to be 18% higher for low-NIHSS strokes than high-NIHSS strokes after adjusting for covariates (P < .001). Median DCT times were also higher for low-NIHSS (19 minutes) compared to high-NIHSS (11 minutes) strokes after adjusting for covariates (P < .001), whereas CTN times were unchanged (P = .055). CONCLUSION: In AIS patients receiving IV-tPA in a telestroke network, lower NIHSS scores were associated with longer DTN and DCT times.

Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke.

BACKGROUND AND PURPOSE: An urgent need exists to develop therapies for stroke that have high efficacy, long therapeutic time windows, and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. METHODS: Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. RESULTS: Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically relevant therapeutic time windows of 6 hours and 9 hours in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained on 14th day poststroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests, and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust antiexcitotoxic, antioxidant, and mitochondria protecting activity. CONCLUSIONS: In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.

Cerebral venous and sinus thrombosis associated with subcutaneous immunoglobulin injection and oral contraceptive use.

Although patients of cerebral sinus thrombosis after intravenous immunoglobulin (IVIG) has been previously reported; reports of cerebral venous thrombosis secondary to subcutaneous injection of immunoglobulin (SIG) in conjunction with oral contraceptives are nonexistent in the current literature. We describe here a patient of cerebral venous and sinus thrombosis occurring after the combination of SIG and oral contraceptive use. Furthermore, we shall explore proper clinical precautions for someone who receives IG therapy, especially in conjunction with the use of oral contraceptives.

Sex differences in the use of intravenous rt-PA thrombolysis treatment for acute ischemic stroke: a meta-analysis.

BACKGROUND AND PURPOSE: Some studies report that women are less likely to receive IV rt-PA treatment for stroke than men. We undertook a meta-analysis to determine whether a sex disparity existed. METHODS: We identified studies that reported sex-specific IV rt-PA treatment rates for acute stroke. Eligible studies included acute stroke admissions from single or multiple hospitals, registries, or administrative databases. Random effects odds ratios (OR) and 95% confidence intervals (CI) were generated to quantify sex differences (females versus males) among all ischemic stroke admissions and among the eligible subgroup who arrived within 3 hours without contraindications. Study design and geographic location were explored as sources of heterogeneity. RESULTS: Eighteen studies were included. Study designs included single hospitals (n=5), multiple hospitals (n=6), registries (n=4), and administrative databases (n=3). The summary OR was 0.70 (95% CI=0.55 to 0.88) indicating that women had a 30% lower odds of receiving rt-PA treatment than men. However, substantial between-study variability existed. Among 13 hospital-based studies, the summary OR was 0.78 (95% CI=0.71 to 0.86) with no significant heterogeneity. Among the 3 administrative studies, the OR was 0.55 (95% CI=0.34 to 0.90) but with significant heterogeneity. Among 4 studies that included data on the eligible subgroup, women had a nonsignificant lower odds of treatment (OR=0.81, 95% CI=0.58 to 1.13). CONCLUSIONS: Despite the presence of significant between-study variation, women with acute stroke were consistently less likely to receive thrombolysis treatment compared with men. Further studies to explore the origins of this sex disparity are warranted.

Cardiac dysfunction after left permanent cerebral focal ischemia: the brain and heart connection.

BACKGROUND AND PURPOSE: Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. RESULTS: Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. CONCLUSIONS: This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Chemotherapy-related posterior reversible leukoencephalopathy syndrome.

BACKGROUND: A 45-year-old woman with small-cell lung cancer presented to a hospital emergency department in an acute confusional state, with blurred vision and mild headache. Following progressively increasing lethargy, she subsequently became unresponsive to tactile and verbal stimuli. She had recently been started on chemotherapy with carboplatin and gemcitabine. INVESTIGATIONS: Physical examination, imaging studies including brain MRI, noncontrast brain CT scans and magnetic resonance angiography, continuous EEG monitoring, and cerebrospinal fluid analysis. DIAGNOSIS: Posterior reversible leukoencephalopathy syndrome (PRES) related to chemotherapy, and nonconvulsive status epilepticus related to PRES. MANAGEMENT: Withholding of chemotherapeutic agents, and antiseizure therapy for the status epilepticus.

Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis.

A 56-year-old male with recurrent painless focal neuropathies and a family history of peripheral neuropathy of unknown etiology presented with progressively worsening of impaired sensations and weakness in his lower extremities. His initial electrodiagnostic evaluation was suggestive of severe sensory and motor peripheral polyneuropathy. The genetic testing was performed for familial causes of peripheral neuropathy as there was a family history of peripheral neuropathy of unknown etiology. The patient was found to have 1.5-Mb deletion in the PMP22 gene which was confirmatory of hereditary neuropathy with liability to pressure palsies (HNPP). He developed progressive upper and lower extremity weakness, bulbar dysfunction and widespread fasciculations during the course of his illness. He was subsequently diagnosed with amyotrophic lateral sclerosis (ALS). This is the second reported case of HNPP associated with ALS. We discuss significant clinical and electrodiagnostic findings of this interesting case.

Diffusion-weighted imaging: not all that glitters is gold.

Diffusion-weighted imaging (DWI) is a sophisticated magnetic resonance imaging (MRI) technique with rapid acquisition time and high sensitivity for depicting acute cerebral ischemia. It is currently part of the routine workup in most medical centers when ischemic stroke is in the differential diagnosis. DWI helps establish a diagnosis of acute ischemic infarct even in cases where the clinical presentation is not typical for ischemic stroke. However, contrary to popular belief, not every hyperintensity on DWI is an ischemic stroke. Consequently, DWI with high intensity signals, commonly called "positive" DWI, is sometimes misinterpreted and leads to incorrect medical management. In this report, we briefly discuss some of the essential, technical aspects of DWI and report various clinical scenarios, which may lead to "positive" DWI findings but are not ischemic strokes. Although the sensitivity of DWI for ischemic stroke is very high, the specificity is not as high, and a "positive" DWI does not exclude other diagnoses that should be considered based on each patient's clinical history and examination, and the appearance of other sequences of MRI scans.

Therapeutic role of zonisamide in neuropsychiatric disorders.

Zonisamide (ZNS), a sulfonamide antiepileptic drug, is indicated as an adjunct therapy for partial seizure disorders with and without secondary generalization. ZNS has a favorable pharmacokinetic profile because of its rapid absorption and high bioavailability. Its activity is related to the blockade of voltage gated sodium and calcium channels, modulation of central dopaminergic, GABAergic, and serotonergic functions, as well as inhibition of carbonic anhydrase and monoamine oxidase B. ZNS has potential efficacy for an array of neuropsychiatric disorders including migraine and other headache syndromes, neuropathic pain, Parkinson's disease, essential tremor, stroke, obesity, anxiety, bipolar and binge-eating disorders.

Hemorrhagic colloid cyst in a 9-year-old girl.

Colloid cysts of the third ventricle are benign intracranial tumors that usually become symptomatic in adults, rather than in children. Rare hemorrhages in these cysts can cause acute obstructive hydrocephalus and sudden death. We report a novel pediatric case of hemorrhagic colloid cyst in a 9-year-old girl who presented with headaches, nausea, and had sudden deterioration of her mental status. The patient underwent emergent ventriculostomy and then craniotomy to resect the colloid cyst; she had an excellent recovery.

Periodic lateralized epileptiform discharges: an initial electrographic pattern in reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy (RPLE) is a unique clinicoradiological entity characterized by diverse neurological symptoms with bilateral posterior cerebral white matter edema. It is frequently associated with seizures but rarely with status epilepticus. Periodic lateralized epileptiform discharges (PLEDs) as an initial electrographic pattern in a patient with RPLE have never been reported. We discuss a 47-year-old woman with a newly diagnosed non-small cell carcinoma of the lung on etoposide who was admitted with encephalopathy. Initial EEG demonstrated PLEDs. She later developed nonconvulsive status epilepticus. Magnetic resonance imaging (MRI) revealed bilateral subcortical edema predominantly of the temporo-occipital lobes. Discontinuation of etoposide resulted in full clinical, electrical recovery within 10 days and significant radiological improvement within 15 days. Our case indicates the importance of identifying and addressing any modifiable etiologic factors of RPLE. We emphasize identification of the unique initial electrographic pattern of PLEDs, which may be a predisposing factor to status epilepticus or an indication of structural damage.

The cost-effectiveness of telestroke in the Pacific Northwest region of the USA.

INTRODUCTION: Using real-world data from the Providence Oregon Telestroke Network, we examined the cost-effectiveness of telestroke from both the spoke and hub perspectives by level of financial responsibility for these costs and by patient stroke severity. METHODS: We constructed a decision analytic model using patient-level clinical and financial data from before and after telestroke implementation. Effectiveness was measured as quality-adjusted life years (QALYs) and was combined with cost per patient outcomes to calculate incremental cost effectiveness ratios (ICERs). Outcomes were generated (a) overall; (b) by stroke severity, via the National Institute of Health Stroke Scale (NIHSS) at time of arrival, defined as low (<5), medium (5-14) and high (>15); and (c) by percentage of implementation costs paid by spokes (0%, 50%, 100%). RESULTS: Data for 864 patients, 98 pre- and 766 post-implementation, were used to parameterize our model. From the spoke perspective, telestroke had ICERs of US$1322/QALY, US$25,991/QALY and US$50,687/QALY when responsible for 0%, 50%, and 100% of these costs, respectively. Overall, the ICER ranged from US$22,363/QALY to US$71,703/QALY from the hub perspective. CONCLUSIONS: Our results support previous models showing good value, overall. However, costs and ICERs varied by stroke severity, with telestroke being most cost-effective for severe strokes. Telestroke was least cost effective for the spokes if spokes paid for more than half of implementation costs.

An uncommon cause of transient neurological dysfunction.

Transient neurological dysfunction may be associated with uncommon disorders and should prompt consideration of a broad differential diagnosis when assessing patients with episodic symptoms. The most common causes of transient neurological dysfunction include transient ischemic attack (TIA), seizure disorder, and migraine and its variants. However, underlying unusual pathophysiological processes such as brain tumors can also cause transient neurological dysfunction. Here we present a case of a 68-year-old male with oligodendroglial gliomatosis cerebri (OGC) who presented with TIA-like symptoms. Brain magnetic resonance imaging revealed multiple diffuse T2 hyperintensities within the white and gray matter. Magnetic resonance spectroscopy was suggestive of gliomatosis cerebri and was particularly helpful in this case. The diagnosis of OGC was confirmed by histopathology and molecular genetic studies on brain biopsy tissue. In this report, we discuss the clinical and radiological characteristics of OGC and highlight the unusual presentation of this case.

Incorporating diffusion-weighted magnetic resonance imaging into an observation unit transient ischemic attack pathway: a prospective study.

BACKGROUND AND PURPOSE: National guidelines advocate for early, aggressive transient ischemic attack (TIA) evaluations and recommend diffusion-weighted magnetic resonance imaging (MRI) for brain imaging. The purpose of this study is to examine clinician compliance, the yield of MRI, and patient-centered clinical outcomes following implementation of an emergency department observation unit (EDOU) clinical pathway incorporating routine MRI into the acute evaluation of patients with TIA. METHODS: This is a prospective observational study of patients with TIA admitted from the ED. Patients with low-risk TIA were transferred to an EDOU for diagnostic testing including MRI; high-risk patients were directed to hospital admission. Clinical variables, diagnostic tests, and treatment were recorded for all patients. The primary clinical outcome was the rate of stroke or recurrent TIA, determined through telephone follow-up and medical record review at 7 and 30 days. RESULTS: A total of 116 patients with TIA were enrolled. In all, 92 (79.3%) patients were transferred to the EDOU, of whom 69 (59.5%) were discharged without hospitalization. Compliance with the EDOU pathway was 83 (91.2%) of 92. Magnetic resonance imaging demonstrated acute infarct in 16 (15.7%) of 102 patients. Stroke (n = 2) or TIA (n = 3) occurred in 5 patients with TIA (4.3%, 95% confidence interval: 1.6%-10.0%) within 30 days; no strokes occurred after discharge. CONCLUSIONS: Implementation of a TIA clinical pathway incorporating MRI effectively encouraged guideline-compliant diagnostic testing; however, patient-important outcomes appear similar to diagnostic protocols without routine MRI. Further study is needed to assess the benefits and costs associated with routinely incorporating MRI into TIA evaluation.

Medicolegal considerations with intravenous tissue plasminogen activator in stroke: a systematic review.

Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.