Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12.

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.

The National Institutes of Health Undiagnosed Diseases Program: insights into rare diseases.

Purpose: This report describes the National Institutes of Health Undiagnosed Diseases Program, details the Program's application of genomic technology to establish diagnoses, and details the Program's success rate during its first 2 years.

Methods: Each accepted study participant was extensively phenotyped. A subset of participants and selected family members (29 patients and 78 unaffected family members) was subjected to an integrated set of genomic analyses including high-density single-nucleotide polymorphism arrays and whole exome or genome analysis.

Intra-arterial thrombolysis within three hours of stroke onset in middle cerebral artery strokes.

Background And Purpose: The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial showed improved outcomes in patients with proximal middle cerebral artery (MCA) occlusions treated with intra-arterial (IA) thrombolysis within 6 h of stroke onset. We analyzed outcomes of patients with proximal MCA occlusions treated within 3 h of stroke onset in order to determine the influence of time-to-treatment on clinical and angiographic outcomes in patients receiving IA thrombolysis.

Methods: Thirty-five patients from three academic institutions with angiographically demonstrated proximal MCA occlusions were treated with IA thrombolytics within 3 h of stroke onset.

Older age does not increase risk of hemorrhagic complications after intravenous and/or intra-arterial thrombolysis for acute stroke.

Background: The elderly have significantly higher incidence of ischemic stroke and have higher mortality and morbidity compared with younger patients. Intracranial hemorrhage (ICH) after thrombolysis is one of the causes of unfavorable outcome. However, it is unclear whether age over 80 years is a predictor for hemorrhagic transformation after intravenous, intra-arterial, or a combination of both thrombolytic therapies.

Comparing multislice electrocardiogram-gated spiral computerized tomography and transesophageal echocardiography in evaluating aortic atheroma in patients with acute ischemic stroke.

Objective: The aim of this study was to compare transesophageal echocardiography (TEE) and cardiac-gated computerized tomography (CGCT) in detecting aortic atherosclerosis (AA).

Background: There is evidence that AA can be a source of embolic material causing ischemic stroke. TEE is a well-established tool for detecting cardiac sources of emboli in patients with stroke, but it has distinct limitations in the detection of AA.

Interobserver and intraobserver reliabilities of multislice electrocardiogram-gated spiral computerized tomography in evaluating aortic atheroma in patients with acute ischemic stroke.

Objective: The objective of this study was to demonstrate the reliability of cardiac-gated computerized tomography (CGCT) in diagnosing aortic atheroma in patients with ischemic stroke.

Materials And Methods: Two radiologists each read 32 CGCT studies and estimated aortic atheroma and interreliability/intrareliability measures.

Results: The intraobserver intraclass correlation coefficients (ICCs) were 0.

Reproducibility of transesophageal echocardiography in evaluating aortic atheroma in stroke patients.

Although transesophageal echocardiography (TEE) is a well-established tool in delineating the cardiac and aortic sources of emboli in stroke patients, its reproducibility in detecting aortic atherosclerosis (AA) that may lead to stroke is not well documented. The aim of this study is to demonstrate the inter- and intra-observer agreement in diagnosing AA based on the TEE study. During the study period, 2 echocardiographers read 32 TEE studies performed on a group of stroke patients.

Thrombolytic therapy of acute ischemic stroke: correlation of angiographic recanalization with clinical outcome.

Background And Purpose: The effect of vessel patency, following recombinant tissue plasminogen activator (rtPA) administration, on clinical outcome in acute ischemic stroke (AIS) has been controversial. We studied the effect of recanalization following intraarterial (IA) and intravenous/IA (IV/IA) rtPA on clinical outcome in AIS.

Methods: Recanalization was classified angiographically as complete (as compared with unoccluded vessel, thrombolysis in myocardial infarction classification [TIMI] 3), none (with no change from prethrombolysis, TIMI 0), and partial (when a change in the flow from baseline was noted, TIMI 1-2).

Intra-arterial thrombolytic therapy in peri-coronary angiography ischemic stroke.

Background: Intra-arterial thrombolysis (IAT) for peri-coronary angiography (CA) stroke may be safe and efficacious. However, IAT may increase the risk of intracranial hemorrhage (ICH).

Methods: A retrospective study was performed involving 3 university hospitals.

Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy.

Background And Purpose: Although long-term outcome determinants in acute ischemic stroke (AIS) patients have been defined, less is known about those predicting hyperacute worsening after thrombolytic therapy (TT). We investigated predictors of short-term clinical worsening (National Institutes of Health Stroke Scale [NIHSS] change > or =4 within 24 hours of admission).

Methods: We studied 201 AIS patients who received TT within 6 hours of symptom onset.

Cuyahoga County Operation Stroke speed of emergency department evaluation and compliance with National Institutes of Neurological Disorders and Stroke time targets.

Background And Purpose: Although the National Institutes of Neurological Disorders and Stroke (NINDS) has established time targets for the evaluation of acute stroke patients, little is known about how often these targets are met in the community. To track compliance with NINDS guidelines, Cuyahoga County Operation Stroke implemented a countywide data collection process that provides comparative reporting of hospital performance.

Methods: Data on the emergency department evaluation of stroke patients have been retrospectively collected since January 2000 by hospitals participating in Cuyahoga County Operation Stroke.

Response to intra-arterial and combined intravenous and intra-arterial thrombolytic therapy in patients with distal internal carotid artery occlusion.

Background And Purpose: The objective of this study was to determine the clinical features, angiographic findings, and response to treatment with thrombolytic therapy in patients with ischemic stroke caused by acute occlusion of the distal internal carotid artery.

Methods: This is a retrospective case series from a prospectively collected stroke database for patients with acute internal carotid occlusion presenting within 6 hours of stroke onset to evaluate safety, feasibility, and response to thrombolytic therapy. The University Hospital-based brain attack database was reviewed over a 5-year period.

Endovascular administration after intravenous infusion of thrombolytic agents for the treatment of patients with acute ischemic strokes.

Objective: To determine the feasibility of combined intravenous and intra-arterial thrombolytic therapy for acute ischemic strokes and to evaluate its associated risks, using magnetic resonance imaging as a triage tool. Intravenous treatment followed by intra-arterial infusion may increase the rate of recanalization and lead to better clinical results, with reduced frequency of intracranial hemorrhage.

Methods: Our Brain Attack Team evaluated patients who presented within 3 hours after symptom onset.