QTc-prolongation in posterior circulation stroke.

BACKGROUND AND PURPOSE: To evaluate the relationship between infarct location and QTc-prolongation in patients with posterior circulation strokes. METHODS: Admission electrocardiograms (ECG) of 131 patients among a prospective sample of 407 consecutive adult patients in the New England Medical Center Posterior Circulation Registry were retrospectively analyzed. The QT interval (ms) was measured and corrected using Bazett's formula (QTcBazett) as well as linear regression functions (QTcLinear). QTcBazett > 440 ms and QTcLinear ≥ 450 ms for men (≥460 ms for women) were considered prolonged. Multivariable linear and logistic regression analyses were used to identify independent predictors of the QTc. RESULTS: Overall, 34% of patients had a prolonged QTcBazett and 7% had a prolonged QTcLinear noted on the admission ECG. There was a significant association between temporal lobe infarction and QTcBazett and QTcLinear (p < 0.001 for both) in multivariable linear regression analyses adjusting for demographics, ECG parameters, and preadmission medication use. In multivariable logistic regression analysis, temporal lobe infarction emerged as an independent predictor of prolonged QTcBazett (p = 0.009) and QTcLinear (p = 0.008), respectively. Sensitivity analyses excluding patients with transient ischemic attack yielded similar results. Exploratory analyses indicated that patients with temporal lobe infarction had worse functional 30-day outcomes in multivariable logistic regression (p = 0.022). However, there was no significant association between QTc and 30-day functional outcome. CONCLUSIONS: QTc-prolongation is common after posterior circulation stroke and associated with temporal lobe infarction. Prospective studies are needed to confirm these preliminary findings and to examine potential long-term consequences.

Symptoms and signs of posterior circulation ischemia in the new England medical center posterior circulation registry.

OBJECTIVE: To evaluate the frequencies of symptoms and signs in patients with posterior circulation ischemia in a large case series of prospectively collected patients. DESIGN: Case series. SETTING: Outpatient and inpatient setting at the New England Medical Center, a tertiary care referral center in Boston, Massachusetts. PATIENTS: Consecutive sample of 407 adult patients who had stroke and/or transient ischemic attacks in the posterior circulation within 6 months of study inclusion. All patients were examined by senior stroke neurologists. All patients had either computed tomography or magnetic resonance imaging of the brain as well as vascular imaging of the head and neck. The study included 256 men (63%) and 151 women (37%). MAIN OUTCOME MEASURES: Frequencies of posterior circulation ischemic symptoms and signs. These outcome measures were planned before data collection began. Correlations between symptoms and signs with separate vascular territories of the posterior circulation were then analyzed. RESULTS: The most frequent posterior circulation symptoms were dizziness (47%), unilateral limb weakness (41%), dysarthria (31%), headache (28%), and nausea or vomiting (27%). The most frequent signs were unilateral limb weakness (38%), gait ataxia (31%), unilateral limb ataxia (30%), dysarthria (28%), and nystagmus (24%). Logistic regression analysis reveals that the clinical features dysphagia (P = .004; 95% CI, 1.8-24.4), nausea or vomiting (P = .002; 95% CI, 1.6-8.2), dizziness (P = .047; 95% CI, 1.0-5.4), and Horner syndrome (P = .001; 95% CI, 2.4-26.6) were positively correlated with the proximal vascular territory. Unilateral limb weakness (P = .001; 95% CI, 1.7-8.7) and cranial nerve VII deficits (P = .02; 95% CI, 1.1-5.3) were positively correlated with the middle territory. Limb sensory deficit (P = .001; 95% CI, 1.8-7.8), lethargy (P = .001; 95% CI, 2.3-12.4), and visual field loss (P = .001; 95% CI, 5.3-23.9) were positively correlated with the distal territory. CONCLUSIONS: We report the most frequent symptoms and signs in the largest published registry, the New England Medical Center Posterior Circulation Registry, of patients with posterior circulation ischemia who had complete neurological examinations and extensive cerebrovascular imaging. Knowledge of the vascular territory involved aids in the diagnosis of the causative vascular lesion and stroke mechanism.

Can ABCD score predict the need for in-hospital intervention in patients with transient ischemic attacks?

BACKGROUND: The ABCD(2) score is increasingly being used to triage patients with transient ischemic attack (TIA). Whether the score can predict the need for in-hospital intervention (IHI), other than initiation of antiplatelets and statins, is unknown. AIMS: The ability of the ABCD(2) score to predict IHI would strengthen the rationale to use it as a decision-making tool. We thus conducted this study to investigate the relationship between the ABCD(2) score and IHI. METHODS: We analyzed prospectively collected data from consecutive TIA patients over 12 months. We determined ABCD(2) upon admission and collected the results of in-hospital evaluation, treatments initiated during hospitalization, and follow-up status. We defined IHI as arterial revascularization or anticoagulation required during admission. We used chi-square for trend to examine the association between ABCD(2) and IHI. RESULTS: We studied 121 patients. Fourteen (12%) had small infarcts on diffusion magnetic resonance imaging; 38 (31%) had a new risk factor recognized during admission [hyperlipidemia (n = 9), hypertension (1), diabetes (1), carotid stenosis >/= 50% (16), other arterial occlusive lesions (7), and potential cardioembolic source (4)]. Their percentages increased with higher ABCD(2) scores. However, among 12 patients (10%) with IHI, ABCD(2) score categories were equally distributed (10% in 0-3, 9% in 4-5, and 10% in 6-7; p = 0.8). One patient (0.8%) worsened during hospitalization; none had a stroke during follow-up. CONCLUSION: Patients with an ABCD(2) score

Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies.

OBJECTIVE: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. METHODS: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases-9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. RESULTS: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients < or =60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. CONCLUSION: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Unusual presentations of nervous system infection by Cryptococcus neoformans.

Nervous system infections by Cryptococcus neoformans may occur not only in congenital or acquired immunodeficiency syndromes, but also in immunocompetent hosts. Neurological manifestations of C. neoformans infection include meningitis and, less commonly, parenchymal CNS granulomatous disease. This paper provides detailed clinical descriptions of highly unusual neurological manifestations of cryptococcal nervous system infections. Medical records and diagnostic data including magnetic resonance imaging, histopathology, serology, and CSF analysis were reviewed. A conus medullaris abscess was found in a patient infected with the human immunodeficiency virus (HIV). A patient with Hodgkin's disease was diagnosed with cryptococcal meningitis and dermatitis mimicking ophthalmic zoster. An immunocompetent patient presented with recurrent cerebral infarctions in the setting of cryptococcal meningitis. Cryptococcal infections of the nervous system can cause severe neurological disability when diagnosis is delayed. Sensitive and specific tests are readily available and should be considered when an unusual clinical presentation is encountered.

Cerebrovascular disease.

Effective management of patients who have cerebrovascular disease depends on accurate diagnosis. Many conditions cause clinical findings that closely mimic cerebrovascular disorders and are often ruled out through brain imaging or laboratory findings. Diagnosis of cerebrovascular disorders is based on the presence of risk factors for vascular disease, the tempo of onset, the presence of concurrent conditions, and the clinical course of development of neurologic symptoms and signs. This article shares a process by which clinicians can combine a patient's history, neurologic examination, and brain and vascular imaging to localize a lesion and diagnose cerebrovascular disease.

The HAT Score: a simple grading scale for predicting hemorrhage after thrombolysis.

OBJECTIVE: To develop a grading scale to predict the risk of intracerebral hemorrhage (ICH) and prognosis after treatment with IV tissue-plasminogen activator (t-PA) in patients with ischemic stroke. METHODS: We constructed a five-point scale based on NIH Stroke Scale score, extent of hypodensity on CT scan, serum glucose at baseline, and history of diabetes to predict the risk of hemorrhage after thrombolysis (HAT score). We evaluated the predictive ability of this scale, using c-statistics, in two independent cohorts: the t-PA treated group in the National Institute of Neurological Disorders and Stroke study, and consecutive patients treated with IV t-PA at our institution. RESULTS: The percentage of patients who developed any ICH after t-PA increased with higher scores in both cohorts. Collectively, the rate of any symptomatic ICH was 2% (0 point), 5% (1 point), 10% (2 points), 15% (3 points), and 44% (>3 points). The c-statistic was 0.72 (95% CI 0.65-0.79; p < 0.001) for all hemorrhages; 0.74 (0.63-0.84; p < 0.001) for symptomatic hemorrhages; and 0.79 (0.70-0.88; p < 0.001) for hemorrhages with final fatal outcome. Similar results were obtained when each cohort was analyzed separately. The score also reasonably predicted good (mRS < or = 2) (c-statistic 0.75; 0.69-0.80; p < 0.001) and catastrophic (mRS > or = 5) (0.78; 0.72-0.84; p < 0.001) functional outcomes on day 90 in the National Institute of Neurological Disorders and Stroke t-PA-treated patients. CONCLUSIONS: The hemorrhage after thrombolysis (HAT) score is a practical, quick, and easy-to-perform scale that allows reasonable risk stratification of intracerebral hemorrhage after IV tissue-plasminogen activator (t-PA). However, the prognostic value of this scale and its use to predict the net benefit from t-PA needs to be refined and prospectively confirmed in a larger cohort of patients before it can be used in clinical decision-making.

From Jabberwocky to genome: Lewis Carroll and computational biology.

In addition to his literary output, Lewis Carroll created a vast range of games and puzzles that depend upon wordplay of various kinds, especially the manipulation of alphabetic symbols in diverse contexts. Such wordplay reveals a turn of mind well suited to methodologies used in modern computational biology.

Bioinformatics tools for whole genomes.

The advent of whole-genome data resources--not only sequence but also other genome-scale data collections such as gene expression, protein interaction, and genetic variation--is having two marked, complementary effects on the relatively new discipline of bioinformatics. First, the veritable flood of data is creating a need and demand for new tools for dealing adequately with the deluge, and, second, the unprecedented extent, diversity, and impending completeness of the data sets are creating opportunities for new approaches to discovery based on computational methods.

Analysis of EST-driven gene annotation in human genomic sequence.

We have performed a systematic analysis of gene identification in genomic sequence by similarity search against expressed sequence tags (ESTs) to assess the suitability of this method for automated annotation of the human genome. A BLAST-based strategy was constructed to examine the potential of this approach, and was applied to test sets containing all human genomic sequences longer than 5 kb in public databases, plus 300 kb of exhaustively characterized benchmark sequence. At high stringency, 70%-90% of all annotated genes are detected by near-identity to EST sequence; >95% of ESTs aligning with well-annotated sequences overlap a gene. These ESTs provide immediate access to the corresponding cDNA clones for follow-up laboratory verification and subsequent biologic analysis. At lower stringency, up to 97% of annotated genes were identified by similarity to ESTs. The apparent false-positive rate rose to 55% of ESTs among all sequences and 20% among benchmark sequences at the lowest stringency, indicating that many genes in public database entries are unannotated. Approximately half of the alignments span multiple exons, and thus aid in the construction of gene predictions and elucidation of alternative splicing. In addition, ESTs from multiple cDNA libraries frequently cluster over genes, providing a starting point for crude expression profiles. Clone IDs may be used to form EST pairs, and particularly to extend models by associating alignments of lower stringency with high-quality alignments. These results demonstrate that EST similarity search is a practical general-purpose annotation technique that complements pattern recognition methods as a tool for gene characterization.

Linguistic approaches to biological sequences.

Biologists have long made use of linguistic metaphors in describing and naming cellular processes involving nucleic acid and protein sequences. Indeed, it is very natural to view the genetic 'text' and its sequential transliterations in these terms. However, a metaphor is not a tool, and it is necessary to ask whether the techniques used in analyzing other kinds of languages, such as human and computer languages, can in fact be of any use in tackling problems in molecular biology. This paper reviews the work of the author and others in applying the methods of computational linguistics to biological sequences.

Computational gene discovery and human disease.

Bioinformatics is now an essential tool in many aspects of human molecular genetics research. Methods for the prediction of gene structure are essential components in genomic sequencing projects and provide the key to deriving protein sequence and locating intron/exon junctions. Sequence comparison and database searching are the pre-eminent approaches for predicting the likely biochemical function of new genes, although sequence profiles derived from families of aligned sequences have advantages in the detection of remote sequence relationships. The use of sequence database analysis for large-scale comparative analysis of genome sequence data from model organisms is emerging as the most important recent development in the application of bioinformatics methods for characterizing candidate disease genes.

Attention-deficit hyperactivity disorder: a longitudinal case study of handwriting characteristics.

This longitudinal case study focuses on handwriting samples of a female diagnosed with Attention-Deficit/Hyperactivity Disorder from 12 years of age to 21 years of age. Diaries and journals produced for class assignments and later for this research yielded 293 handwriting samples. 15 characteristics of handwriting were measured and statistically analyzed to follow changes in handwriting across time. At seven years of age while in elementary school the subject was diagnosed with ADHD and placed on Ritalin (methylphenidate). At puberty the drug was discontinued. During two summers she visited grandparents, once alone and once with two sisters with whom she was in conflict. Her handwriting deviated from its pattern of general decrease in size and increase in uniformity during these visits. The changes over time of three handwriting characteristics (slant of "l," heights and areas of the lower loop of the "g," and area of the left loop of the "I") also deviated from the general pattern of her handwriting change.

bioTk:componentry for genome informatics graphical user interfaces.

bioTk is a collection of graphical "widgets" and utilities that support application programming in the domain of bioinformatics. It is intended to establish a framework that encourages the development of communicating window-based applications and flexible, non-modal user interaction. The current release of bioTk has domain-specific widgets for chromosome ideogram displays, genome maps, and scrolling sequence windows.

Automata-theoretic models of mutation and alignment.

Finite-state automata called transducers, which have both input and output, can be used to model simple mechanisms of biological mutation. We present a methodology whereby numerically-weighted versions of such specifications can be mechanically adapted to create string edit machines that are essentially equivalent to recurrence relations of the sort that characterize dynamic programming alignment algorithms. Based on this, we have developed a visual programming system for designing new alignment algorithms in a rapid-prototyping fashion.