Michael L. McGarvey

Reliability and Validity of Estimating the NIH Stroke Scale Score from Medical Records

BACKGROUND AND PURPOSE The aim of our study was to determine whether the National Institutes of Health Stroke Scale (NIHSS) can be estimated retrospectively from medical records. The NIHSS is a quantitative measure of stroke-related neurological deficit with established reliability and validity for use in prospective clinical research. Recently, retrospective observational studies have estimated NIHSS scores from medical records for quantitative outcome analysis. The reliability and validity of estimation based on chart review has not been determined. METHODS Thirty-nine patients were selected because their NIHSS scores were formally measured at admission and discharge. Handwritten notes from medical records were abstracted and NIHSS scores were estimated by 6 raters who were blinded to the actual scores. Estimated scores were compared among raters and with the actual measured scores. RESULTS Interrater reliability was excellent, with an intraclass correlation coefficient of 0.82. Scores were well calibrated among the 6 raters. Estimated NIHSS scores closely approximated the actual scores, with a probability of 0.86 of correctly ranking a set of patients according to 5-point interval categories (as determined by the area under the receiver-operator characteristic curve). Patients with excellent outcomes (NIHSS score of </=5) could be identified with sensitivity of 0.72 and specificity of 0.89. There were no significant differences between these parameters at admission and discharge. CONCLUSIONS For the purposes of retrospective studies of acute stroke outcome, the NIHSS can be abstracted from medical records with a high degree of reliability and validity.

Results of a New Surgical Paradigm: Endovascular Repair for Acute Complicated Type B Aortic Dissection

BACKGROUND Conventional open repair of acute complicated type B aortic dissection is associated with significant morbidity and mortality. This study examined the results of thoracic endovascular aortic repair (TEVAR) in acute type B aortic dissection complicated with rupture or malperfusion syndrome. METHODS From 2004 through 2007, 35 patients (22 men) with acute complicated type B aortic dissection were treated with TEVAR. Indications included rupture in 18 (51.4%) and malperfusion syndrome in 17 (48.6%; mesenteric or renal, 5;lower extremities, 3; both, 9). Three types of endograft devices were used (mean per patient, 1.9 devices). Intravascular ultrasound imaging was used in 15 patients (42.8%). In patients with malperfusion syndrome, distal adjunct procedures to expand the true lumen included infrarenal aortic stents in 4, mesenteric/renal stents in 4, and iliofemoral stents in 7. Follow-up was 93.9% during a period of 18.3 months (range, 3 to 47 months). RESULTS The mean age was 58.6 +/- 13.4 years. Technical success (coverage of the primary tear site) was achieved in 34 patients (97.1%). Coverage of the left subclavian artery was required in 25 patients (71.4%). Thirty-day mortality was 2.8%. One-year survival was 93.4% +/- 4.6%. Complications included permanent renal failure (2.8%), stroke (2.8%), spinal cord ischemia (transient [5.7%], permanent [(2.8%]), and vascular access (14.2%). The mean intensive care unit and hospital stay were 4.7 +/- 2.6 and 16.7 +/- 12.0 days, respectively. CONCLUSIONS Endovascular repair of acute complicated type B aortic dissection is associated with low morbidity and mortality and has emerged as the surgical therapy of choice.

New Paradigms and Improved Results for the Surgical Treatment of Acute Type A Dissection

ObjectiveTo examine the effect of an integrated surgical approach to the treatment of acute type A dissections. Summary Background DataAcute type A dissection requires surgery to prevent death from proximal aortic rupture or malperfusion. Most series of the past decade have reported a death rate in the range of 15% to 30%. MethodsFrom January 1994 to March 2001, 104 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) to replace the aortic arch; HCA established after 5 minutes of electroencephalographic (EEG) silence in neuromonitored patients (66%) or after 45 minutes of cooling in patients who were not neuromonitored (34%); reinforcement of the residual arch tissue with a Teflon felt “neo-media”; cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt “neo-media” and aortic valve resuspension (78%) or replacement with a biologic or mechanical valved conduit (22%). ResultsMean age was 59 ± 15 (range 22–86) years, with 71% men and 13% redo sternotomy after a previous cardiac procedure. Mean cardiopulmonary bypass time was 196 ± 50 minutes. Mean HCA with RCP time was 42 ± 12 minutes (range 19–84). Mean cardiac ischemic time was 140 ± 45 minutes. Eleven percent of patients presented with a preoperative neurologic deficit, and 5% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9%. Excluding the patients who presented neurologically unresponsive or with ongoing cardiopulmonary resuscitation (n = 5), the death rate was 4%. In six patients adverse cerebral outcomes were potentially avoided when immediate surgical fenestration was prompted by a sudden change in the EEG during cooling. Forty-five percent of neuromonitored patients required greater than 30 minutes to achieve EEG silence. ConclusionThe authors have shown that the surgical integration of sinus segment repair or aortic root replacement, the use of EEG monitoring, partial or total arch replacement using RCP, routine antegrade graft perfusion, and the uniform use of transesophageal echocardiography substantially decrease the death and complication rates of acute type A dissection repair.

Involvement of skeletal muscle in dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy)

Nephrogenic fibrosing dermopathy (NFD), a newly recognized scleroderma‐like disease, was originally described as a purely cutaneous disorder. More widespread involvement, including fibrosis of pulmonary and cardiac tissues, has been documented only recently, and it has been suggested that a more appropriate designation is dialysis‐associated systemic fibrosis. We report five cases of this novel disorder, spanning a spectrum of primarily skin to primarily muscle involvement. Clinical, radiological, electrophysiological, and pathological studies revealed moderate to severe fibrosis of striated muscles. All patients had end‐stage renal failure on chronic dialysis, subacute to chronic hardening of the skin and muscles, restriction of limb movements with joint contractures, but normal to only mildly weak muscle strength. Limitation of movements was caused predominantly by skin tightness and induration, and by joint contractures rather than muscle weakness. Computerized tomography showed fibrosis of the fascia and muscles in the most severely affected patients, and electromyography showed mild to severe myopathic changes. Histopathology of affected muscles revealed a spectrum of mild to severe fibrosis, degenerating fibers, and chronic inflammatory cells. These results further support the contention that NFD is not a purely cutaneous disease, but is part of a larger systemic fibrotic process that may involve muscles. Muscle Nerve, 2004

Interventions for reversing delayed-onset postoperative paraplegia after thoracic aortic reconstruction

BACKGROUND Delayed postoperative paraplegia is a recognized complication of thoracic (TAA) or thoracoabdominal aortic aneurysm (TAAA) repair. The purpose of this study was to evaluate the effectiveness of interventions to treat delayed-onset paraplegia. METHODS Between January 1, 2000 and August 31, 2001, 99 patients underwent surgical repair of TAA, Crawford type I, II, or III TAAA. Standard intraoperative management included distal aortic perfusion and cerebrospinal fluid (CSF) drainage unless contraindicated. Therapeutic interventions to treat delayed paraplegia included lumbar CSF drainage and vasopressor therapy. RESULTS Three of the 99 patients had paraplegia upon awakening. Delayed-onset paraplegia occurred in 8 patients, 2 of whom had recurrent episodes. In those 8 patients, the initial episode occurred at a median of 21.6 hours (range 6.4 to 110.0 hours) after surgery and the second episode averaged 176 hours after surgery. At the onset of paraplegia, the average mean arterial pressure was 74 mm Hg and CSF pressure was 14 mm Hg. Three of the 8 patients had a functioning CSF catheter at the onset and the other 5 patients had catheters subsequently placed. Therapeutic interventions increased blood pressure to a mean arterial pressure of 95 mm Hg and decreased CSF pressure to 10 mm Hg. Five of the 8 patients with delayed-onset paraplegia made a full neurologic recovery and 3 had partial recovery. CONCLUSIONS Patients with delayed-onset paraplegia had an increased chance of recovery as compared with those patients in whom paraplegia was diagnosed upon emergence from anesthesia. Acute interventions directed to increase spinal cord perfusion by increasing systemic blood pressure and decreasing CSF pressure were effective for the reversal of delayed onset of paraplegia after TAA or TAAA repair, resulting in an overall 3% incidence of permanent paraplegia and 3% incidence of residual paraparesis.

Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2

Childhood onset motor neuron diseases or neuronopathies are a clinically heterogeneous group of disorders. A particularly severe subgroup first described in 1894, and subsequently called Brown-Vialetto-Van Laere syndrome, is characterized by progressive pontobulbar palsy, sensorineural hearing loss and respiratory insufficiency. There has been no treatment for this progressive neurodegenerative disorder, which leads to respiratory failure and usually death during childhood. We recently reported the identification of SLC52A2, encoding riboflavin transporter RFVT2, as a new causative gene for Brown-Vialetto-Van Laere syndrome. We used both exome and Sanger sequencing to identify SLC52A2 mutations in patients presenting with cranial neuropathies and sensorimotor neuropathy with or without respiratory insufficiency. We undertook clinical, neurophysiological and biochemical characterization of patients with mutations in SLC52A2, functionally analysed the most prevalent mutations and initiated a regimen of high-dose oral riboflavin. We identified 18 patients from 13 families with compound heterozygous or homozygous mutations in SLC52A2. Affected individuals share a core phenotype of rapidly progressive axonal sensorimotor neuropathy (manifesting with sensory ataxia, severe weakness of the upper limbs and axial muscles with distinctly preserved strength of the lower limbs), hearing loss, optic atrophy and respiratory insufficiency. We demonstrate that SLC52A2 mutations cause reduced riboflavin uptake and reduced riboflavin transporter protein expression, and we report the response to high-dose oral riboflavin therapy in patients with SLC52A2 mutations, including significant and sustained clinical and biochemical improvements in two patients and preliminary clinical response data in 13 patients with associated biochemical improvements in 10 patients. The clinical and biochemical responses of this SLC52A2-specific cohort suggest that riboflavin supplementation can ameliorate the progression of this neurodegenerative condition, particularly when initiated soon after the onset of symptoms.

Susceptibility Contrast and Arterial Spin Labeled Perfusion MRI in Cerebrovascular Disease

Purpose. To directly compare dynamic susceptibility contrast (DSC) and continuous arterial spin labeled (CASL) magnetic resonance (MR) perfusion techniques in patients with known cerebrovascular disease, with the goals of identifying possible pitfalls in interpretation and determining potential for a complementary role in this setting. Methods. DSC and CASL MR perfusion studies were performed and compared in 11 patients with acute and/or chronic cerebrovascular disease. Using an automated segmentation technique, Pearson correlation coefficients were generated for CASL perfusion measurements compared to DSC perfusion maps (time‐to‐peak [TTP], relative cerebral blood volume [rCBV], cerebral blood flow [rCBF], and mean transit time [MTT]) by hemisphere and vascular territory. Results. TTP maps obtained using DSC perfusion MR correlated best both subjectively and objectively with CASL perfusion MRmeasurements when all patients studied were considered. If patients with a major transit delay were excluded, DSC rCBF correlated best with CASL CBF measurements. Conclusion. There may be a complementary role for CASL and DSC perfusion MR methods in cerebrovascular disease, especially in the setting of a marked transit delay.

Biomarker evidence for mild central nervous system injury after surgically-induced circulation arrest

Previously, we identified 14-3-3 beta and zeta isoforms and proteolytic fragments of alpha-spectrin as proteins released from degenerating neurons that also rise markedly in cerebrospinal fluid (CSF) following experimental brain injury or ischemia in rodents, but these proteins have not been studied before as potential biomarkers for ischemic central nervous system injury in humans. Here we describe longitudinal analysis of these proteins along with the neuron-enriched hypophosphorylated neurofilament H (pNFH) and the deubiquitinating enzyme UCH-L1 in lumbar CSF samples from 19 surgical cases of aortic aneurysm repair, 7 involving cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA). CSF levels of the proteins were near the lower limit of detection by Western blot or enzyme-linked fluorescence immunoassay at the onset of surgical procedures, but increased substantially in a subset of cases, typically within 12-24 h. All cases involving DHCA were characterized by >3-fold elevations in CSF levels of the two 14-3-3 isoforms, UCH-L1, and pNFH. Six of 7 also exhibited marked increases in alpha-spectrin fragments generated by calpain, a protease known to trigger necrotic neurodegeneration. Among cases involving aortic cross-clamping but not DHCA, the proteins rose in CSF preferentially in the subset experiencing acute neurological complications. Our results suggest the neuron-enriched 14-3-3beta, 14-3-3zeta, pNFH, UCH-L1, and calpain-cleaved alpha-spectrin may serve as a panel of biomarkers with clinical potential for the detection and management of ischemic central nervous system injury, including for mild damage associated with surgically-induced circulation arrest.

Vascular distribution of stroke and its relationship to perioperative mortality and neurologic outcome after thoracic endovascular aortic repair

OBJECTIVE This study assessed the vascular distribution of stroke after thoracic endovascular aortic repair (TEVAR) and its relationship to perioperative death and neurologic outcome. METHODS A retrospective review was performed for patients undergoing TEVAR between 2001 and 2010. Aortic arch hybrid and abdominal debranching cases were excluded. Demographics, operative variables, and neurologic complications were examined. Stroke was defined as any new focal or global neurologic deficit lasting>24 hours with radiographic confirmation of acute intracranial pathology. RESULTS Perioperative stroke occurred in 20 of 530 patients (3.8%) undergoing TEVAR. The cohort was 55% male and a mean age of 75.2±8.9 years (range, 57-90 years). Among patients with perioperative strokes, the indication for surgery was degenerative aneurysm in 14 (mean diameter, 6.8 cm), acute type B dissection in four, penetrating atherosclerotic aneurysm in one, and aortic transection in one. Cases were performed urgently or as an emergency in 60%. The proximal landing zone was zone 2 in 11 or zone 3 in nine. All strokes were embolic. The vascular distribution of stroke involved the anterior cerebral (AC) circulation in eight (zone 2, n=5) and the posterior cerebral (PC) circulation in 12 (zone 2, n=6). Laterality of cerebral infarction included five right-sided, eight left-sided, and seven bilateral strokes. Nine strokes were diagnosed<24 hours after operation. There was no difference in baseline demographics, aortic pathology, acuity, zone coverage, preoperative left subclavian artery revascularization, number of stents, or estimated blood loss between stroke groups based on vascular distribution. Independent risk factors for any perioperative stroke were chronic renal insufficiency (odds ratios [OR], 4.65; 95% confidence interval [CI], 1.22-17.7; P=.02) and history of prior stroke (OR, 4.92; 95% CI, 1.69-14.4; P=.004); the risk factor for AC stroke was prior stroke (OR, 7.67; 95% CI, 1.25-46.9; P=.03) and the risk factors for PC stroke were age (OR, 1.11; 95% CI, 1.00-1.23; P=.04), prior stroke (OR, 7.53; 95% CI, 1.78-31.8; P=.006), zone 2 coverage (OR, 6.11; 95% CI, 1.15-32.3; P=.03), and penetrating atherosclerotic ulcer (OR, 32.7; 95% CI, 1.33-807.2; P=.03). Overall in-hospital mortality was 20% (n=4), with those sustaining PC strokes observed to trend toward increased mortality (33% vs 0%; P=.12). Patients with AC strokes were more likely than those with PC strokes to achieve complete recovery of neurologic deficits before discharge (75% vs 17%; P=.02). CONCLUSIONS Perioperative stroke after TEVAR is primarily an embolic event. Although infrequent, stroke was associated with significant morbidity and death, particularly among those with strokes involving the PC circulation.

Modified National Institutes of Health Stroke Scale Can Be Estimated From Medical Records

Background and Purpose— The 15-item National Institutes of Health Stroke Scale (NIHSS) is a quantitative measure of stroke-related neurological deficit with established reliability and validity for use in clinical research. An abridged 11-item modified NIHSS (mNIHSS) has been described that simplifies or eliminates redundant and less reliable items. We aimed to determine whether the mNIHSS could be accurately abstracted from medical records to facilitate retrospective research. Methods— We selected 39 patient records for which NIHSS scores were formally measured. Handwritten notes from medical records were abstracted, and NIHSS item scores were estimated by 5 raters blinded to actual scores. Estimated scores were compared among raters and with actual measured scores. Results— Interrater reliability for total NIHSS on admission and discharge was excellent, with intraclass correlation coefficients (ICCs) of 0.85 and 0.79, respectively. However, ICCs for 2 items (facial palsy and dysarthria) were poor (<0.40). Interrater reliability for total mNIHSS was slightly greater, with ICCs of 0.87 and 0.89 on admission and discharge, respectively. None of the 11 mNIHSS items had poor reliability, 4 were moderate (ICC, 0.40 to 0.75), and 7 were excellent (ICC >0.75). Sixty-two percent of estimated total NIHSS scores were within 2 points of actual scores and 91% were within 5 points, whereas 70% of estimated total mNIHSS scores were within 2 points and 95% were within 5 points. Conclusions— The mNIHSS can be estimated from medical records with a high degree of reliability and validity. In retrospective assessment of stroke severity, the mNIHSS performs better than the standard NIHSS and may be easier to use because it has fewer and simpler items.