Pablo R. Castillo

Recombinant Factor VIIa for Rapid Reversal of Warfarin Anticoagulation in Acute Intracranial Hemorrhage

OBJECTIVE To assess the effects of recombinant factor VIIa (rFVIIa) on hemorrhage volume and functional outcomes in warfarin-related acute intracranial hemorrhage (ICH), which has a 30-day mortality of more than 50%. PATIENTS AND METHODS We reviewed the clinical, laboratory, and radiographic features of a consecutive series of 7 patients (median age, 87 years; 5 women) with symptomatic, nontraumatic warfarin-related acute ICH treated with intravenous rFVIIa at St. Lukes Hospital in Jacksonville, Fla, between December 2002 and September 2003. Prestroke baseline functional status was assessed with the modified Rankin Scale. Outcome was assessed with the Glasgow Outcome Scale. RESULTS The international normalized ratio decreased from a mean of 2.7 before administration of rFVIIa to 1.08 after administration of rFVIIa. The median prestroke score on the modified Rankin Scale was zero. The median presenting score on the Glasgow Coma Scale was 14 (range, 4-15). The mean time from onset to treatment was 6.2 hours. The mean initial dose of rFVIIa was 62.1 microg/kg. One patient underwent placement of an external ventricular drain, and another underwent craniotomy and hematoma evacuation. Five of the 7 patients survived and were dismissed from the hospital with severe disability (Glasgow Outcome Scale, 3); 2 patients died during hospitalization. CONCLUSIONS Intravenous bolus administration of rFVIIa can rapidly lower the international normalized ratio and appears to be safe for patients with warfarin-related ICH. Prospective controlled studies are needed to determine whether rFVIIa can prevent hematoma expansion and improve neurologic outcomes in patients with warfarin-related ICH.

EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis

OBJECTIVE To analyze the electroencephalogram (EEG) findings of patients with steroid-responsive encephalopathy associated with autoimmune (Hashimoto) thyroiditis. METHODS We reviewed 51 EEGs and the clinical records of 17 patients (5 men and 12 women, 27-84 years old). RESULTS All patients had mild to severe generalized slowing on the EEG which corresponded to the clinical severity of the underlying encephalopathy. Other findings included triphasic waves, epileptiform abnormalities, photomyogenic response, and photoparoxysmal response. Follow-up EEGs of 13 patients showed slowing in 7 and a return to normal in 6. Myoclonic jerks were recorded during the EEG study of 8 patients but did not have an EEG correlate. The EEG and clinical condition improved after treatment with corticosteroids. When encephalopathy recurred, the EEG showed corresponding abnormalities. CONCLUSIONS EEG findings in steroid-responsive encephalopathy associated with autoimmune thyroiditis consist mainly of slow wave abnormalities that reflect the degree of severity of the underlying encephalopathy. The EEG findings often paralleled the course of the disease, showing improvement with improvement in the clinical condition and worsening with recurrence of symptoms. SIGNIFICANCE The EEG is helpful in evaluating and following patients with steroid-responsive encephalopathy associated with autoimmune thyroiditis in reflecting the degree of central nervous system (CNS) involvement, in determining whether their condition is better or worse, and in ruling out other causes of encephalopathy.

Neurocysticercosis and oncogenesis.

Recent studies suggest that neurocysticercosis may be a risk factor for human cancer. Pathogenetic mechanisms explaining possible oncogenic effects of cysticerci include the following: (a) parasite-induced modulation of the host immune response that may be associated with loss of regulatory mechanisms implicated in the immunological surveillance against cancer; (b) transfer of genetic material from the parasite to the host, causing DNA damage and malignant transformation of host cells, and (c) chronic inflammation with liberation of nitric oxide and inhibition of tumor suppressor genes. Further research is needed to confirm the potential role of cysticercosis in the development of cancer. These studies should determine the presence of cysticercotic factors responsible for the transfer of genetic material and potential mutations in the tumor suppressor genes in proliferating astrocytes surrounding cysticercotic lesions. Additionally, the complex interaction between the immune state of the host with variable cytokine release and the presence of inflammatory cells releasing nitric oxide that cause DNA damage and impair tumor suppressive mechanisms needs to be investigated.

Spanish Cross-Cultural Adaptation and Validation of the National Institutes of Health Stroke Scale

OBJECTIVES To adapt and validate a Spanish-language version (SV) of the National Institutes of Health Stroke Scale (NIHSS) to facilitate its use in Spanish-speaking contexts. PATIENTS AND METHODS The methods recommended by the International Quality of Life Assessment Project were followed. Two forward translations and 1 back translation of the NIHSS were developed to ensure lingual and cultural equivalence. A final revised SV-NIHSS was administered by 8 physicians to patients with stroke in 3 clinics in Buenos Aires, Argentina, from September 2003 to December 2003. RESULTS The study included 102 patients (mean +/- SD age, 73.3+/-6.5 years; 56% women) with stroke (86% ischemic). The SV-NIHSS mean baseline score was 9.78+/-7.04. Interrater reliability was Independently evaluated for 98 patients, showing a high agreement: kappa, 0.77 to 0.99 for the 15 items; interrater correlation coefficient, 0.991 (95% confidence Interval, 0.987-0.994). Intrarater reliability was excellent: kappa, 0.86 to 1.00 for the 15 items; mean intrarater correlation coefficient, 0.994 (95% confidence interval, 0.991-0.996). Construct validity was also adequate; the SV-NIHSS had a negative correlation with baseline Glasgow Coma Scale (Spearman coefficient = -0.574, P < .001) and with Barthel index at 3 months (Spearman coefficient = -0.658, P < .001). Patients with different Rankin scores at 3 months also had significantly different baseline SV-NIHSS scores, from a mean of 4.29+/-2.21 for Rankin score of 0 to a mean of 29.40+/-3.97 for Rankin score of 6 (P < .001). CONCLUSION This study shows that a Spanish-language version of the NIHSS developed with internationally recommended methods is reliable and valid when applied in a Spanish-speaking setting.

Poor sleep quality and silent markers of cerebral small vessel disease: a population-based study in community-dwelling older adults (The Atahualpa Project)

BACKGROUND/OBJECTIVES Evidence of a relationship between non-breathing-related sleep symptoms and silent markers of cerebral small vessel disease (SVD) is scarce. The present study aimed to evaluate this association in older people living in rural Ecuador, where the burden of stroke is on the rise. METHODS A group of Atahualpa residents, aged ≥60 years, were interviewed with a validated Spanish version of the Pittsburgh Sleep Quality Index, and underwent magnetic resonance imaging (MRI) for identification of silent markers of SVD. Using multinomial logistic regression analysis, after adjusting for demographics and cardiovascular health status, it was evaluated whether sleep quality is associated with the severity of white matter hyperintensity (WMH), lacunar infarcts, and deep microbleeds. RESULTS Out of 311 people aged ≥60 years, 237 (76%) were enrolled into the study. Mean age was 70 ± 8 years, 59% were women, 83% had primary school education only, and 73% had a poor cardiovascular health status. Seventy-eight (33%) had poor sleep quality. The MRI showed: WMH in 154 (65%) participants (moderate-to-severe in 52); silent lacunar infarcts in 28 (12%); and deep microbleeds in 17 (7%). Poor sleep quality was associated with WMH presence (OR 2.44, 95% CI 1.26 to 4.71, p = 0.008) and severity (β coefficient 0.77, SE 0.37, p = 0.037), but not with silent lacunar infarcts or deep microbleeds. CONCLUSIONS The present study showed an association between poor sleep quality and WMH severity. Further longitudinal studies would help to elucidate the cause and effect of this relationship.

Prevalence of Restless Legs Syndrome in Blood Donors

Iron deficiency anemia has been linked to restless legs syndrome (RLS) and regular blood donation may lead to iron deficiency. It has been reported that blood donations may be associated with RLS. A recent study from Sweden found that 25% of the women donors were affected by RLS. However, this type of study has not been replicated in the United States. We conducted a study in our blood donation unit between September and October 2008. To identify those with RLS, we used the RLS diagnostic index questionnaire by Benes et al. The proportion of blood donors with RLS was estimated and the number of blood donations and hemoglobin levels were compared according to RLS status. One hundred and fifty one patients were interviewed; 7 patients who donated only platelets were excluded, leaving 144 patients for analysis. There were 13 (9.0%, 95% confidence interval [CI]: 4.9–14.9%) patients with RLS. Of these, 7 (4.9%, 95% CI: 2.0–9.8%) had possible RLS and 6 (4.2%, 95% CI: 1.5–8.9%) had major or clinically relevant RLS. There was no dramatic association between RLS and number of blood donations or hemoglobin level (all P ≥ 0.21). In our sample of blood donors in the United States, the prevalence of major RLS was 4%. We could not demonstrate an association between RLS and the frequency of blood donation or hemoglobin level in our relatively small sample; a larger sample is needed to better identify any associations.

Dietary fish intake and sleep quality: a population-based study

BACKGROUND/OBJECTIVES Due to the content of omega-3 and vitamin D, fish consumption is likely to be associated with better sleep. However, current data are limited to a single study that is not representative of the population at large. The present study aimed to assess the effects of oily fish consumption on sleep quality in community dwelling adults living in rural coastal Ecuador. METHODS Atahualpa residents aged ≥40 years and who were identified during a door-to-door survey were interviewed with field instruments directed at assessing cardiovascular risk factors, sleep quality, and fish consumption. Using parametric regression and generalized linear models adjusted for demographics and cardiovascular risk factors, the study evaluated whether oily fish consumption is associated with a lower Pittsburgh sleep quality index (PSQI). RESULTS Out of 721 eligible people, 677 (94%) were enrolled. Mean oily fish consumption was 9 ± 6 servings per week (one serving = 140 grams). Poor sleep quality was noticed in 187 (28%) individuals. Oily fish intake was higher in individuals with good sleep quality (p = 0.013). There was an inverse association between the PSQI score and oily fish servings per week in both parametric regression (β = -0.040; 95% CI -0.690 to -0.011, p = 0.007) and the adjusted generalized linear model (β = -0.032; 95% CI -0.605 to -0.004, p = 0.025). CONCLUSIONS Oily fish consumption is associated with better sleep quality. Even in people who ingest more than the recommended amount of fish, an increase in fish intake is associated with further improvement in the quality of sleep.

Creation of a bilingual Spanish-English version of the questionnaire for verifying stroke-free status

Spanish-language versions of standardized questionnaires are important for facilitating inclusion of Hispanic populations in epidemiologic, genetic, and clinical studies. We aimed at producing a culturally adapted Spanish translation of the Questionnaire for Verifying Stroke-free Status (QVSS), an instrument used to screen for cerebrovascular end points and to ensure that subjects serving as controls in studies on stroke are indeed stroke free. Five professional translators and ten bilingual physicians independently translated the English-language version of the QVSS into Spanish. Blinded back-translation confirmed conceptual equivalence of the original English-language and final Spanish-language versions.

Key findings from the Atahualpa Project: what should we learn?

Owing to increased life expectancy and changes in lifestyles, the burden of noncommunicable neurological diseases is on the rise in rural areas of developing countries, to the point of being considered the new epidemics in these regions. However, knowledge on the impact of these conditions in rural setting is limited because the practice of populationbased studies is complicated due to several cross-cultural factors. For example, the common practice of telephone interviews in population-based studies conducted in developed countries is next to impossible in rural areas, where face-toface interviews are mandatory to get correct information. In addition, reliable prevalence rates of conditions associated with stigma can better be assessed if acquainted field personnel conduct the interviews [1]. Moreover, accurate diagnosis of most noncommunicable neurological diseases requires the use of sophisticated technology that is not available in these areas.

The Effect of Age in the Association between Frailty and Poor Sleep Quality: A Population-Based Study in Community-Dwellers (The Atahualpa Project).

PURPOSE To assess the effect of age in the association between poor sleep quality and frailty status. DESIGN AND SETTING Population-based, cross-sectional study conducted in Atahualpa, a rural village located in coastal Ecuador. METHODS Out of 351 Atahualpa residents aged ≥ 60 years, 311 (89%) were interviewed with the Pittsburgh Sleep Quality Index (PSQI) and the Edmonton Frail Scale (EFS). The independent association between PSQI and EFS scores was evaluated by the use of a generalized linear model adjusted for relevant confounders. A contour plot with Shepard interpolation was constructed to assess the effect of age in this association. RESULTS Mean score in the PSQI was 5 ± 2 points, with 34% individuals classified as poor sleepers. Mean score in the EFS was 5 ± 3 points, with 46% individuals classified as robust, 23% as prefrail, and 31% as frail. In the fully adjusted model, higher scores in the PSQI were significantly associated with higher scores in the EFS (β 0.23; 95% CI 0.11-0.35; P < .0001). Several clusters depicted the strong effect of age in the association between PSQI and EFS scores. Older individuals were more likely to have high scores in the EFS and the PSQI, and younger individuals had low EFS scores and were good sleepers. Clusters of younger individuals who were poor sleepers and had high EFS scores accounted for the independent association between PSQI and EFS scores. CONCLUSIONS This study shows the strong effect of age in the association between poor sleep quality and frailty status.