Mary-Ellen Meadows

Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 μg/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague–Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 ± 1.0 in vehicle-treated and 1.5 ± 1.3 in bFGF-treated rats (mean ± SD; TV = 12 vs. 11; p = 0.009). Infarct volume was 297 ± 65 mm3 in vehicle- and 143 ± 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood–brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

Memory impairment and depression in patients with Lyme encephalopathy Comparison with fibromyalgia and nonpsychotically depressed patients

Lyme encephalopathy, primarily manifested by disturbances in memory, mood, and sleep, is a common late neurologic manifestation of Lyme disease. We compared 20 patients with Lyme encephalopathy with 11 fibromyalgia patients and 11 nonpsychotically depressed patients using the California Verbal Learning Test, Wechsler Memory Scale, Rey-Osterrieth Complex Figure Test, Minnesota Multiphasic Personality Inventory (MMPI), and Beck Depression Inventory. Compared with patients with fibromyalgia or depression, the Lyme encephalopathy group showed mild, but statistically significant, memory deficits on two of the three memory tests. In contrast, the patients with fibromyalgia scored significantly higher than both other groups on the MMPI scale most sensitive to somatic concerns (scale l), while the depressed patients scored higher than the Lyme patients on the scales most sensitive to depression (scale 2) and anxiety (scale 7). Physical complaints and depression were not major factors in memory performance among Lyme patients. These data support the hypothesis that Lyme encephalopathy is caused by CNS dysfunction and cannot be explained as a psychological response to chronic illness.

Dissociation of autonomic and subjective responses to emotional slides in right hemisphere damaged patients

Autonomic and subjective responses to emotional and neutral slides were studied in patients with right hemisphere damage (RHD), left hemisphere damage (LHD) and normal controls (CON). Orienting and habituation to a series of pure tones (1000 Hz) were also examined. All subjects showed appropriate slide recognition and there were no group differences in subjective ratings. The CON group showed higher skin conductance responses (SCRs) to the emotional slides relative to the neutral slides, while the RHD group showed lower SCRs to both sets of slides. The LHD group showed higher SCRs independent of slide type. The results support the hypothesis (Heilman and Watson, Handbook of Neurology, Elsevier Science, 1989) that emotional paucity in RHD patients may be related to reduced autonomic arousal. However, there were no significant differences between groups in the orienting response or habituation to loud tones, suggesting that decreased arousal following RHD is not ubiquitous.

Threshold-independent functional MRI determination of language dominance: A validation study against clinical gold standards

Functional MRI (fMRI) is often used for presurgical language lateralization. In the most common approach, a laterality index (LI) is calculated on the basis of suprathreshold voxels. However, strong dependencies between LI and threshold can diminish the effectiveness of this technique; in this study we investigated an original methodology that is independent of threshold. We compared this threshold-independent method against the common threshold-dependent method in 14 patients with epilepsy who underwent Wada testing. In addition, clinical results from electrocortical language mapping and postoperative language findings were used to assess the validity of the fMRI lateralization method. The threshold-dependent methodology yielded ambiguous or incongruent lateralization outcomes in 4 of 14 patients in the inferior frontal gyrus (IFG) and in 6 of 14 patients in the supramarginal gyrus (SMG). Conversely, the threshold-independent method yielded unambiguous lateralization in all the patients tested, and demonstrated lateralization outcomes incongruent with clinical standards in 2 of 14 patients in IFG and in 1 of 14 patients in SMG. This validation study demonstrates that the threshold-dependent LI calculation is prone to significant within-patient variability that could render results unreliable; the threshold-independent method can generate distinct LIs that are more concordant with gold standard clinical findings.

Delayed Treatment with a Noncompetitive NMDA Antagonist, CNS-1102, Reduces Infarct Size in Rats

The cerebroprotective effects of noncompetitive N-methyl- D -aspartate (NMDA) antagonists are well documented in animal focal ischemia models when the agents are administered prior to

Habituation and sensitization of the orienting response following bilateral anterior cingulotomy

Skin conductance response (SCR) was measured in an orienting response (OR) and habituation paradigm in 10 post-cingulotomy and age-matched control subjects. While both groups habituated, the cingulotomy patients exhibited a slower habituation rate, and greater variability across trials compared to controls. Habituation abnormalities were not associated with increased sensitization, as neither extended habituation training or dishabituation differentiated the groups. An increased frequency of spontaneous SCR activations occurred post-cingulotomy. The results suggest that the cingulate cortex influences the temporal stability of habituation. These findings are consistent with the subtle attentional dysfunction noted following cingulate damage.

Cognitive recovery with vitamin B12 therapy: A longitudinal neuropsychological assessment

3. Abe K, Tanzi RE, Kogure K. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex. Neurosci Lett 1991;125:172-174. 4. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimers disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimers disease. Neurology 1984;34:939-944. 5. Van Straaten F, Muller R, Curran T, Van Beveren C, Verina IM. Complete nucleotide sequences of a human c-oncogene deduced amino acid sequence of the human c-fos protein. Proc Natl Acad Sci USA 1983;80:3 183-3 187. 6. Myers RM, Maniatis T, Lerman LS. Detection and localization of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol 1987;155:501-527. 7. Rogaev EI, Lukiw WJ, Vaula G, et al. Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimers disease. Neurology 1993;43:2275-2279. 1993;33:457-464.

DEVELOPMENTAL PERSPECTIVES ON OPTIMIZING EDUCATIONAL AND VOCATIONAL OUTCOMES IN CHILD AND ADULT SURVIVORS OF CANCER

Over the last few decades, long-term survival rates of children diagnosed with the two most common forms of childhood cancer, acute lymphoblastic leukemia (ALL) and brain tumors have improved substantially. Neurodevelopmental and psychosocial sequelae resulting from these diseases and their treatment have a direct impact on the developing brain and on the quality of life of these children and their families. The focus of this article is on optimizing neuropsychological and adaptive outcomes for children who have been successfully treated for these cancers and whose prospects for long-term survival are increasingly encouraging. We present a model for understanding systemic interactions among the multiple factors that influence the childs development over time and take into account contextual variables. Strategies for optimizing cognitive and psychosocial outcomes or ameliorating late effects need to consider treatment histories, specific stages of development, the contextual demands/developmental challenges associated with each, and the resources (internal and external to the child) available to meet these challenges. The challenges faced by survivors at the early childhood, middle childhood, adolescent, and emerging adulthood stages are discussed. We review different types of interventions and discuss how these can contribute to optimal functioning in survivors of childhood ALL and brain tumors.

The use of eye movement desensitization and reprocessing in the treatment of psychogenic seizures

We present a case illustrating the use of eye movement desensitization and reprocessing (EMDR) in the treatment of psychogenic seizures. These seizures were events lasting many hours, necessitating frequent emergency room visits and an extensive medical work up. Given the patients history, posttraumatic stress disorder (PTSD) was diagnosed. EMDR is widely used as a treatment modality for PTSD, and the patient was referred for once-per-week treatment, with complete recovery after 18 months of therapy. The impact of her recovery on her quality of life was astonishing. This case supports the notion that EMDR can be an effective alternative treatment for psychogenic seizures, especially when the history reveals a traumatic event or abusive experiences.

Mental Status Changes after Hematopoietic Stem Cell Transplantation

The growing numbers of survivors of innovative cancer treatments, such as hematopoietic stem cell transplantation (HSCT), often report subsequent cognitive difficulties. The objective of this study was to evaluate and compare neurocognitive changes in patients with chronic myelogenous leukemia (CML) or primary myelodysplastic syndrome (MDS) after allogeneic HSCT or other therapies.