Methods: We used a pre- and post-test design with an educational intervention in between using neurology residents at the University of Iowa as subjects. Each test had 40 questions of research methodology. The educational intervention consisted of a biweekly, structured, topic-centered, research methodology-oriented elective seminar following a year-long predefined curriculum. An exit survey was offered to gather resident’s perceptions about the course.

Results: While a majority of residents agreed that the intervention enhanced their knowledge of research methodology, only 23% attended more than 40% of the sessions. There was no difference between pretest and post-test scores (p = 0.40).

Conclusions: Our experience suggests that, in order to accomplish the Accreditation Council for Graduate Medical Education goals regarding increasing competency of residents in knowledge about research methodology, a major restructuring in the neurology residency curriculum with more intense formal training would be necessary.

Methods: We studied a 50-year-old man with X-linked PHK deficiency using ischemic forearm and cycle ergometry exercise tests to define the derangement of muscle metabolism. We compared our findings with those in patients with McArdle disease and in healthy subjects.

Results: Sequencing of PHKA1 showed a novel pathogenic mutation (c.831G>A) in exon 7. There was a normal increase of plasma lactate during forearm ischemic exercise, but lactate did not change during dynamic, submaximal exercise in contrast to the fourfold increase in healthy subjects. Constant workload elicited a second wind in all patients with McArdle disease, but not in the patient with PHK deficiency. IV glucose administration appeared to improve exercise tolerance in the patient with PHK deficiency, but not to the same extent as in the patients with McArdle disease. Lipolysis was higher in the patient with PHK deficiency than in controls.

Conclusion: These findings demonstrate that X-linked PHK deficiency causes a mild metabolic myopathy with blunted muscle glycogen breakdown and impaired lactate production during dynamic exercise, which impairs oxidative capacity only marginally. The different response of lactate to submaximal and maximal exercise is likely related to differential activation mechanisms for myophosphorylase.

Methods: Indirect immunofluorescence screening of sera from 130,000 patients performed on a service basis for markers of paraneoplastic neurologic autoimmunity identified 80 patients whose IgG bound to the synapse-rich molecular layer of mouse cerebellar cortex in a pattern consistent with VGKC immunoreactivity. Antibody specificity was confirmed in all cases by immunoprecipitation of detergent-solubilized brain synaptic proteins complexed with ¹²⁵I-alpha-dendrotoxin.

Results: Clinical information was available for 72 patients: 51% women, median age at symptom onset 65 years, and median follow-up period 14 months. Neurologic manifestations were acute to subacute in onset in 71% and multifocal in 46%; 71% had cognitive impairment, 58% seizures, 33% dysautonomia, 29% myoclonus, 26% dyssomnia, 25% peripheral nerve dysfunction, 21% extrapyramidal dysfunction, and 19% brainstem/cranial nerve dysfunction. Creutzfeldt-Jakob disease was a common misdiagnosis (14%). Neoplasms encountered (confirmed histologically in 33%) included 18 carcinomas, 5 adenomas, 1 thymoma, and 3 hematologic malignancies. Hyponatremia was documented in 36%, other organ-specific autoantibodies in 49%, and a co-existing autoimmune disorder in 33% (including thyroiditis 21%, type 1 diabetes mellitus 11%). Benefit was reported for 34 of 38 patients (89%) receiving immunotherapy and was marked in 50%.

Conclusions: The spectrum of neurologic manifestations and neoplasms associated with voltage-gated potassium channel (VGKC) autoimmunity is broader than previously recognized. Evaluation for VGKC antibodies is recommended in the comprehensive autoimmune serologic testing of subacute idiopathic neurologic disorders.

Methods: We used an extensive neuropsychological battery assessing IQ, memory, attention/concentration, executive functions, and language. Fatigue and depression were also measured. An interview on school and daily living activities was obtained from the parents. Performance of cases was compared with that of demographically matched healthy controls.

Results: Sixty-three patients and 57 healthy controls were assessed. Five patients (8%) exhibited a particularly low IQ (<70). Criteria for cognitive impairment (failure on at least three tests) were fulfilled in 19 patients (31%), whereas 32 patients (53%) failed at least two tests. Beyond deficits in memory, complex attention, and executive functions, the profile of deficits was characterized by involvement of linguistic abilities. In the regression analysis, the only significant predictor of cognitive impairment was an IQ score lower than 90 (odds ratio [OR] 18.2, 95% CI 4.6–71.7, p < 0.001). Considering the IQ score as a dependent variable, the only significant predictor was represented by younger age at onset (OR 0.7, 95% CI 0.5–0.9, p = 0.009). Depressive symptoms were reported by 6% of the cases, and fatigue was reported by 73% of the cases. MS negatively affected school and everyday activities in 56% of the subjects.

Conclusions: In childhood and juvenile cases, multiple sclerosis (MS) is associated with cognitive impairment and low IQ scores, the latter related to younger age at onset. These aspects are of critical importance in helping children and adolescents with MS to manage their difficulties and psychosocial challenges.

Methods: This study uses functional MRI to investigate blood oxygenation level dependent changes in the parietal lobe in a high-risk sample of 18 asymptomatic offspring of autopsy-confirmed AD cases, compared to 15 matched controls. The cognitive activation paradigm was a mental rotation task, which requires individuals to rotate three-dimensional cube stimuli to judge their similarity.

Results: We found no differences in either reaction time or performance accuracy between groups. However, the at-risk individuals showed increases in activation in the right superior parietal lobule (BA 7), the right insula (BA 13), the right middle frontal gyrus (BA 10), and the right inferior frontal gyrus (BA 47).

Conclusions: We present evidence for a compensatory mechanism for those at increased risk for Alzheimer disease (AD). This study examines and confirms parietal changes with increased risk for late-onset AD, despite normal cognitive performance. Added to the previous findings from this group, these results demonstrate the sensitivity of functional imaging measures to brain changes that are not yet reflected in cognitive performance, which may ultimately serve as an important indicator of disease.

Background: Obesity is a risk factor for headache "chronification." Adiponectin (ADP) is an adipocytokine secreted primarily by adipose tissue. ADP and its oligomers (high-molecular-weight [HMW], middle-molecular-weight [MMW], and low-molecular-weight [LMW] ADP) have been shown to modulate several inflammatory pathways that have also been shown to be associated with migraine pathophysiology.

Methods: Age- and body mass index (BMI)-matched women participants were enrolled. Anthropometric measures (including waist-to-hip ratio [WHR] and BMI) were measured in all participants. Serum total ADP (T-ADP) levels and its oligomers were measured in EMs during headache-free periods and CDH sufferers at baseline level of pain, as compared with healthy control subjects using ELISA.

Results: Although total body obesity as estimated by BMI showed no significant association between participants, visceral obesity as estimated by WHR was significantly associated with CDH as compared with EMs and controls. WHR was also inversely related to both T-ADP (p = 0.008) and HMW-ADP (p = 0.002). After adjusting for WHR, serum T-ADP levels were higher in CDH sufferers (10.1 ± 4.0) than in both EMs (8.6 ± 3.5) and controls (7.5 ± 2.4) (p = 0.024). In addition, HMW-ADP was higher in CDH (6.1 ± 2.8) as compared with EMs (4.2 ± 1.7) and controls (3.9 ± 1.5) (p = 0.003). MMW-ADP was also higher in CDH (2.0 ± 1.2) as compared with EMs (1.5 ± 0.7) and controls (1.1 ± 0.4) (p = 0.009).

Conclusion: Serum adiponectin levels are increased in women chronic daily headache (CDH) sufferers. In addition, visceral obesity, as measured by waist-to-hip ratio, is a risk factor for CDH in women.