Neurology March 2009 Volume 72 Issue 10

Background: Optic neuritis is often the initial presentation of multiple sclerosis (MS). As established by the Optic Neuritis Treatment Trial, an abnormal baseline brain MRI is a strong predictor of MS after isolated optic neuritis in adults. However, the rate of conversion to MS after optic neuritis in children based upon brain MRI findings is unknown.Methods: We reviewed the medical records of children (<18 years) presenting with optic neuritis between 1993 and 2004 at the Children's Hospital of Philadelphia. Children with a history of demyelinating disease or prior optic neuritis were excluded. Symptoms, ophthalmologic findings, MRI findings, and clinical outcomes were recorded.Results: We identified 29 consecutive children with idiopathic optic neuritis. Eleven patients (38%) had white matter T2/FLAIR lesions in the brain (not including the optic nerves). Eighteen patients were followed for more than 24 months, and 3 of the 18 (17%) developed MS. All 3 patients had an abnormal brain MRI scan at their initial presentation of optic neuritis. None of the patients with a normal brain MRI scan at presentation developed MS over an average follow-up of 88.5 months. Patients with one or more white matter lesions on MRI were more likely to develop MS (3/7 vs 0/11, p = 0.04, Fisher exact test).Conclusions: Children with brain MRI abnormalities at the time of the diagnosis of optic neuritis have an increased risk of multiple sclerosis. Larger collaborative studies are needed to further define the prognosis for childhood optic neuritis.GLOSSARY: CHOP = Children's Hospital of Philadelphia; FLAIR = fluid-attenuated inversion recovery; MS = multiple sclerosis; NMO = neuromyelitis optica; ONTT = Optic Neuritis Treatment Trial.(C)2009AAN Enterprises, Inc.

Objective: The American Headache Society developed an innovative Web-based neurology resident educational program to 1) meet the objectives of the Accreditation Council for Graduate Medical Education Outcomes Project; 2) provide measurable improvement of a neurology resident's understanding of headache and the performance within each core competency; 3) assist residents and program directors in identifying knowledge gaps; and, ultimately, 4) improve the quality of patient care through enhanced educational initiatives.Methods: Quantitative analysis focused on pretest and post-test results, level attainment on case-based simulations, competency achievement, and interactions between cases. One of four validated global scores was related to each resident response on all competency learning opportunities and was measured, from one case to another, to determine improvement and understanding. The pretest and post-test each consisted of 50 randomized questions that tested baseline and improvement on specific core competencies and understanding of headache.Results: The pretest mean score was 30.08, and the post-test mean score was 34.79. A paired sample t test analysis showed a significant difference from pretest to post-test scores (M = -4.72, SD = 4.88, t[91] = -9.269, p < 0.001). There was significant improvement in the competencies as the residents moved through the cases as well as in each of the competencies from the pretest to the post-test. Results showed that residents increased their knowledge and performance by synthesizing the content.Conclusions: This outcomes analysis demonstrates the effectiveness of the American Headache Society Neurology Resident's Program in improving the resident's knowledge of headache medicine and Accreditation Council for Graduate Medical Education core competencies.GLOSSARY: ACGME = Accreditation Council for Graduate Medical Education; AHS = American Headache Society; GME = graduate medical education; NS = not significant; OSCCE = objective simulated computerized clinical encounter; PGY = postgraduate year.(C)2009AAN Enterprises, Inc.

Objective: The frequency and impact of apathy in subcortical ischemic vascular dementia (SIVD) remain undetermined. The frequency, clinical, neuropsychological, and imaging correlates of apathy were assessed in a large cohort of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a genetic model of SIVD.Methods: Apathy was diagnosed based on Neuropsychiatric Inventory assessment. Degree of disability was assessed by modified Rankin scale, cognitive impairment by Mattis Dementia Rating Scale (MDRS) and Mini-Mental State Examination (MMSE), autonomy by the Instrumental Activities of Daily Living (IADL) scale, and quality of life by SEP-59 self-questionnaire. Validated imaging methods were used to determine the total burden of cerebral lesions.Results: Among 132 patients, 54 (41%) were apathetic. Apathetic patients were older than nonapathetic subjects, had a lower MMSE and MDRS score, had more global disability, and were more limited in IADL. Apathetic patients were more frequently depressed compared to nonapathetic patients and more frequently presented additional neuropsychiatric symptoms. Multiple regression modeling showed a significant and independent association between apathy and a lower score of overall quality of life and between apathy and a higher load of white matter and lacunar lesions.Conclusions: The results suggest that apathy is common in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), appears in association with cognitive impairment, global functional disability, and severe neuropsychiatric symptoms during the course of the disease, and can occur separately from depression. Apathy has an independent impact on the overall quality of life in CADASIL.GLOSSARY: CADASIL = cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; IADL = Instrumental Activities of Daily Living; ICC = intracranial cavity; LL = lacunar lesions; MDRS = Mattis Dementia Rating Scale; MMSE = Mini-Mental State Examination; mRS = modified Rankin scale; NA = not applicable because of insufficient observations; nCM = number of cerebral microhemorrhages; nLL = normalized volume of lacunar lesions; NPI = Neuropsychiatric Inventory; nWMH = normalized volume of white matter hyperintensities; QOL = quality of life; SIVD = subcortical ischemic vascular dementia; TIA = transient ischemic attack; WMH = white matter hyperintensities.(C)2009AAN Enterprises, Inc.

Background: Tenecteplase is a modified tissue plasminogen activator with a longer half-life and higher fibrin specificity than alteplase.Methods: We conducted a prospective, nonrandomized, pilot study of 0.1 mg/kg IV tenecteplase given 3 to 6 hours after ischemic stroke onset. For a control group, we used patients contemporaneously treated with sub-3-hour 0.9 mg/kg IV alteplase following standard selection criteria. All patients underwent pretreatment and 24-hour perfusion/angiographic imaging with CT or MRI. Eligibility criteria for tenecteplase (but not alteplase) treatment included a perfusion lesion at least 20% greater than the infarct core, with an associated vessel occlusion. Primary outcomes, assessed blind to treatment group, were reperfusion (reduction in baseline-24-hour mean transit time lesion) and major vessel recanalization.Results: Fifteen patients received tenecteplase, and 35 patients received alteplase. The tenecteplase group had greater reperfusion (mean 74% vs 44% in the alteplase group, p = 0.01) and major vessel recanalization (10/15 tenecteplase vs 7/29 alteplase, p = 0.01). Despite later time to treatment, more tenecteplase patients (10/15 vs 7/35 alteplase, p = 0.001) had major neurologic improvement at 24 hours (NIH Stroke Scale reduction >=8). Four of the alteplase patients and none of the tenecteplase patients had parenchymal hematoma at 24 hours.Conclusions: Tenecteplase 0.1 mg/kg, using advanced imaging guidance in an extended time window, may have significant biologic efficacy in acute ischemic stroke. The imaging selection differences between the tenecteplase and alteplase groups prevent a conclusive efficacy comparison. Nonetheless, these results lend support for randomized trials comparing tenecteplase with alteplase, preferably incorporating penumbral/angiographic imaging selection.GLOSSARY: CBV = cerebral blood volume; CTA = CT angiography; CTP = perfusion CT; DWI = diffusion-weighted echo-planar spin-echo sequence; ICH = intracranial hemorrhage; MNI = major neurologic improvement; MR = magnetic resonance; mRS = modified Rankin Scale; MTT = mean transit time; NCCT = noncontrast CT; NIHSS = NIH Stroke Scale; PH = parenchymal hematoma; TIMI = Thrombolysis in Myocardial Infarction.(C)2009AAN Enterprises, Inc.

Background: In amnestic mild cognitive impairment (aMCI), functional neuronal connectivity may be altered, as suggested by quantitative EEG and neuroimaging data. In young healthy humans, the execution of linguistic tasks modifies the excitability of the hand area of the dominant primary motor cortex (M1hand), as tested by transcranial magnetic stimulation (TMS). We used TMS to investigate functional connectivity between language-related cortical areas and M1hand in aMCI.Methods: Ten elderly women with aMCI and 10 age-matched women were recruited. All participants were right handed and underwent a neuropsychological evaluation. In the first TMS experiment, participants performed three different tasks: reading aloud, viewing of non-letter strings (baseline), and nonverbal oral movements. The second experiment included the baseline condition and three visual searching/matching tasks using letters, geometric shapes, or digits as target stimuli.Results: In controls, motor evoked potentials (MEP) elicited by suprathreshold TMS of the left M1hand were significantly larger during reading aloud (170% baseline) than during nonverbal oral movements, whereas no difference was seen for right M1hand stimulation. Similarly, MEP elicited by left M1hand stimulation during letter and shape searching/matching tasks were significantly larger compared to digit task. In contrast, linguistic task performance did not produce any significant MEP modulation in patients with aMCI, although neuropsychological evaluation showed normal language abilities.Conclusions: Findings suggest that functional connectivity between the language-related brain regions and the dominant M1hand may be altered in amnestic mild cognitive impairment. Follow-up studies will reveal whether transcranial magnetic stimulation application during linguistic tasks may contribute to characterize the risk of conversion to Alzheimer disease.GLOSSARY: AD = Alzheimer disease; aMCI = amnestic mild cognitive impairment; ANOVA = analysis of variance; FDI = first dorsal interosseous; M1 = primary motor cortex; MEP = motor evoked potentials; MMSE = Mini-Mental State Examination; pvIQ = premorbid verbal intelligence; RMT = resting motor threshold; TMS = transcranial magnetic stimulation.(C)2009AAN Enterprises, Inc.