From Brain Disease to Brain Health: Primary Prevention of Alzheimer's Disease and Related Disorders in a Health System Using an Electronic Medical Record-Based Approach.

BACKGROUND: Alzheimer's disease and aging brain disorders are progressive, often fatal neurodegenerative diseases. Successful aging, modern lifestyles and behaviors have combined to result in an expected epidemic. Risks for these diseases include genetic, medical, and lifestyle factors; over 20 modifiable risks have been reported. OBJECTIVES: We aim to primarily prevent Alzheimer's disease and related disorders through electronic medical record (EMR)-based screening, risk assessments, interventions, and surveillance. DESIGN: We identified modifiable risks; developed human, systems and infrastructural resources; developed interventions; and targeted at-risk groups for the intervention. SETTING: A Community Based Health System. PARTICIPANTS: In year one (June 2015 to May 2016), 133 at-risk patients received brain health services with the goal of delaying or preventing Alzheimer's disease and related disorders. MEASUREMENTS: We created mechanisms to identify patients at high risk of neurodegenerative disease; EMR-based structured clinical documentation support tools to evaluate risk factors and history; evidence-based interventions to modify risk; and the capacity for annual surveillance, pragmatic trials, and practice-based and genomic research using the EMR. RESULTS: This paper describes our Center for Brain Health, our EMR tools, and our first year of healthy but at-risk patients. CONCLUSION: We are translating research into primary prevention of Alzheimer's disease and related disorders in our health system and aim to shift the paradigm in Neurology from brain disease to brain health.

Alpha-synuclein, pesticides, and Parkinson disease: a case-control study.

BACKGROUND: Aggregation and fibrillization of the alpha-synuclein protein (encoded by the SNCA gene) may represent key events in the pathogenesis of Parkinson disease (PD). Variability in the length of a dinucleotide repeat sequence (REP1) within the SNCA promoter confers susceptibility to sporadic PD. Pesticide exposures may also confer susceptibility to PD. Our objective was to test possible joint effects of SNCA REP1 genotypes and pesticide exposures on the risk of PD. METHODS: This was a case-control study. Cases were recruited prospectively from the Department of Neurology of the Mayo Clinic, Rochester, MN, after June 1, 1996. The control subjects included unaffected siblings of cases and unrelated population control subjects. We assessed pesticide exposures by telephone interview and genotyped SNCA REP1. Odds ratios (ORs) and 95% CIs were determined using conditional logistic regression models. RESULTS: There were 833 case-control pairs. We observed an increased risk of PD with increasing SNCA REP1 bp length (OR, 1.18 for each score unit; 95% CI, 1.02-1.37; p = 0.03). Pesticide exposures were associated with PD in younger subjects only (lowest quartile of age at study,

Education and occupations preceding Parkinson disease: a population-based case-control study.

OBJECTIVE: To investigate the association of Parkinson disease (PD) with education and occupations using a case-control study design. METHODS: The authors used the medical records-linkage system of the Rochester Epidemiology Project to identify all subjects who developed PD in Olmsted County, MN, from 1976 through 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control. The authors collected information about education and occupations using two independent sources of data: a review of the complete medical records in the system and a telephone interview. Occupations were coded using the 1980 Standard Occupational Classification. RESULTS: Subjects with 9 or more years of education were at increased risk of PD (OR = 2.0; 95% CI = 1.1 to 3.6; p = 0.02), and there was a trend of increasing risk with increasing education (test for linear trend, p = 0.02; medical records data). Physicians were at significantly increased risk of PD using both sources of occupational data. By contrast, four occupational groups showed a significantly decreased risk of PD using one source of data: construction and extractive workers (e.g., miners, oil well drillers), production workers (e.g., machine operators, fabricators), metal workers, and engineers. These associations with increased or decreased risk did not change noticeably after adjustment for education. CONCLUSION: Subjects with higher education and physicians have an increased risk of Parkinson disease (PD), while subjects with some occupations presumed to involve high physical activity have a decreased risk of PD.

Atypical facial pain: clinical considerations and differential diagnosis.

Atypical facial pain (ATFP), recently defined as persistent idiopathic facial pain by the revision of the Classification of the International Headache Society (IHS), is a poorly understood condition, which still lacks clear diagnostic criteria and proper treatment. The pain is described as "persistent facial pain that does not have the characteristics of cranial neuralgias and is not attributable to another disorder". In general, however, according to the IHS criteria, a diagnosis of ATFP is possible when the pain in the face is present daily and persists for most or all of the day. The pain is confined at onset to a limited area on one side of the face, often in the nasolabial fold or side of the chin and may spread to the upper or lower jaw or a wider area of the face of neck and is deep and poorly localised. It is not associated with sensory loss or other physical signs. Laboratory investigations including X-ray of face and jaws do not demonstrate relevant abnormality. Pain may be initiated by operation or injury to face, teeth or gums but persists without any demonstrable local cause. But, the definition and the diagnostic criteria are over-simplified when we face the reality of the clinical practice. Many different disorders may be included in this diagnostic category, making differential diagnosis very complex. Diagnosis of ATFP is therefore, usually, a process of elimination. A targeted history and an accurate examination are crucial to correctly classify this facial pain.

Controversies in optic neuritis pain diagnosis.

Optic neuritis (ON) refers to any inflammatory disorder of the optic nerve. In clinical practice ON is mainly diagnosed by ophthalmologists and less frequently by neurologists. ON diagnostic criteria are included in different classification systems both in neurologic and ophthalmologic fields. Diagnosis of ON is still very unsatisfactory. Indeed diagnostic criteria are not uniform and therefore the diagnosis is still mainly formulated according to the clinical experience only. A consensus on practice guidelines for ON diagnosis might be useful. Ocular pain is a milestone in ON diagnosis, but it is too often mistreated by both the patient and the clinician. The International Headache Society (IHS) Classification of Headache Disorders provides in its 1988 and 2004 versions the diagnostic criteria for ON. These criteria are not spread and followed by the large majority of neurologists, but they are mainly applied by the experts in headache disorders. On the other hand, ON is a disorder widely encountered by neurologists and ophthalmologists. The latest IHS version defines the criteria of the pain features more precisely, but it is still unsatisfactory. In a future revision, the pain should be further detailed. Further studies aimed at validation of the diagnostic criteria of ON are strongly needed.

Management of headache in emergency room.

Headache is one of the most common symptoms that leads patients to the emergency room (ER) and is often related to diseases requiring prompt diagnosis and immediate treatment. This consideration brought us to consider the importance of the neurologist in improving the management of patients arriving in the ER with headache. We carried out a study for testing the degree of agreement between ER physician and neurologist using patient evaluation at headache centre (HC) as the gold standard. One hundred and seventeen patients with idiopathic (78) or symptomatic (39) headache were evaluated by the ER physician, the ER neurologist and the HC expert. The ER physician and the HC expert reached a fair agreement (Kappa=0.40); the other two pairs reached a moderate agreement (Kappa=0.57-0.60). There was no significant difference in the agreement of the three evaluators in patients with impairment of daily living activities or aged over 40. The agreement between the ER physician and the neurologist was lower (Kappa=0.58), especially in patients with their first headache episode. Based on our results, patients seen at the ER for a headache episode can be fairly successfully managed by the ER physician, except those who present a first attack, for whom neurological consultation is needed.

MIDAS questionnaire in the emergency setting.

Migraine is a common disorder and is a major cause of disability and loss of working performance in western countries. Therefore, many tools have been developed to assess migraine related disability. Among these, the Migraine Disability Assessment (MIDAS) questionnaire has been shown to be of particular interest, as it is valid, reliable and useful for therapeutic decisions. In this pilot study, we address the validity of the MIDAS questionnaire in an unselected population of migraine patients in the emergency setting. We found that the MIDAS scores in the emergency room were similar to those collected in a specialised headache centre. This result suggests that the MIDAS questionnaire could be reliably used in the emergency setting, hence avoiding unnecessary delays in the treatment of migraine patients.

Visual evoked potentials in migraine.

Migraine is a chronic disorder. Visual symptoms and hypersensitivity to light stimuli are common. The aim of this study is the analysis of visual system in migraineurs by visual evoked potentials (VEP). We studied 53 migraineurs (21 with prophylactic migraine treatment and 32 without preventive therapy) and 20 healthy control subjects. We found lower P100 latencies in migraineurs without therapy compared to controls. In treated patients, P100 latencies showed the same trend seen in the control group. We speculate a different responsiveness of the visual system in migraineurs probably due to a dysmodulation of sensor input leading to facilitation of visual processing.

Optic neuritis: diagnostic criteria application in clinical practice.

Optic neuritis (ON) refers to any inflammatory optic neuropathy. In clinical practice ON is mainly diagnosed by ophthalmologists and less frequently by neurologists. ON diagnostic criteria are included in the Classification of International Headache Society (IHS) and in other classification systems, both in neurological and ophthalmologic fields. The aims of this study were to verify the application of IHS ON diagnostic criteria in clinical practice and the role of the ocular pain qualitative aspects. We performed a partially retrospective (140 cases) and prospective (43 cases) study analysing the clinical characteristics of patients with ON. We observed retro orbital pain in a huge percentage of patients; it was provoked or spontaneous and worsened by eye movements. We found that the new IHS classification criteria (IHS 2004) do not fully satisfy the requirements for ON diagnosis. Further study is necessary to validate the diagnostic criteria of ON in clinical practice.

Migrainous cerebral infarction: case reports.

Migraine is a common and chronic disorder. It is considered benign but several studies have suggested it as a rare risk factor for ischaemic stroke. The association is still conflicting and seems to be restricted to particular subgroups of patients (i.e., women under the age of 45, with migraine with aura, and particularly ones who smoke and use oral contraceptives). The pathogenetic mechanisms underlying this condition are not known. We describe 6 cases of migrainous stroke fully meeting the diagnostic criteria of the International Headache Society (IHS). For each patient, demographic and anamnestic data, clinical features, results of laboratory tests and neuroimaging findings were recorded. Five of the 6 cases were women (median age of 29, range from 23 to 40). The man was 36. All patients fulfilled the IHS criteria for migraine with aura. At the time of the event, 2 patients were taking oral contraceptives and smoked, one patient smoked and three patients had no vascular risk factors. The stroke manifested as homonymous hemianopia in 3 patients, lower homonymous quadrantopia in 1 patient and sensory symptom in 1 patient. The neurological examination was normal in 1 case. All patients underwent several tests with negative results: blood test (antithrombin III, protein C or S, autoantibodies), transthoracic and transoesophageal echocardiography, extracranial and intracranial Doppler sonography, and angiography which was not performed in 1 patient. All patients had a cerebral infarct visible on neuroimaging study (MRI): posterior cerebral artery in 4, middle cerebral artery in 1 and anterior cerebral artery in 1. We support the findings reported by others that migrainous stroke is more common in young women affected by migraine with aura. In consideration of the high prevalence of migraine in the population, further research is indicated and necessary to establish if migraine is independent from other vascular risk factors.

Antiepileptic drugs in the treatment of chronic headaches.

In recent years, anticonvulsant drugs (AEDs) have been considered promising drugs in the prevention of migraine and other forms of headache, based on their action on the metabolism of gamma-aminobutyric acid (GABA) and glutamate. To date many AEDs are being evaluated for headache preventive treatment. The results are often encouraging even if not conclusive except for valproate, which has been extensively investigated and has been found to be effective and well tolerated in the preventive therapy of migraine. Other AEDs seem to be important in the treatment of patients with resistant headaches, with both migraine and epilepsy comorbid with mood and anxiety disorders or in neuropathic pain syndromes.

Molecular and biochemical data on some glucose-6-phosphate dehydrogenase variants from southern Sardinia.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD; E.C.1.1.1.49) deficiency is the most common human enzymopathy; nearly 400 different biochemical variants of the enzyme have been described. Sardinia is the Italian region with the highest frequency of this defect. METHODS: We examined genomic DNA of 16 subjects with G6PD Mediterranean, 2 with G6PD Athens-like, 1 with G6PD Ferrara 2 (all as biochemically defined). RESULTS: All G6PD Mediterranean subjects had a C-->T mutation at nucleotide 563 and a C-->T transition at nucleotide 1311; G6PD Athens-like and Ferrara 2 subjects had a G-->C mutation at nucleotide 844 (the same mutation has been found in G6PD Seattle-like). CONCLUSIONS: This study suggests that in Southern Sardinia G6PD mutations are relatively homogeneous and that the results of biochemical characterization studies must be carefully evaluated, because the same mutations might be responsible for different biochemical behavior.

Listeria monocytogenes serotypes in Italian meat products.

Listeria monocytogenes was isolated and enumerated in Italian fresh ground beef, fresh pork meat and industrial sausages. All the samples contained less than 2000 L. monocytogenes/g of meat. The main serotype isolated was 1/2c (56.9%). Other serotypes isolated included 1/2a, 1/2b, 3c, 4b and 4c. A prevalence of less virulent serotypes over more virulent was thus noted. It seems that the low incidence of listeriosis from these products is related to the low concentration and virulence of L. monocytogenes present.

Iron overload and lysosomal stability in beta zero-thalassaemia intermedia and trait: correlation between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels.

Increased iron storage represents a characteristic condition in patients with beta zero-thalassaemia intermedia. Iron overload is an important factor in cellular damage. Recent studies have shown an enhanced lysosomal fragility due to increased iron storage. 13 patients with beta-thalassaemia intermedia, aged 17-44 years, were studied. Both serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were evaluated in all subjects studied. A significant linear correlation (P less than 0.05) between serum ferritin and serum N-acetyl-beta-D-glucosaminidase levels were found.