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1.  Potential risk factors for diabetic neuropathy: a case control study 
BMC Neurology  2005;5:24.
Background
Diabetes mellitus type II afflicts at least 2 million people in Iran. Neuropathy is one of the most common complications of diabetes and lowers the patient's quality of life. Since neuropathy often leads to ulceration and amputation, we have tried to elucidate the factors that can affect its progression.
Methods
In this case-control study, 110 diabetic patients were selected from the Shariati Hospital diabetes clinic. Michigan Neuropathic Diabetic Scoring (MNDS) was used to differentiate cases from controls. The diagnosis of neuropathy was confirmed by nerve conduction studies (nerve conduction velocity and electromyography). The multiple factors compared between the two groups included consumption of angiotensin converting enzyme inhibitors (ACEI), blood pressure, serum lipid level, sex, smoking, method of diabetes control and its quality.
Results
Statistically significant relationships were found between neuropathy and age, gender, quality of diabetes control and duration of disease (P values in the order: 0.04, 0.04, < 0.001 and 0.005). No correlation was found with any atherosclerosis risk factor (high BP, hyperlipidemia, cigarette smoking).
Conclusion
In this study, hyperglycemia was the only modifiable risk factor for diabetic neuropathy. Glycemic control reduces the incidence of neuropathy, slows its progression and improves the diabetic patient's quality of life. More attention must be paid to elderly male diabetic patients with poor diabetes control with regard to regular foot examinations and more practical education.
doi:10.1186/1471-2377-5-24
PMCID: PMC1343576  PMID: 16336693
2.  The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study 
BMC Neurology  2005;5:23.
Background
Obesity causes or exacerbates a host of medical conditions, including cardiovascular, pulmonary, and endocrine diseases. Recently obesity in elderly women was associated with greater risk of dementia, white matter ischemic changes, and greater brain atrophy. The purpose of this study was to determine whether body type affects global brain volume, a marker of atrophy, in middle-aged men and women.
Methods
T1-weighted 3D volumetric magnetic resonance imaging was used to assess global brain volume for 114 individuals 40 to 66 years of age (average = 54.2 years; standard deviation = 6.6 years; 43 men and 71 women). Total cerebrospinal fluid and brain volumes were obtained with an automated tissue segmentation algorithm. A regression model was used to determine the effect of age, body mass index (BMI), and other cardiovascular risk factors on brain volume and cognition.
Results
Age and BMI were each associated with decreased brain volume. BMI did not predict cognition in this sample; however elevated diastolic blood pressure was associated with poorer episodic learning performance.
Conclusion
These findings suggest that middle-aged obese adults may already be experiencing differentially greater brain atrophy, and may potentially be at greater risk for future cognitive decline.
doi:10.1186/1471-2377-5-23
PMCID: PMC1325254  PMID: 16321166
3.  A chronic fatigue syndrome – related proteome in human cerebrospinal fluid 
BMC Neurology  2005;5:22.
Background
Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects.
Methods
Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 μl/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 μl/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis.
Results
Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of ≥1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were α-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described.
Conclusion
This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared.
doi:10.1186/1471-2377-5-22
PMCID: PMC1326206  PMID: 16321154
4.  Regional variation in hospitalization for stroke among Asians/Pacific Islanders in the United States: a nationwide retrospective cohort study 
BMC Neurology  2005;5:21.
Background
In Asia, stroke incidence varies dramatically from country to country. Little is known about stroke incidence in Asians/Pacific Islanders in the US, where regional heterogeneity in Asian/Pacific Islander sub-populations is great. We sought to characterize both the national and regional incidences of first and recurrent hospitalized acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage in Asians/Pacific Islanders compared to non-Hispanic whites.
Methods
We used the National Inpatient Sample of the 1997 Healthcare Cost and Utilization Project. It is a 20% stratified sample of hospitalizations to nonfederal hospitals in the US. National and regional projections were made using sampling weights specific for patients and hospitals. We identified stroke subtypes using previously validated ICD-9 codes. Age-adjusted incidence rates were calculated using the direct method with the US population in 2000 as the standard.
Results
There were 169,386 stroke hospitalizations in the database. Nationally, compared to whites, Asians/Pacific Islanders were more likely to have subarachnoid hemorrhage (incidence rate ratio {RR} female: 1.53, 95% CI 1.41–1.65; male RR: 1.13, 95% CI 1.00–1.27) and intracerebral hemorrhage (female RR 1.29, 95% CI 1.22–1.36; male RR: 1.58, 95% CI 1.50–1.67). However, when examined by geographic regions, Asians/Pacific Islanders had higher incidence rates of subarachnoid hemorrhage and intracerebral hemorrhage predominantly in the West, and lower rates of stroke elsewhere.
Conclusion
Stroke incidence varies 3-fold among Asians/Pacific Islanders residing in different US regions. Geographic variation is less dramatic in whites. Whether genetic or cultural differences are responsible for dramatic heterogeneity among Asian/Pacific Islander populations is unclear and deserves further study.
doi:10.1186/1471-2377-5-21
PMCID: PMC1308818  PMID: 16280090
5.  Family history and stroke outcome in a bi-ethnic, population-based stroke surveillance study 
BMC Neurology  2005;5:20.
Background
The genetic epidemiology of ischemic stroke remains relatively unstudied, and information about the genetic epidemiology of ischemic stroke in populations with significant minority representation is currently unavailable.
Methods
The Brain Attack Surveillance in Corpus Christi project (BASIC) is a population-based stroke surveillance study conducted in the bi-ethnic community of Nueces County, Texas, USA. Completed ischemic strokes were identified among patients 45 years or older seen at hospitals in the county between January 1, 2000 – December 31, 2002. A random sample of ischemic stroke patients underwent an in-person interview and detailed medical record abstraction (n = 400). Outcomes, including initial stroke severity (NIH stroke scale), age at stroke onset, 90-day mortality and functional outcome (modified Rankin scale ≥2), were studied for their association with family history of stroke among a first degree relative using multivariable logistic and linear regression. A chi-square test was used to test the association between family history of stroke and ischemic stroke subtype.
Results
The study population was 53.0% Mexican American and 58.4% female. Median age was 73.2 years. Forty percent reported a family history of stroke among a first degree relative. Family history of stroke was borderline significantly associated with stroke subtype (p = 0.0563). Family history was associated with poor functional outcome in the multivariable model (OR = 1.87; 95% CI: 1.14–3.09). Family history was not significantly related to initial stroke severity, age at stroke onset, or 90-day mortality.
Conclusion
Family history of stroke was related to ischemic stroke subtype and to functional status at discharge. More research is needed to understand whether stroke subtype would be a useful selection criterion for genetic association studies and to hypothesize about a possible genetic link to recovery following ischemic stroke.
doi:10.1186/1471-2377-5-20
PMCID: PMC1295588  PMID: 16262890
6.  Early B-cell Factor gene association with multiple sclerosis in the Spanish population 
BMC Neurology  2005;5:19.
Background
The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients.
Methods
The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038.
Results
Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03).
Conclusion
Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them.
doi:10.1186/1471-2377-5-19
PMCID: PMC1291372  PMID: 16255771
7.  Prevalence of abnormal findings on brain magnetic resonance (MR) examinations in adult participants of brain docking 
BMC Neurology  2005;5:18.
Background
To determine the prevalence of abnormal findings on brain magnetic resonance (MR) examinations in adult participants of brain docking in order to assess its usefulness.
Methods
We analyzed screening brain MR examinations for 1113 adults (age, 52.6+/-8.5 years; range, 22–84; 761 male and 352 female) performed during 6-year period from April 1998 to March 2004. All participants voluntarily sought a brain MR examination at their own expense. All subjects were studied using the same 1.0-T MR scanner, on axial T1-weighted spin echo (SE) images, proton-density-weighted and T2-weighted fast SE images, and intracranial MR angiography (MRA). All abnormal findings were classified into three basic categories: (1) findings with no referral necessary; (2) findings not requiring further evaluation, but which needed to be reported to the referring physician; (3) findings requiring further evaluation.
Results
Participants with abnormal MR findings requiring further evaluation accounted for 1.3 %, but five of seven suspected intracranial aneurysms were not confirmed by other imaging modalities (false positive). No malignant tumors or other life-threatening pathology was detected, and only three participants (0.27 %) with abnormalities underwent surgical treatment. No participant groups were identified from our data as being high risk for MR abnormal findings requiring further evaluation.
Conclusion
Brain-docking participants had a variety of abnormalities on brain MR examinations, but only a small percentage of these findings required further evaluation. The usefulness of the brain docking with MRI and MRA has yet to be proven, and at this time we cannot approve this screening procedure.
doi:10.1186/1471-2377-5-18
PMCID: PMC1266373  PMID: 16207376
8.  Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report 
BMC Neurology  2005;5:17.
Background
After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants.
Case Presentation
The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age.
Conclusion
Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation.
doi:10.1186/1471-2377-5-17
PMCID: PMC1249577  PMID: 16185359
9.  Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report 
BMC Neurology  2005;5:16.
Background
Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation.
Case presentation
A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system.
Conclusion
Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.
doi:10.1186/1471-2377-5-16
PMCID: PMC1236932  PMID: 16162278
10.  Self-reported parkinsonian symptoms in the EPIC-Norfolk cohort 
BMC Neurology  2005;5:15.
Background
Parkinsonian symptoms have been associated with increased morbidity and mortality. Several studies have reported on the prevalence of signs and symptoms. Symptoms questionnaires can identify potential PD cases for further neurological examination to save resources. They can also provide information about how much of the population reports specific signs and symptoms. The objective of the study was to determine the self-reported prevalence of parkinsonian symptoms from a questionnaire, and to examine their association with age and self-reported Parkinson's disease in a large cohort.
Methods
A cross-sectional study was conducted within a sub-cohort of the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study.
Results
The prevalence of six self-reported parkinsonian symptoms are reported for 11539 individuals who answered all symptoms questions (62% of sub-cohort): rest tremor (4%), difficulty starting to walk (4%), difficulty getting out of a chair (6%), slower walking (34%), smaller handwriting (micrographia- 9%), and less acute sense of smell (olfactory dysfunction- 9%). The presence of individual symptoms increased with age except for difficulty getting out of a chair.
Conclusion
The results support previous findings that the presence of self-reported parkinsonian symptoms is strongly associated with age and self-reported PD diagnosis. The data also provide information regarding the prevalence of symptoms in a large, younger population of adults than previously reported in the literature.
doi:10.1186/1471-2377-5-15
PMCID: PMC1208899  PMID: 16120210
11.  Observations on comatose survivors of cardiopulmonary resuscitation with generalized myoclonus 
BMC Neurology  2005;5:14.
Background
There is only limited data on improvements of critical medical care is resulting in a better outcome of comatose survivors of cardiopulmonary resuscitation (CPR) with generalized myoclonus. There is also a paucity of data on the temporal dynamics of electroenephalographic (EEG) abnormalities in these patients.
Methods
Serial EEG examinations were done in 50 comatose survivors of CPR with generalized myoclonus seen over an 8 years period.
Results
Generalized myoclonus occurred within 24 hours after CPR. It was associated with burst-suppression EEG (n = 42), continuous generalized epileptiform discharges (n = 5), alpha-coma-EEG (n = 52), and low amplitude (10 μV <) recording (n = 1). Except in 3 patients, these EEG-patterns were followed by another of these always nonreactive patterns within one day, mainly alpha-coma-EEG (n = 10) and continuous generalized epileptiform discharges (n = 9). Serial recordings disclosed a variety of EEG-sequences composed of these EEG-patterns, finally leading to isoelectric or flat recordings. Forty-five patients died within 2 weeks, 5 patients survived and remained in a permanent vegetative state.
Conclusion
Generalized myoclonus in comatose survivors of CPR still implies a poor outcome despite advances in critical care medicine. Anticonvulsive drugs are usually ineffective. All postanoxic EEG-patterns are transient and followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavourable sign. Different EEG-patterns in anoxic encephalopathy may reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process finally leading to severe neuronal loss.
doi:10.1186/1471-2377-5-14
PMCID: PMC1190185  PMID: 16026615
12.  A new approach to estimation of the number of central synapse(s) included in the H-reflex 
BMC Neurology  2005;5:13.
Background
Among the main clinical applications of the H-reflex are the evaluation of the S1 nerve root conductivity such as radiculopathy and measurement of the excitability of the spinal motoneurons in neurological conditions. An attempt has been made to reduce the pathway over which H-reflex can be obtained in a hope to localize a lesion to the S1 nerve root, so the S1 central loop has been suggested. The main goal of this study is the estimation of the H-reflex number of synapse(s) for better understanding of the physiology of this practical reflex.
Methods
Forty healthy adult volunteers (22 males, 18 females) with the mean age of (37.7 ± 10.2) years participated in this study. They were positioned comfortably in the prone position, with their feet off the edge of the plinth. Recording electrodes were positioned at the mid point of a line connecting the mid popliteal crease to the proximal flare of the medial malleolus. Stimulation was applied at the tibial nerve in the popliteal fossa and H, F and M waves were recorded. Without any change in the location of the recording electrodes, a monopolar needle was inserted as cathode at a point 1 cm medial to the posterior superior iliac spine, perpendicular to the frontal plane. The anode electrode was placed over the anterior superior iliac spine, and then M and H waves of the central loop were recorded. After processing the data, sacral cord conduction delay was determined by this formula:
* Sacral cord conduction delay = central loop of H-reflex – (delays of the proximal motor and sensory fibers in the central loop).
Results
The central loop of H-reflex was (6.77 ± 0.28) msec and the sacral cord conduction delay was (1.09 ± 0.06) msec.
Conclusion
The sacral cord conduction time was estimated to be about 1.09 msec in this study and because at least 1 msec is required to transmit the signal across the synapse between the sensory ending and the motor cell, so this estimated time was sufficient for only one central synapse in this reflex.
doi:10.1186/1471-2377-5-13
PMCID: PMC1177957  PMID: 16011802
13.  Efficacy of the epidural blood patch for the treatment of post lumbar puncture headache BLOPP: A randomised, observer-blind, controlled clinical trial [ISRCTN 71598245] 
BMC Neurology  2005;5:12.
Background
Post dural punction headache (PDPH) occurs in 10% to 40% of the patients who had a lumbar puncture. Its symptoms can be severe and incapacitating. The epidural blood patch is widely accepted as the treatment of choice for postdural puncture headache. Uncontrolled studies report rapid recovery after patching in 90% to 100% of treated patients. However, sufficient evidence from randomised, controlled clinical trials is lacking.
Methods
BLOPP (blood patch for post dural puncture headache) is a randomised, single centre, observer-blind clinical trial. Patients with PDPH for at least 24 hours and at most 7 days after lumbar puncture will be randomised to treatment with an epidural blood patch (EDBP) or to conventional treatment, i.e. 24 hours bed rest and ample fluid intake. PDPH 24 hours after treatment, classified on a 4-point scale (no, mild, moderate, severe) is the primary outcome. The secondary outcome is the presence of PDPH 7 days after treatment. We estimated that a sample size of 2 × 20 patients would provide us with a power of 80% to detect a relative reduction in number of patients with persisting PDPH after 24 hours of 50% at the usual significance level α = 5%, taking into account that in approximately 10% of the patients the PDPH will have resolved spontaneously after one day.
Discussion
The EDBP is accepted as the treatment of choice for PDPH although randomised, controlled data is scarce. Our randomised, observer-blind clinical trial enables us to compare the efficacy of two clinically practiced methods of PDPH treatment; EDBP versus conventional treatment, as they are applied in clinical practise.
doi:10.1186/1471-2377-5-12
PMCID: PMC1180449  PMID: 15998467
14.  Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients 
BMC Neurology  2005;5:11.
Background
Fibroblast growth factor 20 (FGF20) is a neurotrophic factor preferentially expressed in the substantia nigra of rat brain and could be involved in dopaminergic neurons survival. Recently, a strong genetic association has been found between FGF20 gene and the risk of suffering from Parkinson's disease (PD). Our aim was to replicate this association in two independent populations.
Methods
Allelic, genotypic, and haplotype frequencies of four biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls from Greece, and 144 sporadic PD patients and 135 controls from Finland.
Results
No association was found in any of the populations studied.
Conclusion
Taken together, these findings suggest that common genetic variants in FGF20 are not a risk factor for PD in, at least, some European populations.
doi:10.1186/1471-2377-5-11
PMCID: PMC1183215  PMID: 15967032
15.  Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity 
BMC Neurology  2005;5:10.
Background
Recent trials suggest that angiotensin-converting enzyme inhibitors (ACEI) are effective in prevention of ischemic stroke, as measured by reduced stroke incidence. We aimed to compare stroke severity between stroke patients who were taking ACEI before their stroke onset and those who were not, to examine the effects of pretreatment with ACEI on ischemic stroke severity.
Methods
We retrospectively studied 126 consecutive patients presenting within 24 hours of ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance imaging (DWI). We calculated the NIHSS score at presentation, as the primary measure of clinical stroke severity, and categorized stroke severity as mild (NIHSS [less than or equal to] 7), moderate (NIHSS 8–13) or severe (NIHSS [greater than or equal to] 14). We analyzed demographic data, risk-factor profile, blood pressure (BP) and medications on admissions, and determined stroke mechanism according to TOAST criteria. We also measured the volumes of admission diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions, as a secondary measure of ischemic tissue volume. We compared these variables among patients on ACEI and those who were not.
Results
Thirty- three patients (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5 (range 2–21) among ACEI-treated patients vs. 9 (range 1–36) in non-ACEI patients (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated patients. However, none of these differences were significant. Predictably, a higher percentage of patients on ACEI had a history of heart failure (p = 0.03). Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant therapy with lipid lowering, other antihypertensives or antithrombotic agents, or admission BP were comparable between the two groups.
Conclusion
Our results suggest that ACE-inhibitors may reduce the clinical severity of stroke, as measured by NIHSS score. Further, larger-scale, prospective studies areneeded to validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits in patients with ischemic stroke.
doi:10.1186/1471-2377-5-10
PMCID: PMC1175849  PMID: 15949043
16.  Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality 
BMC Neurology  2005;5:9.
Background
To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke.
Methods
Diabetes was diagnosed in 393 (21.3%) of 1,840 consecutive patients with cerebral infarction included in a prospective stroke registry over a 12-year period. Demographic characteristics, cardiovascular risk factors, clinical events, stroke subtypes, neuroimaging data, and outcome in ischemic stroke patients with and without diabetes were compared. Predictors of in-hospital mortality in diabetic patients with ischemic stroke were assessed by multivariate analysis.
Results
People with diabetes compared to people without diabetes presented more frequently atherothrombotic stroke (41.2% vs 27%) and lacunar infarction (35.1% vs 23.9%) (P < 0.01). The in-hospital mortality in ischemic stroke patients with diabetes was 12.5% and 14.6% in those without (P = NS). Ischemic heart disease, hyperlipidemia, subacute onset, 85 years old or more, atherothrombotic and lacunar infarcts, and thalamic topography were independently associated with ischemic stroke in patients with diabetes, whereas predictors of in-hospital mortality included the patient's age, decreased consciousness, chronic nephropathy, congestive heart failure and atrial fibrillation
Conclusion
Ischemic stroke in people with diabetes showed a different clinical pattern from those without diabetes, with atherothrombotic stroke and lacunar infarcts being more frequent. Clinical factors indicative of the severity of ischemic stroke available at onset have a predominant influence upon in-hospital mortality and may help clinicians to assess prognosis more accurately.
doi:10.1186/1471-2377-5-9
PMCID: PMC1097737  PMID: 15833108
17.  Validation of multi-stage telephone-based identification of cognitive impairment and dementia 
BMC Neurology  2005;5:8.
Background
Many types of research on dementia and cognitive impairment require large sample sizes. Detailed in-person assessment using batteries of neuropyschologic testing is expensive. This study evaluates whether a brief telephone cognitive assessment strategy can reliably classify cognitive status when compared to an in-person "gold-standard" clinical assessment.
Methods
The gold standard assessment of cognitive status was conducted at the University of Southern California Alzheimer Disease Research Center (USC ADRC). It involved an examination of patients with a memory complaint by a neurologist or psychiatrist specializing in cognitive disorders and administration of a battery of neuropsychologic tests. The method being evaluated was a multi-staged assessment using the Telephone Interview of Cognitive Status-modified (TICSm) with patients and the Telephone Dementia Questionnaire (TDQ) with a proxy. Elderly male and female patients who had received the gold standard in-person assessment were asked to also undergo the telephone assessment. The unweighted kappa statistic was calculated to compare the gold standard and the multistage telephone assessment methods. Sensitivity for classification with dementia and specificity for classification as normal were also calculated.
Results
Of 50 patients who underwent the gold standard assessment and were referred for telephone assessment, 38 (76%) completed the TICS. The mean age was 78.1 years and 26 (68%) were female. When comparing the gold standard assessment and the telephone method for classifying subjects as having dementia or no dementia, the sensitivity of the telephone method was 0.83 (95% confidence interval 0.36, 1.00), the specificity was 1.00 (95% confidence interval 0.89,1.00). Kappa was 0.89 (95% confidence interval 0.69, 1.000). Considering a gold-standard assessment of age-associated memory impairment as cognitive impairment, the sensitivity of the telephone approach is 0.38 (95% confidence interval 0.09, 0.76) specificity 0.96 (CI 0.45, 0.89) and kappa 0.61 (CI 0.37, 0.85).
Conclusion
Use of a telephone interview to identify people with dementia or cognitive impairment is a promising and relatively inexpensive strategy for identifying potential participants in intervention and clinical research studies and for classifying subjects in epidemiologic studies.
doi:10.1186/1471-2377-5-8
PMCID: PMC1090587  PMID: 15829005
18.  Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations 
BMC Neurology  2005;5:7.
Background
Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells.
Methods
We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient) or Lama2-/- (laminin-α2-deficient) mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation.
Results
We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2-/- muscles showed similar significant increases in CD45+ cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2-/- muscles compared to healthy muscles. In particular, the most abundant Sca-1-/CD45- subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2-/- muscles.
Conclusion
The similar increases in CD45+ cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases.
doi:10.1186/1471-2377-5-7
PMCID: PMC1084348  PMID: 15817132
19.  Enucleation and development of cluster headache: a retrospective study 
BMC Neurology  2005;5:6.
Background
Cluster headache (CH) is a neurovascular, primary headache disorder. There are, however, several case reports about patients whose CH started shortly after a structural brain disease or trauma. Motivated by a patient who developed CH 3 weeks after the removal of an eye and by similar case reports, we tested the hypothesis that the removal of an eye is a risk factor for CH.
Methods
A detailed headache questionnaire was filled out by 112 patients on average 8 years after enucleation or evisceration of an eye.
Results
While 21 % of these patients experienced previously unknown headaches after the removal of an eye, no patient fulfilled the diagnostic criteria for CH.
Conclusion
Our data does not suggest that the removal of an eye is a major risk factor for the development of CH.
doi:10.1186/1471-2377-5-6
PMCID: PMC1079865  PMID: 15784136
20.  Validity of Simpson-Angus Scale (SAS) in a naturalistic schizophrenia population 
BMC Neurology  2005;5:5.
Background
Simpson-Angus Scale (SAS) is an established instrument for neuroleptic-induced parkinsonism (NIP), but its statistical properties have been studied insufficiently. Some shortcomings concerning its content have been suggested as well. According to a recent report, the widely used SAS mean score cut-off value 0.3 of for NIP detection may be too low. Our aim was to evaluate SAS against DSM-IV diagnostic criteria for NIP and objective motor assessment (actometry).
Methods
Ninety-nine chronic institutionalised schizophrenia patients were evaluated during the same interview by standardised actometric recording and SAS. The diagnosis of NIP was based on DSM-IV criteria. Internal consistency measured by Cronbach's α, convergence to actometry and the capacity for NIP case detection were assessed.
Results
Cronbach's α for the scale was 0.79. SAS discriminated between DSM-IV NIP and non-NIP patients. The actometric findings did not correlate with SAS. ROC-analysis yielded a good case detection power for SAS mean score. The optimal threshold value of SAS mean score was between 0.65 and 0.95, i.e. clearly higher than previously suggested threshold value.
Conclusion
We conclude that SAS seems a reliable and valid instrument. The previously commonly used cut-off mean score of 0.3 has been too low resulting in low specificity, and we suggest a new cut-off value of 0.65, whereby specificity could be doubled without loosing sensitivity.
doi:10.1186/1471-2377-5-5
PMCID: PMC555761  PMID: 15774006
21.  parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism 
BMC Neurology  2005;5:4.
Background
parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage.
Methods
We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons.
Results
Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations.
Conclusion
Anticipation is not linked to parkin, and may signify a distinct disease entity.
doi:10.1186/1471-2377-5-4
PMCID: PMC551608  PMID: 15725358
22.  Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report 
BMC Neurology  2005;5:3.
Background
Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown.
Methods
We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity), were measured.
Results
Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship.
Conclusion
Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders.
doi:10.1186/1471-2377-5-3
PMCID: PMC552306  PMID: 15717934
23.  Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus 
BMC Neurology  2005;5:2.
Background
Autonomic nervous system (ANS) dysfunction is present in up to one third of patients with tetanus. The prognostic value of ANS dysfunction is known in severe tetanus but its value is not well established in mild to moderate tetanus.
Methods
Medical records of all patients admitted with tetanus at two academic tertiary care centers in Karachi, Pakistan were reviewed. The demographic, clinical and laboratory data was recorded and analyzed. ANS dysfunction was defined as presence of labile or persistent hypertension or hypotension and sinus tachycardia, tachyarrythmia or bradycardia on EKG. Patients were divided into two groups based on presence of ANS dysfunction (ANS group and non ANS group). Tetanus severity was classified on the basis of Ablett criteria.
Results
Ninety six (64 males; 32 females) patients were admitted with the diagnosis over a period of 10 years. ANS group had 31 (32%) patients while non ANS group comprised of 65 (68%) patients. Both groups matched for age, gender, symptom severity, use of tetanus immunoglobulin and antibiotics. Twelve patients in ANS group had mild to moderate tetanus (Ablett I and II) and 19 patients had severe/very severe tetanus (Ablett III and IV). Fifteen (50%) patients in ANS group required ventilation as compared to 28 (45%) in non-ANS group (p = 0.09). Fourteen (47%) patients died in ANS group as compared to 10 (15%) in non ANS group (p= 0.002). Out of those 14 patients died in ANS group, six patients had mild to moderate tetanus and eight patients had severe/ very severe tetanus. Major cause of death was cardiac arrhythmias (13/14; 93%) in ANS group and respiratory arrest (7/10; 70%) in non ANS group. Ten (33%) patients had complete recovery in ANS group while in non ANS group 35(48%) patients had complete recovery (p= 0.05).
Conclusions
ANS dysfunction was present in one third of our tetanus population. 40% patients with ANS dysfunction had only mild to moderate tetanus. ANS dysfunction, irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome.
doi:10.1186/1471-2377-5-2
PMCID: PMC548694  PMID: 15679900
24.  Suppression of MMP-9 by doxycycline in brain arteriovenous malformations 
BMC Neurology  2005;5:1.
Background
The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs).
Methods
Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured.
Results
Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 μg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%; active: 100 ± 8 vs 48 ± 16 vs 59 ± 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 ± 1.94 vs 3.26 ± 3.58, P = .50; active: 0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg protein, P = .25).
Conclusions
A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.
doi:10.1186/1471-2377-5-1
PMCID: PMC547916  PMID: 15667660

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