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1.  A cross-sectional study of the nutritional status of community-dwelling people with idiopathic Parkinson's disease 
BMC Neurology  2010;10:124.
Background
Parkinson's disease (PD) patients have an increased risk of under-nutrition, but we are unaware of any population based prevalence studies of under-nutrition in PD. The main objective of this study was to identify the prevalence, and nature, of under-nutrition in a representative population of people with PD.
Methods
People diagnosed with idiopathic PD from within two PD prevalence study sites in North-East England were asked to participate in this study. Those who participated (n = 136) were assessed using a number of standard rating scales including Hoehn & Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS). Body mass index (BMI), mid-arm circumference (MAC), triceps skin fold thickness (TSF) and grip strength were recorded together with social and demographic information.
Results
BMI < 20 identified over 15% of the study group to have under-nutrition. The Malnutritional Universal Screening Tool (MUST) scoring system identified 23.5% of participants at medium or high risk of malnutrition. Low BMI, indicating under-nutrition, was associated with greater age and disease duration, lower MAC, TSF, mid-arm muscle circumference (MAMC), reduced grip strength and a report of unintentional weight loss. Problems increased with increasing age and disease duration and were greater in females.
Conclusions
Under-nutrition is a problem for around 15% of community dwelling people with PD. All PD patients should be screened for under-nutrition; the MUST score is a useful early screening tool.
doi:10.1186/1471-2377-10-124
PMCID: PMC3022770  PMID: 21192784
2.  Mood after stroke: a case control study of biochemical, neuro-imaging and socio-economic risk factors for major depression in stroke survivors 
BMC Neurology  2010;10:125.
Background
Though vascular factors may be important in the aetiology of late-life depression, it is not clear whether they have a major effect on the risk of depression after a stroke. We investigated the relationship between physiological, biochemical, neuro-imaging and socio-economic factors and late-phase post-stroke depression in a cross-sectional case-control study.
Methods
People living at home at least 9 months after a stroke were interviewed using a structured proforma. Depression was diagnosed according to DSM-IV criteria, together with a Montgomery Asberg (MADRS) score >17. Stroke survivors of similar age and functional status but without symptoms of, or recent treatment for, depression and with MADRS score <7, were recruited as controls.
Results
Stroke survivors with depression were more likely than controls to have been smokers, to have had hypertension or peripheral arterial disease, and to have had more than one stroke or multiple discrete brainscan lesions. In univariate analysis they had significantly higher blood pressure, lower Mini-Mental State (MMSE) scores, higher serum homocysteine and lower folate levels, as well as more extensive white matter and basal ganglia changes on brainscan. In logistic regression, previous hypertension (OR 3.4), peripheral vascular disease (OR 4.7), number of strokes (OR 2), MMSE score (OR 0.76) and basal ganglia changes (OR 2.2), were independently associated with depression.
Conclusion
These results suggest that patients with hypertension, hyperhomocysteinaemia and other factors associated with cerebral small vessel disease, may be more susceptible to post-stroke depression. Future intervention trials should focus on such high risk groups.
doi:10.1186/1471-2377-10-125
PMCID: PMC3022771  PMID: 21192808
3.  Abnormal cortical responses to somatosensory stimulation in medication-overuse headache 
BMC Neurology  2010;10:126.
Background
Medication-overuse headache (MOH) is a frequent, disabling disorder. Despite a controversial pathophysiology convincing evidence attributes a pivotal role to central sensitization. Most patients with MOH initially have episodic migraine without aura (MOA) characterized interictally by an absent amplitude decrease in cortical evoked potentials to repetitive stimuli (habituation deficit), despite a normal initial amplitude (lack of sensitization). Whether central sensitization alters this electrophysiological profile is unknown. We therefore sought differences in somatosensory evoked potential (SEP) sensitization and habituation in patients with MOH and episodic MOA.
Methods
We recorded median-nerve SEPs (3 blocks of 100 sweeps) in 29 patients with MOH, 64 with MOA and 42 controls. Episodic migraineurs were studied during and between attacks. We measured N20-P25 amplitudes from 3 blocks of 100 sweeps, and assessed sensitization from block 1 amplitude, and habituation from amplitude changes between the 3 sequential blocks.
Results
In episodic migraineurs, interictal SEP amplitudes were normal in block 1, but thereafter failed to habituate. Ictal SEP amplitudes increased in block 1, then habituated normally. Patients with MOH had larger-amplitude block 1 SEPs than controls, and also lacked SEP habituation. SEP amplitudes were smaller in triptan overusers than in patients overusing nonsteroidal anti-inflammatory drugs (NSAIDs) or both medications combined, lowest in patients with the longest migraine history, and highest in those with the longest-lasting headache chronification.
Conclusions
In patients with MOH, especially those overusing NSAIDs, the somatosensory cortex becomes increasingly sensitized. Sensory sensitization might add to the behavioral sensitization that favors compulsive drug intake, and may reflect drug-induced changes in central serotoninergic transmission.
doi:10.1186/1471-2377-10-126
PMCID: PMC3024248  PMID: 21192822
4.  Decrease in shunt volume in patients with cryptogenic stroke and patent foramen ovale 
BMC Neurology  2010;10:123.
Background
In patients with patent foramen ovale (PFO) there is evidence supporting the hypothesis of a change in right-to-left shunt (RLS) over time. Proven, this could have implications for the care of patients with PFO and a history of stroke. The following study addressed this hypothesis in a cohort of patients with stroke and PFO.
Methods
The RLS volume assessed during hospitalisation for stroke (index event/T0) was compared with the RLS volume on follow-up (T1) (median time between T0 and T1 was 10 months). In 102 patients with a history of stroke and PFO the RLS volume was re-assessed on follow-up using contrast-enhanced transcranial Doppler/duplex (ce-TCD) ultrasound. A change in RLS volume was defined as a difference of ≥20 microembolic signals (MES) or no evidence of RLS during ce-TCD ultrasound on follow-up.
Results
There was evidence of a marked reduction in RLS volume in 31/102 patients; in 14/31 patients a PFO was no longer detectable. An index event classified as cryptogenic stroke (P < 0.001; OD = 39.2, 95% confidence interval 6.0 to 258.2) and the time interval to the follow-up visit (P = 0.03) were independently associated with a change in RLS volume over time.
Conclusions
RLS volume across a PFO decreases over time, especially in patients with cryptogenic stroke. These may determine the development of new strategies for the management in the secondary stroke prevention.
doi:10.1186/1471-2377-10-123
PMCID: PMC3022769  PMID: 21190569
5.  Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial): a multi-centred, randomised controlled trial 
BMC Neurology  2010;10:122.
Background
Despite lack of outward signs, most individuals after non-disabling stroke (NDS) and transient ischemic attack (TIA) have significant cardiovascular and cerebrovascular disease and are at high risk of a major stroke, hospitalization for other vascular events, or death. Most have multiple modifiable risk factors (e.g., hypertension, physical inactivity, hyperlipidaemia, diabetes, tobacco consumption, psychological stress). In addition, accelerated rates of depression, cognitive decline, and poor quality of sleep have been reported following TIA, which correlate with poor functional outcomes and reduced quality of life. Thus, NSD and TIA are important warning signs that should not be overlooked. The challenge is not unlike that facing other 'silent' conditions - to identify a model of care that is effective in changing people's current behaviors in order to avert further morbidity.
Methods/Design
A single blind, randomized controlled trial will be conducted at two sites to compare the effectiveness of a program of rehabilitative exercise and education versus usual care in modifying vascular risk factors in adults after NDS/TIA. 250 adults within 90 days of being diagnosed with NDS/TIA will be randomly allocated to a 12-week program of exercise and education (PREVENT) or to an outpatient clinic assessment and discussion of secondary prevention recommendations with return clinic visits as indicated (USUAL CARE). Primary outcome measures will include blood pressure, waist circumference, 12-hour fasting lipid profile, and 12-hour fasting glucose/hemoglobin A1c. Secondary measures will include exercise capacity, walking endurance, physical activity, cognitive function, depression, goal attainment and health-related quality of life. Outcome assessment will be conducted at baseline, post-intervention, and 6- and 12-month follow-ups. Direct health care costs incurred over one year by PREVENT versus USUAL CARE participants will also be compared. Ethical approval for the trial has been obtained from the relevant Human Research Ethics Boards.
Discussion
Whether timely delivery of an adapted cardiac rehabilitation model is effective in attaining and maintaining vascular risk reduction targets in adults after NDS/TIA is not yet known. We anticipate that the findings of this trial will make a meaningful contribution to the knowledge base regarding secondary stroke prevention.
Trial registration
This trial is registered with the Clinical Trials.gov Registry (NCT00885456).
doi:10.1186/1471-2377-10-122
PMCID: PMC3004878  PMID: 21143864
6.  Synesthesia and Migraine: Case Report 
BMC Neurology  2010;10:121.
Background
Synesthesia is, as visual migraine aura, a common and fascinating perceptual phenomenon. Here we present a unique case with synesthesias exclusively during visual migraine auras.
Case presentation
A 40-year-old woman with a cyclic mood disorder had suffered from migraine with visual aura for several years. On several occasions she had experienced "mixing of senses" during the aura phase. Staring at strong bright light she could experience intense taste of lemon with flow from the salivary glands.
Conclusion
Acquired synesthesia, exclusively coincident with migraine aura, gives support to the idea of an anomalous cortical processing underlying the phenomenon.
doi:10.1186/1471-2377-10-121
PMCID: PMC3004877  PMID: 21138558
7.  Usefulness of multimodal MR imaging in the differential diagnosis of HaNDL and acute ischemic stroke 
BMC Neurology  2010;10:120.
Background
Syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid Lymphocitosis (HaNDL) is a rare disease which can present with focal neurological deficits and mimic stroke. A neurologist-on-duty faced with a HaNDL patient in the first hours might erroneously decide to use thrombolytic drugs, a non-innocuous treatment which has no therapeutic effect on this syndrome.
Case Presentation
We present a case where neuroimaging, together with the clinical picture, led to a presumed diagnosis of HaNDL avoiding intravenous thrombolysis.
Conclusions
This report shows the usefulness of multimodal MR imaging in achieving early diagnosis during an acute neurological attack of HaNDL. Our experience, along with that of others, demonstrates that neuroimaging tests reveal the presence of cerebral hypoperfusion in HaNDL syndrome
doi:10.1186/1471-2377-10-120
PMCID: PMC3017035  PMID: 21126373
8.  Endothelial function in migraine: a cross-sectional study 
BMC Neurology  2010;10:119.
Background
Migraine has been associated with cardiovascular disorders. Endothelial dysfunction may be a mechanism underlying this association. The present study tested the hypothesis that endothelium-dependent vasodilation, basal endothelial nitric oxide release and endothelial fibrinolytic capacity are impaired in migraine patients.
Methods
Graded doses of sodium nitroprusside (SNP, 0.2 to 0.8 μg.min-1.dL-1 forearm), substance P (0.2 to 0.8 pmol.min-1.dL-1 forearm) and NG-monomethyl-L-arginine (L-NMMA, 0.1 to 0.4 μmol.min-1.dL-1 forearm) were infused into the brachial artery of 16 migraine patients with or without aura during a headache-free interval and 16 age- and sex-matched subjects without a history of migraine. Forearm blood flow (FBF) was measured by strain-gauge venous occlusion plethysmography. Local forearm release of tissue plasminogen activator (t-PA) in response to substance P infusion was assessed using the arteriovenous plasma concentration gradient. Responses to infused drugs were compared between patients and matched controls by analysis of variance.
Results
In both migraine patients and control subjects, SNP and substance P caused a dose-dependent increase, and L-NMMA a dose-dependent decrease in FBF (P < 0.001 for all responses). In both groups, substance P caused an increase in t-PA release (P < 0.001). FBF responses and t-PA release were comparable between migraine patients and control subjects.
Conclusions
The absence of differences in endothelium-dependent vasodilation, basal endothelial nitric oxide production and stimulated t-PA release between migraine patients and healthy control subjects argues against the presence of endothelial dysfunction in forearm resistance vessels of migraine patients.
doi:10.1186/1471-2377-10-119
PMCID: PMC3017034  PMID: 21122149
9.  Systemic panca-associated vasculitis with central nervous involvement causing recurrent myelitis: case report 
BMC Neurology  2010;10:118.
Background
We report on the case of an established perinuclear antineutrophil cytoplasmic antibody (pANCA) associated renal vasculitis being treated with prednisolone and rituximab, where the patient presented with leg weakness, urinary and faecal incontinence and buttock pain consistent with transverse myelitis.
Case presentation
The patient underwent MRI scanning showing patchy cord enhancement from T10 to the conus, which was suggestive of a cord malignancy. Prior to a cord biopsy, he was treated with steroids and a repeat MRI showed resolution of the original lesion with a new similar lesion from C7 to T3.
Conclusions
He made a marked recovery after further treatment with high dose steroids and plasma exchange.
doi:10.1186/1471-2377-10-118
PMCID: PMC3001708  PMID: 21118568
10.  Severe course of Lyme neuroborreliosis in an HIV-1 positive patient; case report and review of the literature 
BMC Neurology  2010;10:117.
Background
Lyme Neuroborreliosis (LNB) in a human immunodeficiency virus (HIV) positive patient is a rare co-infection and has only been reported four times in literature. No case of an HIV patient with a meningoencephalitis due to LNB in combination with HIV has been described to date.
Case presentation
A 51 year old woman previously diagnosed with HIV presented with an atypical and severe LNB. Diagnosis was made evident by several microbiological techniques. Biochemical and microbiological recovery during treatment was rapid, however after treatment the patient suffered from severe and persistent sequelae.
Conclusions
A clinician should consider LNB when being confronted with an HIV patient with focal encephalitis, without any history of Lyme disease or tick bites, in an endemic area. Rapid diagnosis and treatment is necessary in order to minimize severe sequelae.
doi:10.1186/1471-2377-10-117
PMCID: PMC3009961  PMID: 21118561
11.  Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review 
BMC Neurology  2010;10:116.
Background
Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2nd line or later in UK patients with neuropathic pain.
Methods
A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies) that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed.
Results
Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design.
Conclusions
Little evidence is available relevant to the treatment of refractory neuropathic pain despite the clinical need. There is a notable lack of high-quality comparative studies. It is evident that there is a need for future, high quality trials, particularly "gold-standard" RCTs in this refractory patient population.
doi:10.1186/1471-2377-10-116
PMCID: PMC3003252  PMID: 21092100
12.  Congenital Abnormalities and Multiple Sclerosis 
BMC Neurology  2010;10:115.
Background
There is a strong maternal parent-of-origin effect in determining susceptibility to multiple sclerosis (MS). One hypothesis is that an abnormal intrauterine milieu leading to impaired fetal development could plausibly also result in increased susceptibility to MS. A possible marker for this intrauterine insult is the presence of a non-fatal congenital anomaly.
Methods
We investigated whether or not congenital anomalies are associated with MS in a population-based cohort. We identified 7063 MS index cases and 2655 spousal controls with congenital anomaly information from the Canadian Collaborative Project on Genetic Susceptibility to MS (CCPGSMS).
Results
The frequency of congential anomalies were compared between index cases and controls. No significant differences were found.
Conclusions
Congenital anomalies thus do not appear to be associated with MS. However, we did not have complete data on types and severity of congenital anomalies or on maternal birth history and thus this study should be regarded as preliminary.
doi:10.1186/1471-2377-10-115
PMCID: PMC3020672  PMID: 21080921
13.  Focused ultrasound-mediated bbb disruption is associated with an increase in activation of AKT: experimental study in rats 
BMC Neurology  2010;10:114.
Background
The Blood Brain Barrier (BBB) maintains the homeostasis of central nervous system by preventing the free passage of macromolecules from the systemic circulation into the brain. This normal physiological function of the BBB presents a challenge for delivery of therapeutic compounds into the brain. Recent studies have shown that the application of focused ultrasound together with ultrasound contrast agent (microbubbles) temporarily increases the permeability of the BBB. This effect is associated with breakdown of tight junctions, the structures that regulate the paracellular permeability of the endothelial cell layer. The influence of this ultrasound effect on the activation of intracellular signaling proteins is currently not well understood. Therefore, the aim of this study was to investigate the activation of cell survival signaling molecules in response to ultrasound-mediated BBB opening;
Methods
The BBB was disrupted in two four-spot lines (1-1.5 mm spacing) along the right hemisphere of rat brain with ultrasound beams (0.3 MPa, 120 s, 10 ms bursts, repetition frequency = 1 Hz) in the presence Definity microbubbles. Contrast-enhanced MRI images were acquired to assess the extent of BBB opening upon which the animals were sacrificed and the brains removed and processed for biochemical and immunohistochemical analyses;
Results
Immunoblotting of sonicated brain lysates resolved by SDS-PAGE demonstrated an increase in phosphorylation of Akt and its downstream signaling molecule, GSK3β, while the phosphorylation of MAPK remained unchanged. The elevated levels of pAkt and pGSK3β are still evident after 24 hours post-sonication, a time point where the integrity of the BBB is known to be re-established. Furthermore, immunofluoresence staining localized this increase in pAkt and pGSK3β levels to neuronal cells flanking the region of the disrupted BBB;
Conclusions
Our data demonstrates that ultrasound-mediated BBB disruption causes an activation of the Akt signaling pathway in neuronal cells surrounding the disrupted BBB.
doi:10.1186/1471-2377-10-114
PMCID: PMC3020671  PMID: 21078165
14.  Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica 
BMC Neurology  2010;10:113.
Background
The role of different chemokine receptors in the pathogenesis of multiple sclerosis (MS) has been extensively investigated; however, little is known about the difference in the role of chemokine receptors between the pathogenesis of neuromyelitis optica (NMO) and MS. Therefore, we examined the expression of chemokine receptors on peripheral blood lymphocytes (PBL) in MS and NMO.
Methods
We used flow cytometry to analyse lymphocyte subsets in 12 patients with relapsing NMO, 24 with relapsing-remitting MS during relapse, 3 with NMO and 5 with MS during remission.
Results
Compared with healthy controls (HC), the percentage of lymphocytes in white blood cells was significantly lower in NMO and MS patients. The percentage of T cells expressing CD4+CD25+ and CD4+CD45RO+ was higher, while that of CD4+CC chemokine receptor (CCR)3+ (T helper 2, Th2) was significantly lower in MS patients than in HC. The ratios of CD4+CXC chemokine receptors (CXCR)3+/CD4+CCR3+ (Th1/Th2) and CD8+CXCR3+/CD8+CCR4+ (T cytotoxic 1, Tc1/Tc2) were higher in MS patients than in HC. The percentage of CD8+CXCR3+ T cell (Tc1) and CD4+CXCR3+ T cell (Th1) decreased significantly during remission in MS patients (P <0.05). No significant differences were identified in the expression of the chemokine receptors on PBL in NMO patients compared with MS patients and HC.
Conclusions
Th1 dominance of chemokine receptors on blood T cells and the correlation between CXCR3+ T cell (Th1 and Tc1) and disease activity in MS patients were confirmed by analysing chemokines receptors on PBL. In contrast, deviation in the Th1/Th2 balance was not observed in NMO patients.
doi:10.1186/1471-2377-10-113
PMCID: PMC2992493  PMID: 21067621
15.  Identification of novel biomarker candidates by proteomic analysis of cerebrospinal fluid from patients with moyamoya disease using SELDI-TOF-MS 
BMC Neurology  2010;10:112.
Background
Moyamoya disease (MMD) is an uncommon cerebrovascular condition with unknown etiology characterized by slowly progressive stenosis or occlusion of the bilateral internal carotid arteries associated with an abnormal vascular network. MMD is a major cause of stroke, specifically in the younger population. Diagnosis is based on only radiological features as no other clinical data are available. The purpose of this study was to identify novel biomarker candidate proteins differentially expressed in the cerebrospinal fluid (CSF) of patients with MMD using proteomic analysis.
Methods
For detection of biomarkers, CSF samples were obtained from 20 patients with MMD and 12 control patients. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with an anion exchange chip in three different buffer conditions. After expression difference mapping was undertaken using the obtained protein profiles, a comparative analysis was performed.
Results
A statistically significant number of proteins (34) were recognized as single biomarker candidate proteins which were differentially detected in the CSF of patients with MMD, compared to the control patients (p < 0.05). All peak intensity profiles of the biomarker candidates underwent classification and regression tree (CART) analysis to produce prediction models. Two important biomarkers could successfully classify the patients with MMD and control patients.
Conclusions
In this study, several novel biomarker candidate proteins differentially expressed in the CSF of patients with MMD were identified by a recently developed proteomic approach. This is a pilot study of CSF proteomics for MMD using SELDI technology. These biomarker candidates have the potential to shed light on the underlying pathogenesis of MMD.
doi:10.1186/1471-2377-10-112
PMCID: PMC2992492  PMID: 21059247
16.  Alcohol drinking and risk of Parkinson's disease: a case-control study in Japan 
BMC Neurology  2010;10:111.
Background
Although some epidemiologic studies found inverse associations between alcohol drinking and Parkinson's disease (PD), the majority of studies found no such significant associations. Additionally, there is only limited research into the possible interactions of alcohol intake with aldehyde dehydrogenase (ALDH) 2 activity with respect to PD risk. We examined the relationship between alcohol intake and PD among Japanese subjects using data from a case-control study.
Methods
From 214 cases within 6 years of PD onset and 327 controls without neurodegenerative disease, we collected information on "peak", as opposed to average, alcohol drinking frequency and peak drinking amounts during a subject's lifetime. Alcohol flushing status was evaluated via questions, as a means of detecting inactive ALHD2. The multivariate model included adjustments for sex, age, region of residence, smoking, years of education, body mass index, alcohol flushing status, presence of selected medication histories, and several dietary factors.
Results
Alcohol intake during peak drinking periods, regardless of frequency or amount, was not associated with PD. However, when we assessed daily ethanol intake separately for each type of alcohol, only Japanese sake (rice wine) was significantly associated with PD (adjusted odds ratio of ≥66.0 g ethanol per day: 3.39, 95% confidence interval: 1.10-11.0, P for trend = 0.001). There was no significant interaction of alcohol intake with flushing status in relation to PD risk.
Conclusions
We did not find significant associations between alcohol intake and PD, except for the daily amount of Japanese sake. Effect modifications by alcohol flushing status were not observed.
doi:10.1186/1471-2377-10-111
PMCID: PMC2991300  PMID: 21054827
17.  Saliva levels of Abeta1-42 as potential biomarker of Alzheimer's disease: a pilot study 
BMC Neurology  2010;10:108.
Background
Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson's disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of β amyloid (Aβ) using a highly sensitive ELISA kit.
Results
We found a small but statistically significant increase in saliva Aβ42 levels in mild AD patients. In addition, there were not differences in saliva concentration of Aβ42 between patients with PD and healthy controls. Saliva Aβ40 expression was unchanged within all the studied sample. The association between saliva Aβ42 levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity.
Conclusions
We suggest that saliva Aβ42 levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD.
doi:10.1186/1471-2377-10-108
PMCID: PMC2987856  PMID: 21047401
18.  Cranio-spinal migration of a metallic clip placed during arteriovenous malformation resection - A case report, review of the literature, and management strategies 
BMC Neurology  2010;10:109.
Background
Microclip placement during AVM resection is generally accepted to be a safe practice in neurosurgery. Here, we describe an unusual complication involving cranio-spinal clip migration discovered five years after the initial AVM surgery.
Case Presentation
A 53-year-old man underwent resection of a superior vermian AVM that required the placement of two microclips during the procedure. Five years after surgery, the patient suffered from descending sensory radiculopathy that resolved spontaneously. The workup revealed cranio-spinal migration of one of the previously placed microclips.
Conclusions
AVM clip migration is a rare phenomenon; however, the diagnosis should be entertained in patients with posterior fossa instrumentation who suffer from unusual neurologic symptoms.
doi:10.1186/1471-2377-10-109
PMCID: PMC2988762  PMID: 21047415
19.  Charting the progression of disability in parkinson disease: study protocol for a prospective longitudinal cohort study 
BMC Neurology  2010;10:110.
Background
People with Parkinson disease (PD), even in the presence of symptomatic relief from medical, surgical, and rehabilitative interventions, face a persistent worsening of disability. This disability is characterized by diminished quality of life, reduced functional mobility, declining performance in activities of daily living and worsening neurological impairments. While evidence has emerged supporting the clinically meaningful benefits of short-term exercise programs on these underlying factors, assertions regarding the effects of sustained programs of exercise and physical activity on the trajectory of disablement in PD are made in the absence of direct evidence. Indeed, the natural decline in quality of life and functional mobility in people diagnosed with PD is poorly understood. Moreover, outcome measures commonly used in clinical exercise trials typically do not capture the full spectrum of disability as defined by the World Health Organization (WHO).
Methods/Design
The objective of this multicenter prospective study will be to examine the 2-year trajectory of disablement in a cohort of persons with PD. Two hundred sixty participants will be recruited to produce an expected final sample size of 150 individuals. Participants will be included if they are greater than 40 years of age, have a neurologist confirmed diagnosis of idiopathic PD, and are at Hoehn and Yahr stages 1 through 4. Data will be collected every 6 months during the study period. Primary outcome measures reflecting a broad spectrum of disablement will include, but will not be limited to, MDS-UPDRS, Timed Up and Go, Berg Balance Test, Nine Hole Peg Test, PDQ-39, and directly monitored ambulatory activity. Self-reported exercise and physical activity data also will be recorded. Statistical analyses will be used to characterize the trajectory of disablement and examine the influence of its underlying contributing factors.
Discussion
Tertiary prevention is an important component of contemporary healthcare for individuals living with degenerative disease. For individuals with PD, there is growing recognition that exercise and/or physical activity efforts to slow the rate of functional mobility decline, in particular, may be critical for optimizing quality of life. By describing the natural trajectory of disablement, exercise habits, and physical activity in a cohort of persons with PD, this investigation will establish an important foundation for future intervention research. Specifically, through the evaluation of the influence of sustained exercise and physical activity on disablement, the study will serve as a preliminary step toward developing a randomized controlled trial of long-term exercise in persons with PD.
doi:10.1186/1471-2377-10-110
PMCID: PMC2988763  PMID: 21047426
20.  Ophthalmodynamometry for ICP prediction and pilot test on Mt. Everest 
BMC Neurology  2010;10:106.
Background
A recent development in non-invasive techniques to predict intracranial pressure (ICP) termed venous ophthalmodynamometry (vODM) has made measurements in absolute units possible. However, there has been little progress to show utility in the clinic or field. One important application would be to predict changes in actual ICP during adaptive responses to physiologic stress such as hypoxia. A causal relationship between raised intracranial pressure and acute mountain sickness (AMS) is suspected. Several MRI studies report that modest physiologic increases in cerebral volume, from swelling, normally accompany subacute ascent to simulated high altitudes.
Objectives
1) Validate and calibrate an advanced, portable vODM instrument on intensive patients with raised intracranial pressure and 2) make pilot, non-invasive ICP estimations of normal subjects at increasing altitudes.
Methods
The vODM was calibrated against actual ICP in 12 neurosurgical patients, most affected with acute hydrocephalus and monitored using ventriculostomy/pressure transducers. The operator was blinded to the transducer read-out. A clinical field test was then conducted on a variable data set of 42 volunteer trekkers and climbers scaling Mt. Everest, Nepal. Mean ICPs were estimated at several altitudes on the ascent both across and within subjects.
Results
Portable vODM measurements increased directly and linearly with ICP resulting in good predictability (r = 0.85). We also found that estimated ICP increases normally with altitude (10 ± 3 mm Hg; sea level to 20 ± 2 mm Hg; 6553 m) and that AMS symptoms did not correlate with raised ICP.
Conclusion
vODM technology has potential to reliably estimate absolute ICP and is portable. Physiologic increases in ICP and mild-mod AMS are separate responses to high altitude, possibly reflecting swelling and vasoactive instability, respectively.
doi:10.1186/1471-2377-10-106
PMCID: PMC2987855  PMID: 21040572
21.  A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy 
BMC Neurology  2010;10:105.
Background
Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables.
Results
We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011).
Conclusions
In this Italian setting, we found a biphasic pattern (peaks in spring and autumn) in severe MS relapses requiring medical consultation by doctors of the MS specialty center, apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.
doi:10.1186/1471-2377-10-105
PMCID: PMC2988761  PMID: 21040535
22.  Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis 
BMC Neurology  2010;10:107.
Background
Extracellular gelsolin (GSN) and GC-globulin/Vitamin D-binding protein (DBP) appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS) development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF) of patients with MS.
Methods
We measured GSN and DBP concentrations in blood and CSF obtained from patients diagnosed with MS (n = 56) in comparison to a control group (n = 20) that includes patients diagnosed with conditions such as idiopathic cephalgia (n = 11), idiopathic (Bell's) facial nerve palsy (n = 7) and ischialgia due to discopathy (n = 2). GSN and DBP levels were measured by Western blot and ELISA, respectively.
Results
We found that the GSN concentration in the blood of the MS group (115 ± 78 μg/ml) was significantly lower (p < 0.001) compared to the control group (244 ± 96 μg/ml). In contrast, there was no statistically significant difference between blood DBP concentrations in patients with MS (310 ± 68 μg/ml) and the control group (314 ± 82 μg/ml). GSN and DBP concentrations in CSF also did not significantly differ between those two groups.
Conclusions
The decrease of GSN concentration in blood and CSF of MS subjects suggests that this protein may be involved in chronic inflammation associated with neurodegeneration. Additionally, the results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Reversing plasma GSN deficiency might represent a new strategy in MS treatment.
doi:10.1186/1471-2377-10-107
PMCID: PMC2989318  PMID: 21040581
23.  Pregabalin versus gabapentin in partial epilepsy: a meta-analysis of dose-response relationships 
BMC Neurology  2010;10:104.
Background
To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy.
Methods
Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies) and gabapentin (4 studies) over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures) and "change from baseline in seizure-free days over the last 28 days (SFD)". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations.
Results
The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25) and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27). Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg) were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg) in terms of SFD over the last 28 days.
Conclusion
In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.
doi:10.1186/1471-2377-10-104
PMCID: PMC2989949  PMID: 21040531
24.  The impact of stroke on emotional intelligence 
BMC Neurology  2010;10:103.
Background
Emotional intelligence (EI) is important for personal, social and career success and has been linked to the frontal anterior cingulate, insula and amygdala regions.
Aim
To ascertain which stroke lesion sites impair emotional intelligence and relation to current frontal assessment measurements.
Methods
One hundred consecutive, non aphasic, independently functioning patients post stroke were evaluated with the Bar-On emotional intelligence test, "known as the Emotional Quotient Inventory (EQ-i)" and frontal tests that included the Wisconsin Card Sorting Test (WCST) and Frontal Systems Behavioral Inventory (FRSBE) for correlational validity. The results of a screening, bedside frontal network syndrome test (FNS) and NIHSS to document neurological deficit were also recorded. Lesion location was determined by the Cerefy digital, coxial brain atlas.
Results
After exclusions (n = 8), patients tested (n = 92, mean age 50.1, CI: 52.9, 47.3 years) revealed that EQ-i scores were correlated (negatively) with all FRSBE T sub-scores (apathy, disinhibition, executive, total), with self-reported scores correlating better than family reported scores. Regression analysis revealed age and FRSBE total scores as the most influential variables. The WCST error percentage T score did not correlate with the EQ-i scores. Based on ANOVA, there were significant differences among the lesion sites with the lowest mean EQ-i scores associated with temporal (71.5) and frontal (87.3) lesions followed by subtentorial (91.7), subcortical gray (92.6) and white (95.2) matter, and the highest scores associated with parieto-occipital lesions (113.1).
Conclusions
1) Stroke impairs EI and is associated with apathy, disinhibition and executive functioning. 2) EI is associated with frontal, temporal, subcortical and subtentorial stroke syndromes.
doi:10.1186/1471-2377-10-103
PMCID: PMC2987854  PMID: 21029468
25.  Gender differences in self reported long term outcomes following moderate to severe traumatic brain injury 
BMC Neurology  2010;10:102.
Background
The majority of research on health outcomes after a traumatic brain injury is focused on male participants. Information examining gender differences in health outcomes post traumatic brain injury is limited. The purpose of this study was to investigate gender differences in symptoms reported after a traumatic brain injury and to examine the degree to which these symptoms are problematic in daily functioning.
Methods
This is a secondary data analysis of a retrospective cohort study of 306 individuals who sustained a moderate to severe traumatic brain injury 8 to 24 years ago. Data were collected using the Problem Checklist (PCL) from the Head Injury Family Interview (HIFI). Using Bonferroni correction, group differences between women and men were explored using Chi-square and Wilcoxon analysis.
Results
Chi-square analysis by gender revealed that significantly more men reported difficulty setting realistic goals and restlessness whereas significantly more women reported headaches, dizziness and loss of confidence. Wilcoxon analysis by gender revealed that men reported sensitivity to noise and sleep disturbances as significantly more problematic than women, whereas for women, lack of initiative and needing supervision were significantly more problematic in daily functioning.
Conclusion
This study provides insight into gender differences on outcomes after traumatic brain injury. There are significant differences between problems reported by men compared to women. This insight may facilitate health service planners and clinicians when developing programs for individuals with brain injury.
doi:10.1186/1471-2377-10-102
PMCID: PMC3006373  PMID: 21029463

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