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1.  Clinical Characteristics of Symptomatic Vertebral Artery Dissection. A Systematic Review 
The neurologist  2012;18(5):245-254.
Vertebral artery dissection (VAD) is an important cause of stroke in the young. It can present nonspecifically and may be misdiagnosed with adverse consequences. We assessed the frequency of head/neck pain, other neurological symptoms, and cerebrovascular events in symptomatic VAD.
We conducted a systematic review of observational studies, searching electronic databases (MEDLINE, EMBASE) for English-language manuscripts with >5 subjects with clinical or radiological features of VAD. Two independent reviewers selected studies for inclusion; a third adjudicated differences. Studies were assessed for methodological quality and clinical data were abstracted. Pooled proportions were calculated.
Of 3996 citations, we screened 511manuscripts and selected 75 studies describing 1,972 VAD patients. The most common symptoms were dizziness/vertigo (58%), headache (51%) and neck pain (46%). Stroke was common (63%), especially with extracranial dissections (66% vs. 32%, p<0.0001), while TIA (14%) and subarachnoid hemorrhage (SAH) (10%) were uncommon. SAH was seen only with intracranial dissections (57% vs. 0%, p=0.003). Fewer than half of the patients had obvious trauma, and only 7.9% had a known connective tissue disease. Outcome was good (modified Rankin scale (mRS) 0-1) in 67% and poor (mRS 5-6) in 10%.
VAD is associated with nonspecific symptoms such as dizziness, vertigo, headache, or neck pain. Ischemic stroke is the most common reported cerebrovascular complication. VAD should be considered in the diagnostic assessment of patients presenting with dizziness or craniocervical pain, even in the absence of other risk factors. Future studies should compare clinical findings as predictors in well-defined, undifferentiated populations of clinical VAD suspects.
PMCID: PMC3898434  PMID: 22931728
vertebral artery dissection; dizziness; meta-analysis
2.  Imaging Characteristics of Symptomatic Vertebral Artery Dissection: A Systematic Review 
The neurologist  2012;18(5):255-260.
Vertebral artery dissection (VAD) is an important cause of stroke in the young. VAD can present with a range of imaging findings. We sought to summarize the diagnostic value of various imaging findings in patients with symptomatic VAD.
We conducted a systematic review of observational studies, searching electronic databases (MEDLINE, EMBASE) for English-language manuscripts with >5 subjects with clinical or radiological features of VAD. Two independent reviewers selected studies for inclusion; a third adjudicated differences. Studies were assessed for methodological quality and imaging data were abstracted. Pooled proportions were calculated.
Of 3996 citations, we screened 511 manuscripts and selected 75 studies describing 1,972 VAD patients. Most studies utilized conventional angiography or magnetic resonance angiography (MRA) to diagnose VAD; CT angiography (CTA) and Doppler ultrasonography were described less frequently. Imaging findings reported were vertebral artery stenosis (51%), string and pearls (48%), arterial dilation (37%), arterial occlusion (36%), and pseudoaneurysm, double lumen, and intimal flap (22% each). In cases where conventional angiography was the reference standard, CTA was more sensitive (100%) than either MRA (77%) or Doppler ultrasonography (71%) (p=0.001).
Imaging findings vary widely in patients with VAD, with no single radiographic sign present in the majority of VAD patients. Non-specific radiographic signs predominate. CTA probably has greater sensitivity for dissection than MRA or ultrasound relative to conventional angiography. Higher quality studies on imaging techniques and radiographic criteria in subjects with VAD are needed. Future studies should compare imaging techniques in well-defined, undifferentiated populations of clinical VAD suspects.
PMCID: PMC3786429  PMID: 22931729
vertebral artery dissection; neuroimaging; meta-analysis
3.  Novel pathophysiological markers are revealed by iTRAQ-based quantitative clinical proteomics approach in vascular dementia 
Journal of Proteomics  2014;99(100):54-67.
Vascular dementia (VaD) is a leading cause of dementia in the elderly together with Alzheimer's disease with limited treatment options. Poor understanding of the pathophysiology underlying VaD is hindering the development of new therapies. Hence, to unravel its underlying molecular pathology, an iTRAQ-2D-LC–MS/MS strategy was used for quantitative analysis of pooled lysates from Brodmann area 21 of pathologically confirmed cases of VaD and matched non-neurological controls. A total of 144 differentially expressed proteins out of 2281 confidently identified proteins (false discovery rate = 0.3%) were shortlisted for bioinformatics analysis. Western blot analysis of selected proteins using samples from individual patients (n = 10 per group) showed statistically significant increases in the abundance of SOD1 and NCAM and reduced ATP5A in VaD. This suggested a state of hypometabolism and vascular insufficiency along with an inflammatory condition during VaD. Elevation of SOD1 and increasing trend for iron-storage proteins (FTL, FTH1) may be indicative of an oxidative imbalance that is accompanied by an aberrant iron metabolism. The synaptic proteins did not exhibit a generalized decrease in abundance (e.g. syntaxin) in the VaD subjects. This reported proteome offers a reference data set for future basic or translational studies on VaD.
Biological significance
Our study is the first quantitative clinical proteomic study where iTRAQ-2D-LC–MS/MS strategy has been used to identify the differential proteome in the VaD cortex by comparing VaD and matched control subjects. We generate testable hypothesis about the involvement of various proteins in the vascular and parenchymal events during the evolution of VaD that finally leads to malfunction and demise of brain cells. This study also establishes quantitative proteomics as a complementary approach and viable alternative to existing neurochemical, electron microscopic and neuroimaging techniques that are traditionally being used to understand the molecular pathology of VaD. Our study could inspire fellow researchers to initiate similar retrospective studies targeting various ethnicities, age-groups or sub-types of VaD using brain samples available from brain banks across the world. Meta-analysis of these studies in the future may be able to shortlist candidate proteins or pathways for rationale exploration of therapeutic targets or biomarkers for VaD.
Graphical abstract
•A quantitative proteomics study to identify the differential proteome in vascular dementia (VaD)•Identification of 2281 proteins (FDR = 0.3%) from Brodmann area 21 by iTRAQ•Significant alteration of SOD1, NCAM and ATP5A in VaD compared to matched control•No generalized decline in the abundance of synaptic proteins (e.g. syntaxin)•Probable involvement of non-apoptotic modes of cell death in VaD cortex
PMCID: PMC4024194  PMID: 24448401
Vascular dementia; Clinical proteomics; Mass spectrometry; iTRAQ; Vascular dysfunction; Oxidative stress
4.  Vertebral artery dissection and cerebellar infarction following chiropractic manipulation 
Vertebral artery dissection (VAD) associated with chiropractic cervical manipulation is a rare but potentially disabling condition. In this report, we present a young patient manifesting with repeated vertigo. Owing to the initial misdiagnosis, the patient later developed cerebellar stroke with inability to stand or walk. Vertigo and disequilibrium are the usual presenting symptoms of this condition, which can result from inner ear or vestibular nerve dysfunction, vertebrobasilar insufficiency, and even lethal cerebellar infarction or haemorrhage; these last two, although rarely seen in young adults, can be caused by traumatic or spontaneous arterial injury, including injury secondary to chiropractic cervical manipulation. A number of cases of VAD associated with chiropractic cervical manipulation have been reported, but rarely in the emergency medicine literature. We present a case of this rare occurrence, and discuss the diagnostic pitfalls.
PMCID: PMC2564146  PMID: 16373786
vertebral artery dissection; manipulation
5.  Spontaneous Intradural Vertebral Artery Dissection: A Single-Center Experience and Review of the Literature 
Skull Base  2009;19(3):209-218.
Objectives: To define the natural history of spontaneous intracranial vertebral artery dissections (VADs) and to review current treatment strategies. Material and methods: We searched the MEDLINE database for all existing English and French literature on VADs through January 2008. Keywords employed were intradural/intracranial vertebral artery dissection, vertebral artery dissection, and vertebral artery dissection treatment. We also reviewed our series of patients with spontaneous VAD treated in the past 5 years. Data were collected, categorized, and analyzed. Results: In our sample of 457 patients, men were more frequently affected than women, and the mean age was 51.8 years. The majority of patients (79%) presented with subarachnoid hemorrhage (SAH). We experienced a high incidence (37%) of recurrent SAH, particularly within the first 24 hours after SAH first occurred. Angiographic fusiform dilatation and pearl-and-string lesions were the most common finding. Patients who presented with SAH fared worse than those who presented with ischemia. Conclusions: Due to a high rate of recurrent bleeding, we concluded that early treatment by either surgical or endovascular route is indicated in patients who present with SAH secondary to spontaneous intradural VADs. Treatment decisions should take into account the site and type of dissection, vertebral artery dominance, and involvement of posterior inferior cerebellar artery.
PMCID: PMC2702199  PMID: 19881901
Vertebral artery; arterial dissection; intradural vertebral artery; vertebral artery dissection; vertebral artery dissection treatment
6.  Vertebral Artery Dissection Associated with Generalized Convulsive Seizures: A Case Report 
Case Reports in Neurology  2013;5(2):125-129.
A 46-year-old male with juvenile myoclonic epilepsy was admitted to the neurological department for convulsive seizures just after lamotrigine was discontinued. On admission he was awake but had a right-sided hemiparesis with Babinski sign and ataxic finger-nose test on the left side. An MR scan showed a left-sided pontine infarction, an infarct in the left cerebellar hemisphere and a right vertebral artery dissection (VAD). The patient was treated with heparin and an oral anticoagulant for 6 months. Recovery of neurologic function was excellent. In patients with symptoms of disturbances of posterior circulation after epileptic seizures, VAD should be considered.
PMCID: PMC3728598  PMID: 23904852
Seizure; Vertebral artery; Dissection; Stroke
7.  Vertebral artery dissection presenting as isolated vertigo 
Vertigo is not an uncommon presentation to the emergency department. It is most commonly caused by benign peripheral processes, such as inner ear or vestibular nerve dysfunction, but can be due to central brain lesions. In this report, we present a central cause of isolated vertigo: brainstem infarct secondary to vertebral artery dissection (VAD). VAD is increasingly being recognised as an important cause of stroke in young people. We discuss the important features that need to be elicited to distinguish central from peripheral disease and the relevance of VAD.
PMCID: PMC2658449  PMID: 17901283
8.  Multidetector computed tomography angiography: Application in vertebral artery dissection 
Background and Purpose:
Multidetector computed tomography angiography (MDCTA) is a minimally invasive radiological technique providing high-resolution images of the arterial wall and angiographic images of the lumen. We studied the radiological features of vertebral artery dissection (VAD) in a consecutive series of patients investigated for acute stroke and subarachnoid hemorrhage (SAH) in order to confirm and define the diagnostic features of VAD on MDCTA.
Patients and Methods:
Review of patients identified prospectively over a 4-year period with VAD assessed by MDCTA was conducted. Radiological features of VAD on MDCTA were reanalyzed utilising previously reported criteria for VAD.
Thirty-five patients (25 males, mean age 49.6 years) with a total of 45 dissected vertebral arteries were reviewed. MDCTA features of VAD included increased wall thickness in 44/45 (97.7%) arteries and increased total vessel diameter in 42/45 arteries (93.3%). All dissected arteries had either lumen stenosis (21/45) or associated segmental occlusion (24/45). An intimal flap was detected in 6/45 (13.3 %) vessels. Twenty-five patients had follow-up imaging, 14/32 vessels returned to normal, 4 showed improvement in stenosis but did not return to normal and 14 demonstrated no change. The majority of non-occluded vessels became normal or displayed improved patency. Only 4/17 occluded arteries demonstrated re-establishment of flow. No adverse effects were recorded.
MDCTA is a safe and reliable technique for the diagnosis of VAD. Increased wall thickness (97.7%) and increased vessel wall diameter (93.3%) were the most frequently observed features.
PMCID: PMC3098522  PMID: 21633613
Multidetector computed tomographic angiography; vertebral artery dissection; stroke; sub-arachnoid hemorrhage
9.  Are Blood Blister-Like Aneurysms a Specific Type of Dissection? A Comparative Study of Blood Blister-Like Aneurysms and Ruptured Mizutani Type 4 Vertebral Artery Dissections 
Blood blister-like aneurysms (BBAs) resemble arterial dissections. The purpose of this study was to investigate the relationship between these two disease entities and highlight commonalities and distinct features.
Among 871 consecutive patients with aneurysmal subarachnoid hemorrhage, 11 BBAs of internal carotid artery and seven vertebral artery dissections (VADs) with a short segmental eccentric dilatation (Mizutani type 4), which is morphologically similar to a BBA, were selected. The following clinical factors were studied in each group : age, gender, risk factors, Hunt and Hess grade (HHG), Fisher grade (FG), vasospasms, hydrocephalus, perioperative rebleeding rate, and treatment outcome.
The mean age was 47.9 years in the BBAs group and 46.4 years in the type 4 VADs group. All the BBA patients were female, whereas there was a slight male predominance in the type 4 VAD group (male : female ratio of 4 : 3). In the BBA and type 4 VAD groups that underwent less aggressive treatment to save the parent artery, 29% (n=2/7) and 66.6% (n=2/3), respectively, eventually required retreatment. Perioperative rebleeding occurred in 72.7% (n=8) and 28.6% (n=2) of patients in the BBA and type 4 VAD groups, respectively. There was no statistical difference in the other clinical factors in both groups, except for the male dominancy in the type 4 VAD group (p=0.011).
BBAs and ruptured type 4 VADs have a similar morphological appearance but there is a distinct clinical feature in gender and perioperative rebleeding rates. Complete isolation of an aneurysm from the parent artery might be the most important discipline for the treatment of these diseases.
PMCID: PMC4272997  PMID: 25535516
Aneurysm; Dissection; Internal carotid artery; Subarachnoid hemorrhage; Vertebral artery
10.  Traumatic vertebral artery dissection presenting with incomplete congruous homonymous quadrantanopia 
BMC Ophthalmology  2010;10:14.
To describe a rare presentation of vertebral artery dissection (VAD) as a small but congruous incomplete homonymous hemianopia demonstrating use of visual field testing in the diagnosis.
Case presentation
A 30 year old woman had been unwell for 4 months with difficulty focusing, vertigo, dizziness and a feeling of falling to the right. A small but congruous right inferior homonymous quadrantanopia was found on examination leading to further investigation that uncovered a vertebral artery dissection and multiple posterior circulation infarctions including a left occipital stroke matching the field defect.
We describe an atypical case of VAD presenting with a small congruous quadrantanopia. This is a rare but significant condition that predisposes to multiple thromboembolic infarction that may be easily misdiagnosed and a high index of suspicion is required to make the diagnosis.
PMCID: PMC2885997  PMID: 20482837
11.  The profile of the systemic inflammatory response in children undergoing ventricular assist device support 
Serum C-reactive protein (CRP) has been used as a systemic inflammatory response (SIR) marker in the critical ill, including children after cardiopulmonary bypass surgery. Ventricular assist devices (VAD) have been increasingly used as a bridge support to heart transplantation in children. We aimed to examine the profiles of CRP in children receiving VAD support.
Charts of 13 children receiving Berlin Heart EXCOR® from 2005 to 2009 were reviewed. The data obtained prior to and during VAD support included: CRP, white blood cells, inotropes and steroid use, VAD mode and duration of VAD support. Ten patients received left VAD (LVAD) and 3 biventricular VAD (BiVAD).
The median duration of VAD support was 59 days (ranged 3–678 days). Pre-VAD CRP was 35 ± 51 mg/l and increased to 109 ± 59 mg/l on days 1–3 after the VAD implantation (P = 0.01), then gradually decreased to 28 ± 28 mg/l by 4 months and normalized by 5 months (P < 0.0001). CRP was higher in BiVAD than in LVAD patients throughout the study period (P = 0.003). CRP positively correlated with the doses of the epinephrine and norepinephrine and the monocyte counts, and negatively correlated with the lymphocyte count. The lymphocyte count was 2.5 ± 0.4 × 109/l prior to implantation, and decreased to 2.1 ± 1.3 × 109/l on days 1–3 (P = 0.5) and then to 0.6 ± 0.1 × 109/l by 6 months (P = 0.08). It tended to be lower in BiVAD patients (P = 0.06).
SIR exists in children prior to VAD support. VAD implantation is associated with a significant and prolonged increase in CRP and a decrease in lymphocyte count, indicating a suppressed immune function, being more pronounced in BiVAD patients.
PMCID: PMC3422931  PMID: 22617505
C-reactive protein; Systemic inflammatory response; Ventricular assist device; Berlin heart; Paediatrics
12.  Cerebral Arachidonate Cascade in Dementia: Alzheimer’s Disease and Vascular Dementia 
Current Neuropharmacology  2006;4(1):87-100.
Phospholipase A2 (PLA2), cyclooxygenase (COX) and prostaglandin (PG) synthase are enzymes involved in arachidonate cascade. PLA2 liberates arachidonic acid (AA) from cell membrane lipids. COX oxidizes AA to PGG2 followed by an endoperoxidase reaction that converts PGG2 into PGH2. PGs are generated from astrocytes, microglial cells and neurons in the central nervous system, and are altered in the brain of demented patients. Dementia is principally diagnosed into Alzheimer’s disease (AD) and vascular dementia (VaD). In older patients, the brain lesions associated with each pathological process often occur together. Regional brain microvascular abnormalities appear before cognitive decline and neurodegeneration. The coexistence of AD and VaD pathology is often termed mixed dementia. AD and VaD brain lesions interact in important ways to decline cognition, suggesting common pathways of the two neurological diseases. Arachidonate cascade is one of the converged intracellular signal transductions between AD and VaD. PLA2 from mammalian sources are classified as secreted (sPLA2), Ca2+-dependent, cytosolic (cPLA2) and Ca2+-independent cytosolic PLA2 (iPLA2). PLA2 activity can be regulated by calcium, by phosphorylation, and by agonists binding to G-protein-coupled receptors. cPLA2 is upregulalted in AD, but iPLA2 is downregulated. On the other hand, sPLA2 is increased in animal models for VaD. COX-2 is induced and PGD2 are elevated in both AD and VaD. This review presents evidences for central roles of PLA2s, COXs and PGs in the dementia.
PMCID: PMC2430680  PMID: 18615138
Alzheimer’s disease; arachidonic acid; cyclooxygenase; mixed dementia; phospholipase A2; prostaglandin; vascular dementia; PGD2; 15d-Δ12,14-PGJ2
13.  Current understanding of the relationship between cervical manipulation and stroke: what does it mean for the chiropractic profession? 
The understanding of the relationship between cervical manipulative therapy (CMT) and vertebral artery dissection and stroke (VADS) has evolved considerably over the years. In the beginning the relationship was seen as simple cause-effect, in which CMT was seen to cause VADS in certain susceptible individuals. This was perceived as extremely rare by chiropractic physicians, but as far more common by neurologists and others. Recent evidence has clarified the relationship considerably, and suggests that the relationship is not causal, but that patients with VADS often have initial symptoms which cause them to seek care from a chiropractic physician and have a stroke some time after, independent of the chiropractic visit.
This new understanding has shifted the focus for the chiropractic physician from one of attempting to "screen" for "risk of complication to manipulation" to one of recognizing the patient who may be having VADS so that early diagnosis and intervention can be pursued. In addition, this new understanding presents the chiropractic profession with an opportunity to change the conversation about CMT and VADS by taking a proactive, public health approach to this uncommon but potentially devastating disorder.
PMCID: PMC2922298  PMID: 20682039
14.  The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction 
Velvet antler of deer (VAD) is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N = 36) or to sham operation (N = 12). One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP) concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.
PMCID: PMC3348708  PMID: 22611434
15.  Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
The objective of this analysis was to determine the effectiveness of the influenza vaccination and the pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) in reducing the incidence of influenza-related illness or pneumococcal pneumonia.
Clinical Need: Condition and Target Population
Influenza Disease
Influenza is a global threat. It is believed that the risk of a pandemic of influenza still exists. Three pandemics occurred in the 20th century which resulted in millions of deaths worldwide. The fourth pandemic of H1N1 influenza occurred in 2009 and affected countries in all continents.
Rates of serious illness due to influenza viruses are high among older people and patients with chronic conditions such as COPD. The influenza viruses spread from person to person through sneezing and coughing. Infected persons can transfer the virus even a day before their symptoms start. The incubation period is 1 to 4 days with a mean of 2 days. Symptoms of influenza infection include fever, shivering, dry cough, headache, runny or stuffy nose, muscle ache, and sore throat. Other symptoms such as nausea, vomiting, and diarrhea can occur.
Complications of influenza infection include viral pneumonia, secondary bacterial pneumonia, and other secondary bacterial infections such as bronchitis, sinusitis, and otitis media. In viral pneumonia, patients develop acute fever and dyspnea, and may further show signs and symptoms of hypoxia. The organisms involved in bacterial pneumonia are commonly identified as Staphylococcus aureus and Hemophilus influenza. The incidence of secondary bacterial pneumonia is most common in the elderly and those with underlying conditions such as congestive heart disease and chronic bronchitis.
Healthy people usually recover within one week but in very young or very old people and those with underlying medical conditions such as COPD, heart disease, diabetes, and cancer, influenza is associated with higher risks and may lead to hospitalization and in some cases death. The cause of hospitalization or death in many cases is viral pneumonia or secondary bacterial pneumonia. Influenza infection can lead to the exacerbation of COPD or an underlying heart disease.
Streptococcal Pneumonia
Streptococcus pneumoniae, also known as pneumococcus, is an encapsulated Gram-positive bacterium that often colonizes in the nasopharynx of healthy children and adults. Pneumococcus can be transmitted from person to person during close contact. The bacteria can cause illnesses such as otitis media and sinusitis, and may become more aggressive and affect other areas of the body such as the lungs, brain, joints, and blood stream. More severe infections caused by pneumococcus are pneumonia, bacterial sepsis, meningitis, peritonitis, arthritis, osteomyelitis, and in rare cases, endocarditis and pericarditis.
People with impaired immune systems are susceptible to pneumococcal infection. Young children, elderly people, patients with underlying medical conditions including chronic lung or heart disease, human immunodeficiency virus (HIV) infection, sickle cell disease, and people who have undergone a splenectomy are at a higher risk for acquiring pneumococcal pneumonia.
Influenza and Pneumococcal Vaccines
Trivalent Influenza Vaccines in Canada
In Canada, 5 trivalent influenza vaccines are currently authorized for use by injection. Four of these are formulated for intramuscular use and the fifth product (Intanza®) is formulated for intradermal use.
The 4 vaccines for intramuscular use are:
Fluviral (GlaxoSmithKline), split virus, inactivated vaccine, for use in adults and children ≥ 6 months;
Vaxigrip (Sanofi Pasteur), split virus inactivated vaccine, for use in adults and children ≥ 6 months;
Agriflu (Novartis), surface antigen inactivated vaccine, for use in adults and children ≥ 6 months; and
Influvac (Abbott), surface antigen inactivated vaccine, for use in persons ≥ 18 years of age.
FluMist is a live attenuated virus in the form of an intranasal spray for persons aged 2 to 59 years. Immunization with current available influenza vaccines is not recommended for infants less than 6 months of age.
Pneumococcal Vaccine
Pneumococcal polysaccharide vaccines were developed more than 50 years ago and have progressed from 2-valent vaccines to the current 23-valent vaccines to prevent diseases caused by 23 of the most common serotypes of S pneumoniae. Canada-wide estimates suggest that approximately 90% of cases of pneumococcal bacteremia and meningitis are caused by these 23 serotypes. Health Canada has issued licenses for 2 types of 23-valent vaccines to be injected intramuscularly or subcutaneously:
Pneumovax 23® (Merck & Co Inc. Whitehouse Station, NJ, USA), and
Pneumo 23® (Sanofi Pasteur SA, Lion, France) for persons 2 years of age and older.
Other types of pneumococcal vaccines licensed in Canada are for pediatric use. Pneumococcal polysaccharide vaccine is injected only once. A second dose is applied only in some conditions.
Research Questions
What is the effectiveness of the influenza vaccination and the pneumococcal vaccination compared with no vaccination in COPD patients?
What is the safety of these 2 vaccines in COPD patients?
What is the budget impact and cost-effectiveness of these 2 vaccines in COPD patients?
Research Methods
Literature search
Search Strategy
A literature search was performed on July 5, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 to July 5, 2010. The search was updated monthly through the AutoAlert function of the search up to January 31, 2011. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. Data extraction was carried out by the author.
Inclusion Criteria
studies comparing clinical efficacy of the influenza vaccine or the pneumococcal vaccine with no vaccine or placebo;
randomized controlled trials published between January 1, 2000 and January 31, 2011;
studies including patients with COPD only;
studies investigating the efficacy of types of vaccines approved by Health Canada;
English language studies.
Exclusion Criteria
non-randomized controlled trials;
studies investigating vaccines for other diseases;
studies comparing different variations of vaccines;
studies in which patients received 2 or more types of vaccines;
studies comparing different routes of administering vaccines;
studies not reporting clinical efficacy of the vaccine or reporting immune response only;
studies investigating the efficacy of vaccines not approved by Health Canada.
Outcomes of Interest
Primary Outcomes
Influenza vaccination: Episodes of acute respiratory illness due to the influenza virus.
Pneumococcal vaccination: Time to the first episode of community-acquired pneumonia either due to pneumococcus or of unknown etiology.
Secondary Outcomes
rate of hospitalization and mechanical ventilation
mortality rate
adverse events
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses. The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Efficacy of the Influenza Vaccination in Immunocompetent Patients With COPD
Clinical Effectiveness
The influenza vaccination was associated with significantly fewer episodes of influenza-related acute respiratory illness (ARI). The incidence density of influenza-related ARI was:
All patients: vaccine group: (total of 4 cases) = 6.8 episodes per 100 person-years; placebo group: (total of 17 cases) = 28.1 episodes per 100 person-years, (relative risk [RR], 0.2; 95% confidence interval [CI], 0.06−0.70; P = 0.005).
Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] < 50% predicted): vaccine group: (total of 1 case) = 4.6 episodes per 100 person-years; placebo group: (total of 7 cases) = 31.2 episodes per 100 person-years, (RR, 0.1; 95% CI, 0.003−1.1; P = 0.04).
Patients with moderate airflow obstruction (FEV1 50%−69% predicted): vaccine group: (total of 2 cases) = 13.2 episodes per 100 person-years; placebo group: (total of 4 cases) = 23.8 episodes per 100 person-years, (RR, 0.5; 95% CI, 0.05−3.8; P = 0.5).
Patients with mild airflow obstruction (FEV1 ≥ 70% predicted): vaccine group: (total of 1 case) = 4.5 episodes per 100 person-years; placebo group: (total of 6 cases) = 28.2 episodes per 100 person-years, (RR, 0.2; 95% CI, 0.003−1.3; P = 0.06).
The Kaplan-Meier survival analysis showed a significant difference between the vaccinated group and the placebo group regarding the probability of not acquiring influenza-related ARI (log-rank test P value = 0.003). Overall, the vaccine effectiveness was 76%. For categories of mild, moderate, or severe COPD the vaccine effectiveness was 84%, 45%, and 85% respectively.
With respect to hospitalization, fewer patients in the vaccine group compared with the placebo group were hospitalized due to influenza-related ARIs, although these differences were not statistically significant. The incidence density of influenza-related ARIs that required hospitalization was 3.4 episodes per 100 person-years in the vaccine group and 8.3 episodes per 100 person-years in the placebo group (RR, 0.4; 95% CI, 0.04−2.5; P = 0.3; log-rank test P value = 0.2). Also, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD.
Fewer patients in the vaccine group compared with the placebo group required mechanical ventilation due to influenza-related ARIs. However, these differences were not statistically significant. The incidence density of influenza-related ARIs that required mechanical ventilation was 0 episodes per 100 person-years in the vaccine group and 5 episodes per 100 person-years in the placebo group (RR, 0.0; 95% CI, 0−2.5; P = 0.1; log-rank test P value = 0.4). In addition, no statistically significant differences between the 2 groups were observed for the 3 categories of severity of COPD. The effectiveness of the influenza vaccine in preventing influenza-related ARIs and influenza-related hospitalization was not related to age, sex, severity of COPD, smoking status, or comorbid diseases.
Overall, significantly more patients in the vaccine group than the placebo group experienced local adverse reactions (vaccine: 17 [27%], placebo: 4 [6%]; P = 0.002). Significantly more patients in the vaccine group than the placebo group experienced swelling (vaccine 4, placebo 0; P = 0.04) and itching (vaccine 4, placebo 0; P = 0.04). Systemic reactions included headache, myalgia, fever, and skin rash and there were no significant differences between the 2 groups for these reactions (vaccine: 47 [76%], placebo: 51 [81%], P = 0.5).
With respect to lung function, dyspneic symptoms, and exercise capacity, there were no significant differences between the 2 groups at 1 week and at 4 weeks in: FEV1, maximum inspiratory pressure at residual volume, oxygen saturation level of arterial blood, visual analogue scale for dyspneic symptoms, and the 6 Minute Walking Test for exercise capacity.
There was no significant difference between the 2 groups with regard to the probability of not acquiring total ARIs (influenza-related and/or non-influenza-related); (log-rank test P value = 0.6).
Summary of Efficacy of the Pneumococcal Vaccination in Immunocompetent Patients With COPD
Clinical Effectiveness
The Kaplan-Meier survival analysis showed no significant differences between the group receiving the penumoccocal vaccination and the control group for time to the first episode of community-acquired pneumonia due to pneumococcus or of unknown etiology (log-rank test 1.15; P = 0.28). Overall, vaccine efficacy was 24% (95% CI, −24 to 54; P = 0.33).
With respect to the incidence of pneumococcal pneumonia, the Kaplan-Meier survival analysis showed a significant difference between the 2 groups (vaccine: 0/298; control: 5/298; log-rank test 5.03; P = 0.03).
Hospital admission rates and median length of hospital stays were lower in the vaccine group, but the difference was not statistically significant. The mortality rate was not different between the 2 groups.
Subgroup Analysis
The Kaplan-Meier survival analysis showed significant differences between the vaccine and control groups for pneumonia due to pneumococcus and pneumonia of unknown etiology, and when data were analyzed according to subgroups of patients (age < 65 years, and severe airflow obstruction FEV1 < 40% predicted). The accumulated percentage of patients without pneumonia (due to pneumococcus and of unknown etiology) across time was significantly lower in the vaccine group than in the control group in patients younger than 65 years of age (log-rank test 6.68; P = 0.0097) and patients with a FEV1 less than 40% predicted (log-rank test 3.85; P = 0.0498).
Vaccine effectiveness was 76% (95% CI, 20−93; P = 0.01) for patients who were less than 65 years of age and −14% (95% CI, −107 to 38; P = 0.8) for those who were 65 years of age or older. Vaccine effectiveness for patients with a FEV1 less than 40% predicted and FEV1 greater than or equal to 40% predicted was 48% (95% CI, −7 to 80; P = 0.08) and −11% (95% CI, −132 to 47; P = 0.95), respectively. For patients who were less than 65 years of age (FEV1 < 40% predicted), vaccine effectiveness was 91% (95% CI, 35−99; P = 0.002).
Cox modelling showed that the effectiveness of the vaccine was dependent on the age of the patient. The vaccine was not effective in patients 65 years of age or older (hazard ratio, 1.53; 95% CI, 0.61−a2.17; P = 0.66) but it reduced the risk of acquiring pneumonia by 80% in patients less than 65 years of age (hazard ratio, 0.19; 95% CI, 0.06−0.66; P = 0.01).
No patients reported any local or systemic adverse reactions to the vaccine.
PMCID: PMC3384373  PMID: 23074431
16.  MR diagnosis of vertebral artery dissection: value of 3D time-of-flight and true fast imaging with steady-state precession fusion imaging 
Insights into Imaging  2012;4(1):135-142.
We hypothesized that 3D time-of-flight (TOF) and true fast imaging with steady-state precession (true-FISP) fusion imaging could provide more information regarding the arterial vessel wall. The purpose of this study was to compare the accuracy of lesion detection and the diagnostic confidence of VAD between TOF images alone and fused TOF and true-FISP images.
Fifty patients were studied: 17 had VAD and 33 had vertebral artery hypoplasia. Fusion images of the vertebral artery were reconstructed using a workstation. A receiver-operating characteristic (ROC) analysis was conducted with a continuous rating scale from 1 to 100 to compare observer performance in VAD detection. Five radiologists participated in the observer performance test, and their performances with TOF images were compared with those using fused images.
The observers found that the mean areas under the best-fit ROC curve for TOF images alone and fused TOF images were 0.66 ± 0.05 and 0.93 ± 0.04, which were significantly different (P < 0.01).
The fusion images provided more information regarding the arterial vessel wall. Fused images aided distinction between vertebral artery dissection versus vertebral artery hypoplasia.
Key Points
• New MR techniques can help to differentiate flowing blood from static blood products.
• Fused TOF and true-FISP images differentiate the lumen and the arterial wall, improving diagnostic performance.
• Fused images may be superior to time-of-flight MR angiography alone.
PMCID: PMC3579991  PMID: 23203816
Fusion image; Vertebral artery dissection; MR angiography; True FISP; Magnetic resonance imaging
17.  The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia 
The objective of this study was to compare the occurrence and severity of behavioral and psychological symptoms of dementia (BPSD) between vascular dementia (VaD) and vascular cognitive impairment-no dementia (VCI-ND).
Materials and Methods:
Consecutive patients presenting with cognitive impairment at least 3 months after an ischemic stroke and with a Hachinski Ischemic Score ≥4 were included. VaD was diagnosed as per National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for probable VaD and VCI-ND on the lines of the Canadian study of health and aging. The severity of cognitive impairment and the behavioral/psychological symptoms were studied by means of the clinical dementia rating scale and the neuropsychiatric inventory (NPI) respectively.
All patients with VaD and 89% of those with VCI-ND had at least one BPSD. The mean no. of symptoms per patient and the total NPI scores were higher in VaD than in VCI-ND. Apathy and night-time behavior disturbances were significantly more common and severe in VaD.
BPSD are very common both in VCI-ND and in VaD. The profile of BPSD is similar in both groups, albeit more severe in VaD. The net burden of BPSD is higher in VaD as compared to VCI-ND.
PMCID: PMC3841609  PMID: 24339588
Behavioral and psychological symptoms; neuropsychiatric inventory; vascular cognitive impairment; vascular cognitive impairment-no dementia; vascular dementia
18.  Early, Planned Institution of Biventricular Mechanical Circulatory Support Results in Improved Outcomes Compared to Delayed Conversion of LVAD to BiVAD 
It is generally accepted that patients who require biventricular mechanical support (BiVAD) have poorer outcomes than those requiring isolated left ventricular support (LVAD). However, it is unknown how the timing of BiVAD insertion affects outcomes. We hypothesized that planned BiVAD insertion improves survival compared to delayed conversion of LVAD to BiVAD.
We reviewed and compared outcomes of 266 patients undergoing LVAD or BiVAD placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided BiVAD patients into planned BiVAD (P-BiVAD) and delayed BiVAD (D-BiVAD) groups, based on the timing of RVAD insertion. We defined D-BiVAD as any failure of isolated LVAD support.
Of 266 LVAD patients, 99 required BiVAD (37%). We compared preoperative characteristics, successful bridging to transplant, survival to hospital discharge, and Kaplan-Meier one-year survival between P-BiVAD (n=71) and D-BiVAD (n=28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. LVAD (n=167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD outcomes. Further, P-BiVAD patients had superior survival to discharge than D-BiVAD patients (51% v 29% p<0.05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend towards improved bridging to transplant in P-BiVAD (n=55) vs. D-BiVAD (n=22) patients (65% v 45% p=0.10).
When patients at risk for isolated LVAD support failure are identified, proceeding directly to BiVAD implantation is advised, as early institution of biventricular support results in dramatic improvement in survival.
PMCID: PMC3232461  PMID: 19327526
19.  TandemHeart Insertion via a Femoral Arterial GORE-TEX Graft Conduit in a High-Risk Patient 
Texas Heart Institute Journal  2008;35(4):462-465.
The TandemHeart® percutaneous ventricular assist device (pVAD), which provides temporary circulatory support of the left ventricle, can be used in high-risk and hemodynamically unstable patients. The easily inserted TandemHeart provides cardiac support superior to that from the use of intra-aortic balloon pumps. Herein, we discuss TandemHeart implantation via end-to-side femoral arterial grafting in a cardiac patient whose sepsis and multiorgan failure were complicated by coagulopathy and thromboembolism.
A 47-year-old woman, on intra-aortic balloon and intravenous inotropic support after an acute myocardial infarction and emergency coronary artery bypass grafting, was transferred to our institution via helicopter. She developed sepsis and multiorgan failure. Her condition was further complicated by coagulopathy and a left-lower-extremity thromboembolism. After 6 weeks of aggressive pharmacologic and intermittent intra-aortic balloon treatment, the patient developed cardiogenic shock and received a TandemHeart pVAD for short-term circulatory support. A GORE-TEX® access graft, sewn end-to-side to the femoral artery because of the patient's leg ischemia and very small vessels, served as a conduit for the TandemHeart's femoral arterial inflow cannula. Her difficult circulatory, anatomic, and coagulopathic status stabilized after 2 weeks of TandemHeart support, and she was bridged to the long-term MicroMed DeBakey VAD® Child in anticipation of heart transplantation.
The case of our patient shows that high-risk patients who have experienced cardiogenic shock with multiorgan failure and coagulopathy can benefit from the TandemHeart pVAD as a bridge to other therapeutic options, even when creative approaches to treatment and to TandemHeart insertion are required.
PMCID: PMC2607081  PMID: 19156243
Cardiac output, low/therapy; equipment design; heart failure/surgery/therapy; heart valve prosthesis implantation/methods; heart-assist devices; patient selection; risk factors; shock, cardiogenic/therapy; treatment outcome; ventricular dysfunction, left/therapy
20.  Bridge to Transplantation with the TandemHeart 
Texas Heart Institute Journal  2008;35(3):340-341.
Herein, we report a successful bridge to heart transplantation by use of the TandemHeart® percutaneous ventricular assist device (pVAD) in a chronic aortic dissection patient who was experiencing postcardiotomy shock. The patient had undergone an aortocoronary bypass to treat an acute, extensive myocardial infarction that had resulted from severe stenosis of a Cabrol-like graft to the left main coronary artery. The TandemHeart was used successfully, despite classic contraindications for pVAD support. The outcome shows that, in critically ill cardiogenic shock patients, a permissive approach to pVAD use is valuable in screening candidates for long-term ventricular assist device support or for heart transplantation. This case also reveals the validity of direct bridging to transplantation from a pVAD in carefully selected patients.
PMCID: PMC2565541  PMID: 18941602
Aneurysm, dissecting; aortic aneurysm/mortality/surgery; cardiac output/physiology; heart transplantation; heart-assist devices; myocardial infarction/etiology; postoperative complications; shock, cardiogenic/therapy; treatment outcome; ventricular dysfunction, left/physiopathology/therapy
21.  Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia 
The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD).
Materials and Methods:
We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l’Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively.
We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD.
BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.
PMCID: PMC4162022  PMID: 25221405
Alzheimer disease; behavioral and psychological symptoms of dementia; neuropsychiatric inventory; small vessel disease; vascular dementia
22.  Use of Impella Ventricular Assist Device in Patients with Severe Coronary Artery Disease Presenting with Cardiac Arrest 
Impella (Abiomed, Danvers, MA) is a percutaneously inserted ventricular assist device (VAD). It has been increasingly used in patients with severe heart failure, cardiogenic shock, and high-risk percutaneous intervention (PCI). However, the use and efficacy of Impella in patients with severe coronary artery disease (CAD) presenting with cardiac arrest has rarely been reported.The objective of this study is to report our center experience in using Impella VAD in CAD patients presenting with cardiac arrest. From December 2010 to March 2011, three patients with severe CAD presented to our center with cardiac arrest underwent PCI with Impella support. We reported three cases of severe CAD presenting with cardiac arrest successfully treated with PCI and Impella support. Our experience demonstrated that Impella VAD may play an adjunctive role in obtaining hemodynamic stability in these high-risk patients undergoing PCI. One of the patients was supported to left VAD implantation, and the other two had excellent neurological and functional recovery. Our reports suggest an important role of Impella in cardiac arrest population. Earlier Impella implantation after cardiac arrest might provide cardiac support and tissue perfusion until recovery or high-risk PCI.
PMCID: PMC3578627  PMID: 23997562
ventricular assist devices; coronary artery disease; percutaneous coronary intervention; ST segment elevation myocardial infarction; cardiopulmonary resuscitation; cardiac; catheterization; intra-aortic balloon pump
23.  Heart failure reversal by ventricular unloading in patients with chronic cardiomyopathy: criteria for weaning from ventricular assist devices 
European Heart Journal  2010;32(9):1148-1160.
Unloading-promoted reversal of heart failure (HF) allows long-term transplant-free outcome after ventricular assist device (VAD) removal. However, because few patients with chronic cardiomyopathy (CCM) were weaned from VADs (the majority only recently), the reliability of criteria used for weaning decisions to predict long-term post-weaning success is barely known. After 15 years of weaning experience, we assessed this issue.
Methods and results
In 47 patients with CCM as the underlying cause for HF, who were part of a total of 90 patients weaned from bridge-to-transplant-designed VADs since 1995, we analysed data on cardiac morphology and function collected before VAD implantation, echocardiographic parameters recorded during ‘off-pump’ trials, duration of HF before implantation, and stability of recovery before and early after VAD removal. Post-weaning 5 year freedom from HF recurrence reached 66%. Only five patients (10.6%) died due to HF recurrence or weaning-related complications. Pre-explantation off-pump left ventricular ejection fraction (LVEF) of ≥50 and ≥45% revealed predictive values for cardiac stability lasting ≥5 years after VAD removal of 91.7 and 79.1%, respectively. With each unit of LVEF reduction, the risk of HF recurrence became 1.5 times higher. The predictive value of LVEF ≥45% also became >90% if additional parameters like pre-explantation LV size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and HF duration before VAD implantation were also considered. Definite cut-off values for certain parameters (including tissue-Doppler-derived LV wall motion velocity) allowed formulation of weaning criteria with high predictability for post-weaning stability, also in patients with incomplete cardiac recovery.
Ventricular assist device removal in CCM patients is feasible and can be successful even after incomplete cardiac recovery. Parameters of pre-explantation cardiac function, LV size and geometry, their stability during final off-pump trials, and HF duration allow detection of patients with the potential to remain stable for >5 post-weaning years.
PMCID: PMC3086897  PMID: 20929978
Cardiomyopathy; Heart failure; Ventricular assist devices; Myocardial recovery; Survival; Risk factors
24.  Diagnosis and treatment of a dural arteriovenous fistula presenting with progressive parkinsonism and dementia: A case report and literature review 
A dural arteriovenous fistula (DAVF) presenting with parkinsonism and dementia is rare; thus, is easily misdiagnosed. The present study reports the case of a 62-year-old male with mobility disabilities and a cognitive disorder. The initial symptoms were progressive symmetrical limb stiffness and weakness without significant limb tremor, and subsequently the appearance of progressive memory loss, behavioral abnormalities and a decline in the activities of daily living. Cranial magnetic resonance imaging (MRI) revealed an enlarged vascular shadow at the meninges of the left temporal lobe. In addition, digital subtraction angiography (DSA) revealed a DAVF in the left temporal region, fed by the bilateral middle meningeal arteries and meningeal branches of the vertebral artery, which were enlarged abnormally, with poor venous reflux to the superior sagittal sinus. The patient was treated with transarterial embolization therapy. Intraoperative angiography showed almost complete embolization of the DAVF. At day 3 following the surgery, the muscle tension of the bilateral limbs decreased significantly. After two weeks, the memory ability of the patient had recovered to the level prior to the onset, and the gait was stable. At one month post-surgery, the patient was able to take care of himself completely, and after three months, a stereotactic treatment was conducted for the residual fistula. At the one year follow-up, neurological examination revealed that the patient had recovered normally. In conclusion, progressive parkinsonism and dementia with an abnormal flow void shadow on cranial MRI films should be considered as a possible diagnosis of a DAVF. In these cases, DSA and endovascular treatment are recommended as soon as possible.
PMCID: PMC4280959  PMID: 25574227
dural arteriovenous fistula; parkinsonism; dementia; digital subtraction angiography; transarterial embolization
25.  Vertebral artery dissection in a patient practicing self-manipulation of the neck 
Journal of Chiropractic Medicine  2011;10(4):283-287.
The purpose of this case report is to describe a patient who regularly practiced self-manipulation of her neck who presented with shoulder and neck pain and was undergoing a vertebral artery dissection.
Clinical Features
A 42-year-old female patient sought care for left shoulder pain with a secondary complaint of left lower neck pain. Twelve days prior, she had had “the worst headache of her life,” which began in her left lower cervical spine and extended to her left temporal region. The pain was sudden and severe, was described as sharp and burning, and lasted 3 hours. She reported nausea, vomiting, and blurred vision.
Intervention and Outcome
Initial history and examination suggested that the patient's head and neck pain was not musculoskeletal in origin, but vascular. She repeatedly requested that an adjustment be performed, but instead was referred to the local emergency department for further evaluation. Magnetic resonance angiogram revealed a dissection of the left vertebral artery from C6 to the C2-C3 interspace and a 3-mm dissecting pseudoaneurysm at the C3 level. She underwent stent-assisted percutaneous transluminal angioplasty combined with antiplatelet therapy (clopidogrel) and experienced a good outcome.
This case suggests that careful history taking and awareness of the symptoms of VAD are necessary in cases of sudden head and neck pain. More research is needed on the relationship between vertebral artery dissection and self-manipulation of the neck.
PMCID: PMC3315865  PMID: 22654686
Vertebral artery dissection; Chiropractic

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