Byron Center, MI, United States
Byron Center, MI, United States

Time filter

Source Type

Wardlaw J.M.,University of Edinburgh | Smith E.E.,University of Calgary | Biessels G.J.,Rudolf Magnus Institute of Neuroscience | Cordonnier C.,Lille University Hospital Center | And 33 more authors.
The Lancet Neurology | Year: 2013

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE). © 2013 Elsevier Ltd.


Benskey M.J.,Michigan State University | Perez R.G.,Texas Tech University | Manfredsson F.P.,Michigan State University | Manfredsson F.P.,Hauenstein Neuroscience Center
Journal of Neurochemistry | Year: 2016

The aggregation of alpha synuclein (α-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α-syn gene result in familial PD. The high correlation between α-syn burden and PD has led to the hypothesis that α-syn aggregation produces toxicity through a gain-of-function mechanism. However, α-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α-syn results in toxicity because of a toxic loss of necessary α-syn function, following sequestration of functional forms α-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α-syn to PD and the knowledge gained from current α-syn-based animal models of PD. We will then interpret these data from the viewpoint of the α-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of α-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.


Farooq M.U.,Hauenstein Neuroscience Center
Current atherosclerosis reports | Year: 2013

Vascular cognitive impairment (VCI) is a term used to capture the entire spectrum of cognitive impairment from mild to more severe forms and includes all forms of stroke (e.g., ischemic and hemorrhagic forms) associated and underlying cognitive impairment related with subclinical vascular brain injury. Vascular contributions to cognitive impairment are common, especially as one ages. Therefore, both stroke and Alzheimer's disease may be important causes of cognitive impairment in later life, and the concomitant occurrence of these disorders may synergize to increase the risk of poor cognition in later life. In this review we discuss the definition and clinical presentation, mechanisms, cardiovascular risk factors and possible prevention and treatment of VCI. VCI is a potentially treatable and preventable cause of cognitive impairment in later life, and familiarity with this condition will help the practitioner provide better care to patients.


Farooq M.U.,Hauenstein Neuroscience Center | Gorelick P.B.,Michigan State University
Current Atherosclerosis Reports | Year: 2013

Vascular cognitive impairment (VCI) is a term used to capture the entire spectrum of cognitive impairment from mild to more severe forms and includes all forms of stroke (e.g., ischemic and hemorrhagic forms) associated and underlying cognitive impairment related with subclinical vascular brain injury. Vascular contributions to cognitive impairment are common, especially as one ages. Therefore, both stroke and Alzheimer's disease may be important causes of cognitive impairment in later life, and the concomitant occurrence of these disorders may synergize to increase the risk of poor cognition in later life. In this review we discuss the definition and clinical presentation, mechanisms, cardiovascular risk factors and possible prevention and treatment of VCI. VCI is a potentially treatable and preventable cause of cognitive impairment in later life, and familiarity with this condition will help the practitioner provide better care to patients. © 2013 Springer Science+Business Media New York.


Marechal E.,University of Antwerp | Denoiseux B.,University of Antwerp | Thys E.,University of Antwerp | Crosiers D.,University of Antwerp | And 6 more authors.
Journal of Neurology | Year: 2015

Parkinson’s disease (PD) is the second most common neurodegenerative brain disorder and is characterized by motor symptoms such as tremor, bradykinesia, rigidity and postural instability. A majority of the patients also develop non-motor symptoms. Impulse control disorders (ICD) are behavioural changes that often fail to be detected in clinical practice. The prevalence of ICD in PD varies widely from 6.1 to 31.2 % and treatment with dopaminergic medication is considered to be the greatest risk factor. Management consists mainly of reducing dopaminergic medication. In our experience, ICD has a tremendous impact on the quality of life of the patients and their families and should therefore not be disregarded. Studies addressing the role of ICD in PD caregiver strain are imperative. We attempt to give a comprehensive overview of the literature on the complicated neurobiology of ICD and discuss risk factors, genetic susceptibility, screening modalities and management. © Springer-Verlag Berlin Heidelberg 2014.


Gorelick P.B.,Hauenstein Neuroscience Center | Gorelick P.B.,Michigan State University | Farooq M.U.,Hauenstein Neuroscience Center
Stroke Research and Treatment | Year: 2013

We review the role of aspirin and clopidogrel for prevention of ischemic stroke and explore the concept of antiplatelet therapy resistance both from a laboratory and clinical perspective and genetic polymorphisms that might influence platelet reactivity with clopidogrel administration. Debates have raged over the years about the application of platelet function tests in clinical practice. We conclude that platelet function testing is not indicated in routine clinical practice. This recommendation is supported by clinical guideline statements, a lack of a global platelet function measure, and limitations of current platelet function test methods as applied in practice. We discuss a recently hypothesized hierarchy of patient characteristics in relation to which patients are most likely to benefit from platelet function studies based on acuity (i.e., risk) of cardiovascular disease. A focus of antiplatelet therapy administration should include emphasis on compliance/adherence and in the example of aspirin, use of well-absorbed forms of aspirin and avoidance of drugs that may interact with aspirin to inhibit its mechanism of action (e.g., certain nonsteroidal anti-inflammatory drugs). © 2013 Philip B. Gorelick and Muhammad U. Farooq.


Kanaan N.M.,Michigan State University | Kanaan N.M.,Hauenstein Neuroscience Center | Cox K.,Michigan State University | Alvarez V.E.,VA Boston Healthcare System | And 6 more authors.
Journal of Neuropathology and Experimental Neurology | Year: 2016

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PADexposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n146, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. © 2015 American Association of Neuropathologists, Inc. All rights reserved.


Grysiewicz R.,Illinois College | Gorelick P.B.,Hauenstein Neuroscience Center | Gorelick P.B.,Michigan State University
European Neurological Review | Year: 2012

Cerebral congophilic or amyloid angiopathy (CAA) is a clinicopathological entity that is considered a common cause of primary non-traumatic brain haemorrhage in the elderly. CAA is frequently associated with Alzheimer's disease (AD) and has become a primary focus of scientific inquiry. The spectrum of intracerebral haemorrhage (ICH) that may occur in CAA includes: cerebral lobar haemorrhages, deep haemorrhages, purely subarachnoid and subdural haemorrhages and cerebral microbleeds. CAA is also associated with microinfarcts, leukoencephalopathy and superficial siderosis. This brief article will provide an update on the advances in our understanding of CAA-associated ICH with a focus on the following topics: neuropathology and mechanism of CAA-related haemorrhage; epidemiology, including genetic and other possible risk factors; clinical presentation; diagnosis, including newer imaging modalities; and prospects for prevention and treatment. © TOUCHBRIEFINGS 2012.


PubMed | Providence Neurological Specialties, Michigan State University and Hauenstein Neuroscience Center
Type: Journal Article | Journal: The Neurohospitalist | Year: 2014

Transient neurological dysfunction may be associated with uncommon disorders and should prompt consideration of a broad differential diagnosis when assessing patients with episodic symptoms. The most common causes of transient neurological dysfunction include transient ischemic attack (TIA), seizure disorder, and migraine and its variants. However, underlying unusual pathophysiological processes such as brain tumors can also cause transient neurological dysfunction. Here we present a case of a 68-year-old male with oligodendroglial gliomatosis cerebri (OGC) who presented with TIA-like symptoms. Brain magnetic resonance imaging revealed multiple diffuse T2 hyperintensities within the white and gray matter. Magnetic resonance spectroscopy was suggestive of gliomatosis cerebri and was particularly helpful in this case. The diagnosis of OGC was confirmed by histopathology and molecular genetic studies on brain biopsy tissue. In this report, we discuss the clinical and radiological characteristics of OGC and highlight the unusual presentation of this case.


PubMed | Hauenstein Neuroscience Center
Type: Journal Article | Journal: Current atherosclerosis reports | Year: 2013

Vascular cognitive impairment (VCI) is a term used to capture the entire spectrum of cognitive impairment from mild to more severe forms and includes all forms of stroke (e.g., ischemic and hemorrhagic forms) associated and underlying cognitive impairment related with subclinical vascular brain injury. Vascular contributions to cognitive impairment are common, especially as one ages. Therefore, both stroke and Alzheimers disease may be important causes of cognitive impairment in later life, and the concomitant occurrence of these disorders may synergize to increase the risk of poor cognition in later life. In this review we discuss the definition and clinical presentation, mechanisms, cardiovascular risk factors and possible prevention and treatment of VCI. VCI is a potentially treatable and preventable cause of cognitive impairment in later life, and familiarity with this condition will help the practitioner provide better care to patients.

Loading Hauenstein Neuroscience Center collaborators
Loading Hauenstein Neuroscience Center collaborators