Andreas Otte

Influence of spinal cord injury on cerebral sensorimotor systems: a PET study.

OBJECTIVES: To assess the effect of a transverse spinal cord lesion on cerebral energy metabolism in view of sensorimotor reorganisation. METHODS: PET and 18F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 11 patients with complete paraplegia or tetraplegia after spinal cord injury and 12 healthy subjects. Regions of interest analysis was performed to determine global glucose metabolism (CMRGlu). Statistical parametric mapping was applied to compare both groups on a pixel by pixel basis (significance level P = 0.001). RESULTS: Global absolute CMRGlu was lower in spinal cord injury (33.6 (6.6) mumol/100 ml/min (mean (SD)) than in controls (45.6 (6.2), Mann-Whitney P = 0.0026). Statistical parametric mapping analysis disclosed relatively increased glucose metabolism particularly in the supplementary motor area, anterior cingulate, and putamen. Relatively reduced glucose metabolism in patients with spinal cord injury was found in the midbrain, cerebellar hemispheres, and temporal cortex. CONCLUSIONS: It is assumed that cerebral deafferentiation due to reduction or loss of sensorimotor function results in the low level of absolute global CMRGlu found in patients with spinal cord injury. Relatively increased glucose metabolism in brain regions involved in attention and initiation of movement may be related to secondary disinhibition of these regions.

PET and SPECT in Neurology

BASICS: Nuclear Medicine Imaging Tracers for Neurology.- 18F-Fluorodeoxyglucose Positron Emission Tomography Procedures.- Tracer-Kinetic Modeling.- Quantification in Brain SPECT.- MRI/PET Brain Imaging.- An Investigation of Statistical Power of [15O]-H2O PET Perfusion Imaging.- Molecular Imaging Using Magnetic Resonance Spectroscopy in Neurology.- The Default Network of the Brain.- DEMENTIA: Dementia Due to Neurodegenerative Disease - Molecular Imaging Findings.- Abeta Imaging in Aging, Alzheimers Disease and Other Neurodegenerative Conditions.- PET Imaging of the Alpha4Beta2*-Nicotinic Acetylcholine Receptors in Alzheimers.- Neuroimaging Findings in Mild Cognitive Impairment.- Impact of the IWG/Dubois Criteria for Alzheimers Disease in Imaging Studies.- Perfusion SPECT.- Nuclear Imaging in Frontotemporal.- Parkinson Dementia: PET Findings.- SPECT/PET Findings in Lewy Body Dementia.- Vascular.- Value of MIBG in the Differential Diagnosis of Neurodegenerative Disorders.- Linking Molecular Biology to Therapeutic Approaches for Alzheimer Disease with PET.- CEREBROVASCULAR DISORDERS: PET and SPECT Studies of Ageing and Cardiovascular Risk Factors for Alzheimers Disease.- Carotid Plaque Imaging with SPECT-CT and PET-CT.- ET in Brain Arteriovenous Malformations and Cerebral Proliferative Angiopathy.- Transient Ischemic Attack.- PET Reveals Pathophysiology in Ischemic Stroke.- MOVEMENT DISORDERS: Parkinson Disease.- SPECT Imaging for Idiopathic M.Parkinson and Parkinsonian Syndromes.- PET and SPECT Imaging in Parkinsonian Syndromes.- Amyotrophic Lateral Sclerosis.- PET in Huntingtons Disease.- PET and SPECT Imaging in Dystonia.- PET and SPECT Imaging in Hyperkinetic Movement Disorders.- Clinical Applications of [123I]FP-CIT SPECT Imaging.- INFLAMMATORY DISORDERS: PET Imaging of Microglia Activation in Neuropsychiatric Disorders with Potential Infectious Origin.- PET Imaging in Multiple Sclerosis.- PET and SPECT Imaging of Neurotoxicity.- PET and SPECT in Hepatic and Uremic Encephalopathy.- EPILEPSY: PET in Epilepsy.- Subtraction ictal SPECT coregistered to MRI (SISCOM).- Nuclear Medicine Neuroimaging and Electromagnetic Source Localization in Nonlesional Drug-Resistant Focal.- TUMORS OF THE NERVOUS SYSTEM: PET Imaging of Gliomas.- Single-Photon Emission Computed Tomography [Neuro-SPECT] Imaging of Brain Tumors.- The Value of 11C-Methionine PET in the Differential Diagnosis between Brain Tumor Recurrence and Radionecrosis.- Imaging Brain Metastases of Neuroendocrine Tumors.- OTHER SUBJECTS: Traumatic Brain Injury.- Whiplash: real or not real? A review and new concept.- Positron Emission Tomography Imaging in Altered States of Consciousness.- Anaesthesia and PET of the Brain.- Modulation of Brain Functioning by Deep Brain Stimulation.- Radionuclide Imaging Studies in Pediatric Neurology.

PET and SPECT of Neurobiological Systems

BASICS: Animal Models for Brain Research.- Cerebral Glucose Metabolism.- Cerebral Blood Flow Measurements with Oxygen-15 Water PET.- Principles of Brain Perfusion SPECT.- The Impact of Genetic Polymorphisms on Neuroreceptor Imaging.- SYSTEMS: Imaging of Adenosine Receptors.- PET Tracers for Beta-Amyloid and Other Proteinopathies.- Imaging of Central Benzodiazepine Receptors in Chronic Cerebral Ischemia.- PET and SPECT Imaging of the Central Dopamine System in Humans.- PET Imaging of Endocannabinoid System.- Imaging Type 1 Glycine Transporters in the Central Nervous System Using PET.- Imaging Histamine Receptors Using PET and SPECT.- PET and SPECT Imaging of Brain Steroid Hormone Receptors.- Current Radioligands for the PET Imaging of Metabotropic Glutamate Receptors.- PET Imaging of Muscarinic Receptors.- Preclinical Aspects of Nicotinic Acetylcholine Receptor Imaging.- Development of Radioligands for In Vivo Imaging of NMDA Receptors.- Progress in PET Imaging of the Norepinephrine Transporter System.- PET Imaging of Opioid Receptors.- PET Imaging of ABC Transporters in the Blood-Brain Barrier.- PET Imaging of Translocator Protein Expression in Neurological Disorders.- Imaging of the Serotonin System: Radiotracers and Applications in Memory Disorders.- Serotonin Synthesis Studied with PET.- Monoamine Oxidase A and Serotonin Transporter Imaging with PET.- PET Imaging of Sigma-1 Receptors.- Radioligands for Imaging Vesicular Monoamine Transporters.

Functional neuroimaging in whiplash injury

Sir, In the last two decades many has been published on whiplash injury, which is sometimes looked upon as an accident causing extensive symptomatology without the presence of objective findings. Diagnostics of the late whiplash syndrome is an even more challenging endeavour. So far, functional neuroimaging was rarely utilized in contrast to morphological imaging tools, the latter being inconspicuous in most cases, the first showing significant deficits mainly in the posterior parietal occipital region, as first described in 1995 from Otte et al. with perfusion single-photon emission tomography (SPET) to be followed by some other groups and imaging devices (e.g., Freitag et al., 2001; Lass and Lyczak, 2004). In this scenario, we were intrigued by the work of Linnman et al. (2009), who found elevated regional cerebral blood flow (rCBF) bilaterally in the posterior parahippocampal and the posterior cingulate gyri, in the right thalamus and the right medial prefrontal gyrus as well as lowered rCBF in the temporo-occipital regions compared to healthy volunteers. One point in the authorś discussion is, however, rather misleading: Never have we stated that our hypoperfusion in the posterior parietal occipital region (which is matching the hypoperfusion reported by Linnman et al. (2009)) is caused by contusion as they write in their discussion section: we always followed the Moskowitz hypothesis in this region with nociceptive afferents causing increased levels of vasopeptides triggering vasoconstriction in the posterior watershed region (Moskowitz and Buzzi, 1991). To test the hypothesis of nociceptive afferences versus contusion mechanism, we also had re-evaluated our large group of whiplash patients scanned with perfusion SPET and from this identified 15 whiplashinjured drivers who all could remember that they looked to the right side when the rear-end car collision happened (Otte et al., 1998). Ten of the 15 patients reported that they had hit their heads on the steering wheel, the other five could not remember. In statistical parametric mapping, the whiplash patients revealed a significant hypoperfusion in the posterior parietal occipital region of both hemispheres and in the left frontal region (Fig. 1). As the patients looked to the right side during the accident, a contusion mechanism could be discussed for the left frontal and the right posterior parietal occipital region, regardless if this was produced directly by hitting the head to the steering wheel or by the acceleration forces producing indirect head impact. If whiplash injury only was a form of mild head injury with a contusion mechanism, the additional left posterior parietal occipital hypoperfusion in the above patients could not be explained. This analysis, even more, supports the aforementioned Moskowitz hypothesis in whiplash pain syndrome.

Whiplash, Real or Not Real? : A Review and New Concept

Whiplash-associated disorder (WAD) describes a heterogeneous group of symptoms, which develops frequently after an unexpected rear-end car collision. In some of these patients, the symptoms persist for years. There is an ongoing scientific debate about the existence of tissue injury to support this disorder, due to the lack of findings with current diagnostic techniques and the prevalence of emotional traits as risk factors. The purpose of this chapter is to (1) overview the scientific data regarding the presence of an injury mechanism as a consequence of the whiplash trauma, (2) remark the unexpectedness of the accident as essential, and (3) present a new concept according to which WAD symptoms are the result of a mismatch between aberrant information from the cervical spinal cord and the information from the vestibular and visual systems, all of which are integrated in the mesencephalic periaqueductal gray and adjoining regions.

Chronic whiplash-associated disorders

1 Michaleff ZA, Maher CG, Lin CW, et al. Comprehensive physiotherapy exercise programme or advice for chronic whiplash (PROMISE): a pragmatic randomised controlled trial. Lancet 2014; 384: 133–41. 2 Otte A, Mueller-Brand J, Fierz L. Brain SPECT fi ndings in late whiplash syndrome. Lancet 1995; 345: 1513–14. 3 Linnman C, Appel L, Fredrikson M, et al. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal infl ammation. PLoS One 2011; 6: e19182. 4 Moskowitz MA, Buzzi MG. Neuroeff ector functions of sensory fi bers. Implications for headache mechanisms and drug actions. J Neurol 1991; 238 (suppl 1): S18–22. 5 Vallez Garcia D, Dierckx RAJO, Otte A, Holstege G. Whiplash, real or not? A review and new concept. In: Dierckx RAJO, Otte A, de Vries EFJ, van Waarde A, Leenders KL, eds. PET and SPECT in Neurology. Heidelberg, New York, Dordrecht, London: Springer, 2014: 947–63. ventilator-associated pneumonia, and scheduled total body bathing of patients in intensive care units with aqueous chlorhexidine has been shown in large multicentre randomised trials to independently reduce incidence of central venous CRBSI and surface colonisation by methicillin-resistant Staphyl ococcus aureus and other multidrug-resistant nosocomial pathogens. As we concluded in our Article, “we do not claim to have answered the question of which is the most eff ective antiseptic for cutaneous disinfection with vascular catheters...we strongly encourage other investigators to examine this important issue in randomised clinical trials...”.

18F-Fluorodeoxyglucose PET Procedures: Health Economic Aspects in Neurology

Whole-body 18F-FDG PET procedures in oncology have demonstrated utility in patient management in the clinic, especially with the emergence of new hybrid systems such as PET-CT or, more recently, PET-MR. Consequently, the use of 18F-FDG PET brain procedures, which currently represent on average <5 % of all PET procedures, is expected to increase significantly in the coming years. Indeed, driven mostly by the epidemiological burden of neurodegenerative diseases, principally Alzheimer’s disease, functional neuroimaging using PET is expected to become an equally important clinical tool as oncological PET procedures. However, before being implemented as a first-line procedure in neurology, 18F-FDG PET brain imaging must face several health economic challenges: for example, the emergence of direct competitors such as PET amyloid imaging, the availability of resources for tracer and image production, the impact of Health Technology Assessment reports and approval and reimbursement issues. Based on a SWOT analysis (Strengths, Weaknesses, Opportunities, and Threats) highlighting uncertainty parameters that may affect neuroimaging policies, the purpose of this chapter is to provide to decision makers some key health economic components which may remove barriers to the development of 18F-FDG PET in neurology.

The Neural Bypass: New Hope for Spinal Cord Injury Patients

The aim of this data collection is to enforce evidence of SCS effectiveness in treating neuropathic chronic pain and the very low percentage of undesired side effects of complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals.

Nuclear Medicine Imaging in Concussive Head Injuries in Sports

Concussions in sports and during recreational activities are a major source of traumatic brain injury in our society. This is mainly relevant in adolescence and young adulthood, where the annual rate of diagnosed concussions is increasing from year to year. Contact sports (e.g., ice hockey, American football, or boxing) are especially exposed to repeated concussions. While most of the athletes recover fully from the trauma, some experience a variety of symptoms including headache, fatigue, dizziness, anxiety, abnormal balance and postural instability, impaired memory, or other cognitive deficits. Moreover, there is growing evidence regarding clinical and neuropathological consequences of repetitive concussions, which are also linked to an increased risk for depression and Alzheimer’s disease or the development of chronic traumatic encephalopathy. With little contribution of conventional structural imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) to the evaluation of concussion, nuclear imaging techniques (i.e., positron emission tomography (PET) and single-photon emission computed tomography (SPECT)) are in a favorable position to provide reliable tools for a better understanding of the pathophysiology and the clinical evaluation of athletes suffering a concussion.

Perfusion SPECT: Its Role in the Diagnosis and Differential Diagnosis of Alzheimer’s Disease, with Particular Emphasis on Guidelines

Dementia is a clinical diagnosis reflecting many possible underlying pathologies, including, for example, vascular dementia and neurodegenerative disorders such as frontotemporal dementia, Lewy body-type disorder or Alzheimer’s disease (AD). The breakthrough of 99mtechnetium-labelled perfusion tracers in the 1990s resulted in many SPECT studies of flow changes in AD. In the first decade of 2000, the role of perfusion SPECT was shifted from diagnosis towards differential diagnosis, parallel to the growing attention for diagnosing early stages of dementia. This evolution is reflected in the upcoming guidelines, which are detailed in this chapter.