The complexity of movement disorders poses challenges for clinical management and research. Functional imaging with PET or SPECT allows in-vivo assessment of the molecular underpinnings of movement disorders, and biomarkers can aid clinical decision making and understanding of pathophysiology, or determine patient eligibility and endpoints in clinical trials. Imaging targets traditionally include functional processes at the molecular level, typically neurotransmitter systems or brain metabolism, and more recently abnormal protein accumulation, a pathologic hallmark of neurodegenerative diseases. Functional neuroimaging provides complementary information to structural neuroimaging (e.g. anatomic MRI), as molecular/functional changes can present in the absence of, prior to, or alongside structural brain changes. Movement disorder specialists should be aware of the indications, advantages and limitations of molecular functional imaging. An overview is given of functional molecular imaging in movement disorders, covering methodologic background information, typical molecular changes in common movement disorders, and emerging topics with potential for greater future importance.

Gait and balance are fundamental human abilities. When assessing a patient, a certain phenomenologic gait pattern is identified based on characteristic signs that we relate to anatomic systems (topo-diagnosis). According to their functional complexity, these systems can be categorized into lower-level systems (bones, muscles, nerves); intermediate-level systems (basal ganglia, cerebellum, sensory systems); and higher-level systems (cortex–basal ganglia loops). In a second step, we relate this to an underlying etiology, giving rise to a two-axis diagnosis. Gait examination can show direct stepping disturbances as well as indirect, i.e., compensatory changes mainly related to dysbalance (e.g., broad-based gait). The most common disorders include the “ataxias,” related to disturbances of the cerebellum or the sensory systems; basal ganglia gait disorders with parkinsonian or hyperkinetic phenomenology; and higher-level gait disorders, related to disturbances within the cortex–basal ganglia loops, which lead to inappropriate selection and organization of gait and balance programs, resulting in impaired stepping (with freezing of gait) and balance.

PSP was identified in 1963 by Richardson, Steele and Olszewski, as an “unusual syndrome” characterized by axial rigidity, bradykinesia, postural instability with falls, cognitive deficits, and supranuclear vertical gaze palsy, with uniform tau pathology predominating in the neurons of the pallido-nigro-luysian axis. The classical view is that tau protein and neuropil thread accumulation appears mainly in the subthalamic nucleus, red nucleus, substantia nigra, pontine tegmentum, striatum, oculomotor nucleus, medulla, and dentate nucleus, but there is growing evidence that cortical tau pathology is also common. Tau pathology uniformly predominates in the neurons of the pallido-nigro-luysian axis, but clinical PSP subtypes confirmed differential distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies both in total tau load and cell-type specific vulnerability patterns of brain regions, suggesting distinct dynamics or circuit-specific segregation of propagation of tau pathologies with accumulation of brainstem neurofibrillary tangles. Here, the novel clinicopathologic classification of PSP syndromes with specifically underlying neuropathology is discussed.

Such was the aesthetic appeal of a Roman ruin that English grand tourists began to decorate their parkland back home, now landscaped in a sort of ‘faux-naturalism’, with sham ruins. The eighteenth-century fashion for the English garden swept over continental Europe, and many gardens, surprisingly even in Rome itself, have sham Roman ruins after the English fashion. The fashion for sham ‘Roman’ ruins continued into the twentieth century and was extended to the United States and Japan.

Secondary dystonia comprises a group of diverse dystonia syndromes, including hereditary diseases with a clinical phenotype exceeding dystonia as well as acquired dystonia. The first step in the classification of dystonic symptoms should be according to its clinical characteristics – age at onset, body distribution, temporal pattern and associated features. Limb dystonia in adulthood, as well as craniocervical dystonia presentation in childhood and young adolescence, point away from primary dystonia causes. Associated clinical features such as oculomotor disturbances, parkinsonism, cognitive and neuropsychiatric symptoms, and systemic involvement can be instructive for identifying the underlying dystonia syndrome. The diagnostic workup in patients with secondary dystonia depends on the suspected dystonia syndrome and can include laboratory tests in serum and cerebrospinal fluid (CSF), magnetic resonance (MR) imaging, genetic testing, etc. It is important to identify potential treatable causes, e.g., dopa-responsive dystonia, Wilson’s disease, Niemann–Pick Type C, infectious and autoimmune diseases, etc. Symptomatic treatments are also available.

Neurodegenerative disorders are complex multisystem disorders mainly characterized by aggregations of misfolded proteins (such as misfolded amyloid-beta protein in Alzheimer’s disease) in select regions in the central, peripheral, and autonomic nervous systems. In this chapter the various proteinopathic neurodegenerative movement disorders will be dealt with: synucleinopathies, tauopathies, frontotemporal lobar degenerations with TAU, TAR DNA binding protein-43 (TDP), and/or fused in sarcoma (FUS) proteinopathies, polyglutamine CAG-repeat disorders, and misfolded prion proteins. Abnormal protein deposits can be visualized post mortem with immunohistochemical methods that define the diseases, allow the staging schemes, and establish correlations between neuropathologic and clinical phenotypes. As neurodegenerative disorders often display comorbidity, immunohistochemistry with antibody panels has to be performed to enable assessment of the specific protein aggregations in various regions.