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.

When remembering America’s first ladies, there is a general assumption that these women were the wives of the presidents. This is not surprising since, with the exception of James Buchanan, all the presidents have been married men. However, several presidents were widowers or husbands of women who could not assume their duties. These men had to rely on women who were neither their wives nor their companions as stand-in first ladies with the primary duty of entertaining visitors to the White House. They included daughters Martha “Patsy” Jefferson Randolph, Martha Johnson Patterson, and Margaret Woodrow Wilson; nieces Emily Tennessee Donelson and Harriet Lane Johnston; daughters-in-law Angelica Singleton Van Buren and Priscilla Cooper Tyler; and sisters Mary Arthur McElroy and Rose Cleveland. They were real persons who each brought a unique experience to their work, which, unlike the service of their more famous married counterparts, has long been forgotten.

“Trendsetter” first ladies show new ways of modeling femininity in a given era, often through attention to the visual. Because women in public long have been expected to be seen and not heard, fashion and image historically have provided a way of communicating nonverbally. Thus, first ladies who were considered trendsetters typically circulated new “looks” or images to a given public, drawing from the culture in which they operated to influence norms around femininity, beauty, and celebrity. This chapter assesses seven first ladies for their visual influence. Dolley Madison (1809-1817), Julia Tyler (1844-1845), and Frances Cleveland (1886-89, 1893-97) were the most notable of the nineteenth-century first ladies who found themselves positioned as style icons. Following in their footsteps were Mamie Eisenhower (1952-1960), Jacqueline Kennedy (1960-1963), Nancy Reagan (1980-1988), and Michelle Obama (2008-2016), who each leveraged the trendsetter role during their time in the White House.

Despite being unelected and unappointed, first ladies of the United States have served as notable political assets and liabilities before, during, and after their time in the White House. This chapter uses a variety of examples to illustrate the positive and negative impacts of first ladies as they have exerted their influence domestically and internationally, sometimes in alignment with and other times in opposition to their husband’s public agenda. These pages delineate the ways these women have been strategically deployed as emissaries for their husbands and as advocates for party policies, initiatives, and candidates up and down the ballot, as well as how they have instigated and mitigated scandals. The amorphous and often contradictory criteria for being an effective first lady expose every presidential spouse to criticism that is not always reasonable given the nebulous nature of the position.

"Ataxia" refers to both the neurologic syndrome of motor coordination and to a large and diverse group of diseases that have motor coordination impairment as their main clinical feature. The brain structure most consistently affected is the cerebellum. Although many different brain diseases may manifest with ataxia, the vast majority of slowly progressive ataxias are genetic diseases. Indeed, genetic molecular analysis has become the cornerstone of both diagnosis and classification of this complex group of conditions. In this overview, the basics of the clinical features and the classification of these diseases, as well as common conditions, and recently defined novel forms of ataxia are discussed.

The chief interest of the antiquarian in Rome’s ruins was topographical, identifying them if possible with structures known and described in Latin literature. Attempts to picture the layout of the ancient city generated numerous maps and disquisitions, which gradually morphed into guidebooks for tourists, many of which focussed on only the ancient remains to the exclusion of the modern city. The development of tourism is one of the capital outcomes of the fascination with the ruins of Rome. There does not seem to have been any other city or site in the world that was visited for the sake of its ruins. Topographical studies were, however, hampered by their reliance on more (or in one case, less) ancient texts in which buildings and their locations were mentioned, not always reliably. It became clear in due course that the only way forward lay in archaeological excavation.

Magnetic resonance-guided focused ultrasound (MRgHiFUS) can be used to create lesions in the depth of the brain without opening the skull, which opens up new treatment options. For patients who are not eligible for deep brain stimulation (DBS) for various reasons (for example, too much atrophy, vessels in the area of the trajectory, or advanced age) this can be a useful addition to the therapeutic armamentarium. To date, more than 3,500 patients have been treated with this method, with a focus on patients with essential tremor (ET) and tremor-dominant Parkinson’s disease (PD).

In 235 years, only about two dozen women have experienced the role of “mourner in chief” as current or former first ladies grieving a presidential husband. This chapter examines the performances of six of these women in different historical contexts and under very different circumstances: Martha Washington, Mary Lincoln, Lucretia Garfield, Eleanor Roosevelt, Jacqueline Kennedy, and Nancy Reagan. This analysis considers first ladies’ performances of mourning during presidents’ illness or assassination; funerals and memorial services; and the expanse of time for which they survived their husbands. Through these case studies, the authors consider how a first lady’s mourning can shape her husband’s legacy, and what it can teach us about how Americans grieve.

This chapter provides an overview of the basic features of the macroscopic and microscopic anatomy, physiology and potential functioning of the human cerebellum. Apart from its certain role in movement control by coordinating complex movements, additional hypotheses on the role of the cerebellum in adapting, conditioning and learning, or automating, movements are described. Views that portray the cerebellum as a timing device or as a structure that serves to optimize the quality of sensory input are also mentioned. As the cerebellum not only participates in movement control, understanding and appreciating its functioning may also explain its role in cognition, emotion, and autonomic functions. Finally, cerebellar disorders and clinical manifestations of cerebellar dysfunction in movement control are discussed.

The presence of parkinsonism is required for the diagnosis of certain clinical syndromes and, together with demographic, clinical, and genetic features, can be highly predictive of underlying pathology, usually α-synuclein or tau aggregation. Nevertheless, parkinsonian features may be present in clinical syndromes not typically associated with parkinsonism and, therefore, complicate differential diagnosis. On the other hand, certain tauopathies have a variable frequency of associated parkinsonian disturbances, further challenging clinical to pathologic diagnostic accuracy. In this chapter, we briefly describe less-common clinical syndromes that may present with, or eventually manifest, extrapyramidal symptoms characteristic of parkinsonism but for which parkinsonism is not typically considered a core clinical feature. Although some of these clinical syndromes are primarily associated with tauopathies (frontotemporal degeneration with parkinsonism linked to chromosome 17, primary progressive apraxia of speech and traumatic encephalopathy syndrome), tauopathy is seldom the underlying pathology in cases of primary progressive aphasia.

Dystonia, defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both, results in patterned, twisted, and sometimes tremulous movements. When dystonia is the sole manifestation, it is known as primary dystonia. Primary dystonia is an uncommon disorder and includes genetic forms of dystonia as well as idiopathic dystonia. Dystonia can involve one body part, when it is called focal; more than one contiguous body part, when it is known as segmental; or involving the trunk and more than two body parts, when it is called generalized. This chapter reviews primary dystonia: the epidemiology, the current theories of pathophysiology, the clinical description, and available treatments of genetic as well as the various forms of focal dystonia, including blepharospasm, oromandibular dystonia, laryngeal dystonia, cervical dystonia, focal hand dystonia and truncal dystonia.

This chapter summarizes current knowledge concerning illicit drugs and specific toxins, such as some street drugs, organic solvents, pesticides and herbal extracts like Cycas circinalis, known to induce signs and symptoms of motor parkinsonism. Special attention is given to differential diagnosis and therapeutical strategies. Marketed drugs such as antipsychotics, anti-emetics, calcium channel blockers, selective serotonin reuptake inhibitors, antiepileptics, antidepressants, antiarrhythmics, immunosuppressants, statins, and trimeazidine, also identified to cause drug-induced parkinsonism, are also dealt with in this chapter.

Petrarch initiated ruin-tourism, and that flowered in the period of the eighteenth-century Grand Tour. Arguably, the ruins of Rome were the first to generate the production of a considerable variety of souvenirs, portable objects manufactured expressly for visitors to take away. Now a souvenir is only desirable if the object it represents is deemed attractive: the ruin-aesthetic was so well established by the time of the Grand Tour that ruins moved from the background of paintings into the foreground; they became the subject. In the engravings of Piranesi the ruins of Rome reached their peak of aesthetic appeal. The aesthetic validation of ruins is to the fore, since the English decorated the interiors of their houses with scenes of ruination. They also brought home architectural models of ruins in cork or marble for display; their porcelain and fans were decorated with ruin motifs.

The clinical and pathologic hallmarks of Parkinson’s disease (PD) are motor parkinsonism due to underlying progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta accompanied by an accumulation of intracytoplasmic protein inclusions known as Lewy bodies and Lewy neurites. The diagnostic criteria/guidelines based on the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria have guided clinicians and researchers in the diagnosis of PD for many decades. This chapter discusses whether this description represents our current understanding of PD, and why it is time to integrate new research findings and accommodate our definition and diagnostic criteria of PD, such as Parkinson-associated non-motor symptoms, genetics, biomarkers, imaging findings, or heterogeneity of phenotypes and underlying molecular mechanisms. In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson’s disease, which were designed specifically for use in research but also as a general guide to clinical diagnosis of PD. These criteria and some of their limitations are also discussed.