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BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) encompasses a broader range of disease courses than previously appreciated. The most frequent clinical presentations of PSP are Richardson syndrome (RS) and PSP with a predominant Parkinsonism phenotype (PSP-P). Time to reach gait dependence and cognitive impairment have been proposed as prognostic disease milestones. Genetic polymorphisms in TRIM11 and SLC2A13 genes have been associated with longer disease duration (DD). METHODS: Methods used include retrospective chart review, genetic single nucleotide polymorphism analyses (in three cases), and neuropathology. RESULTS: We identified four cases with long (>10–15 years) or very long (>15 years) DD. Stage 1 PSP tau pathology was present in two cases (one PSP-P and one undifferentiated phenotype), whereas pallidonigroluysian atrophy (PSP-RS) and Stage 4/6 (PSP-P) PSP pathology were found in the other two cases. Three cases were homozygous for the rs564309-C allele of the TRIM11 gene and the H1 MAPT haplotype. Two were heterozygous for rs2242367 (G/A) in SLC2A13, whereas the third was homozygous for the G-allele. CONCLUSIONS: We propose a protracted course subtype of PSP (PC-PSP) based on clinical or neuropathological criteria in two cases with anatomically restricted PSP pathology, and very long DD and slower clinical progression in the other two cases. The presence of the rs564309-C allele may influence the protracted disease course. Crystallizing the concept of PC-PSP is important to further understand the pathobiology of tauopathies in line with current hypotheses of protein misfolding, seeding activity, and propagation.

Introduction: Dystonia is a neurologic movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. The etiology of dystonia is diverse and it includes genetic and other causes. Since the advent of botulinum toxin and deep brain stimulation, the treatment of dystonia has markedly improved and is still evolving.Areas covered: This review gives a historical overview of the treatment options for dystonia. In the absence of pathogenesis-targeted, disease-modifying therapies, the treatment of dystonia remains symptomatic. Botulinum toxin is the first line treatment for some forms of focal and segmental dystonias. Oral medications, including anticholinergics, baclofen, benzodiazepines and antidopaminergic drugs are used primarily in patients with generalized dystonia. Levodopa is an effective treatment for patients with dopa-responsive-dystonia. The use of deep brain stimulation, intrathecal and intraventricular baclof...