Faculty Bibliography

Early-onset parkinsonism (EO parkinsonism), defined as subjects with disease onset before the age of 40 or 50 years, can be the main clinical presentation of a variety of conditions that are important to differentiate. Although rarer than classical late-onset Parkinson's disease (PD) and not infrequently overlapping with forms of juvenile onset PD, a correct diagnosis of the specific cause of EO parkinsonism is critical for offering appropriate counseling to patients, for family and work planning, and to select the most appropriate symptomatic or etiopathogenic treatments. Clinical features, radiological and laboratory findings are crucial for guiding the differential diagnosis. Here we summarize the most important conditions associated with primary and secondary EO parkinsonism. We also proposed a practical approach based on the current literature and expert opinion to help movement disorders specialists and neurologists navigate this complex and challenging landscape.

Although tardive and neuroleptic-induced movement disorders are not typically viewed as neurologic emergencies, in rare instances they may manifest in ways that can produce severe bodily discomfort or even threaten vital functions like breathing and swallowing. The continued widespread use of dopamine receptor-blocking agents in the hospital and outpatient setting has necessitated their recognition, as prompt diagnosis and treatment are critical for the prevention of sometimes life-threatening complications. In this chapter, we review the history, clinical presentation, and management of neuroleptic-induced respiratory and gastrointestinal phenomena and oculogyric crisis.
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An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesize that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we have generated transcriptomic profiles of monocytes from 230 individuals with sporadic PD and healthy subjects. We observed a dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, is altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.

Background/UNASSIGNED:Reports of drummers' dystonia are rare, particularly compared to the literature on dystonia in string, piano and brass players. Several cases of drummers' dystonia have been included in large series of multiple instrumentalists, but there are few reports comprised exclusively of drummers with musicians' dystonia. We present here a series of 12 drummers with task-specific, focal dystonia affecting their upper limbs while drumming and spanning multiple playing techniques and musical styles. Methods/UNASSIGNED:We conducted a retrospective chart review of drummers with dystonia seen at academic Movement Disorders centers. Results/UNASSIGNED:All 12 patients were male, and the majority eventually developed spread of dystonia to tasks other than drumming. Ten of the 12 had dystonia affecting their fingers, while 8/12 had dystonia affecting the wrist. Only 1/12 had involvement proximal to the wrist. Pharmacologic interventions were largely ineffective; 3 had some benefit from botulinum toxin injections, but this was limited by problematic weakness in one drummer. Discussion/UNASSIGNED:The phenomenology in our series is concordant with prior reported cases, demonstrating frequent wrist involvement, though we also found that a greater proportion of patients had dystonia affecting the fingers. It could be hypothesized that different drumming techniques or musical styles modulate the relative risk of dystonic involvement of the different anatomical regions of the upper limb. Highlights/UNASSIGNED:Drummers' dystonia is one of the least common forms of musicians' dystonia, though this may reflect fewer numbers of these instrumentalists. We present the largest series of drummers' dystonia and review previously published cases. Our cohort, representing diverse drumming styles, showed frequent involvement of dystonia in the wrists and fingers.

Sialidosis type 1 is a rare lysosomal storage disorder caused by mutations of the neuraminidase gene. Specific features suggesting this condition include myoclonus, ataxia and macular cherry-red spots. However, phenotypic variability exists. Here, we present detailed clinical and video description of three patients with this rare condition. We also provide an in-depth characterization of eye movement abnormalities, as an additional tool to investigate pathophysiological mechanisms and to facilitate diagnosis. In our patients, despite phenotypic differences, eye movement deficits largely localized to the cerebellum.

The use of stem cell-derived dopamine neurons or deep brain stimulation (DBS) represents two alternative approaches to treat Parkinson's Disease. DBS is a widely used FDA-approved treatment and stem cell-derived dopamine neuron replacement has now evolved to the first in-human clinical trials. In this debate, we discuss which of these approaches will evolve to be the treatment of choice for Parkinsonian patients in the future.