© Springer-Verlag Italia 2015Angelo Sghirlanzoni, Giuseppe Lauria and Luisa Chiapparini (eds.)Prognosis of Neurological Diseases10.1007/978-88-470-5755-5_29
29. Extrapyramidal Diseases: Atypical Parkinsonisms
Fondazione Giancarlo Quarta Milano, Milan, Italy
KeywordsParkinsonismMovement disordersExtrapyramidal syndromesProgressive supranuclear palsyMultiple system atrophyCortical-basal syndromeNatural history
Term inology and definitions
Parkinsonisms are a heterogeneous spectrum of movement disorders, having as shared core a severe impairment of motor programming skills.
Rigidity and bradykinesia develop more aggressively in atypical parkinsonisms than idiopathic PD. Non-motor symptoms with early deterioration of global performances characterize these syndromes.
PSP – Prevalence 6/100,000. Onset ~66 years with gaze palsy, abrupt falls, bradykinesia, proximal and axial rigidity.
MSA – Prevalence 4.4/100,000. Onset ~55–65 years with autonomic failure, parkinsonism, pyramidal signs, and/or cerebellar ataxia.
CBD – Prevalence 4.9/100,000. Onset ~64 years with asymmetrical parkinsonism, apraxia, and psyco-cognitive dysfunction.
Genetics – Sporadic. Exceptionally, autosomal dominant transmission (PSP, CBD).
Imaging – Usually nonspecific. MRI: midbrain tectum atrophy (PSP). Sporadically, “hot cross bun sign” at MRI and/or normal cardiac uptake of [123I]MIBG (MSA), unlike PD. Asymmetrical cortical and cerebral peduncle atrophy (CBD).
Top differential diagnoses
Parkinson Disease; Lewy Body Disease; Alzheimer Disease, especially in its “Lewy Body” variant; Psychosis.
Range 5–10 years from clinical onset.
Principles of treatment – No effective treatments for PSP, MSA, CBD. Unstained/absent response to levodopa.
Disability – Chronic progressive (PSP; MSA, CBD).
AD, Alzheimer dementia; CBD, Cortical-Basal degeneration; LBD, Lewy Body Disease; MRI, Magnetic Resonance Imaging; MSA, Multiple System Atrophy; OPCA, OlivoPontoCerebellar Atrophy; PD, Parkinson Disease; PSP, Progressive Supranuclear Palsy; SDS, Shy-Drager Syndrome; SND, StrioNigral Degeneration; CNS, Central Nervous System
Parkinsonism configures the clinical prototype of a large and heterogeneous set of movement disorders, having as shared core a remarkable impairment of motor programming skills. Basal nuclei are primarily involved in the pathogenesis of parkinsonisms.
Atypical parkinsonisms are a various group of neurological syndromes where the rigidity and bradykinesia develop more quickly and aggressively than idiopathic Parkinson disease. The emergence of non-motor symptoms with early and significant deterioration of the global patient performances accounts for the poor prognosis characterizes these unusual neurological syndromes.
29.1 Progressive Supranuclear Palsy (PSP)
Synonym: Steele–Richardson–Olzewski Syndrome.
Later adult life tauopathy, characterized by severe progressive parkinsonism and by slowly progressive dementing syndrome.
PSP appears to favor no racial, ethnic, geographical, or occupational group and it affects both genders, despite a slight male predominance. Average age at onset is 66 years, although earlier onset may occur. Approximately, 6 people per 100,000 population have PSP .
29.1.3 Clinical Features
PSP is chronically progressive syndrome usually beginning in the sixth decade with some combination of difficulty in balance, ocular and visual disturbances, abrupt falls, garbled speech, and dysphagia . The most ordinary early complaint is unsteadiness of gait and unexplained backwards falling. The gaze palsy is generally downward. Doll’s eye sign is normal, denoting the supranuclear topography of the disorder.
Other features are facial hypomimia, bradyphrenia, frontal type dementia with impairment of executive functions, mood disorder with changes of personality. Unlike Parkinson disease (PD), PSP seldom produces tremor; besides, rigidity is classically axial, with relative saving of the limbs .
PSP is a sporadic tauopathy that presents neurofibrillary tangles in neurons and glia in specific basal nuclei, brainstem, and neocortical areas. The etiology of PSP is unknown .
PSP suspected diagnosis is clinical. National Institute for Neurological Diseases and Stroke-Society for PSP (NINDS-SPSP) proposed clinical criteria to diagnose PSP .
MRI has an ancillary role, especially useful in the differential diagnosis.
The atrophy of the midbrain tectum, seldom with peculiar “penguin configuration” and volumetric conservation of the pons are the main neuroradiological signs of PSP .
PSP is a sporadic neurodegenerative syndrome. However, rare familial clusters have been described in which the pattern of inheritance is compatible with autosomal dominant transmission .
29.1.6 Top Differential Diagnoses
Parkinson Disease; Multiple System Atrophy; Cortical-Basal Syndrome; Lewy Body Disease; Alzheimer dementia (AD-LBD variant).
Currently, there are no effective treatments for PSP.
Only a few patients respond to dopaminergic drugs; however, pharmacological responsiveness often is short-lived and incomplete .
There are two main clinical subtypes in PSP:
Richardson’s syndrome (RS): prominent postural instability, supranuclear vertical gaze palsy and frontal dysfunction.
PSP-Parkinsonism (PSP-P): asymmetrical onset, tremor, and dim initial therapeutic response to levodopa.
Walking and stability problems are commonly premature features of the disease. Visual and oculomotor deficit tend to occur early as well. Late in the course of the pathology, all these symptoms advance. Therefore, the walking becomes very problematic, if not impossible; eye movement problems get to be more disabling; finally, cognitive injury progresses to dementia.
Disease time course oscillates from 5 to 10 years after onset, with a median survival of approximately 6 years. RS patients seem to have an analogues age at syndrome onset but more quick disease evolution than patients with PSP-P. Individuals with RS show recurrent falls and develop wheelchair dependency earlier than those with PSP-P .
Generally, death in PSP is due to pneumonia or other internistic diseases .