The PSP Association

Researchers Peter P. Pramstaller (Clinical Research Fellow)

Supervisors Professor C. D. Marsden, Professor A.J. Lees

Institution University Department of Clinical Neurology, Institute of Neurology, National Hospital Queen Square, London, UK

Duration 12 months (1994-1995)

Aim of research
To gain a better understanding of higher motor deficits (apraxia) as compared to lower (elementary) motor deficits (akinesia, rigiditiy, tremor) in PSP and related parkinsonian disorders such as Parkinson's disease (PD), multiple system atrophy (MSA) and drug induced parkinsonism.

Brief details of what the research involved
Apraxia is defined as an inability to execute a voluntary motor movement despite being able to demonstrate normal muscle function. Apraxia is not related to a lack of understanding or to any kind of physical paralysis or more elemental motor disorders typical of patients with parkinsonism but is caused by a problem in the cortex of the brain and the basal ganglia.

The aim of this study was to determine whether a standard comprehensive assessment of different praxic functions would demonstrate specific types of errors not attributable to bradykinesia (slowing of movement), rigidity, tremor or any other abnormal elementary motor deficit. For this we studied 45 non-demented patients with PD, 12 with PSP, 10 with MSA and 12 with neuroleptic-induced parkinsonism (NIP) for the presence of apraxia.

Research findings
Based on our apraxia assessment "higher motor deficits" (ideomotor apraxia) were found only in PSP and PD cases. Neither MSA nor NIP patients showed any disturbance of praxic functions. The presence or absence of cortical involvement, and its severity and distribution seemed to determine the presence and type of apraxia in PD and PSP. Apraxia in these conditions would therefore reflect combined cortico-striatal dysfunction.

Interestingly, some of the PSP cases also showed signs of limbkinetic apraxia as distinct from classical ideomotor limb apraxia. Limbkinetic apraxia typically refers to the inability to make precise movements with the limb, especially the fingers (clumsy hand) and represents a real challenge in distinguishing it from other elementary motor disturbances characteristic of extrapyramidal disorders, particularly bradykinesia.

What does the outcome of this research mean for people with PSP?
This study for the first time clearly demonstrated that higher motor cortical deficits are present also in PSP and that their severity and distribution seems to be related to involvement of the brain cortex. This work catalyzed many more studies into this important higher movement disorder aspect.

Beside this particular project on Apraxia in PSP during my PSP fellowship I had the opportunity be actively involved in other important PSP research issues, ranging from historical aspects of PSP, PSP and its potential link to postencephalitic parkinsonism, spinal cord pathology and sphincter disturbances in PSP, and familial and genetic aspects of PSP.

Publications arising from the work
Leiguarda RC, Pramstaller PP, Merello M, Starkstein S, Lees AJ, Marsden CD. Apraxia in Parkinson's disease, progressive supranuclear palsy, multiple system atrophy and neurolepic-induced parkinsonism. Brain, 1997; 120:75-90.

Pramstaller PP, Marsden CD. The Basal Ganglia and Apraxia. Brain, 1996;119:319-40.

Pramstaller PP, Lees AJ, Luxon LM. Possible clinical overlap between postencephalitic parkinsonism and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 1996;60:589-90.

Brusa A, Pramstaller PP. Ante litteram description of atypical parkinsonian cases. Neurol Sci 2000;21:407-9.

Brusa A, Stoehr R, Pramstaller PP. Progressive Supranuclear Palsy: New Disease or Variant of Postencephalitic Parkinsonism ? Mov Disord. 2004 Mar;19:247-52.

Scaravilli T, Pramstaller PP, Salerno A, Egarter-Vigl E, Giometto B, Vitaliani R, An SF, Revesz T. Neuronal loss in Onuf's nucleus in three patients with progressive supranuclear palsy. Ann Neurol 2000;48:97-101.

Vitaliani R, Scaravilli T, Egarter-Vigl E, Giometto B, Klein C, Scaravilli F, An SF, Pramstaller PP. The pathology of the spinal cord in progressive supranuclear palsy. J Neuropathol Exp Neurol 2002;61:268-74.

Rojo A, Pernaute RS, Fontán A, Ruíz PG, Honnorat J, Lynch T, Chin S, Gonzalo I, Rábano A, Martínez A, Daniel S, Pramstaller PP, Morris H, Wood N, Lees A, Tabernero C, T Nygaard, Jackson AC, Hanson A, de Yébenes JG. Clinical genetics of familial progressive supranuclear palsy. Brain 1999;122:1233-45.

Di Maria E, Tabaton M, Vigo T, Abbruzzese G, Bellone E, Donati C, Frasson E, Marchese R, Montagna P, Munoz DG, Pramstaller PP, Zanusso G, Ajmar F, Mandich P. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann Neurol 2000; 47:374-77.

Piccini P, DeYebenez J, Lees AJ, Ceravolo R, Turjanski N, Pramstaller PP, Brooks DJ. Familial progressive supranuclear palsy: detection of subclinical cases using 18F-dopa and 18FDG PET. Arch Neurol. 2001;58:1846-51.

Weblinks
EURAC Institute of Genetic Medicine
EURAC Research

How has the grant you received influenced your future research?
My PSP Association Clinical Research Fellowship allowed me the opportunity to prolong my research stage at the National Hospital Queen Square under mentorship of Professors. David Marsden and Andrew Lees. It gave me the opportunity to meet many key PSP researchers worldwide and collaborate on many interesting PSP research topics.

I am now Professor of Neurology at the University of Luebeck (Germany) and Director of the Institute of Genetic Medicine at the Euroepan Academy (EURAC research) and the Parkinson Clinic at the Central Hospital in Bolzano (Italy). My whole professional career has definitely been influenced by my working experience at Queen Square and with The PSP Association.

I am particularly grateful to have had the opportunity to meet Sara and Michael Koe, who made me part of an unforgettable experience on human relationships.