PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of neurologyNeurologyAmerican Academy of Neurology
 
Neurology. 2013 May 14; 80(20): 1856–1861.
PMCID: PMC3908351

The midbrain to pons ratio

A simple and specific MRI sign of progressive supranuclear palsy
Luke A. Massey, MRCP,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. I was funded by a grant from the PSP Association Europe while some of this work was performed up until August 2010.

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Hans R. Jäger, MD, FRCR,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. I have received royalties for the following bookchapters: 1. Saunders D, Jager HR, Murray A, Stevens J. In: Grainger RG, Allison DJ, Adams A, Dixon A, editors. Grainger and Allison Diagnostic Radiology: A Textbook of Medical Imaging. Churchill Livingstone

Employment, Commercial Entity:

  1. Sponsor: Biogen Activity: reader of MRI scans in context of large multicenter drug trial in multiple sclerosis Year: 2005

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. University of Cambridge Fees for Examining PhD thesis 2008

Research Support, Foundations and Societies:

  1. Smantha Dickenson Brain Tumour Trust (uk) and Brain Research Trust (UK). Grant money to suport a longitudinal MR imaging study of low-grade gliomas Years 2005-2008

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Dominic C. Paviour, PhD,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Sean S. O’Sullivan, PhD, MRCPI,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. Honoraria from UCB Pharmaceuticals and Britannia Pharmaceuticals to travel to the Movement Disorders Society annual meetings

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. Health Service Executive, Ireland. Consultant Neurologist

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. Parkinson's UK

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Helen Ling, BScMed, BMBS, MSc,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. Reta Lila Weston Institute of Neurological Studies

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. PSP association fellowship grant

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
David R. Williams, PhD,

Scientific Advisory Boards:

  1. Novartis, Hospira, Ipsen

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Commercial: Abbott Pharma, funding for travel to EFNS and Duodopa training in Sweden

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. Monash Univeristy, Melbourne (Assocaite Professor)

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Constantinos Kallis, PhD,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Janice Holton, PhD, FRCPath,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. 1. Merck-Serono. Agreement to cover travel expenses to give a seminar in Geneva 8.4.2011.

Editorial Boards:

  1. Member of the editorial board Neuropathology Applied Neurobiology 2007- present Executive Editor Neuropathology Applied Neurobiology 2012- present

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. University College London, full time employment.

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. Alzheimer's Research Trust. January 2008 - December 2010 The Margaret Watson Memorial Trust Grant from The Sarah Matheson Trust. January 2008 - December 2008 Action Medical Research November 2007 - October 2009 Brain Net Europe: Support for the Queen Square Brain Bank for Neurological Disorders July 2007 - June 2009 The Sarah Matheson Trust. January 2009 - December 2011 Myositis Support Group June 2009 - May 2010 The Multiple System Atrophy Trust. August 2012 - July 2014 Michael J Fox Foundation for Parkinson's Research December 2010 - November 2011 Alzheimer's Research UK March 2012 - February 2013

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Tamas Revesz, MD, FRCPath,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. IV International Symposium on Parkinson's disease and movement disorders - sponsered by Boehringer-Ingelheim - honorarium Teaching visiting Turkish Neurologists Teaching visiting Swedish Neurologists

Editorial Boards:

  1. Member of editorial boards: Acta Neuropathological Clinical Neuropathology Member of Editorial Advisory Board: Neuropathology and Applied Neurobiology Associate Editor Journal of Parkinson's Disease

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. Merck Serono - Consultancy

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. Orion Pharma: Research Grant (Does Levodopa have toxic effects in Parkinson's disease brain?)

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. 1.) Alzheimer's Research Trust (PI: T Revesz, J Holton; M Rossor; A. Lees), (ART/PG2007/2), (ART/PG2007/2); Title: Clinicopathol. correlation in frontotemporal lobar degeneration, 1/1/2008-31/12, 2011 2.) Alzheimer's Research Trust Research Fellowship; (F Plattner - fellow;T Revesz - sponsor), (ART/RD2005/1), Title: Analysis of molec. mechanisms in tau hyperphosphorylation, 1/3/2006-31/8/2009 3.) European Commission, Programme Grant (LSHM-CT-2004-503039), BrainNet Europe II. Network of Excellence, one of UK Components (PI T Revesz, AJ Lees, JL Holton); 01/07/2007-30/06/2009 4.) Sarah Matheson Trust (PI: T Revesz; J Holton), (Margaret Watson Memorial Grant) Title: The role of p25 in GCI formation in multiple system atrophy; 1/1/2008-31/12/2008 5.) Sarah Matheson Trust, (J. Holton, T Revesz, H. Houlden, J. Hardy, AJ Lees), Title: The central role of oligodendroglia in the pathogenesis of multiple system atrophy, 01/03/2008 - 28/02/2011 6.) Parkinson's Disease Society, UK (PI: T Revesz; J Holton) (PDS/4062), Titlle: Support for Parkinson's Disease brain banking, 15/9/2004 - 31/12/2007 7.) Parkinson's UK (Parkinson's Disease Society): Understanding pathological spread in Parkinson's disease. 2010-2013. PI: Tamas Revesz 8.) MRC/Wellcome Trust: Understanding Parkinson's disease: lessons from biology. 2010-2015. Co-applicant.

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
David J. Burn, MD, FRCP,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Teva-Lundbeck: payment for speaking / chairing annual meetings in 2010-2013 in UK UCB: speaker at national meetings 2010-2013

Editorial Boards:

  1. Movement Disorder Journal: Associate Editor (1st Jan 2010- present)

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. GSK in 2011-2012(payment made to Newcastle University)

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. GSK

Research Support, Government Entities:

  1. Multicentre UK Study of the acetylcholinesterase inhibitor donepezil in early dementia associated with Parkinson's disease (MUSTARDD-PD). NIHR Health Technology Assessment Programme Project REF: 08/14/13: 1st Sept 2010 - 31st Aug 2015; (Burn DJ, Barker RA, Braithwaite B, Burns A, Clarke CE, Hindle JV, Knapp M, Lees AJ, Leroi I, McColl E, McKeith IG, O'Brien JT, Steen IN, Wheatley K). A Biomedical Research Unit in Lewy Body Dementia. NIHR: 1st April 2012 - 31st March 2017; (Burn DJ, McKeith IG, O'Brien JT, Kirkwood TBL, Chinnery PF, Ford GA).

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. Parkinson's UK: Visual symptoms in Parkinson's disease and Parkinson's disease dementia: Association with ocular and retinal pathology, visuo-perceptual deficits and impact on daily living and quality of life. Parkinson's UK: November 2007- October 2010; (Archibald N, Mosimann UP, Clarke MP, Burn DJ). Predicting Dementia in Parkinson's disease: A genotypic and phenotypic study (ICICLE-PD). Parkinson's UK REF J0802, UK: October 2007 - September 2012; (Burn DJ, Barker RA, Brooks DJ, O'Brien JT, McKeith IG, Chinnery PF, Owen AM, Brayne CEG, Robbins T, Sawcer S, Coleman S). The Parkinson's Repository of Biomarkers and Networked Datasets (PROBAND) programme: A UK national clinical consortium linking novel biomarker research to clinical expression, and progression rates, in Parkinson's disease. Parkinson's UK: 2011-2015; (Grosset D, Burn DJ, Barker RA, Ben-Shlomo Y, Bajaj N, Hardy J, Wood NW, Morris HR). Apomorphine: A modifier of amyloid deposition in Parkinson's disease? Parkinson's UK REF K-1101: October 2011 - April 2012;(Burn DJ, Revesz T, Lees AJ). Michael J Fox Foundation Clinical trial to compare cognitive scales. Michael J Fox Foundation: 1st October 2011 - 30th September 2016; (Burn DJ, Weintraub D). Predicting cognitive profiles in Parkinson's disease: A multimodal approach. Michael J Fox Foundation: 1st November 2011 - 31st October 2013; (Burn DJ, Rochester L, O'Brien JT, Coleman SY, Baker MR).

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Tarek Yousry, Dr med Habil, FRCR,

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. 1. Philips, Travel 2. Biogen, Travel and speaker honoraria

Editorial Boards:

  1. 1. The Egyptian Journal of Radiology and Nuclear Medicine , Associate Editor, 2012-2013 2. Neuroradiology, Board member, 2012-2013

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. 1. ESOR

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. 1. GlaxoSmithKline 2. Novartis 3. Biogen Idec

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. 1. NIHR Comprehensive Biomedical Research Centre 2. Medical Research Council 3. MS Society of Great Britain and Northern Ireland 4. Stroke Association 5. British Heart Foundation 6. Wellcome Trust

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Andrew J. Lees, MD, FRCP,

Scientific Advisory Boards:

  1. Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Roche

Gifts:

  1. NONE

Funding for travel or speaker honoraria:

  1. Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Roche

Editorial Boards:

  1. 2006 Archivas de Nevropsiquiatria (Brazil) 1995-03 Co-Editor in Chief, Movement Disorders Journal and Historical Section Editor 1994-98 Founder Editor, Behavioural Neurology 1994- Neurologia Espana 1994-00 Revista Neurologica, Argentina 1994-95 European Journal of Neurology 1993- Revue Neurologique 1993-03 Brain 1991-95 Journal Neurology, Neurosurgery & Psychiatry 1989-95 Journal of Neurology 1988-95 Journal of Neural Transmission

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. Institute of Neurology, UCL

Consultancies:

  1. Genus

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. PSP Association, Weston Trust - The Reta Lila Howard Foundation

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
Nick C. Fox, MD, FRCP,

Scientific Advisory Boards:

  1. (1) Bristol-Myers Squibb, Advisory Board, 2010, 2011, 2012; (2) Eisai Inc, Advisory Board, 2011; (3) GE Healthcare Advisory Board, 2011, 2012 (4) AVID (subsidiary of Eli Lilly), 2011; (5) Johnson & Johnson, 2010; (6) Janssen Alzheimer's Immunotherapy, 2011 (7) Eli Lilly Research Laboratories, 2012

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. (1) Alzheimer's Disease and Associated Disorders - Editorial Board 2004 to present; (2) Neurodegenerative Diseases - Editorial Board - 2004 to present; (3) Alzheimer's Research and Therapy - Editorial Board - 2008 to present

Patents:

  1. QA Box; Application PCT/GB2008/001537; Filed 4 May 2007

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. I have provided consultancy to the following companies. I did not receive personal compensation for this however consultancy fees were paid to our research group. Abbott Laboratories, AstraZeneca, AVID, Bristol-Myers Squibb, Elan Pharmaceuticals, Eisai, Eli Lilly, GE Healthcare, IXICO, Janssen, Lundbeck, neurochem Inc, Pfizer Inc, Sanofi-Aventis, Wyeth Pharmaceuticals.

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. Payments were made to the Dementia Research Centre (no personal compensation to me) for contracted research - image analysis of multi-centre studies. Over the last 2 years these included Elan/Wyeth; Lundbeck; Sanofi; IXICO; Pfizer; Neurochem; Janssen; Pfizer/Wyeth

Research Support, Government Entities:

  1. MRC - PI - [Grant G0801306] - 2009-13; Grant [G0601846] - 2007-2012; NIH - Co-investigator - Grant [U01 AG024904] - 2005-2014; NIHR Senior Investigator - 2009-2013 [Five year term]

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE
and Caroline Micallef, MD, FRCR

Scientific Advisory Boards:

  1. NONE

Gifts:

  1. NONE

Funding for Travel or Speaker Honoraria:

  1. NONE

Editorial Boards:

  1. NONE

Patents:

  1. NONE

Publishing Royalties:

  1. NONE

Employment, Commercial Entity:

  1. NONE

Consultancies:

  1. NONE

Speakers' Bureaus:

  1. NONE

Other Activities:

  1. NONE

Clinical Procedures or Imaging Studies:

  1. NONE

Research Support, Commercial Entities:

  1. NONE

Research Support, Government Entities:

  1. NONE

Research Support, Academic Entities:

  1. NONE

Research Support, Foundations and Societies:

  1. NONE

Stock/Stock Options/Board of Directors Compensation:

  1. NONE

License Fee Payments, Technology or Inventions:

  1. NONE

Royalty Payments, Technology or Inventions:

  1. NONE

Stock/Stock Options, Research Sponsor:

  1. NONE

Stock/Stock Options, Medical Equipment & Materials:

  1. NONE

Legal Proceedings:

  1. NONE

Abstract

Objectives:

MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP.

Methods:

Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21).

Results:

The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm.

Conclusions:

We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.

Neurodegenerative diseases presenting with parkinsonism including idiopathic Parkinson disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) can be difficult to differentiate clinically particularly early in the disease course.1 Characteristic midbrain atrophy in PSP and pontine atrophy in MSA can be assessed on MRI2; however, many magnetic resonance–based measurements proposed as diagnostic for PSP or MSA lack pathologic verification and are often not easy to apply routinely.3,9

Our hypothesis was that simple measurements of the midbrain and pons (or their ratio) on midsagittal MRI would identify confirmed PSP and MSA.

METHODS

Standard protocol approvals, registrations, and patient consents.

A pathologically confirmed cohort of PSP, PD, and MSA subjects (table 1) was selected from the Queen Square Brain Bank at UCL Institute of Neurology; brains were donated following ethically approved protocols under license from the Human Tissue Authority. A cohort of PSP, PD, MSA, and healthy subjects was prospectively recruited at the National Hospital for Neurology and Neurosurgery, as part of an ethically approved study with written informed consent.

Table 1
Demographic and clinimetric features of the pathologically confirmed and clinically diagnosed groupsa

Participants and protocols.

In the pathologically confirmed group, the diagnosis was determined using standard neuropathologic criteria.10 In the clinically diagnosed group, participants fulfilled operational criteria11,13 and were assessed with clinimetric scales including Hoehn and Yahr,14 the Unified Parkinson's Disease Rating Scale,15 Folstein Mini-Mental State Examination,16 the Frontal Assessment Battery,17 Golbe Progressive Supranuclear Palsy Rating Scale,18 or the Unified Multiple System Atrophy Rating Scale.19 Healthy controls had no history of neurologic illness at the time of imaging (figure 1).

Figure 1
Flow diagram in the pathologically confirmed group (A) and application of cutoff values to the clinically defined group (B)

In the pathologically confirmed group, cases were selected in which conventional 1.5-tesla, midsagittal, T1-weighted images were electronically available. In the clinically diagnosed group, all had 3-tesla MRI with volumetric T1-weighted images.

Midbrain and pons measurements and the midbrain to pons ratio.

The measurements were taken as described in figure 2. The midbrain to pons ratio was derived by dividing the midbrain by the pons measurements. In the pathologically confirmed group (n = 29), measurements were made blinded to clinical and pathologic information (C.M., neuroradiologist); a randomly chosen subset (n = 8) was measured by another rater (N.F., neurologist) for interrater assessment. In the clinically diagnosed group (n = 62), a third rater (L.M., neurology trainee) performed all measurements.

Figure 2
Measuring the anterior-posterior distance of the pons and midbrain

Statistical analysis.

Group characteristics were compared using multivariate analysis with post hoc Bonferroni correction. An intraclass correlation coefficient was used to assess interrater agreement and receiver operating characteristic curve analysis to define cutoff values (maximal sum of sensitivity and specificity) in the pathologically confirmed group that were subsequently applied to the clinical group. Pearson correlation coefficient was used to assess correlation of the midbrain measurement and ratio with age at onset, age at scan, and disease duration in the pathologically confirmed group, and in the clinically diagnosed group clinical scores. SPSS 20.0 (IBM SPSS Statistics, Armonk, NY) for Mac was used for statistical analysis.

RESULTS

The demographic features of both cohorts are described in table 1. In pathologically confirmed PSP, the mean midbrain measurement and the midbrain to pons ratio were significantly smaller than in controls and MSA; in the MSA group, there was a trend for the pons measurement to be smaller than in controls. Additionally, in the clinically diagnosed group, the pons was significantly smaller and the midbrain to pons ratio was significantly increased in MSA relative to PSP, to PD, and to controls (table 2, figure 3). Single-measure, intraclass correlation coefficients were 0.97 for the midbrain measurement and 0.94 for the pontine measurement (p < 0.001 for both).

Table 2
Measurements in the pathologically confirmed and clinically diagnosed groupsa
Figure 3
Scatterplots of the midbrain and pons measurements showing both pathologically confirmed and clinically diagnosed groups, and receiver operating characteristic curve analysis in the pathologically confirmed group comparing PSP and MSA

Defined by the maximum sum of sensitivity and specificity from the receiver operating characteristic curve in pathologically confirmed cases, a midbrain measurement of <9.35 mm had 83% sensitivity, 100% specificity, and positive predictive value for PSP (area under the curve 0.94; p = 0.002), and a ratio of <0.52 had 67% sensitivity, 100% specificity, and positive predictive value for PSP (area under the curve 0.95; p = 0.001) when compared with MSA (figure 3).

In the clinically diagnosed PSP group, a threshold of 9.35 mm for midbrain diameter had 100% specificity and positive predictive value for PSP and only 2 cases are not classified as PSP (2/21 = 9.5%). Outliers included 1 probable PSP with a disease duration of 3.7 years and 1 possible PSP with a disease duration of 4.7 years. For a diagnosis of PSP using a threshold of 0.52 for the midbrain to pons ratio, there was a specificity and positive predictive value of 100% and sensitivity of 85.7%.

No correlation was found between age, disease duration, or clinimetric scores with the midbrain or pons measurements or ratio.

DISCUSSION

We found that in normal controls the midbrain tegmentum was approximately two-thirds of the pontine base, whereas in PSP it was half or less of the pontine base and in MSA it was greater than two-thirds (table 2, figure 3). All non-PSP subjects had a midbrain to pons ratio >52%; 67% (pathologically confimed PSP) and 86% (clinically diagnosed PSP) had a ratio of <52%. There was excellent interrater reliability in the measures.

The strengths of our study lie in the pathologic validation of the diagnosis and the rationalized approach to developing simple measurement based on knowledge of the pathologic topography measured on readily available, conventional, midsagittal MRI. Although there was a relatively small sample size of the pathologically confirmed group, our findings appeared to be confirmed in a larger, albeit clinically diagnosed, cohort.

The midbrain measurement and midbrain to pons ratio are approximately equivalent in terms of area under the curve in predicting the diagnosis: the midbrain measurement has higher sensitivity but the ratio controls for head size, which is a confounding factor of simpler measurements. Furthermore, a ratio is easier to estimate using visual inspection. Previous work has shown the hummingbird sign to be a useful indicator of midbrain atrophy in PSP.2,4 Midsagittal images are more reliably reproducible than axial images and linear measurements,3 and manual segmentation for measurement of area4,5 has been studied in clinically diagnosed cases. Our midsagittal midbrain measurement performed better than qualitative visual assessment where a hummingbird sign may be seen in only 67%.2 Furthermore, our results compare favorably with previous reports of midsagittal linear measurements,9 area measurements,5,20 and more detailed analysis of the area of the midbrain tegmentum.4,21

Our results support the hypothesis that because of differential patterns of atrophy, a simple ratio measurement of midbrain to pons helps in differentiating PSP and MSA (figure 3). This is part of the rationale used in the Magnetic Resonance Parkinson Index.6

A previous study has reported a correlation of disease severity with midsagittal midbrain area and a midbrain to pons area ratio5 but other studies using linear measurements do not report this.4,6−8 It may be too much to expect correlation of linear measurements with disease severity—others reported that midsagittal midbrain area measurements do not correlate with disease severity, although a 3-dimensional technique may be helpful.20,22

Although promising, this method will need to be corroborated in larger cohorts and also assessed in early disease where diagnostic uncertainty is greatest. Ideally, these studies would also include pathologic confirmation.

ACKNOWLEDGMENT

The authors are indebted to the donors to the Queen Square Brain Bank for Neurological Disorders without whom this work would not have been possible. The authors are very grateful to Adrienne Wallis who retrieved many of the MRIs used in this study.

GLOSSARY

MSA
multiple system atrophy
PD
Parkinson disease
PSP
progressive supranuclear palsy

AUTHOR CONTRIBUTIONS

Luke A. Massey: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, statistical analysis. Hans R. Jäger: drafting/revising the manuscript, study concept or design, analysis or interpretation of data. Dominic C. Paviour: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data, study supervision. Sean S. O'Sullivan: drafting/revising the manuscript, study concept or design, acquisition of data, study supervision. Helen Ling: analysis or interpretation of data, acquisition of data. David R. Williams: drafting/revising the manuscript, study concept or design, study supervision. Constantinos Kallis: analysis or interpretation of data, statistical analysis. Janice L. Holton: drafting/revising the manuscript, acquisition of data. Tamas Revesz: drafting/revising the manuscript, study concept or design, acquisition of data. David J. Burn: drafting/revising the manuscript, acquisition of data. Tarek A. Yousry: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision, obtaining funding. Andrew J. Lees: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision. Nick C. Fox: drafting/revising the manuscript, study concept or design, analysis or interpretation of data. Caroline Micallef: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, study supervision.

STUDY FUNDING

L.A.M. has been supported by a grant from the PSP (Europe) Association. N.F. has been supported by the Medical Research Council, Alzheimer Research UK, and the National Institute for Health Research. This work was undertaken at UCLH/UCL who received a proportion of funding from the UK Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme (UCLH/UCL Comprehensive Biomedical Research Trust).

DISCLOSURE

L. Massey has been supported by a grant from the PSP (Europe) Association. H. Jäger has been supported by grants from the Stroke Association/British Heart Foundation Joint Program Grant in Stroke and receives royalties from Churchill Livingstone (chapter in Grainger & Allison’s Textbook of Diagnostic Radiology). D. Paviour, C. Kallis, and C. Micallef report no disclosures. S. O’Sullivan has received honoraria from UCB Pharmaceuticals and Teva Pharmaceuticals. H. Ling is supported by the PSP Association research grant (6AJV) and is employed by the Reta Lila Weston Trust for Medical Research, University College London. D. Williams has consultancies with Ipsen, and has received honoraria from Ipsen, Allergen, Hospira, and Novartis. He is supported by grants from NHMRC, Cure PSP, and the Brain Foundation. J. Holton has received honoraria from Merck Serono and has been supported by grants from Parkinson’s UK, the Multiple System Atrophy Trust, and Alzheimer’s Research UK. She has been supported by the Reta Lila Weston Institute for Neurological Studies, the Multiple System Atrophy Trust, Alzheimer's Research UK and Parkinson's UK. T. Revesz has consultancies with and has received honoraria from Merck Serono and Novartis and was supported by a grant from Orion. He has been supported by grants from Parkinson’s UK, Alzheimer’s Research UK, and the Multiple System Atrophy Trust. D. Burn has had consultancies with the Michael J. Fox Foundation and GSK. He has received honoraria from Teva-Lundbeck and UCB. He is supported by grants from Parkinson’s UK, NIHR, Wellcome Trust, and the Michael J. Fox Foundation. T. Yousry has received honoraria from UCB, Bristol-Myers Squibb, and Biogen Idec. He is supported by grants from NIHR CBRC, MRC, MS Society, PSP, Stroke, BHF, Wellcome Trust, GSK, Biogen Idec, and Novartis. A. Lees has a consultancy with Stada. He has received honoraria from Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Merck, Abbott, and Roche. He is supported by grants from the PSP Association, Weston Trust–The Reta Lila Howard Foundation. N. Fox has consultancies with AVID, Bristol-Myers Squibb, Elan/Janssen, Eisai, Eli Lilly, GE Healthcare, IXICO, and Pfizer/Wyeth. He is supported by grants from the MRC, NIH, Alzheimer Research UK, NIHR (Senior Investigator), and EPSRC. This work was also supported by the NIHR’s Biomedical Research Centre funding scheme and Biomedical Research Unit–Dementia. Go to Neurology.org for full disclosures.

REFERENCES

1. Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002;125:861–870. [PubMed]
2. Massey LA, Micallef C, Paviour DC, et al. Conventional magnetic resonance imaging in confirmed progressive supranuclear palsy and multiple system atrophy. Mov Disord 2012;27:1754–1762. [PubMed]
3. Asato R, Akiguchi I, Masunaga S, Hashimoto N. Magnetic resonance imaging distinguishes progressive supranuclear palsy from multiple system atrophy. J Neural Transm 2000;107:1427–1436. [PubMed]
4. Kato N, Arai K, Hattori T. Study of the rostral midbrain atrophy in progressive supranuclear palsy. J Neurol Sci 2003;210:57–60. [PubMed]
5. Oba H, Yagishita A, Terada H, et al. New and reliable MRI diagnosis for progressive supranuclear palsy. Neurology 2005;64:2050–2055. [PubMed]
6. Quattrone A, Nicoletti G, Messina D, et al. MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy. Radiology 2008;246:214–221. [PubMed]
7. Righini A, Antonini A, De Notaris R, et al. MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol 2004;25:927–932. [PubMed]
8. Schrag A, Good CD, Miszkiel K, et al. Differentiation of atypical parkinsonian syndromes with routine MRI. Neurology 2000;54:697–702. [PubMed]
9. Warmuth-Metz M, Naumann M, Csoti I, Solymosi L. Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol 2001;58:1076–1079. [PubMed]
10. Ince PG, Clarke B, Holton JL, Revesz T, Wharton S. Disorders of movement and system degenerations. In: Love S, Louis DN, Ellison DW, editors. , editors. Greenfield's Neuropathology, 8th ed, Vol 1 Boca Raton, FL: CRC Press; 2008:889–1030.
11. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996;47:1–9. [PubMed]
12. Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:94–98. [PubMed]
13. Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 1988;51:745–752. [PMC free article] [PubMed]
14. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;17:427–442. [PubMed]
15. Fahn S, Elton R.; members of the UPDRS Development Committee Recent Developments in Parkinson's Disease, Vol 2 Florham Park, NJ: Macmillan Health Care Information; 1987.
16. Folstein MF, Folstein SE, McHugh PR. "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–198. [PubMed]
17. Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a Frontal Assessment Battery at bedside. Neurology 2000;55:1621–1626. [PubMed]
18. Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain 2007;130:1552–1565. [PubMed]
19. Wenning GK, Tison F, Seppi K, et al. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord 2004;19:1391–1402. [PubMed]
20. Groschel K, Kastrup A, Litvan I, Schulz JB. Penguins and hummingbirds: midbrain atrophy in progressive supranuclear palsy. Neurology 2006;66:949–950. [PubMed]
21. Slowinski J, Imamura A, Uitti RJ, et al. MR imaging of brainstem atrophy in progressive supranuclear palsy. J Neurol 2008;255:37–44. [PubMed]
22. Groschel K, Hauser TK, Luft A, et al. Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration. Neuroimage 2004;21:714–724. [PubMed]

Articles from Neurology are provided here courtesy of American Academy of Neurology