Category Archives: PSP

“Applause sign” may be due to frontal lobe impairment

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PSP and CBD folks –

This is further evidence that the “applause sign” is not a very useful tool when diagnosing PSP or, by inference, CBD. This research shows that the applause sign can occur in FTD (only the behavioral variant of FTD was included) and AD. (Previously others have argued that it is unique to PSP. More recently, researchers have argued that it is specific to parkinsonian disorders.)

Here’s a description of the applause sign from the article: “The applause sign was detected using the three clap test which was administered and scored according to the literature: subjects were asked ‘to clap three times as quickly as possible after demonstration of the examiner’. The subject’s performance was considered normal when he/she clapped three times (score=3), abnormal when the subject clapped more than three times (2=four times, 1=five to ten times; 0= more than 10 times).”

“An abnormal applause sign was present in all patient groups (80% in PSP, 70% in FTD and 31% in AD) while it was absent in normal controls. …[P]oor specificity and low positive predictive value of the applause sign should raise questions about its diagnostic usefulness.”

Robin

Journal of Neurology, Neurosurgery and Psychiatry. 2011 Jan 18. [Epub ahead of print]

Applause sign: is it really specific for Parkinsonian disorders? Evidence from cortical dementias.

Luzzi S, Fabi K, Pesallaccia M, Silvestrini M, Provinciali L.
Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy.

Abstract

Objective
The applause sign, originally reported as a specific sign of progressive supranuclear palsy (PSP), has recently been found in several parkinsonian disorders. Its nature is still uncertain. It has been interpreted as a motor perseveration or a form of apraxia.

The present study aims to: (a) verify the specificity of the applause sign for parkinsonian disorders, examining the presence of the applause sign in cortical dementias which should be error free and (b) clarify the nature of the applause sign (resulting or not from apraxia).

Methods
77 subjects were included: 10 PSP, 15 frontotemporal dementia (FTD), 29 Alzheimer’s disease (AD) and 23 normal
controls. The presence of apraxia was an exclusion criterion. All patients underwent a detailed neuropsychological examination, and cognitive performance was correlated to the applause sign.

Results
All patient groups showed the applause sign and differed significantly from normal subjects who were error free.

No difference was found when comparing PSP with FTD and FTD with AD.

AD differed significantly from PSP but they were not error free (31% of patients with AD showed the applause sign).

The only correlation with background neuropsychology was found for measures of executive functions.

Conclusions
The presence of the applause sign in cortical dementia does not confirm the specificity of the applause sign for parkinsonian disorders. The applause sign should be interpreted as a sign of frontal lobe dysfunction rather than a form of apraxia, and can likely be detected in any kind of disease which involves frontal lobe structures to some extent.

Pub Med ID#: 21245475 (see pubmed.gov for this abstract only)

Patterns of brain atrophy – PSP, MSA, PD

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This paper from Italian researchers addresses the amount of atrophy in various regions of the brain in those with clinical diagnoses of Parkinson’s Disease (PD), PSP, and MSA. I *think* standard MRIs were given and the volumetric analysis is done by software.

Researchers concluded: “Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.”

Robin

Parkinsonism and Related Disorders. 2011 Jan 12. [Epub ahead of print]

Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy.

Messina D, Cerasa A, Condino F, Arabia G, Novellino F, Nicoletti G, Salsone M, Morelli M, Lanza PL, Quattrone A.
Institute of Neurological Sciences, National Research Council, Piano-Lago, Mangone, Italy; Institute of Neurology, University “Magna Graecia”, Germaneto, Catanzaro, Italy.

Abstract
BACKGROUND AND PURPOSE: Quantitative analysis of brain atrophy may be useful in differentiating Parkinson’s Disease (PD) from Progressive Supranuclear Palsy (PSP) and parkinsonian variant of Multiple System Atrophy (MSA-P); the aim of this study was to identify the volumetric differences of subcortical structures in patients with PD, PSP and MSA-P using a novel and validated fully-automated whole brain segmentation method.

METHODS: Volumetric MRIs were obtained in 72 patients with PD, 32 patients with PSP, 15 patients with MSA-P, and in 46 control subjects. Subcortical volume was measured automatically by FreeSurfer. Multivariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences.

RESULTS: No volumetric differences were found between PD and controls group; otherwise the volumes of the cerebellum, the thalamus, the putamen, the pallidum, the hippocampus, and the brainstem were significantly reduced in PSP and MSA-P compared to patients with PD and control subjects. PSP and MSA-P patients only differed in thalamus volume which was smaller in PSP group (p < 0.001). Moreover, patients with PSP and MSA-P showed a ventricular system (including lateral, third and fourth ventricles) larger than that detected in PD and controls (p < 0.001).

CONCLUSIONS: Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.

Copyright 2010 Elsevier Ltd. All rights reserved.

PubMed ID#: 21236720 (see pubmed.gov for this abstract only)

PSP: “new concepts” – summary article

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This nice summary article, “Progressive supranuclear palsy: new concepts,” is available online at no charge. It reviews the all of the clinical subtypes of PSP, including the two most common types (Richardson’s Syndrome and PSP-Parkinsonism). A photo of a PSP patient with retrocollis is shown.

Given my advocacy for brain donation, I found these points interesting: “[L]ess than a half of patients with pathologically-proven PSP will have received the diagnosis of PSP at presentation. The National Institute of Neurological Disorders and Stroke/ Society for PSP (NINDS/SPSP) criteria detect only 50-70% of patients within 3 years of disease onset.”

Let me know if anything caught your eye.

Here’s a link to the full article:

http://www.scielo.br/scielo.php?script= … so&tlng=en

If this link doesn’t work for you, then go to pubmed.gov and type 21243256 into the search box. Then an abstract will appear along with a logo. Click on the logo to get the article.

Robin

Arquivos de Neuro-Psiquiatria. 2010 Dec;68(6):938-46.

Progressive supranuclear palsy: new concepts.

Barsottini OG, Felício AC, Aquino CC, Pedroso JL.
Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil.

Abstract
Progressive supranuclear palsy (PSP) is a distinctive form of neurodegenerative disease which affects the brainstem and basal ganglia. Patients present supranuclear ophthalmoplegia, postural instability and mild dementia. PSP is defined neuropathologically by the accumulation of neurofibrillary tangles in the subthalamic nucleus, pallidum, red nucleus, substantia nigra, striatum, pontine tegmentum, oculomotor nucleus, medulla and dentate nucleus. Over the last decade many lines of investigations have helped refine PSP in many aspects and it is the purpose of this review to help neurologists identify PSP, to better understand its pathophysiology and to provide a more focused, symptom-based treatment approach.

PubMed ID#: 21243256

‘Bicycle Sign’ May Distinguish PD From Atypical Parkinsonism

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This is a news article based upon some new research published in the latest issue of The Lancet. “New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism,” such as PSP, CBD, MSA, LBD, and vascular parkinsonism.

“Making the differential diagnosis … is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging,” the researchers note. “Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism.”

Could it be this easy?

The short, two-page article in The Lancet is available at present at no charge online. See:
http://www.thelancet.com/journals/lance … 40-6736(11)60018-4/fulltext

The table is worth a quick look.

Here’s a link to the news article in Medscape and the full text.

Robin

http://www.medscape.com/viewarticle/735425

‘Bicycle Sign’ May Distinguish Parkinson’s From Atypical Parkinsonism
Susan Jeffrey
From Medscape Medical News > Neurology

January 7, 2011 — New research suggests the preserved ability to ride a bicycle after onset of symptoms may accurately differentiate between Parkinson’s disease (PD) and atypical parkinsonism.

The investigators, with senior study author Bastiaan R. Bloem, MD, PhD, medical director of the Parkinson Center Nijmegen at Radboud University Nijmegen Medical Center, the Netherlands, had previously reported a case study of a patient with advanced PD who showed an astonishing residual ability to ride a bicycle.

Now they have found in a new series of patients that preserved cycling ability is limited to patients with PD but is lost after disease onset among those with atypical parkinsonism.

“Simply asking about cycling abilities could be added to the list of red flags that can assist clinicians in their early differential diagnosis of parkinsonism,” the study authors conclude.

They report their findings as correspondence in the January 8 issue of The Lancet.

Freezing of Gait

In April 2010, Dr. Bloem and colleague Anke Snijder, MD, reported the case of a 58-year-old man with advanced PD and severe freezing of gait who could nonetheless ride his bicycle for up to 15 miles per day. After meeting this patient, Professor Bloem reported having found an additional 20 PD patients in his outpatient clinic, where he specializes in gait and balance disorders, all of whom could still ride a bicycle (N Engl J Med. 2010;362:13).

“In hindsight, it’s not a unique observation, and we’ve just missed out, maybe because we failed to ask about it or patients fail to volunteer this, but it’s certainly not a unique observation,” he told Medscape Medical News at that time.

Making the differential diagnosis between PD and atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy, or Lewy body dementia, is important clinically for counseling patients and accurate inclusion of suitable patients into trials but remains challenging, they note.

“Here, we suggest that the answer to 1 simple question — ‘Can you still ride a bicycle?” — offers good diagnostic value for separating Parkinson’s disease from atypical parkinsonism,” they write.

To look at this prospectively, investigators performed an observational study of 156 consecutive patients who presented with parkinsonism but did not yet have a definitive diagnosis. All had a structured interview, comprehensive neurological assessment, and cerebral magnetic resonance imaging (MRI) at baseline. Standard questions in the interview asked “whether, when, and why” cycling had become impossible for them.

The gold standard for diagnosis was at 3 years of follow-up, based on clinical examination, response to treatment, and MRI.

Of these patients, 111 had ridden a bicycle before first manifestation of their disease; 45 developed PD and 64 some form of atypical parkinsonism, mostly multiple system atrophy (n = 35, 31.5%) or vascular parkinsonism (n = 17, 15.3%).

At the time of inclusion in the study, occurring at a median disease duration of about 30 months, 34 of 64 patients ultimately diagnosed as having atypical parkinsonism had stopped cycling compared with only 2 of the 45 PD patients, yielding a sensitivity of 52%, and a specificity of 96% (area under the curve, 0.74; 95% confidence interval, 0.64 – 0.83).

The loss of cycling ability was seen with all atypical parkinsonism conditions, they note, and regression analysis showed no significant effect of age, parkinsonism, or ataxia on this ability, “suggesting this was an independent marker of atypical parkinsonism,” they write.

Cycling requires a highly coordinated interplay among balance, coordination, and rhythmic pedaling of the legs, Dr. Bloem and colleagues point out. “This skilled task is probably sensitive to subtle problems with balance or coordination, caused by the more extensive extranigral pathology in atypical parkinsonism,” they speculate.

“We suggest that loss of the ability to cycle after disease onset might serve as a new red flag, signaling the presence of atypical parkinsonism,” the study authors conclude. “The diagnostic value of the ‘bicycle sign’ was good: its presence was highly specific for the diagnosis of atypical parkinsonism.”

The study was supported by a research grant from the Internationaal Parkinson Fonds. The study authors have disclosed no relevant financial relationships.

In vivo comparison of the two most common PSP types

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This looks like a carefully-done study for 23 PSP patients though I don’t think there’s pathological confirmation of the diagnosis. Of the 23, 14 had the Richardson’s syndrome (RS) type of PSP, called “classic PSP.” Nine had PSP-parkinsonism, the second most common type of PSP.

Previous studies suggest “that the clinical presentation of the two subtypes differs especially in the first 2 years of disease and then converges.” This German study attempted to confirm that view.

They found that “RS and PSP-P show considerable symptoms overlap during the disease course when using routine assessments, with persisting differences regarding non-motor symptoms.” Those non-motor symptoms include psychological, cognitive, and behavioral deficits.

We can glean two other points from the abstract:

* “RS patients showed shorter time from disease onset to diagnosis…”

This is certainly because RS patients have “classic PSP” so neurologists are better able to recognize it as being PSP.

” Shorter disease duration of the comparably affected RS patients indicates that this subtype has an accelerated disease progression at early disease stages.”

We know from previous studies that those with the RS type of PSP have a shorter survival time than those with the PSP-P type.

Robin

Journal of Neural Transmission. 2011 Jan 5. [Epub ahead of print]

In vivo comparison of Richardson’s syndrome and progressive supranuclear palsy-parkinsonism.

Srulijes K, Mallien G, Bauer S, Dietzel E, Gröger A, Ebersbach G, Berg D, Maetzler W.
Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany

Abstract
Richardson’s syndrome (RS) and progressive supranuclear palsy-parkinsonism (PSP-P) are the most common subtypes of PSP.

Post-mortem data suggests that the clinical presentation of the two subtypes differs especially in the first 2 years of disease and then converges. This hypothesis has, to our knowledge, never been confirmed in a living cohort.

Medical history was used to define subtypes retrospectively in 23 consecutive PSP patients from our outpatient clinic specialized in movement disorders. 14 patients suffered from RS, and 9 from PSP-P.

Using a prospective cross-sectional approach, clinical, cognitive, behavioral, speech and biochemical (cerebrospinal fluid tau levels) features were compared.

RS patients showed shorter time from disease onset to diagnosis and more neuropsychological and neurobehavioral deficits than PSP-P patients, but differed not significantly with regard to clinical and biochemical features.

RS and PSP-P show considerable symptoms overlap during the disease course when using routine assessments, with persisting differences regarding non-motor symptoms.

Shorter disease duration of the comparably affected RS patients indicates that this subtype has an accelerated disease progression at early disease stages.

PubMed ID#: 21207078