PSP: “new concepts” – summary article

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

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.

Sinemet shortage in early 2011?

Those of you who take Sinemet may be interested in this news relayed by the National Parkinson’s Foundation…

The “issue” with taking the generic form of Sinemet is that the FDA requires the bioequivalence of any generic product to be between 80% and 125% of that of the innovator product. This is a rather large range.

————-
Email from National Parkinson’s Foundation
1/7/11

Merck & Co. Inc. has informed the Parkinson’s disease community that in early 2011, there may be a potential temporary supply shortage in the U.S. for SINEMET® (carbidopa-levodopa) and SINEMET CR® (carbidopa-levodopa controlled release tablets).

While there is currently no shortage, it is advisable to speak with your health care provider about appropriate steps should a shortage occur. Your health care provider can give you relevant information about potential short-term alternative therapies, including the availability of alternative generic equivalents.

The FDA has shown generic SINEMET® to be effective against the symptoms of Parkinson’s disease, but dosing may need to be slightly adjusted due to differences in manufacturing and formulation. Should you need to temporarily switch to a generic version of SINEMET®, be aware that some people may experience a change in how the medication works. If you do experience a change, contact your health care provider who may prescribe a different dose or timing regimen.

Patients, caregivers and health care professionals in the U.S. who have more questions about the availability of SINEMET® can contact the Merck National Service Center at 1-800-NSC-MERCK.

NPF is committed to keeping you informed of developments on this issue. We will alert you if we get any more information about either a shortage developing or the crisis being averted. If you are informed by your doctor or pharmacist that SINEMET® is not available in your area, please contact us at 1-800-4PD-INFO (473-4636) or [email protected]. If you have any questions, Dr. Okun is prepared to address issues about the shortage and generic substitution on our Ask the Doc online discussion forum.

In vivo comparison of the two most common PSP types

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

First AD patient with PIB scans

Those of you interested in advances in imaging for neurodegenerative disorders and the correlations between imaging studies (while a patient is alive) and brain pathology (seen on post-mortem autopsy) will LOVE this news.

The PET is a type of brain scan. Currently, nearly all PET scans employ FDG, which picks up on glucose in the brain. For the last several years, the latest in PET scans for Alzheimer’s or other dementia patients employs PIB, Pittsburgh Compound B. PIB picks up on amyloid plaques. (The dye is retained by the insoluble amyloid protein.) Alzheimer’s disease is a disorder of two proteins — amyloid (which forms plaques) and tau (which forms tangles).

Hopefully, one day, we’ll have PET scans that can detect tau tangles (which would help diagnose PSP and CBD). Also, PSP and CBD can co-occur with Alzheimer’s Disease, so this news may be relevant to some in the PSP/CBD community also. (I’ve forgotten the exact percentage but it’s something like 20-30% of the time.)

The Alzheimer Research Forum has a (mostly-understandable) summary of a recently published article in the December 13th issue of the journal Brain about a woman with Alzheimer’s Disease who “volunteered for the first PET-PIB scan ever performed. She received another PIB scan two years later, and over the course of her disease also got an MRI and three PET scans using fluorodeoxyglucose (FDG), a marker for glucose use and therefore brain metabolism.” The woman died at the age of 61. She donated her brain for autopsy.

“Over the eight years she was studied, the woman’s score on the Mini-Mental State Examination declined from a near-normal score of 27 down to five. The FDG data showed that her brain’s glucose metabolism decreased in parallel with her cognitive powers. By contrast, PIB retention, already high at first examination, showed little change over two years during which her cognition declined steeply. The amount of amyloid deposition seen at autopsy three years later also looked similar to PIB estimates…suggesting no further change in amyloid between the second PIB scan and death three years later. This pattern matches the data from numerous previous studies, in which PIB retention increases during mild cognitive impairment, then seems to plateau during AD.”

“Autopsy results confirmed the patient’s diagnosis of pure AD. … The results confirmed that in vivo PIB retention correlates quite well with amyloid deposits, but does not correlate closely with tau and neurofibrillary tangles, as previous studies have found. … In addition, the authors performed detailed studies not done before and turned up intriguing correlations between amyloid accumulation and synaptic receptor density, as well as a surprising lack of correlation with markers of inflammation.”

The summary on the Alzheimer Research Forum discusses four clinical trials with compounds targeting amyloid in Alzheimer’s patients. The trials were all negative. This PET-PIB study gives additional insight as to why that may be the case.

Here’s the summary on ARF about the recently-published study:
http://www.alzforum.org/new/detail.asp?id=2653

Note that some of the comments are well worth reading, though harder to understand than the summary. Some of the comments (posted in 2004) give historical info on PIB.

The recently-published study is available at no charge through the journal Brain. See:
http://brain.oxfordjournals.org/content/134/1/301.long (for HTML version)