Use of Requip and Mirapex in 3 Path-confirmed PSP Cases

This UK team, most of whom are at the University College London, is probably top in the world in terms of clinical-pathological correlations on PSP.

This recently-published article is about three cases of pathologically confirmed PSP who developed impulsive-compulsive spectrum behaviors (ICBs) when taking dopamine agonists (DA). Dopamine agonists are Requip (ropinirole) and Mirapex (pramipexole).

In one case, the brain pathology was consistent with PSP-parkinsonism. (During life, that case was diagnosed clinically with PD.) In the two other cases, the brain pathology was consistent with Richardson’s syndrome. (These are the two most common types of PSP.) “All cases had some degree of vascular pathology, minimal Alzheimer-type pathology, and Lewy body pathology was absent.”

Quite a bit has been published about the ICBs that can occur in PD when dopamine agonists are used; these ICBs include “pathological gambling, hypersexuality, compulsive shopping, binge eating, punding and compulsive use of” dopamine replacement therapy. About 14% of those with PD who use dopamine agonists develop ICBs.

(“Punding” is the compulsive performance of a repetitive, purposeless activity. It could include collecting things and arranging them in a very precious manner. Or disassembling something and putting it together again and again.)

The authors conclude: “Our cases are notable for the relatively early development of ICBs on DA, whereas in the PD ICB literature, longer treatment duration are described. … Our cases add to the argument that DA themselves can be a major risk factor for the development of ICBs, irrespective of the underlying pathological reason for their use. .. Extra caution regarding ICBs is required amongst clinicians considering DA use in PSP.

I’ve copied the abstract below.

Robin

Movement Disorders. 2010 Mar 8. [Epub ahead of print]

Impulsive-compulsive spectrum behaviors in pathologically confirmed progressive supranuclear palsy.

O’Sullivan SS, Djamshidian A, Ahmed Z, Evans AH, Lawrence AD, Holton JL, Revesz T, Lees AJ.
Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, United Kingdom.

There is growing awareness of impulsive-compulsive spectrum behaviors (ICBs) in patients with Parkinson’s disease (PD) treated with dopamine replacement therapy (DRT). These include pathological gambling, hypersexuality, compulsive shopping, binge eating, punding and compulsive use of DRT, or dopamine dysregulation syndrome. In PD, difficulties exist in separating the effects of DRT from the underlying disease process and aberrant dopaminergic systems in determining the aetiology of ICBs. Recent reports of ICBs associated with dopamine agonist use for conditions other than PD may suggest a significant etiological role for these medications, but currently published cases thus far lack pathological confirmation of diagnoses. We present three cases of pathologically confirmed progressive supranuclear palsy who developed ICBs in association with dopamine agonist use. Pathological comparisons between these three cases and other case series of progressive supranuclear palsy are made.

PubMed ID#: 20213825 (see pubmed.gov for this abstract only)

Biomarkers summary article

An article summarizing the “investigations addressing the field of the early neurochemical differential diagnosis of Parkinson syndromes and the early diagnosis of Parkinson dementia” and providing an overview of the tested biomarkers was published over the summer 2090 by German researchers.

The authors conclude that “the specific biomarker for a certain neurological disease is yet to be identified—or better, several biomarkers. We think that a combination of multiple or at least two proteins will be necessary to differentiate [parkinsonian syndromes] as well as dementing syndromes from each other, as demonstrated for AD (tau/Aß) and CJD (tau, protein S-100B, and protein 14–3-3). Furthermore, we assume that the diagnostic question has to be very precise (e.g., PD or PDD, MSA versus PD).”

This full article is available online for free. See:
http://www.ncbi.nlm.nih.gov/pmc/article … ool=pubmed –> HTML version
http://www.ncbi.nlm.nih.gov/pmc/article … 5-0157.pdf –> PDF version

This table, in particular, lists all of the possible biomarkers for PD, PDD, DLB, PSP, and MSA:
http://www.ncbi.nlm.nih.gov/pmc/article … ble/tbl17/

For me, the most interesting section of the article was about metals and whether they increase the risk for these diseases. (See “Metals: Believed to Be (Co)Factors of Aggregation”) I understood very little of that section of the article but others of you will have a better chance.

Using transcranial sonography to differentiate PSP-P and RS

This recently-published German research is about transcranial sonographic findings when PSP patients are examined. The findings correspond to which type of PSP the patients have — Richardson’s Syndrome (RS) or PSP-Parkinsonism (PSP-P).

Reading between the lines, it seems that the findings for those with PSP-P are similar to the findings of those with Parkinson’s Disease (eg, a hyperechogenic substantia nigra). So, transcranial sonography may not be a good tool to differentiate between PSP and PD.

Robin

Movement Disorders. 2010 Mar 2. [Epub ahead of print]

Substantia nigra echogenicity in progressive supranuclear palsy.

Ebentheuer J, Canelo M, Trautmann E, Trenkwalder C.
Paracelsus-Elena-Klinik, Center of Parkinsonism and Movement Disorders, Kassel, Germany.

A normoechogenic substantia nigra (SN) is a typical finding in transcranial sonography in patients with progressive supranuclear palsy (PSP), whereas in patients with Parkinson’s disease a hyperechogenic SN is characteristic.

A recent classification scheme recommends the differentiation of PSP patients into those with Richardson’s syndrome (RS) and those with PSP-Parkinsonism (PSP-P).

We investigated 34 PSP patients (27 RS, 7 PSP-P) with ultrasound of the substantia nigra in search of differentiations in the two groups.

We found that most of the PSP-P patients, according to recently published criteria, had a hyperechogenic SN (6 of 7): right (cm(2)) median 0.22, 25% percentile 0.21 and 75% percentile 0.36 (cm(2)); left (cm(2)) median 0.21, 25% percentile 0.20 and 75% percentile 0.30 and a normal third ventricle (mean mm) +/-SD: 7.1 +/- 2.43).

In RS patients a normoechogenic SN (26 of 27) and an enlarged third ventricle (mean mm) +/-SD: 10.3 +/- 2.41) was found.

These differences may elucidate the pathological differences of RS and PSP-P.

PubMed ID#: 20198715 (see pubmed.gov for this abstract only)

Hyposmia (poor sense of smell) in PSP

One thing clear to me from reading research articles over the last few years on PSP is that even though the Queen Square Brain Bank doesn’t have the number of brains that Mayo Jax has, QSBB does loads more research and publishes more based on what they do have.

This (mostly) British research is about hyposmia (poor sense of smell) in PSP.

Researchers gave 36 patients with PSP who had scored more than 18 on the MMSE the University of Pennsylvania Smell Identification Test (UPSIT). 140 patients with PD and 126 controls were also tested.

PSPers had worse sense of smell than controls but better sense of smell than those with PD.

“For patients with PSP, UPSIT scores correlated with MMSE but not disease duration…”

Though people may have PSP pathology in regions of the brain responsible for smell, their sense of smell may not be affected. “The brains of six of the patients with PSP were examined postmortem and all revealed neurofibrillary tangles and tau accumulation in the rhinencephalon, although only three had hyposmia.”

“Further prospective studies including patients with early PSP and PSP-P with postmortem confirmation might help clarify if smell tests could be useful when the differential diagnosis lies between PD and PSP.”

Robin

Research Article
Hyposmia in progressive supranuclear palsy

Movement Disorders, Published Online: 5 Mar 2010

ABSTRACT
Previous studies suggested that olfaction is normal in progressive supranuclear palsy (PSP). We applied the University of Pennsylvania Smell Identification Test (UPSIT) to 36 patients with PSP who scored more than 18 on the Mini Mental State Examination (MMSE), 140 patients with nondemented Parkinson’s disease (PD) and 126 controls. Mean UPSIT scores in PSP were lower than in controls (P < 0.001) but higher than in PD (P < 0.001) after adjusting for age, gender, and smoking history. For patients with PSP, UPSIT scores correlated with MMSE (r = 0.44, P = 0.006) but not disease duration (P = 0.6), motor subscale of the Unified Parkinson’s Disease Rating Scale (P = 0.2), or Frontal Assessment Battery (P = 0.5). The brains of six of the patients with PSP were examined postmortem and all revealed neurofibrillary tangles and tau accumulation in the rhinencephalon, although only three had hyposmia. Further prospective studies including patients with early PSP and PSP-P with postmortem confirmation might help clarify if smell tests could be useful when the differential diagnosis lies between PD and PSP.

Authors:
Laura Silveira-Moriyama, MD 1, Graham Hughes, MD 2, Alistair Church, MD 3, Hilary Ayling, MSc 4, David R. Williams, MD, PhD 1 5, Aviva Petrie, MSc, CStat 6, Janice Holton, MD, PhD 1 4, Tamas Revesz, MD 4, Ann Kingsbury, PhD 1, Huw R. Morris, MD, PhD 7, David J. Burn, MD 2, Andrew J. Lees, MD 1 4 *
1Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, United Kingdom
2Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, United Kingdom
3Department of Neurology, Royal Gwent Hospital, Newport, Gwent, United Kingdom
4Queen Square Brain Bank, UCL Institute of Neurology, London, United Kingdom
5Department of Neurology, Faculty of Medicine (Neurosciences), Monash University (Alfred Hospital Campus), Melbourne, Australia
6Biostatistics Unit, UCL Eastman Dental Institute, London, United Kingdom
7Department of Neurology, Cardiff University School of Medicine, Cardiff University, Cardiff, United Kingdom

This abstract isn’t available yet on PubMed but is available on the publisher’s website.
http://www3.interscience.wiley.com/jour … 0/abstract