PSP: Subtypes, Clinicopathological correlation; Biomagnification on Guam

Subject: PSP: Subtypes, Clinicopathological correlation; Biomagnification on Guam

Date: 5/26/2005

1. Characteristics of two clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson’s syndrome and PSP-parkinsonism
DR Williams, R de Silva, DC Paviour, A Pittman, HC Watt, L Kilford, JL Holton, T Revesz, AJ Lees
Brain 2005;128:1247-1258

Most cases of PSP can be classified into one of two subtypes based on clinical features, which coincide with differences in tau isoform ratios, according to this study.

All available medical records from 103 consecutive cases of pathologically diagnosed PSP were reviewed for presence or absence of 19 disease aspects, including a variety of movement abnormalities, cognitive disturbance, a variety of visual signs and symptoms, autonomic dysfunction, and response to treatment with levodopa. Complete information in all 19 categories were available from the first 2 years after diagnosis for 29 cases. Principal components analysis was used to group the cases into two types; the remaining cases were then analyzed according to this scheme.

Based on this analysis, the authors propose that PSP cases fall into two predominant clinical phenotypes. “Richardson’s syndrome” (RS) cases are characterized by falls, cognitive dysfunction, supranuclear gaze palsy, abnormal saccadic/pursuit movements, and postural instability. “PSP-parkinsonism” (PSP-P) cases are characterized by asymmetric onset, tremor, bradykinesia, extra-axial dystonia, and response to levodopa. Of the 103 cases, 54% were classified as RS, 33% as PSP-P, and 14% as unclassifiable.

RS patients were more often male (64%), while sex distribution was equal in PSP-P. Age of onset was not different between the two groups, but RS patients had a shorter and more severe disease course (5.9 vs. 9.1 years until death). Mean 4-repeat:3-repeat tau ratio was 2.84 in RS and 1.63 in PSP-P (p<0.003). The H1, H1 genotype was significantly more common in RS patients than PSP-P patients. There were no significance differences in H2 alleles, ApoE alleles, or ApoE genotype.

“Prospective clinicopathological studies are now needed to confirm these proposed subgroups further and could potentially identify less common, but distinct clinical phenotypes,” the authors state.

In a Commentary accompanying the report, David Burn writes, “The low percentage of cases unclassified and the additional neurobiological plausibility reflected by the tau isoform differences between Richardson’s syndrome and PSP-P reinforce the notion that these two clinical groupings are likely to be real and not spurious.”

2. Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy
NJ Cordato, AJ Duggins, GM Halliday, JGL Morris, C Pantelis
Brain 2005;128:1259-1266

In patients with PSP, motor disability and frontal behavioral disturbance correlate with atrophy in functionally related brain regions, according to this study.

Twenty-one patients with PSP, 17 with PD, and 23 controls underwent MRI brain scans with voxel-based morphometry analysis. Mean disease duration was 48 months for PSP patients, and 94 months for PD patients, each chosen to approximate the midpoint of the disease process.

In PD patients, only the grey matter surrounding the left intraparietal sulcus showed significant tissue loss. In PSP patients, symmetrical tissue loss was seen in grey matter in both subcortical and cortical areas, principally the midbrain, caudate, thalamus, hypothalamus, and frontal cortex. White matter loss was greatest in the rostro-dorsal midbrain, mid-corpus callosum, and tissue surrounding the lateral ventricles. In PSP patients, but not in PD patients, motor disability correlated with caudate and motor cingulate cortex atrophy, while frontal behavioral disturbance correlated with grey matter loss in the midbrain and the orbitofrontal cortex surrounding the inferior frontal sulcus.

The authors conclude, “These data suggest that intrinsic neurodegeneration of specific subcortical nuclei and frontal cortical subregions together contribute to motor and behavioral disturbances in PSP and differentiate this disorder from Parkinson’s disease within 2-4 years of symptom onset.”

3. The Tangle: An ethnobotanist tries to solve the mystery of neurological disease on Guam
J Weiner
The New Yorker April 11, 2005, pp43-51

The New Yorker features an article about the controversy surrounding the biomagnification hypothesis and the cause of lytico-bodig, or ALS-parkinsonism dementia complex of Guam, first described by John Steele. An E-MOVE report on evidence for this hypothesis is archived at http://www.mdvu.org/emove/article.asp?ID=597

Excerpts from the article:

“Cox and his team believed they had now followed the BMAA from the cyanobacteria in the cycad roots, to the cycad seeds, to the bats, to the brains of Chamorros who ate the bats…on Guam, Cox argued, the bats seemed to have concentrated the cycads’ neurotoxins the way algae-eating fish concentrate PCBs…”

“Cox’s hypothesis cut across many fields, and in every one of them there were specialists who thought he had built a very big story out of very little evidence.”

4. FDA Approves Ropinirole for RLS

The United States Food and Drug Administration has approved the use of ropinirole to treat moderate-to-severe restless legs syndrome. Ropinirole becomes the first drug specifically approved for RLS. The FDA’s notice regarding this approval can be found at http://www.fda.gov/bbs/topics/ANSWERS/2005/ANS01356.html
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5. World Parkinson Congress: Call for Abstracts

The World Parkinson Congress seeks abstracts for its inaugural Congress, to be held in Washington, DC, February 22-26 2006. WE MOVE is an Organizational Partner for the Congress. The submission period is open from Monday, August 1, 2005 to Wednesday, September 21, 2005.

The World Parkinson Congress is looking for original abstracts for its inaugural Congress to be held in Washington, DC, USA, February 22-26, 2006. The submission period is open from Monday, August 1, 2005 to Wednesday, September 21, 2005 with submissions closing at 11:59pm (CST).

Abstract submission will be open to anyone doing research related to Parkinson's disease in the areas of basic and clinical science as well as quality-of-life and best-care practices. Abstracts are encouraged from people who are engaged in cutting-edge scientific research and/or who are researching ways to improve quality-of-life for people living with Parkinson's disease. Professionals working in the fields of physical and occupational therapy, speech pathology, nutrition and neuroscience nursing as well as social work and mental health to are also strongly encouraged to submit an abstract of their research.

All accepted abstracts will be printed in a supplement journal of the Movement Disorder Society to be disseminated during the Congress in February 2006.

To review the eligibility requirements and guidelines for submitting an abstract and to learn more about the World Parkinson Congress, please visit www.worldpdcongress.org .

About The World Parkinson Congress
The World Parkinson Congress, Inc. is a nonprofit organization dedicated to providing an international forum for the best scientific discoveries, medical practices and caregiver initiatives related to Parkinson's disease. By bringing physicians, scientists, allied health professionals, caregivers and people with Parkinson's disease together, they hope to create a worldwide dialogue that will help expedite the discovery of a cure and best treatment practices for this devastating disease.

Contact: Kerry Granwehr: (202) 367-2406, kgranwehr@worldpdcongress.org