The last line of this abstract caught my eye: “It is suggested that olfactory bulb biopsy be considered to confirm the diagnosis in PD subjects being assessed for surgical therapy.” In the article, the authors indicate that one of their concerns is that MSAers, misdiagnosed as having PD, will get deep brain stimulation and will be harmed by that. They say:
“It has been reported that patients with multiple system atrophy (MSA) misdiagnosed as PD have undergone placement of deep brain stimulators and have not had a lasting benefit. As the characteristic glial cytoplasmic synuclein-immunoreactive inclusions of MSA are also present and diagnostic in the olfactory bulb, as reported by Kovacs et al. (we have confirmed this finding in five MSA cases), olfactory bulb biopsy would differentiate between PD and MSA. Olfactory bulb biopsy might therefore be useful for the evaluation of candidates for surgical therapy of PD, where the risks of biopsy might be justified if it would spare non-PD subjects the greater risks associated with pallidotomy, thalamotomy, deep brain stimulation or neural transplantation.”
In one of the response letters, scientists asked specifically about PSP and MSA. The authors of the main article reply:
“The authors question whether olfactory bulb biopsy could distinguish PD from MSA or PSP, especially since Lewy bodies may be present in sparse numbers in both of the latter two conditions. We have utilized olfactory bulb alpha-synuclein stains in six MSA cases, and found all had numerous and characteristic flame-shaped glial cytoplasmic inclusions, unambiguously identifying these as MSA. It may be more difficult to distinguish PD from PSP. Our data show that 15 of 45 PSP cases had olfactory bulb Lewy bodies. Of these 15, the majority also had Lewy bodies in the brainstem and limbic region, suggesting that these subjects had both PD and PSP. Whether or not these subjects would differ in surgical outcome from those with pure PD or pure PSP is not known at this time. We are currently testing methods for detecting glial tauopathy to determine whether these might positively identify PSP subjects from olfactory bulb material.”
So an olfactory bulb biopsy — which is a relatively minor surgical procedure done while someone is alive — would differentiate PD from MSA but not PD from PSP. To increase the success rate of deep brain stimulation going forward, it sounds like researchers may require an olfactory bulb biopsy to weed out the MSAers.
And I thought the part about “testing methods for detecting glial tauopathy to determine whether these might positively identify PSP subjects from olfactory bulb material” was interesting too.
Probably not many of you will want to read the abstract (or the full paper). But if you do and you pick up a different facet, please share!
Robin
Acta Neuropatholpgica. 2009 Feb;117(2):169-74. Epub 2008 Nov 4.
Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.
Beach TG, White CL 3rd, Hladik CL, Sabbagh MN, Connor DJ, Shill HA, Sue LI, Sasse J, Bachalakuri J, Henry-Watson J, Akiyama H, Adler CH; Arizona Parkinson’s Disease Consortium.
Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ.
Involvement of the olfactory bulb by Lewy-type alpha-synucleinopathy (LTS) is known to occur at an early stage of Parkinson’s disease (PD) and Lewy body disorders and is therefore of potential usefulness diagnostically. An accurate estimate of the specificity and sensitivity of this change has not previously been available. We performed immunohistochemical alpha-synuclein staining of the olfactory bulb in 328 deceased individuals. All cases had received an initial neuropathological examination that included alpha-synuclein immunohistochemical staining on sections from brainstem, limbic and neocortical regions, but excluded olfactory bulb. These cases had been classified based on their clinical characteristics and brain regional distribution and density of LTS, as PD, dementia with Lewy bodies (DLB), Alzheimer’s disease with LTS (ADLS), Alzheimer’s disease without LTS (ADNLS), incidental Lewy body disease (ILBD) and elderly control subjects. The numbers of cases found to be positive and negative, respectively, for olfactory bulb LTS were: PD 55/3; DLB 34/1; ADLS 37/5; ADNLS 19/84; ILBD 14/7; elderly control subjects 5/64. The sensitivities and specificities were, respectively: 95 and 91% for PD versus elderly control; 97 and 91% for DLB versus elderly control; 88 and 91% for ADLS versus elderly control; 88 and 81% for ADLS versus ADNLS; 67 and 91% for ILBD versus elderly control. Olfactory bulb synucleinopathy density scores correlated significantly with synucleinopathy scores in all other brain regions (Spearman R values between 0.46 and 0.78) as well as with scores on the Mini-Mental State Examination and Part 3 of the Unified Parkinson’s Disease Rating Scale (Spearman R -0.27, 0.35, respectively). It is concluded that olfactory bulb LTS accurately predicts the presence of LTS in other brain regions. It is suggested that olfactory bulb biopsy be considered to confirm the diagnosis in PD subjects being assessed for surgical therapy.
PubMed ID#: 18982334
The comments are:
Acta Neuropathologica. 2009 Feb;117(2):213-4; author reply 217-8. Epub 2008 Nov 25.
Can olfactory bulb biopsy be justified for the diagnosis of Parkinson’s disease?
Parkkinen L, Silveira-Moriyama L, Holton JL, Lees AJ, Revesz T.
Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
PubMed ID#: 19031077
Acta Neuropathologica. 2009 Feb;117(2):215-6; author reply 217-8. Epub 2008 Nov 5.
Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.
Jellinger KA.
Institute of Clinical Neurobiology, Vienna, Austria.
PubMed ID#: 18985364