Neurodegenerative Disease Parkinson’s Disease Figure 3: Olfactory Bulb Volumes in Parkinson’s Disease 75
in patients with psychotic depression treated with D2-blocking neuroleptic drugs.35
Here, the severity of motor symptoms was 50
positively correlated with the degree of olfactory dysfunction, which might indicate patients with a latent basal ganglia dysfunction. Similar to the results seen in drug-induced parkinsonism, data from a recent study reveal that Wilson’s disease patients with neurological symptoms show a significant olfactory dysfunction compared with hepatic-type patients.36
Individuals who are more severely 25 0 Controls Left OB PD Right OB
Olfactory bulb (OB) volumes (standard error of the mean) separately for the left (red) and right side (blue) in patients with Parkinson’s disease (PD) (n=11) and healthy controls (n=9).38
to be more likely for atypical parkinsonism such as multiple system atrophy (MSA; n=29), progressive supranuclear palsy (PSP; n=15) or corticobasal degeneration (CBD; n=7), whereas markedly pronounced olfactory loss appeared to suggest PD (n=118). Similar to the results of Wenning et al., in a study on 50 parkinsonian patients12,13
we also found
evidence for olfactory loss in MSA (n=8), but little or no olfactory loss in (the few investigated) patients with PSP (n=2) and CBD (n=1). Nineteen PD patients were found to suffer from anosmia and another 13 had severe hyposmia, while five showed moderate hyposmia. In terms of the differentiation between MSA and PD at a cut-off of a TDI score (combined results for odour thresholds, odour discrimination and odour identification; see also reference 26) of 19.5, psychophysical testing had a sensitivity of 78% and a specificity of 100%. When the cut-off TDI score was increased to 24.8, sensitivity in this sample was 100% while specificity fell to 63%. This moderate specificity seems to be the limiting parameter for diagnostic purposes. A recent American Academy of Neurology practice parameter on the diagnosis and prognosis of PD concluded that olfactory testing “should be considered” to differentiate PD from PSP and CBD but not from MSA.27
Furthermore, Liberini et al.28 reported a significant olfactory
describe even more marked olfactory impairment in patients with mild dementia with Lewy bodies than in those with mild Alzheimer’s disease. This lends significance to the role of Lewy body pathology in olfactory dysfunction30
that would be in line with the
observation that patients with non-degenerative causes of parkinsonism such as vascular parkinsonism31
present with preserved
suggested that PARK8 individuals present with impaired olfactory identification, while the small number of tested asymptomatic carriers showed normal olfactory performance.
1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced parkinsonism is generally thought not to affect olfaction.33 Miwa et al.34
However,
demonstrated that MPTP causes both PD-like symptoms and olfactory disturbance in animals. We found an association between medication-induced parkinsonism and olfactory dysfunction
smell function. There is also evidence for less olfactory disturbance in familial parkinsonism. In PARK2 the olfactory sense is relatively well preserved whereas PARK1 subjects are mildly hyposmic.31 data32
Recent
Heinz Reichmann is a Professor of Neurology, Chairman of the Department of Neurology and Dean of the Medical Faculty at the University of Dresden Medical School. In addition, he is President of the German Neurological Society and Vice President of the German Parkinson Society. His major research interests are energy metabolism, neuroprotection, premotor symptoms in Parkinson’s disease (PD), aetiopathogenesis and treatment in PD. Professor
Reichmann is a member of numerous scientific societies including the European Neurological Society (ENS), the American Academy of Neurology (AAN), the American Neurological Association (ANA), the Royal Society of Medicine and the Movement Disorder Society (MDS), and serves on the Editorial Boards of a number of prestigious neurology journals.
impairment in Lewy body disease (LBD), which does not allow differentiation from PD. In a sample of 116 patients with mild LBD, mild Alzheimer’s disease, mild cognitive impairment and controls, Williams et al.29
Structural and Functional Studies of the Olfactory System in Parkinson’s Disease It is still unclear which lesion causes olfactory loss in PD. There is little information on structural changes at the level of the olfactory epithelium. Recently, we compared bioptic material from PD patients with that from patients with olfactory dysfunction due to other reasons, e.g. congenital anosmia or post-infectious olfactory loss.37 However, the results of the study did not reveal specific histological or histochemical changes in the nasal mucosa of PD patients. Therefore, PD-related olfactory impairment seems not to be directly associated with specific changes in the olfactory epithelium. In terms of volumetrics of the olfactory bulb (OB), results indicated that there is little or no difference between PD patients and healthy controls in terms of OB volume (see Figure 3).38 et al.,39
However, in a study by Scherfler
voxel-wise analysis of diffusion-weighted imaging revealed disruption of the olfactory tract in PD compared with age-matched healthy controls. Finally, studies based on functional magnetic resonance imaging (MRI) suggested that neuronal activity in the amygdala and hippocampus is reduced in PD patients compared with controls, which may specifically affect olfactory function.40
In
addition, neuronal activity in components of cortico-striatal loops appears to be upregulated, indicating compensatory processes involving the dopaminergic system. Results from Wattendorf et al.41 indicated that cortical atrophy in olfactory regions correlate with olfactory dysfunction. Thus, it seems that cerebral changes are the basis of the olfactory loss observed in PD patients.
Currently, none of the structural measurements of the olfactory system mentioned above is routinely used. Consequently, validated psychophysical tests of olfactory function should be a mandatory part of the early and differential diagnosis of PD. n
neurologically affected also present with more pronounced olfactory deficits. Based on these observations, olfactory testing should not be considered to differentiate PD from these specific conditions. However, olfactory testing has been shown to be important in cases where patients present with parkinsonian features but preserved olfaction; here the diagnosis of PD should be re-considered.
28
EUROPEAN NEUROLOGICAL REVIEW
Olfactory bulb volume (ccm)
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