Functional correlates of vertical gaze palsy and other ocular motor deficits in PSP: an FDG-PET study.

OBJECTIVE: To determine the functional correlates of vertical gaze palsy and other ocular motor deficits in patients with progressive supranuclear palsy (PSP) using [(18)F]fluorodeoxyglucose (FDG-)PET. METHODS: Twenty-six patients with PSP underwent clinical examination of vertical gaze combined with FDG-PET scans to assess regional cerebral glucose metabolism as a marker of neuronal activity. Of these, eighteen PSP patients were also investigated by electrical nystagmography to determine horizontal ocular motor deficits. Statistical parametric mapping analyses were performed to correlate regional neuronal activity with ocular motor functions. RESULTS: In categorical comparisons, patients with downward gaze palsy showed a significantly reduced glucose metabolism in bilateral anterior cingulate gyrus and right lingual gyrus compared to those without downward gaze palsy. Maximum velocity of horizontal saccades was positively correlated with glucose metabolism of the rostral vermis and lingual gyrus; regional metabolism of oculomotor vermis was associated with peak velocity of the optokinetic reflex. Analysis of smooth pursuit eye movement amplitude and peak velocity of corrective saccades showed positive correlation with metabolism in bilateral inferior parietal lobe and inferior part of the frontal eye field. All paradigms of smooth pursuit showed positive association with glucose metabolism in V5. CONCLUSIONS: Ocular motor functions in PSP are correlated with neuronal activity in distinct anatomical regions. These include the anterior cingulate gyrus (downward gaze palsy), rostral cerebellum (saccades), oculomotor vermis (optokinetic reflex) and inferior parietal as well as temporal regions and frontal eye field (smooth pursuit). These findings provide a deeper insight into the pathophysiology of PSP-associated ocular motor abnormalities.

Neuronal correlates of clinical asymmetry in progressive supranuclear palsy.

PURPOSE: Progressive supranuclear palsy (PSP) is characterized by a symmetric hypokinetic syndrome with early falls and vertical supranuclear gaze palsy. However, clinically asymmetric manifestations occur, resembling idiopathic Parkinson disease or corticobasal degeneration. The aim of this study was to determine the neuronal correlates of patients suffering from PSP with a lateralized disease manifestation (hemi-PSP) in comparison to patients with symmetric clinical presentation (symPSP) and corticobasal degeneration. METHODS: Twenty-three patients with PSP and 8 patients with corticobasal degeneration according to standard diagnostic criteria underwent F-fluorodeoxyglucose (FDG) PET scans to assess disease-specific patterns of regional cerebral glucose metabolism reflecting neuronal activity. Group differences were analyzed by statistical parametric mapping and region-of-interest analyses. RESULTS: Clinically, 14 patients presented with symPSP while 9 patients were considered as hemi-PSP. Patients with symPSP or hemi-PSP showed similar bilateral medial frontal hypometabolism compared to corticobasal degeneration patients. In contrast, corticobasal degeneration patients exhibited a prominent parietal hypometabolism compared to both symPSP and hemi-PSP patients. SymPSP patients showed no significant hypometabolism compared to hemi-PSP, whereas hemi-PSP patients presented with significant hypometabolism of the motor thalamus, middle cingulate gyrus, and sensorimotor cortex contralateral to the most affected body side compared to symPSP patients. CONCLUSIONS: The present study demonstrates that a more pronounced and asymmetric involvement of cortical and subcortical motor areas is associated with a lateralized disease manifestation of PSP. Furthermore, these findings strongly suggest that FDG PET imaging may assist the challenging clinical differentiation between hemi-PSP and corticobasal degeneration by depicting disease-specific patterns of regional cerebral glucose metabolism.

Neural correlates of cognitive dysfunction in Lewy body diseases and tauopathies: combined assessment with FDG-PET and the CERAD test battery.

We investigated disease-specific cognitive profiles and their neural correlates in Lewy-body diseases (LBD) and tauopathies by CERAD assessment and FDG-PET. Analyses revealed a significant interaction between reduced semantic fluency in tauopathies and impaired verbal learning in LBD. Semantic fluency discriminated between groups with high accuracy (83%). Compared to LBD, tauopathy patients showed bilateral hypometabolism of midbrain, thalamus, middle cingulate gyrus and supplementary motor/premotor cortex. In the reverse contrast, LBD patients exhibited bilateral hypometabolism in posterior parietal cortex, precuneus and inferior temporal gyrus extending into occipital and frontal cortices. In diagnosis-independent voxel-based analyses, verbal learning/memory correlated with left temporal and right parietal metabolism, while fluency was coupled to bilateral striatal and frontal metabolism. Naming correlated with left frontal metabolism and drawing with metabolism in bilateral temporal and left frontal regions. In line with disease-specific patterns of regional glucose metabolism, tauopathies and LBD show distinct cognitive profiles, which may assist clinical differentiation.

123I-iodobenzamide SPECT is not an independent predictor of dopaminergic responsiveness in patients with suspected atypical parkinsonian syndromes.

UNLABELLED: The prediction of dopaminergic responsiveness in patients with parkinsonism is desirable for effective treatment strategies. We investigated whether striatal dopamine D2/D3 receptor (D2R) binding assessed by (123)I-iodobenzamide SPECT is an independent predictor of dopaminergic responsiveness in patients with parkinsonism. METHODS: Seventy-eight patients with clinically suspected atypical parkinsonian syndrome (APS) were prospectively recruited for imaging. To quantify striatal D2R binding, (123)I-iodobenzamide SPECT datasets were subjected to an observer-independent, regions-of-interest analysis. A final clinical diagnosis of Lewy-body disease (LBD) or APS was made after a mean follow-up of 12 mo. On the basis of follow-up data, dopaminergic responsiveness was classified as 0 (none), 1 (transient), 2 (sustained mild), or 3 (sustained strong). Uni- and multivariate analyses of the relationship between treatment response, D2R binding, and confounding variables were conducted. RESULTS: Sixty patients with clinically verified LBD (n = 28; 22/28 with Parkinson disease) or APS (n = 32), in whom dopaminergic responsiveness could be assessed (n = 19/13/15/13 in categories 0/1/2/3; 18 were excluded because of insufficient dosing), were included in the statistical analysis. Univariate analyses revealed that a sustained treatment response was significantly associated with higher D2R binding, clinical diagnosis of LBD, lower Hoehn and Yahr scores, and younger age. After multivariate correction of D2R binding for diagnosis, age, symptom duration, Hoehn and Yahr score, and dopaminergic pretreatment, no association was found between D2R binding and treatment response, either in the pooled group or in LBD or APS subgroups. CONCLUSION: Striatal D2R binding assessed by (123)I-iodobenzamide SPECT does not provide additional predictive information about treatment response beyond other clinical variables, most notably the clinical diagnosis.

[¹8F]FDG-PET is superior to [¹²³I]IBZM-SPECT for the differential diagnosis of parkinsonism.

OBJECTIVE: Imaging of regional cerebral glucose metabolism with PET and striatal dopamine D2/D3 receptors (D2R) with SPECT improves the differential diagnosis of parkinsonism. We prospectively investigated 1) the diagnostic merits of these approaches in differentiating between Lewy body diseases (LBD; majority Parkinson disease [PD]) and atypical parkinsonian syndromes (APS); 2) the diagnostic value of [¹8F]fluorodeoxyglucose (FDG)-PET to differentiate among APS subgroups. METHODS: Ninety-five of 107 consecutive patients with clinically suspected APS referred for imaging were recruited. [¹8F]FDG-PET scans were analyzed by visual assessment (including individual voxel-based statistical maps). Based on a priori defined disease-specific patterns, patients with putative APS were differentiated from LBD (first level) and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) (second level). [¹²³I] iodobenzamide (IBZM)-SPECT datasets were subjected to an observer-independent regions-of-interest analysis to assess striatal D2R availability. Movement disorder specialists made final clinical diagnoses after a median follow-up time of 12 months. RESULTS: Seventy-eight patients with clinically verified APS (n = 44) or LBD (n = 34) were included in the statistical analysis. The area under the receiver operating characteristic curve for discrimination between APS and LBD was significantly larger for [¹8F]FDG-PET (0.94) than for [¹²³I]IBZM-SPECT (0.74; p = 0.0006). Sensitivity/specificity of [¹8F]FDG-PET for diagnosing APS was 86%/91%, respectively. Sensitivity/specificity of [¹8F]FDG-PET in identifying APS subgroups was 77%/97% for MSA, 74%/95% for PSP, and 75%/92% for CBD. CONCLUSIONS: The diagnostic accuracy of [¹8F]FDG-PET for discriminating LBD from APS is considerably higher than for [¹²³I]IBZM-SPECT. [¹8F]FDG-PET reliably differentiates APS subgroups.