Jim Patterson

Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake

The variability in clinical features and the masking effects of drug therapy in Parkinsons disease (PD) can affect clinical assessment of disease severity. The aim of this study was to assess the imaging of dopamine transporters using 123I‐FP‐CIT SPECT and its correlation with disease staging, severity, and duration. Differences between the clinical severity of the onset and non‐onset side and the corresponding striatal uptake ratios were also examined. Forty‐one patients with PD (nine unilateral, 32 bilateral clinical features) were studied. Clinical severity was determined by using the Unified Parkinsons Disease Rating Score (UPDRS). Unilateral UPDRS was calculated from unilateral arm and leg resting and action tremor, rigidity, finger taps, hand movements, alternating movements, and leg agility. 123I‐FP‐CIT striatal uptake was expressed as the ratio of specific:nonspecific (SP:NS) uptake for defined brain areas. Patients with PD who had unilateral symptoms showed a significant difference between the ipsilateral and contralateral SP:NS ratios in both the caudate and putamen, but there was a considerable overlap between between the two sides. This result was repeated in patients with bilateral symptoms and there was overlap of SP:NS ratios between the two groups. For the whole group of patients with PD, striatum, caudate, and putamen SP:NS ratios correlated with disease severity assessed by UPDRS and duration of disease. The SP:NS ratios correlated with the bradykinesia subscore but not with rigidity or tremor subscore. In conclusion, this study provides further evidence that the SP:NS ratio is a robust measure of disease severity correlating with duration of PD. However, variability in uptake values suggest that factors other than nigrostriatal degeneration may contribute to disease severity. Correlation with bradykinesia but not with tremor may indicate an origin for tremor outwith the dopamine transporter system. 123I‐FP‐CIT SPECT offers significant potential in defining the nigrostriatal changes in PD.

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT

Overdiagnosis of Parkinsons disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP‐CIT (DaTSCAN™, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video‐recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on‐site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP‐CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter‐reader agreement for rating scans as normal or abnormal was high (Cohens

Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

\hat{\kappa}

Measurements of regional cerebral blood flow and cognitive performance in Alzheimer's disease.

= 0.94–0.97).

Prospective study of presynaptic dopaminergic imaging in patients with mild parkinsonism and tremor disorders: Part 1. Baseline and 3-month observations

Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.

Image non-uniformity in magnetic resonance imaging: its magnitude and methods for its correction

Single photon emission computed tomography (SPECT) with 99mTc-HMPAO was used to image 26 patients with dementia of the Alzheimer type (DAT) and 10 healthy controls. Regional cerebral blood flow (rCBF) data indicated a relative sparing of the occipital regions in DAT. Normalisation to occipital flow illustrated highly significant CBF deficits in a number of cortical regions, particularly in the left and right posterior--temporal cortex in DAT compared to controls. The cognitive performance of DAT patients was measured using a clinical cognitive assessment procedure (CAMCOG) and numerous correlations between these scores and rCBF were obtained. The implications and value of this investigative technique are discussed.

Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging.

To record prospectively, from early presentation, the clinical features of parkinsonism and tremor disorders, in relation to evidence of dopaminergic deficit shown with [123I]‐FP‐CIT (DaTSCAN, Amersham Health) single photon emission computerised tomography (SPECT). Clinical signs were recorded in 62 patients, of whom 24 failed standard Parkinsons disease (PD) and essential tremor criteria, and 38 fulfilled UK Brain Bank step 1 PD criteria. Striatal radioligand uptake was graded visually as normal or abnormal, and specific:nonspecific ratios were calculated. Bradykinesia and rigidity showed significant overall association with abnormal scans (P ≤ 0.003), but rest tremor did not (P = NS). In the 24 patients not fulfilling specific criteria (mean age 63 [SD 9] years, disease duration 3 [SD 4] years), 10 (42%) had abnormal visual SPECT assessment and 14 (58%) had normal scans. Of 38 patients with early PD by clinical criteria (mean age 60 [SD 9] years, disease duration 3 [SD 1.7] years), 33 (87%) were visually abnormal. Baseline clinical diagnosis corresponded with SPECT imaging results in 51 of 62 cases (82%), which increased to 56 of 62 cases (90%) with amendment of seven clinical diagnoses at 3 months (blind to SPECT results). Akinetic–rigid cardinal diagnostic features of parkinsonism associate well with dopaminergic deficit in patients with early and mild clinical features. When these clinical features are uncertain, or the patient fails clinical diagnostic criteria, testing for dopaminergic deficit with [123I]‐FP‐CIT SPECT may assist the diagnostic process.

Associative encoding of pictures activates the medial temporal lobes

Image non-uniformity in magnetic resonance imaging (MRI) is a recognised problem when using surface coils but is rarely mentioned with respect to standard head coils, yet it can be a source of error in clinical interpretation of images. Figure 1 demonstrates the type of artefacts due to image non-uniformity for a large, homogeneous solution of water and copper sulphate. The image was acquired in the coronal section using a standard head coil, and vertical (i.e. read direction) and horizontal (i.e. phase encode direction) pixel intensity profiles through the centre of the image are illustrated. The standard deviation of pixel intensities, expressed as a percentage of the mean value, is greater than ±27% along the 23 cm length of this phantom. Figure 2 demonstrates how these image nonuniformities can affect the sagittal image of a normal volunteer. The display window width and level have been chosen to produce optimum visual contrast at the level of the cerebellum and brain stem but, as a result to image no...

Deficits in iodine-labelled 3-quinuclidinyl benzilate binding in relation to cerebral blood flow in patients with Alzheimer's disease.

Background and aims Functional pre-synaptic dopamine brain imaging is generally abnormal when parkinsonism is degenerative (such as in idiopathic Parkinsons disease) and normal in patients with non-degenerative movement disorder (such as essential tremor). However, some patients diagnosed as early Parkinsons disease have normal presynaptic dopamine imaging. Follow-up of patients with normal imaging should help determine whether such patients truly have degenerative parkinsonism (and therefore represent false negative imaging results), or emerge as cases of non-degenerative parkinsonism (and therefore represent initial clinical over-diagnosis of Parkinsons disease). Methods and results One hundred and fifty cases with normal 123I-FP-CIT SPECT undertaken during routine care over a 3-year period were reviewed 2.4 years (interquartile range, 2.2–3.1 years) after SPECT. Diagnosis after follow-up was non-degenerative parkinsonism or tremor in 146 (97%), who did not progress clinically, and degenerative parkinsonism in four (3%), in whom clinicial progression was noted. Anti-Parkinson therapy was used in 36, and withdrawn in 27 with no deterioration in 25. Patients strictly fulfilling Brain Bank criteria (part 1) were more likely to undergo a trial of anti-Parkinson therapy (P<0.05) but were no more likely to maintain or respond to anti-Parkinson therapy than those not fulfilling criteria. Conclusion The clinical profile and therapy response during follow-up of patients with normal presynaptic dopamine imaging supports the diagnosis of a non-degenerative movement disorder in nearly all cases.

CT, MR and SPECT imaging in temporal lobe epilepsy.

It remains unresolved whether the medial temporal lobe activations found in recent neuroimaging studies are mediated by novelty detection alone, by specific kinds of encoding or consolidation operations, or both. This study attempted to see whether associative encoding or consolidation is sufficient to cause such activation by matching for novelty across conditions. Using single‐photon emission computer tomography (SPECT) (with Tc99mHMPAO), we compared the activation patterns produced by the associative encoding and the perceptual matching of novel complex scenes in 10 normal subjects using both statistical parametric mapping (SPM) and a regions‐of‐interest (ROI) approach. During the encoding condition, significant activations were detected in the left hippocampal/parahippocampal region, the left cingulate cortex, and the right prefrontal cortex, using both statistical techniques. Additionally, activation was found in the right cingulate cortex, and a trend towards activation was found in the right hippocampal/parahippocampal region using the ROI approach. In contrast, no medial temporal activations were found during the matching condition, which produced bilateral occipito‐parietal and right posterior inferior parietal (supramarginal gyrus) activations. These results not only confirm that the associative encoding and/or consolidation of complex scenes is partially mediated by medial temporal lobe structures, but also demonstrate, for the first time, that associative encoding/consolidation is sufficient to produce such an activation. The implications of the high degree of consistency revealed by the results of the SPM and ROI comparison are discussed. Hum. Brain Mapping 6:85–104, 1998.