Cardiac sympathetic innervation in Parkinson's disease versus multiple system atrophy.

PURPOSE: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy. METHODS: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests. RESULTS: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001). CONCLUSIONS: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients.

Topography of Dopamine Transporter Availability in the Cerebellar Variant of Multiple System Atrophy.

BACKGROUND: Voxel-wise comparison of [123I]-2ß-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]ß-CIT) radioligand distribution measured by single-photon emission computed tomography (SPECT) revealed distinct patterns of reduced dopamine transporter (DAT) availability in the Parkinson's variant of MSA (MSA-P). The aim of this study was to identify the monoamine transporter distribution pattern in patients with the cerebellar variant of MSA (MSA-C). Additionally, monoamine transporter availability was investigated in a small cohort of patients with sporadic adult-onset ataxia (SAOA). METHODS: [123I]ß-CIT SPECT was performed in patients with MSA-C (n = 12), MSA-P (n = 14), SAOA (n = 5), and controls (n = 15) matched for age. Parametric images of [123I]ß-CIT binding potential (BPND) were generated and analyzed by statistical parametric mapping (SPM) and region of interest (ROI) analysis. RESULTS: SPM localized significant reductions of [123I]ß-CIT BPND in the striatum, midbrain, and pons in MSA-C compared to controls. When compared with MSA-P, the striatal DAT decline was significantly less affected in MSA-C. ROI analysis revealed reductions of striatal and midbrain [123I]ß-CIT binding in MSA-C compared to SAOA, whereas no significant difference was apparent between the SAOA and control groups. CONCLUSIONS: Midbrain and pontine monoaminergic transporter binding was severely impaired in MSA-C, matching the underlying pathological features. Striatal DAT availability was relatively less affected in MSA-C compared to MSA-P, reflecting measureable, but less-profound, degeneration of the nigrostriatal dopaminergic projections. Preliminary results of reduced striatal and midbrain [123I]ß-CIT binding in MSA-C, compared to SAOA, suggest that the potential of DAT-SPECT as a surrogate marker in the diagnostic workup of patients with adult-onset cerebellar ataxia should be further investigated.

Low bone mineral density in Friedreich ataxia.

Friedreich ataxia (FRDA) is the most common inherited neurodegenerative ataxia. Apart from predominant neurological features an involvement of the skeletal system in terms of scoliosis and foot deformities is frequent. Disease-related falls, mobility restrictions, and wheelchair-dependency in later disease stages might additionally compromise bone structure in FRDA. The aim of this pilot study was to systematically evaluate the bone status in a representative FRDA cohort. Twenty-eight FRDA patients became enrolled in this cross-sectional study. Neurological assessment, a questionnaire comprising the history of fractures and osteoporosis as well as osteodensitometric measurements complemented with general and bone-specific laboratory parameters were performed. The WHO Fracture Risk Assessment tool (FRAX®) was applied, calculating the 10-year risk of suffering an osteoporotic fracture. Six patients (21.4 %) presented with a bone mineral density below the expected range for age in at least one of the examined sites (femoral neck, lumbar spine, and forearm) irrespective of their gender. Corresponding Z scores were significantly lower compared to normative values for the femoral neck and lumbar spine. Vitamin D status was insufficient in 11 and deficient in 8 FRDA patients. There was a strong negative correlation between ataxia severity, GAA repeat expansion and bone density in the femoral neck of FRDA patients. This is the first report of an increased rate of low bone mineral density in FRDA. Given the increased risk of falls, this data rectifies routine bone mineral density measurements in FRDA which may help to initiate therapeutic interventions to prevent this condition.

Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease.

Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor score (r = -0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson's disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies.

Left hemispheric predominance of nigrostriatal dysfunction in Parkinson's disease.

The aim of this study was to investigate the distribution and the degree of asymmetric putaminal dopamine transporter availability in right-handed patients with Parkinson's disease and its association with the severity of lateralized motor signs. Asymmetry of motor symptoms was defined by the difference between right- and left-sided scores for lateralized items assessed by the Unified Parkinson's Disease Rating Scale Motor Score in a series of 68 patients with Parkinson's disease (disease duration 2.1 ± 1.5 years; Unified Parkinson's Disease Rating Scale Motor Score 22.7 ± 9). Putaminal dopamine transporter availability was measured with the radioligand [(123)I]ß-carboxymethyoxy-3 -ß-(4-iodophenyl) tropane ([(123)I]ß-CIT) and single photon emission computed tomography. We found that in the right-handed Parkinson's disease cohort, the number of patients who had lower dopamine transporter uptake in the left posterior putamen was significantly greater compared with those with lower uptake in the right posterior putamen (Parkinson's disease-left group, n = 49; Parkinson's disease-right group, n = 19; P < 0.001). In addition, one-way analysis of variance revealed significant reductions of mean total putaminal [(123)I]ß-CIT binding of the Parkinson's disease-right patients compared with Parkinson's disease-left patients (P < 0.05).The preponderance of reduced left putaminal dopamine transporter availability strengthens clinical observations of a greater proportion of right-handed patients with Parkinson's disease with predominantly right-sided motor signs and argues against a randomly distributed asymmetric vulnerability of substantia nigra dopaminergic neurons. The coexistence of a subgroup of right-handed patients with Parkinson's disease with more severe and predominant ipsilateral putaminal dopamine transporter decline suggests that asymmetry of dopaminergic denervation and motor dysfunction in Parkinson's disease cannot be fully explained by hemispheric dominance alone, but that other factors must be involved.

Progression of dopamine transporter decline in patients with the Parkinson variant of multiple system atrophy: a voxel-based analysis of [123I]ß-CIT SPECT.

PURPOSE: We characterized the progression of dopamine transporter (DAT) decline in the striatum and extrastriatal regions including the midbrain and pons of patients with the Parkinson variant of multiple system atrophy (MSA-P) and compared longitudinally collected SPECT results with those in a cohort of patients with Parkinson's disease (PD). METHODS: Eight patients with MSA-P (age 60.4 ± 7.7 years, disease duration 2.4 ± 1 years, UPDRS-III motor score 39.7 ± 4.7), and 11 patients with PD (age 61.2 ± 6.4 years, disease duration 2.4 ± 1.1 years, UPDRS-III motor score 18.9 ± 7.6) underwent a baseline and follow-up [(123)I]ß-CIT SPECT investigation within a time period of 1.3 years. Statistical parametric mapping (SPM) and a repetitive ANOVA design were used to objectively localize the decline in DAT availability without having to make an a priori hypothesis as to its location. RESULTS: SPM localized significant reductions in [(123)I]ß-CIT uptake in the dorsal brainstem of MSA-P patients compared to PD patients (p < 0.001) at baseline. Additional reductions in the DAT signal were localized in the caudate and anterior putamen of patients with MSA-P patients compared to PD patients at the follow-up examination (p < 0.001). Relative decline in tracer binding was evident in the caudate and anterior putamen of MSA-P patients compared to PD patients in the longitudinal analysis (p < 0.05), whereas no significant relative signal alteration was observed in the brainstem. CONCLUSION: In contrast to PD, the relatively higher rate of signal reduction in the caudate and anterior putamen is consistent with the faster disease progression reported in MSA-P. At baseline, the tracer uptake in the brainstem was already at very low levels in the MSA-P patients compared to that in healthy control subjects and did not progress any further, suggesting that the degeneration of monoaminergic neurons is almost complete early in the disease course.

Supernumerary phantom limb as a rare symptom of epileptic seizures--case report and literature review.

Supernumerary phantom limbs, that is, the awareness of an illusory extra limb is a fascinating neurologic symptom that has been described in a number of neurologic diseases including stroke, spinal injury, and epilepsy. Herein we report a case of a 70-year-old male patient with new-onset focal seizures with left-sided supernumerary phantom arm and leg as the only seizure manifestation. Ictal single-photon emission computed tomography (SPECT) revealed a hyperperfusion in the right temporoparietal junction and allowed localization of the seizure-onset zone. This report is accompanied by a discussion of phenomenology and terminology in the context of existing literature.

A novel computer-assisted image analysis of [123I]ß-CIT SPECT images improves the diagnostic accuracy of parkinsonian disorders.

PURPOSE: The purpose of this study was to develop an observer-independent algorithm for the correct classification of dopamine transporter SPECT images as Parkinson's disease (PD), multiple system atrophy parkinson variant (MSA-P), progressive supranuclear palsy (PSP) or normal. METHODS: A total of 60 subjects with clinically probable PD (n = 15), MSA-P (n = 15) and PSP (n = 15), and 15 age-matched healthy volunteers, were studied with the dopamine transporter ligand [(123)I]ß-CIT. Parametric images of the specific-to-nondisplaceable equilibrium partition coefficient (BP(ND)) were generated. Following a voxel-wise ANOVA, cut-off values were calculated from the voxel values of the resulting six post-hoc t-test maps. The percentages of the volume of an individual BP(ND) image remaining below and above the cut-off values were determined. The higher percentage of image volume from all six cut-off matrices was used to classify an individual's image. For validation, the algorithm was compared to a conventional region of interest analysis. RESULTS: The predictive diagnostic accuracy of the algorithm in the correct assignment of a [(123)I]ß-CIT SPECT image was 83.3% and increased to 93.3% on merging the MSA-P and PSP groups. In contrast the multinomial logistic regression of mean region of interest values of the caudate, putamen and midbrain revealed a diagnostic accuracy of 71.7%. CONCLUSION: In contrast to a rater-driven approach, this novel method was superior in classifying [(123)I]ß-CIT-SPECT images as one of four diagnostic entities. In combination with the investigator-driven visual assessment of SPECT images, this clinical decision support tool would help to improve the diagnostic yield of [(123)I]ß-CIT SPECT in patients presenting with parkinsonism at their initial visit.

Successful surgical treatment of insular epilepsy with nocturnal hypermotor seizures.

Nocturnal hypermotor seizures (NHSs) suggest seizure onset in the frontal lobe. We present a patient with NHSs and insular seizure onset who underwent successful surgical treatment. A 29-year-old right-handed man suffered from intractable NHSs since the age of 12 years. High-resolution MRI, [(18)F]FDG-PET, and neuropsychological examination gave normal results, ictal EEG was obscured by artifacts. Ictal [(99m)Tc]HMPAO-SPECT revealed hyperperfusion in the right anterior part of the insula and right frontal operculum. The seizure onset zone was localized in the right anterior insula based on invasive recordings. Electrical stimulation in that area elicited habitual seizures. A limited resection of the anterior part of the right insula and the right frontal operculum was performed rendering the patient seizure-free (follow-up 1 year). To our knowledge, this is the first reported nonlesional patient with an insular seizure onset and NHSs who underwent successful epilepsy surgery.

Topography of dopamine transporter availability in progressive supranuclear palsy: a voxelwise [123I]beta-CIT SPECT analysis.

BACKGROUND: Dopaminergic loss can be visualized by means of iodine I 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) single-photon emission computed tomography (SPECT) in several neurodegenerative parkinsonian disorders. Most previous SPECT studies have adopted region-of-interest methods for analysis, which are subjective and operator dependent. OBJECTIVE: To objectively localize the cerebral dopamine transporter status in the early stages of progressive supranuclear palsy (PSP). DESIGN: Prospective study. SETTING: Parkinson disease outpatient clinic. PATIENTS: Fourteen patients with PSP, 17 with Parkinson disease (PD), 15 with Parkinson-variant multiple-system atrophy (MSA-P), and 13 healthy control subjects, matched for age and disease duration. INTERVENTIONS: Statistical parametric mapping applied to [(123)I]beta-CIT SPECT. MAIN OUTCOME MEASURES: Differences in [(123)I]beta-CIT uptake. RESULTS: All patients with the different parkinsonian disorders showed a significant decrease in striatal [(123)I]beta-CIT uptake without any overlap with the control group. In patients with MSA-P and PSP, an additional reduction in brainstem [(123)I]beta-CIT signal compared with controls and patients with PD was identified with statistical parametric mapping. Midbrain [(123)I]beta-CIT uptake discriminated atypical parkinsonian disorders from PD with an overall correct classification of 91.3%. On the other hand, [(123)I]beta-CIT SPECT failed to discriminate PSP and MSA-P. CONCLUSION: By applying statistical parametric mapping to [(123)I]beta-CIT SPECT images of patients with PSP, a widespread decline of monoaminergic transporter availability including the striatum and brainstem was localized in PSP, discriminating patients with PSP from patients with PD, but not from those with MSA-P. Quantification of midbrain dopamine transporter signal may therefore enhance the utility of SPECT imaging in the differential diagnosis of patients with parkinsonism.

Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.

PURPOSE: The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [(123)I]beta-CIT SPECT. METHODS: Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson's disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V (3)''), which is proportional to the receptor density (B (max)), were generated. In order to objectively localise focal changes in beta-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V (3)'' values between groups, were transformed onto the individual V (3)'' image to obtain mean regional uptake values. RESULTS: Both SCA2 and YOPD patients showed significant decreases in striatal [(123)I]beta-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [(123)I]beta-CIT uptake were localised with SPM. CONCLUSION: Voxel-wise analysis of [(123)I]beta-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [(123)I]beta-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation.

Voxel-wise analysis of [123I]beta-CIT SPECT differentiates the Parkinson variant of multiple system atrophy from idiopathic Parkinson's disease.

To investigate the cerebral dopamine transporter status in the early stages of the parkinson-variant of multiple system atrophy (MSA-P), 15 patients with MSA-P and a disease duration up to 3 years were studied with [123I]beta-CIT single photon emission computed tomography (SPECT). Data were compared with 13 age-matched healthy control subjects and 15 patients with idiopathic Parkinson's disease (IPD), matched for age and disease duration. Parametric SPECT images of the specific-to-nondisplaceable equilibrium partition coefficient (V3''), which is proportional to the receptor density (Bmax) have been generated. To objectively localize focal changes in dopaminergic function throughout the entire brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to our [123I]beta-CIT SPECT study. Both MSA-P and IPD patients showed significant decreases in striatal [123I]beta-CIT SPECT uptake. However, in MSA-P patients an additional reduction in midbrain [123I]beta-CIT signal was localized with SPM compared with control subjects (MSA-P, V3'': 0.89 +/- 0.37 versus controls V3'': 1.81 +/- 0.38; P < 0.001) and patients with IPD (V3'': 1.84 +/- 0.26; P < 0.001). Stepwise linear discriminant analysis of mean [123I]beta-CIT uptake in the putamen, caudate and midbrain identified the caudate and midbrain as indices to classify correctly 95.2% of subjects as either normal, patients with MSA-P or IPD. Voxel-wise analysis of [123I]beta-CIT SPECT revealed more widespread decline of monoaminergic transporter availability in MSA-P compared with IPD, matching the underlying pathological features. We suggest that the quantification of midbrain DAT signal should be included in the routine clinical analysis of [123I]beta-CIT SPECT in patients with uncertain parkinsonism.

Evaluation of [123I]IBZM pinhole SPECT for the detection of striatal dopamine D2 receptor availability in rats.

Single photon emission computed tomography (SPECT) and MRI coregistration have been assessed to characterize striatal dopamine D2/D3 receptor (D2/D3R) availability in rats following injection of the D2 and D3R radioligand [123I] iodobenzamide ([123I]IBZM). High-resolution SPECT data were obtained with a pinhole collimator. In order to precisely estimate brain regions of low radioligand uptake, SPECT images were coregistered onto a MRI template with high accuracy (maximum mismatch 1.1 mm). To evaluate an adequate dose of radioligand to be administered without exceeding the radioligand-to-receptor occupancy >5% and to define an appropriate time period for image acquisition, three untreated groups of animals received 29.6, 37, and 44.4 MBq of [123I]IBZM and underwent five consecutive SPECT acquisitions lasting 64 min each. Ratio calculations between specific striatal radioligand uptake and nondisplaceable cerebellar uptake revealed a secular equilibrium between 75 and 355 min post-tracer application in all three animal groups. Consequently, since the highest regional uptake values were obtained in the animal group receiving 44.4 MBq [123I]IBZM, this injection dose was considered to be appropriate. Finally, the capacity of the imaging method to detect distinct severity levels of striatal dopamine D2/D3 receptor loss was tested in a low, medium, and high dose quinolinic acid (QA) animal model of Huntington's disease. Motor impairment indicative of striatal dysfunction was monitored using amphetamine-induced rotational behavior and locomotor activity. Loss of striatal D2/D3R bearing medium-sized spiny neurons was assessed by DARPP-32 immunohistochemistry and compared to [123I]IBZM binding. Optical density measures of DARPP-32 immunohistochemistry demonstrated QA dose-dependent mild to subtotal unilateral striatal lesions ranging from 29.4% to 96.9% when compared to the nonlesioned side. Linear regression analysis showed that measurements of striatal DARPP-32 optical density and striatal [123I]IBZM uptake of the lesioned side were highly correlated (r2=0.83; P<0.001) whereas correlation with locomotor activity was less tight (r2=0.23; P<0.05; amphetamine-induced rotational behavior was not significantly correlated). This is the first study to demonstrate that in vivo [123I]IBZM SPECT and MRI coregistration are highly sensitive and, in contrast to behavioral measures, accurately detect mild to subtotal striatal lesions by measuring loss of D2/D3R availability. SPECT-MRI-based estimation of regional [123I]IBZM uptake provides a cost effective and widely available in vivo imaging technique for assessing striatal integrity in animal studies.

Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease.

Both dopamine D2 receptor (D2R) binding single-photon emission computed tomography (SPECT) with [123I]iodobenzamide (IBZM) and diffusion-weighted imaging (DWI) have been shown to contribute to the differential diagnosis of patients with the Parkinson variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD). We aimed to compare these two routinely available functional imaging modalities in differentiating patients with MSA-P from PD. For this purpose, results obtained by DWI and IBZM-SPECT were intraindividually compared in a cross-sectional study of 15 MSA-P and 17 PD patients matched for age and disease duration. The activity ratios of striatal to frontal cortex uptake (S/FC ratio) were used as a semiquantitative measure of the relative density of basal ganglia dopamine receptors labeled by IBZM. Regional apparent diffusion coefficients (rADC) were determined in the striatum. MSA-P patients had significantly lower S/FC ratios and significantly higher striatal rADCs than both PD patients and healthy volunteers. There were no significant differences in S/FC ratios and striatal rADC between PD patients and healthy volunteers. Sensitivity of IBZM-SPECT versus DWI for the differentiation of MSA-P from PD was 80% versus 93%, specificity 71% versus 100%, the predictive accuracy 75% versus 97%, the positive predictive value 71% versus 100%, and the negative predictive value 80% versus 94%. Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM-SPECT in the differential diagnosis of MSA-P versus PD.

Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study.

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and beta-CIT as well as IBZM. Age-matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of beta-CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.

Linguistic deficits following left selective amygdalohippocampectomy: a prospective study.

Language deficits in 10 patients with medically intractable left-sided temporal lobe epilepsy prior to and following selective amygdalohippocampectomy are described. Preoperatively, a pattern of minor linguistic deficits was observed in three patients; isolated minor naming deficits were detectable in one additional patient. Three months after surgery, six patients' linguistic functions were unchanged, whereas in four patients, a significant decline in linguistic functions could be observed. All four patients revealed a very similar language syndrome characterized by reduced language comprehension and fluency, well-articulated speech, frequent word-finding difficulties, circumlocutions, and semantic paraphasias in the absence of any phonological disorder. These deficits remained stable during the 12-month follow-up period. However, magnetic resonance imaging did not show any neocortical lesions outside the resection area. Possible explanations for these findings include neuronal cell loss and deafferentiation in cortical areas, disruption of the basal temporal language area pathways, reorganization of the language network in chronic temporal lobe epilepsy, and neocortical lesions due to the surgical intervention. Furthermore, correlations between linguistic and demographic data for our patients suggest that patients older at epilepsy onset are at greater risk for developing postoperative language deficits.

An individual dosimetric approach to 153Sm-EDTMP therapy for pain palliation in bone metastases in correlation with clinical results.

BACKGROUND: The clinical results of therapy using 153Sm ethylenediamine-N,N,N'N'-tetrakis(methylene phosphonic acid) (153Sm-EDTMP) were correlated with radiation dose indices in metastases, with the intention of improving the therapeutic efficacy. METHODS: Fifty-six patients with disseminated bone metastases were treated. Prior to therapy, whole-body scans and single photon emission computed tomography (SPECT) of the trunk were performed. Whole-body retention of 99mTc labelled phosphonates was compared with 153Sm-EDTMP retention after therapy. Estimations of the volumes of bone lesions were done by SPECT. Assuming a solid tumour but a thin metabolically active boundary zone between tumour and healthy bone that absorbed the beta radiation, we estimated an 'irradiated volume' by using a spherical shell model of 6 mm thickness. Local tracer uptake in lesions was assessed by regions of interest techniques on conjugated views of whole-body scans with homogeneous attenuation correction. Calculation of the dose index by applying the Medical Internal Radiation Dosimetry (MIRD) scheme was done retrospectively in 10 patients and prospectively in 22 cases. Depending on changes in pain/mobility scores, results were classified as 'very good', 'good' and 'no response'. RESULTS: A mean dose index > or =10 per lesion was estimated under the condition of a homogeneous uptake within the idealized, spherical, tumour volume. Assuming that the uptake of the radiopharmaceutical occurs mostly within an outer shell of the tumour, dose indices to this 'irradiated volume' can increase to more than twice that value. CONCLUSION: Very good clinical results for bone pain palliation by using 153Sm-EDTMP therapy could be found in patients receiving a dose index >15 per lesion. Even this approximate dosimetric approach, considering the individual differences in tumour spread and the varying intensity of 153Sm uptake, could improve the impact of 153Sm-EDTMP for pain control in cancer patients.

99mTc-EDDA/HYNIC-TOC and (18)F-FDG in thyroid cancer patients with negative (131)I whole-body scans.

Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, (99m)Tc-EDDA/HYNIC-TOC ((99m)Tc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22-90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A ( n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B ( n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive (99m)Tc-TOC findings was positively correlated ( P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with (18)F-FDG PET ( P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohen's kappa of 0.62 (0.47-0.78)]. In conclusion, scintigraphy with (99m)Tc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.