Dravet syndrome with parkinsonian symptoms and intact dopaminergic neurons: A case report

IntroductionDravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms.Case reportCase 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of ¹²³I–N–ω–fluoropropyl–2β–carbomethoxy–3β–(4–iodophenyl) nortropane (¹²³I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms.DiscussionThe normal DAT SPECT and ¹²³I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.     

Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism

Summary. We studied 8 large Polish families with parkinsonism, 6 of which were newly identified. Thirty-six family members had well-documented levodopa-responsive parkinsonism. The phenotype of affected individuals was indistinguishable from that of persons with idiopathic Parkinson disease (PD). The pattern of inheritance in 5 families was consistent with autosomal dominant transmission; in 3 families the mode of inheritance was uncertain. Single photon emission computed tomography (SPECT) studies with the dopamine transporter radioligand [¹²³I]FP-CIT were performed in 1 family. The SPECT study showed striatal presynaptic dopaminergic degeneration consistent with sporadic PD in 1 affected family member and no signs of nigrostriatal dopaminergic dysfunction in 5 at-risk individuals. Sequence analysis in all 8 families excluded known genes associated with familial parkinsonism. Genome-wide 2-point linkage studies in the largest 2 families did not identify significant linkage (z > 3.0), although positive scores were obtained for 5q23 (D5S1462 and D5S2501), a locus previously implicated in disease susceptibility.     

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease

Summary. We investigated the applicability [¹²³I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43–73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [¹²³I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [¹²³I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [¹²³I]FP-CIT binding ratios in whole striatum. Our findings indicate that [¹²³I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies. Received August 30, 2000; accepted February 19, 2001     

123I‐Ioflupane SPECT in the diagnosis of suspected psychogenic Parkinsonism

Psychogenic Parkinsonism (PsyP) can be clinically difficult to differentiate from Parkinson's disease (PD). Striatal dopamine transporter (DAT) imaging could be helpful in differentiating them. We performed ¹²³I‐Ioflupane single‐photon emission computed tomography (SPECT) in 9 patients with suspected PsyP. In 1 patient, ¹²³I‐Ioflupane SPECT disclosed bilateral decrease of striatal tracer uptake that indicated nigrostriatal degeneration. In this patient, a parkin gene mutation was detected. In the other 8 patients, ¹²³I‐Ioflupane SPECT was normal and supported the initial suspicion of PsyP. Normal DAT imaging supports the diagnosis of PsyP, whereas reduced striatal tracer uptake suggests an underlying neurodegenerative Parkinsonism and should encourage the search for additional causes for the syndrome. © 2006 Movement Disorder Society     

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease

Background

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [¹²³I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Objectives

To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

Methods

We assessed clinical features, the peripheral immune profile, and striatal [¹²³I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort).

Results

A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β = −0.01, p < 0.001; PPMI-cohort: β = −0.05, p = 0.05) and the putamen (primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = −0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β = +0.09, p < 0.05; PPMI-cohort: β = +0.11, p = 0.02) and the putamen (primary-cohort: β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = −0.04, p = 0.08; PPMI-cohort: β = −0.01, p = 0.73).

Conclusions

Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

[123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys

[¹²³I]FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by biodistribution studies in rats and by single photon emission computed tomography (SPECT) studies in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–lesioned monkeys. In rats, intravenous injection of [¹²³I]FP-CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high densities of serotonergic uptake sites. While striatal uptake of radioactivity after injection of [¹²³I]FP-CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain areas known to be rich of serotonin transporters. Monkeys which were unilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [¹²³I]FP-CIT uptake at the side of treatment. The results of this study indicate that [¹²³I]FP-CIT, although not being a selective radioligand, binds specifically to the striatal DA transporter in vivo and thus suggest that [¹²³I]FP-CIT promises to be a suitable radioligand for SPECT imaging of DA transporters in humans. Synapse 27:183–190, 1997. © 1997 Wiley-Liss, Inc.     

Dopamine transporter density measured by [123I]β-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia

The clinical distinction between dopa-responsive dystonia (DRD) and juvenile Parkinson's disease (JPD) can pose a diagnostic challenge. Both conditions are dopa responsive. However, long-term L-dopa benefit is very different between the two. The difference in the prognosis is due to presence or absence of nigral cell loss. In JPD, there is degenerative nigral cell loss, wherease there are enzymatic defects in dopamine synthesis without cell loss in DRD. Mutations have been found in the GTP cyclohydrolase I (GCH-I) and tyrosine hydroxylase genes in DRD. As the discovered mutations are multiple and more are expected to be found, it is difficult to confirm or exclude DRD by mutation studies. Measurement of cerebrospinal fluid (CSF) neopterin will detect DRD from mutations in the GCH-I gene but not from mutations in tyrosine hydroxylase. The dopamine transporter (DAT) is a protein in the dopaminergic nerve terminals. (1R)-2β-Carbomethoxy-3β-(4-[¹²³I]iodophenyl)tropane ([¹²³I]β-CIT) is a ligand for the DAT, and it was shown to be a useful nuclear imaging marker for neurons that degenerate in Parkinson's disease (PD). As DRD was shown to have a normal DAT without nigral cell loss in a postmortem study, we predicted that the DAT measured in vivo by nuclear imaging will be normal in DRD and will differentiate DRD from JPD. Therefore, we performed [¹²³I]β-CIT single-photon emission computed tomography ([¹²³I]β-CIT SPECT) in clinically diagnosed DRD, PD, and JPD, and examined whether DAT imaging can differentiate DRD from PD and JPD. We then examined whether DAT imaging can provide a screening tool for molecular genetic studies, by studying mutations in the candidate gene GCH-I and measuring CSF neopterin. Five females (4 from two families, and 1 sporadic) were diagnosed as DRD based on early-onset foot dystonia and progressive parkinsonism beginnig at ages 7 to 12. All patients were functioning normally on L-dopa 100 to 250 mg/day for up to 8 years. SPECT imaging was obtained after intravenous injection of [¹²³I]β-CIT; 15 healthy volunteers served as normal control, and 6 PD and 1 JPD as disease controls. [¹²³I]β-CIT striatal binding was normal in DRD, whereas it was markedly decreased in PD and JPD. Gene analysis showed a novel nonsense mutation in the GCH-I gene in one family. No mutation was found in the other family or in the sporadic case. CSF neopterin was markedly decreased in the 4 tested patients. [¹²³I]β-CIT SPECT is a sensitive method for probing the integrity of nitegrity of nigrostriatal dopaminergic nerve terminals. A normal striatal DAT in a parkinsonian patient is evidence for a nondegenerative cause of parkinsonism and differentiates DRD from JPD. Finding a new mutation in one family and failure to demonstrate mutations in the putative gene in other cases supports the usefulness of DAT imaging in diagnosing DRD.     

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinson's disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinson's disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinson's disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinson's disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinson's disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinson's disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinson's disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.     

Striatal FP-CIT uptake differs in the subtypes of early Parkinson’s disease

Summary. In idiopathic Parkinson’s disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I-123]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p<0.01). Contralateral putamen and caudate nucleus FP-CIT uptake correlated significantly with severity of rigidity (p<0.01) and hypokinesia (p<0.01) but not with severity of resting or postural tremor (p>0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor.     

The role of <Superscript>123</Superscript>I-FP-CIT-SPECT in the differential diagnosis of Parkinson and tremor syndromes: a critical assessment of 125 cases

¹²³I-FP-CIT-SPECT is useful in the differential diagnosis of Parkinson’s disease (PD) and tremor syndromes. Recently, there have been reports on normal nigrostriatal uptake of radio ligands in PD patients, referred to as scans without evidence of dopaminergic deficit (SWEDDs). Furthermore, a dopaminergic deficit has been described in some cases of different tremor types. We sought to clarify the occurrence of SWEDDs in PD and a possible association of various tremor types with PD. We performed a retrospective case analysis of 125 patients with diagnostically uncertain Parkinsonian or non-Parkinsonian tremor syndromes with clinical assessments and ¹²³I-FP-CIT-SPECT. A total of 36/40 (90%) patients with the predominant clinical feature of a postural and/or kinetic tremor showed normal DAT SPECT; 73/85 (86%) with predominant clinical symptoms of PD showed abnormal DAT SPECT with lower overall radio ligand uptake and a significant asymmetry contralateral to the clinically more affected side. In all, 4/40 (10%) of non-Parkinsonian tremor patients had abnormal DAT SPECT, but no corresponding asymmetry of radio ligand uptake. Probable essential tremor was considered clinically in follow-up assessments although final diagnosis of these four tremor cases remains inconclusive. A total of 12/85 (14%) clinically suspected PD patients had normal DAT SPECT (SWEDDs). Clinical reassessment identified two patients with dystonic tremor. Five patients with a positive response to levodopa remained unclear. In four cases of suspected PD with normal DAT SPECT, non-neurologic diseases were identified. One case showed a complete and spontaneous remission of symptoms. DAT SPECT offers an objective method to confirm or exclude a dopaminergic deficit in tremor predominant parkinsonism for clinically inconclusive cases. There was no evidence of a decrease in DAT binding in the majority of patients with postural and/or kinetic tremor. The striatal asymmetry index is a further helpful tool for differentiating PD from non-PD tremor syndromes.     

Dopamine transporter imaging in adult patients with attention-deficit/hyperactivity disorder

The aim of this study was to provide in vivo evidence for the hypothesis that dopaminergic neurotransmission is altered in adult patients with attention-deficit/hyperactivity disorder (ADHD). We used high-resolution brain-dedicated single-photon emission computed tomography and the dopamine transporter (DAT) marker [¹²³I]FP-CIT in 17 adult treatment-naïve ADHD patients and 14 age-matched controls. Magnetic resonance imaging-based region of interest analysis was performed to quantify the DAT availability (expressed as a ratio of specific to non-displaceable binding, V₃″) in the striatum. Additionally, the specific radiotracer binding was assessed in the thalamus and the midbrain/brainstem regions (reflecting also the availability of the serotonin transporter to which [¹²³I]FP-CIT binds with moderate affinity). In the striatal areas of the ADHD patients, a significantly reduced specific tracer binding was found (V₃″: 5.18 ± 0.98; controls 6.36 ± 1.34). In contrast, the specific [¹²³I]FP-CIT binding did not differ from controls in the thalamus and midbrain/brainstem areas. These data indicate a reduced dopaminergic but not serotonergic transmitter reuptake function in adult ADHD. Further studies will have to deal with the question of whether these findings have the potential to influence treatment decisions in this complex disorder.     

Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients.MethodsWe performed TCS in 30 subjects and SPECT with [^99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [^99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared.ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere.ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.     

Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT

Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied.Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included.Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication.     

Clinical and [<Superscript>123</Superscript>I]FP-CIT SPET imaging follow-up in patients with drug-induced parkinsonism

We recently found that patients with drug-induced parkinsonism (DIP) may have normal (group I) or abnormal (group II) putamen [¹²³I]FP-CIT DAT (dopamine transporter) binding. In this study we reassessed clinical features and DAT binding in 19 of the original 32 patients (10 of group I and 9 of group II) after a 19–39-month follow-up period and tested the effects of chronic levodopa treatment in both cohorts of patients. In group I patients, [¹²³I]FP-CIT SPET (single photon emission tomography) was still normal in all patients at follow-up; DAT binding and UPDRS (Unified Parkinson’s Disease Rating Scale) motor score values did not differ from baseline. In group II patients, [¹²³I]FP-CIT SPET was still abnormal at follow-up; putamen DAT binding was significantly reduced and UPDRS III score higher compared to baseline. Levodopa treatment improved motor symptoms in three out of ten patients of group I and in eight out of nine patients of group II. No adverse psychiatric effects were observed in any of the patients. This study shows that DAT binding imaging may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals in the context of a progressive degenerative parkinsonism. Patients with DIP may benefit from levodopa therapy, particularly when dopamine nerve terminal defects are present, and this should be considered in the therapeutic management of these patients.     

Effects of subthalamic nucleus stimulation on striatal dopaminergic transmission in patients with Parkinson’s disease within one-year follow-up

The mechanisms by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) leads to clinical benefit in Parkinson's disease (PD), especially with regard to dopaminergic transmission, remain unclear. Therefore, the objective of our study was to evaluate alterations of synaptic dopaminergic signaling following bilateral STN-DBS in advanced PD within a one-year follow-up. We used [(123)I]FP-CIT single-photon emission computed tomography (SPECT) to measure dopamine transporter (DAT) availability and [(123)I]IBZM SPECT to assess dopamine D(2) receptor (D2R) availability (stimulator ON condition).Patients (n=18) showed a tendency towards a better suppression of symptoms after STN-DBS (Unified Parkinson's Disease Rating Scale motor score with medication decreased from 24.1+/-16.1 to 15.4+/-7.45; p=0. 002) while medication was strongly reduced (61% reduction of levodopa equivalent units; p<0. 0001). No changes of striatal [(123)I]FP-CIT binding and an increase of [(123)I]IBZM binding up to 16% (p<0. 05) between pre-surgery and follow-up investigations were noticed. These data show that clinical improvement and reduction of dopaminergic drugs in patients with advanced PD undergoing bilateral STN-DBS are paralleled by stable DAT and recovery of striatal D2R availability 12 months after surgery.     

123I]FP-CIT striatal binding in early Parkinson's disease patients with tremor vs. akinetic-rigid onset

We performed [123I]FP-CIT/SPECT in 20 drug-naive Parkinson's disease (PD) patients, 10 with unilateral akinesia/rigidity at onset (arPD) and 10 with additional tremor-at-rest (tPD), to evaluate whether resting tremor at onset is associated with differences in striatal dopamine transporter binding. Patients of the two cohorts were matched for age, disease duration (<3 years) and severity of non-tremor motor symptoms; 31 healthy participants served as controls. Mean striatal dopamine transporter binding reduction in PD patients vs. controls was 42% for arPD and 50% for tPD; mean ipsilateral striatum and caudate nucleus uptake values were lower by 12 and 24%, respectively, in tPD than arPD. We conclude that widespread degeneration of the nigrostriatal dopaminergic pathway might be necessary for the development of parkinsonian tremor-at-rest.     

Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

Clinical features and nigrostriatal dysfunction in patients with combined postural and resting tremors

BackgroundThe characteristics of clinical features and nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors have been less clearly reported.MethodsThe present study examined 43 patients with a visible persistent bilateral postural tremor and a unilateral/bilateral resting tremor involving the hands and forearms. The patients had experienced tremors for more than 3 years, with no evidence of Parkinson's disease or other parkinsonian disorders. Visual and quantitative analyses of [¹⁸F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET in 36 patients were performed. Seventeen age-matched normal controls were also studied.ResultsOn visual analysis, 28 patients (78%) showed normal [¹⁸F] FP-CIT uptake and eight (22%) showed significantly reduced uptake, suggesting nigrostriatal dopaminergic neuronal degeneration. The reduced [¹⁸F] FP-CIT uptake was significantly associated with earlier age-at-onset of tremor and asymmetric presentation of resting tremor. On quantitative analysis, there were statistically significant differences in the [¹⁸F] FP-CIT uptake ratio in the posterior putamen between patients with reduced uptake (2.37 ± 1.83) and patients with normal uptake (6.39 ± 1.35) (P < 0.001). However, posterior putamen uptake levels in patients with normal [¹⁸F] FP-CIT uptake on visual analysis were similar to those in normal controls (7.22 ± 1.29) (P = 0.291).ConclusionThe nigrostriatal dopaminergic dysfunction in patients with combined postural and resting tremors may be associated with earlier age-at-onset of tremor and asymmetric pattern of resting tremor, which might help to correctly diagnose patients with mixed tremors.     

Evidence of delayed nigrostriatal dysfunction in corticobasal syndrome: A SPECT follow-up study

ObjectiveTo demonstrate that degeneration of substantia nigra neurons may occur at later stages of disease in some patients with corticobasal syndrome (CBS) who evidenced preserved nigrostriatal pathway at a baseline FP-CIT SPECT study.BackgroundCurrent pathological criteria for the definite diagnosis of corticobasal degeneration consider substantia nigra cell loss as a mandatory finding. However, dopamine transporter SPECT imaging performed in a large cohort of CBS patients showed about 10% of normal scans.MethodsWe describe 4 patients with clinical diagnosis of CBS and normal FP-CIT SPECT at baseline whose tracer uptake resulted pathological at 1-year follow-up scan. Clinical assessment has been performed at the time of SPECT scan. A semi-quantitative approach was performed for striatal FP-CIT binding values.ResultsBaseline SPECT scans have been performed after 2.3 ± 1.5 years from onset. All CBS patients presented asymmetric rigid-akinetic parkinsonism (mean Hoehn-Yahr stage 2.5; UPDRS motor score 18) with poor levodopa response and ideo-motor limb apraxia. At follow-up, neurological examination revealed some additional features, including limb dystonia, language impairment, postural instability, ocular gaze impairment, alien limb. All patients showed pathological FP-CIT uptake at the SPECT performed 10–15 months apart from the baseline scan.ConclusionsOur longitudinal FP-CIT SPECT findings support in vivo the hypothesis that substantia nigra neuronal loss may occur at later stages in some patients with CBS, despite early extrapyramidal symptoms.