Correlations between dopamine transporter density measured by 123I-FP-CIT SPECT and regional gray matter volume in Parkinson's disease.

PURPOSE: Parkinson's disease (PD) is caused by a selective degeneration of dopamine neurons. The relationship between dopamine transporter (DAT) density and gray matter volume has been unclear. Here we investigated the voxelwise correlation between gray matter volume and DAT binding measured by 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography (SPECT; DaTscan™ imaging) in PD. MATERIALS AND METHODS: Thirty-one male patients with PD were examined with MRI and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships between the regional gray matter volume and the SBR in the striatum. RESULTS: There were significant positive correlations between the SBR and the gray matter volume in the right pulvinar and posterior middle temporal gyrus and a trend level in the left pulvinar, all of which are associated with the second visual pathway. CONCLUSION: The nigrostriatal dopaminergic degeneration might affect the secondary visual pathway, leading to visual dysfunctions in PD.

Computed-tomography-guided anatomic standardization for quantitative assessment of dopamine transporter SPECT.

PURPOSE: For the quantitative assessment of dopamine transporter (DAT) using [123I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson's disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization. METHODS: We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images. RESULTS: The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups. CONCLUSION: CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.

Mutations in GNAL: a novel cause of craniocervical dystonia.

IMPORTANCE: Mutations in the GNAL gene have recently been shown to cause primary torsion dystonia. The GNAL-encoded protein (Gαolf) is important for dopamine D1 receptor function and odorant signal transduction. We sequenced all 12 exons of GNAL in 461 patients from Germany, Serbia, and Japan, including 318 patients with dystonia (190 with cervical dystonia), 51 with hyposmia and Parkinson disease, and 92 with tardive dyskinesia or acute dystonic reactions. OBSERVATIONS: We identified the following two novel heterozygous putative mutations in GNAL: p.Gly213Ser in a German patient and p.Ala353Thr in a Japanese patient. These variants were predicted to be pathogenic in silico, were absent in ethnically matched control individuals, and impaired Gαolf coupling to D1 receptors in a bioluminescence energy transfer (BRET) assay. Two additional variants appeared to be benign because they behaved like wild-type samples in the BRET assay (p.Ala311Thr) or were detected in ethnically matched controls (p.Thr92Ala). Both patients with likely pathogenic mutations had craniocervical dystonia with onset in the fifth decade of life. No pathogenic mutations were detected in the patients with hyposmia and Parkinson disease, tardive dyskinesias, or acute dystonic reactions. CONCLUSIONS AND RELEVANCE: Mutations in GNAL can cause craniocervical dystonia in different ethnicities. The BRET assay may be a useful tool to support the pathogenicity of identified variants in the GNAL gene.

[Dystonia genes and elucidation of their roles in dystonia pathogenesis].

Identification of causative genes for hereditary dystonia and elucidation of their functions are crucial for better understanding of dystonia pathogenesis. As seen in other hereditary neurologic disorders, intra- and inter-familial clinical variations have been demonstrated in hereditary dystonia. Asymptomatic carriers can be found due to alterations in penetrance, generally reduced in succeeding generations. Current known dystonia genes include those related to dopamine metabolism, transcription factor, cytoskeleton, transport of glucose and sodium ion, etc. It has been reported that effects of deep brain stimulation can vary significantly depending on genotype. Accumulation of genotype-outcome correlations would contribute to treatment decisions for dystonia patients.

[Use of botulinum neurotoxin for spasticity].

Spasticity is characterized by increased muscle resistance. It is usually associated with muscle weakness or poor motor control. This condition not only reduces activities of daily living (ADLs), but also interferes personal hygiere and causes caregiuer's difficulty. The use of botulinum neurotoxin (BoNT) intramuscular injections is a simple and effective therapy for spasticity. The use of BoNT to treat adult patients with spasticity was first reported in 1989, since then, using the neurotoxin to treat spasticity became popular in some European countries. Now in Japan, BoNT can be used to treat only torticollis, blepharospasm and hemifacial spasm because of the legal limitation on its use. However, clinical research on the use of BoNT in spasticity caused by stroke is presently underway, and an adaptation of the toxin may be available in the near future. This article reviews the characteristics of BoNT and the techniques for injecting this neurotoxin.