Metaiodobenzylguanidine Myocardial Scintigraphy Research Articles

Long-standing preservation of levodopa response in progressive supranuclear palsy

The clinical and neuropathological characteristics of progressive supranuclear palsy (PSP) with preservation of levodopa (L-dopa) response are described in this report. We present the case of a 73-year-old Japanese man with a 13-year history of dopa-responsive Parkinsonism and abnormalities observed in metaiodobenzylguanidine (MIBG) myocardial scintigraphy, suggesting Parkinson's disease. However, autopsy results revealed PSP pathology, including tuft-shaped astrocytes and globose-type neurofibrillary tangles, without Lewy body pathology. The degeneration was moderately to severely distributed in the globus pallidus, subthalamic nucleus, and substantia nigra, whereas striatal degeneration was mild. These findings suggest an intact response to L-dopa therapy throughout the patient's lifetime. Pathological examination of cardiac sympathetic nerves revealed intact nerves, suggesting functional involvement in the MIBG abnormality. This study provides further evidence of the clinical and pathological heterogeneity of PSP. Homozygosity for both the rs564309-C allele at TRIM11 and the rs2242367-G allele at SLC2A13 might have played a protective role. This case indicates a protracted course-PSP, which may hold promise for future treatments.

Utility of Combining Transcranial Sonography and MIBG Myocardial Scintigraphy to Evaluate Substantia Nigra in Patients with Parkinson's Disease.

The utility of transcranial sonography (TCS) remains unclarified for the auxiliary diagnosis of Parkinson's disease (PD). We investigated iodine-123 metaiodobenzylguanidine (MIBG) and TCS during the examination and diagnosis of high-signal-intensity substantia nigra lesion (HSI-SNL) incidence in PD patients previously diagnosed with dopamine transporter scintigraphy (DAT). The subjects were 67 patients with definitively diagnosed PD after DAT evaluation. Patients with midbrain substantia nigra visible during TCS who previously underwent MIBG were analyzed. The SN+ group comprised patients with extensive pathological HSI-SNL of Okawa class III/IV observed during TCS. The MIBG+ group comprised patients with a heart-to-mediastinum ratio of ≤2.2 during MIBG. TCS was performed to divide patients into the SN+ and SN- groups, and patient characteristics and MIBG findings were compared between the groups. PD was definitively diagnosed in 67 patients, among whom midbrain was visualized during TCS in 43 (64.1%) patients and pathological HSI-SNL was observed in 24 (35.8%). The MIBG findings were normal in six patients (27.3%) with HSI-SNL, and abnormal in seven (63.6%) without HSI-SNL. No significant differences were noted by Okawa classification in clinical characteristics based on the presence or absence of HSI-SNL. Multiple patients with normal findings during MIBG may have HSI-SNL. Thus, confirmatory imaging of HSI-SNL with TCS may be useful for diagnosis.

A case of left posterior cortical atrophy presenting with kana-predominant reading impairment

The patient was an 85-year-old man with a one-year history of difficulty reading kana. Neuropsychological evaluation revealed kana (phonogram)-selective reading impairment and kanji (ideogram)-dominant writing impairment. MRI revealed significant cerebral atrophy in the left occipital cortex, leading to the clinical diagnosis of posterior cortical atrophy (PCA). Cerebrospinal fluid amyloid β1-42 levels were reduced, and amyloid PET showed accumulation in the posterior cingulate cortex, precuneus, and frontal lobe. In contrast, tau PET showed no accumulation in the atrophied brain areas. Episodes of REM sleep behavior disorder and decreased uptake on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy suggested the involvement of Lewy body pathology. PCA with distinct laterality has been rarely reported, and ‍this is the first case to present Kana-selective reading impairment and Kanji-dominant writing impairment with neurodegenerative background.

Autonomic dysfunction in dementia with Lewy bodies: Focusing on cardiovascular and respiratory dysfunction.

Dementia with Lewy bodies (DLB) is the second most common cause of dementia after Alzheimer's disease. The disease is characterized by many Lewy bodies appearing in the patient's cerebrum. DLB frequently presents with a variety of autonomic symptoms from the early or prodromal stages of the disease, and these are listed as supportive features in the diagnostic criteria. As several useful assessment methods for evaluating autonomic function in DLB have been reported, this review will focus on cardiovascular and respiratory dysfunction and its assessments. Cardiovascular disorders, such as orthostatic hypotension and abnormal heart rate variability, have been reported in DLB patients. Decreased myocardial uptake by metaiodobenzylguanidine myocardial scintigraphy has been added as an indicative biomarker for DLB in the 2017 revision of the diagnostic criteria. We have reported reduced ventilatory response to hypercapnia, abnormal respiratory rhythm, and high frequency of sleep-disordered breathing as abnormalities of the respiratory regulatory system associated with DLB. Since autonomic dysfunction is highly prevalent in DLB from the early or prodromal phase of the disease and is associated with reduced activities of daily living and quality of life, the evaluation of autonomic dysfunction is also useful in the differential diagnosis of DLB from Alzheimer's disease. There are fewer studies on the respiratory regulatory system than on the cardiovascular system, thus further research is needed to explore its role in DLB.

High clinical diagnostic accuracy of combined salivary gland and myocardial metaiodobenzylguanidine scintigraphy in the diagnosis of Parkinson's disease.

Decreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson's disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well. To evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD). Thirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios. The combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively. 131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

Genotype-phenotype correlation of Parkinson's disease with PRKN variants

To investigate the prevalence and genotype-phenotype correlations of parkin RBR E3 ubiquitin protein ligase (PRKN) variants in Parkinson's disease (PD), we first included 2,527 patients with PD. Through the defined selection, we enrolled 2,322 patients, including 1,204 with familial and 1,118 with sporadic PD. We identified 242 patients harboring PRKN variants, which were thought to be susceptibility factors, comprising 137 patients with familial and 105 with sporadic PD; among the 26 identified variants, 13 were novel. We divided our cohort into 2 groups: heterozygote (hereafter called one-allele) and homozygote or compound heterozygote (hereafter called two-allele). The patients with two-allele were significantly younger at onset than those with one-allele. Six families harbored the complex forms of one- and two-allele in different individuals of the same family. The presence of two-allele reflected more frequent normal values of [123I] metaiodobenzylguanidine myocardial scintigraphy. The log-rank test revealed an exacerbation associated with two-allele over 15 years of the disease course. The patients with PRKN variants showed specific symptoms dependent on the number of mutated alleles.

Renal function and cardiac adrenergic impairment in patients affected by heart failure

Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P < .001). Dividing the population into moderate-to-severe eGFR reduction and normal-to-mildly reduced eGFR (cutoff ≤ 60 mL·min−1·1.73 m−2), a statistically significant reduction of late H/M value was found in patients with RD compared to patients with preserved eGFR (P = .030). By multivariable linear regression analysis, eGFR resulted in the prediction of impaired late H/M in patients with RD (P = .005). Patients with RD and HF show more impaired cardiac sympathetic activity than HF patients with preserved renal function, and reduced eGFR is a predictor of reduced late H/M.

Meta-iodobenzylguanidine myocardial scintigraphy in Perry disease

IntroductionPerry disease (Perry syndrome), a hereditary TAR DNA-binding protein 43 (TDP-43) proteinopathy, is caused by dynactin subunit 1 (DCNT1) mutations and is characterized by rapidly progressive parkinsonism accompanied by depression, apathy, unexpected weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is considered a diagnostic biomarker for Lewy body disease (LBD), as denervation of cardiac sympathetic nerves is a pathological feature in LBD. However, our previous studies have reported a decreased cardiac uptake of MIBG in patients with Perry disease. In this study, we aimed to correlate the MIBG myocardial scintigraphy findings with clinical features in Perry disease. MethodsWe evaluated data obtained from a multicenter survey of patients of Japanese origin with suspected Perry disease, who visited neurology departments in Japan from January 2010 to December 2018. We screened each patient's DNA for the DCTN1 mutation using Sanger sequencing and obtained the clinical details of all patients including findings from their MIBG myocardial scintigraphy. ResultsWe identified two novel mutations, p.G71V and p.K68E, in DCTN1 in patients from two different families. The majority of patients (7/8, 87.5%) showed a decrease in cardiac uptake (heart to mediastinum ratio) in MIBG myocardial scintigraphy. These patients commonly presented with symptoms related to autonomic dysfunction: constipation, fecal incontinence, urinary disturbance, and orthostatic hypotension. ConclusionsMIBG myocardial scintigraphy may be a useful biomarker of autonomic dysfunction in Perry disease.

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [123I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants.

A comprehensive analysis of the clinical characteristics and laboratory features in 179 patients with autoimmune autonomic ganglionopathy

The clinical importance of autoantibodies against the ganglionic acetylcholine receptor (gAChR) remains to be fully elucidated. We aimed to identify the clinical characteristics of autoimmune autonomic ganglionopathy (AAG) in patients with gAChR autoantibodies. For this cohort investigation, serum samples were obtained from patients with AAG between 2012 and 2018 in Japan. We measured the levels of autoantibodies against gAChRα3 and gAChRβ4 and evaluated clinical features, as well as assessing the laboratory investigation results among the included patients. A total of 179 patients tested positive for antibodies, including 116 gAChRα3-positive, 13 gAChRβ4-positive, and 50 double antibody-positive patients. Seropositive AAG patients exhibited widespread autonomic dysfunction. Extra-autonomic manifestations including sensory disturbance, central nervous system involvement, endocrine disorders, autoimmune diseases, and tumours were present in 118 patients (83%). We observed significant differences in the frequencies of several autonomic and extra-autonomic symptoms among the three groups. Our 123I-metaiodobenzylguanidine myocardial scintigraphy analysis of the entire cohort revealed that the heart-to-mediastinum ratio had decreased by 80%. The present study is the first to demonstrate that patients with AAG who are seropositive for anti-gAChRβ4 autoantibodies exhibit unique autonomic and extra-autonomic signs. Decreased cardiac uptake occurred in most cases, indicating that 123I- metaiodobenzylguanidine myocardial scintigraphy may be useful for monitoring AAG. Therefore, our findings indicate that gAChRα3 and gAChRβ4 autoantibodies cause functional changes in postganglionic fibres in the autonomic nervous system and extra-autonomic manifestations in seropositive patients with AAG.

Changes in clinical features of multiple system atrophy in Japan

IntroductionMultiple system atrophy (MSA) is an adult-onset progressive neurodegenerative disease that causes parkinsonism, cerebellar ataxia, and/or autonomic failure. MSA is categorized as MSA with predominant cerebellar ataxia (MSA-C) or MSA with predominant parkinsonism (MSA-P) according to the cardinal symptom at diagnosis. MSA-C has been reported to be the predominant presentation in Japan to date. However, major epidemiological studies regarding MSA in Japan were carried out before 2006; thus, the recent advancement of various imaging studies remains unclear. This study aimed to investigate the clinical characteristics of the recent MSA patients in Japan. MethodsIn this retrospective study, we divided 80 probable MSA patients into group A and group B and examined them to reveal whether the clinical features of MSA were different depending on the time periods of diagnosis (1989–2003 and 2004–2018, respectively). ResultsThe age at onset was significantly higher in MSA-P patients than in MSA-C patients (p = 0.0039) and was also higher in group B than in group A (p = 0.013). Although MSA-C was the predominant type in both groups, MSA-P was significantly more frequent in group B than in group A (p = 0.039). Although not statistically significant, the early heart/mediastinum ratio in [123I]-meta-iodo benzylguanidine (MIBG) myocardial scintigraphy tended to be lower in patients with MSA-P than in those with MSA-C. ConclusionThe proportion of MSA-P was likely larger than previously recorded due to the aging population in Japan and the improvement of differential diagnosis between PD and MSA-P.

P2624Association between renal dysfunction and cardiac sympathetic innervation in patients with heart failure

Abstract Introduction In heart failure (HF) a strict interaction exists between heart and kidney. Previous studies reported a significant impact of sympathetic overdrive, that causes beta-adrenoceptor desensitization, in both renal and heart failure progression. It can be hypothesized that renal failure might be associated with impaired sympathetic activity assessed directly at the myocardial level in patients affected by HF. Purpose Aim of the present observational study was to assess the relationship between renal dysfunction and cardiac sympathetic innervation in HF patients with mildly and severely reduced ejection fraction (HFrEF and HFmEF). Methods Two-hundred and sixty-three patients (84% males; 66±10.8 years) with mild-to-severe HF (EF 31±6.8%) underwent iodine-123 meta-iodobenzylguanidine (123I-MIBG) myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart to mediastinum (H/M) ratios and washout rate. All patients also underwent clinical evaluation and venous blood sample collection for the assessment of serum creatinine and consequently the estimation of glomerular filtration rate (eGFR) by EPI formula. Results A direct correlation was found between EPI-eGFR and late H/M (r=0,215; p&lt;0.001) (figure 1), with an inverse correlation between NYHA class and late H/M (r=0,152; p=0.013), and a direct correlation between left ventricular EF and late H/M (r=0,348; p&lt;0.001). These results were not confirmed for early H/M, nor washout rate. Dividing the population in reduced eGFR and normal eGFR (cut-off ≤60 ml/min/1,73m2), a statistical significant reduction of late H/M value was found in patients with reduced eGFR (late H/M = 1,49±0,21) compared with patients with preserved eGFR (late H/M = 1,56±0,26) (p=0.020). In a multivariate model, adjusting eGFR for NYHA class and left ventricular EF, reduced eGFR and left ventricular EF remained significant predictors of reduced late H/M (p=0.006 and p&lt;0.001, respectively). Figure 1. linear regression curve Conclusions Patients with impaired renal function and HF show impaired cardiac sympathetic activity compared to HF patients with preserved renal function, and reduced eGFR estimated by EPI formula is a significant predictor of reduced late H/M evaluated by 123I-MIBG. Thus, in future studies, the combination of these two parameters might provide addictive prognostic information in HF patients.

DAT imaging and myocardial MIBG scintigraphy for Lewy body diseases: A clinical‐neuroimaging study

AbstractObjectivesNeuroimaging markers for Lewy body diseases (LBDs) include dopamine transporter (DAT) scanning and metaiodobenzylguanidine (MIBG) myocardial scintigraphy. It is unknown which marker is more useful for identifying the three major LBD subtypes: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and the autonomic‐sleep variant. To answer this question, we analyzed clinical‐neuroimaging data of 450 LBD patients.MethodsThis study was a prospective cohort study with a recruiting period of 3.0 years, prospective follow‐up period of 2.0 ± 1.8 years, and visits at least once a year. We recruited 745 referred subjects who had undergone both DAT and MIBG tests, and the inclusion criteria accorded with published criteria of PD, DLB, and the autonomic/sleep variant (at least one of PD/DLB's known early features: orthostatic hypotension, constipation, overactive bladder, and REM sleep behavior disorder [RBD]).ResultsA total of 450 patients fulfilled the criteria. Among the LBD subtypes, the most common was PD (49.3%), followed by DLB (46.4%) and the autonomic/sleep variant (4.2%). DAT and MIBG tests were almost equally abnormal in PD (98.2%, 79.3%, respectively); however, between the two measures, DAT was more frequently abnormal in DLB (82.3%, 56.9%, respectively) and MIBG in the autonomic/sleep variant (57.9%, 94.7%, respectively). Still, these differences did not reach statistical significance.ConclusionBetween the two neuroimaging tests, the DAT scan tended to parallel brain disease (PD/DLB), while the MIBG test tended to parallel peripheral disease (autonomic/sleep variant).

Parkinsonism Relating to Intoxication with Glyphosate

We herein report the case of a 38-year-old man who developed parkinsonism 4 years after ingesting glyphosate. The patient presented with right-sided bradykinesia and cogwheel rigidity without autonomic symptoms. Magnetic resonance imaging of the brain and [123I]-metaiodobenzylguanidine myocardial scintigraphy were normal. A drastic response to levodopa and the presence of levodopa-induced dyskinesia without strong non-motor symptoms were seen in this patient. We considered that young-onset atypical parkinsonism was associated with a history of sublethal glyphosate ingestion. Epidemiologic investigations have shown that exposure to pesticides is a risk factor for Parkinson’s disease (PD). Our findings support the notion that glyphosate exposure might be related to the onset of PD.

Autonomic Symptoms Correlate with Non-Autonomic Non-Motor Symptoms and Sleep Problems in Patients with Parkinson’s Disease

Objective: The objective of this study was to clarify the relationship between autonomic and non-autonomic non-motor symptoms in patients with Parkinson’s disease (PD). Methods: Sixty-five PD patients were included in this study (27 men and 38 women; aged 68.5 ± 10.0; Hoehn and Yahr (HY) stage 2.6 ± 1.1). The autonomic symptoms were evaluated by the Japanese version of the Scales for outcomes in PD autonomic (SCOPA-AUT) questionnaire. The patients were assessed with the mini-mental state examination (MMSE), PD sleep evaluation scale-2 (PDSS-2), Epworth sleepiness scale (ESS) and Beck’s depression inventory II (BDI-II). The Non-Motor Symptom Scale (NMSS) total scores and subscores of non-autonomic non-motor symptom domains (sleep/fatigue, mood/cognition, perceptual problems/hallucination, and attention/memory) were evaluated. A dopamine transporter (DAT) scan, metaiodobenzylguanidine (MIBG) myocardial scintigraphy, and card type olfactory identification test (open essence [OE, Wako]) were performed. Results: The SCOPA-AUT total score was positively correlated with the disease duration, HY stage, levodopa equivalent dose, PDSS-2, ESS, BDI-II and non-autonomic NMSS and inversely correlated with the MMSE. The high-SCOPA-AUT group (≥9) had lower MMSE scores and higher PDSS-2, ESS, BDI-II and non-motor NMSS scores than the low-SCOPA-AUT group (< 9). The DAT scan, MIBG uptake and OE score did not differ between the groups. In a stepwise linear regression analysis, which excluded possibly overlapping items among the scales, the subtotals of PDSS-2 items, except for item 8 (nocturia), (p < 0.0001) and non-autonomic NMSS domains (p = 0.00040) were significant predictors of the total SCOPA-AUT score. Conclusion: Our study shows significant correlations among autonomic symptoms, PD-related sleep problems and non-autonomic non-motor symptoms in PD patients.

The usefulness of [123I]‐metaiodobenzylguanidine myocardial scintigraphy in patients with subacute myelo‐optico‐neuropathy

AbstractBackgroundPatients with subacute myelo‐optico‐neuropathy (SMON), caused by clioquinol intoxication more than 40 years ago, had been suffered from various kinds of autonomic disorders, such as diarrhea, constipation, and incontinence. [123I]‐metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a sensitive test for diagnosis of Parkinson's disease (PD).AimWe tried to clarify the usefulness of MIBG myocardial scintigraphy in SMON patients for diagnosing PD.MethodsThe MIBG myocardial scintigraphy was investigated in fifteen SMON patients who were suffered from various kinds of autonomic symptoms. In these SMON patients, four patients (mean age ± SD; 73.3 ± 6.8) showed early stage of PD, whose Hoehn–Yahr (H–Y) stage was stage I or stage II, but the other eleven patients (mean age ± SD; 78.0 ± 7.6) had not any signs or symptoms of Parkinsonism.ResultsFour patients with early stages of PD showed significantly reduced MIBG uptake. Eleven patients except one without Parkinsonism showed normal MIBG uptake. No apparent relation between the degree of the autonomic symptoms and the MIBG uptake was observed. One patient without Parkinsonism showed significantly reduced MIBG uptake and was suggested to be suffered from a preclinical state of PD, since the [123I]‐ioflupane single‐photon emission computed tomography scintigraphy showed decreased uptake of isotopes in the bilateral striate regions 8 years after the MIBG myocardial scintigraphy.ConclusionThe MIBG myocardial scintigraphy in SMON patients with various kinds of autonomic symptoms is useful as a highly sensitive and specific tool for diagnosing PD.

MIBG Myocardial Scintigraphy Identifies Premotor PD/DLB During a Negative DAT Scan Period: Second Report.

Neuroimaging markers for Parkinson's disease (PD)/dementia with Lewy bodies (DLB) include dopamine transporter (DAT) scanning and metaiodobenzylguanidine (MIBG) myocardial scintigraphy. It is unknown which marker is useful to identify the premotor phase PD/DLB. We reported four patients who, during a negative DAT scan period, had a positive MIBG result that suggested premotor PD/DLB. Here we report 18 additional patients. This study was a prospective cohort study. The recruiting period was five years; prospective follow-up period, 5.5 ± 3.0 years; and a once a year (minimum) follow-up visit. We recruited 745 referred subjects. The inclusion criteria were having at least one of the following known PD nonmotor features: (1) autonomic: postural hypotension (pure autonomic failure [PAF]), constipation, bladder dysfunction; (2) sleep: REM sleep behavior disorder (RBD); and (3) cognitive: mild cognitive impairment or psychiatric symptoms. Also, the patient had to have undergone both DAT and MIBG tests. Only 18 patients fulfilled these criteria. Their characteristics were: elderly (mean age 75.5 years), with long histories (onset 61.0 years; duration 14.5 years), and predominately male (14 men, four women). The patients' neurologic diagnoses were constipation/RBD in 10, constipation/RBD/PAF in six, and constipation/PAF in two. During the follow-up period, seven patients developed PD or DLB. An abnormal MIBG result was noted in 94%, and an abnormal DAT result was noted in 56%. MIBG has the potential to be a useful marker during the DAT scan negative period to identify premotor PD/DLB, but further studies are needed.

GCH1 mutations in dopa-responsive dystonia and Parkinson's disease.

Guanosine triphosphate cyclohydrolase I (GCH1) mutations are associated with increased risk for dopa-responsive dystonia (DRD) and Parkinson's disease (PD). Herein, we investigated the frequency of GCH1 mutations and clinical symptoms in patients with clinically diagnosed PD and DRD. We used the Sanger method to screen entire exons in 268 patients with PD and 26 patients with DRD, with the examinations of brain magnetic resonance imaging scans, striatal dopamine transporter scans, and [123I] metaiodobenzylguanidine (MIBG) myocardiac scintigraphy scans. We identified 15 patients with heterozygous GCH1 mutations from seven probands and five sporadic cases. The prevalence of GCH1 mutations in probands was different between PD [1.9% (5/268)] and DRD [26.9% (7/26)] (p value < 0.0001). The onset age tends to be different between PD and DRD patients: 35.4 ± 25.3 and 16.5 ± 13.6, respectively (average ± SD; p = 0.08). Most of the patients were women (14/15). Dystonia was common symptom, and dysautonomia and cognitive decline were uncommon in our PD and DRD. All patients presented mild parkinsonism or dystonia with excellent response to levodopa. Seven of seven DRD and three of five PD presented normal heart-to-mediastinum ratio on MIBG myocardial scintigraphy. Five of six DRD and three of four PD demonstrated normal densities of dopamine transporter. Our findings elucidated the clinical characteristics of PD and DRD patients due to GCH1 mutations. PD patients with GCH1 mutations also had different symptoms from those seen in typical PD. The patients with GCH1 mutations had heterogeneous clinical symptoms.

123I-MIBG myocardial scintigraphy for the diagnosis of DLB: a multicentre 3-year follow-up study

Background and purposeWe previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) in a cross-sectional multicentre study....

Questionnaire survey of Scans Without Evidence of Dopaminergic Deficit (SWEDD) in Japan

We conducted a questionnaire survey to collect epidemiological information on patients with Scans Without Evidence of Dopaminergic Deficit (SWEDD). We sent questionnaires to 4,970 neurology specialists in Japan in July 2015 and received responses from 933 of them. The total number of patients reported to have Parkinson's disease was 39,532, which included 237 cases of SWEDD in patients (111 males, 125 females, and 1 case without a gender description). The disease duration in patients with SWEDD was short; 127 cases (53.6%) had a duration less than 3 years, and 78 cases (32.9%) had a duration of 3 years or more but less than 7 years. By age, 59 cases (24.9%) occurred in individuals in their 60s, and 106 cases (44.7%) occurred in individuals in their 70s. Sixty-three neurologists stated that they performed dopamine transporter single photon emission computed tomography (DaT SPECT) on almost all patients with Parkinson's disease. They treated a total of 3,600 patients with Parkinson's disease which included 107 cases of SWEDD; therefore, approximately 3.0% of Parkinson's patients were estimated have SWEDD. The causes of SWEDD were unknown (101 cases), essential tremor (22 cases), vascular Parkinsonism (14 cases), and drug-induced Parkinsonism (14 cases). The majority of neurologists had doubts about the diagnosis of Parkinson's disease prior to confirming the diagnosis using DaT SPECT for reasons such as: normal findings on meta-iodobenzylguanidine (MIBG) myocardial scintigraphy, poor responses to anti-Parkinson drugs, lack of true akinesia, unchanged symptoms, and atypical symptoms. Two hundred and nineteen cases included reports on treatment paradigms following the SWEDD diagnosis. Of those cases, patients in 159 cases were maintained on the same treatment following diagnosis.