123I-MIBG cardiac uptake,smell identification and 123I-FP-CIT SPECT in the differential diagnosis between vascular parkinsonism and Parkinson's disease

Vascular parkinsonism (VP) may occur as a distinct clinicopathological entity but the comorbid presence of vascular damage in Parkinson's disease (PD) is very frequent too. This differential diagnosis has therapeutic and prognostic implications but remains challenging as the usefulness of a number of supporting tools is still controversial.ObjectiveTo ascertain the clinical value of cardiac ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) SPECT, olfactory function and ¹²³I-FP-CIT SPECT as supporting tools in the differential diagnosis between VP and PD.MethodsCross-sectional study of 15 consecutive patients with suspected VP, 15 PD patients and 9 healthy subjects. Cardiac ¹²³I-MIBG SPECT (heart-to-mediastinum ratio) and olfactory testing (University of Pennsylvania Smell Identification Test-UPSIT) were performed in all of them. ¹²³I-FP-CIT SPECT was performed in VP-suspected patients.ResultsHeart-to-mediatinum ratio was significant lower in suspected VP (mean 1.45) and PD (mean 1.16) compared to control group (mean 1.69) (p = 0.017 and p < 0.0001). VP patients presented a higher ratio than PD patients (p = 0.001). Control group presented a significant higher UPSIT score (mean 30.71) when compared to both VP (mean 18.33) and PD (mean 15.29) (p = 0.001 for both groups). Those VP with a cardiac ¹²³I-MIBG non suggestive of PD were more likely to have a higher UPSIT score (p = 0.006). ¹²³I-FP-CIT SPECT imaging was heterogeneous (7/15 VP normal, 3/15 abnormal suggestive of PD and 5/15 abnormal but atypical for PD).ConclusionsThe use of cardiac ¹²³I-MIBG SPECT and to a lesser extent UPSIT could assist the differential diagnosis between VP and PD in subjects in which the diagnosis remains uncertain despite ¹²³I-FP-CIT SPECT imaging.     

Systemic blood pressure profile correlates with cardiac 123I-MIBG uptake in patients with Parkinson's disease

To examine the correlation between the systemic blood pressure profile and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we monitored circadian blood pressure patterns of 37 PD patients of 49 to 85 years of age (mean, 71.8±8.4 years) using a portable blood pressure monitoring device. The duration of PD was 0.5 to 15 years, and the disability level (modified Hoehn and Yahr stage) ranged from 1.0 to 4.0 (mean, 2.7±0.7). There were 37 age- and sex-matched control subjects. Cardiac MIBG scintigraphy was performed for the 37 PD patients. Based on the nocturnal fall in mean arterial blood pressure (MABP), we classified patients into extreme dippers (nocturnal reduction of MABP >20%), dippers (>10% but <20%), nondippers (<10% but >0%), and inverted dippers (<0%). Average 24-hour MABP values revealed reduced BP variability in PD patients. The percentage nocturnal fall in MABP was significantly different between PD patients and control subjects (p<0.05). Significant correlations were found between % MABP reduction and the heart-to-mediastinum (H/M) ratio on early and delayed images (p<0.01). The UPDR motor score, early and delay H/M ratios were also significantly different between patients who were and were not dippers (p<0.05). The present results reported for the first time a significant correlation between the systemic blood pressure profile and cardiac (123)I-MIBG uptake in patients with PD. The degeneration between the brainstem and the postganglionic neurons of myocardial sympathetic nerves may progress in parallel in patients with PD.     

Correlation between cardiac 123I-MIBG and odor identification in patients with Parkinson's disease and multiple system atrophy.

We investigated an association between olfaction and cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). There was a significant positive correlation between cardiac MIBG uptake and the Cross-Cultural Smell Identification (CCSI) score in patients with PD (r = 0.56; P = 0.003) independent of the disease duration or clinical rating of motor status. However, patients with MSA did not show a significant correlation between cardiac MIBG uptake and the CCSI score. Our findings suggest that the functional losses of the olfactory and cardiac sympathetic systems are closely coupled in PD.     

Long-term effect of acetyl-L-carnitine on myocardial123I-MIBG uptake in patients with diabetes

Carnitine derivatives may have beneficial effects on cardiac and nerve function in patients with diabetes. The aim of this study was to investigate the effect of acetyl-L-carnitine (ALC) on myocardial sympathetic nervous function as measured with¹²³I-meta-iodobenzyl guanidine (MIBG) and single-photon emission tomography (SPET) in 19 patients with diabetes (placebo group,n=6; ALC group,n=13) at the beginning and at the end of a 1-year randomized, placebo-controlled, doubleblind trial. The coefficient of variation for the MIBG analysis was 4%. In patients who were given a placebo, global myocardial MIBG uptake deteriorated during the study (MIBG uptake 1-year follow-up/baseline, 0.86±0.05, mean±standard error of mean), whereas in patients treated with ALC, MIBG uptake did not change significantly (1-year follow-up/baseline, 1.07±0.08; p=0.03 between the groups). On the basis of these preliminary data, we conclude that long-term treatment with ALC may be of potential value in preventing the progressive loss of myocardial sympathetic nervous function in patients with diabetes. MIBG-SPET is a sensitive and thus valuable method in assessing the development of myocardial sympathetic nervous dysfunction.     

Screening for LRRK2 mutations in patients with Parkinson's disease in Russia: identification of a novel LRRK2 variant

Background and purpose:  Mutations in LRRK2 , encoding leucine-rich repeat kinase 2 (or Dardarin), cause autosomal dominant Parkinson's disease (AdPD) and are also found in sporadic PD (sPD). To investigate the frequency of LRRK2 mutations in a sample of Russian PD patients.
Methods:  We sequenced the complete coding region of LRRK2 in 65 patients with AdPD and in 30 patients with sPD. Furthermore, in 20 patients with AdPD and in 159 patients with sPD we screened several common LRRK2 mutations (G2019S, R1441C/G/H, I2012T and I2020T).
Results:  Five AdPD patients had the LRRK2 G2019S mutation (5.9%, 5/85). In addition, we discovered a novel LRRK2 variant V1613A in a family with a tremor dominant form of AdPD; this variant was not present in controls. We identified two patients with LRRK2 mutations in sPD: one with the G2019S mutation (0.5; 1/189) and another with the previously described R1441C mutation (0,5; 1/189).
Conclusions:  LRRK2 mutations are common amongst patients with PD in Russia. The results also show that the G2019S mutation is the most frequent. We identified one novel mutation in a functional region of LRRK2.     

Autonomic dysfunction in parkinsonian LRRK2 mutation carriers

IntroductionThe aim of this study was to compare autonomic function in PD symptomatic carriers of the LRRK2 mutations and idiopathic Parkinson's disease (iPD) patients.Material and methodsWe studied 25 PD patients: 12 with the LRRK2 mutation (6 G2019S and 6 R1441G), and 13 with iPD. All patients underwent blood pressure and heart rate monitoring during head up tilt, Valsalva maneuver and deep breathing, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy.ResultsThree of the patients with iPD and one of the LRRK2 carriers had orthostatic hypotension. Arterial pressure “overshoot” during phase IV of Valsalva maneuver was less pronounced in patients with iPD. During passive tilt, LRRK2 carries had higher increase of blood pressure than iPD patients MIBG late myocardial/mediastinal uptake ratios were higher in LRRK2 mutation carriers (1.51 ± 0.28 vs 1.32 ± 0.25; p < 0.05).DiscussionCarriers of the LRRK2 mutation had less autonomic impairment than those with iPD as shown by higher cardiac MIBG uptake and a tendency to less impairment of autonomic non-invasive tests. It is important to carry out larger studies comparing the clinical, functional and pathological characteristics of these patients.     

Cardiac 123I-MIBG scintigraphy in patients with drug induced parkinsonism

Cardiac sympathetic dysfunction was investigated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 20 patients with drug induced parkinsonism (DIP). The mean heart to mediastinum ratio was significantly greater in patients with DIP than in those with Parkinson's disease (mean (SD): 2.07 (0.39) v 1.28 (0.15), p<0.001). MIBG uptake was not different between the DIP patients and controls. Two DIP patients whose MIBG uptake was significantly reduced showed persistent parkinsonism and responded dramatically to levodopa.     

Cardiac 123I-MIBG scintigraphy in patients with essential tremor.

In some cases, it is difficult to differentiate essential tremor (ET) from Parkinson's disease (PD), especially in the early stages of the disease. We investigated cardiac sympathetic dysfunction using (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 22 patients with ET, in comparison with early PD and tremor-dominant PD (TDPD). The mean ratio of (123)I-MIBG uptake in the region of interest in the heart to that in the mediastinum (H/M ratio) was significantly greater in patients with ET (1.99 +/- 0.21) than in those with either TDPD (1.28 +/- 0.11) or early PD (1.28 +/- 0.17; each P < 0.001). The H/M ratio in all patients with ET was greater than two standard deviations above the range of the ratio in the patients with early PD or TDPD.     

Genetic analysis of LRRK2 mutations in patients with Parkinson disease

In addition to the G2019S mutation in the leucine-rich repeat kinase 2 gene (LRRK2), which is particularly frequent in patients of Ashkenazi Jewish and Northern African origin, three amino acid substitutions (R1441C, R1441G, and R1441H), all at the same residue (R1441), have been identified as important genetic causes of Parkinson disease (PD). To evaluate the frequency of R1441C/G/H and G2019S mutations in the LRRK2 gene in North American patients with PD and to explore genotype-phenotype correlations, we screened 496 PD patients from North America. One Hispanic female was heterozygous for the LRRK2 R1441G mutation, and six other cases including 2 non-Jewish/non-Hispanic whites, 3 Ashkenazi Jewish, and 1 Hispanic, were found to be heterozygous for the LRRK2 G2019S mutation. G2019S mutation in the LRRK2 gene is a common mutation associated with PD in a North American population, especially in Jewish PD patients (10.7%), while the R1441C/G/H mutation occurs at a relatively low frequency in North Americans except possibly in Hispanics for R1441G. All six G2019S carriers shared a common haplotype with that observed in Europeans and North Africans. The clinical features of all seven cases with LRRK2 mutation were quite broad and included early and late disease onset. These finding may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling.     

LRRK2 mutations in patients with Parkinson's disease from Peru and Uruguay

Variation in the leucine-rich repeat kinase 2 (LRRK2) gene represents the most common genetic determinant of Parkinson's disease (PD) identified to date. While the frequency and distribution of LRRK2 mutations have been well-studied in Europe and North America, few data are available from South America. To address this gap in knowledge, we screened two cohorts of patients with PD from Peru (n=240) and Uruguay (n=125) for the three most common LRRK2 mutations (R1441C, R1441G, G2019S). We identified at total of seven patients with mutations, one with R1441G, and six with G2019S. The carrier frequency was significantly greater in the Uruguayan cohort (4.8%) than in the Peruvian cohort (0.4%; p=0.007). This likely resulted from a greater admixture proportion in the Peruvian sample. Haplotype analyses suggested that G2019S was probably brought to Peru and Uruguay by European settlers. In contrast, the origin of R1441G in our cohort was not clear, as the patient with this mutation had a background haplotype that was clearly distinct from that reported in carriers from Europe and North America. Our data add to a growing body of evidence indicating that LRRK2 mutations are widely distributed across South America but might differ by region in prevalence.     

LRRK2 mutations and risk variants in Japanese patients with Parkinson's disease

Mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson's disease (PD) in European‐derived populations, but far less is known about LRRK2 mutations and susceptibility alleles in Asians. To address this issue, we sequenced the LRRK2 coding region in 36 patients with familial PD, then genotyped variants of interest in an additional 595 PD cases and 1,641 controls who were all of Japanese ancestry. We also performed a meta‐analysis of studies on G2385R, a polymorphism previously reported to associate with PD. One pathogenic (G2019S) and one putative pathogenic (R1067Q) mutation were each observed in two patients with sporadic PD. The overall mutation frequency among patients was 0.6%. G2385R was highly associated with PD under a dominant model in our dataset (adjusted OR, 1.83; 95% CI, 1.31–2.54; P = 3.3 × 10^?4) and similar results were seen in the meta‐analysis (summary OR assuming fixed effects, 2.55; 95% CI, 2.10–3.10). G2385R represents the first consistently replicated common PD susceptibility variant in a non‐European population and its effect size is substantially greater than that reported for other well‐validated genetic risk factors for the disease. However, LRRK2 mutations appear to be rare among Japanese patients with PD. © 2009 Movement Disorder Society     

Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder

Idiopathic REM sleep behavior disorder (RBD) may represent prodromal synucleinopathies. We report markedly reduced cardiac (123)I-metaiodobenzylguanidine uptake, consistent with the loss of sympathetic terminals, in idiopathic RBD. We also demonstrate that this reduction is of the same magnitude as that found in patients with Parkinson disease. The results are consistent with the hypothesis that idiopathic RBD in older patients is a forme fruste of Lewy body disease.     

Myocardial 123I-MIBG scintigraphy in patients with PSP,CBD and MSA

Journal of Neurology - Reduced cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) is considered to represent dysfunction of the postganglionic neurons of the cardiac sympathetic nervous system....     

SCOPA-AUT scale in different parkinsonisms and its correlation with (123) I-MIBG cardiac scintigraphy

IntroductionOur objective was to assess the usefulness of the Scales for Outcomes in Parkinson’s disease – Autonomic (SCOPA-AUT) in the differential diagnosis of Parkinsonisms and clarify its relation with 123-I-MIBG cardiac scintigraphy.MethodsA total of 112 patients with Parkinson’s disease (PD), 12 with multiple system atrophy parkinsonian variant (MSA-P) and 20 with progressive supranuclear palsy (PSP) participated in the study. The following variables were collected: age, sex, age at onset, length of illness, type and dose of anti-Parkinson medication, and score on the Unified Parkinson’s Disease Rating Scale. The Unified Multiple System Atrophy Rating Scale was administered to patients with MSA and the Progressive Supranuclear Palsy Rating Scale to those with PSP. Finally, the SCOPA-AUT was administered to all the patients. Cardiac 123I-MIBG SPECT scans were performed on a subset of patients (25 with PD and 5 with MSA-P).ResultsStatistically significant differences were observed (p < 0.01) in the SCOPA-AUT scores between patients with PD (14.75+/?8.09) and those with MSA (21.07+/?5.56), the latter having higher scores on the bowel function (20.07+/?13.40 vs 34.92+/?14.91) and urinary domains (30.21+/?21.55 vs 49.26+/?21.40) (p < 0.01). No correlation was found between the SCOPA-AUT score and anti-Parkinson’s medication and heart:mediastinum (H/M) MIBG uptake ratio in the cardiac SPECT (at 4 h).DiscussionSeverity of dysautonomia as measured by the SCOPA-AUT was not correlated with clinical severity, time since onset or the H/M ratio. In the patients with PD, the only variable associated with the H/M ratio was age at onset of the disease.