Kyeong Joon Kim

Loss of substantia nigra hyperintensity on 7 Tesla MRI of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

BACKGROUND Seven Tesla (7T) MRI can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in Parkinsons disease (PD). OBJECTIVE We investigated whether 7T MRI can detect the loss of substantia nigra hyperintensity in patients with PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). METHODS Using 7T MRI, we evaluated 26 healthy subjects, 30 patients with PD, 7 patients with MSA, and 3 patients with PSP. Two blinded readers independently assessed the images. We carried out a comparative analysis of five patients with hemiparkinsonism via (123)I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane ((123)I-FP-CIT) SPECT. RESULTS 7T MRI revealed a definitive shape of nigral hyperintensity in healthy subjects, nearly identical to neuropathological characterization of nigrosome 1, and enabled instantaneous determination of its presence or absence in all subjects. Nigral hyperintensity was lost in all patients with PD, MSA with predominant parkinsonism, and PSP. One of five patients with MSA with predominant cerebellar ataxia showed an intact nigral hyperintensity. The side effects were mild and tolerable, and imaging was successful in patients with dyskinesia. Motion artifact incidence was higher in elderly subjects. In hemiparkinsonism cases, we observed partial loss of nigral hyperintensity on the side of less reduced (123)I-FP-CIT binding, suggesting an ongoing iron deposition on the unaffected side in hemiparkinsonism. CONCLUSIONS The present findings suggest that 7T MRI represents an excellent tool for evaluating nigral hyperintensity in PD, MSA, and PSP, with tolerable side effects and limited motion artifacts. Thus, imaging of parkinsonism may benefit from using 7T MRI.

Loss of Nigral Hyperintensity on 3 Tesla MRI of Parkinsonism: Comparison With 123I‐FP‐CIT SPECT

The aim of this study was to investigate whether 3 Tesla susceptibility‐weighted imaging can detect the alteration of substantia nigra hyperintensity in Parkinsons disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) and to assess the concordance between the loss of nigral hyperintensity on 3 Tesla susceptibility‐weighted imaging and the nigrostriatal dopaminergic degeneration indicated by 123I‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane single photon emission computerized tomography.

Validation of FLAIR Hyperintense Lesions as Imaging Biomarkers to Predict the Outcome of Acute Stroke after Intra-Arterial Thrombolysis following Intravenous Tissue Plasminogen Activator

Background: Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis. Methods: With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions. Results: Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores. Conclusions: This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.

Association between hepatitis C virus infection and Parkinson's disease

Hepatitis C virus (HCV)-induced neuroinflammation may lead to dopaminergic neuronal loss, suggesting a possible association between HCV infection and Parkinson’s disease (PD). To date, there are two Taiwanese studies using community-based data that showed an increased PD risk by around 2-fold with HCV infection. We investigated the association between HCV infection and PD through a hospital-based, case-control study. The study sample comprised 1,558 PD patients and 1,558 ageand sex-matched controls—randomly selected from 70,926 health-check examinees (Supporting Data). Overall anti-hepatitis C virus antibody (anti-HCV) prevalence in the PD group was significantly higher than that in the control group (Fig. 1). Anti-HCV positivity was significantly associated with PD for overall age groups. In elderly subjects 70 years, a significant association between anti-HCV positivity and PD was observed; however, in younger subjects, the association was not noted. In contrast, the association between hepatitis B surface antigen (HBsAg) and PD was not observed for overall age groups; however, in elderly subjects, HBsAg positivity was negatively associated with PD. The difference of anti-HCV positivity between age groups may be attributed to lower prevalence of HCV infection, as well as PD, in younger subjects. However, the Taiwanese study showed a significant association in those younger than 65 years. This may be attributed to different prevalence and risk factors of HCV infection between the two countries. In the Korean population, anti-HCV prevalence increases with age, and there are only a few intravenous drug users among anti-HCV-positive subjects. Further studies in other populations are needed to firmly establish the association between HCV infection and PD. Among the 27 anti-HCV-positive PD cases, detection of anti-HCV positivity anteceded the diagnosis of PD by 4.7 6 3.4 years in 13 patients, whereas anti-HCV positivity was concomitantly detected at the time of PD diagnosis in the other 14 patients. Among the 27 patients, 15 exhibited no clinical evidence of liver disease, and in 9 patients who underwent the HCV RNA test, 4 showed negativity, suggesting that even remote exposure to HCV without severe liver damage may be associated with PD. A recent study showed immune crossreactive potential of viral peptides, including HCV, which was shared with human brain antigens associated with neurodegenerative disorders. Further studies investigating the pathomechanism of the association between HCV and PD are needed. Our study had several limitations. First, given the crosssectional design of this study, it was not possible to determine the temporal sequence of HCV infection and onset of PD. Second, anti-HCV-positive subjects may seek medical services more frequently, which may increase the chance of PD diagnosis. However, the number of physician visits did not differ between anti-HCV-positive and -negative patients (Supporting Table 5). Third, besides age and sex, there may be other factors related to HCV infection, confounding the association between HCV infection and PD. Finally, the number of anti-HCV-positive subjects was small, particularly for the age-stratified analysis; thus, future prospective and longitudinal studies including more subjects are necessary. In conclusion, HCV infection was significantly associated with PD.

Serum Ceruloplasmin and Striatal Dopamine Transporter Density in Parkinson Disease: Comparison With 123I-FP-CIT SPECT

Purpose In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin—along with its related serum markers— and striatal presynaptic dopaminergic denervation measured with 123I-FP-CIT SPECT. Methods We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism). Serum ceruloplasmin and related serum markers, such as copper, iron, total iron-binding capacity, and ferritin, were measured. Specific binding ratios of the striatum, caudate nucleus, putamen, and posterior putamen were obtained by 123I-FP-CIT SPECT. Results There was no difference in the serum markers, except for ceruloplasmin, between the 2 groups. Ceruloplasmin level was significantly lower in PD patients with longer symptom duration (>2 years) than in the disease control group (21.4 ± 3.4 vs 24.0 ± 3.8, P = 0.03). Serum ceruloplasmin had a significant correlation with specific binding ratios of the striatum, caudate nucleus, and putamen in a subgroup with longer symptom duration (P = 0.01, P = 0.02, P = 0.02, respectively, for the subgroup with symptom duration >1 year, and P < 0.01, P < 0.01, P = 0.04, respectively, for the subgroup with symptom duration >2 years). Conclusions Decrease in serum ceruloplasmin had a positive correlation with a decrease in dopamine transporter density in PD patients with symptom duration of more than 1 year.

Coexistence of ocular neuromyotonia and hemifacial spasm.

A 47-year-old woman presented with facial jerky movement and intermittent diplopia for 2 years. Paroxysmal deviation of the right eye was observed together with right hemifacial spasm (video on the Neurology® Web site at Neurology.org). Right anterior inferior cerebellar artery was shown to intersect with both facial and abducens nerves, and exodeviation of the right eye, compatible with ocular neuromyotonia, was recorded (figure). In ocular neuromyotonia, ephaptic neural transmission related to mechanical irritation has been suggested as its mechanism, similar to hemifacial spasm.1,2 Although 2 different terms, neuromyotonia and spasm, are used, co-occurrence of these 2 conditions in this patient suggests the similar pathophysiology in common.

Neurogenic bladder in progressive supranuclear palsy: A comparison with Parkinson's disease and multiple system atrophy

Progressive supranuclear palsy (PSP) can present urinary symptoms, similar to other parkinsonian disorders. We investigated the urodynamic parameters of PSP and compared them with those of idiopathic Parkinsons disease (IPD) and multiple system atrophy (MSA)

Loss of Substantia Nigra Hyperintensity at 3.0-T MR Imaging in Idiopathic REM Sleep Behavior Disorder: Comparison with 123I-FP-CIT SPECT

Purpose To examine whether the loss of nigral hyperintensity (NH) on 3.0-T susceptibility-weighted (SW) magnetic resonance (MR) images can help identify high synucleinopathy risk in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). Materials and Methods Between March 2014 and April 2015, 18 consecutively recruited patients with iRBD were evaluated with 3.0-T SW imaging and iodine 123-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single photon emission computed tomography and compared with 18 healthy subjects and 18 patients with Parkinson disease (PD). Two readers blinded to clinical diagnosis independently assessed the images. 123I-FP-CIT uptake ratios were compared by using the Kruskal-Wallis test, and intra- and interobserver agreements were assessed with the Cohen κ. The synucleinopathy conversion according to NH status was evaluated in patients with iRBD after follow-up. Results NH was intact in seven patients with iRBD and lost in 11. The 123I-FP-CIT uptake ratios were comparable between those with intact NH (mean, 3.22 ± 0.47) and healthy subjects (mean, 3.37 ± 0.47) (P = .495). The 123I-FP-CIT uptake ratios in the 11 patients with iRBD and NH loss (mean, 2.48 ± 0.44) were significantly lower than those in healthy subjects (mean, 3.37 ± 0.47; P < .001) but higher than those in patients with PD (mean, 1.80 ± 0.33; P < .001). The intra- and interobserver agreements were excellent (κ > 0.9). Five patients with iRBD and NH loss developed symptoms of parkinsonism or dementia 18 months after neuroimaging. Conclusion NH loss at 3.0-T SW imaging may be a promising marker for short-term synucleinopathy risk in iRBD.