"Depressed" caudate and ventral striatum dopamine transporter availability in de novo Depressed Parkinson's disease

Depression can occur before the onset of motor symptoms in Parkinson's disease (PD) patients. The pathophysiology of depression in PD involves various brain regions and relevant functional circuits. This study investigated whether there exist distinctive patterns of presynaptic monoamine transporter densities in the basal ganglia depending on the degree of depression in patients with PD. A total of 123 early and drug-naïve PD patients were enrolled. Their affective status was evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), and subjects were subgrouped into one of the following three groups according to their MADRS scores: no depression, mild depression, and moderate-to-severe depression. All patients underwent positron emission tomography (PET) using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane. The PET images were normalized, and differences in the regional standardized uptake value ratios (SUVRs) for each side of the caudate, putamen, globus pallidus, thalamus, and ventral striatum were analyzed and compared between the three groups. A trend analysis was performed across the groups to discern any associations between SUVR values of the basal ganglia and depression severity. The SUVR values of the caudate, anterior caudate nuclei, and ventral striatum declined as MADRS increased. The SUVR values of the striatum showed an inverse dose-dependent trend of antero- and ventroposterior gradient across the groups. This result indirectly revealed the involvement of the associative and limbic circuitry of the brain that are modulated by monoamines in early PD with depression. This might suggest an in vivo causal relationship between the ventral striatum, caudate and depression.ope

Temporal trajectory of biofluid markers in Parkinson's disease

Full dynamics of biofluid biomarkers have been unknown in patients with Parkinson's disease (PD). Using data from 396 PD patients and 182 controls in the Parkinson's Progression Markers Initiative (PPMI) database, we estimated long-term temporal trajectories of CSF α-synuclein (α-syn), amyloid-β (Aβ), total tau (t-tau), phosphorylated tau (p-tau) and serum neurofilament light chain (NfL) by integrating function between the baseline levels and annual changes. At baseline, PD patients showed lower CSF α-syn, Aβ, t-tau and p-tau levels than those of the controls. In all PD patients, CSF α-syn and Aβ decreased in a negative exponential pattern before the onset of motor symptoms, whereas CSF t-tau and p-tau, and serum NfL increased. Patients with cognitive impairment exhibited faster decline of Aβ and α-syn and faster rise of t-tau, p-tau and NfL, when compared to those without. Similarly, low Aβ group showed earlier decline of α-syn, faster rise of t-tau, p-tau and NfL, and faster decline of cognitive performances, when compared to high Aβ group. Our results suggest that longitudinal changes in biomarkers can be influenced by cognitive impairment and Aβ burden at baseline. PD patients with Aβ pathology may be associated with early appearance of α-synuclein pathology, rapid progression of axonal degeneration and neurodegeneration, and consequently greater cognitive decline.ope

원발성 가역적뇌혈관수축증후군에 의한 가역적후뇌병증

Background: Reversible cerebral vasoconstriction syndrome (RCVS) is an underdiagnosed disease characterized by severe headaches with or without seizures, focal neurological deficits, and constriction of cerebral arteries which resolves spontaneously in 1-3 months. Posterior reversible encephalopathy syndrome (PRES) is typically characterized by headache, altered mental functioning, seizures, and visual loss associated with imaging findings of bilateral subcortical and cortical edema with a predominantly posterior distribution. Case Report: We present 49-year-old and 46-year-old females with thunderclap headache and seizure. MRI shows reversible cortical and subcortical lesions in both fronto-parieto-occipital lobes. And magnetic resonance angiography shows reversible multifocal luminal narrowing of distal cerebral vessels. Conclusion: Primary RCVS may occur as a cause of PRES. We report two cases of non-hypertensive PRES with seizure due to primary RCVS presenting thunderclap headache.ope

Novel Ferritin Light Chain Gene Mutation in a Korean Patient with Neuroferritinopathy

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PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects

BACKGROUND: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using 11C-PBR28. Total distribution volume (VT, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression. RESULTS: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen's d = 0.64, p = .038, 95% CI 0.04-1.24) and ACC (d = 0.60, p = .049, 95% CI 0.001-1.21), though these comparisons missed the corrected threshold for statistical significance (α = .025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers. CONCLUSIONS: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.ope

Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study

Background: Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS. Materials and methods: A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes. Results: The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p < 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008). Conclusions: This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.ope

Impact of Prolonged Temporal Discrimination Threshold on Finger Movements of Parkinson's Disease

INTRODUCTION: Sensory information is essential for the precise control of movement. Patients with Parkinson's disease (PD) have higher-order sensory dysfunctions including prolonged temporal discrimination threshold (TDT). However, the impact of prolonged TDT on parkinsonian motor deficits is uncertain. METHODS: This study includes 33 PD patients and 24 healthy controls. TDT values were measured in the index finger. Using coin rotation task (CRT), dexterous finger movement was assessed. Using an inertial sensor, the speed, amplitude, and frequency of finger tapping were measured. The impact of prolonged index finger TDT on two different finger movements was analyzed using the general estimating equation. RESULTS: Compared to healthy controls, TDT was prolonged in the PD patients. There was no impact of TDT on mean values or decrement for amplitude and speed, as well as mean values, decrement and variability of tapping frequency. However, prolonged TDT had a significant impact on the variability in amplitude (B = 436.905 × 10-4, Wald χ2 = 9.140, p = 0.014) and speed (B = 425.655 × 10-4, Wald χ2 = 9.876, p = 0.014) of finger tapping. There was a marginal correlation between TDT and CRT. In addition, CRT correlated with variability in amplitude and speed of finger tapping. CONCLUSION: In PD, cutaneous temporal discriminative sensory dysfunction appears to be related to increased variabilities in the speed and amplitude of fast repetitive finger movements and disturbed finger dexterity.ope

Presynaptic Dopaminergic Dysfunction Was Overestimated in Huntington's Disease Presenting as Young Age-Onset Parkinsonism

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Premorbid cancer and motor reserve in patients with Parkinson's disease

Decreased cancer risk has been reported in patients with Parkinson's disease (PD), and cancer prior to PD can have a protective effect on PD risk. We investigated cancer history prior to PD diagnosis to determine if such history can enhance motor reserve in PD by assessing the association between motor deficits and striatal subregional dopamine depletion. A total of 428 newly diagnosed, drug-naïve PD patients was included in the study. PD patients were categorized into three groups of no prior neoplasia, premorbid precancerous condition, and premorbid malignant cancer before PD diagnosis. Parkinsonian motor status was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) motor score and modified Hoehn and Yahr stage score. All patients underwent positron emission tomography (PET) with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (18F-FP-CIT), and the regional standardized uptake value ratios (SUVRs) were analyzed with a volume-of-interest template among the groups. The UPDRS motor score negatively correlated with SUVRs in the posterior putamen for all patient groups. Groups with neoplasia, especially those with premorbid cancer, showed lower motor scores despite similar levels of dopamine depletion in the posterior putamen relative to those without neoplasia. These results suggest that premorbid cancer acts as a surrogate for motor reserve in patients with PD and provide imaging evidence that history of cancer has a protective effect on PD.ope

Decreased thalamic monoamine availability in drug-induced parkinsonism

Drug-induced parkinsonism (DIP) is caused by a dopamine receptor blockade and is a major cause of misleading diagnosis of Parkinson's disease (PD). Striatal dopamine activity has been investigated widely in DIP; however, most studies with dopamine transporter imaging have focused on the clinical characteristics and prognosis. This study investigated differences in striatal subregional monoamine availability among patients with DIP, normal controls, and patients with early PD. Thirty-five DIP patients, the same number of age-matched PD patients, and 46 healthy controls were selected for this study. Parkinsonian motor status was examined. Brain magnetic resonance imaging and positron emission tomography with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were performed, and the regional standardized uptake values were analyzed with a volume-of-interest template and compared among the groups. The groups were evenly matched for age, but there were numerically more females in the DIP group. Parkinsonian motor symptoms were similar in the DIP and PD groups. Monoamine availability in the thalamus of the DIP group was lower than that of the normal controls and similar to that of the PD group. In other subregions (putamen, globus pallidus, and ventral striatum), monoamine availability in the DIP group and normal controls did not differ and was higher than that in the PD group. This difference compared to healthy subject suggests that low monoamine availability in the thalamus could be an imaging biomarker of DIP.ope