Sook Keun Song

A randomized trial of mesenchymal stem cells in multiple system atrophy

Neuroprotective or regenerative strategies are invaluable in multiple system atrophy (MSA) due to its rapid progression with fatal prognosis. We evaluated the efficacy of autologous mesenchymal stem cells (MSC) in patients with MSA‐cerebellar type (MSA‐C).

The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status.

Background: Cognitive dysfunction is common in Parkinsons disease (PD), and along with PD with dementia (PDD), the concept of mild cognitive impairment in PD (PD‐MCI) has been introduced. Methods: To identify structural candidates according to cognitive status in PD, we compared gray matter (GM) density across PD‐intact cognition (PD‐IC, n = 23), PD‐MCI (n = 27), and PDD (n = 18) using voxel‐based morphometry. Results: The demographic data among PD subjects were similar, however, general cognition and disease duration were more severe in PD‐MCI and PDD than in PD‐IC. Compared with controls, GM density was significantly decreased in the left occipital area in PD‐IC; the bilateral temporal, left prefrontal and insular, and right occipital areas in PD‐MCI; and in widespread brain areas in PDD. Compared with PD‐IC, patients with PD‐MCI had significantly decreased GM density in the right middle frontal area, and those with PDD had decreased GM density in the right parietal, middle frontal, insular, and lentiform areas. GM density in patients with PDD was significantly decreased in the bilateral middle temporal, right inferior temporal, and left middle and superior prefrontal areas. PDD patients with shorter disease duration before dementia (<5 year) showed greater GM atrophy in the posterior cingulate area than did those with longer disease duration (≥5 year). Conclusions: These data suggest that cortical atrophy in PD exhibits a greater extent with increasing levels of cognitive impairment, and different anatomical substrates would correspond to each cognitive status.

A comparative analysis of cognitive profiles and white matter alterations using voxel-based diffusion tensor imaging between patients with Parkinson's disease dementia and dementia with Lewy bodies

Background Despite clinical and neuropsychological similarities between Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. Methods 19 patients with probable PDD and 18 patients with probable DLB who had a similar overall severity of dementia and demographic characteristics were examined by a standardised neuropsychological test and voxel-based analysis of fractional anisotropy (FA) using diffusion tensor imaging (DTI). Results The patients with DLB performed significantly worse in visual recognition memory, semantic fluency and ideomotor praxis than those with PDD (p<0.05). Compared with controls, the FA value in patients with PDD was significantly lower in bilateral frontal, left temporal and left parietal white matter. In patients with DLB, the pattern of FA reduction was similar to that of patients with PDD; however, white-matter abnormalities were more severe and extended into bilateral insular, bilateral posterior cingular and bilateral visual association regions. In a direct comparison between PDD and DLB, the FA value in patients with DLB was significantly decreased in bilateral posterior temporal, posterior cingular and bilateral visual association fibres extending into occipital areas. Conclusions Despite global similarities in cognitive performance and white-matter pathology between DLB and PDD patients, those with DLB had more severely impaired frontal and temporal area-associated cognitive subsets, and more severe white-matter pathology in temporal and visual association fibres. These data suggest that differences in the underlying nature of PDD and DLB may exist with global similarities in their cognitive performance and white-matter pathology.

Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson's disease

Background Parkinsons disease with mild cognitive impairment (PD-MCI) is a heterogeneous entity in terms of cognitive profiles and conversion to dementia. However, the risk factors for ongoing cognitive decline in patients with PD-MCI are not clearly defined. Methods 51 patients with PD-MCI were prospectively followed-up for a minimum of 2 years. Subjects were classified as MCI converters (n=15) or MCI non-converters (n=36) based on whether they were subsequently diagnosed with PD dementia. We explored cognitive profiles and neuroanatomical characteristics of PD-MCI converters using voxel based morphometry (VBM) of grey matter (GM) density and region of interest based volumetric analysis of the substantia innominata (SI). Results PD-MCI converters showed more severe cognitive deficits in frontal executive functions, immediate verbal memory and visual recognition memory compared with PD-MCI non-converters. VBM analysis revealed that PD-MCI converters had significantly lower GM density in the left prefrontal areas, left insular cortex and bilateral caudate nucleus compared with that in PD-MCI non-converters. The mean normalised SI volume was significantly smaller in both PD-MCI converters (1.19±0.35, p<0.001) and PD-MCI non-converters (1.52±0.27, p<0.001) compared with that in controls (1.87±0.19). PD-MCI converters had a significantly smaller normalised SI volume than PD-MCI non-converters (p<0.001). Conclusions Our data show that atrophy in the frontostriatal areas and cholinergic structures, as well as frontal lobe associated cognitive performance, may act as predictors of dementia in PD-MCI patients, suggesting distinctive patterns of cognitive profiles and a neuroanatomical basis for progressive PD-MCI.

A comparison of gray and white matter density in patients with Parkinson's disease dementia and dementia with Lewy bodies using voxel-based morphometry†

Despite clinical and neuropsychological similarities between Parkinsons disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. We used voxel‐based morphometry using a 3‐T MRI scanner to compare gray and white matter densities in 20 patients with probable PDD and 18 patients with probable DLB, who had similar overall severity of dementia and similar demographic characteristics. The gray matter density was significantly decreased in the left occipital, parietal, and striatal areas in patients with DLB compared with patients with PDD. The white matter density was significantly decreased in bilateral occipital and left occipito‐parietal areas in patients with DLB compared with those with PDD. The degree of white and gray matter atrophy was similar in patients with DLB; in contrast, there was markedly less atrophy in the white matter than in the gray matter in patients with PDD. On analyzing the change of WM density relative to that of GM density in patients with DLB compared to those with PDD, the area of WM atrophy in the occipital areas was more extensive than that of GM atrophy. Our data demonstrate that atrophy of both gray and white matter was more severe in patients with DLB and that white matter atrophy relative to gray matter atrophy was less severe in patients with PDD. These data may reflect a difference in the underlying nature of PDD and DLB.

Blood-brain barrier impairment is functionally correlated with clinical severity in patients of multiple system atrophy

Multiple system atrophy (MSA) has been regarded as a unique entity within the spectrum of oligodendrogliopathy. However, the pathomechanisms underlying the initial trigger and aggravating factors responsible for disease progression remain unknown. Even though the implication of blood-brain barrier (BBB) dysfunction has not been fully elucidated, this dysfunction may act as a modifier of disease progression in neurodegenerative disease. We evaluated the integrity of the BBB and its functional significance in patients with MSA using the CSF/serum albumin index (CSF-AI) and the volume transfer coefficient (K(trans)) in dynamic contrast-enhanced MRI (DCE-MRI). CSF-AI and K(trans) values increased significantly in patients with MSA compared to the control (5.1 μg vs 3.6 μg, p=0.02; 0.16/mim(-1) vs 0.05/mim(-1), p=0.001, respectively). There were positive relationships between both CSF-AI and K(trans) and unified MSA rating scale (UMSARS). K(trans) in the periventricular white matter was significantly correlated with the volume of white matter hyperintensities among all subjects (r=0.58, p=0.001) and within patients with MSA (r=0.58, p=0.019), but not within controls (r=0.42, p>0.05). In addition, a significant positive correlation was detected between CSF-AI and K(trans) (r=0.81, p=0.002). Multiple linear regression analysis showed that only UMSARS score was a significantly independent predisposing factor for CSF-AI (β=0.193, p=0.04). Our data suggest that BBB dysfunction is related to the underlying nature of MSA and its dysfunction is closely coupled to disease severity.

A Case-Control Study of Multiple System Atrophy in Korean Patients

A few case–control studies of multiple system atrophy (MSA) have been reported in Western populations. In this study, we included various epidemiological factors to evaluate whether the risk factors for MSA differed in Korean and Western populations. A total of 100 consecutive MSA patients and 104 controls at two referral hospitals participated. Information was obtained through face‐to‐face interviews using a structured questionnaire: history of living area, occupational history, food habits, alcohol and tobacco consumption, and use of drugs. Odds ratios and 95% confident intervals (OR [95% CI]) were computed using logistic regression. The multivariate logistic regression analysis revealed that use of antihypertensive medication (OR = 0.30 [0.12–0.78]) and vitamins (OR = 0.30 [0.14–0.64]) and consumption of meat and poultry (OR = 0.27 [0.13–0.56]) were associated with decreasing risk for MSA, whereas use of herbal medications (OR = 3.17 [1.28–7.84]) was associated with increasing risk for MSA. In univariate analysis adjusted for age, sex, education level, and recruitment center, use of aspirin (OR = 0.21 [0.07–0.61]) and coffee consumption (OR = 0.44 [0.23–0.84]) were significantly less frequent in MSA patients than in controls, whereas heavy smoking (≥40 pack‐years) was significantly more prevalent in MSA patients than in controls (OR = 3.44 [1.05–11.23]). There was no difference in living area, participation in farming, or exposure to agrichemicals and solvents between groups. This study showed that MSA in Korea is characterized by risk factors that are both similar to and different from those affecting Western populations and that herbal medicines constitute a new MSA risk factor for the Korean population.

Olfactory performance acts as a cognitive reserve in non-demented patients with Parkinson's disease

OBJECTIVE To explore whether olfactory performance acts as a cognitive reserve in non-demented patients with Parkinsons disease (PD). METHODS Patients with non-demented PD (n = 119) underwent T1-weighted MRI and olfactory identification tests. According to their olfactory performance, PD patients were subdivided into three groups of high score (PD-H, n = 38), middle score (PD-M, n = 48), and low score (PD-L, n = 33). We investigated the pattern of gray matter (GM) density according to olfactory performance using voxel-based morphometry (VBM) and analyzed the correlation between GM density and olfactory performance. RESULTS No significant differences in demographic characteristics were observed among the groups. A neuropsychological test showed that cognitive deficits in verbal memory function were more severe in the PD-L group than in the PD-H group. However, a VBM analysis revealed that patients in the PD-H group possessed significantly decreased GM density in the bilateral temporal areas, orbitofrontal areas, mesiofrontal areas extending into the cingulate gyrus, and prefrontal areas, compared with patients in the PD-L group. No areas exhibiting a significant difference in GM density were observed between the PD-H and PD-M groups. Olfactory performance in patients with PD was negatively correlated with both the brain GM volume and intracerebral volume; in particular, GM density in the caudate nucleus and putamen exhibited a negative correlation with olfactory performance. CONCLUSIONS Our data show that a high olfactory performance may compensate GM volume loss in order to minimize the exhibition of cognitive impairment and thus may act as a cognitive reserve in non-demented patients with PD.

Uric acid as a potential disease modifier in patients with multiple system atrophy.

Recent studies have suggested that mitochondrial dysfunction and oxidative stress play a key role in the pathogenesis of multiple system atrophy.

Palilalia, echolalia, and echopraxia–palipraxia as ictal manifestations in a patient with left frontal lobe epilepsy

Palilalia is a relatively rare pathologic speech behavior and has been reported in various neurologic and psychiatric disorders. We encountered a case of palilalia, echolalia, and echopraxia–palipraxia as ictal phenomena of left frontal lobe epilepsy. A 55‐year‐old, right‐handed man was admitted because of frequent episodes of rapid reiteration of syllables. Video‐electroencephalography monitoring revealed stereotypical episodes of palilalia accompanied by rhythmic head nodding and right‐arm posturing with ictal discharges over the left frontocentral area. He also displayed echolalia or echopraxia–palipraxia, partially responding to an examiner’s stimulus. Magnetic resonance imaging revealed encephalomalacia on the left superior frontal gyrus and ictal single photon emission computed tomography showed hyperperfusion just above the lesion, corresponding to the left supplementary motor area (SMA), and subcortical nuclei. This result suggests that the neuroanatomic substrate involved in the generation of these behaviors as ictal phenomena might exist in the SMA of the left frontal lobe.