Myung Sik Lee

Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a meta-analysis of 53 cases including four present cases.

BACKGROUND Chorea associated with non-ketotic hyperglycemia and high signal intensity lesions on T1-weighted brain magnetic resonance images (C-H-BG) is recognized as a unique syndrome that affects elderly women exclusively. However, its overall clinical features are unclear. MATERIAL AND METHODS The literature describing patients with C-H-BG from 1985 to 2001 was reviewed using MEDLINE. Their clinical features and those of four patients with C-H-BG at this hospital were analyzed. RESULTS This study included 49 patients from the literature and four patients at this hospital. Their mean age at the onset was 71.1 years (range=22-92 years). Women were affected more frequently than men (men/women=17:30). The mean serum glucose level measured after the onset of chorea was 481.5 mg/dl (ranging from 169 to 1264), HbA1c level was 14.4% (ranging from 9.9 to 19.2), and the serum osmolarity was 305.9 mmol/kg (ranging from 291 to 335). Forty-seven patients developed hemichorea. Six patients developed bilateral chorea, and magnetic resonance imaging (MRI) showed bilateral basal ganglia lesions. MRI showed that putamen was involved in all cases (isolated putamen=31 patients, additional basal ganglia lesions=22 patients). None had lesions confined to the caudate nucleus or the globus pallidus. In all, except one, the anterior limb of the internal capsule was spared. Follow-up MRI studies were performed in 22 patients. In most, hemichorea improved along with the disappearance of the lesions. In 39 patients, chorea had ameliorated completely. The remaining 14 cases showed some improvement during the follow-up period. The chorea recurred in seven patients. CONCLUSION C-H-BG is a benign disorder affecting the elderly. It affects men much more frequently than has been reported. The high signal intensity basal ganglia lesion on the T1-weighted brain MRI study was reversible, and correlated with the clinical improvement in chorea.

Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson's disease is related to disability of the patients.

We investigated neuronal number and size in the pars compacta of the pedunculopontine nucleus (PPN) in Parkinsons disease (PD). In PD, the number of Luxol fast blue (LFB) neurons was reduced by 27% from the mean control value (p=0.04) and the cholinergic (choline acetyltransferase, ChAT-positive) neuron number was reduced by 36% (p=0.03). In addition to neuronal loss, the remaining neurons in the PPN in PD were smaller than in controls. The profile area of LFB neurons was reduced by 14% (p=0.009) and that of ChAT-positive neurons by 26% (p=0.001). There was more severe loss of ChAT-positive neurons with a more severe stage of the disease, evaluated by the modified Hoehn and Yahr scale (r=-0.66, p=0.03). The neuron number decreased much more than could be expected on the basis of decrease in cell size alone.

Dystonia after head trauma

Dystonia is a rare consequence of head trauma. We describe 10 such cases and review 19 similar patients reported in the literature. Twenty-two of the 29 patients suffered head injury during the first or second decade of life. There was a variable delay between the head trauma and the onset of dystonia. In 18 cases with severe head injury, this interval (median, 18 months; range, 1 month to 9 years) was longer than in 11 cases with mild head injury (median, 14 days; range, 3 days to 5 years). In our series, nine of the 10 cases started as a focal dystonia and one as a hemidystonia. The dystonia progressed and spread over several months or years. Two cases remained as focal dystonias, but the others developed segmental, hemi-, multifocal, or generalized dystonia. On brain imaging studies (CT or MRI), the most frequent lesion site was in the contralateral basal ganglia or thalamus, but two cases had normal brain scans. Dysfunction of the lenticulothalamic neuronal circuit seems to be related to the development of dystonia following head trauma.

Analysis of PARK genes in a Korean cohort of early-onset Parkinson disease

Mutations in five PARK genes (SNCA, PARKIN, DJ-1, PINK1, and LRRK2) are well-established genetic causes of Parkinson disease (PD). Recently, G2385R substitution in LRRK2 has been determined as a susceptibility allele in Asian PD. The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of the aforementioned genes was studied using multiple ligation-dependent probe amplification. We found four patients with PARKIN mutations, which were homozygous deletion of exon 4, compound heterozygous deletion of exon 2 and exon 4, heterozygous deletion of exon 4, and heterozygous nonsense mutation (Q40X). Four patients had PINK1 mutations; a compound heterozygous mutation (N367S and K520RfsX522) and three heterozygous mutations (G32R, R279H, and F385L). A missense mutation of SNCA (A53T) was found in a familial PD with autosomal dominant inheritance. Nine patients (12.5%) had heterozygous G2385R polymorphism of LRRK2, whereas none had G2019S mutation. However, no mutations were detected in DJ-1 and UCHL1 in our series. We identified genetic variants in PARKIN, PINK1, LRRK2, and SNCA as a cause or genetic risk factors for PD in 25% of Korean EOPD, and mutation of PARKIN was the most common genetic cause.

In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum

To determine the in vivo cortical spreading pattern of tau and amyloid and to establish positron emission tomography (PET) image‐based tau staging in the Alzheimer disease (AD) spectrum.

123I-IPT brain SPECT study in essential tremor and Parkinson’s disease

Objective: To investigate nigral neuronal damage in patients with isolated postural tremor and those with postural and rest tremor without parkinsonism. Methods: Using [123I]-N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β-(4-chlorophenyl) tropane SPECT, we measured the basal ganglia-occipital cortex/occipital cortex ([BG-OCC]/OCC) uptake ratios in 21 control subjects and patients with isolated postural tremor (n = 9), postural and rest tremor (n = 6), and PD (n = 11). Results: In the patients with PD, the means (±SD) of the (BG-OCC)/OCC ratios of the ipsilateral (2.35 ± 0.37) and the contralateral (1.97 ± 0.33) sides to the more severely affected limbs were significantly lower than the mean of the bilateral (BG-OCC)/OCC ratios of the age-matched control subjects (3.83 ± 0.66). The mean (±SD) of the bilateral (BG-OCC)/OCC ratios of the patients with isolated postural tremor (3.60 ± 0.83) was comparable with that of the age-matched control subjects. However, the mean (±SD) of the bilateral (BG-OCC)/OCC ratios of the patients with postural and rest tremor (2.61 ± 0.18) was lower than that of the control subjects (p < 0.05). The mean of the bilateral (BG-OCC)/OCC ratios of the patients with postural and rest tremor was comparable with that of the side ipsilateral to the severely affected limbs of the patients with PD. However, it was higher than that of the side contralateral to the limbs more severely affected by PD. Four of the six patients with postural and rest tremor had (BG-OCC)/OCC ratios lower than 2 standard deviations from the mean of the age-matched control subjects. Conclusions: Later in their clinical courses, some patients with postural tremor may acquire rest tremor in association with mild substantia nigra neuronal loss.

Topographical distribution of cerebral cortical thinning in patients with mild Parkinson's disease without dementia.

The pathology of Parkinsons disease (PD) is not confined to the brainstem regions, but spreads to involve the neocortical areas. Using surface‐based cortical thickness analysis, we studied the topographical distribution of cortical thinning in nondemented patients with mild PD. The high‐resolution magnetic resonance imaging (MRI) studies were performed in 48 patients with PD without dementia and 56 age‐matched healthy controls. Using the Freesurfer software, surface‐based analysis was done to find changes in cerebral cortical thickness in patients with PD. Compared to the controls, patients with PD showed significant cortical thinning in the temporal, inferior parietal, rostral frontal, and orbitofrontal cortical areas. Thinning of the cerebral cortex occurs even in nondemented patients with mild PD, and its topographical distribution was similar to that of the neocortical Lewy bodies. Further studies are needed to find pathological and clinical correlates of thinned cerebral cortex found in nondemented patients with mild PD.

Tau PET in Alzheimer disease and mild cognitive impairment.

Objective: To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using 18F-AV-1451 PET. Methods: We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as 18F-florbetaben (for amyloid) and 18F-AV-1451 (for tau) PET scans. By using the regional volume-of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy. Results: 18F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, 18F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of 18F-AV-1451 binding, especially in the medial temporal regions. The 18F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex. Conclusions: Tau PET imaging with 18F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than β-amyloid.

Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: Report of seven patients and a meta-analysis

We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae.

“Off” gait freezing and temporal discrimination threshold in patients with Parkinson disease

Objective: To investigate the relationship between temporal discrimination threshold (TDT) and “off” period gait freezing (OGF) in patients with fluctuating Parkinson disease (PD). Methods: TDT values were measured at the dorsum of the toes in 11 control subjects and 22 patients with PD with a wearing-off phenomenon (16 patients with OGF and 6 patients without OGF). Results: During the l-dopa “off” period, TDT values increased abnormally in both patient groups but were significantly higher in patients with OGF than in those without OGF. A positive correlation was found between the severity of OGF and TDT values measured by different point stimulation. In patients with OGF, a single dose of l-dopa treatment normalized TDT values and ameliorated OGF. Conclusions: Dopa-responsive abnormal discriminative sensory processing may be a possible cause of “off” period gait freezing observed in patients with fluctuating Parkinson disease.