Kyoung Gyu Choi

Different clinical and magnetic resonance imaging features between Charcot–Marie–Tooth disease type 1A and 2A

Charcot-Marie-Tooth disease type 1A (CMT1A) is the more frequent cause of demyelinating CMT, and CMT2A is the most common cause of axonal CMT. We conducted a magnetic resonance imaging (MRI) study on 39 CMT1A and 21 CMT2A patients to compare their neuroimaging patterns and correlate with clinical features. CMT1A patients showed selective fatty infiltration with a preference for anterior and lateral compartment muscles, whereas CMT2A patients showed a preference for superficial posterior compartment muscles. Early-onset CMT2A patients showed more severe leg fatty atrophy than late-onset CMT2A patients. In late-onset CMT2A, soleus muscle was the earliest, and most severely affected than the other leg muscles. Selective involvement of intrinsic foot muscles is a characteristic pattern of minimal CMT1A and CMT2A. Our MRI study demonstrates different patterns of fatty infiltration involving superficial posterior compartment muscles in CMT2A (partial T-type), and peroneal nerve innervated muscles in CMT1A (P-type).

A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's Disease

OBJECTIVE: To assess the efficacy and safety of Cerebrolysin over 4 weeks in patients with probable Alzheimers disease (AD).

Multiplex analysis of cytokines in the serum and cerebrospinal fluid of patients with Alzheimer's disease by color-coded bead technology.

Background and purpose The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimers disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests. Methods In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinsons disease [PD]). Results MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group. Conclusions The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.

A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss is linked to an autosomal dominant mutation in MYH14

Both peripheral neuropathy and distal myopathy are well‐established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. A complex phenotype of peripheral neuropathy, myopathy, hoarseness, and hearing loss was diagnosed in a large autosomal dominant Korean family. A high density single nucleotide polymorphism (SNP)‐based linkage study mapped the underlying gene to a region on chromosome 19q13.3. The maximum multipoint LOD score was 3.794. Sequencing of 34 positional candidate genes in the segregating haplotype revealed a novel c.2822G>T (p.Arg941Leu) mutation in the gene MYH14, which encodes the nonmuscle myosin heavy chain 14. Clinically we observed a sequential pattern of the onset of muscle weakness starting from the anterior to the posterior leg muscle compartments followed by involvement of intrinsic hand and proximal muscles. The hearing loss and hoarseness followed the onset of distal muscle weakness. Histopathologic and electrodiagnostic studies revealed both chronic neuropathic and myopathic features in the affected patients. Although mutations in MYH14 have been shown to cause nonsyndromic autosomal dominant hearing loss (DFNA4), the peripheral neuropathy, myopathy, and hoarseness have not been associated with MYH14. Therefore, we suggest that the identified mutation in MYH14 significantly expands the phenotypic spectrum of this gene. Hum Mutat 32:1–9, 2011.

Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2

The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.

Comparison between Clinical Disabilities and Electrophysiological Values in Charcot-Marie-Tooth 1A Patients with PMP22 Duplication

Background and Purpose Charcot-Marie-Tooth disease (CMT) type 1A (CMT1A) is the demyelinating form of CMT that is significantly associated with PMP22 duplication. Some studies have found that the disease-related disabilities of these patients are correlated with their compound muscle action potentials (CMAPs), while others have suggested that they are related to the nerve conduction velocities. In the present study, we investigated the correlations between the disease-related disabilities and the electrophysiological values in a large cohort of Korean CMT1A patients. Methods We analyzed 167 CMT1A patients of Korean origin with PMP22 duplication using clinical and electrophysiological assessments, including the CMT neuropathy score and the functional disability scale. Results Clinical motor disabilities were significantly correlated with the CMAPs but not the motor nerve conduction velocities (MNCVs). Moreover, the observed sensory impairments matched the corresponding reductions in the sensory nerve action potentials (SNAPs) but not with slowing of the sensory nerve conduction velocities (SNCVs). In addition, CMAPs were strongly correlated with the disease duration but not with the age at onset. The terminal latency index did not differ between CMT1A patients and healthy controls. Conclusions In CMT1A patients, disease-related disabilities such as muscle wasting and sensory impairment were strongly correlated with CMAPs and SNAPs but not with the MNCVs or SNCVs. Therefore, we suggest that the clinical disabilities of CMT patients are determined by the extent of axonal dysfunction.

X-linked dominant Charcot-Marie-Tooth disease with connexin 32 (Cx32) mutations in Koreans.

Kim Y, Choi K‐G, Park KD, Lee KS, Chung KW, Choi B‐O. X‐linked dominant Charcot‐Marie‐Tooth disease with connexin 32 (Cx32) mutations in Koreans.

Anatomical correlates of primary progressive aphasia subtypes using SPGR 3D volumetric analysis

to that of AD. Compared with patiens with AD, the PIB-positive SVaD group exhibited more PIB retention in bilateral peri-rolandic area and mid-cerebellar peduncle, where there is known to be rarely involved in AD. Conclusions: PIB-positive SVaD had a similar but also different distribution of amyloid deposition in the cerebral cortex from AD. Small vessel disease associated with SVaD may alter the distribution of amyloid deposition in the cortex.

IC-P-121: Effects of cerebrovascular risk factors in subcortical ischemic hyperintensities in Alzheimer’s disease

Background: Subcortical ischemic hyperintensities (SIH) in MRI are divided into deep white matter (DWM), periventricular white matter (PVWM) and deep gray matter (DGM) regions. These regional SIH have been proposed to have different etiologies in development. The cerebrovascular risk factors (CvRF) are known to play a causative role in these lesions in AD, but relations are still uncertain. Objectives: We aimed to find out correlations between each regional SIH to cerebrovascular risk factors in AD. Methods: One hundred twenty-seven patients diagnosed as clinical probable AD using NINCDS-ADRDA criteria were recruited. All patients underwent Brain MRI, laboratory evaluation, neurologic examination, semi-structured interview for dementia, and neuropsychological test battery. Hyperintensities were assessed with MR FLAIR, T2-W and T1-W images. Hypertension, diabetes mellitus, hypercholesterolemia, ischemic heart disease, valvular heart disease, history of heart surgery, smoking, heavy alcohol and previous stroke history were evaluated for correlation to SIH. Results: The mean ages were 75.8 8.7 years, with the mean MMSE scores of 19 6, Hachinski’s ischemic scales of 3.7 2.9 and CDR of 1.3 0.8. Frequencies of hypertension, diabetes mellitus and previous stroke were 43.9%, 21% and 12.3%. SIHs were frequently observed, raging from 84% (DWMH) to 100% (PVWM). Positive correlations were DGM to smoking, alcohol, previous stroke history (p 0.05) and DWM to hypertension (p 0.05). PVWM were not related with any risk factors. Analysis between AD with and without stroke group revealed, lower MMSE, higher CDR scores and higher SIH prevalence in DGM in AD with stroke group (p 0.05). Conclusions: The presence of CvRF affects the presence of hyperintensities in gray and deep, but not in PVWM in AD. Regarding the cerebrovascular disease progresses as the aging and dementic symptoms with Alzheimer’s disease, appropriate intervention is warranted to halt neurodegenerative process in AD with CVD.