K.S. Park

Brain abnormalities in neuromyelitis optica

BACKGROUND Differentiating neuromyelitis optica (NMO) from multiple sclerosis (MS) is a real challenge in the clinical field. In the past, NMO (not MS), was inferred when abnormality was not detected in the brain magnetic resonance imaging (MRI). Recently, some studies have reported abnormalities in the brain MRIs of NMO, but only few among the Asian population. The aim of this study was to evaluate the frequency of brain MRI among Korean NMO patients and characterize findings that might be helpful to distinguish NMO from MS. METHODS Medical records, NMO-IgG, and brain MRI of 17 patients diagnosed with NMO by the revised diagnostic criteria of Wingerchuk et al. (2006) [6] from 2008 to 2010, were reviewed. RESULTS 11 out of 17 patients (64.7%) had abnormal MRI findings. More than two lesions were detected in most patients. The majority of patients with brain MRI abnormality showed nonspecific (5 patients) or atypical (6 patients) findings. Cerebral white matter was most frequently involved (58.8%). 3 patients (17.6%) involved corpus callosum, 4 (23.5%) with internal capsule, 2 (11.8%) with cerebellum, and 3 (17.6%) with brainstem. There were 5 (29.4%) patients who met the Paty et al. criteria (1988) [15] and 3 patients (35.3%) who met the multiple sclerosis (MS) spatial distribution diagnostic criteria of Barkhof et al. (1997) [14] in their brain MRI. CONCLUSIONS Brain abnormalities have been frequently found among Korean NMO patients and the frequencies have been reported to be higher than that of Caucasians. Current MS spatial distribution criteria, such as Paty et al. (1988) [15] or Barkhof et al. (1997) [14], are not sufficient to discriminate NMO from MS in brain MRI findings. Our results will provide valuable information that would be useful in establishing future revising criteria for NMO.

Exercise-induced cramp, myoglobinuria, and tubular aggregates in phosphoglycerate mutase deficiency

We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise‐induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests produced subnormal increases of venous lactate. Muscle biopsies showed subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were markedly decreased (3% of the normal mean) and molecular genetic studies showed that both patients were homozygous for a described missense mutation (W78X). A review of 15 cases with tubular aggregates in the muscle biopsies from our laboratory and 15 cases with PGAM deficiency described in the literature showed that this clinicopathological triad is highly suggestive of PGAM deficiency. Muscle Nerve, 2006

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants

Introduction: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). Methods: We evaluated the pattern difference of intrinsic hand muscles of upper limb‐onset ALS (UL‐ALS), upper limb‐onset progressive muscular atrophy (UL‐PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. Results: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL‐ALS than other variants, but a considerable proportion of UL‐ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL‐ALS. Conversely, an absent ADM CMAP was identified only in UL‐PMA and BAD. Conclusions: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS. Muscle Nerve 51: 333–337, 2015

Nocturnal hypoxia in ALS is related to cognitive dysfunction and can occur as clusters of desaturations.

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to progressive weakness of the respiratory and limb muscles. Consequently, most patients with ALS exhibit progressive hypoventilation, which worsens during sleep. The aim of this study was to evaluate the relationship between nocturnal hypoxia and cognitive dysfunction and to assess the pattern of nocturnal hypoxia in patients with ALS. Method Twenty-five patients with definite or probable ALS underwent neuropsychologic testing, nocturnal pulse oximetry, and capnography. Patients were grouped according to the presence of nocturnal hypoxia (SpO2<95% for ≥10% of the night) and their clinical characteristics and cognitive function were compared. Results Compared to patients without nocturnal hypoxia, those with nocturnal hypoxia (n = 10, 40%) had poor memory retention (p = 0.039) and retrieval efficiency (p = 0.045). A cluster-of-desaturation pattern was identified in 7 patients (70%) in the Hypoxia Group. Conclusions These results suggest that nocturnal hypoxia can be related to cognitive dysfunction in ALS. In addition, a considerable number of patients with ALS may be exposed to repeated episodes of deoxygenation–reoxygenation (a cluster-of-desaturation pattern) during sleep, which could be associated with the generation of reactive oxygen species. Further studies are required to define the exact causal relationships between these phenomena, the exact manifestations of nocturnal cluster-of-desaturation patterns, and the effect of clusters of desaturation on ALS progression.

Effect of JGK-263 as a new glycogen synthase kinase-3β inhibitor on extrinsic apoptosis pathway in motor neuronal cells

Glycogen synthase kinase-3β (GSK-3β) has been identified as one of the important pathogenic mechanisms in motor neuronal death. GSK-3β inhibitor has been investigated as a modulator of apoptosis and has been shown to confer significant protective effects on cell death in neurodegenerative diseases. However, GSK-3β is known to have paradoxical effects on apoptosis subtypes, i.e., pro-apoptotic in mitochondrial-associated intrinsic apoptosis, but anti-apoptotic in death receptor-related extrinsic apoptosis. In this study, we evaluated the effect of a new GSK-3β inhibitor (JGK-263) on motor neuron cell survival and apoptosis, by using low to high doses of JGK-263 after 48 h of serum withdrawal, and monitoring changes in extrinsic apoptosis pathway components, including Fas, FasL, cleaved caspase-8, p38α, and the Fas-Daxx interaction. Cell survival peaked after treatment of serum-deprived cells with 50 μM JGK-263. The present study showed that treatment with JGK-263 reduced serum-deprivation-induced motor neuronal apoptosis by inactivating not only the intrinsic, but also the extrinsic apoptosis pathway. These results suggest that JGK-263 has a neuroprotective effect through effective modulation of the extrinsic apoptosis pathway in motor neuron degeneration.

A novel splicing mutation (c.870+3A>G) in SPG4 in a Korean family with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of genetically heterogenous neurodegenerative disorders characterized by progressive spasticity and weakness of both lower extremities. Herein, we report a novel splicing mutation (c.870+3A>G) in SPG4 in a Korean family with an autosomal dominant-inherited pure HSP. The mutation is located in intron 5, and results in a deletion of the 188bp-sized exon 5. It is likely that the exon 5 deletion leads to spastin dysfunction and cause the typical symptoms and signs of patients.

Is thyrotoxic periodic paralysis a disease caused by muscle membrane dysfunction

Introduction: Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of reversible paralysis with hyperthyroidism. It is clinically similar to hypokalemic periodic paralysis (HOPP), which features significant ion‐channel dysfunction and reduced muscle fiber conduction velocity (MFCV). However, the muscle membrane function in TPP is not known. Methods: For 13 patients with TPP and 15 age‐matched controls, clinical assessment and serial neurophysiological testing, including nerve conduction, prolonged exercise (PE) testing, and MFCV. were performed. Results: MFCV values were elevated up to 1 year from the paralytic attack in TPP patients. In the group with a positive PE test, MFCV values were higher. There was no significant relationship between MFCV values and either hypokalemia or hyperthyroidism. Conclusions: Although clinical manifestations in TPP are similar to those observed in HOPP, TPP appears to feature an alternate pathogenic mechanism. Specifically, MFCV values increased rather than decreased. Further studies are needed to support these findings. Muscle Nerve, 2016 Muscle Nerve 56: 780–786, 2017

P566: Factors associated with the time to next attack in neuromyelitis optica: accelerated failure time models with random effects

S.-M. Kim1, S.-Y. Park2, J.Y. Kim3, J.-J. Sung1, K.S. Park3, O. Kwon4, S.H. Kim5, J. Park5, K.-W. Lee1 1Seoul Nationl University Hospital, Neurology, Seoul, Republic of Korea; 2National cancer center, Neurology, Seoul, Republic of Korea; 3Seoul National University, Bundang Hospital, Neurology, Gyeonggi, Republic of Korea; 4Eulji General Hospital, Neurology, Seoul, Republic of Korea; 5Seoul National University Hospital, Medical Research Collaborating Center, Seoul, Republic of Korea

P7-3 Motor unit number estimation in evaluating disease progression in patients with amyotrophic lateral sclerosis

Therefore, we investigated differences in electrophysiological findings and clinical symptoms of ALS by comparing patients with rapid and slow clinical courses. In 40 ALS patients, 14 patients showed a clinical course lasting less than one year and 13 patients showed a clinical course lasting more than three years. The mean interval from onset to diagnosis of ALS patients with a rapid clinical course was shorter than that of patients with a slow clinical course (4.3 months vs. 20 months P< 0.05). Patients with a rapid clinical course showed FPs in almost all muscles in the examined extremities. The muscle number showing FPs was more than that of patients with a slow clinical course (96.3% vs. 53.1% P< 0.05). However, the rate of muscle with fibs-sw between these groups did not differ significantly. Conclusion: The rate of muscle showing FPs may assist in predicting the clinical prognosis.

P7-4 Reproducibility of the motor unit number index (MUNIX) in normal and ALS subjects

Therefore, we investigated differences in electrophysiological findings and clinical symptoms of ALS by comparing patients with rapid and slow clinical courses. In 40 ALS patients, 14 patients showed a clinical course lasting less than one year and 13 patients showed a clinical course lasting more than three years. The mean interval from onset to diagnosis of ALS patients with a rapid clinical course was shorter than that of patients with a slow clinical course (4.3 months vs. 20 months P< 0.05). Patients with a rapid clinical course showed FPs in almost all muscles in the examined extremities. The muscle number showing FPs was more than that of patients with a slow clinical course (96.3% vs. 53.1% P< 0.05). However, the rate of muscle with fibs-sw between these groups did not differ significantly. Conclusion: The rate of muscle showing FPs may assist in predicting the clinical prognosis.