Myasthenia Gravis Presenting Hyperacusia and Ptosis

Myasthenia gravis (MG), which is the most common autoimmune neuromuscular junction disorder, is characterized by weakness of musdes and increased fatigability after repetitive use, and recovery after rest. The diagnosis is based on a detailed history, physical examination, and pharmacological, electrophysiological, and immunological testing. Stapedial reflex abnormalities are noted, so the stapedial reflex decay test (SRDT) can be attempted. There are no reports regarding the SRDT in Korea. We report a case of MG presenting hyperacusia and ptosis that was diagnosed by the SRDT. We recommend using the SRDT in the clinical diagnosis of MG.

Monitoring Platelet Inhibition by Clopidogrel Using Rapid Platelet Function Assay in Patients With Ischemic Stroke

BACKGROUND: Clopidogrel inhibits platelet P2Y12 adenosine diphosphate (ADP) receptors and has been widely used in patients with ischemic stroke. However, a considerable number of patients suffer from cerebrovascular events despite the use of clopidogrel. The rapid platelet function assay (RPFA) has been used for monitoring the antiplatelet effects on the P2Y12 ADP receptor. This study was performed to measure the platelet response to clopidogrel using RPFA in patients with ischemic stroke, and to identify the clinical factor related with clopidogrel resistance. METHODS: A total of 86 patients taking clopidogrel (75 mg/day) were enrolled. Demographic data, vascular risk factors, the presence of obesity and metabolic syndrome, drug history, hemoglobin, platelet counts, and stroke subtypes were recorded. RPFA presented the results as P2Y12 Reaction Units (PRU), base PRU (BASE), and Inhibition (%). Inhibition was calculated as (1-PRU/BASE)x100. The patients showing ineffective aggregation- inhibition (percentage of Inhibition < 20) on RPFA were defined as non-responders to clopidogrel. RESULTS: The response of platelet aggregation-inhibition to clopidogrel showed a variable distribution with mean and standard deviation of 32.2+/-22.3%. Twenty four (27.9%) patients showed the inhibition below 20%. There was no difference between responders and non-responders regarding the clinical factors above. We found no influence of co-medication with the statins on platelet response to clopidogrel. CONCLUSIONS: There is a patient variability in response to clopidogrel and a considerable portion of stroke patients have clopidogrel resistance on the platelet function test. The clinical usefulness of routine platelet function test requires further validation.

Pneumocephalus in Patients With Orthostatic Headache

Cerebrospinal fluid (CSF) leak or shunt overdrainage is a well-known cause of orthostatic headaches and low CSF pressures. We report two cases of orthostatic headache with pneumocephalus on brain imaging. The orthostatic headache developed after drainage of spinal operation site and epidural block. Brain MRI revealed characteristic findings of CSF hypovolemia including pachymeningeal enhancement and mild subdural fluid collections. Air was also observed in the ventricular or subarachnoid space in both patients, which might enter the subarachnoid or ventricular space during a procedure via the pressure gradient or an injection.

3-Dimensional Analyses of Eye Motion in Oculopalatal Tremor

BACKGROUND: Oculopalatal tremor (OPT) is a delayed complication of damage to the dentato-rubro-olivary pathway (Guillain-Mollaret triangle) and subsequent hypertrophic olivary degeneration. Mixed torsional-vertical pendular nystagmus in OPT has been considered to signify unilateral brainstem damage while symmetrical vertical nystagmus has been regarded to indicate bilateral disease. However, 3-dimensional oculographic analysis of OPT has been sparse. METHODS: In 8 patients with OPT; binocular 3-dimensional analyses of ocular oscillations were performed by using a magnetic search coil technique. Lateralization of the lesions was determined by the imaged olivary hypertrophy in the MRI. RESULTS: One patient had conjugate vertical pendular nystagmus and four showed mixed torsional-vertical pendular nystagmus. Two patients showed mixed horizontal-torsional-vertical nystagmus. One patient had predominantly horizontal pendular nystagmus. MRI demonstrated increased signal or hypertrophy of the inferior olivary nucleus, unilateral in six and bilateral in two. Unilateral olivary changes were associated with mixed torsional-vertical nystagmus in three patients, mixed horizontal-torsional-vertical nystagmus in another two patients, and predominantly horizontal pendular nystagmus in the remaining one patient. Bilateral olivary changes were visible in one patient with conjugate vertical pendular nystagmus and in the other patient with mixed torsional-vertical nystagmus. Palatal tremor appeared to be symmetrical in all patients. CONCLUSIONS: Three-dimensional analyses of OPT indicate that conjugate vertical and mixed torsional-vertical pendular nystagmus do not correspond to the laterality of signal changes in the inferior olivary nucleus. Ocular oscillations often have all the vertical, horizontal and torsional components.

Korean Familial Amyotrophic Lateral Sclerosis Family with a Novel Gly10Val Mutation in the SOD1 Gene

BACKGROUND: Approximately 5 to 10% of amyotrophic lateral sclerosis (ALS) patients have recorded family history (FALS) and in most cases, the pattern of inheritance is autosomal dominant (DFALS). Twenty percent of DFALS families are linked to chromosome 21q22.1, which is associated to a mutation in the Cu/Zn superoxide dismutase (SOD1) gene. However, these cases, especially with SOD1 gene mutations have not yet been reported in Korea. We investigated the clinical features of familial ALS pedigrees and screened the SOD1 gene in search of potential mutations. METHODS: The clinical histories and neurological findings of the family members were obtained. Genomic DNA was extracted from leukocytes of whole blood samples and PCR and direct sequencing analyzed the coding region of the SOD1 gene. RESULTS: Five affected members in a three-generation family exhibited early onset and rapid progression. The family has a novel missense mutation in the SOD1 gene, which was heterozygous for point mutation GGC to GTT, causing a substitution of valine for glycine at codon 10 (Gly10Val) in exon 1. CONCLUSIONS: Familial ALS with a novel Gly10Val mutation in the SOD1 gene showed severe clinical features. The mutation lies in a region involved in a dimer contact in the third-dimensional structure of the SOD1 protein. This study is the first report of familial ALS cases in Korea and contributes to expand the number of ALS-associated SOD1 gene mutations.

Extracellular Toxicity of Motor Neuronal Cells Expressing Mutant Cu/Zn Superoxide Dismutase in Familial ALS Cell Line Model

BACKGROUND: The objective of this study is to identify the extracellular toxicity of motor neuronal cells expressing mutant copper-zinc superoxide dismutase in the model of familial amyotrophic lateral sclerosis (FALS), and to investi-gate their possible mechanisms in motor neuron death. METHODS: We have set up a model for FALS by transfecting the motor neuron cell line VSC4.1 with plasmids directing the constitutive expression of either wild-type human Cu/Zn superoxide dismutase or a mutant of this enzyme, G93A. The co-culture model of motor neuronal cells expressing both mutant and wild-type Cu/Zn superoxide dismutases were used. Cell toxicity was induced by aphidocholin and viability was determined by a MTT assay. The observed values were compared with predictive values in G93A+VSC4.1 as well as WT+VSC4.1 co-culture groups. RESULTS: In the co-culture group with G93A and VSC4.1, the observed cell viability was significantly lower than what was predicted, suggesting that the G93A affected the viability of VSC4.1. However, in the co-culture group with WT and VSC4.1, WT did not decrease the viability of VSC4.1. CONCLUSIONS: The G93A cells have extracellular toxicity, which could be a result of some kind of cell-to-cell communications between motor neuronal cells.