Jeong-Geun Lim

Phenotypic variability in Kennedy's disease: implication of the early diagnostic features

Objectives –  The clinical diagnosis of Kennedys disease (KD) is not easy when the typical manifestations are lacking, especially in early stage of the disease. In our study, we tried to identify the relative frequency of common clinical features and early symptoms in KD.

Autosomal dominant nocturnal frontal lobe epilepsy and mild memory impairment associated with CHRNB2 mutation I312M in the neuronal nicotinic acetylcholine receptor

Certain paroxysmal nocturnal behaviors have been established as features of nocturnal frontal lobe epilepsy (NFLE). Despite insight into its genetics, the majority of patients with NFLE are not linked to a known mutation and clinical diagnosis remains a challenge. We describe a family presenting with stereotyped nocturnal arousals from non-rapid eye movement sleep, bilateral hand posturing, and pelvic thrusting in the mother, but subtle motor activity in the daughter, and minimal or no epileptiform EEG discharges. Despite normal IQ, there were moderate and severe verbal memory deficits in the mother and daughter, respectively. Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. Phenotypic similarities in unrelated families suggest the determining role of this mutation in NFLE, whereas different inter- and intrafamilial cognitive profiles point to other factors. The absence of clear motor features of NFLE in the daughter emphasizes the shortcomings of current clinical criteria and the potential for genetic testing to further guide clinical diagnostic criteria.

Autonomic dysfunction in patients with orthostatic dizziness: Validation of orthostatic grading scale and comparison of Valsalva maneuver and head-up tilt testing results

OBJECTIVES To investigate whether the Korean version of the Orthostatic Grading Scale (KOGS) is a reliable and valid measure for evaluating the severity of symptoms of orthostatic intolerance (OI) and to compare the diagnostic accuracy of Valsalva maneuver (VM) and head-up tilt test (HUTT) in identifying sympathetic adrenergic failure (SF). METHODS A back-translation approach was used to develop the KOGS. One hundred seventy two patients with orthostatic dizziness (OD) as a presenting symptom of OI and 133 healthy controls were enrolled. All patients completed the 5-item, self-report KOGS and 58% (100/172) of patients were randomly selected for a retest with the questionnaire. The degree of the severity of autonomic dysfunction was measured by the composite autonomic severity score (CASS). RESULTS The incidence of orthostatic hypotension (OH) in HUTT was 21%. The KOGS scores in patients showed good internal consistency (Cronbachs α=0.90) and test-retest reliability (correlation coefficient=0.77 to 0.89). The total and each item scores of KOGS correlated with the degree of the severity of autonomic dysfunction estimated as CASSs in patients. Approximately 70% (116/172) of patients showed at least one abnormality in either HUTT or VM. The incidence (43%) of an abnormal BP response in VM was two times higher than the incidence of OH in HUTT. DISCUSSION The KOGS is a reliable and valid tool for screening patients with OD. VM is superior to HUTT in detecting SF. Thus, VM and HUTT should be combined to evaluate adrenergic sympathetic function in patients with OD.

Identification of lysosomotropic compounds based on the distribution and size of lysosomes.

Lysosomal accumulation of drugs with their specific physicochemical properties is of key importance to drug distribution in the body. Several attempts have been made to treat various human diseases by employing the accumulation of lysosomal drugs, and many methods to identify lysosomal accumulation of drugs have been proposed. Among those, the use of high-content screening has increased tremendously because of improved efficiency and accuracy as well as the development of automatic image acquisition and analytical techniques. Conventional methods to identify lysosomal accumulation of drugs by evaluating changes in the lysosomal area are unable to maximize the advantages of phenotypic high-content screening. Lysosomal distribution and the size of lysosomes are affected by lysosomal accumulating drugs. Therefore, we present image acquisition conditions and analytical methods to utilize lysosomal distribution and size as parameters for identifying lysosomal accumulating drugs. These two parameters will help to improve the reliability of the screening methods for identifying lysosomal accumulation of drugs by maximizing usage of information from image-based screening.

PO6.3 Protective Effect of N-Acetylcysteine and Vitamin E against Oxidative Stress- and Glutamate-Induced Damage of Motor Neuron-Like NSC-34 Cells

Background: Amyotrophic lateral sclerosis functional rating scale (ALSFRS), an index for evaluating the illness severity of patient with motor neuron disease (MND), was important but less sensitive. Our aim is to explore the correlation between ALSFRS and motor nerve conduction studies and their prognostic significance. Methods: Forty MND patients with different levels of diagnostic certainty were enrolled, according to revised criteria of E1 Escorial; 102 healthy volunteers with ageand gender-matched were served as controls. In all patients, ALSFRS was performed; and CMAP amplitude and distal motor latencies (DML) were measured using surface electrodes for stimulating ulnar (at wrist), tibial (at ankle) nerve and recording on abductor digiti minimi (ADM) and adductor hallucis (AH), respectively; and correlation between ALSFRS and motor conduction was analyzed. Results: There were 20 patients diagnosed as definite, 10 probably, 4 possible ALS and 6 progressive spinal muscular atrophy. Compared with controls, the CMAP amplitudes of both ADM (mV) (10.18±1.99 vs.6.80±4.06, p < 0.001) and AH (11.73±2.77 vs.9.86±5.39, p = 0.042) decreased significantly in the patient group. DML of ulnar nerve prolonged significantly (p 0.001). ALSFRS correlated significantly with CMAP amplitude of ADM (r = 0.653, P= 0.000), AH (r = 0.446, P= 0.004) and DML of ulnar nerve (r = 0.529, P= 0.000), respectively; and those with ALSFRS < 30 all had decreased CMAP amplitude in 9 (9/9, 100%) cases, whereas those with ALSFRS 30 had decreased CMAP amplitude in 17 (17/31, 54.8%) cases (c2 = 6.25, P= 0.012). In 8 followed-up patients, the ALSFRS were 28.75±4.10, among which there were 6 cases with ALSFRS < 30; compared with the first investigation, both the ALSFRS (t = 6.164, P= 0.000) and CMAP amplitude of ADM (t = 5.073, P= 0.001) decreased significantly in the followed-up patients. The ALSFRS correlated positively with CMAP amplitude (mV) of both ADM (r = 0.836, p = 0.01) and AH (r = 0.822, p = 0.012), respectively, and there was no significant correlation of ALSFRS with DML of ulnar nerve. Conclusions: Decreased amplitude of CMAP and delayed DML may be present in MND patients; ALSFRS correlated significantly with CMAP amplitude, and decrease of both could predict poor prognosis, which could be served as objective and reliable indication.