Jong Sam Baik

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.

Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection.

We report a case of unilateral blindness and panophthalmoplegia after hyaluronic acid injection into the dorsum of the nose in a healthy young woman. Microspheres of hyaluronic acid are popular fillers for facial rejuvenation. While ocular side effects from injections in the nose and face have been reported following turbinate injection, rhinoplasty and infraorbital nerve block, ocular side effects from injection into the dorsum of the nose are extremely rare. We presume that the symptoms were due to obstruction of the branches of the ophthalmic artery. Under high injection pressure, the microspheres travelled to the ophthalmic artery and were propelled by the blood flow to the central retinal artery and the anterior and posterior long ciliary arteries, leading to her symptoms. Alternatively, there are several arterio-venous anastomotic channels in the nasal mucosa that aid heat exchange. These may have been the conduit for reflux of the filler into the arterial side of the regional circulation. Physicians must remain aware of serious complications during cosmetic injections to this region.

Primary lingual dystonia induced by speaking.

We describe a 46‐year‐old woman who presented with lingual dystonia induced only by speaking, which responded well to anticholinergic treatment.

Scoliosis in Patients with Parkinson's Disease

Background and purpose Scoliosis is more common in patients with Parkinsons disease (PD) than in the general elderly population. We compared clinical characteristics between PD patients with and without scoliosis, to identify the relationship between the direction of scoliosis and the laterality of the dominant symptoms of PD. We also studied the associations between dopaminergic pharmacotherapy and scoliosis (defined by a spinal curvature deviation of 10° or larger). Methods The study population comprised 97 patients (42 men and 55 women) with idiopathic PD. All of the patients submitted to a whole-spine scanograph to allow measurement of the degree of scoliosis by Cobbs method. Results True scoliosis was found in 32 of the 97 PD patients, and was observed more frequently in women than in men (28 vs. 4, respectively; p=0.006). The age of patients without scoliosis was significantly lower than that of those with scoliosis (66.5±9.2 years vs. 72.8±7.3 years, respectively, mean±SD, p<0.001). There was no correlation between PD symptom laterality and scoliosis. The rate of occurrence of scoliosis did not differ between de novo and levodopa (L-dopa)-treated patients. Conclusions We suggest that neither L-dopa treatment nor the laterality of the initial symptoms of PD is related to the appearance of scoliosis.

Association of mutations in the glucocerebrosidase gene with Parkinson disease in a Korean population

Recent studies have shown an association between Parkinson disease (PD) and mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA), which is deficient in patients with Gaucher disease. In Asian populations, 2 mutational analysis studies have been performed in all exons of GBA; one study in a Japanese population showed the highest odds ratio among all ethnic groups, whereas the other study in ethnic Chinese observed a trend of a higher frequency of GBA mutation in PD patients without statistical significance. To investigate whether there is an association between PD and mutations of GBA in a Korean population, we analyzed mutations of GBA and compared mutation frequencies between Korean PD patients and a control population. We analyzed mutations in GBA by sequencing exons of GBA in 277 Korean PD patients and 291 control subjects. All exons of GBA were sequenced in all PD cases and 100 control subjects. Exon 2 and exons 5-11, where mutations of GBA were found in our PD patients, were analyzed in an additional 191 control subjects. Five different pathogenic heterozygous GBA mutations, including N188S, P201H, R257Q, S271G, and L444P, were identified in 9 PD cases (3.2%), whereas there were no GBA mutations found in control subjects (p<0.01, OR 20.6, 95% CI 1.2-356.4). The mean age-at-onset of heterozygous GBA variants carriers was younger than that of non-carriers (48.6±11.9 versus 57.9±13.5, p<0.05, Mann-Whitney test). Our results suggest that heterozygous mutations of GBA represent a risk factor for PD in Koreans.

Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease

Background and Purpose Non-motor symptoms are common in Parkinsons disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD. Methods In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinsons Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinsons Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient. Results The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbachs α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearmans rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001). Conclusions The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.

Postural instability and cognitive dysfunction in early Parkinson's disease

BACKGROUND Postural instability is one of the most disabling features of Parkinsons disease, usually occurring in late and advanced stages. The aim of this study was to investigate the postural performance of early-stage de novo Parkinsons disease patients with no clinical postural instability using computerized dynamic posturography. We sought to understand the relationship between postural sway and disease severity and the relationship between postural instability quantitatively measured by computerized dynamic posturography and cognitive impairment in early-stage Parkinsons disease patients. METHOD Thirty-one subjects with Parkinsons disease and 20 healthy controls were assessed by the computerized dynamic posturography protocol using the sensory organization test and the motor control test. A neuropsychological assessment was also administered. RESULTS The mean equilibrium score for sensory organization test and the vestibular input ratio were significantly correlated with Hoehn-Yahr stage. No associations between motor latency for any motor control test condition and Hoehn-Yahr stage were found. The equilibrium score for sensory organization test correlated with the mini-mental status examination scores. There was a significant correlation between motor latency for large backward translation and mini-mental status examination scores. There were significant correlations between visual perception/construction/ memory of the neuropsychological battery test and the equilibrium score for sensory organization test and between verbal word learning test, controlled word association test and motor latency for large backward translation. CONCLUSION These findings showed the postural instability present in early-stage (Hoehn-Yahr stage 2-2.5) Parkinsons disease. We also found a close relationship between postural instability and cognitive function in Parkinsons disease patients.

Sonographic abnormalities in idiopathic restless legs syndrome (RLS) and RLS in Parkinson’s disease☆

We aimed to investigate and compare sonographic abnormalities in the substantia nigra (SN) in patients with idiopathic restless legs syndrome (iRLS), those with RLS and Parkinsons disease (RLS-PD), those with idiopathic Parkinsons disease (iPD), and healthy controls. Study participants totaled 60 patients with RLS (41 iRLS, 19 RLS-PD), 25 iPD patients, and 35 age-matched healthy controls. Comparing all groups, the SN regions echogenicity area in the iRLS patients was significantly decreased compared with that in the PD-RLS, iPD, and control groups (p < 0.0001), and the PD-RLS group demonstrated a significantly increased echogenicity area compared with the control group (p < 0.05) and iRLS group (p < 0.0001). We found that the RLS-PD groups sonological results and clinical findings were different from those of the iRLS group.

Sagittal spinopelvic malalignment in parkinson disease: Prevalence and associations with disease severity

Study Design. Prospective study. Objective. Our objectives were to evaluate the prevalence of sagittal spinopelvic malalignment in a consecutive series of patients with Parkinson disease (PD) and to identify factors associated with sagittal spinopelvic deformity in this population. Summary of Background Data. PD is a degenerative neurological condition characterized by tremor, rigidity, bradykinesia, and loss of postural reflexes. The prevalence of spinal deformity in PD is higher than that of age-matched adults without PD. Methods. This study was a prospective assessment of consecutive patients with PD presenting to a neurology clinic during 12 months. Inclusion criteria included age more than 21 years and diagnosis of PD. Age- and sex-matched control group was selected from patients with cervical spondylosis. Clinical and demographic factors were collected including Unified Parkinson Disease Rating Scale score and Hoehn and Yahr stage. Full-length standing spine radiographs were assessed. Patients were grouped into either low C7 sagittal vertical axis (SVA) (<5 cm) or high C7 SVA (≥5 cm) and into matched (⩽10°) or mismatched (>10°) pelvic incidence (PI)-lumbar lordosis. Results. Eighty-nine patients met criteria (41 males/48 females), including 52 with low C7 SVA and 37 with high C7 SVA. Significantly higher prevalence of high C7 SVA was found in PD (41.6 vs. 16.8%; P < 0.001). The high C7 SVA group was significantly older (72.4 vs. 65.1 yr; P < 0.001) and had a higher proportion of females (68% vs. 44%; P = 0.034), greater severity of PD based on Hoehn and Yahr stage (1.89 vs. 1.37; P < 0.001) and Unified Parkinson Disease Rating Scale (30.5 vs. 17.2; P = 0.002. Unified Parkinson Disease Rating Scale significantly correlated with C7 SVA (r = 0.474). Compared with the matched (⩽10°) PI-lumbar lordosis group, the mismatch PI-lumbar lordosis group had higher C7 SVA, higher PI, higher pelvic tilt, lower lumbar lordosis, and lower thoracic kyphosis (P ⩽ 0.003). Conclusion. Patients with PD have a high prevalence of sagittal spinopelvic malalignment than control group patients. Greater severity of PD is associated with sagittal spinopelvic malalignment. Level of Evidence: 3

Movement disorders associated with moyamoya disease: A report of 4 new cases and a review of literatures†

The aim of this study was to define the clinical characteristics of patients who developed movement disorders in association with moyamoya disease (MMD). Using PubMed and medical records of our hospital from 1985 to 2008, we searched for patients who developed movement disorders in association with MMD. This study included 38 patients described in previous studies and 4 patients found in the medical records. The onset of movement disorders was thought to be sudden. In 13 patients, the movement disorders were precipitated by hyperventilation or emotional stress. Twenty‐seven of the 42 patients developed chorea, 4 patients developed dystonia, and 4 developed a mixture of both. The movement disorders of the remaining 7 patients were described as dyskinesia. A third of the 42 patients developed bilateral movement disorders, and their mean age was younger than that of those with unilateral movement disorders. In 37 of the 42 patients, brain imaging studies showed ischemic lesions, but the remaining 5 patients showed no parenchymal lesions. Cerebral perfusion studies showed hypoperfusion in the basal ganglia and in the cerebral cortical areas. Most patients improved whether they were treated or not. MMD must be included in the differential diagnosis of the sudden onset of dyskinesias, particularly chorea and focal dystonia. Even in patients with no parenchymal lesion in brain imaging studies, cerebral angiography and cerebral blood perfusion studies must be performed, if they develop a sudden onset or recurrent movement disorders preceded by emotional stress or hyperventilation.