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Neuroleptic malignant syndrome (NMS) is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS) surgery in a cerebral palsy (CP) patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

Objective Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). Results Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

Impulse control disorders (ICD) in Parkinson’s disease (PD) are a disabling non-motor symptom with frequencies of 13–35% among patients receiving dopamine replacement therapy. ICD in PD is strongly associated with dopaminergic drug use, especially non-ergot dopamine agonists (DA). However, individual susceptibility and disease-related neural changes are also important contributors to the development of ICD. Discrepancies between nigrostriatal and mesolimbic dopaminergic degeneration and non-physiological administration of dopaminergic drugs may induce abnormal ’hyperstimulation’ of the mesolimbic system, which alters reward-learning behaviors in PD patients. In addition, DA can make patients more impulsive during decision-making and seek risk-taking behaviors. DA intake is also related to the biased representation of rewards. Ultimately, loss of negative feedback control due to dysfunctional frontostriatal connections is necessary for the establishment of ICD in PD. The subsequent behavioral and neural changes are affected by PD treatment and disease progression; thus, proper treatment guidelines for physicians are needed to prevent the development of ICD. Future studies aimed at producing novel therapeutics to control the risk factors for ICD or treat ICD behaviors in PD are warranted. This review summarizes recent advances from epidemiological and pathophysiological studies on ICD in PD. Management principles and limitations of current therapeutics are briefly discussed.

BACKGROUND:GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. OBJECTIVES:This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. METHODS:Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12-84). RESULTS:The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement. CONCLUSIONS:GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

X-linked adrenoleukodystrophy (X-ALD) is a hereditary neurological disorder affecting the nervous system and adrenal cortex. The phenotype of X-ALD ranges from the rapidly progressive cerebral form to milder adrenomyeloneuropathy. However, cerebellar manifestations are rare. We report a case of adrenoleukodystrophy presenting as progressive cerebellar dysfunction resembling olivopontocerebellar degeneration, with a review of the literature

SCA17 is an autosomal dominant cerebellar ataxia with expansion of the CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. SCA17 can have various clinical presentations including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed by detecting the expanded CAG repeats in the TBP gene; however, in the literature, pathologic repeat numbers as low as 41 overlap with normal repeat numbers.The subjects in this study included patients with involuntary movement disorders such as cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan. 2006 and Apr. 2014 and were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as the control. In total, 5242 chromosomes from 2099 patients and 522 normal controls were analyzed.The total number of patients included in the analysis was 2099 (parkinsonism, 1706; ataxia, 345; chorea, 37; and dystonia, 11). In the normal control, up to 44 repeats were found. In the 44 repeat group, there were 7 (0.3%) patients and 1 (0.2%) normal control. In 43 repeat group, there were 8 (0.4%) patients and 2 (0.4%) normal controls. In the 42 repeat group, there were 16 (0.8%) patients and 3 (0.6%) normal controls. In 41 repeat group, there were 48 (2.3%) patients and 8 (1.5%) normal controls. Considering the overlaps and non-significant differences in allelic frequencies between the patients and the normal controls with low-expansions, we could not determine a definitive cutoff value for the pathologic CAG repeat number of SCA17.Because the statistical analysis between the normal controls and patients with low range expansions failed to show any differences so far, we must consider that clinical cases with low range expansions could be idiopathic movement disorders showing coincidental CAG/CAA expansions. Thus, we need to reconsider the pathologic role of low range expansions (41-42). Long term follow up and comprehensive investigations using autopsy and imaging studies in patients and controls with low range expansions are necessary to determine the cutoff value for the pathologic CAG repeat number of SCA17.

BACKGROUND: Classical and data-driven classifications of Parkinson's disease (PD) are based primarily on motor symptoms, with little attention being paid to the clustering of nonmotor manifestations. METHODS: Clinical data on demographic, motor and nonmotor features, including the Korean version of the sniffin' stick (KVSS) test results, and responses to the screening questionnaire of the nonmotor features were collected from 56 PD patients with disease onset within 3 years. Nonmotor subgroups were classified using unsupervised hierarchical cluster analysis (HCA). In addition to unsupervised HCA, we performed a cross-sectional analysis comparing the performance on the KVSS olfactory test with other nonmotor manifestations of the patients. RESULTS: Forty-nine patients (87.5%) had hyposmia based on the KVSS test. HCA suggested three nonmotor clusters for all PD patients and two nonmotor clusters in de novo PD patients, without a priori assumptions about the relatedness. In the cross-sectional analysis, dream-enactment behavior was more prevalent in patients with lower olfactory scores, implying impaired olfactory function (P = 0.029 for all PD patients; P = 0.046 for de novo PD patients). CONCLUSION: We propose the existence of different clusters of nonmotor manifestations in early PD by using unsupervised hierarchical clustering. To our knowledge, this study is the first to report the identification of nonmotor subgroups based on unsupervised HCA of multiple nonmotor manifestations in the early stage of the disease.

Background: Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA. Methods: PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time. Results: Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in =5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC. Conclusions: Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit. [ABSTRACT FROM AUTHOR]

A question to be addressed in the present study is how different the eyes-closed (EC) and eyes-open (EO) resting states are across frequency bands in terms of efficiency and centrality of the brain functional network. We investigated both the global and nodal efficiency and betweenness centrality in the EC and EO resting states from 39 volunteers. Mutual information was used to obtain the functional connectivity for each of the four frequency bands (theta, alpha, beta, and gamma). We showed that the cortical hubs with high betweenness centrality were maintained in the EC and EO resting states. We further showed that these hubs were associated with more than three frequency bands, suggesting that these hubs play an important role in the brain functional network at multiple temporal scales in the resting states. Enhanced global efficiency values were found in the theta and alpha bands in the EO state compared with those in the EC state. Moreover, it turned out that in the EO state the functional network was reorganized to enhance nodal efficiency at the nodes related to both the default mode and the dorsal attention networks and sensory-related resting-state networks. This result suggests that in the EO state the brain functional network was efficiently reorganized, facilitating the adaptation of the brain network to the change in state, which could help in understanding brain disorders that have a disturbance in communication with external environments by using the adaptation ability of brain functional networks. [ABSTRACT FROM AUTHOR]

Advances in deep brain stimulation (DBS) in relation to neuroimaging techniques and with intraoperative electrophysiological microrecordings and stimulations have replaced ablative procedures for medication-refractory movement disorders such as Parkinson's disease, dystonia, and essential tremor. DBS is an effective surgical treatment for these conditions and is now being extended to psychiatric diseases such as obsessive-compulsive disorder, depression, and addiction. Despite the proven clinical improvement by DBS, its precise mechanism of action re-mains unclear. Clinical improvement depends on the selection of the appropriate patients and the precise implantation of the stimulation electrodes, which is based on careful stereotactic targeting and extensive electrophysiological monitoring of the target area. Further studies are being performed to better understand the mechanism of action and identify new anatomical targets and clinical applications of DBS. We briefly introduce the surgical procedure and current clinical applications of DBS in this review. [ABSTRACT FROM AUTHOR]

Purpose: MRI has been utilized to localize the electrode after deep brain stimulation, but its accuracy has been questioned due to image distortion. Under the hypothesis that MRI is not adequate for evaluation of electrode position after deep brain stimulation, this study is aimed at validating the accuracy of MRI in electrode localization in comparison with CT scan. Methods: Sixty one patients who had undergone STN DBS were enrolled for the analysis. Using mutual information technique, CT and MRI taken at 6 months after the operation were fused. The x and y coordinates of the centers of electrodes shown of CT and MRI were compared in the fused images to calculate average difference at five different levels. The difference of the tips of the electrodes, designated as the z coordinate, was also calculated. Results: The average of the distance between the centers of the electrodes in the five levels estimated in the fused image of brain CT and MRI taken at least 6 months after STN DBS was 1.33 mm (0.1-5.8 mm). The average discrepancy of x coordinates for all five levels between MRI and CT was 0.56 ± 0.54 mm (0-5.7 mm), the discrepancy of y coordinates was 1.06 ± 0.59 mm (0-3.5 mm), and for the z coordinate, it was 0.98 ± 0.52 mm (0-3.1 mm) (all p values < 0.001). Notably, the average discrepancy of x coordinates at 3.5 mm below AC-PC level, i.e., at the STN level between MRI and CT, was 0.59 ± 0.42 mm (0-2.4 mm); the discrepancy of y coordinates was 0.81 ± 0.47 mm (0-2.9 mm) ( p values < 0.001). Conclusions: The results suggest that there was significant discrepancy between the centers of electrodes estimated by CT and MRI after STN DBS surgery. [ABSTRACT FROM AUTHOR]

Objective: We compared the electrode positions of subthalamic nucleus (STN) deep brain stimulation (DBS) estimated at the immediate postoperative period with those estimated 6 months after surgery. Methods: Brain CT scans were taken immediately and 6 months after bilateral STN DBS in 53 patients with Parkinson's disease. The two images were fused using the mutual information technique. The discrepancies of electrode positions in three coordinates were measured in the fused images, and the relationship with the pneumocephalus was evaluated. Results: The average discrepancy of x- and y-coordinates of electrode positions at the level of STN (3.5 mm below the anterior commissure-posterior commissure line) were 0.6 ± 0.5 mm (range, 0~2.1 mm) and 1.0 ± 0.8 mm (range, 0~5.2 mm), respectively. The average discrepancy of z-coordinates of the electrode tips of the fused images was 1.0 ± 0.8 mm (range, 0.1~4.0 mm). The volume of pneumocephalus (range, 0~76 ml) was correlated with the y-coordinate discrepancies ( p < 0.005). Conclusion: The electrode positions in the immediate postoperative CT might have significant discrepancies with those in the CT taken at a stable period after STN DBS especially when there is a large amount of pneumocephalus. [ABSTRACT FROM AUTHOR]

Hemimasticatory spasm is a rare neurologic disorder characterized by unilateral, paroxysmal involuntary contraction of the masticatory muscles. It can be confused with other unilateral facial spasms. In this report, we present two patients with hemimasticatory spasm who were initially misdiagnosed with other disorders. The first patient was a 54-year-old man with a 9-year history of right facial spasm. He underwent microvascular decompression, without benefit, at another hospital with the diagnosis of hemifacial spasm two years prior to presenting at our hospital.On examination, right masseter and temporalis muscles had irregular contractions with twitches and prolonged spasms. His brain magnetic resonance imaging was normal.He showed a good response to carbamazepine. The second case was a 60-year-old man presented with a 10-year history of jaw-closing movement. Previous treatment for temporomandibular joint disorder was ineffective. He was previously diagnosed as oromandibular dystonia at another hospital, and biperiden and diazepam treatment resulted in slight improvement. There was tonic contraction and hypertrophy of the left masseter. He improved with carbamazepine. These cases illustrate the importance of hemimasticatory spasm as differential diagnosis, and the good response to carbamazepine. [ABSTRACT FROM AUTHOR]

We present the first case report of fragile X-associated tremor ataxia syndrome (FXTAS) in the Republic of Korea. A 75-year-old male developed progressive gait ataxia, parkinsonism, and a mood disorder. Magnetic resonance imaging revealed T2 high signal intensity within the middle cerebellar peduncles. Analysis of the fragile X mental retardation 1 gene revealed a CGG trinucleotide repeat number of 136. FXTAS should be considered when a patient has atypical parkinsonism, cerebellar ataxia, and specific MRI abnormalities. [ABSTRACT FROM AUTHOR]