Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

One-year outcomes of deep brain stimulation in refractory Tourette syndrome.

AIM: Deep brain stimulation (DBS) is one option for treating refractory Tourette syndrome (TS); however, it remains unclear which preoperative factors are predictive of DBS outcomes. This study investigated the efficacy of DBS targeting the anteromedial globus pallidus internus and evaluated predisposing factors affecting the outcomes of DBS in a single center in Korea. METHOD: Twenty patients who had undergone DBS for refractory TS were reviewed retrospectively. Tic symptoms were followed up at 3-month intervals for up to 1 year after surgery. The Yale Global Tic Severity Scale was used to evaluate preoperative/postoperative tic symptoms. Scores from the Yale-Brown Obsessive Compulsive Scale, Beck Depression Inventory-II, and Beck Anxiety Inventory were also evaluated. RESULTS: Patients with refractory TS achieved improvement in tic symptoms within 1 year after DBS. Initial responders who achieved a 35% reduction in Yale Global Tic Severity Scale total score within the first 3 months after DBS showed larger treatment effects during 1-year follow-up. Although no clinical or demographic factors were predictive of initial responses, patients with serious self-injurious behaviors tended to show delayed responses. CONCLUSION: This is the first study to our knowledge to report the DBS outcomes of 20 patients with TS in a single center in Asia. Our study supports the efficacy of DBS targeting anteromedial globus pallidus internus in refractory TS with no evident serious adverse events. Initial responses after DBS seem to be a predictor of long-term outcomes after surgery.

A Single Injection of rAAV-shmTOR in Peripheral Nerve Persistently Attenuates Nerve Injury-Induced Mechanical Allodynia.

Activation of mammalian target of rapamycin (mTOR) has been known as one of the contributing factors in nociceptive sensitization after peripheral injury. Its activation followed by the phosphorylation of downstream effectors causes hyperexcitability of primary sensory neurons in the dorsal root ganglion. We investigated whether a single injection of rAAV-shmTOR would effectively downregulate both complexes of mTOR in the long-term and glial activation as well. Male SD rats were categorized into shmTOR (n = 29), shCON (n = 23), SNI (n = 13), and Normal (n = 8) groups. Treatment groups were injected with rAAV-shmTOR or rAAV-shCON, respectively. DRG tissues and sciatic nerve were harvested for Western blot and immunohistochemical analyses. Peripheral sensitization was gradually attenuated in the shmTOR group, and it reached a peak on PID 21. Western blot analysis showed that both p-mTORC1 and p-mTORC2 were downregulated in the DRG compared to shCON and SNI groups. We also found decreased expression of phosphorylated p38 and microglial activation in the DRG. We first attempted a therapeutic strategy for neuropathic pain with a low dose of AAV injection by interfering with the mTOR signaling pathway, suggesting its potential application in pain treatment.

Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis.

RATIONALE: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. OBJECTIVE: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. METHODS AND RESULTS: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)-induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade-driven and hypertension-induced retinal leakage. CONCLUSIONS: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.

Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder.

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-compulsive disorder treated with focused ultrasound to discern the optimal lesion location and elucidate the efficacious network underlying symptom alleviation. Postoperative images of 11 patients who underwent focused ultrasound capsulotomy were used to correlate lesion characteristics with symptom improvement at 1-year follow-up. Normative resting-state functional MRI and normative diffusion MRI-based tractography analyses were used to determine the networks associated with successful lesions. Patients with obsessive-compulsive disorder treated with inferior thalamic peduncle deep brain stimulation (n = 5) and lesions from the literature implicated in obsessive-compulsive disorder (n = 18) were used for external validation. Successful long-term relief of obsessive-compulsive disorder was associated with lesions that included a specific area in the dorsal anterior limb of the internal capsule. Normative resting-state functional MRI analysis showed that lesion engagement of areas 24 and 46 was significantly associated with clinical outcomes (R = 0.79, P = 0.004). The key role of areas 24 and 46 was confirmed by (i) normative diffusion MRI-based tractography analysis, showing that streamlines associated with better outcome projected to these areas; (ii) association of these areas with outcomes in patients receiving inferior thalamic peduncle deep brain stimulation (R = 0.83, P = 0.003); and (iii) the connectedness of these areas to obsessive-compulsive disorder-causing lesions, as identified using literature-based lesion network mapping. These results provide considerations for target improvement, outlining the specific area of the internal capsule critical for successful magnetic resonance-guided focused ultrasound outcome and demonstrating that discrete frontal areas are involved in symptom relief. This could help refine focused ultrasound treatment for obsessive-compulsive disorder and provide a network-based rationale for potential alternative targets.

A Fully Implantable Miniaturized Liquid Crystal Polymer (LCP)-Based Spinal Cord Stimulator for Pain Control.

Spinal cord stimulation is a therapy to treat the severe neuropathic pain by suppressing the pain signal via electrical stimulation of the spinal cord. The conventional metal packaged and battery-operated implantable pulse generator (IPG) produces electrical pulses to stimulate the spinal cord. Despite its stable operation after implantation, the implantation site is limited due to its bulky size and heavy weight. Wireless communications including wireless power charging is also restricted, which is mainly attributed to the electromagnetic shielding of the metal package. To overcome these limitations, here, we developed a fully implantable miniaturized spinal cord stimulator based on a biocompatible liquid crystal polymer (LCP). The fabrication of electrode arrays in the LCP substrate and monolithically encapsulating the circuitries using LCP packaging reduces the weight (0.4 g) and the size (the width, length, and thickness are 25.3, 9.3, and 1.9 mm, respectively). An inductive link was utilized to wirelessly transfer the power and the data to implanted circuitries to generate the stimulus pulse. Prior to implantation of the device, operation of the pulse generator was evaluated, and characteristics of stimulation electrode such as an electrochemical impedance spectroscopy (EIS) were measured. The LCP-based spinal cord stimulator was implanted into the spared nerve injury rat model. The degree of pain suppression upon spinal cord stimulation was assessed via the Von Frey test where the mechanical stimulation threshold was evaluated by monitoring the paw withdrawal responses. With no spinal cord stimulation, the mechanical stimulation threshold was observed as 1.47 ± 0.623 g, whereas the stimulation threshold was increased to 12.7 ± 4.00 g after spinal cord stimulation, confirming the efficacy of pain suppression via electrical stimulation of the spinal cord. This LCP-based spinal cord stimulator opens new avenues for the development of a miniaturized but still effective spinal cord stimulator.

Prognostic Value of P25/30 Cortical Somatosensory Evoked Potential Amplitude After Cardiac Arrest.

OBJECTIVES: The aim of this study was to evaluate the prognostic performance of the peak amplitude of P25/30 cortical somatosensory evoked potentials in predicting nonawakening in targeted temperature management-treated cardiac arrest patients. DESIGN: Prospective analysis. SETTING: Four academic tertiary care hospitals. PATIENTS: Eighty-seven cardiac arrest survivors after targeted temperature management. INTERVENTIONS: Analysis of the amplitude of P25/30. MEASUREMENTS AND MAIN RESULTS: In all participants, somatosensory evoked potentials were recorded after rewarming, and bilaterally absent pupillary and corneal reflexes were evaluated at 72 hours after the return of spontaneous circulation. We analyzed the amplitudes of the N20 and P25/30 peaks and the N20-P25/30 complex in cortical somatosensory evoked potentials. Upon hospital discharge, 87 patients were dichotomized into the awakening and nonawakening groups. The lowest amplitudes of N20, P25/30, and N20-P25/30 in the awakening patients were 0.17, 0.45, and 0.73 µV, respectively, and these thresholds showed a sensitivity of 70.5% (95% CI, 54.8-83.2%), 86.4% (95% CI, 72.7-94.8%), and 75.0% (95% CI, 59.7-86.8%), respectively, for nonawakening. The area under the curve of the P25/30 amplitude was significantly higher than that of the N20 amplitude (0.955 [95% CI, 0.912-0.998] vs 0.894 [95% CI, 0.819-0.969]; p = 0.036) and was comparable with that of the N20-P25/30 amplitude (0.931 [95% CI, 0.873-0.989]). Additionally, adding resuscitation variables or an absent brainstem reflex to the P25/30 amplitude showed a trend toward improving prognostic performance compared with the use of other somatosensory evoked potential amplitudes (area under the curve, 0.958; 95% CI, 0.917-0.999 and area under the curve, 0.974; 95% CI, 0.914-0.996, respectively). CONCLUSIONS: Our results provide evidence that the absence of the P25/30 peak and a reduction in the P25/30 amplitude may be considered prognostic indicators in these patients.

Radiosurgery vs. microsurgery for newly diagnosed, small petroclival meningiomas with trigeminal neuralgia.

Trigeminal neuralgia (TN) is an excruciating pain that can occur with petroclival meningiomas (PCMs). Gamma knife radiosurgery (GKRS) is an appealing option for small PCMs, but the role of microsurgery (MS) compared to GKRS is not well defined for small PCMs with regard to TN relief. From January 2009 to September 2019, 70 consecutive patients were treated by GKRS or MS for newly diagnosed, small (< 3.5 cm) PCMs with TN. GKRS or MS were performed for 35 patients each. The surgical outcome and TN control according to Barrow Neurological Institute (BNI) score were retrospectively analyzed and compared between GKRS and MS. The predominant origin of PCMs was upper clival (49%) with trigeminal nerve compression at the medial dorsal root entry zone. Tumor control rates were equally 94% with GKRS or MS for a mean tumor size and volume of 2.3 cm and 5.3 cm3, respectively. The preoperative BNI scores were mostly II (40%) and IV (37%) with GKRS and MS, respectively. TN relief without medications (BNI scores I and II) was achieved in 13 of 35 patients (37%) with GKRS and 32 of 35 patients (91%) with MS during a mean follow-up of 50.5 months. The most common complications after GKRS and MS were dysesthesia (23%) and diplopia (9%), respectively. MS could be more effective than GKRS in providing prompt, medication-free pain relief from TN for small PCMs. The risks of MS have to be considered carefully in experienced hands, especially for small PCMs.

A novel rat robot controlled by electrical stimulation of the nigrostriatal pathway.

OBJECTIVE: Artificial manipulation of animal movement could offer interesting advantages and potential applications using the animal's inherited superior sensation and mobility. Although several behavior control models have been introduced, they generally epitomize virtual reward-based training models. In this model, rats are trained multiple times so they can recall the relationship between cues and rewards. It is well known that activation of one side of the nigrostriatal pathway (NSP) in the rat induces immediate turning toward the contralateral side. However, this NSP stimulation-induced directional movement has not been used for the purpose of animal-robot navigation. In this study, the authors aimed to electrically stimulate the NSP of conscious rats to build a command-prompt rat robot. METHODS: Repetitive NSP stimulation at 1-second intervals was applied via implanted electrodes to induce immediate contraversive turning movements in 7 rats in open field tests in the absence of any sensory cues or rewards. The rats were manipulated to navigate from the start arm to a target zone in either the left or right arm of a T-maze. A leftward trial was followed by a rightward trial, and each rat completed a total of 10 trials. In the control group, 7 rats were tested in the same way without NSP stimulation. The time taken to navigate the maze was compared between experimental and control groups. RESULTS: All rats in the experimental group successfully reached the target area for all 70 trials in a short period of time with a short interstimulus interval (< 0.7 seconds), but only 41% of rats in the control group reached the target area and required a longer period of time to do so. The experimental group made correct directional turning movements at the intersection zone of the T-maze, taking significantly less time than the control group. No significant difference in navigation duration for the forward movements on the start and goal arms was observed between the two groups. However, the experimental group showed quick and accurate movement at the intersection zone, which made the difference in the success rate and elapsed time of tasks. CONCLUSIONS: The results of this study clearly indicate that a rat-robot model based on NSP stimulation can be a practical alternative to previously reported models controlled by virtual sensory cues and rewards.

Optimization of Medial Forebrain Bundle Stimulation Parameters for Operant Conditioning of Rats.

BACKGROUND: The medial forebrain bundle (MFB) is involved in the integration of pleasure and reward. Previous studies have used various stimulation parameters for operant conditioning, though the effectiveness of these parameters has not been systematically studied. OBJECTIVES: The purpose of the present study was to investigate the optimal MFB stimulation parameters for controlling the conditioned behavior of rats. METHODS: We evaluated four factors, including intensity, frequency, pulse duration, and train duration, to determine the effect of each on lever pressure applied by animals. We further compared burst and tonic stimulation in terms of learning and performance abilities. RESULTS: The number of lever presses increased with each factor. Animals in the burst stimulation group exhibited more lever presses. Furthermore, the average speed in the maze among burst stimulation group subjects was higher. CONCLUSION: We determined the optimal parameters for movement control of animals in operant conditioning and locomotor tasks by adjusting various electrical stimulation parameters. Our results reveal that a burst stimulation is more effective than a tonic stimulation for increasing the moving speed and number of lever presses. The use of this stimulation technique also allowed us to minimize the training required to control animal behavior.

The long-term effects of microvascular decompression on social phobia and health-related quality of life in patients with hemifacial spasm: a 3-year prospective study.

BACKGROUND: Although not a life-threatening condition, hemifacial spasm (HFS) frequently leads to social phobia because it causes significant facial disfigurement and consequently reduces health-related quality of life (HRQoL). The purpose of the current study was to examine the long-term effects of MVD on psychological aspects and HRQoL in HFS patients with social anxiety over a 36-month follow-up. METHODS: Thirty patients with HFS who underwent MVD from January 2015 to May 2015 were included in this prospective study. Clinical data, including standardized measures of general anxiety and depression (Hospital Anxiety Depression Scale (HADS)), social anxiety (Liebowitz Social Anxiety Scale (LSAS)), and the severity of HFS, were collected postoperatively, and 6 months and 36 months after MVD. Likewise, data on HRQoL were collected at baseline, and 6 months and 36 months after MVD using the Korean version of the Short Form 36 (SF-36). RESULTS: Twenty-two patients who completed the 36-month follow-up were classified into social phobia group and non-social phobia group based on the LSAS total scores of 60. Repeated measures analysis of variance demonstrated significant differences between the two groups over time for the total LSAS score (p < 0.001), anxiety subscale score of the HADS (p = 0.002), and the Mental Component Summary (MCS) (p = 0.046) of the SF-36. A comparison of these two groups in terms of differences observed in their scales at 6 months after MVD has shown that the improvements of the social phobia group in HADS anxiety subscale (p = 0.010), LSAS total score (p = 0.008), and MCS (p = 0.040) were significantly more improved than the those of non-social phobia group. And at 36 months after surgery, the improvement of the scales mentioned above was maintained, and additionally Vitality (p = 0.040) and Mental Health (p = 0.040) dimensions showed a statistically significant improvement. CONCLUSIONS: The improvements previously observed in psychological aspects and HRQoL over a short-term follow-up after MVD in HFS patients with social phobia were maintained for at least 36 months after MVD.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up.

BACKGROUND: Recently, a new thermal lesioning approach using magnetic-resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS: Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS: After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS: The main limitations of this study were the small sample size and the open-label design. CONCLUSION: Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

Cerebellar infarction following accidental inhalation of toluene-mixed paint.

We report a case of atypical cerebellar infarction following accidental inhalation of toluene mixed paint. An unconscious 57-year-old housewife with hypertension arrived at our emergency department by ambulance. She had been rescued from a basement (30 m3) 12 h after exposure to paint containing toluene (34%). On arrival, she was comatose (E1V1M1) with a mild fever (37.4 °C). Physical examination showed chemical burns on her buttocks and rales on the left lung. Initial arterial blood gas with 15 L/min of oxygen showed a pH of 7.142, PCO2 of 47.3 mmHg, and PaO2 of 204.7 mmHg. She received endotracheal intubation and mechanical ventilation. Laboratory tests showed elevated white blood cells (26.86 × 109/L), C-reactive protein (0.18 mg/dL), glucose (238 mg/Dl), and CPK (1389 U/L). At 5.5 h after arrival, she became responsive to verbal commands. On day 3, after removal of the endotracheal tube, she began to complain of an occipital headache without neurologic abnormalities. Brain magnetic resonance angiography (MRA) performed on day 6 showed a tiny acute infarction on the right cerebellar hemisphere. We serially measured urinary hippuric acid concentrations (reference range, ≤2.5 g/g creatinine) from 74 h (3.88) after hospital arrival to 218 h (0.5). She was discharged on day 14. Herein we presented a near fatal toluene intoxication (>45,000 mg/m3 estimated based on the basement volume and quantity of paint used) with atypical cerebellar infarction, compared with prior findings of bilateral involvement or reversibility.

Estimating Accurate Target Coordinates with Magnetic Resonance Images by Using Multiple Phase-Encoding Directions during Acquisition.

BACKGROUND: Stereotactic procedures are image guided, often using magnetic resonance (MR) images limited by image distortion, which may influence targets for stereotactic procedures. OBJECTIVES: The aim of this work was to assess methods of identifying target coordinates for stereotactic procedures with MR in multiple phase-encoding directions. METHODS: In 30 patients undergoing deep brain stimulation, we acquired 5 image sets: stereotactic brain computed tomography (CT), T2-weighted images (T2WI), and T1WI in both right-to-left (RL) and anterior-to-posterior (AP) phase-encoding directions. Using CT coordinates as a reference, we analyzed anterior commissure and posterior commissure coordinates to identify any distortion relating to phase-encoding direction. RESULTS: Compared with CT coordinates, RL-directed images had more positive x-axis values (0.51 mm in T1WI, 0.58 mm in T2WI). AP-directed images had more negative y-axis values (0.44 mm in T1WI, 0.59 mm in T2WI). We adopted 2 methods to predict CT coordinates with MR image sets: parallel translation and selective choice of axes according to phase-encoding direction. Both were equally effective at predicting CT coordinates using only MR; however, the latter may be easier to use in clinical settings. CONCLUSION: Acquiring MR in multiple phase-encoding directions and selecting axes according to the phase-encoding direction allows identification of more accurate coordinates for stereotactic procedures.

Effects on cognition and quality of life with unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

OBJECTIVE Although neurosurgical procedures are effective treatments for controlling involuntary tremor in patients with essential tremor (ET), they can cause cognitive decline, which can affect quality of life (QOL). The purpose of this study is to assess the changes in the neuropsychological profile and QOL of patients following MR-guided focused ultrasound (MRgFUS) thalamotomy for ET. METHODS The authors prospectively analyzed 20 patients with ET who underwent unilateral MRgFUS thalamotomy at their institute in the period from March 2012 to September 2014. Patients were regularly evaluated with the Clinical Rating Scale for Tremor (CRST), neuroimaging, and cognition and QOL measures. The Seoul Neuropsychological Screening Battery was used to assess cognitive function, and the Quality of Life in Essential Tremor Questionnaire (QUEST) was used to evaluate the postoperative change in QOL. RESULTS The total CRST score improved by 67.3% (from 44.75 ± 9.57 to 14.65 ± 9.19, p < 0.001) at 1 year following MRgFUS thalamotomy. Mean tremor scores improved by 68% in the hand contralateral to the thalamotomy, but there was no significant improvement in the ipsilateral hand. Although minimal cognitive decline was observed without statistical significance, memory function was much improved (p = 0.031). The total QUEST score also showed the same trend of improving (64.16 ± 17.75 vs 27.38 ± 13.96, p < 0.001). CONCLUSIONS The authors report that MRgFUS thalamotomy had beneficial effects in terms of not only tremor control but also safety for cognitive function and QOL. Acceptable postoperative changes in cognition and much-improved QOL positively support the clinical significance of MRgFUS thalamotomy as a new, favorable surgical treatment in patients with ET.

Predictive factors of early distant brain failure after gamma knife radiosurgery alone in patients with brain metastases of non-small-cell lung cancer.

The objective of this study was to elucidate the predictive factors for early distant brain failure in patients with brain metastases of non-small-cell lung cancer (NSCLC) who were treated with gamma knife radiosurgery (GKRS) without previous whole-brain radiotherapy (WBRT) or surgery. We retrospectively reviewed clinical and imaging data of 459 patients with brain metastases of NSCLC who underwent GKRS from June 2008 to December 2013. The primary end-point was early distant brain failure, defined as the detection of newly developed metastatic lesions on magnetic resonance imaging (MRI) 3 months after GKRS. Factors such as tumor pathology subtype, concurrent systemic chemotherapy, epidermal growth factor receptor (EGFR) mutation status, use of EGFR tyrosine kinase inhibitors (TKIs), systemic disease status, presence of a metastatic lesion only in delayed MRI, and volume and number of metastases were analyzed. There were no statistically significant differences with respect to pathologic subtype, concurrent systemic chemotherapy, EGFR mutation, and early distant brain failure. Patients treated with EGFR-TKIs (p = 0.004), with a stable systemic disease status (p = 0.028) and 3 or fewer brain lesions (p = 0.000) experienced a significantly lower incidence of early distant brain failure. This study suggests that GKRS alone could be considered for patients treated with EGFR-TKIs who have a stable systemic disease status and 3 or fewer brain lesions. WBRT should be considered for other patients.

Comparative Evaluation of Magnetic Resonance-Guided Focused Ultrasound Surgery for Essential Tremor.

BACKGROUND: Treatment options for patients with drug-resistant essential tremor (ET) are limited. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an emerging technique to treat refractory ET. OBJECTIVES: To present MRgFUS as an alternative to radiofrequency (RF) thalamotomy or deep brain stimulation (DBS) for ET treatment. METHODS: We retrospectively analyzed 59 patients who underwent unilateral surgery for drug-resistant ET. Treatments included RF thalamotomy (n = 17), DBS (n = 19), and MRgFUS (n = 23). The outcomes measured were tremor severity and treatment-related complications. RESULTS: At 1 month postoperatively, 100% of RF thalamotomy patients, 89.5% of DBS patients, and 91.3% of MRgFUS patients exhibited absent/mild tremor (successful treatment); other patients exhibited partial relief. At 12 months postoperatively, treatment success for each procedure was observed in 70.6, 84.2, and 78.3% of patients, respectively. At 1 month postoperatively, treatment-related complications had occurred in 58.8, 5.3, and 13.0% of patients, respectively. At 12 months postoperatively, side effects persisted in 11.8, 21.1, and 4.4% of patients, respectively. No statistical differences in treatment success were observed between treatments or over time. Complication rates differed between treatment modalities (p < 0.01) and were lowest in the MRgFUS group. CONCLUSIONS: Patients with drug-resistant ET received equivalent results from RF thalamotomy, DBS, and MRgFUS. DBS and MRgFUS resulted in fewer treatment-related complications.

Benefits of microvascular decompression on social anxiety disorder and health-related quality of life in patients with hemifacial spasm.

BACKGROUND: Hemifacial spasm (HFS), an involuntary movement disorder characterized by unilateral spasms of the muscles innervated by the facial nerve, is likely to cause social anxiety disorder due to its significant facial disfigurement and may have a significant influence on a patient's health-related quality of life (HRQoL). The goal of this study was to investigate the influence of microvascular decompression (MVD) on the severity of social anxiety symptoms and HRQoL in patients with HFS. METHODS: Patients who underwent MVD from January to May 2015 were included in this study. Demographic data were collected before surgery. Clinical data, including the standardized measures of anxiety and depression (Hospital Anxiety Depression Scale, HADS), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and the severity of HFS were assessed before surgery and 6 months after surgery. HRQoL data were also collected before surgery and 6 months after surgery using the Korean version of the short form 36 (SF-36). RESULTS: Six patients (21.4 %) scored 60 or greater on the preoperative LSAS and were considered to have generalized social anxiety disorder (high-LSAS group). The duration of symptom was significantly higher in the high-LSAS group than in the low-LSAS group (7.8 ± 2.2 vs. 4.1 ± 2.6; p = 0.011). The high-LSAS group was more likely to have psychological comorbidities and had a more impaired quality of life than the low-LSAS group at preoperative evaluation. Six months after MVD, a significant improvement, compared to preoperative scores, was observed for the total LSAS score (p = 0.007) and anxiety subscale score of HADS (p = 0.012) in the high-LSAS group. Other significant improvements were also observed in role-emotional (p = 0.039) and mental component summary (p = 0.024) of the SF-36 in the high-LSAS group compared to the low-LSAS group. CONCLUSIONS: This study shows that HFS patients seem to gain benefits from MVD not only for their facial disfigurement but also for social anxiety symptoms that may be associated with mental health improvements in their quality of life.