Tae-Kyu Lee

Stereotactic lesioning for mental illness

OBJECTIVE The authors report stereotactically created lesioning by radiofrequency or Cyberknife radiosurgery for patients with mental illness. MATERIALS AND METHODS Since 1993, thirty-eight patients have undergone stereotactic psychosurgery for medically intractable mental illnesses. Two patients had aggressive behavior. Twenty-five patients suffered from Obsessive-Compulsive Disorder (OCD) and ten patients had depression. Another patient suffered from atypical psychosis. Bilateral amygdalotomy and subcaudate tractotomy were done for aggressive behavior. Limbic leucotomy or anterior cingulotomy was done for OCD and subcaudate tractotomy with or without cingulotomy was done for depression. In twenty-three patients, the lesions were made by a radiofrequency (RF) lesion generator. In fifteen cases, the lesions were made with CyberKnife Radiosurgery (CKRS). RESULTS The Overt Aggression Scale (OAS) declined from 8 to 2 with clinical improvement during follow up period. With long-term follow up (meaning 57 months) in 25 OCDs, the mean Yale Brown Obsessive Compulsive Score (YBOCS) declined from 34 to 13 (n = 25). The Hamilton Depression scale (HAMD) for ten patients with depression declined from 38.5 to 10.5 (n = 10). There was no operative mortality and no significant morbidity except one case with transient urinary incontinence. CONCLUSION Authors suggest that stereotactic psychosurgery by RF and CKRS could be a safe and effective means of treating some medically intractable mental illnesses.

Temozolomide chemotherapy in patients with recurrent malignant gliomas.

Numerous studies have demonstrated the clinical activity of temozolomide, a second-generation alkylating agent, against malignant brain tumors, however, its activity has not been reported in an Asian population. This study analyzed the efficacy and toxicity of temozolomide in 25 adult patients with recurrent or progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy, enrolled in our institution since July 2000. Sixteen patients had glioblastoma multiforme (GBM), six with anaplastic astrocytoma, and three with anaplastic oligodendroglioma. Of the 25 patients, 3 (12%) achieved a complete response (CR), 8 (32%) achieved a partial response (PR), 6 (24%) had stable disease (SD), and 8 (32%) had progressive disease (PD). Two patients achieved a CR, 4 patients achieved a PR, 3 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 4 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival was 8 weeks in GBM and 22 weeks in the non-GBM patients. The median overall survival of each group was 17 weeks and 28 weeks. Temozolomide demonstrated moderate activity in recurrent and progressive malignant gliomas without serious toxicity.

Regional cerebral blood flow changes in patients with intractable obsessive compulsive disorders treated by limbic leukotomy.

The object of this study is to assess the changes in regional cerebral blood flow (rCBF) following stereotactic limbic leukotomy in patients with medically intractable Obsessive-Compulsive Disorder (OCD). Technetium-99-Hexa Methyl Propylene Amine Oxime (99mTc-HMPAO) Single Photon Emission Computed Tomography (SPECT) data obtained before and after limbic leukotomy were subjected to image fusion with MRI images. Eight samples were obtained from healthy voluteers. After localization of the ROI (Region Of Interest) in anatomical area, rCBF measurements were obtained by METLAB. The results of this study show a change of rCBF following limbic leukotomy in intractable OCD. Postoperative 99mTc-HMPAO SPECT findings implicate the medial frontal cortex, cingulate and striatum, which culd be linked to limbic leukotomy that blocks the functional connection of corticolimbic loop.

High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia

Background:Cytosine arabinoside-based chemotherapy coupled with anthracycline is currently the first-line treatment for acute myeloid leukaemia (AML), but diverse responses to the regimen constitute obstacles to successful treatment. Therefore, outcome prediction to chemotherapy at diagnosis is believed to be a critical consideration.Methods:The mRNA expression of 12 genes closely involved in the actions of cytosine arabinoside and anthracycline was evaluated by real-time reverse transcriptase PCR (RT–PCR), in 54 diagnostic bone marrow specimens of M2-subtype AML.Results:Low expression levels of ribonucleotide reductase M2 (RRM2) and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with longer survival in a univariate analysis. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).Conclusion:Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.

Prevalence and risk factors of periodontitis among adults with or without diabetes mellitus

Background/Aims: This study examined prevalence and risk factors of periodontitis in representative samples of Korean adults, with and without diabetes mellitus (DM). Methods: Data from the 2012 Korean National Health and Nutritional Examination Survey were analyzed. A total of 4,477 adults (≥ 30 years old) were selected from 8,057 individuals who completed a nutrition survey, a self-reported general health behavior questionnaire, an oral examination, an oral hygiene behaviors survey, and laboratory tests. DM was defined as a fasting plasma glucose ≥ 126 mg/dL, or self-reported diagnosed diabetes, or current use of oral hypoglycemic agents and/or insulin. The community periodontal index was used to assess periodontitis status and comparisons between the periodontitis and the non-periodontitis group, were performed, according to the presence of DM. Risk factors for periodontitis in adults with DM and without DM were evaluated by multiple logistic regression analysis. Results: The prevalence of periodontitis was significantly higher in adults with DM (43.7%) than in those without DM (25%, p < 0.001). In adults without DM, risk factors for periodontitis were older age, male, urban habitation, waist circumference, smoking, oral pain, and less frequent tooth brushing. Significant risk factors for periodontitis in adults with DM were the smoking, oral pain, and not-using an oral hygiene product. Conclusions: Adults with DM have an increased risk of periodontitis than those without DM. Current smoking and oral pain increase this risk. Using an oral hygiene product can reduce risk of periodontal disease in adults with DM.

Increased urinary albumin/creatinine ratio is associated with atopic dermatitis in Korean males: The 2011-2013 Korea National Health and Nutrition Examination Survey

academic institution (Table I). Improved rates of alcohol and tobacco screening and of alcohol, tobacco, and obesity counseling were observed compared to the study published in 2014. Academicians averaged higher rates of screening based on guidelines. Although alcohol and tobacco screening rates were moderately high, less than half of both academicians and nonacademicians screened for hypertension, dyslipidemia, and diabetes mellitus. Approximately one-fifth of dermatologists reported never screening patients with psoriasis or referring them for management of cardiovascular risks, with worse screening rates in nonacademic (15.2%) versus academic (6.8%) dermatologists. A larger proportion of academic (16.9%) versus nonacademic (10.3%) dermatologists determined disease severity as the stimulating factor for screening, while more nonacademicians relied on history. A majority of respondents (61.6%) refer screening to PCPs. No respondents reported always handling the screening themselves and never referring out for screening. Despite geographically wide distribution, it is uncertain whether the subjects surveyed are truly representative of the entire dermatologic community. As with all surveys, ours was subject to response bias, which we attempted to mitigate by piloting and incorporating feedback from 20 initial respondents. Our results suggest that screening and counseling for modifiable lifestyle factors are the most commonly completed preventive efforts; however, more effort should be made to refer patients to PCPs or cardiologists to screen and manage hypertension, dyslipidemia, obesity, and diabetes mellitus. A possible explanation is the easier nature of verbally screening for the earlier factors; whereas, hypertension, dyslipidemia, diabetes mellitus, and obesity all require more time-consuming quantified measurements. Furthermore, dermatologists may be the primary/ exclusive providers for many patients with psoriasis, emphasizing our need to advise them to see their PCPs or order lab tests ourselves. Our results reinforce the benefit for both academic and nonacademic dermatologists’ involvement in Performance Improvement activities to maintain proper preventive practices for better patient outcomes.

Monosymptomatic rest tremor due to a midbrain arteriovenous malformation

A monosymptomatic rest tremor (mRT) is an uncertain clinical condition defined as a pure or predominant resting tremor without other parkinsonian motor signs. The relationship between mRT and Parkinson’s disease (PD) continues to be debated and remains a frequent diagnostic problem. We report a patient with a mRT caused by a brainstem arteriovenous malformation (AVM) without apparent hemorrhage. A 60-year-old man was admitted to our neurology department with the complaint of tremor of the left hand. The patient was well until 2 years earlier when the tremor of the left hand was suddenly noted. The tremor was evident at rest and regressed during activity and with an out-stretched hand posture. There were no symptoms such as slowness of body movements, rigidity, or gait disturbance. The patient also had the diagnosis of an essential tremor of the right hand for 10-years. His grandfather, father, and elder sister also had a history of tremor. There was no significant medical history or neuroleptic exposure. The neurological examination showed a mild resting tremor of the left hand, which had a frequency of 4–5 Hz. The postural tremor of the right hand was observed when the arms were outstretched and during drawing a spiral (video segment 1). There was no bradykinesia or rigidity with cogwheeling noted in the arms and legs. The posture was upright and the gait was normal. The cranial nerves were normal and there was no evidence of a pyramidal or sensory disturbance. The deep tendon reflexes in all extremities were symmetric and normoactive and both plantar reflexes were flexor. T2-weighted magnetic resonance imaging (MRI) of the brain showed an AVM in the interpeduncular cistern and right midbrain near the substantia nigra with flow voids. The T1-weighted contrast enhanced MRIs revealed contrastenhanced vessels extending into the right substantia nigra (see Fig. 1). Digital subtraction angiography showed that the AVM was fed by thalamoperforating arteries from the basilar artery and the right posterior communicating artery. The venous drainage was through the superior ophthalmic vein, vein of Galen, and vein of Labe (see Fig. 2). A small dose of levodopa-carbidopa (100 mg twice daily) was prescribed. After 100 mg of L-dopa was started, the patient reported an almost complete resolution of the left hand tremor within 2 hours. However, there was no improvement in his right hand postural tremor. This report is the first description of a mRT associated with an unruptured cerebral AVM. There have been several reports of movement disorders secondary to cerebral AVMs. As for the association with Parkinsonism, only two papers in the literature to date, describe patients with ruptured cerebral AVMs with tremor, bradykinesia, rigidity, and gait disorders typical of PD. The left hand tremor in this case was consistent with the definition of mRT proposed by the Consensus Statement of the Movement Disorder Society on Tremor including the following: (1) pure or predominant resting tremor; (2) no signs of bradykinesia, rigidity, or problems with stance-stability sufficient to diagnose PD; and (3) a minimum of 2 years duration of the tremor. The 2-year period proposed is arbitrary but reasonable according to the natural course of typical PD. The etiology of mRT and its relation to PD continues to be debated. However, one recent study, using positron emission tomography scanning with fluorodopa and raclopride showed a nearly identical striatal dopaminergic deficit and postsynaptic D2-receptor upregulation in both mRT and PD groups. Accordingly, it seems that mRT originate from dompaminergic deficits in the brain, a mechanism similar to PD. In this case, the AVM was near the substantia nigra on the right side where the dopamine neurons are located. It is, thus, likely that the left hand tremor in this patient was due to the effect of the AVM lesion on the right dopaminergic pathways in the brain. In addition, the therapeutic response to levodopa, in our patient, suggests that the dopaminergic paths were involved in the pathogenesis of mRT. Several possible explanations for mRT associated with midbrain AVM have been proposed but remain speculative. First, the extension of an unruptured AVM may act as a mass effect on the substantia nigra leading to the damage of dopamine neurons. Second, in this context, locally altered hemodynamics attributable to a high-flow AVM may cause a relatively low perfusion in nearby vascular regions, resulting in more extensive dysfunction of brain areas associated with dopamine activity. This concept of ‘‘steal’’ has been proposed as a mechanism underlying the neurological symptoms in patients with AVM, unexplained by the anatomical location or extent of the lesion. In summary, we describe a patient with a cerebral AVM near the substantia nigra on the right side of the brain that developed a mRT of the left hand. The symptoms may be Additional Supporting Information may be found in the online version of this article. No potential conflict of interest. Published online 29 August 2008 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.22213

Development of a rapid planning technique based on heuristic target shaping for stereotactic radiosurgery.

Stereotactic radiosurgery (SRS) is a technique to delivering a high dose to a target region and a low dose to a critical organ by using only one or a few irradiations. Traditionally, SRS is performed using a Gamma knife with using 201 cobalt 60 sources or a linear accelerator with equally spaced noncoplanar arcs. Finding a specific condition that includes the target in the prescription dose while sparing the critical organ is tedious, because there are many combinations of positions and collimator sizes for each isocenter. Many methods of identifying suitable planning condition automatically have been proposed. However, there are some limitations using these methods. These include a long calculation time to obtain the final plan, and difficulties finding a unique solution due to different tumor shapes. This study uses three steps to solve these problems. (1) The dose distribution of one isocenter is modeled as a sphere. This makes it possible to reduce the time needed to obtain the result due to the absence of a dose calculation. (2) The target was constructed by piling up cylinders along a virtual axis, which was the longest line in a given target. (3) Spheres were then packed in each cylinder according to the position and diameter of each cylinder in order to cover each target divided by the height of the cylinder. The results of applying three imaginary targets were found to be satisfactory in terms of: target coverage-more than 50%, the reproducibility of the result and the calculation time-several tens of seconds. The PITV ratio was less than 2.0. However, the dose applied to normal tissue around the target must be reduced slightly. Planner or conventional optimization algorithms might easily solve this limitation.

Role of bifrontal basal interhemispheric approach in recurrent suprasellar tumors; craniopharyngioma and pituitary tumors

Abstract Recurrent suprasellar tumors, including craniopharyngiomas and pituitary tumors, can be approached with minimal brain retraction, a wider operative field with better orientation and a good view of important neurovascular structures via a bifrontal basal interhemispheric approach (BFBIHA). The authors present their experience of using BFBIHA for removal of recurrent suprasellar tumors, during which they recorded the size and location of each tumor and the degree of tumor extension. Two hundred fifty-four cases of pituitary tumors and 80 cases of craniopharyngiomas were operated on. Recurrent cases were 25 (9.8%) in pituitary tumors and 14 (17.5%) in craniopharyngiomas. Among recurrent cases, nine patients (five recurrent pituitary tumors, four recurrent craniopharyngiomas) were included. Preoperatively, suprasellar extension of the tumors was measured with the aid of radiological images (MRI, MRA, CT). Using line C (mid-sella), the tumors were divided into three groups according to the direction of tumor growth. Group I (one case) contained those with a prechiasmatic location, group II (two cases), those with a suprasellar location, and group III (five cases), those with a retrochiasmatic location. All of the recurrent patients underwent operations by the same approach. All tumors but one were totally resected. There was no operative mortality. In our experience, recurrent suprasellar tumors were safely manipulated with this BFBIHA, preserving important neurovascular structures and hypothalamo–pituitary functions.

Prevalence and risk factors for reduced pulmonary function in diabetic patients: The Korea National Health and Nutrition Examination Survey

Background/Aims An association between reduced pulmonary function and diabetes has been observed. Our aim was to evaluate the prevalence and risk factors associated with reduced pulmonary function in diabetic patients. Methods We analyzed data from the Korea National Health and Nutrition Examination Survey 2011 to 2013. The study population included data from 8,784 participants (including 1,431 diabetics) aged ≥ 40 years. Reduced pulmonary function was defined as patients with restrictive (forced expiratory volume in 1 second/forced vital capacity [FEV1/FVC] ≥ 0.7 and FVC < 80% of predicted value) or obstructive (FEV1/FVC < 0.7) patterns. Results Subjects with diabetes had a higher prevalence of restrictive (18.4% vs. 9.4%, p < 0.001) and obstructive impairments (20% vs. 12.6%, p < 0.001) than those without diabetes. The adjusted odds ratios (aORs) (95% confidence interval [CI]) for obstructive and restrictive pulmonary impairment were 0.91 (0.75 to 1.11) and 1.57 (1.30 to 1.89), respectively. In the diabetes population, age (aOR, 1.04; 95% CI, 1.02 to 1.06), male sex (aOR, 1.40; 95% CI, 1.04 to 1.88), and body mass index (aOR, 1.15; 95% CI, 1.10 to 1.21) were independently associated with restrictive pulmonary impairment. Age (aOR, 1.12; 95% CI, 1.09 to 1.14), male sex (aOR, 4.24; 95% CI, 2.42 to 7.44), and smoking at any point (ever-smoker: aOR, 1.96; 95% CI, 1.16 to 3.33) were independent risk factors for obstructive pulmonary impairment in diabetics. Diabetes duration or glycated hemoglobin had no association with pulmonary impairment in diabetes. Conclusions Subjects with diabetes had a higher risk of restrictive pulmonary impairment than those without diabetes after adjusting for confounding factors. Older age, male sex, body mass index, and smoking were associated with reduced lung function in diabetes.