Hui-Jun Yang

The significance of gemistocytes in astrocytoma

Background. A retrospective clinical analysis of astrocytomas which contained a significant proportion of gemistocytes was carried out in order to evaluate their effect on prognosis, and other factors influencing prognosis. Method. From 253 consecutive cases of astrocytic tumours in adults, 25 were selected who had more than 20% gemistocytes in every high-power field examined. 9 of these had anaplasia, the remainder did not. They were divided into two groups according to the proportion of gemistocytes; group A, contained more than 60% gemistocytes, and group B, had between 20 and 60% gemistocytes. TUNEL and immunohistochemical staining for PCNA, p53, Ki-67, bcl-2 were performed in the 20 available cases. Findings. The median follow-up period was 46 months. There were 14 recurrences, with a median time to recurrence of 15 months. Thirteen repeat operations were performed in nine cases, and two cases showed recurring malignant transformation. The overall median survival time following diagnosis was 73 months and the 5-year survival rate was 52%. There were no significant differences in median survival between groups A and B with different proportions of gemistocytes. On the other hand the median survival of the gemistocytic astrocytomas with anaplasia was 25 months, compared with 158 months for those without anaplasia (p=0.0005). The significant impact of anaplasia on survival persisted in both groups. There were no significant differences in immunohistochemical staining between the two groups, with the exception of staining for Ki-67 (means of the two groups: group A 1.40; group B 2.50). Conclusions. It is suggested that the proportion of gemistocytes does not itself affect prognosis.

Patients' reluctance to undergo deep brain stimulation for Parkinson's disease

BACKGROUND Many patients with advanced Parkinsons disease (PD) are reluctant to undergo the subthalamic nucleus deep brain stimulation (STN-DBS) when surgery is warranted. Reasons for this reluctance have not been examined. We undertook to establish the rate and causes of this reluctance for STN-DBS in patients with advanced PD. METHODS A reluctant group was defined as patients who were hesitant to undergo DBS. Clinical information included age, onset age, disease duration, the Unified Parkinson Disease Rating Scale, Hoehn and Yahr stage and levodopa equivalent dose when they were evaluated with a view to consider surgery. RESULTS We enrolled 186 patients who underwent STN-DBS. 84 patients (45%) belonged to the reluctant group. Between the reluctant and the non-reluctant, there were no differences in preoperative characteristics. Main reasons for hesitation were fear of complications (74%) and economic burden (50%). The main reasons that they finally underwent the DBS were confidence in the doctors decision (80%) and encouragement from their family (36%). CONCLUSIONS Building trust between patients and physicians is an important factor in guiding patients to undergo this treatment. To reduce the reluctance to undergo DBS at the appropriate time, we need to find effective ways of reducing their psychological and economic burden.

Amantadine Induced Corneal Edema in a Patient with Primary Progressive Freezing of Gait

Amantadine is commonly used for Parkinsonism. However amantadine can induce adverse corneal reaction. Here we report a patient with primary progressive freezing of gait who had severe corneal edema associated with amantadine, which was reversible after discontinuation of the amantadine. This report alerts neurologists for this reversible but potentially critical corneal edema in patients with Parkinsonism who are receiving amantadine.

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

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.

Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl

Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson’s disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.

Sudden loss of the deep brain stimulation effect with high impedance without macroscopic fracture: a case report and review of the published literature

The number of deep brain stimulation (DBS) hardware complications has increased during the past decade. In cases of abnormally high lead impedance with no evidence of a macroscopic fracture, optimal treatment options have not yet been established. Here, we present the case of a 49-year-old woman with a 12-year history of Parkinson’s disease who received bilateral subthalamic nucleus DBS in March 2006. The patient showed good control of parkinsonism until December 24, 2010, when she awoke with abrupt worsening of parkinsonian symptoms. At telemetric testing, lead impedances were found at >2,000 Ω in all four leads on the left side. Fracture of a lead or an extension wire was suspected. However, radiological screening and palpation revealed no macroscopic fracture. In June 2011, the implantable pulse generator (IPG) was changed under local anesthesia without any complications. Postoperatively, her parkinsonism immediately improved to the previous level, and the lead impedance readings by telemetry were also normalized. The disconnection of the neurostimulator connector block and the hybrid circuit board of the IPG was confirmed by destructive analysis. The present report illustrates that a staged approach that starts with simple IPG replacement can be an option for some cases of acute DBS effect loss with high impedance, when radiological findings are normal, thereby sparing the intact electrodes and extension wires.

Amantadine and the Risk of Dyskinesia in Patients with Early Parkinson’s Disease: An Open-Label, Pragmatic Trial

Objective We examined whether amantadine can prevent the development of dyskinesia. Methods Patients with drug-naïve Parkinson’s disease (PD), younger than 70 years of age and in the early stage of PD (Hoehn and Yahr scale < 3), were recruited from April 2011 to December 2014. The exclusion criteria included the previous use of antiparkinsonian medication, the presence of dyskinesia, significant psychological disorders, and previous history of a hypersensitivity reaction. Patients were consecutively assigned to one of 3 treatment groups in an open label fashion: Group A-1, amantadine first and then levodopa when needed; Group A-2, amantadine first, dopamine agonist when needed, and then levodopa; and Group B, dopamine agonist first and then levodopa when needed. The primary endpoint was the development of dyskinesia, which was analyzed by the Kaplan-Meier survival rate. Results A total of 80 patients were enrolled: Group A-1 (n = 27), Group A-2 (n = 27), and Group B (n = 26). Twenty-four patients were excluded from the analysis due to the following: withdrawal of amantadine or dopamine agonist (n = 9), alternative diagnosis (n = 2), withdrawal of consent (n = 1), and breach in the protocol (n = 12). After exclusion, 5 of the 56 (8.93%) patients developed dyskinesia. Patients in Group A-1 and A-2 tended to develop dyskinesia less often than those in Group B (cumulative survival rates of 0.933, 0.929, and 0.700 for A-1, A-2, and B, respectively; p = 0.453). Conclusion Amantadine as an initial treatment may decrease the incidence of dyskinesia in patients with drug-naïve PD.

Liquid levodopa-carbidopa in advanced Parkinson's disease with motor complications

While levodopa, carbidopa, ascorbic acid solution (LCAS) therapy has been used in patients with advanced Parkinsons disease (PD) for many years, long-term follow-up data is scarce. The present study aimed to determine the long-term retention rate for LCAS therapy, and to identify the causes of LCAS therapy withdrawal. Our study included a series of 38 patients with PD (14 men and 24 women) who underwent LCAS treatment between 2011 and 2013 to alleviate motor complications that were not satisfactorily controlled by optimized conventional anti-parkinsonian treatment at the Seoul National University Hospital. All patients were admitted to educate them about and initiate LCAS treatment for 2-5days, and were then followed up as outpatients. The mean follow-up duration was 12.8months, and three main reasons for LCAS treatment discontinuation were worsening of wearing-off symptoms (8 patients), persistent dyskinesia (4 patients), and poor drug adherence (4 patients). Fourteen patients (36.8%) maintained the LCAS treatment after 12months, and were categorized as the treatment-retention group. The mean percentage of on time without dyskinesia significantly increased from 33.6±17.6% to 57.0±27.7% after LCAS initiation (p=0.016) in the treatment-retention group. Twelve patients (31.6%) were still receiving LCAS treatment after 30months. LCAS treatment can be a non-device assisted therapeutic option for patients who have no access to advanced therapies such as deep brain stimulation and infusional treatments.

In need of something better than sleep

In July, 2010, a 32-year-old woman was refered to us with history of mild fever and headache. She had no other symptoms and signs and initial clinical examination and laboratory tests including chest X-ray and urine analysis were done to fi nd the origin of fever. Results of the examination and laboratory tests were negative, and aseptic meningitis was suspected. Cerebrospinal fl uid showed 125 cells (64% neutrophils and 27% lymphocytes) and protein and glucose at 0·57 g/L and 3·28 mmol/l, respectively. She was diagnosed with aseptic meningitis and treated conservatively. However, she became more drowsy and a follow-up CSF test on the fi fth day in hospital showed 500 cells (96% lymphocytes), protein 1·2 g/L, and glucose 3·44 mmol/L,. MRI of the brain showed bilateral sym metrical hyperintensity in the midbrain on the T2weighted images (fi gure A). Laboratory tests for infectious agents, including Japanese B virus, herpes simplex virus, and HIV were negative. A diagnosis of encephalitis was made, and acyclovir and antituber culosis agents were started. Her level of consciousness improved over the next 3 days; however, she began to develop severe generalised rigidity of the limbs and bulbofacial muscles. She could not move her limbs or open her mouth at all. Tizanidine, clonazepam, and levodopa were tried without benefi t and continuous intravenous diazepam with oral baclofen gave her some relief. Her symptoms began to improve 3 weeks later, and at discharge in September, 2010, she was able to talk and swallow. She continued to improve and by December, 2010, she had only mild diffi culties in daily life activities. In January, 2011, a striking change occurred in her symptoms. She woke each morning with good motor function which lasted only 10–15 min, after which she developed severe generalised rigidity (see video)—which only partly and transiently improved by taking a nap. The condition continued until December, 2011, when she was reff ered to our hospital. Neurological examination in the Lancet 2013; 381: 598

Musculoskeletal Problems Affect the Quality of Life of Patients with Parkinson’s Disease

Objective Musculoskeletal problems are more common in patients with Parkinson’s disease (PD) than in normal elderly, but the impact of musculoskeletal problems on health-related quality of life (HRQoL) in patients with PD is unknown. Methods Four hundred consecutive patients with PD were enrolled for the evaluation of musculoskeletal problems and HRQoL. HRQoL was assessed by the 36-Item Short Form Health Survey, which comprised physical health and mental health. Results Of the total patients, 265 patients had musculoskeletal problems, and 135 patients did not have musculoskeletal problems. Patients with musculoskeletal problems reported lower levels of HRQoL in terms of physical health than did patients without musculoskeletal problems (p < 0.05). In women, all components of physical health were lower in patients with musculoskeletal problems than in patients without musculoskeletal problems (p < 0.05). Meanwhile, in men, only the bodily pain score of physical health was lower in patients with musculoskeletal problems than in patients without musculoskeletal problems. Mental health and physical health were negatively correlated with depression, Unified Parkinson’s Disease Rating Scale I & II scores, and pain severity from musculoskeletal problems, in that order (p < 0.01 for all). Conclusion These results suggest that musculoskeletal problems in patients with PD affect HRQoL significantly, mainly in terms of physical health rather than mental health and especially in women rather than men. Musculoskeletal problems should not be overlooked in the care of patients with PD.