Objective To assess the effectiveness and safety of flunarizine for refractory epilepsy. Methods Relevant randomized controlled trials (RCTs) were searched from the database of PubMed, EMbase, Cochrane Library, CNKI, CBM, and VIP, and the related references were traced to obtain the information. The methodological quality of included RCTs was assessed using Jadad scale and meta-analysis was performed using RevMan 5.0 software. Results A total of eight studies involving 545 patients were included. The results of meta-analyses showed that: based on the conventional therapy, compared with placebo and none-treatment, flunarizine was more effective on adults and children with refractory epilepsy (OR=2.98, 95%CI 1.88 to -4.73; OR=33.75, 95%CI 4.13 to -276.00). Major adverse events of flunarizine were fatigue, dizziness, headache, and weight gain etc. All those symptoms except for the weight gain were observed in the early stage of medication, which might get self-cured or could disappear by constant medication or reducing the dose or symptomatic treatment. Conclusion The present study shows that based on the conventional therapy, flunarizine is effective and safe for refractory epilepsy.
Objective To observe the efficacy and safety of pars plana vitrectomy (PPV) combined with subretinal injection of dexamethasone in treating refractory diabetic macular edema (DME). MethodsA prospective case study. From January 2024 to March 2024, 9 cases with 10 eyes of refractory DME diagnosed at Tianjin Eye Hospital were included in the study. All eyes had a central macular thickness (CMT) of greater than 275 μm despite receiving intravitreal injection of anti-vascular endothelial growth factor (VEGF) drug at least 5 times. All eyes underwent 25G PPV combined with internal limiting membrane (ILM) peeling and subretinal injection of dexamethasone sodium phosphate. Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography examinations were performed on all eyes before and 1 and 3 months after surgery. BCVA was assessed using an international standard visual acuity chart and converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Paired t-tests were used to compare changes in BCVA, mean macular sensitivity (MS), and CMT before and after surgery. The intraoperative and postoperative complications were recorded. ResultsAmong the 9 cases with 10 eyes, there were 4 males with 5 eyes and 5 females with 5 eyes. Age ranged from 43 to 79 (65.3±10.8) years. Preoperative and postoperative logMAR BCVA at 1 and 3 months were 0.84±0.25, 0.72±0.31, and 0.63±0.22, respectively. MS was (16.48±5.03), (16.6±6.31), and (18.0±5.33) dB, respectively. CMT was (437.5±90.4), (306.9±87.4), and (288.7±87.3) μm, respectively. Compared with data before surgery, BCVA: the difference was not statistically significant at 1 month (t=2.025, P=0.074), but was statistically significant at 3 months (t=5.161, P=0.001), MS: the differences at 1 and 3 months were not statistically significant (t=-0.078, -1.022, P=0.940, 0.334), CMT: the differences were of statistical significance at both 1 and 3 months (t=2.892, 3.175, P=0.018, 0.011), and the difference between 1 and 3 months post-surgery was also statistically significant (t=2.427, P=0.038). No complications such as macular hole, vitreous hemorrhage, or retinal detachment occurred during or after surgery in any eyes. No cases of increased intraocular pressure or cataracts were reported during the follow-up period. ConclusionPPV combined with ILM peeling and subretinal injection of dexamethasone can effectively reduce CMT in refractory DME eyes and improve visual acuity, with good safety.
Objective To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV). MethodsA prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance. ResultsEighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA (F=50.298) gradually increased, CRT (F=25.220), PED height (F=144.16), SFCT (F=69.77), LVCT (F=136.69), CVI (F=72.70) gradually decreased after treatment. The differences were statistically significant (P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. ConclusionSubretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.
ObjectiveTo investigate the association between mTOR pathway and pharmacoresistance of Sprague-Dawley rat epilepsy model kindled by coriaria lactone. MethodsA kindling model of pharmacoresistant temporal lobe epilepsy was developed by injecting Sprague-Dawley (SD) rats with coriaria lactone (CL) (1.75 mg/kg, every 84 h). Normal SD rats were injected with normal sodium (NS) served as control group. Rats with five or more consecutive stage 5 seizures were included in kindled group. Immunohistochemistry was used to detect the levels of P-S6 in both groups. ResultsThe expressions of P-S6 in CA1 and CA3 were significantly higher compared with control group, and were mainly in astrocytes (P < 0.001). In addition, the expression of P-S6 in DG area was significantly higher than that in control group, with more granular cell and neuron (P < 0.001). ConclusionsThe mTOR pathway may be correlated with the drug resistance of refractory lobe epilepsy kindled by coriaria lactone.
Ketogenic diet (KD) is one of the effective treatments for refractory epilepsy (RE) and is recommended when anti-seizure medications (ASMs) are ineffective or less effective, inoperable or ineffective. The efficacy of the medium-chain triglyceride (MCT) ketogenic diet is as good as the classical KD (CKD), which has been demonstrated in several retrospective, prospective, and randomized studies, and MCT is more ketogenic than long-chain triglycerides, so MCTD allows more carbohydrate and protein foods, which makes MCTD more palatable than CKD more palatable. Research advances in the mechanisms and clinical efficacy associated with MCTD in the treatment of refractory epilepsy are reviewed.
Objective To observe the therapeutic effect of autologous neurosensory retinal transplantation in repairing unhealed giant macular hole after pars plana vitrectomy (PPV). MethodsA prospective clinical study. From July 2022 to December 2023, 12 patients (12 eyes) with refractory large macular hole who received autologous neurosensory retinal transplantation treatment in Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University were selected for the study. The macular hole in affected eyes still did not close after PPV combined with inner limiting membrane removal or tamponade, and the diameter of macular hole were greater than 600 μm. All affected eyes received best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. The BCVA examination employed the international standard visual acuity chart, with results converted to logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. During the surgery, a piece of healthy retinal neuroepithelial tissue, approximately 0.3 optic disc diameters larger than the macular hole, was removed from the upper retinal periphery and used as a graft. The graft was inserted into the macular hole with the aid of intraoperative OCT. Post-surgery, the vitreous cavity was filled with silicone oil or sterile air. The follow-up period after surgery was 6 months. The thickness of the retinal grafts was measured using the same equipment as before surgery at 3 days, 1, 3, and 6 months post-surgery. The primary focus was on observing the macular hole closure rate and changes in BCVA at 6 months post-operation. A paired t-test was used to compare BCVA before and after surgery. Results In the sample of 12 cases (12 eyes), there were 5 males with 5 eyes and 7 females with 7 eyes. The mean age was (50.4±12.6) years. The mean macular hole diameter was (1 085.6±344.0) μm; The mean eye axis length was (27.64±4.19) mm. At 6 months after surgery, all affected eyes showed macular hole were completely closed (100.0%, 12/12). The thickness of the retinal graft was measured as (206.8±21.0), (170.8±23.3), (165.6±31.6), and (157.9±31.1) μm at 3 days, 1, 3, and 6 months post-surgery, respectively. At before and 6 months after surgery, the logMAR BCVA of the affected eyes was 1.28±0.39 and 0.95±0.22, respectively. The difference in logMAR BCVA before and after surgery was statistically significant (t=3.40, P<0.05). Conclusion Autologous neurosensory retinal transplantation could effectively improve the closure rate of refractory large macular hole and improve or stabilize vision in the short run.
ObjectiveTo discuss the practical methods of clinical drug therapy with clinical pharmacists' participation. MethodThe patient was male and at the age of 88. Because of "exertional heart tiredness for 4 years, coughing sputum for 10 days, and sudden inarticulate condition", he was admitted into the hospital on November 22nd, 2013. The diagnosis was cerebral infarction with pulmonary infection. Clinical pharmacists participated in the consultation on February 19th, 2014 because the uncontrollable repeated pulmonary infection. By analyzing the therapeutic scheme, clinical pharmacists made and adjusted the treatment scheme for one patient with refractory infections. ResultsAfter the treatment scheme was adjusted, several laboratory test results of the patient returned to normal, including respiratory rate, body temperature, white blood cell count and neutrophils. Sputum volume decreased obviously and sputum culture was negative. Lung signs and image were significantly improved. ConclusionsClinical pharmacists should pay more attention to the analysis of the clinical therapeutic scheme to improve therapeutic efficacy for patients with refractory infections.
ObjectiveTuberous sclerosis complex (TSC) is a multisystem disease, which often manifests as refractory epilepsy in the nervous system and multifocality in Magnetic resonance imaging (MRI). We summarized patients with TSC whose peripheral blood gene test was negative,and analyzed their medical history, EEG, MRI and postoperative conditions. MethodsWe summarized and analyzed 205 patients with TSC diagnosed clinically and pathologically and underwent surgery from April 2008 to February 2024. 11 patients with TSC whose peripheral blood gene test was negative and underwent surgery were screened out.All patients underwent gene examination, MRI and long-range video EEG monitoring. All patients underwent detailed preoperative evaluation and direct resection surgery, intracranial electrode thermocoagulation surgery or laser surgery. ResultsOf the 11 patients with peripheral blood gene test negative, 11 (100%) patients achieved Engel Ⅰ within 1 year after surgery, and 10 (91%) patients achieved Engel Ⅰwithin 2 years. The median age of onset of 11 patients was 6 months, and 8 patients (73%) had onset less than 1 year old. All patients had multiple nodules in the brain. Except for the brain, the changes of the other organs were polycystic kidney and skin changes in 2 patients, skin changes in 8 patients, and normal in 1 patients. ConclusionTSC patients with peripheral blood gene negative who have young onset age, frequent seizures, and multiple nodules on MRI often present with refractory epilepsy. However, the postoperative effect is good, and the postoperative EEG of most patients is normal.
Objective To assess the effectiveness and safety of progabide (PGB) for refractory epilepsy. Methods Randomized controlled trials (RCTs) on PGB treating refractory epilepsy were searched from the following databases as PubMed, EMbase, The Cochrane Library, CNKI, CBM and VIP from the date of their establishment to July 2011. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods by two reviewers independently, and after the quality was evaluated and cross-checked, meta-analyses were conducted using RevMan 5.1 software. Results A total of seven studies involving 231 patients were included. The results of Meta-analyses showed that based on the conventional therapy, PGB was ineffective in treating refractory partial epilepsy compared with the placebo (OR=1.76, 95%CI 0.40 to 7.65, P=0.45), but it was superior to the placebo in treating refractory partial and generalized epilepsy (OR=4.46, 95%CI 2.06 to 9.65, P=0.000 1). The main adverse events of PGB were somnolence, dizziness and headache, which were mild and transient, which could turn to normal after reducing the dose of PGB and only a few patients needed to stop taking PGB. Conclusion Current studies shows that progabide may be effective in treating refractory partial and generalized epilepsy, but its effectiveness in treating refractory partial epilepsy is still unknown. The side effects of PGB are mostly mild. For the possibility of moderate selection bias existing in the quality of the included studies which may affect the authenticity of outcomes, so this conclusion still needs to be further proved by conducting more high-quality, large-scale and double-blinded RCTs.
Objective To summarize the clinical experience in the treatment of refractory decubitus ulcers.Methods From May 1998to March 2005, 22 patients with decubitus ulcers(29 decubitus ulcers) were admitted, whose age was 3692 years. The lesion size was 4 cm×2 cm to 18 cm×15 cm. The locations of decubitus ulcers were the sacrococcygeal region(18 cases), the tuber ischiadicum region (6 cases) and the trochanter major region(5 cases).Enteral nutrientwas given orally and the wound was treated with Wuhuangyihao 8-15 days. Three diabetic patients were injected with insulin. According to patient’s age, ulcer position, ulcer extent and ulcer degree, the flap type was determined. Three wounds were repaired by local flaps, the flap size was 6 cm×4 cm-12 cm×10 cm; 10 by fasciocutaneous flaps, 10 cm×7 cm-20 cm×17 cm; 9 by gluteus maximusmyocutaneous flaps, 13 cm×11 cm-17 cm×14 cm; and 6 by longhead of biceps femoris flaps,11 cm×6 cm-14 cm×7 cm. One was sutured directly. After operation, the patients were placed on airflow suspended bed 7-14 days.Results General nutritional status was improved, hemoglobin was greaterthan 100 g/L, albumen was greater than 30 g/L. Necrosis tissue was removed, granulation tissue turned into fresh, secretion reduced and no redness and swelling occurred in wound. All flaps survived and the wounds healed by first intention. After a followup of 6 months to 5 years, no patient had a recurrence, the color and texture of the flaps were good, the appearance was satisfactory.Conclusion Applying the technique of combined treatment can accelerate the healing of refractory decubitus ulcers and improves the success of operation.