Volume 97  ·  Issue 37  ·  2017

International Consensus on the Management of myasthenia gravis (MG) (2016)^[1]The International Consensus (hereinafter referred to as International Consensus) follows the Japanese Guide^[2]European Guide^[3,4], UK Guide^[5,6]And China Guide^[7]After the most complete and innovative treatment management consensus. This article will interpret the innovation of this consensus in MG treatment and its impact on the treatment of MG patients in China.

To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis.

We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc.

(1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO₂) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the increased blood PCO₂ (P=0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood PCO₂ (P=0.007). The perioperative period of thymectomy would not increase the risk of crisis.

Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO₂, expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.

To evaluate the expression and clinical significance of plasma platelet derived growth factor (PDGF) in the patients with myasthenia gravis (MG).

Plasma samples from 44 MG patients and 34 healthy people were collected from August 2015 to December 2016 from the Second Affiliated Hospital of Harbin Medical University. The expression of PDGF was detected by MILLIPLEX MAP Reagent kit. Furthermore, we analyzed the associations between PDGF expression level and quantitative myasthenia gravis score (QMG).

The expression of PDGF in plasma was significant lower in MG patients (5.8±1.3) compared with control group (10.1±2.2), and the difference was statistically significant (t′=-9.767, P<0.001). Meanwhile it was positively related to QMG (r=0.777, P<0.01). However, no significant difference in expression of PDGF in MG subgroups was observed.

The expression of PDGF decreases in MG patients, has positive correlation with MG severity, and is not related to age, sex and the pathology of thymus samples.

To explore the clinical and electrophysiological features and prognosis of distal myasthenia gravis (MG).

Data of MG patients in Beijing Tiantan Hospital from October 2016 to March 2017 were reviewed, including thorough neurological examinations, nerve conduction studies, repetitive nerve stimulations (RNS) and needle electromyographies. Distal MG patients were included and were analyzed as to their clinical and electrophysiological features and response to treatments.

Four patients (7.7%) could be classified as distal type among 52 definitely diagnosed MG patients. They had initial symptoms at age 36 to 64 and developed distal limb muscle weakness in the first month to 6 years after the onset of this disease. Hand muscles were preferentially involved in a non-uniform way. And one patient also had leg weakness on his tibialis anterior muscles. RNS showed a more significant decrement at slow rates in distal muscles, compared with proximal muscles. The baseline compound muscle action potentials (CMAP) of the distal affected muscles presented with slightly decreased or fluctuating amplitudes. Their weakness of ocular, bulbar, proximal and distal limb muscles improved generally after administration of acetylcholinesterase inhibitors or steroids plus acetylcholinesterase inhibitors. Electrophysiological reexaminations revealed increased baseline CMAPs, reduced decrement on RNS, and relief of myogenic changes on needle electromyography.

Relatively prominent distal limb muscle weakness can be found in a minority of MG patients. Besides profound decrement on slow rate RNS, the involved distal muscles may have a characteristic decreased baseline CMAP, sometimes with a diurnal fluctuation. Distal MG responds well to regular treatments. Its short-term prognosis seems similar to that of common MG with proximal predominance.

To discuss the correlation of permeability surface (PS) with hematoma and edema volume in acute spontaneous putaminal and thalamic hematoma using CT perfusion imaging.

A total of 48 acute spontaneous putaminal and thalamic hemorrhage patients were enrolled in this study during October 2015 and December 2016 at the First Affiliated Hospital of Wenzhou Medical University. At the image slice with maximum size of hematoma, PS was measured by drawing various regions of interest (ROI) including"hot spots", perihematomal regions, outward regions, hemisphere regions and contralateral mirror regions. The relative PS (rPS) was calculated as the ratio of ipsilateral to contralateral PS value in each ROI. Hematoma and edema volumes were traced and obtained with commercial software.

The"hot spots"PS ((2.8±1.5) ml·100 g^-1·min^-1) and perihematomal PS ((2.1±1.4) ml·100 g^-1·min^-1) were both significantly higher than the PS of the contralateral mirror regions ((1.1±0.5) ml·100 g^-1·min^-1) (P<0.001). There was no significant difference in outward regions PS and contralateral mirror regions PS (P>0.05), nor in hemisphere regions PS and contralateral mirror regions PS (P>0.05). There was no significant difference in"hot spots"rPS and perihematomal rPS (P=0.218). The"hot spots"rPS and Perihematomal rPS were both higher than the rPS of the outward and hemisphere regions (P<0.01). There was no significant difference in the outward and hemisphere regions (P<0.01). The median hematoma volume was 12.63 ml and the median edema volume was 12.36 ml. The edema volume had a positive association with the hematoma volume(r=0.799, P<0.001) and perihematomal PS(r=0.465, P=0.001). Perihematomal PS had a positive association with the hematoma volume (r=0.386, P=0.007).

The damage of blood-brain barrier around acute spontaneous hematoma can be measured via CT perfusion imaging. Perihematomal PS was associated with the hematoma and edema volume.

To investigate the diagnostic value of diffusion-weighted imaging (DWI) and apparent diffusion coefficient(ADC) values in the differentiation of sellar malignant germ cell tumors and raniopharyngioma.

This retrospective study included 36 patients(14 cases of malignant germ cell tumor and 22 patients with raniopharyngioma) with histopathologically-confirmed sellar tumors from January 2013 to April 2017 in the First Affiliated Hospital of Zhengzhou University.All patients underwent conventional MRI and DWI before the treatment. ADC maps were reconstructed, and ADC values of the sellar lesions were calculated and compared between the groups. Diagnostic value of ADC was evaluated by receiver operating characteristic(ROC) curves.

The mean ADC values of malignant germ cell tumors were significantly lower than that in raniopharyngioma[(0.93±0.23)×10^-3 mm²/s vs (1.69±0.21)×10^-3 mm²/s, t=-10.19, P<0.01]. The area under the ROC curves of ADC values diagnosing malignant germ cell tumors and raniopharyngioma was 0.987. The optimal cutoff values of ADC for differential diagnosis of malignant germ cell tumors and raniopharyngioma was 1.52×10^-3 mm²/s, the sensitivity, specificity and accuracy was 81.2%, 100%, 88.9%, respectively. ADC value had a high consistency with pathological results (Kappa value was 0.887).

Malignant germ cell tumors and raniopharyngioma have different ADC value, which can improve the diagnostic accuracy.

To evaluate the value of mDIXON-Quant sequence, diffusion-weighted imaging (DWI) in quantitative diagnosing of the sacroiliitis stages in patients with ankylosing spondylitis (AS).

Based on the Bath Ankylosing Spondylitis Activity Index (BASDAI) and laboratory parameters, a total of 51 patients were diagnosed with AS. They were divided into two groups as early active group (n=20) and chronic active group (n=31), and at the same time, 25 healthy people from Tianjin were included as control group. The regular MRI sequences and mDIXON-Quant sequence, DWI were obtained. The apparent diffusion coefficient (ADC) and fat-signal fraction (FF) value of bone marrow with edema of the sacroiliac joints in early active group and chronic active group and of subchondral bone marrow of sacroiliac joint in control group all were measured by ADC maps and FF maps. Mean (FF, ADC) values were compared between groups.

The ADC value of the early active group, chronic active group and the control group is (1.07±0.20)×10^-3mm²/s, (1.00±0.22)×10^-3mm²/s, (0.25±0.07)×10^-3mm²/s, respectively, and the differences of ADC value between early active group and control group, chronic active group and control group were significant (P<0.01), but the difference of the ADC value between early active group and chronic active group was not significant (P=0.394). That is to say, the ADC value can′t distinguish the early active group and chronic active group. The differences of FF value between groups was significant (P<0.01), and the FF value of bone marrow with edema in chronic active group were higher than that in early active group.

The mDIXON-Quant sequence can quantitatively diagnose early active group and chronic active group, and the diagnostic value is better than DWI. Thus, it can provide guidance for clinical treatment and prognosis.

To determine the anatomical relation between the carotid artery or laryngopharynx and the needle path via anterolateral oblique approach to C2 vertebral body, and whether the simulated path can direct the actual procedure.

Contrast agent was injected into bilateral carotid arteries of 10 fresh cadavers (20 sides), and then CT scans were performed on each subject. Bilateral simulated puncture paths were simulated on the image of two-dimensional reconstruction CT. The distance between the puncture site and middle line(AC), the angle between the simulated puncture paths and the median sagittal plane (AOB), the distance between the simulated puncture paths and the side wall of hypopharynx, or the carotid artery was measured respectively. Under the guidance of fluoroscopy, oblique puncture via anterolateral to C2 was performed according to the simulated parameters, and then CT was done. The actual needle path was measured on the image of two-dimensional reconstruction CT. The outcomes were compared by using paired t test between groups.

Bilateral simulated puncture paths in all 10 cadavers were achieved on the image of CT. The bilateral punctures via anterolateral to C2 were successfully performed under fluoroscopic guidance in 10 cadavers, and the actual needle path could be showed on the image of two-dimensional reconstruction CT. The AC, angle AOB, the distance to carotid artery and side wall of laryngopharyngeal of the left simulated path was(4.7±1.0)cm, (33±8)°, (6.7±2.6)mm, (6.6±2.8)mm, respectively; and those in the right side was(5.2±1.3) cm, (36±8)°, (7.5±2.2) mm, (7.2±2.5) mm, respectively.The AC, angle AOB, the distance to carotid artery and side wall of laryngopharyngeal of the left actual needle was(4.5±1.1) cm, (33±9) °, (6.7±3.0) mm, (7.1±3.9) mm, respectively; and those in the right side was(5.1±1.5) cm, (35±10) °, (7.4±2.1) mm, (7.2±2.6) mm, respectively.And the actual and simulation data of both sides were compared and no significant differences was found by t test (t=0.104-1.882, all P>0.05).

The simulated approach via anterolateral to C2 can be achieved on the image of two-dimensional reconstruction CT, it is consistent with the real needle path and can be used to direct the actual practice to improve the accuracy and safety.

To evaluate the application and clinical results of two-stage total hip arthroplasty in the treatment of the deep hip infection following the internal fixation of hip fractures.

From May 2007 to November 2014, 21 patients with active hip infection secondary to internal fixation of hip fractures were treated with two-stage total hip arthroplasty using a temporary antibiotic-loaded cement spacers. Of 21 cases, 15 were males and 6 were females, aged from 27 to 64 years (mean, 45); there are 18 cases of femoral neck fractures and 3 cases of intertrochanteric fractures. The serologic examination and X-ray were taken at 1 month, 3 months, 6 months, 12 months and annually thereafter post-operatively to evaluate the clinical results and prosthesis status. Harris hip score system was used to evaluate the joint function.

All patients were successfully treated with two stage operations under general anesthesia. The operational interval was 12-44 weeks (mean, 21) and 1 spacer breakage. For the arthroplasty, cementless components were used in 20 cases and cemented component was use in 1 case. The patients were followed up 25-102 months ( mean, 55 ) and infections were eradicated in all hips. The Harris hip score was improved from 23.24±11.81 pre-operatively to 90.24±3.92 post-operatively and the difference was statistically significant (P<0.05). According to this scoring criteria, the excellent and good rate reached up to 95%. At latest fellow-up, the location of prosthesis were well and the function of hip joint was satisfied. All cases had no dislocation, periprosthetic fracture, ectopic ossification or any other complications at the latest fellow-up.

By means of an antibiotic-loaded cement spacer, two-stage total hip arthroplasty is an effective salvage procedure eradicating infection and providing functional improvement to the infected internal fixation of hip fractures. The early and mid-term clinical effects are satisfied.

To investigate the percutaneously looped thread transection for treatment of stenosing tenosynovitis and evaluate its treatment outcome.

From January 2014 to October 2016, Eighty-four patients with stenosing tenosynovitis were randomly divided into the open decompressionand group (42 cases) and percutaneously looped thread transection group (42 cases) in Department of Orthopedics, Affiliated Laiwu Hospital of Taishan Medical College. Incision near the digit horizontal stripes, tendon sheath were cut off in the open decompressionand group. Percutaneously looped thread transection was under the guidance of ultrasound, threading from the deep and shallow transverse tendon sheath, respectively, forming loops to cut off and decompressed the flexor tendon. Visual analog scale(VAS) was used to evaluate the extent of pain before the operation and 1 or 4 weeks after the operation, the comprehensive curative effect were evaluated 3 months after the operation.

In the two groups pain was alleviated. The VAS improved from (7.0±1.3)prior operation to(5.2±1.6) and (2.8±1.1)1 week and 4 weeks after the operation in the open decompressionand group , respectively. The difference before and after the operation was significant(P<0.05). The VAS improved from (7.1±1.4) prior operation to(2.7±1.3) and (0.6±0.2)1 week and 4 weeks after the operation in the percutaneously looped thread transection group, respectively. The difference before and after the operation was significant(P<0.05). The difference of VAS scores between two groups at 1 week and 4 weeks after the operation were different(P<0.05). The difference of the comprehensive curative effect between two groups at 3 months after the operation were not different(P>0.05). There were no infection, poor healing, blood vessel and nerve damage after operation in both two groups.

Percutaneously looped thread transaction under ultrasound for the surgical treatment of stenosing tenosynovitis has less trauma and rapid recovery. It has such advantage as being effective, simple , and reach the same effects as the open decompression surgery.

By the preliminary comparison study on the constituent ratio and clinical characteristics of polycystic ovary syndrome (PCOS) in Tibetan and Han women in Tibetan Plateau, we aimed to find the relevance of its pathogenic factors, and to guide the treatment of PCOS in the plateau region and improve the prognosis.

The general situation and clinical data of 165 patients who were diagnosed with PCOS from December 1, 2015 to November 30, 2016 in the Department of Obstetrics and Gynecology of the People′s Hospital of Tibet Autonomous Region were analyzed retrospectively. The prevalence of PCOS among Tibetan and Han women in Tibetan Plateau were compared.

(1) A total of 1 520 patients were treated in the Tibet Autonomous Region People′s Hospital gynecological endocrinology clinics in one year (Tibetan 865 cases, Han 617 cases, other ethnic groups 38 cases), of which patients with PCOS accounted for 10.9% (165/1520). (2) The incidence of Tibetan PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 21.2% (35/165), 20.6% (34/165), 16.4% (27/165), 28.5% (47/165), 17% (28/165), 38.2% (63/165), 23.6% (39/165), and 36.4% (60/165), respectively. The incidence of Han PCOS patients with oligomenorrhea, infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI≥24), and waist circumference >80 cm were 7.9% (13/165), 10.3% (17/165), 9.1% (15/165), 15.2% (25/165), 9.7% (16/165), 14.5% (24/165), 10.9% (18/165) and 19.4% (32/165), respectively. The proportion of high testosterone in Tibetan PCOS patients was higher than that in Han PCOS patients with statistically significant. (3) The chief complaint of Tibetan PCOS patients were oligomenorrhea and infertility, and the chief complaint of Han PCOS patients were infertility and amenorrhea. (4) The constituent ratio of outpatient clinics in Nyingchi who were with PCOS at an average elevation of about 3 000 meters in the Tibetan Plateau was 7.9% (13/165), and the average constituent ratio in Lhasa, Xigatse and Nagqu over 3 500 meters above sea level was 35.8% (59/165), 16.9% (28/165) and 15.8% (26/165), respectively.

The prevalence of PCOS in Tibetan areas is slightly higher than that in the international community. The clinical manifestations of Tibetan patients with PCOS are significantly different from those of Han patients with PCOS. The higher the altitude, the higher the incidence of PCOS.

To summarize the clinical features of patients with ovarian tumor and anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis, and to explore the influence of operation patterns on the prognosis.

The clinical information of patients with ovarian tumor and anti-NMDAR encephalitis in The 3rd Affiliated Hospital of Sun Yat-Sen University and The Zhujiang Hospital of Southern Medical University were collected and analyzed.

There were 15 patients were enrolled in this study, with the average age of 24.5±5.0 years old. The most frequent first symptom was psychosis. The main clinical features were psychosis, seizures, conscious disturbance, autonomic dysfunction, dyskinesia, central hypoventilation and impaired memory. Most patients′ symptoms were relieved after immunotherapy and surgery. The number of favorable prognosis of patients (mRS score 0-2) with ovariectomy was higher than that of the patients with ovarian cystectomy (5 vs 3). But the difference had no statistical significance (P=0.529).

For young female patients with psychosis, we should be alert to the possibility of anti-NMDAR encephalitis and screen for tumor. Treated with immunotherapy and operation, most patients can get a favorable prognosis.

To analyze the ultrasonographic and clinicopathological features of primary thyroid lymphoma(PTL).

The ultrasonographic and clinicopathological featuresof 21 cases of pathologically-confirmed PTLs were analyzed retrospectively.

Of all 21 PTLs, 15 cases were diffuse large B-cell lymphoma, 4 were mucosal-associated lymphoid tissue extranodular marginal zone B-cell lymphoma, 1 was small B-cell lymphoma and 1 was classical Hodgkin lymphoma. Eight cases were proved by pathology with concomitant Hashimoto′s thyroiditis. Ultrasonography observed bilateral or unilateral asymmetric goiter (21/21, 100.0%), marked hypoechogenicity (21/21, 100.0%) with posterior acoustic enhancement (19/21, 90.5%), heterogeneous echo texture with interspersed linear echogenic strands or intensive reticular echogenic strands or cloud echogenic, heterogeneous echo texture of thyroid gland (21/21, 100.0%), focal nodular hypoechoic(2/21, 9.5%) with regular or irregular shape, increased vascularity (13/21, 61.9%) and cervical lymphadenopathy (12/21, 57.1%). Two cases involved the anterior cervical muscle and 1 infiltrated trachea. Rapidly enlarging cervical mass were found in 13 cases (13/21, 61.9%)with associated compressive symptoms such as dyspnea, dysphagia and hoarseness. There was no any indisposed symptom in 3 cases.

PTL has some common ultrasonographic and clinical features, core needle biopsy should be warranted to prove PTL.Surgical resection should be considered when needed to reduce misdiagnosis.

To evaluate the influence of serum procalcitonin in the diagnosis and treatment of pulmonary infection in patients with central nervous system injury.

From October 2014 to February 2017, a retrospective study was performed. A total of 1 852 patients were screened in Department of Intensive Care Unite, First Affiliated Hospital of Sun Yat-sen University.Among them, 173 patients were identified with different kinds of infection. Finally, a total of 42 patients with pulmonary infection were enrolled. The clinical data of patients with pulmonary infection and central nervous system (CNS) injury was collected. A univariate and multivariate regression analysis was performed to study the correlation of serum procalcitonin (PCT) with clinical symptoms and signs of the pulmonary infection, body temperature(T), white blood cell count (WBC), percentage of neutrophils (NEU) and the severity of the pulmonary infection (CPIS). The relationship of serum PCT with type of CNS injury, GCS, and exogenous glucocorticoid was further studied.

During the period of pulmonary infection, the peak PCT was 0.83 (0.29, 2.79) μg/L and the CPIS was 5.50 (5.00, 7.00). In 9 of 42 patients, the peak PCT was less than 0.25 μg/L. In 7 of 42 patients, the peak PCT was ranged from 0.25 to 0.5 μg/L. In 12 of 42 patients, PCT was ranged from 0.5 to 2 μg/L. Only 10 patients had a PCT 2-10 μg/L and 4 patients had a PCT more than 10 μg/L. There is no correlation between serum PCT and body temperature, white blood cell, percentage of neutrophils and CPIS. There was no significant differences in patients with PCT<0.5 or ≥0.5 μg/L regarding the body temperature, white blood cell, percentage of neutrophils and CPIS. However, serum PCT in patients with pulmonary infection had independent correlation with the post CNS injury day ( β=0.17, 95% CI (0.02, 0.32), P<0.05). The serum PCT was 1.26 (0.47, 2.7) μg/L and 29.41% patients with a PCT less than 0.5 μg/L within 3 days post CNS injury. Serum PCT level was 0.23 (0.16, 0.39) μg/L, and 77.78% patients with a PCT less than 0.5 μg/L at day 4 to day 7 post-injury. The PCT level was 0.52 (0.33, 1.12) μg/L, and 44.44% patients with a PCT less than 0.5 μg/L at day 8 to day 14. The PCT was 3.26 (2.07, 12.40) μg/L, and no patient with a PCT less than 0.5 μg/L after day 15 post-injury. There were no significant relationship found between serum PCT level and type of the disease and surgery, GCS, and use of exogenous glucocorticoid.

Serum PCT had no significant increase and was not able to be used in guiding the antibiotics use in patients with CNS injury and pulmonary infection.

Uterine rupture is a serious complication of obstetrics. If it is not discovered in time and dealt with decisively, it will endanger the life of mothers and infants. Quick and timely diagnosis is of great significance to clinical active treatment. The Children's Hospital affiliated to Jiaxing University retrospectively analyzed the case data of 7 patients with uterine rupture confirmed by surgery between June 2009 and March 2016, and compared the preoperative ultrasound diagnostic images and clinical surgical results, aiming to explore the significance of ultrasound in rapid diagnosis of uterine rupture in pregnancy. The results are reported below.

The 21-year-old female was admitted to the First Affiliated Hospital of PLA General Hospital on July 13, 2015 due to repeated lumbosacral pain and multiple joint swelling and pain accompanied by fever for more than one year. The patient has experienced lumbosacral pain without trigger since February 2014, which occurs at night and can be relieved with slight activity, accompanied by morning stiffness for about 30 min. At the same time, there was intermittent fever, with a maximum body temperature of 38.5 ℃, and no chills and chills. Later, swelling and pain of shoulder and knee joints and limited movement appeared. Visited a hospital affiliated to a medical university, and was given total glycosides of paeony paeony capsules, sulfasalazine enteric-coated tablets orally and infliximab intravenously (the first dose was 3 mg·kg) according to "ankylosing spondylitis"^－1• d^－1and administered the same dose once each at the end of Week 2 and Week 6). At first, the above symptoms were significantly alleviated, but after 3 months, the symptoms worsened again, resulting in difficulty in walking and self-care. After several adjustments of the types and dosages of oral drugs, the symptoms did not improve significantly, so infliximab was adjusted to 5 mg · kg^－1• d^－1Once every 8 weeks, the course of treatment was about 1 year, and the improvement of symptoms was not obvious. During the course of the disease, in October 2014, he developed blurred vision in his right eye. He went to a hospital in Beijing and was diagnosed with papilledema and papillitis. After being injected with hormone bulbs, his symptoms improved slightly. In late June 2015, blurred vision in both eyes appeared, obviously in the right eye, and the symptoms did not improve after hormone bulb injection, followed by general numbness after sitting for a long time, transient loss of consciousness (consciousness became clear on its own for about 2 to 3 minutes) and labor in urinating and defecating. The body weight has been reduced by 15 kg in the past 1 year. The past history is not special, and his father has a history of "ankylosing spondylitis". Physical examination at admission: temperature 36.5 ℃, pulse 72 beats/min, breathing 18 beats/min, blood pressure 114/70 mmHg (1 mmHg =0.133 kPa). Edema of the right eyelid, subbulbar conjunctival hemorrhage (occurring after retrobulbar injection in the external hospital). Subcutaneous induration about 4 cm in diameter in the posterior part of the right occipital, tough in texture, no tenderness, and poor mobility; There were no obvious abnormalities in heart, lung and abdomen. Both shoulder joints are not swollen, with tenderness and limited lift. Both the bilateral four-word test and pelvic squeeze test were positive, and the straight leg elevation test was negative. The positional sensation of both lower limbs and lumbosacral region was normal, the reflexes of knee tendon and biceps tendon were not drawn out, and the Buchner sign, Babinsky sign and Hoffman sign were all negative.

The patient was a 73-year-old female with a history of primary Parkinson's disease for 8 years, mainly tremor in the limbs, switching phenomenon and dyskinesia for 1 year, and hypertension was denied. On physical examination, the muscle tone of the limbs was slightly increased, accompanied by quiescent tremor. Head MRI showed mild brain atrophy. Medications include dopaserazide tablets, carbazolidopa controlled-release tablets, entacapone, selegiline, amantadine, and pramipexole. The patient was admitted to the First Affiliated Hospital of Dalian Medical University on March 9, 2015. Surgery is strongly required due to the seriousness of drug-related complications. Bilateral microelectrode recordings were recorded once each during the operation. On the postoperative day, head CT showed obvious intracranial gas accumulation (FIG. 1A)。 Six days after surgery, head MR showed bilateral frontal subdural effusion (FIG. 1B), with a maximum width of about 1.96 cm. There was no significant electrode displacement. The patient had no new neurological symptoms and signs, and conservative treatment promoted hematoma absorption. Head MR was re-examined before program control at 4 weeks postoperatively (Figure 1C), with a large circulation mode, a pulse width of 90 μ s, a frequency of 110 Hz, and a voltage gradually increasing to 1.8 V, the patient experienced obvious stimulus-related adverse reactions as emotional uncontrolled crying. Adverse reactions disappeared after changing to small circulation stimulation mode. Three months after surgery, the head CT reexamination showed that the bilateral frontal subdural effusion was absorbed significantly (Figure 1D)。

Itraconazole (ITZ) is a second generation triazole broad-spectrum antifungal drug, which is widely used in various superficial and deep fungal diseases. It mainly acts on ergosterol synthase, a key enzyme on fungal cell membrane, and exerts antifungal effects^[1]。 Itraconazole is weakly basic, pK_a=3.7, ionizable only in acidic solution, while being fat-soluble, proteophilic and extremely low solubility in water. Because of its low solubility and good intestinal permeability, it is classified as Class II drug in the classification of biological drugs. The dissolution degree of drugs in digestive juice has a great influence on drug absorption^[2]。 Itraconazole oral liquid and capsule preparations are widely used all over the world, and oral liquid dosage forms are mainly used for patients with hematological tumors^[3]Children^[4], oral and esophageal candidiasis patients^[5]The capsule formulation is used in people with normal swallowing function. However, the bioavailability of oral itraconazole in human body is very low, especially in capsule preparations. After oral administration of 200 mg capsules in healthy adults, if all of them are absorbed, the theoretical blood concentration is about 5×10 based on 4 000 ml of blood⁴ng/ml, while the peak value of itraconazole in blood was only about 270 ng/ml^[6]。 Due to the low solubility of itraconazole itself and the first-pass effect, the drug is mostly inactivated and metabolized in the mucosa of the digestive tract and the liver. In the elderly and patients with gastrointestinal dysfunction, gastric acid secretion is reduced. Due to decreased absorption function, the effect of oral itraconazole is not good, and it is often necessary to increase the dose or prolong the course of treatment, causing psychological and economic burden. Therefore, how to improve the bioavailability of oral itraconazole has become a concern for clinicians and researchers, and in some research reports, food has a significant effect on the bioavailability of itraconazole (Table 1), the research progress in this aspect is summarized as follows.