Injury to the bilateral internal branch of superior laryngeal nerve (ibSLN) brings on an impairment of the laryngeal cough reflex that could potentially result in aspiration pneumonia and other respiratory illnesses. We describe a patient with traumatic cervical injury who underwent bilateral ibSLN palsy after anterior cervical discectomy with fusion (ACDF). An 75-year-old man visited with cervical spine fracture and he underwent ACDF through a right side approach. During the post-operative days, he complained of high pitched tone defect, and occasional coughing during meals. With a suspicion of SLN injury and for the work up for the cause of aspiration, we performed several studies. According to the study results, he was diagnosed as right SLN and left ibSLN palsy. We managed him for protecting from silent aspiration. Swallowing study was repeated and no evidence of aspiration was found. The patient was discharged with incomplete recovery of a high pitched tone and improved state of neurologic status. The SLN is an important structure; therefore, spine surgeons need to be concerned and be cautious about SLN injury during high cervical neck dissection, especially around the level of C3-C4 and a suspicious condition of a contralateral nerve injury.
Superior laryngeal nerve; Cervical discectomy; Cough reflex
The purpose of this study was to evaluate the different patterns of bone loss between the lumbar spine and the femur after ovariectomy in rats.
Twenty-four female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight weeks after operation, six rats from each of the two groups were euthanized. Serum biochemical markers of bone turnover including osteocalcin and alkaline phosphatase (ALP), which are sensitive biochemical markers of bone formation, and the telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption, were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae and femur were determined by micro-computed tomography.
Ovariectomized rats were found to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally, 8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss after ovariectomy was more extensive in the 4th lumbar spine compared to the femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular thinning, but in the femur, it was mainly caused by trabecular elimination.
The present study demonstrates different patterns of bone loss between the 4th lumbar spine and the femur in ovariectomized rats. Therefore, when considering animal models of osteoporosis, it is important that bone sites should be taken into account.
Bone loss; Micro-CT; Osteoporosis; Ovariectomy; Rat
The purpose of this study was to verify the appropriateness of ovariectomized rats as the osteoporosis animal model.
Twelve female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum biochemical markers of bone turnover were analyzed; osteocalcin and alkaline phosphatase, which are sensitive biochemical markers of bone formation, and C-terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption. Bone histomorphometric parameters and microarchitectural properties of 4th lumbar vertebrae were determined by micro-computed tomographic (CT) scan.
The OVX group showed on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham group, indicating increased bone turnover. Micro-CT analysis showed significantly lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX group. Furthermore, the OVX group was found to have a significantly lower trabecular bone volume fraction (p=0.002).
Our results showed that bone turnover was significantly increased and bone mass was significantly decreased 8 weeks after ovariectomy in rats. Thus, we propose that the ovariectomized rat model be considered a reproducible and reliable model of osteoporosis.
Bone loss; Bone turnover; Osteoporosis; Ovariectomy; Rat
Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.
Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.
Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).
VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.
Valproic acid; Spinal cord injury; Clip compression model; Acetylation; HDAC inhibitor
It is debatable whether an anterior oblique fracture orientation is really a contraindication to anterior odontoid screw fixation. The purpose of this study was to investigate the feasibility of anterior odontoid screw fixation of type II and rostral shallow type III fracture with an anterior oblique fracture orientation.
The authors evaluated 16 patients with type II and rostral shallow type III odontoid fracture with an anterior oblique fracture orientation. Of these 16 patients, 8 (group 1) were treated by anterior odontoid screw fixation, and 8 (group 2) by a posterior C1-2 arthrodesis.
Of the 8 patients in group 1, seven patients achieved solid bone fusion (87.5%), and one experienced screw back-out of the C-2 body two months after anterior screw fixation. All patients treated by posterior C1-C2 fusion in group 2 achieved successful bone fusion. Mean fracture displacements and fracture gaps were not significantly different in two groups. (p=0.075 and 0.782). However, mean fracture orientation angles were 15.3±3.2 degrees in group 1, and 28.6+8.1 degrees in group 2 (p=0.002), and mean fragment angulations were 3.2±2.1 degrees in group 1, and 14.8±6.7 degrees in group 2 (p=0.001).
Even when the fracture lines of type II and rostral shallow type III fractures are oriented in an anterior oblique direction, anterior odontoid screw fixation can be feasible in carefully selected patients with a relatively small fracture orientation angle and relatively small fragment angulation.
Fracture; Fracture orientation; Internal fixation; Odontoid process
Vertebral artery (VA) injury is a rare and serious complication of cervical spine surgery; this is due to difficulty in controlling hemorrhage, which can result in severe hypotension and cardiac arrest, and uncertain neurologic consequences. The authors report an extremely rare case of a 56-year-old woman who underwent direct surgical repair by end-to-end anatomosis of an unanticipated VA injury during C2 pedicle screwing. Postoperatively, the patient showed no neurological deterioration and computed tomography angiography of the VA demonstrated normal blood flow. Although direct occlusion of an injured VA by surgical ligation or endovascular embolization has been used for management of an unanticipated VA injury during surgery, these methods may be associated with significant morbidity and mortality. However, despite its technical demand, microvascular primary repair can restore normal blood flow and minimizes the risk of immediate or delayed ischemic complications. Here we report an iatrogenic VA injury during C2 pedicle screwing, which was successfully treated by end-to-end anastomosis.
Vertebral artery injury; End-to-end anastomosis; Atlantoaxial complex
Intermittent claudication (IC) is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). In order to prevent misdiagnosis of vascular disease, it is important to know the incidence of and risk factors for PAD in patients with LSS. Therefore, the aim of our study was to evaluate the incidence of and risk factors for PAD in patients with typical and severe LSS who underwent spinal surgical treatment.
The occurrence of PAD was examined retrospectively in 171 consecutive patients with LSS and severe IC who underwent surgical treatment at our hospital from June 2012 to June 2013. Data were collected on background characteristics (sex, age) and known risk factors for PAD, such as hypertension, diabetes mellitus, smoking, hyperlipidemia, stroke, and ischemic heart disease.
Of the 171 patients enrolled, 7 had an abnormal ankle-brachial index (ABI). Computed tomography angiography (CTA) was performed in these patients, and a final diagnosis of PAD was established for all 7 patients. The incidence of PAD in all patients with LSS was 4.1%(7 of 171). Stroke and ischemic heart disease were significantly more common in the LSSPAD group compared with the LSS group. Multiple logistic regression analyses with a forced-entry method revealed that age and stroke (p<0.05) were independent risk factors for PAD.
To prevent misdiagnosis of fatal PAD, we recommend ABI be assessed in patients with LSS and history of stroke.
Peripheral arterial disease; Ankle brachial pressure index; Lumbar spinal stenosis
The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs.
We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun NH2-terminal kinases (JNKs) and β-actin as the control group.
Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, 1 µM) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and 1 µM, p<0.05).
Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.
Curcumin; Spinal cord neural progenitor cell; Mitogen activated protein kinase
Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats.
Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015).
The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.
Curcumin; Micro-computed tomography; Osteoporosis; Ovariectomy; Rat
Lumbar microdiscectomy (MD) is the gold standard for treatment of lumbar disc herniation. Generally, the surgeon attempts to protect the facet joint in hopes of avoiding postoperative pain/instability and secondary degenerative arthropathy. We believe that preserving the facet joint is especially important in young patients, owing to their life expectancy and activity. However, preserving the facet joint is not easy during lumbar MD. We propose several technical tips (superolateral extension of conventional laminotomy, oblique drilling for laminotomy, and additional foraminotomy) for facet joint preservation during lumbar MD.
Lumbar disc herniation; Microdiscectomy; Facet joint; Laminotomy; Foraminotomy
It remains debatable whether cervical spine fusion cages should be filled with any kind of bone or bone substitute. Cortical and subcortical bone from the anterior and posterior osteophytes of the segment could be used to fill the cage. The purposes of the present study are to evaluate the clinical outcomes and radiological outcomes including bone fusion and subsidence that occurred after anterior cervical discectomy and fusion using a stand-alone cage packed with local autobone graft.
Thirty-one patients who underwent anterior cervical fusion using a stand-alone polyetheretherketone (PEEK) cage packed with local autobone graft from July 2009 to december 2011 were enrolled in this study. Bone fusion was assessed by cervical plain radiographs and computed tomographic scan. Nonunion was evaluated according to the absence of bony bridge on computed tomographic scan. Subsidence was defined as a ≥2 mm decrease of the interbody height at the final follow-up compared to that measured at the immediate postoperative period.
Subsidence was observed in 7 patients (22.6%). Of 7 patients with subsidence greater 2 mm, nonunion was developed in 3. Three patients with subsidence greater 2 mm were related with endplate damage during intraoperative endplate preparation. Solid bone fusion was achieved in 28 out of 31 patients (90.3%).
With proper patient selection and careful endplate preparation, anterior cervical discectomy and fusion (ACDF) using a stand-alone PEEK cage packed with local autobone graft could be a good alternative to the standard ACDF techniques with plating.
Cage; Cervical spine; Discectomy; Local bone
Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is rare manifestation and most of them are treated by adjuvant treatment modalities like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy has been preferred as the first-line treatment modality of ISCM from RCC and only a few cases underwent surgical treatment. We describe a case of ISCM from RCC, which underwent surgical excision and pathologically confirmed. A 44-yr-old man was presented with rapid deterioration of motor weakness during focal radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass and spinal cord decompression, his motor power was dramatically improved to ambulate by himself. We report the first published Korean case of ISCM from RCC confirmed pathologically and describe our surgical experience and his clinical characteristics.
Intramedullary Spinal Cord Neoplasm; Metastasis; Renal Cell Carcinoma
We report a case of 29-year-old man diagnosed as a primary eosinophilic granuloma (EG) lesion of the seventh cervical vertebra. He had paresthesia on both arms, and grasping weakness for 10 days. Cervical magnetic resonance image (MRI) showed an enhancing mass with ventral epidural bulging and cord compression on the seventh cervical vertebra. Additionally, we performed spine series MRI, bone scan and positive emission tomography for confirmation of other bone lesions. These studies showed no other pathological lesions. He underwent anterior cervical corpectomy of the seventh cervical vertebra and plate fixation with iliac bone graft. After surgical management, neurological symptoms were much improved. Histopathologic evaluation confirmed the diagnosis of EG. There was no evidence of tumor recurrence at 12 months postoperative cervical MRI follow-up. We reported symptomatic primary EG of cervical spine successfully treated with surgical resection.
Eosinophilic granuloma; Adult cervical tumor; Surgical approach
This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model.
Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively.
Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group.
Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI.
Neural stem/progenitor cell; Spinal cord injury; Valproic acid; Nestin; SOX2
To evaluate the effect of calcium supplementation on spinal bone fusion in ovariectomized (OVX) rats.
Sixteen female Sprague Dawley rats underwent bilateral ovariectomy at 12 weeks of age to induce osteoporosis and were randomly assigned to two groups : control group (n=8) and calcium-supplemented group (OVX-Ca, n=8). Autologous spinal bone fusion surgery was performed on both groups 8 weeks later. After fusion surgery, the OVX-Ca group was supplemented with calcium in drinking water for 8 weeks. Blood was obtained 4 and 8 weeks after fusion surgery. Eight weeks after fusion surgery, the rats were euthanized and the L4-5 spine removed. Bone fusion status and fusion volume were evaluated by manual palpation and three-dimensional computed tomography.
The mean fusion volume in the L4-5 spine was significantly greater in the OVX-Ca group (71.80±8.06 mm3) than in controls (35.34±8.24 mm3) (p<0.01). The level of osteocalcin, a bone formation marker, was higher in OVX-Ca rats than in controls 4 weeks (610.08±10.41 vs. 551.61±12.34 ng/mL) and 8 weeks (552.05±19.67 vs. 502.98±22.76 ng/mL) after fusion surgery (p<0.05). The level of C-terminal telopeptide fragment of type I collagen, a bone resorption marker, was significantly lower in OVX-Ca rats than in controls 4 weeks (77.07±12.57 vs. 101.75±7.20 ng/mL) and 8 weeks (69.58±2.45 vs. 77.15±4.10 ng/mL) after fusion surgery (p<0.05). A mechanical strength test showed that the L4-5 vertebrae in the OVX-Ca group withstood a 50% higher maximal load compared with the controls (p<0.01).
Dietary calcium given to OVX rats after lumbar fusion surgery improved fusion volume and mechanical strength in an ovariectomized rat model.
Osteoporosis; Ovariectomized rat; Calcium; Spinal bone fusion
The purpose of the present study was to determine the incidence of dural tears and predictable factors suggesting dural tears in patients who had lumbar burst fractures with vertical laminar fractures.
A retrospective review was done on thirty-one patients who underwent operative treatment for lumbar burst fractures with vertical laminar fractures between January 2003 and December 2008. All patients were divided into two groups according to existence of dural tears, which were surgically confirmed; 21 patients with dural tears and 10 patients without dural tears. Clinical and radiographic findings were analyzed for their association with dural tears.
Among a total of 31 patients, dural tears were detected in 21 (67%) patients. A preoperative neurological deficits and mean separation distances of the edges in laminar fractures were found to be the reliable factors of dural tears (p=0.001 and 0.002, respectively). Decreased ratio of the central canal diameter and interpedicular distance were also the reliable factors suggesting dural tears (p=0.006 and 0.015, respectively). However, dural tears showed no significant association with age, sex, level of injury, absence of a posterior fat pad signal, the angle of retropulsed segment, or site of laminar fracture.
Our study of lumbar burst fracture combined laminar fracture revealed that dural tears should be ruled out in cases of a preoperative neurological deficits, wide separation of the laminar fracture, severe canal encroachment, and wider interpedicular distance.
Burst fracture; Dural tear; Laminar fracture
The purpose of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can be used to assess the therapeutic response of brain abscess.
A study was conducted on 10 consecutive patients with brain abscess. Magnetic resonance imaging (MRI) with diffuse-weighted imaging (DWI) was performed at 3 and 6 weeks after surgical treatment and intravenous antibiotics therapy and FDG-PET at 6 weeks after treatment. The extent of the abscess, signal changes on MRI, and FDG-PET standardized uptake values were analyzed and correlated with the response to therapy.
Aspiration or craniotomy with excision of the abscess followed by intravenous antibiotics for 6-8 weeks resulted in good recovery with no recurrence. In 10 patients, two had low signal intensity on the DWI; one had no uptake on FDG-PET imaging after 6 weeks antibiotics and discontinued intravenous treatment, but the other patient had diffuse, increased uptake on FDG-PET imaging after 6 weeks antibiotics and underwent an additional 2 weeks of intravenous antibiotics. The remaining eight patients had high signals on the DWI. Four had no uptake on FDG-PET imaging and the treatment period varied from 6 to 8 weeks (mean, 6.75 weeks). Among the other four patients, FDG was accumulated in a diffuse or local area corresponding to a high signal area within the DWI and 2 weeks of intravenous antibiotics was added.
MRI plus FDG-PET improved the accuracy of assessing therapeutic responses to antibiotics treatment of brain abscess and aided in optimizing therapy.
Brain abscess; 18F-Fluorodeoxyglucose positron emission tomography; Magnetic resonance imaging; Diffusion-weighted imaging; Antibiotics
Extramedullary hematopoiesis (EMH) is occasionally reported in idiopathic myelofibrosis and is generally found in the liver, spleen, and lymph nodes several years after diagnosis. Myelofibrosis presenting as spinal cord compression, resulting from EMH tissue is very rare. A 39-yr-old man presented with back pain, subjective weakness and numbness in both legs. Sagittal magnetic resonance imaging showed multiple anterior epidural mass extending from L4 to S1 with compression of cauda equina and nerve root. The patient underwent gross total removal of the mass via L4, 5, and S1 laminectomy. Histological analysis showed islands of myelopoietic cells surrounded by fatty tissue, consistent with EMH, and bone marrow biopsy performed after surgery revealed hypercellular marrow and megakaryocytic hyperplasia and focal fibrosis. The final diagnosis was chronic idiopathic myelofibrosis leading to EMH in the lumbar spinal canal. Since there were no abnormal hematological findings except mild myelofibrosis, additional treatment such as radiothepary was not administered postoperatively for fear of radiotoxicity. On 6 month follow-up examination, the patient remained clinically stable without recurrence. This is the first case of chronic idiopathic myelofibrosis due to EMH tissue in the lumbar spinal canal in Korea.
Hematopoiesis, Extramedullary; Myelofibrosis; Spinal Canal
Combined antero-posterior fixation has been a standard method for bilateral interfacetal dislocation
in cervical spine. The purpose of this study is to evaluate the efficacy and complication of anterior cervical
stabilization in treatment of bilateral interfacetal dislocation.
A total of 65 cases of traumatic bilateral interfacetal dislocation in cervical spine who were managed
in our institution, from Mar. 1997 to Feb. 2006, were included in this study. Closed reduction was tried in all cases
before operation. If closed reduction was accomplished successfully, only anterior cervical fixation was performed
(Group I), and attempted to place screws bicortically as possible with unicortical screws. If failed, posterior open
reduction with fixation was first tried, followed by anterior cervical fixation (Group II). All patients were evaluated
for neurological outcome and radiological evidence of healing.
The Group I included 47 patients and the Group II, 18 patients. The improvement of Frankel grade and
increase of mean cervical lordosis angles were not statistically different between two groups. Screw-plate
system used did not influence the outcome. On follow up, solid bone fusion was evident and there were no
cases of instability in both groups.
Our study demonstrated that anterior cervical fixation on BID is safe and effective in comparison
with combined antero-posterior cervical fixation.
Cervical spine; Dislocation; Antero-posterior; Fixation; Stabilization
Inflammatory myofibroblastic tumors (IMTs) are benign neoplasms that can occur at different anatomic sites with nonspecific clinical symptoms. A 48-yr-old woman presented with a 2-month history of a relapsed oral ulcer, progressive dyspnea, and a thoracic pain induced by breathing. A tumorous mass was noticed in the right costodiaphragmatic recess on chest computed tomography and magnetic resonance imaging, and the patient underwent a right costotransversectomy with excision of the tumor, which originated from the 12th intercostal nerve. Histology and immunohistochemistry showed that the tumor was an IMT of the intercostal nerve. The patient's postoperative course was not favorable; dyspnea persisted after surgery, and a progressive pulmonary compromise developed. The cause of the respiratory failure was found to be bronchiolitis obliterans, which in this case proved to be a fatal complication of paraneoplastic pemphigus associated with an IMT. This case of IMT of the spinal nerve in the paravertebral region is unique in terms of its location and presentation in combination with paraneoplastic pemphigus, which is rare. A brief review of the heterogeneous theories concerning the pathogenesis, clinicopathological features, and differential diagnosis of this disease entity is presented.
Inflammatory Myofibroblastic Tumor; Intercostal Nerves; Paraneoplastic Pemphigus