Current and Future Perspectives in Craniosynostosis.

Craniosynostosis has a varied clinical spectrum, ranging from isolated single suture involvement to multi-sutural fusions. Greater understanding of the pathogenesis of craniosynostosis has led to the development of practical treatment protocols. Three stages of growth have determined the approach to managing craniosynostosis : the early period, up to 12 months; the intermediate period, from 1 to 10 years; and the late period, beginning at 10 years. This review discusses current surgical management and future perspectives in craniosynostosis.

Foraminoplastic Superior Vertebral Notch Approach with Reamers in Percutaneous Endoscopic Lumbar Discectomy : Technical Note and Clinical Outcome in Limited Indications of Percutaneous Endoscopic Lumbar Discectomy.

To describe the details of the foraminoplastic superior vertebral notch approach (FSVNA) with reamers in percutaneous endoscopic lumbar discectomy (PELD) and to demonstrate the clinical outcomes in limited indications of PELD. Retrospective data were collected from 64 patients who underwent PELD with FSVNA from August 2012 to April 2014. Inclusion criteria were high grade migrated disc, high canal compromised disc, and disc protrusion combined with foraminal stenosis. The clinical outcomes were assessed using by the visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. Complications related to the surgery were reviewed. The procedure used a unique approach, using the superior vertebral notch as the target and performing foraminoplasty with only reamers under C-arm control. The mean age of the 55 female and 32 male patients was 52.73 years. The mean F/U period was 12.2±4.2 months. Preoperative VAS (8.24±1.25) and ODI (67.8±15.4) score improved significantly at the last follow-up (VAS, 1.93±1.78; ODI, 17.14±15.7). Based on the modified MacNab criteria, excellent or good results were obtained in 95.3% of the patients. Postoperative transient dysthesia (n=2) and reoperation (n=1) due to recurred disc were reported. PELD with FSVNA could be a good method for treating lumbar disc herniation. This procedure may offer safe and efficacious results, especially in the relatively limited indications for PELD.

Radicular compression by intraspinal epidural gas bubble occurred in distant two levels after lumbar microdiscectomy.

The authors report a case of symptomatic epidural gas accumulation 2 weeks after the multi-level lumbar surgery, causing postoperative recurrent radiculopathy. The accumulation of epidural gas compressing the dural sac and nerve root was demonstrated by CT and MRI at the distant two levels, L3-4 and L5-S1, where vacuum in disc space was observed preoperatively and both laminectomy and discectomy had been done. However, postoperative air was not identified at L4-5 level where only laminectomy had been done in same surgical field, which suggested the relationship between postoperative epidural gas and the manipulation of disc structure. Conservative treatment and needle aspiration was performed, but not effective to relieve patient's symptoms. The patient underwent revision surgery to remove the gaseous cyst. Her leg pain was improved after the second operation.

Surgical management and outcome of tethered cord syndrome in school-aged children, adolescents, and young adults.

OBJECTIVE: The adolescent presentation of tethered cord syndrome (TCS) is well-recognized, but continues to pose significant diagnostic and management controversies. The authors conducted a retrospective study of clinical outcomes after surgical intervention in 24 school-aged children, adolescents, and young adults with TCS. METHODS: All 83 patients with a lipomyelomeningocele (LMMC) underwent untethering surgery for caudal cord tethering between 1987 and 2007. The clinical charts and follow-up data were reviewed. Of these patients, 24 school-aged children, adolescents, and young adults with TCS were studied with respect to the clinical, radiologic, pathologic features, and surgical outcomes. RESULTS: Untethering procedures were performed in 24 patients (age range, 7-25 years) for TCS of various origins (lipoma, lipomyelomeningocele, and tight filum terminale). Specific circumstances involving additional tugging of the already tight conus, and direct trauma to the back precipitated the onset of symptom in 50% of the patients. Diffuse and non-dermatomal leg pain, often referred to the anorectal region, was the most common presenting symptom. Progressive sensorimotor deficits in the lower extremities, as well as bladder and bowel dysfunction, were also common findings, but progressive foot and spinal deformities were noted less frequently. The most common tethered lesions were intradural lipomas, thickened filum and fibrous band adhesions into the placode sac. The surgical outcome was gratifying in relation to pain and motor weakness, but disappointing with respect to resolution of bowel and bladder dysfunction. Of the 24 patients with TCS, pre-operative deficits improved after surgery in 14 (58.3%), remained stable in 8 (33.4%), and worsened in 2 (8.3%). CONCLUSION: The pathologic lesions of tethered cord syndrome in school-aged children, adolescents, and young adults, are mostly intradural lipomas and tight filum. It is suggested that the degree of cord traction results in neurologic dysfunction in late life due to abnormal tension, aggravated by trauma or repeated tugging of the conus during exercise. Early diagnosis and adequate surgical release might be the keys to the successful outcome in school-aged children, adolescents, and young adults with TCS.

Surgical decompression of supratentorial arachnoid cysts in pediatric patients younger than one year.

BACKGROUND: There has been much debate about the optimal surgical management of arachnoid cysts in infants younger than 1 year of age. The authors present the clinical and neuroimaging findings in pediatric patients with supratentorial arachnoid cysts treated by surgical decompression. METHODS: A retrospective chart review was conducted to identify all pediatric patients who had been diagnosed with arachnoid cysts since 2003. Five infants with symptomatic supratentorial arachnoid cysts underwent surgery at Kangnam St. Mary's Hospital. RESULTS: The initial surgery in 4 patients involved a craniotomy with the excision of the cyst wall and fenestration into the basal cisterns. Three of the four patients needed additional procedures, such as cyst-peritoneal or subdural-peritoneal shunting due to failure of cyst resolution. A shunting procedure was performed as initial therapy in 1 patient who presented with increased intracranial pressure. CONCLUSION: Our strategy for approaching arachnoid cysts in pediatric patients has been to diagnose and treat the cysts as early as possible and to avoid the complications of shunts whenever possible. However, open craniotomy with excision and fenestration of the cyst is associated with a relatively high failure rate in pediatric patients younger than 1 year of age with supratentorial arachnoid cysts.

Simple excision and periosteal reattachment for the treatment of calcified cephalhematoma. Technical note.

Until now, calcified cephalhematoma has been treated by excision of the lesion and the use of an onlay autograft. The authors report their use of a less complicated alternative, simple excision and periosteal reattachment, in a 3-month-old male infant. They excised the calcified cap of cephalhematoma and reattached the periosteum to the exposed bone surface instead of using an onlay autograft technique. A follow-up CT scan demonstrated a smooth skull contour and good cosmetic appearance. The authors note that this is the first report of the successful use of simple excision and periosteal reattachment for the treatment of a case of calcified cephalhematoma in which there was a depressed area after the calcified cap was removed. They conclude that in cases of calcified cephalhematoma it may be unnecessary to perform a complicated cranioplasty with bone harvested from the top of the calcification.

Temozolomide chemotherapy in patients with recurrent malignant gliomas.

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

Anatomy of neurovascular structures around the carpal tunnel during dynamic wrist motion for endoscopic carpal tunnel release.

OBJECTIVE: The purpose of this study is to investigate the anatomic relationship between neurovascular structures and the transverse carpal ligament (TCL) so as to avoid complications during an endoscopic carpal tunnel release procedure. METHODS: Fresh cadaver hands from seven men and 12 women (age range, 48-74 yr) were used. The neurovascular structures just over and under the TCL were meticulously dissected under loupe magnification. Several anatomic landmarks were calculated (average length of the TCL; average distance between the TCL distal margin and the neurovascular structures; and average lengths of the superficial palmar arch, ramus communicantes, recurrent motor branch, and palmar cutaneous branch of the median nerve). The ulnar neurovascular structure was studied with the wrist positioned in neutral, ulnar flexion, and radial flexion. RESULTS: The anatomic relationships between the TCL and vascular and neural structures were measured. The ulnar neurovascular structures usually passed just over ulnar to the superior portion of the hook of the hamate. However, in 11 hands, a looped ulnar artery coursed 1 to 4 mm radial to the hook of the hamate and continued to the superficial palmar arch. The looped ulnar artery migrates on the ulnar side of Guyon's canal (-2-2 mm radial to the hook of the hamate) with the wrist in radial flexion (of the wrist). During ulnar flexion of the wrist, the ulnar artery shifts more radially beyond the hook of the hamate (2-7 mm). CONCLUSION: It is appropriate to transect the ligament over 4 mm apart from the lateral margin of the hook of the hamate without placing the edge of the scalpel toward the ulnar side. We would also recommend not transecting the TCL in the ulnar flexed wrist position to protect the ulnar neurovascular structure. The proximal portal could be made just ulnar to the palmaris longus tendon to spare the neurovascular structures in the proximal portion of the TCL.

Cytotoxicity of rat marrow stromal cells against malignant glioma cells.

OBJECTS: Marrow stromal cells (MSCs) have been shown to have the capacity of orthodox and unorthodox plasticity. In this study, the authors tried to access in vitro cytotoxicity of MSCs from rat and also to differentiate MSCs into immune effector cell. METHODS: Rat MSCs (rMSCs) were isolated by standard methodology and were activated by interleukin-2 (IL-2), interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor, and combinations, which were effector cells. Cytotoxicity of rMSCs and activated rMSCs against the target cells (9L rat glioma cell line) was estimated using visual survival cell assay. Phenotypes of these various activated cells were determined using flow cytometry. The secreted protein from effector cells was estimated by enzyme-linked immunosorbent assay. The expression of immune response-related genes in activated cells was measured. RESULTS: There was a significant cytotoxicity of rMSCs activated with various cytokine combinations. After various cytokine activations of rMSCs, the population of immune effector cells (CD8, CD161a) and immune reaction-related proteins (IL-4, gamma-INF) might increase. Apoptosis may be one of the lysis mechanisms of target cells by activated rMSCs. The contributing genes could be gamma-INF, FasL, and perforin. CONCLUSION: This study suggests that rMSC may be used as adoptive transfer therapy in patients suffering from malignant brain tumor, but we have to investigate orthotopic animal study for the proper translation.

Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic activity.

The neurofibromatosis type 2 gene-encoded protein, merlin, is related to the ERM (ezrin, radixin, and moesin) family of membrane-cytoskeleton-associated proteins. Recent studies suggest that the loss of neurofibromatosis type 2 function contributes to tumor development and metastasis. Although the cellular functions of merlin as a tumor suppressor are relatively well characterized, the cellular mechanism whereby merlin controls cell proliferation from membrane locations is still poorly understood. During our efforts to find potential merlin modulators through protein-protein interactions, we identified transactivation-responsive RNA-binding protein (TRBP) as a merlin-binding protein in a yeast two-hybrid screen. The interaction between TRBP and merlin was confirmed by glutathione S-transferase pull-down assays, co-immunoprecipitation, and co-localization experiments. The carboxyl-terminal regions of each protein were responsible for their interaction. Cells overexpressing TRBP showed enhanced cell growth in cell proliferation assays and also exhibited transformed phenotypes, such as anchorage-independent cell growth and tumor development in mouse xenografts. Merlin efficiently inhibited these oncogenic activities of TRBP in our experiments. These results provide the first clue to the functional interaction between TRBP and merlin and suggest a novel mechanism for the tumor suppressor function of merlin both in vitro and in vivo.

Lymphokine activated killer cells from umbilical cord blood show higher antitumor effect against anaplastic astrocytoma cell line (U87) and medulloblastoma cell line (TE671) than lymphokine activated killer cells from peripheral blood.

OBJECTS: The aims of this study were to assess the cytotoxic capability of lymphokine-activated killer (LAK) cells from umbilical cord blood (UCB), to compare them with those of peripheral blood (PB)-derived cells against anaplastic astrocytoma cell line (U87) and medulloblastoma cell line (TE671), and to identify which mechanism and genes were involved in cytotoxicity. METHODS: The effector cells were generated by interleukin-2 from UCB and PB. The antitumor property of effector cells against the target cells (U87, TE671) were estimated using a visual survival cell assay. The mixed target and effector (UCB) cells were analyzed for whether DNA fragmentation was present or not. Reverse transcription polymerase chain reaction analysis was then performed to estimate the statement of the perforin and FasL genes in activated and inactivated cells from UCB. RESULTS: The higher in vitro antitumor properties of the LAK cells from UCB were observed in comparison to the LAK cells from PB against the U87 and the TE671 ( p<0.05). Apoptosis may be one of the lysis mechanisms of target cells by the LAK cells from UCB. The contributing genes could be FasL and perforin. CONCLUSIONS: This study suggests that UCB may be used as a source of LAK cells in adults and children suffering from anaplastic astrocytoma or medulloblastoma.

Intraspinal extradural teratoma mimicking neural sheath tumor in infant.

INTRODUCTION: An intraspinal teratoma that is located entirely extradurally is unusual both in children and in adults. CASE HISTORY: The authors present a case of an 8-month-old male infant with an extradurally arising intraspinal mature teratoma located from T-2 to T-4, who had suffered from progressive paraparesis (grade 1). The patient did not have any stigmata or anomalies suggesting spinal dysraphism. Spinal MRI showed a cystic extradural mass markedly compressing the dural sac. On operation, the only way of getting sufficient space for exposure of the whole tumor was to perform hemilaminectomies with preservation of facetal areas to prevent postoperative instability. The tumor was well encapsulated and located entirely extradurally, and the cystic portion was occupied with yellowish fluid. The site of tumor occurrence was the spinal root sheath, mimicking a neural sheath tumor. Paraparesis had improved markedly to grade 4 by the time of the neurological examination 3 months after operation.

Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway.

The neurofibromatosis type 2 (NF2) gene encodes an intracellular membrane-associated protein called merlin or schwannomin, which is known to be a tumor suppressor. Numerous studies have suggested that merlin is involved in the regulation of cell growth and proliferation. Previously, merlin/schwannomin was reported to block Ras-induced cell proliferation and anchorage-independent cell growth. Also, the N-terminus of merlin was found to suppress cell proliferation, although it appears to be less effective than full-length merlin. However, the inhibitory mechanism of merlin is unknown. In this report, merlin is shown to be effective at suppressing serum/Ras-induced and Elk-mediated SRE dependent transactivation, and serum-induced ERK phosphorylation in NIH3T3 cells. In addition, merlin inhibited serum-induced Elk phosphorylation, a downstream effector of ERKs. Also, the N-terminal deficient merlin mutant could not block serum-induced and Elk-mediated SRE dependent transactivation, although the C-terminal deficient merlin mutant could. These results suggest that merlin inhibits SRE dependent transactivation by repressing serum-induced ERK phosphorylation and its downstream effector, Elk phosphorylation. Also, the N-terminus of merlin may be important for its inhibitory effect. Our results show that merlin acts as a negative regulator of the SRE signaling pathway via the Ras-ERKs pathway.

Role of surgery for maintaining urological function and prevention of retethering in the treatment of lipomeningomyelocele: experience recorded in 75 lipomeningomyelocele patients.

OBJECT: The authors tried to reveal some unique features of lipomeningomyelocele (LMMC), including clinical presentation, factors precipitating onset of symptoms, pathologic entities of LMMC associated with tethered cord syndrome, and surgical outcome in LMMC patients. METHODS AND RESULTS: Seventy-five patients with LMMC were enrolled in this study. Neuro-imaging and intraoperative findings allowed classification of LMMC into three types: type I, type II, and type III. The patients were divided into two groups by age: A (51 patients), from birth to 3 years, and B (24 patients), from 3 to 24 years. For prevention of retethering of the cord, a mega-dural sac rebuilding procedure was performed in 15 patients. During a mean postoperative follow-up period of 4 years, the surgical outcome was satisfactory in terms of improved pain and motor weakness, but disappointing with reference to the resolution of bowel and bladder dysfunction. Among these 75 patients with LMMC, preoperative deficits were improved after surgery in 29 (39%), remained stable in 28 (37%), changed slightly in 13(17%), and worsened in 5 (7%). Patients in group A achieved better outcomes than those in group B. Depending on the type of lesion, patients with types I and II LMMC have better outcomes than those with type III LMMC: Finally, retethering of the cord with neurological deterioration occurred in 4 (5.3%) of the 75 patients, but no retethering was found in the 15 patients who were recently treated with a mega-dural sac rebuilding procedure. CONCLUSION: Our data continue to support the opinion that early diagnosis and optimal surgery are still essential for the treatment of patients with LMMC, since there is a high likelihood of residual neurological functions that can be preserved. Based on our surgical experience of untethering and decompression of lipomas, a mega-dural sac repair is useful to prevent retethering of the cord.

Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. Case report.

The authors describe the effectiveness of motor cortex stimulation (MCS) in a patient with complex regional pain syndrome (CRPS) Type II, formerly known as causalgia, with hemibody allodynia. During MCS, a subjective sensation of warm paresthesia developed in the painful hand and forearm and spread toward the trunk. Pain and allodynia in the areas associated with this sensation were alleviated significantly. The analgesic effect of stimulation proved to be long lasting and was still present at the 12-month follow up. The authors speculate that MCS might exert its effect through the modulation of thalamic activity in this particular case of CRPS with hemisensory deficit. A central mechanism associated with functional disturbance in noxious-event processing in the thalamus might have an important role in the pathogenesis of the condition.

Takayasu's arteritis presented with subarachnoid hemorrhage: report of two cases.

Takayasu's arteritis is a chronic inflammatory disease that produces a narrowing of the aorta and its major branches. Fibrosis and thickening of the arterial wall often occur in later stages, resulting in a cerebrovascular accident. The authors report two young women patients who presented with subarachnoid hemorrhage (SAH) and occlusive cerebrovasular disease associated with Takayasu's arteritis. Both patients had sudden headache and hemiparesis. Physical examination showed weak radial pulse, carotid bruit, and asymmetrical blood pressure. Erythrocyte sedimentation rate (ESR) was elevated in both patients. SAH was confirmed by brain computerized tomography (CT) or lumbar puncture. Occlusive cerebrovascular disease was diagnosed by brain magnetic resonance imaging (MRI), brain magnetic resonance angiography (MRA), and cerebral angiography. The findings of aortography and cerebral angiography were compatible with Takayasu's arteritis, but intracranial aneurysm was not found in either patient.

Dose-dependent epidural leakage of polymethylmethacrylate after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures.

OBJECT: The use of polymethylmethacrylate (PMMA) cement by percutaneous injection in cases requiring vertebroplasty provides pain relief in the treatment of osteoporotic vertebral compression fractures. A retrospective study was performed to assess what caused PMMA cement to leak into the epidural space and to determine if this leakage caused any changes in its therapeutic benefits. METHODS: Polymethylmethacrylate was injected into 347 vertebral compression fractures in 159 patients. The cement leaked into the epidural space in 92 (26.5%) of 347 treated vertebrae in 64 (40.3%) of the 159 patients, as demonstrated on postoperative computerized tomography scanning. Epidural leakage of PMMA cement occurred more often when injected above the level of T-7 (p = 0.001) than below. The larger the volume of PMMA injected the higher the incidence of epidural leakage (p = 0.03). Using an injector also increased epidural leakage (p = 0.045). The position of the needle tip within the vertebral body and the pattern of venous drainage did not affect epidural leakage of the cement. Leakage of PMMA into the epidural space reduced the pain relief expected after vertebroplasty. The immediate postoperative visual analog scale scores were higher (and therefore reflective of less pain relief) in patients in whom epidural PMMA leakage occurred (p = 0.009). Three months postoperatively, the authors found the highest number of patients presenting with pain relief, including those in the group with epidural leakage, and at this follow-up stage there were no significant differences between the two groups. CONCLUSIONS: The authors found that epidural leakage of PMMA after percutaneous vertebroplasty was dose dependent. The larger amount of injected PMMA, the higher the incidence of leakage. Injecting vertebral levels above T-7 also increased the incidence of epidural leakage. Epidural leakage of PMMA may attenuate only the immediate therapeutic effects of vertebroplasty.