Hydrocephalus and aquaporins: the role of aquaporin-4.

INTRODUCTION: Aquaporins (AQPs) are membrane proteins that facilitate water and small solute movement in tissues. Hydrocephalus is the major central nervous system disorder associated with defective cerebrospinal fluid turnover. Aquaporin-4 (AQP4) is a water channel located mainly at the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) interfaces and is associated with the elimination of cerebral edema via these routes. The aim of this study is to review the pertinent literature concerning the role of AQP4 in the pathophysiology of hydrocephalus. METHODS: We performed a MEDLINE search using the terms aquaporin AND hydrocephalus. The results of the search were further refined to exclude studies not related to aquaporin-4. RESULTS: Six studies were identified. All studies utilized an animal model such as AQP4-knockout mice, H-Tx rats, and kaolin and L-α-lysophosphatidylcholine (LPC) stearoyl injection models of hydrocephalus. Most studies indicate that there is an up-regulation of AQP4 expression at the BBB and blood-CSF interfaces in cases of hydrocephalus. One study, reported sporadic cases of obstructive hydrocephalus in a subgroup of AQP4-knockout mice. CONCLUSIONS: Few publications have studied the association between aquaporins and hydrocephalus. Currently, all the existing studies rely on animal models. An adaptive and protective role of AQP4 to increase the resolution of the "hydrocephalic" edema at the BBB and blood-CSF interfaces is proposed in the pathophysiology of hydrocephalus. Further research is needed to clarify if this association exists in humans.

Hydrocephalus and aquaporins: the role of aquaporin-1.

INTRODUCTION: Aquaporins (AQPs) are membrane proteins that facilitate water and small solute movement in tissues. Hydrocephalus is a major central nervous system disorder associated with defective cerebrospinal fluid (CSF) turnover. Aquaporin-1 (AQP1) is a water channel located mainly at the choroid plexus epithelium and plays an active role in CSF production. The aim of this study is to review the pertinent literature concerning the role of aquaporin-1 in the pathophysiology of hydrocephalus. METHODS: We performed a MEDLINE search using the terms aquaporin AND hydrocephalus. The results of the search were further refined to exclude studies not related to aquaporin-1. RESULTS: Five studies were identified. Three of these studies utilized an animal model, while only two studies referred to a few human cases of hydrocephalus. Most of the studies indicate that there is a down-regulation of AQP1 expression in choroid plexus in models of hydrocephalus. A small series of human choroid plexus tumors showed that AQP1 expression is up-regulated. In cases of human choroid plexus tumors, there are indications that AQP1 may have alternative physiologic roles, but it is not clear whether this is associated with a specific type of hydrocephalus or the genetic burden of the tumor. CONCLUSION: There has been a paucity of research on the link between aquaporins and hydrocephalus. Most studies have relied on animal models. An adaptive and protective role of AQP1 as a regulator of CSF production is proposed in the pathophysiology of hydrocephalus. Further research is needed to clarify if this association exists in humans.

Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

BACKGROUND: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. METHODS: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. RESULTS: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). CONCLUSIONS: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Hypothalamic hamartomas: Correlation of MR imaging and spectroscopic findings with tumor glial content.

BACKGROUND AND PURPOSE: There is variability in the literature concerning the appearance and histology of hypothalamic hamartomas. This study correlates the MR imaging and proton MR spectroscopic properties of hypothalamic hamartomas with histopathologic findings. METHODS: Studies were performed with 3T and 1.5T scanners. Single voxel hamartoma spectra were acquired by using short-echo-time point-resolved spectroscopy sequences (PRESS). 2D PRESS chemical shift imaging (CSI) spectroscopic sequences were also obtained for comparison of tumor-derived spectra with normal gray matter of the amygdala. Sequences were used to compare choline (Cho), N-acetylaspartate (NAA), and myoinositol (mI) resonances by using a creatine (Cr) reference. Spectral ratios and T2 signal intensity ratios of the hamartomas were then compared with histopathologic findings. RESULTS: Data from single voxel spectroscopic sequences demonstrated a statistically significant decrease in NAA/Cr and an increase in mI/Cr ratios in tumor tissue when compared with values in normal gray matter of the amygdala. In addition, Cho/Cr ratios were also increased when compared with those in normal gray matter controls. Among the 14 hamartomas sampled, a spectrum of increased mI/Cr ratios was seen. Those tumors with markedly elevated mI/Cr demonstrated an increased glial component when compared with the remaining tumors. Increased glial component was also found to have a positive correlation with hyperintensity of lesions on T2-weighted images. CONCLUSION: We have identified a correlation between the glial/neuronal fraction as determined by histopathology and MR spectral and T2 hyperintensity variations among hypothalamic hamartomas.

Pediatric cervical spine injuries: report of 102 cases and review of the literature.

OBJECT: To evaluate and review their experience with pediatric cervical injuries and factors affecting outcome, the authors conducted a retrospective clinical study of 102 cases (65% boys, 35% girls) of pediatric cervical spine injuries treated in the last decade. This study is an extension of and comparison with their earlier experience. METHODS: Patients were divided into two age groups-birth to 9 years (Group I) and 10 to 16 years of age (Group 2)- and managed according to status at presentation and type of injury. Thirty patients were managed surgically and 72 non-surgically (42 wore a halo brace and 30 wore hard collars or custom-molded braces). Motor vehicle accidents were the most common cause of injury, and 40% were associated with head injury. Patients in the younger-age group (Group 1) sustained more neurological injuries than the older patients in Group 2, and most injuries were in the upper cervical spine. Of the 38 children in Group 1, in 39% a subluxation was present and in 29% a fracture or fracture/subluxation was demonstrated. Of the patients in Group 2, 80% had sustained fractures or fracture/subluxations. Vertebral fractures were the most common radiological findings (32%). At late follow-up review (mean 5 years), solid fusions were demonstrated in all patients. Neurological deterioration did not occur in any patient. The mortality rate was 16%. Compared with the authors' earlier report, the incidence of cases with pediatric cervical injuries increased, as did the number managed surgically. Various fusion techniques were used, and neurological and fusion outcomes improved as compared with the previous report. CONCLUSIONS: The prognosis of neurological recovery from pediatric cervical spine injuries is related to the severity of the initial neurological injury. Management must be tailored to the patient's age, neurological status, and type and level of injury. Compared with our earlier experience, fusion and instrumentation procedures were used more frequently. Different types of fusion and instrumentation procedures can be performed safely in children and produce good outcomes.

Pediatric spine and spinal cord trauma. State of the art for the third millennium.

The purpose of this work was to analyze the literature published in English and to review the experience of the Barrow Neurological Institute (BNI) with spine and spinal cord injury (SCI) in children. Standard computerized data bases were queried for information regarding SCI, spinal injury, spinal instability, and spinal cord regeneration to produce a review of the epidemiology, diagnosis, treatment, outcome and directions for future research. We also reviewed our experiences in the management of infants and children with spine injuries and SCIs and with spinal instability from all causes. A total of 132 articles were identified and obtained from the Medical Library at St. Joseph's Hospital and Medical Center in Phoenix, Ariz. and through interlibrary loan. All these articles were read, although not all were used in the final review. A review of all children with SCIs revealed that fractures treated over the past 20 years at the BNI were very rare in preadolescent children, who suffered mostly from ligamentous injury or SCI without radiographic abnormality. A total of 68 children aged 16 years or younger who had been treated over the past 15 years and who had undergone spinal fusions for trauma, congenital anomalies, or tumor resection were identified. Occipitocervical fusion is well tolerated in children as young as 11 months when internal stabilization with a threaded titanium rod is used. Posterior instrumentation, including pedicle screw fixation, is feasible in children as young as 4 years. Fusion techniques derived from the adult spinal instrumentation experience were found appropriate except for the youngest patients. Fusion in the newborn period was futile in our experience. The adolescent spine does not differ from the adult spine in terms of sensitivity or response to fixation. Children past the neonatal period can be successfully instrumented for spinal stability without apparent long-term sequelae. Related advances are needed in the area of prevention. Long-term advances in spinal cord regeneration can be expected from ongoing basic science investigations.

Brainstem dysfunction in chiari malformation presenting as profound hypoglycemia: presentation of four cases, review of the literature, and conjecture as to mechanism.

OBJECTIVE: We report four patients whose cases resulted in our observation that profound hypoglycemia resulting from intermittent hyperinsulinism plays a significant role in patients with brainstem dysfunction from Chiari I or II malformations who have intermittent autonomic dysfunction ("blue spells"). METHODS: The records of four children with severe brainstem dysfunction associated with hindbrain herniation (Chiari I or II malformation) were reviewed retrospectively. Each patient had severe lower cranial nerve dysfunction that required tracheotomy and feeding tube placement. After we found that profound hypoglycemia had occurred during a spell of autonomic dysfunction in one patient, the charts of the other three patients were reviewed for evidence of hypoglycemia. Now, whenever one of them has evidence of autonomic dysfunction, prospective studies of glucose and insulin levels are performed. Three of the patients had Chiari II malformation in association with myelomeningocele, and one patient had a Chiari I malformation resulting from Pfeiffer's syndrome. RESULTS: Hypoglycemia occurred in these patients episodically, and usually when their shunts were functioning. The hypoglycemia was associated with hyperinsulinemia in each patient. The brainstem structures of these children (presumably the dorsal motor nuclei of the vagus) were extremely sensitive to changes in local or regional intracranial pressure. These changes were triggered by intermittent shunt failure, agitation from pain, abdominal distention from constipation, and retention of CO2. In patients with Chiari malformations, even mild increases in intracranial pressure lead to brainstem dysfunction. One possible explanation is that pressure on the deformed Xth cranial nerve nuclei may lead to insulin release and life-threatening hypoglycemia. Continuous-drip feeds are necessary to prevent this complication. CONCLUSION: Patients with severe intermittent brainstem dysfunction after decompression of Chiari I or Chiari II malformations should have laboratory studies of glucose levels performed at the time of the episodes to rule out hypoglycemia.

Plexiform neurofibroma of the cauda equina. Case report.

Plexiform neurofibroma of the cauda equina has been reported only twice previously. The authors report the first pediatric patient in whom such a tumor has been found. A 4-year-old boy presented with low-back pain that radiated bilaterally into the L-4 and L-5 dermatomes. A dermal sinus noted at the midthoracic level was surrounded by a hemangiomatous lesion. Magnetic resonance imaging confirmed the presence of the dermal sinus and revealed a well-defined lumbosacral mass that showed heterogeneous intensity with irregular enhancement. Intraoperatively, a solid mass, which engulfed the entire cauda equina, could not be dissected from the roots. The dermal sinus tract, however, was excised from the thoracic spine. The patient underwent radiotherapy to control the tumor and relieve his pain. Plexiform neurofibromas of the cauda equina are characterized by an insidious and progressive clinical course. The tumor mass may engulf all the roots of the cauda equina. No plexiform neurofibroma of the cauda equina has been reported to be associated with neurofibromatosis Type 1. The authors assume that the thoracic-level dermal sinus observed in this child was an incidental finding.

Sporadic unifocal infantile myofibromatosis involving the skull. Case report.

Infantile myofibromatosis involving the skull is a benign disease if there is a solitary lesion. However, the multifocal form with skull involvement may portend a lethal course in the 1st year of life if there is involvement of the heart, lungs, or gastrointestinal tract. The authors report the case of a 3-year-old boy with an enlarging left parietal skull lesion that had been present since infancy. Increasing pain and the need to obtain tissue for diagnosis led to resection of the lesion by means of a small craniectomy. Further evaluation revealed no other lesions. A distinctly rare disease is presented, and the need for staging in children younger than 2 years of age is suggested to rule out cardiac, pulmonary, or gastrointestinal involvement.

Spinal cord ganglioglioma in a child with neurofibromatosis type 2. Case report and literature review.

Gangliogliomas of the spinal cord are rare disease entities that occur in early childhood. Their occurrence in association with neurofibromatosis Type 2 (NF2) has not been described. The authors describe the unique case of a 2-year-old child with stigmata of NF2 who harbored a spinal cord ganglioglioma that presented as a rapidly growing, exophytic intramedullary mass lesion at the cervicomedullary junction. Treatment consisted of complete surgical resection. Histopathological analysis of the lesion demonstrated a mixed population of neoplastic cells, of both neuronal and glial lineage, that supported the diagnosis of ganglioglioma.

Pediatric intramedullary spinal cord tumors. Critical review of the literature.

The objective of this review was to analyze the literature on the management of intramedullary spinal cord tumors to determine whether enough information was available for treatment guidelines to be established. Using standard computerized search techniques, databases containing medical literature were queried for keywords related to intramedullary spinal cord tumors, beginning in 1966. Of the 445 articles published in English and with potential relevance, only 75 articles were included in the final analyses. Based on the strength of their recommendations for the treatment of this controversial condition, articles were divided into class I, class II and class III data. There were no class I studies related to any aspect of the treatment of intramedullary spinal cord tumors. Based on this critical review of literature, gross total removal of an ependymoma confirmed by immediate postoperative magnetic resonance imaging and adjunctive treatment for high-grade tumors using radiotherapy, with or without chemotherapy, can be recommended as standards of therapy. With the strength of a guideline, radiotherapy should be withheld after gross total removal of intramedullary ependymomas and radical resection of low-grade intramedullary astrocytomas. The use of intraoperative ultrasonography and evoked potentials, important surgical adjuncts, can also be considered guidelines. The radical resection of intramedullary low-grade astrocytomas is an option.

Occipital plagiocephaly: a critical review of the literature.

OBJECT: The literature on occipital plagiocephaly (OP) was critically reviewed to determine the feasibility of establishing treatment recommendations. METHODS: Using standard computerized search techniques, medical literature databases containing peer-review articles dating from 1966 were queried for key words related to OP. The titles of all articles were scanned for relevance, and copies of potentially relevant articles published in English were reviewed. Articles in which treatment was discussed were categorized according to their weight of evidence as Class I (prospective randomized controlled trials), Class II (clinical studies in which data are collected prospectively or retrospective analyses based on clearly reliable data), and Class III (most studies based on retrospectively collected data) to evaluate their contribution to developing a consensus on the treatment of OP. Of the 4308 articles identified, all but 89 were excluded. Based on the review of these articles, the actual incidence of OP is unknown, and no population-based studies of its incidence or prevalence exist. The reported incidence of lambdoid craniosynostosis ranges from 3 to 20% with differences in diagnostic criteria accounting for the variability. With the possible exception of a lambdoid suture that is replaced by a dense ridge of bone, no other diagnostic criteria have been agreed on. There were no Class I studies and only one Class II study provided comparisons of outcomes in more than one treatment group with outcomes in an untreated group. Recommended treatment options included observation only, mechanical interventions, and a variety of surgical techniques. CONCLUSIONS: Controlled clinical trials are needed before any form of intervention can be recommended for the treatment of OP. If surgery, which is expensive and potentially dangerous, is to continue to play a role in the management of this condition, efforts should be made to determine if patients with untreated OP have suffered from lack of treatment.

Ventricular shunt removal: the ultimate treatment of the slit ventricle syndrome.

OBJECT: The aim of this study was to assess the effectiveness of an algorithm used to evaluate and prescribe treatment for patients having slit ventricle syndrome (SVS). METHODS: All patients included in this protocol underwent fiberoptic intracranial pressure monitoring after removal or externalization of their ventricular shunt systems. A significant number of patients did not need extracranial cerebrospinal fluid (CSF) diversion and tolerated removal of their shunt systems without requiring further intervention. Patients who demonstrated a need for CSF drainage underwent an endoscopic third ventriculostomy, regardless of the putative cause of their hydrocephalus. Sixteen (72.7%) of 22 patients experienced resolution of or significant improvement in their SVS complaints after their inclusion in the protocol. Concomitantly, 14 (64%) of 22 patients were no longer shunt dependent after a mean follow-up period of 21.4 months. CONCLUSIONS: A significant number of patients debilitated by SVS may experience improvement in their symptoms and undergo shunt removal according to this protocol, improving their quality of life and simplifying their medical follow up.

Potential pitfalls in the work-up and diagnosis of choanal atresia.

To increase an awareness of the developmental anatomy of the nasal cavity as it applies to the radiologic work-up of choanal atresia and frontoethmoidal cephaloceles, we report two cases that demonstrate potentially serious imaging pitfalls. Two neonates with nasopharyngeal obstruction were imaged with CT and MR. Both patients had surgically proved bilateral bony choanal atresia. In addition to choanal atresia, CT showed a radiolucent, or nonossified cribriform plate and mucoid secretions within the nasal fossa, adjacent to the cribriform plate, which approximated the attenuation of brain parenchyma. In one of the patients, a preoperative diagnosis of nasopharyngeal encephalocele resulted in surgical exploration. At surgery, however, the cartilaginous cribriform plate was found to be intact.

Ventriculoperitoneal shunt failure as a complication of laparoscopic surgery.

OBJECTIVE: The authors report the first documented case of laparoscopically induced ventriculoperitoneal (VP) shunt failure. SUMMARY BACKGROUND DATA: Laparoscopic surgery has become a preferred method of accessing and treating a variety of intraperitoneal pathology. Surgeons can expect to encounter patients who have previously undergone placement of cerebrospinal fluid (CSF) shunts who present as candidates for laparoscopic procedures. Currently, the presence of a CSF shunt is not considered to be a contraindication to laparoscopy. We report the first documented case of laparoscopically induced VP shunt failure. CLINICAL HISTORY: A patient with shunt-dependent hydrocephalus underwent laparoscopic placement of a feeding jejunostomy. Postoperatively, clinical and radiographic evidence of shunt failure was noted. The patient underwent emergent shunt revision. Intraoperatively, an isolated distal shunt obstruction was encountered. Gentle irrigation cleared the occlusion. We believe that this shunt dysfunction was secondary to impaction of either soft tissue or air within the distal catheter as a consequence of peritoneal insufflation. CONCLUSIONS: It is concluded that laparoscopic surgery may represent a potential danger in patients with pre-existing CSF shunts. The risk of neurological injury faced by this patient population during laparoscopy is derived from peritoneal insufflation and relates to two primary concerns. The first is impaired CSF drainage due to a sustained elevated distal pressure gradient or, as in our case, an acute distal catheter obstruction. The second concern relates to the potential for retrograde insufflation of the CSF spaces through an incompetent shunt valve mechanism. Distal shunt catheter externalization performed in conjunction with a neurosurgeon during the laparoscopic procedure would prevent these complications. Internalization of the distal shunt catheter would then be performed at the completion of the laparoscopic procedure.

Craniosynostosis and skull molding.

On February 20-23, 1997 in Scottsdale, Arizona, a symposium was held that was sponsored by the Plastic Surgery Educational Foundation, the American Society of Maxillofacial Surgeons, and the Joint Section on Pediatric Neurological Surgery of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. The chairs of the meeting were Jeffrey C. Posnick and Harold L. Rekate. The symposium examined issues relating to craniosynostosis and skull molding. The program consisted of three parts. Day 1 focused on the basic concepts of craniosynostosis and skull molding. Day 2 focused on evaluation and treatment of craniosynostosis. Day 3 focused on the diagnosis and treatment of craniofacial syndromes. The symposium was significant because it brought craniofacial and pediatric neurosurgeons together for the first time at a combined meeting to discuss important aspects of craniosynostosis and skull molding. This article summarizes the presentations made at the meeting.

Recent advances in the understanding and treatment of hydrocephalus.

Advances in the management of patients with hydrocephalus and other abnormalities of cerebrospinal fluid dynamics and intracranial pressure have come from a variety of sources including an improved understanding of the pathophysiology of the various subtypes of the problem, development of alternative methods of treating the condition without reliance on implantable shunting devices, use of neuroendoscopy, and the development of newer types of shunt valves. The purpose of this review is to put into perspective the relative importance of each of these advances to the overall management of our patients.

Thoughts on the present and future of pediatric neurosurgery. Skull base surgery, spinal instrumentation, and neuroendoscopy.

As part of a series of essays about the first 25 years of the International Society for Pediatric Neurosurgery--what we have accomplished and where we have been--I have decided to turn my attention to where we are now and where we are going. A corollary to consider, perhaps, is where we should be going. In other words, what is the appropriate relationship between pediatric neurosurgery and general neurosurgery?