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.

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.

Choroid plexus carcinoma in siblings: a study by light and electron microscopy with Ki-67 immunocytochemistry.

Choroid plexus carcinomas in siblings aged 11 months and 10 years were examined by light microscopy and immunocytochemistry. One case was studied by electron microscopy. Choroid plexus carcinoma is rare, with approximately 24 reported cases in children. Predicting the behavior of choroid plexus tumors from the histology can be difficult. Neither mitoses nor necrosis were seen in one case, but evaluation of proliferation using Ki-67 monoclonal antibody showed 9% of the cells to be in proliferative phases of the cell cycle, a high value for a glial-derived neoplasm. Ki-67 activity may be a more sensitive measure of proliferation in malignant choroid plexus tumors than the presence of mitoses and necrosis, and additional studies may establish its role in distinguishing between choroid plexus carcinoma and papilloma when histologic classification is equivocal. Both tumors were immunoreactive for keratin, which confirmed previous studies. Both were nonreactive for glial fibrillary acidic protein, S-100, and carcinoembryonic antigen (CEA), unlike a previous study which reported that choroid plexus carcinoma, compared to papilloma, was uniquely S-100-negative and CEA-positive. Choroid plexus carcinoma in siblings has not been reported. Chance occurrence in siblings is extremely unlikely; thus a genetic basis for the neoplasms is likely, although environmental influences cannot be excluded.

Muteness of cerebellar origin.

Acute bilateral damage to large areas of both cerebellar hemispheres including the dentate nuclei led to temporary loss of speech in six children. In each case muteness was unassociated with motor paralysis, loss of higher cognitive functions, or cranial nerve dysfunction. Muteness lasted one to three months. All patients were severely dysarthric during recovery. We conclude that transient muteness may result from acute bilateral cerebellar injury.

Acquired capsular/striatal aphasia in childhood.

We studied a case of language loss caused by an acquired vascular lesion in the putamen, anterior limb of the internal capsule, and lateral aspect of the head of the caudate nucleus in a 7-year-old right-handed girl. Acute right-sided hemiplegia, mutism, oral apraxia, and disturbance in language comprehension but no dysarthria were present. During recovery, a nonfluent aphasia with anomia was evident. After six months, only mild hemiparesis and minor spelling difficulties persisted. We compared this patient with an 11-year-old right-handed girl with right-sided hemiparesis and dysarthria but no language loss following a lesion in the globus pallidus, a portion of the posterior limb of the internal capsule, and the body of the caudate. The presence of a language disturbance in the first but not the second patient was attributed to the difference in lesion location. The symptoms and lesions were similar to those in recent reports of adult patients. To our knowledge, this is the first report of these findings in a child with a left-hemisphere lesion.

Elevated intracranial venous pressure as a universal mechanism in pseudotumor cerebri of varying etiologies.

Pseudotumor cerebri (PTC), or idiopathic intracranial hypertension, is a syndrome associated with multiple clinical conditions. We hypothesize that most if not all etiologies result in an increase in intracranial venous pressure as a final common pathway. We studied 10 patients with PTC. Five had dural venous outflow obstruction as demonstrated by venography, and the five remaining patients had normal venous anatomy. Pressure measurements, made during venography in eight patients, all showed elevated pressures. Pressure measurements in the superior sagittal sinus ranged from 13 to 24 mm Hg (mean, 16.6 mm HG). Patients with obstruction tended to have a high pressure gradient across the stenotic segment. Five patients with normal dural venous anatomy had elevated right atrial pressures (range, 6 to 22 mm Hg; mean, 11.8 mm Hg), which were transmitted up to the intracranial venous sinuses. Endovascular techniques, including angioplasty and infusion of thrombolytic agents in some cases, improved outlet obstruction from a hemodynamic perspective but were ineffective in consistently and reliably alleviating the clinical manifestations of PTC. Patients in both groups tended to respond well to conventional CSF diversion procedures. Our study suggests that elevated intracranial venous pressure may be a universal mechanism in PTC of different etiologies. This elevated venous pressure leads to elevation in CSF and intracranial pressure by resisting CSF absorption. Although the mechanism leading to venous hypertension in the presence of outflow obstruction is obvious, the etiology of increased intracranial and central systemic venous pressure in PTC remains obscure.

Optic atrophy induced by vincristine.

Bilateral optic atrophy developed in a 15-year-old patient receiving concomitant neuraxis radiation therapy and weekly vincristine sulfate for medulloblastoma. Other neurologic manifestations that have been associated with vincristine therapy, including inappropriate secretion of antidiuretic hormone, hypertension, confusion, and a severe peripheral neuropathy, were also observed. Neither increased intracranial pressure nor active tumor was identified. Recovery of visual function followed discontinuation of vincristine. Other neurotoxicities also reversed with drug withdrawal. Visual loss occurring in a patient receiving vincristine should alert the physician to the possibility that the process is drug related. This complication may be more likely in patients receiving concomitant or previous cranial radiation therapy. Other central neurotoxicities of vincristine may also be accentuated by neuraxis radiation. It is recommended that vincristine be discontinued in this situation if an aggressive search for a structural anatomic lesion in the optic mechanism is unrevealing, as the prognosis for recovery of visual function appears excellent.

Intracarotid chemotherapy of glioblastoma after induced blood-brain barrier disruption.

Intracarotid chemotherapy has been suggested as an additional mode of therapy in patients with brain tumors. Seven comatose patients received intracarotid 5-fluorouracil and adriamycin after intracarotid infusion of 25% mannitol to open the blood-brain barrier at the tumor site. Five of seven patients became fully functional for 3-12 months. Another 11 patients entered the study, of which nine are currently receiving therapy and are functional, and two have died, one from brain herniation. The results are encouraging and support the need for further research of this therapeutic method.

Demonstration of diastematomyelia and associated abnormalities with MR imaging.

Three patients were studied with a 0.3 T superconducting magnet to assess the role of magnetic resonance (MR) imaging in the recognition and evaluation of diastematomyelia and associated abnormalities. Comparison was made with other imaging techniques, including metrizamide computed tomographic (CT) myelography. With MR imaging, the divided spinal cord was well imaged in its entire craniocaudal extent, comparable to CT myelography. The bony septum, when it contained a marrow cavity, was also seen well. In two patients, dural ectasia and low position of the spinal cord with and without associated lipoma were clearly imaged. MR imaging demonstrated associated syringohydromyelia in one patient that was not detected by other radiologic studies. This preliminary experience with MR imaging of diastematomyelia suggests that once the bony details of the abnormality are defined, MR imaging can delineate the presence and extent of the divided spinal cord as well as its associated abnormalities adequately, obviating other studies.

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.

Cervicomedullary junction tumor diagnosed by nuclear magnetic resonance scanning: case report.

A neurofibroma of the cervical medullary region was accurately delineated using nuclear magnetic resonance (NMR) scanning. The tumor and its compression of the spinal cord were so well visualized that evaluation by myelography and postmyelographic computed tomography (CT) was unnecessary. NMR scanning should be considered as a replacement for myelography with CT in the initial evaluation of cervicomedullary spinal cord tumors.

The infant whiplash-shake injury syndrome: a clinical and pathological study.

The cases of 13 infants (median age, 3 months) who sustained nonaccidental trauma were reviewed. All presented with profound neurological impairment, seizures, retinal hemorrhages, and intracranial subarachnoid and/or subdural hemorrhages. Of 8 infants who died, autopsy was performed on 6. No patient had a skull fracture, and only one had an extracalvarial contusion. Five of the 6 patients on whom autopsy was performed had injuries at the cervicomedullary junction consisting of sub- or epidural hematomas of the cervical spinal cord with proximal spinal cord contusions. The authors conclude that direct cranial trauma is not an essential element of the injury mechanism in young patients who sustain severe whiplash-shake injuries. In addition to the classic injuries reported to occur with the shaken-baby syndrome, hemorrhages and contusions of the high cervical spinal cord may contribute to morbidity and mortality.

Quadriplegia secondary to hematoma after lateral C-1, C-2 puncture in a leukemic child.

Epidural, subdural, and intramedullary hemorrhage developed after lateral cervical (C-1, C-2) puncture in a thrombocytopenic patient with meningeal leukemia and increased intracranial pressure. Aggressive platelet support before the procedure did not prevent the hemorrhagic complication. Complete recovery from total motor paralysis with respiratory arrest followed immediate surgical decompression and continuing platelet support. The potential dangers of otherwise minor procedures in compromised patients are reiterated. Neurological recovery as seen here argues for immediate surgical intervention with the development of such potentially life-threatening events.

Anatomical evaluation of the caudal regression syndrome (lumbosacral agenesis) with magnetic resonance imaging.

Caudal regression syndrome involves absence of the sacrococcygeal vertebrae with or without lumbar vertebral defects. Since the neurological condition of infants with this syndrome deteriorates, radiographic studies are important to rule out any surgically correctable lesion. A paraplegic male neonate with a vertebral canal ending at T11 is presented. This is the first report of using magnetic resonance imaging to evaluate the spinal cord and surrounding soft tissues involved in this syndrome. Magnetic resonance imaging provides more anatomical details than myelogram with computed tomography, which greatly aids in determining whether surgery is necessary.

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.

Intracranial mycotic aneurysm in an infant: report of a case.

Although mycotic aneurysms tend to occur with greater frequency in children than adults, few cases of intracranial infectious aneurysms have been reported in children less than 1 year of age. The case of a previously healthy 7-month-old patient who suffered intracerebral and subarachnoid hemorrhage from multiple aneurysms of the middle cerebral artery is reported. The aneurysms proved to be infectious, based on culture material obtained at surgery from the aneurysm contents and adjacent brain tissue.

Traumatic atlantooccipital dislocation with survival.

Survival after traumatic atlantooccipital dislocation is rare. Only long-term survivors have been reported in the literature; however, improved prehospital care is likely responsible for the increase in the number of these patients seen at neurotrauma centers over the last decade. Associated severe and persistent neurological deficits are common in the few survivors. We report the case of a 10-year-old boy with traumatic atlantooccipital dislocation and a severe neurological injury. Low-field magnetic resonance imaging provided the additional diagnosis of an associated cervicomedullary epidural hematoma. The patient underwent emergency operative evacuation of the hematoma and an occipital-cervical fusion with internal fixation. He had a remarkable recovery in neurological function and achieved stable bony fusion 3 months postoperatively. With early recognition of this entity, improved neuroradiological imaging techniques, and aggressive treatment, patients may survive with significant neurological recovery.

Giant congenital cellular blue nevus of the scalp of a newborn with an underlying skull defect and invasion of the dura mater.

A case of a giant congenital cellular blue nevus of the scalp of a newborn with focal areas of malignant melanoma is presented. The nevus was associated with focal invasion of the underlying soft tissues, calvarium, epidural space, and dura mater. The later appearance of pigmented nevi in the submandibular region, sternocleidomastoid muscle, and testicular hydrocele raises the question of future metastases despite the nonmalignant microscopic appearance. Therapy consisted of total excision with cranioplasty and rotation and split skin grafts after temporary closure with silicone mesh.

Parenchymal cerebrospinal fluid extravasation as a complication of computerized tomography. Case report.

A case is presented in which neurological deterioration occurred during a computerized tomographic study. Total hemispheric dysfunction was seen in a patient with a postoperative suboccipital pseudomeningocele, whose head was wrapped in a compressive water bag. Cerebrospinal fluid was forced under pressure into the parenchyma of the right hemisphere, around a ventricular catheter. The neurological dysfunction resolved promptly with shunting.