Multiple shunt failures: an analysis of relevant features.
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Publications and source records attributed to J M Drake.
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Because normal cerebrospinal fluid (CSF) has almost no natural Doppler scatterers, patency testing of ventriculoperitoneal cerebrospinal fluid shunts (small silastic tubing with lumen diameter of approximately 1 mm draining excessive CSF from the brain) cannot be performed by Doppler ultrasound. We have developed a low-frequency bubble excitation system that generates microbubble scatterers in both distilled water and CSF. Doppler ultrasound can then be used for flow measurement in a ventriculoperitoneal shunt. By using low duty-cycle (approximately 10%), low-frequency (approximately 30 kHz), and low-amplitude (approximately 30 kPa) ultrasound, a population of microbubbles can be maintained for sufficiently long times (>10 min) for Doppler ultrasound measurement, although bubble initiation is inconsistent. The minimum pressure needed for bubble maintenance was found to decrease with increasing burst length and duty cycle. It has been possible to detect the presence of CSF shunt flow down to a mean flow rate of 3 mL/h (mean velocity approximately 0.6 mm/s). The bubble maintenance scheme developed satisfies the safety parameters specified by the American Institute of Ultrasound in Medicine (AIUM) and the US Food and Drug Administration (FDA). Results from both in vitro and in vivo (externalized shunts) experiments indicate the feasibility of this scheme for determining realistic CSF shunt flows, though some practical problems remain before the technique will be ready for clinical use.
OBJECTIVE: Malignant spinal cord astrocytomas are rare tumors and their specific MR characteristics have not been previously described. We present a detailed MR analysis of four children with malignant astrocytoma. METHODS: A review of the clinical database at the Hospital for Sick Children, Toronto revealed four patients with histologically-verified malignant spinal cord astrocytomas (WHO Grade 3 or 4) with pre-operative MR available for retrospective review. RESULTS: There were three boys and one girl with a mean age at presentation of four years (range 7 months-12 years). Mean duration of symptoms prior to presentation was six weeks (range 3 days-5 months). Pre-operative MR analysis revealed that all tumors were located in the cervical or cervico-thoracic regions and expanded the cord over an average of 6.5 vertebral levels. The signal was usually hypointense on T1-weighted and hyperintense or mixed intensity on T2-weighted images. In the three cases where gadolinium was given, all demonstrated enhancement (one rim enhancement with a discrete border and two with inhomogeneous central enhancement). One tumor appeared to be exophytic, one had a significant cystic component, and none showed evidence of hemorrhage. Pre-operative leptomeningeal spread of tumor was documented in two of four cases and involved intracranial spread in both cases. CONCLUSIONS: There did not appear to be any specific MR characteristics to help differentiate a malignant astrocytoma from a low-grade tumor, except for the high rate of leptomeningeal spread at presentation. It is recommended that full neuraxis MR imaging be performed pre-operatively in children in whom a rapidly progressive clinical course suggests a malignant lesion. This will likely have a high positive yield and provide valuable information prior to surgical intervention.
INTRODUCTION: The frontal and occipital horn ration (FOR) has recently been described as a simple, linear measurement of ventricular size that correlates very well with ventricular volume. This study further characterizes the measurement properties of the FOR by investigating its interobserver reliability and comparing it to a subjective assessment of ventricular size. METHODS: Axial images (CT and MR) of children with hydrocephalus taken before and after third ventriculostomy were reviewed by 4 independent observers. Two observers were blinded to patient identity and clinical status and 2 observers were nonblinded. Each observer independently recorded linear measurements from which the FOR was calculated for each image. Each reviewer also made a separate subjective assessment of the degree of hydrocephalus on a 9-point adjectival scale. Reliability was calculated using a repeated-measures analysis of variance (ANOVA) and an intraclass correlation coefficient (ICC) with random image and observer effects. RESULTS: There were 120 separate observations (4 observers, 30 images). The FOR ranged from 0.33 to 0.75 (mean 0.55, standard deviation 0.11). The reliability coefficient was 0.93 (95% confidence interval, CI 0.80-0.97) between the 2 blinded observers and 0.98 (95% CI, 0.95-0.99) between the 2 nonblinded observer. The overall interobserver reliability for all 4 observers was 0.95 (95% CI 0.92-0.98). The mean FOR for each observer was very similar, regardless of the observer's blinding status. However, the reliability of the observers' subjective assessment of the hydrocephalus was much lower (ICC = 0.77, 95% CI 0. 60-0.88). CONCLUSIONS: The FOR demonstrates excellent interobserver reliability (>0.9) and was superior to subjective assessments of hydrocephalus. In this study, excellent reliability was maintained regardless of the blinding status of the observers. This further demonstrates the properties of the FOR as a simple and reproducible measure of ventricular size. It is suitable for use in clinical studies, possibly even in situations in which observer blinding is not possible.
Ewing's sarcoma (ES) of the skull is rare. Herein, we present 2 cases of ES that involved the cranium in young children. In one case, the lesion originated in the petrous temporal bone; in the other, the frontal bone. Both children were acutely compromised neurologically by signs and symptoms of raised intracranial pressure. In both cases, radiographs revealed massive tumors affecting the skull. Neurosurgical resection of the tumor was undertaken in both instances, and the diagnosis of ES was confirmed by immunohistochemistry, cytogenetic analysis (translocation 11;22), spectral karyotyping and RT-PCR (demonstration of a EWS/FLI1 fusion transcript). Following aggressive surgical resection, both children received intensive chemotherapy. No child has received radiation therapy. One child is alive and well 8 years after diagnosis without any evidence of residual disease. The other is currently undergoing chemotherapy for her tumor. The principles involved in the management of children with cranial-based ES are discussed. These 2 cases serve to illustrate the fact that even children with massive ES tumors of the cranium may be salvaged with aggressive combination therapy.
Primary cerebellar glioblastomas multiforme are exceedingly rare in children. The authors therefore retrospectively characterized the clinical behavior and pathological features of these tumors. A review of the database at the Hospital for Sick Children, Toronto, Canada revealed four patients with cerebellar tumors that displayed significant pleomorphism, hypercellularity, mitoses, and necrosis with pseudopalisading. The authors performed a detailed clinical, radiological, histological, and immunohistochemical analysis of the tumors in these four children (three boys and one girl; average age at presentation 7 years; range 21 months-15 years). Magnetic resonance imaging and computerized tomography most commonly revealed a large lesion with minimal edema, inhomogeneous contrast enhancement, and a discrete border. Tumor resection was subtotal in one patient and gross total in three patients. Immunostaining of the tumor cells with antisera to glial fibrillary acidic protein and vimentin was positive in varying degrees. Initial adjuvant therapy consisted of local radiation only (one patient), chemotherapy only (one patient), and radiation and chemotherapy (one patient). One patient received no adjuvant therapy. Tumor recurrence was documented in all patients: two local recurrences (at 3.5 and 7 months), one spinal recurrence (at 14 months), and one local recurrence with ventricular and spinal spread (at 8 months). Ultimately, three of the four patients developed leptomeningeal tumor spread. Patient follow up ranged from 8 to 17 months (mean 12.5 months). Three patients were dead at last follow up with a mean survival of 15 months. The prognosis for patients with cerebellar glioblastomas is extremely poor, and the tumor has a tendency for cerebrospinal fluid dissemination. The optimal management of patients harboring of these difficult-to-treat tumors, including the role of craniospinal radiation and chemotherapy, has not yet been achieved.
OBJECTIVE: One of the difficulties with lumboperitoneal (LP) shunts has been non-invasively ascertaining shunt function. It has been previously reported that in the presence of a functioning LP shunt the perimesencephalic cisterns become obliterated--the "absent cistern sign". In order to more rigorously test this association we performed a retrospective analysis of LP shunt patients at the Hospital for Sick Children, Toronto. METHODS: The CT scans of all patients undergoing LP shunting over a 17 year period were reviewed. The "absent cistern sign" and ventricular size were compared against the results of either an isotope shunt study or surgical findings performed within 2 days of the CT. RESULTS: There were 38 CT scans (27 patients) performed within 2 days of an isotope shunt study and 15 CT scans (14 patients) performed within 2 days of a surgical intervention. These results give the absent cistern sign a sensitivity of 75% and a specificity of 57% when compared to the shunt isotope findings and a sensitivity of 100% and a specificity of 50% when compared to the surgical findings. Over 30% of the CT scans showed ventriculomegaly in the presence of a functioning shunt and, conversely, nearly 45% of the CT scans had normal or small lateral ventricles in the presence of a malfunctioning shunt. CONCLUSIONS: The "absent cistern sign" appears to reliably rule out a completely blocked shunt, but is less reliable in detecting a normal or partially obstructed shunt. Ventricular size correlates poorly with LP shunt function.
Since 1991, we have performed nearly 300 stereotactic procedures using the ISG viewing wand on a variety of cranial lesions in patients under 22 years of age. Of these, 38 procedures were performed on 34 patients for basal cerebral and skull base lesions. Our patients ranged in age from 3.5 months to 22 years with a mean age of 9.45 years. There were 18 females and 16 males. Twenty-one patients had basal cerebral lesions located in the thalamus (10), basal ganglia (2), third ventricle (2), and hypothalamus (7). Thirteen patients had skull base lesions located within the anterior optic apparatus (3), sella turcica (4), middle and posterior cranial fossae (4), and craniocervical region (2). Preoperative CT and/or MRI scan images were taken as a volume acquisition and transferred to the computer workstation utilizing the ISG Wand software. This workstation was transferred to the operating room where it was calibrated to a faro Surgicom arm which interfaces with the patient and the three-dimensional radiological image. The ISG Wand was utilized to plan the scalp and bone flaps and to select the optional trajectory to lesion. The surgical approaches which were specifically used in this series with the ISG Wand included transcallosal (15), pterional (5), frontal (3), subtemporal (4), transsphenoidal (3), temporal (3), tumor cyst shunt insertion (1), burr hole drainage (1), transoral (2), bifrontal (1), bifrontal mid facial (1), and transnasal (1). Although brain shift occurred following craniotomy and with brain retraction, the relative immobility of these lesions at the skull or cerebral base permitted an accurate targeting of all lesions with an error range of 1.0-2.5 mm throughout the entire procedure. This relatively precise intraoperative feedback led to more accurate recognition of tumor landmarks. It is the authors' impression that a more aggressive resection of these lesions was achieved than could be without the device. We conclude that a frameless stereotactic device such as the ISG Wand is particularly valuable in the approach to skull base and basal cerebral tumors in children.
OBJECTIVE AND IMPORTANCE: The release of a tethered spinal cord by sectioning a thickened filum terminale is a straightforward surgical procedure that can prevent, arrest, or ameliorate neurological deficits. We recently recognized progressive neurological deterioration caused by filum retethering in two patients years after this procedure was performed. This sequela of a recurrent tethered cord after the sectioning of a filum terminale has not previously been described. CLINICAL PRESENTATION: Two female patients, each 13 years of age at presentation, had been previously operated on for tethered spinal cords secondary to fibrolipomatous (fatty) fila terminale. Both presented with bladder dysfunction and one with progressive paraparesis. Magnetic resonance images revealed a low-lying conus medullaris and a sectioned filum with the proximal stump adherent to the posterior dura. INTERVENTION: Each patient underwent neurosurgical exploration of the previous site of sectioning, with the recognition of a retethered proximal stump of the filum terminale. After rerelease of the fatty filum, the patient with only bladder dysfunction stabilized and a motor examination revealed normal results for the patient with progressive paraparesis. CONCLUSION: Retethering of the spinal cord is a rare sequela after the sectioning of a tight filum terminale. The clinical presentation is typical for recurrent cord tethering, and the radiographic findings are subtle. Careful surgical exploration should be offered for spinal cord untethering. Awareness of this rare and hitherto undescribed sequela is necessary for appropriate long-term management of tethered spinal cord caused by a fatty filum terminale.
OBJECTIVE: Forty percent of standard cerebrospinal fluid shunts implanted for the treatment of pediatric hydrocephalus fail within the first year. Two new shunt valves designed to limit excess flow, particularly in upright positions, were studied to compare treatment failure rates with those for standard differential-pressure valves. METHODS: Three hundred-forty-four hydrocephalic children (age, birth to 18 yr) undergoing their first cerebrospinal fluid shunt insertion were randomized at 12 North American or European pediatric neurosurgical centers. Patients received one of three valves, i.e., a standard differential-pressure valve; a Delta valve (Medtronic PS Medical, Goleta, CA), which contains a siphon-control component designed to reduce siphoning in upright positions; or an Orbis-Sigma valve (Cordis, Miami, FL), with a variable-resistance, flow-limiting component. Patients were monitored for a minimum of 1 year. Endpoints were defined as shunt failure resulting from shunt obstruction, overdrainage, loculations of the cerebral ventricles, or infection. Outcome events were assessed by blinded independent case review. RESULTS: One hundred-fifty patients reached an endpoint; shunt obstruction occurred in 108 (31.4%), overdrainage in 12 (3.5%), loculated ventricles in 2 (0.6%), and infection in 28 (8.1%). Sixty-one percent were shunt failure-free at 1 year and 47% at 2 years, with a median shunt failure-free duration of 656 days. There was no difference in shunt failure-free duration among the three valves (P = 0.24). CONCLUSION: Cerebrospinal fluid shunt failure, predominantly from shunt obstruction and infection, remains a persistent problem in pediatric hydrocephalus. Two new valve designs did not significantly affect shunt failure rates.
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Selective dorsal rhizotomy (SDR) is widely used to treat spasticity in children with diplegic cerebral palsy (CP) but has never been shown conclusively to improve functional outcome. The study was designed to measure changes in gross motor function in children 1 year following rhizotomy compared with a control group receiving equivalent physiotherapy (PT) and occupational therapy (OT) with the exception that the rhizotomy group initially underwent a 6-week postoperative in-patient therapy program. Twenty-four children (mean age 58 months) with mild to moderate CP with spastic diplegia were randomly assigned to a therapy-only control group (CG) (N=12) or rhizotomy and therapy group (RG) (N=12). The Gross Motor Function Measure (GMFM) was administered at the baseline, 6-, and 12-month assessments. Extremity tone, range of motion (ROM), biomechanics of the ankle-stretch reflex, isometric contraction, and temporal gait components were also evaluated. GMFM scores in the RG improved by 12.1 percentage points versus 4.4 percentage points in the CG (P<0.02). RG knee and ankle tone was significantly reduced (P<0.005), associated with increased passive ankle ROM (P<0.001), and decreased soleus EMG reflex activity on forced dorsiflexion (P<0.008). Foot-floor contact pattern improved in the RG compared with the CG (P<0.05). In conclusion, SDR combined with PT and OT leads to significantly greater functional motor improvement at 1 year following surgery compared with PT and OT alone. This was achieved in part through reduced knee and ankle tone, increased ankle dorsiflexion ROM, and more normal foot-floor contact during walking.
OBJECTIVE: Measurement of ventricular size is important in pediatric patients with hydrocephalus, especially those who are being followed with cerebrospinal fluid (CSF) shunts. While volumetric techniques are a more accurate estimate of true ventricular volume, they are often impracticable when multiple modalities including ultrasound are used. Volumetric area and linear measurements were compared to find the most reasonable measurement method. METHODS: Sixty-four computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US) scans from 25 children aged 0-17 years with hydrocephalus, before and after treatment, were measured. Measurements included ventricular volume, a ventricular/brain ratio, and four standard linear measures (Evans' ratio, Huckman's measurement, minimal lateral ventricular width, and lateral ventricular span at the body). We also included a new ratio, which accounts for often disproportionate occipital horn expansion in pediatric patients, called the frontal and occipital horn ratio. Volume and linear measurements were compared using the Spearman's correlation coefficients and correlations were further differentiated using a Z test statistic. The frontal and occipital horn ratio was also measured on CT, MRI, and US scans from 44 normal children aged 0-17 years to identify normal values. The effect of age was determined by linear regression. RESULTS: The best linear correlation with ventricular size was the frontal + occipital horn ratio (r = 0.852) and was equivalent to the ventricular/brain ratio (r = 0.891), previously shown to have the highest correlation with ventricular volume. Evans' ratio correlates less well (r = 0.423). The normal frontal and occipital horn ratio is 0.37 and is independent of age. CONCLUSIONS: The frontal and occipital horn ratio is a simple method of evaluating ventricular size in pediatric hydrocephalus patients with CSF shunts.
UNLABELLED: Intellectual impairment has been related to alteration of neuronal innervation in the following regions: cholinergic basal forebrain nuclei (Ch1-Ch6, learning and memory), dopaminergic ventral tegmental area (emotional control), and noradrenergic locus ceruleus (cognition). Recent studies have implicated neuronal injury in the pathogenesis of hydrocephalus. OBJECT: The authors used immunohistochemical techniques to investigate functional injury in these regions in animals with progressive hydrocephalus, following shunt placement for cerebrospinal fluid (CSF) drainage. METHODS: Hydrocephalus was induced in 20 Wistar rats by intracisternal injection of 0.05 ml of 25% kaolin solution. Four control animals (Group 1) received the same volume of saline. Ventriculoperitoneal shunts were inserted in eight rats at 2 and 4 weeks after kaolin injection and the animals were killed at 8 weeks (Group 2). The other 12 hydrocephalic animals were killed at 2, 4, and 8 weeks without undergoing shunt placement (Group 3). Immunoreactive (IR) neurons to choline acetyltransferase (ChAT) in Ch1-Ch6, tyrosine hydroxylase (TH) in the ventral tegmental area, and dopamine B-hydroxylase (DBH) in the locus ceruleus, as well as IR projection fibers in the terminal areas, were compared between groups. The number of ChAT- and TH-IR neurons in rats with and without shunt placement was counted for quantitative analysis. The number of ChAT-IR neurons was progressively reduced during the development of hydrocephalus in Ch1, Ch2, Ch3, and Ch4 (p < 0.05). Tyrosine-hydroxylase-immunoreactive neurons were also reduced in number, and demonstrated decreased projection fibers and terminals. Early shunting (at 2 weeks) restored ChAT and TH immunoreactivity to control levels, but late shunting (at 4 weeks) did not (p < 0.05). The DBH-IR neurons in the locus ceruleus were remarkably compressed by the dilated fourth ventricle, and diminished immunoreactivity was observed in the terminal areas. Shunt placement for CSF also restored the immunoreactivity in this system. CONCLUSIONS: These findings indicate that a progressive functional injury occurs in the cholinergic, dopaminergic, and noradrenergic systems as a result of hydrocephalus. This may contribute to intellectual impairment and might be prevented by early treatment with shunt placement.
Structural and/or functional injury of the basal ganglia can lead to motor functional disabilities, abnormal gait and posture, and intellectual/emotional impairment, disorders also frequently seen in hydrocephalus. Previous reports have documented changes in dopamine levels in the neostriatum in experimental hydrocephalus. The present study was designed to investigate possible functional injury of cholinergic, GABAergic and dopaminergic systems in the basal ganglia immunohistochemically in a model of kaolin-induced hydrocephalus. Hydrocephalus was induced in 12 Wistar rats by intracisternal injection of 0.05 ml volume of 25% kaolin solution under microscopic guidance. Four controls received an equal volume of sterile saline. The animals were killed at 2, 4 and 8 weeks after injection. The numbers of choline acetyltransferase (ChAT)- and glutamic acid decarboxylase (GAD)-immunoreactive (IR) neostriatal neurons and tyrosine hydroxylase (TH)-IR nigral neurons, were counted in 60-micron thick representative sections and the IR cellular densities (counted cell number/neostriatal area) were calculated in the neostriatum. The number of total neostriatal neurons was also counted in 15-micron thick sections stained by cresyl violet (Nissl staining) to calculate the cellular density. The number and cellular density of neostriatal ChAT-IR neurons were significantly reduced at 2, 4, and 8 weeks after injection (P < 0.05), while those of GAD-IR neurons decreased at 4 and 8 weeks (P < 0.05). There was a linear correlation between degree of ventricular enlargement, and reduction in number of ChAT- and GAD-IR neurons (P < 0.001) as well as in the cellular density (P < 0.001). However, Nissl staining revealed no reduction in the cellular density of total neostriatal neurons (P < 0.001). TH immunoreactivity was reduced in neostriatal axons and in nigral compacta neurons, particularly in the medial portion of the dopaminergic nigrostriatal pathway. These findings suggest that progressive hydrocephalus results in functional injuries of cholinergic and GABAergic neurons in the neostriatum and dopaminergic neurons in the substantia nigra compacta by mechanical distortion. The disturbance in balance of these neurotransmitter systems in the basal ganglia may explain some of motor functional disabilities in hydrocephalus.
OBJECTIVE: To review and analyze a contemporary series of 15 neonates who were treated for posterior fossa subdural hematomas (PFSDHs) during the era of computed tomography and magnetic resonance imaging. METHODS: A retrospective chart review identified all neonates with PFSDHs for whom neurosurgical consultations were obtained for treatment planning. RESULTS: There were nine male and six female patients. The mean gestational age was 39 weeks. Nine of the 15 mothers of the patients were primiparous. Instrument-assisted delivery (forceps and/or vacuum extractor) was undertaken for seven patients. The mean birth weight of the infants was 3165 g (range, 2160-3930 g). The mean 5-minute Apgar score was 7.5. Symptoms of PFSDH developed within the first 24 hours of life in 13 neonates. The predominant symptoms and signs were failure to thrive, irritability, seizures, apnea, and bradycardia. Lumbar punctures to rule out central nervous system sepsis were performed in six neonates. Hemograms revealed that six neonates were anemic with low hemoglobins, five had low platelets, and four had abnormal prothrombin and/or partial thromboplastin times at the time of diagnosis. Computed tomography established the diagnosis of PFSDH in all cases. Magnetic resonance imaging was performed for two neonates. The median time to diagnosis by imaging studies was 10 hours after birth. Surgical evacuation of the PFSDHs was performed in eight neonates. Seven neonates were followed conservatively with serial imaging studies. There was no mortality in either treatment group. Follow-up ranged from 2 to 10 years, with a mean of 4.5 years. Functional outcome assessment revealed that seven neonates were neurodevelopmentally normal, three were mildly delayed, two were moderately delayed, and three were profoundly delayed. In addition to traumatic causes of the PFSDHs, three neonates were observed to have coagulation disturbances at birth and one was observed at follow-up to have a posterior fossa medulloblastoma that had bled at birth. CONCLUSION: PFSDHs are rare but important lesions to diagnose early in the neonatal period. Surgery can be life-saving when performed in a timely manner for signs and symptoms of brain stem dysfunction. A search for an underlying cause predisposing to a PFSDH may, on occasion, reveal a coagulation disturbance or a neoplasm that will require additional therapeutic considerations.
We studied 16 children with lesions in the eloquent brain to determine if the amalgamation of information from functional magnetic resonance imaging (fMRI), frameless stereotaxy, and direct cortical mapping and recording could facilitate the excision of these lesions while minimizing potential neurological deficits. The mean age of the children was 10 years. Fourteen children presented with seizures. All lesions were located in or near eloquent cerebral cortex. fMRI was successful in all patients in delineating the relationship between the lesion and regions of task-activated cortex. The ISG wand was utilized in all cases for scalp and bone flap placement, and for intraoperative localization of the lesion. Direct cortical stimulation or recording of phase reversals with somatosensory evoked potentials helped delineate the central sulcus and language cortex in patients with lesions near the motor or language cortex. Intraoperative electrocorticography (ECoG) was utilized in all patients who presented with seizures to guide the extent of resection of the epileptiform cortex. Ten children had benign cerebral neoplasms, nine of which were totally resected. The other diagnoses included vascular malformations, Sturge-Weber, tuberous sclerosis, Rasmussen's encephalitis, and primitive neuroectodermal tumor. Only 1 patient with a left Rolandic AVM developed a new neurological deficit postoperatively. Thirteen of fourteen patients who presented with seizure disorders were rendered either seizure free or improved in terms of seizure control postoperatively. Follow-up has ranged from 12 to 18 months, with a mean follow-up of 15 months. We conclude that the techniques of fMRI, frameless stereotaxy, direct cortical stimulation and recording can be utilized in sequence to accurately localize intracerebral lesions in eloquent brain, and to reduce the morbidity of resecting these lesions in children.
The authors investigated functional neuronal changes in experimental hydrocephalus using immunohistochemical techniques for glutamic acid decarboxylase (GAD) and two neuronal calcium-binding proteins: parvalbumin (PV) and calbindin D28K (CaBP). Hydrocephalus was induced in 16 adult Wistar rats by intracisternal injection of a kaolin solution, which was confirmed microscopically via atlantooccipital dural puncture. Four control rats received the same volume of sterile saline. Immunohistochemical staining for GAD, PV, and CaBP, and Nissl staining were performed at 1, 2, 3, and 4 weeks after the injection. Hydrocephalus occurred in 90% of kaolin-injected animals with various degrees of ventricular dilation. In the cerebral cortex, GAD-, PV-, and CaBP-immunoreactive (IR) interneurons initially lost their stained processes together with a concomitant loss of homogeneous neuropil staining, followed by the reduction of their total number. With progressive ventricular dilation, GAD- and PV-IR axon terminals on the cortical pyramidal cells disappeared, whereas the number of CaBP-IR pyramidal cells decreased, and ultimately in the most severe cases of hydrocephalus, GAD, PV, and CaBP immunoreactivity were almost entirely diminished. In the hippocampus, GAD-, PV-, and CaBP-IR interneurons demonstrated a reduction of their processes and terminals surrounding the pyramidal cells, with secondary reduction of CaBP-IR pyramidal and granular cells. On the other hand, Nissl staining revealed almost no morphological changes induced by ischemia or neuronal degeneration even in the most severe cases of hydrocephalus. Hydrocephalus results in the progressive functional impairment of GAD-, PV-, and CaBP-IR neuronal systems in the cerebral cortex and hippocampus, often before there is evidence of morphological injury. The initial injury of cortical and hippocampal interneurons suggests that the functional deafferentation from intrinsic projection fibers may be the initial neuronal event in hydrocephalic brain injury. Although the mechanism of this impairment is still speculative, these findings emphasize the importance of investigating the neuronal pathophysiology in hydrocephalus.