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Biomedical subjects

David M Frim

Publications and source records attributed to David M Frim.

18 recordsLinked to original sources
PubMed2007

Correction of sagittal craniosynostosis using a novel parietal bone fixation technique: results over a 10-year period.

Isolated sagittal synostosis is a common form of craniosynostosis affecting roughly 1 in 5,000 children at birth. This results in a scaphocephalic head shape with a characteristically elongated anterior-posterior dimension and narrowed biparietal diameter. We present our experience with the correction of scaphocephaly due to sagittal synostosis using cranial vault reconstruction with a novel form of parietal bone fixation in 21 patients over 10 years. The medial fixation results in a hinging effect whereby transverse brain growth at the squamoid suture is enhanced. This results in excellent cosmetic results that are immediate and durable without the need for postoperative molding helmets. Furthermore, the complications associated with this procedure are limited.

Bone Wires↗
PubMed2007

Neuroprotective effect of the surfactant poloxamer 188 in a model of intracranial hemorrhage in rats.

OBJECT: Neuronal injury remains a leading cause of morbidity in both neonates and adults with injuries induced by intracranial hemorrhage, ischemia-reperfusion, and excitotoxicity. To date, a number of neuroprotective strategies have been evaluated, but they have shown little benefit. Poloxamer 188 (P-188), a membrane-active triblock copolymer, has been studied extensively as a cell-membrane sealant. The authors used an animal model to study the neuroprotectant effects of P-188 administered by intracisternal (IC) injection after experimentally induced intraparenchymal hemorrhage. METHODS: Sprague-Dawley rats received an IC injection of either P-188 or vehicle (artificial cerebrospinal fluid) 10 minutes after striatal infusion of 50 microl of autologous blood. Animals from both treatment groups were killed either 2 or 7 days later. In a second experiment, after striatal blood infusion and early IC injection of either P-188 or vehicle, animals received daily IC injections of either P- 188 or vehicle for 5 days, and were killed 7 days after induction of the experimental hemorrhage. Striatal tissues were histologically analyzed for neuronal loss, and lesion volumes were determined. Lesion volumes in the animals that received a single dose of P-188 were significantly smaller (mean+/-standard deviation 18.3+/-4.3 mm(3), six rats; p = 0.04) than those in the control group (31.4+/-4.3 mm(3), seven rats) when measured 2 days postinjection; however, no difference in lesion volumes was present 7 days postinjection. Lesion volumes in the animals who received 5 days of daily P-188 injections were significantly smaller (1.50+/-0.58 mm(3), 10 rats; p = 0.04) than those in the corresponding control group (5.04+/-1.85 mm(3), eight rats) when measured at 7 days. CONCLUSIONS: A single dose of P- 188 protects against early neuronal loss after hemorrhage but has no effect on long-term hemorrhage-induced neuronal loss. However, repeated daily P-188 treatment appears to produce effective long-term neuronal protection.

Animals↗
PubMed2006

Mutually suppressive interrelations of symmetric epileptic foci in bitemporal epilepsy and their inhibitory stimulation.

OBJECTIVES: The goal of this study is to analyze the suppressive interaction of symmetric temporal lobe epileptic foci, assess some failures of epilepsy surgery, and evaluate the possibility of terminating focal seizures with stimulation of symmetric epileptic foci. MATERIALS AND METHODS: One hundred and twenty-nine intractable epilepsy patients (age range 6-53 years) with bitemporal epileptiform abnormalities in multiple scalp EEGs were evaluated with chronically implanted depth and subdural electrodes. Interelectrode coherence and power spectra were studied using internally developed software. RESULTS: Bitemporal epileptic foci were found in 85/129 (66%) patients with reciprocal relations between these foci in 57/85 (67%) patients. Temporal lobectomy was performed for 67/85 patients. 12/67 patients became free of seizures (Engel's Class I), 32/67 improved (Classes II and III), and 23/67 did not improve. 14/23 patients demonstrated post-surgical activation of the contralateral temporal lobe epileptic focus. For 8/14 of these patients, the stereotactic cryoamygdalatomy was performed in the temporal lobe contralateral to the first surgery. 5/8 patients became free of seizures. It was found that stimulation of temporal lobe deep epileptic focus may terminate focal seizures in the contralateral symmetric structures. CONCLUSION: A mutually suppressive relationship is one of variants of the interaction of symmetric epileptic foci. Some epilepsy surgery failures may be a result of post-surgical activation of the intact focus. The increase of coherence between both temporal lobes before the seizure onset of the seizure suggests the establishment of functional interrelations between two epileptic foci at an early, "hidden" phase of seizures, and may predict the direction of seizure spread. Mutually suppressive interrelations of symmetric epileptic foci might be employed for chronic therapeutic stimulation.

Adolescent↗
PubMed2006

A cortical potential imaging study from simultaneous extra- and intracranial electrical recordings by means of the finite element method.

In the present study, we have validated the cortical potential imaging (CPI) technique for estimating cortical potentials from scalp EEG using simultaneously recorded electrocorticogram (ECoG) in the presence of strong local inhomogeneity, i.e., Silastic ECoG grid(s). The finite element method (FEM) was used to model the realistic postoperative head volume conductor, which includes the scalp, skull, cerebrospinal fluid (CSF) and brain, as well as the Silastic ECoG grid(s) implanted during the surgical evaluation in epilepsy patients, from the co-registered magnetic resonance (MR) and computer tomography (CT) images. A series of computer simulations were conducted to evaluate the present FEM-based CPI technique and to assess the effect of the Silastic ECoG grid on the scalp EEG forward solutions. The present simulation results show that the Silastic ECoG grid has substantial influence on the scalp potential forward solution due to the distortion of current pathways in the presence of the extremely low conductive materials. On the other hand, its influence on the estimated cortical potential distribution is much less than that on the scalp potential distribution. With appropriate numerical modeling and inverse estimation techniques, we have demonstrated the feasibility of estimating the cortical potentials from the scalp EEG with the implanted Silastic ECoG gird(s), in both computer simulations and in human experimentation. In an epilepsy patient undergoing surgical evaluation, the cortical potentials were reconstructed from the simultaneously recorded scalp EEG, in which main features of spatial patterns during interictal spike were preserved and over 0.75 correlation coefficient value was obtained between the recorded and estimated cortical potentials. The FEM-based CPI technique provides a means of connecting the simultaneous recorded ECoG and the scalp EEG and promises to become an effective tool to evaluate and validate CPI techniques using clinic data.

Algorithms↗
PubMed2006

The Chiari pseudotumor cerebri syndrome: symptom recurrence after decompressive surgery for Chiari malformation type I.

INTRODUCTION: The etiology of Chiari malformation type I (CM1) as well as other anomalies associated with CM1 remains poorly defined. We have noted the presence of elevated CSF pressures with small ventricles, consistent with the pseudotumor cerebri (PTC) syndrome in a group of CM1 patients that did not respond over the long term to posterior fossa decompression. In order to better understand this association, we reviewed a series of CM1 patients treated by posterior fossa decompression to define the prevalence and nature of post-Chiari PTC. METHODS: We performed a retrospective chart review of 192 patients diagnosed with CM1 and treated by posterior fossa decompression. Patients who failed to respond to surgery were evaluated by CINE MR flow studies to assess presence of CSF flow at the foramen magnum and then by lumbar puncture if flow was present. The diagnosis of Chiari PTC was defined by recurrence of Chiari-like symptoms after decompression, elevated lumbar CSF pressure in the absence of ventriculomegaly, and transient resolution of symptoms with large volume lumbar CSF drainage. RESULTS: Thirty-six of 192 patients did not improve with surgical decompression. Fifteen of 36 operative CM1 patients (41.6%) were found to have Chiari PTC. The most frequent symptoms of CM1/PTC patients were head pain, body aches, and balance difficulties. Three patients also experienced visual complaints. The mean maximum lumbar CSF pressure documented in this cohort was 26 cm of water in adults and 25.3 in children. All patients received treatment for the CM1/PTC that culminated with CSF shunt placement in 14/15. Seven of 9 pediatric patients had significant symptom resolution while 6/6 adult patients remained variably symptomatic. CONCLUSION: CM1 and PTC co-exist in a surprising percentage of failed operative CM1 patients and present with a syndrome that is difficult to treat. The etiology of this association after Chiari decompression is unclear, though perhaps posterior fossa surgery in the setting of abnormal anatomy and potentially anomalous CSF flow dynamics contributes to CSF malabsorption and resultant or coexistant PTC.

Adult↗
PubMed2004

The surfactant poloxamer-188 protects against glutamate toxicity in the rat brain.

Membrane repair of damaged neurons by surfactant poloxamers has been noted in experimental spinal cord injury and in vitro excitotoxicity. We examined poloxamer-188 (P-188)-mediated neuroprotection in a rat model of glutamate toxicity. Quinolinate was infused into the striatum followed 10 min and 4 h later by P-188 administered either i.v. or intracisternally (i.c.), or by vehicle. Mean neuronal loss examined volumetrically 7 days later in control animals was 50% greater (P < 0.01) than after i.c. P-188 treatment; control lesion volumes were 38% greater than lesion volumes after i.v. P-188 treatment; however, that comparison did not reach significance. This robust protection against glutamate toxicity may predict P-188-mediated neuroprotection against a broad range of clinically relevant neural insults.

Animals↗
PubMed2004

Poloxamer 188 volumetrically decreases neuronal loss in the rat in a time-dependent manner.

OBJECTIVE: Excitotoxicity is a multistep process that results in either necrosis or apoptosis. It has been associated with neuronal death in trauma, ischemia, and neurodegeneration. The final step in necrotic cell death is the rupture of a cell's plasma membrane; repair of this membrane rupture is a potentially powerful technique of neuroprotection. Poloxamer 188 (P-188) is a synthetic surfactant that seals experimentally porated membranes. This study investigated the usefulness and time dependence of intrathecal P-188 in protecting neurons in an in vivo model of excitotoxicity in the rat. METHODS: Twenty-eight Sprague-Dawley rats underwent striatal infusion of quinolinic acid to produce a spherical excitotoxic lesion. Each animal then received either vehicle or P-188 at 10 minutes, 4 hours, or both time points after surgery by direct cisterna magna injection. Animals were killed at 1 week, and brains were stained immunohistochemically for the neuronal marker Neu-N. Volumes of neuronal loss were calculated and compared between groups by analysis of variance. RESULTS: All animals were found to have spherical, stereotyped lesions. The animals that received intrathecal poloxamer at the early injection time had statistically smaller lesions (8.16 +/- 6.12 mm(3); n = 5; P = 0.0015) than controls (18.25 +/- 11.42 mm(3); n = 11). Those animals that received poloxamer at both injection times also had statistically smaller lesions (10.57 +/- 9.00 mm(3); n = 7; P = 0.0095). The group that received poloxamer at the late injection time only did not have significantly decreased lesion size (14.86 +/- 7.95 mm(3); n = 5). CONCLUSION: Intrathecal P-188 reduces neuronal loss after excitotoxic injury in the rat only when delivered immediately after the toxin. This observation confirms the potential of surfactant molecules as neuroprotectants but predicts that their usefulness is best realized by early and potentially ongoing treatment.

Animals↗
PubMed2004

Pseudotumor cerebri patients with shunts from the cisterna magna: clinical course and telemetric intracranial pressure data.

OBJECTIVE: Shunting of cerebrospinal fluid (CSF) to an extracranial site is the mainstay of treatment of absorptive hydrocephalus and pseudotumor cerebri. On occasion, both lateral ventricles and the lumbar space become unsuitable for placement of a functioning CSF drainage catheter. We have encountered several such patients and describe our strategy of shunting from the cisterna magna to the pleural space or cardiac atrium. METHODS: We report a retrospective review of the clinical course of five patients with cisternal shunts and intracranial pressure telemonitoring devices. RESULTS: Cisternal shunting was able to successfully drain CSF to a normal pressure in all five patients. CSF pressure data collected from those patients indicate that the CSF pressure dynamics in cisternal shunts is similar to that of ventricular shunts. However, the cisternal shunting and subsequent high revision rate did result in a significant number of complications and two shunt infections. CONCLUSION: Shunting CSF from the cisterna magna in the absence of another suitable drainage site does result in acceptable reduction of elevated intracranial pressure. However, the technique is associated with a high complication rate that may reflect the population of patients in whom this technique is required.

Adult↗
PubMed2004

Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review.

OBJECT: The authors report their experience in six patients with pineal tumors and associated hydrocephalus who underwent an endoscopic biopsy procedure and third ventriculocisternostomy (ETVC) in a single sitting. METHODS: The ETVC was successfully performed without complication in all patients; however, a ventriculoperitoneal shunt was eventually required in four. Histological diagnosis was successfully established in four patients. The authors also reviewed the literature to assess reports involving ETVC and tumor biopsy sampling in patients with pineal tumors and hydrocephalus. A total of 54 cases, including those in this study, have been reported. Fifteen percent of the patients eventually required placement of a ventricular shunt. The transient complication rate was 15% with no death. A positive tissue diagnosis was established in 89% of the cases overall. CONCLUSIONS: The authors conclude that the endoscopic management of patients with pineal region masses and hydrocephalus may be a preferred initial strategy.

Adolescent↗
PubMed2004

Surfactant poloxamer 188-related decreases in inflammation and tissue damage after experimental brain injury in rats.

OBJECT: The surfactant, poloxamer 188 (P-188), has been found to protect against tissue injury in various experimental models. Its protective mechanism may involve the effects of the surfactant against oxidative stress and inflammation. The authors investigated the role of P- 188 in the reduction of tissue injury and macrophage response in a model of excitotoxic brain injury in the rat striatum. METHODS: Fifteen Sprague-Dawley rats underwent stereotactic injection of 120 nmol of quinolinic acid into the striatum and received intracisternal injection of vehicle or P-188 (40 mg/kg) at 10 minutes and 4 hours postinjury. Rats were killed after 1 week, and the histological score was determined based on the degree of overall tissue injury (Grades 1-4) at the lesion site. The number of macrophages within the lesioned striatum was compared with that found within the striatum on the nonoperated contralateral side. The scores related to tissue damage and the macrophage ratios of each group were then compared using t-tests. Striatal injection of the toxin produced a lesion characterized by necrosis and inflammation surrounding the injection site in all six control animals. In rats in which intracisternal P-188 was administered, significantly less tissue injury was demonstrated (mean score 2.45 +/- 0.74) than in controls (mean score 3.14 +/- 0.75) (p = 0.045). The rats that received intracisternal surfactant also had significantly less macrophage infiltrate (mean ratio 1.06 +/- 0.18) than control animals (mean ratio 2.00 +/- 0.48) (p = 0.004). CONCLUSIONS: The surfactant P-188 reduces tissue loss and macrophage infiltrate after excitotoxic brain injury in the rat. Possible mechanisms of this effect may include direct surfactant modulation of inflammatory cell membrane fluidity.

Animals↗
PubMed2003

Seizure anticipation in pediatric epilepsy: use of Kolmogorov entropy.

The purpose of this paper is to demonstrate feasibility of using trends in Kolmogorov entropy to anticipate seizures in pediatric patients with intractable epilepsy. Surface and intracranial recordings of preseizure and seizure activity were obtained from five patients and subjected to time series analysis using Kolmogorov entropy. This metric was compared with correlation dimension and power indices, both known to predict seizures in some adult patients. We used alarm levels and introduced regression analysis as a quantitative approach to the analysis of trends. Surrogate time series evaluated data nonlinearity, as a precondition to the use of nonlinear measures. Seizures were anticipated before clinical or electrographic seizure onset for three of the five patients from the intracranial recordings, and in two of five patients from the scalp recordings. Anticipation times varied between 2 and 40 minutes. This is the first report in which simultaneous surface and intracranial recording are used for seizure prediction in children. We conclude that the Kolmogorov entropy and power indices were as effective as the more commonly used correlation dimension in anticipating seizures. Further, regression analysis of the Kolmogorov entropy time series is feasible, making the analysis of data trends more objective.

Adolescent↗
PubMed2003

Decompressive hemicraniectomy in a 6-year-old male after unilateral hemispheric stroke. Case report and review.

We report the case of a 6-year-old male who underwent a hemicraniectomy after a right-sided middle cerebral arterial infarct. This is the youngest patient reported to have undergone this procedure for stroke-associated brain swelling. This case illustrates that hemicraniectomy for stroke can be performed safely in pediatric patients, with potential brain- and lifesaving benefits.

Age Factors↗
PubMed2003

Recurrence of symptoms after Chiari decompression and duraplasty with nonautologous graft material.

Nonautologous material is commonly used for dural grafting. Although good results have been reported with the use of some of these materials in cranial surgery, there is a paucity of information regarding their use in craniocervical decompressive surgery. We report three cases of patients with Chiari malformation type I who experienced recurrent or new-onset Chiari symptoms after surgical decompression and duraplasty with bovine pericardium, Gore-Tex or cadaveric dura. We review the use of these materials and propose possible mechanisms by which a reaction to a nonautologous graft could cause recurrent Chiari symptoms. The preferential use of autologous material for dural grafts during posterior fossa decompressive surgery should prevent this cause of symptom recurrence.

Adult↗
PubMed2002

Lumboperitoneal shunting as a treatment for slit ventricle syndrome.

OBJECTIVE: Slit ventricle syndrome (SVS) has been described in hydrocephalus patients who continue to have shunt malfunction-like symptoms in the presence of a functioning shunt system and small ventricles on imaging studies. These symptoms usually present years after shunt placement or revision and can consist of headache, nausea and vomiting, lethargy and decreased cognitive skills. Treatments offered range from observation, medical therapy (migraine treatment) and shunt revision to subtemporal decompression or cranial vault expansion. We describe a subset of patients with SVS who were symptomatic with high intracranial pressure (ICP) as measured by sedated lumbar puncture and whose symptoms completely resolved after lumboperitoneal shunt (LPS) placement. METHODS: Seven patients with a diagnosis of SVS underwent lumboperitoneal shunting. The age at shunting ranged from 3 to 18 years. Most had undergone recent ventriculoperitoneal shunt (VPS) revisions for presentation of shunt malfunction-like symptoms. Despite this, all remained symptomatic and underwent a sedated lumbar puncture to measure opening pressure (OP). All had high OP in spite of a functional VPS and underwent LPS placement. RESULTS: All 7 patients had a prolonged period of overdrainage symptoms after lumboperitoneal shunting that resolved completely over several weeks. The initial etiology of hydrocephalus was reported to include trauma, aqueductal stenosis and intraventricular hemorrhage of prematurity. Two patients required revision of their LPS, after which their symptoms again resolved. CONCLUSION: In a certain subset of patients with SVS who are symptomatic from increased ICP, placement of an LPS is an effective treatment option. It appears that this subgroup of patients previously treated with ventriculoperitoneal shunting behave in a fashion similar to pseudotumor cerebri patients and respond well to lumboperitoneal shunting.

Adolescent↗
PubMed2002

Gene therapy for Parkinson's disease.

Significant progress has been made in the field of gene therapy for Parkinson's disease (PD). Successful vehicles for gene transfer into the central nervous system have been developed and clinical efficacy and safety have both been shown in various animal models of PD. Further optimisation of dosing, timing and location of gene therapy delivery as well as the ability to regulate and prolong gene expression will be important for the commencement of human trials. Current gene therapy models for PD have focused on two treatment strategies. One is the replacement of biosynthetic enzymes for dopamine synthesis and the second strategy is the addition of neurotrophic factors for protection and restoration of dopaminergic neurones. Concepts of neuroprotection and restoration of the nigrostriatal pathway will become important themes for future genetic treatment strategies for PD and may include, in addition to neurotrophic factors, genes to prevent apoptosis or detoxify free radical species. This review will highlight the recent literature on gene therapy for PD and summarise general approaches to gene therapy.

Animals↗
PubMedDate not supplied

Endoscopic cyst fenestration outcomes in children one year of age or less.

The use of endoscopic fenestration (EF) is becoming an increasingly common treatment for symptomatic intracranial cysts. Very little data exist regarding outcomes for this procedure in children 1 year of age or younger. We retrospectively reviewed the clinical outcomes of 8 children 1 year of age or less treated at our institution with endoscopic cyst fenestration. The mean follow-up was roughly 2.5 years. These data were combined with 17 other cases obtained from the published literature. EF was successful in rendering patients shunt-free or minimizing the number of ventricular catheters in 18 of 26 operations. There were 8 outright failures -- two in 1 patient. Given the risks and complications of cerebrospinal fluid shunting in children less than 1 year of age, we advocate the consideration of EF as initial treatment of symptomatic intracranial cysts.

Brain↗
PubMedDate not supplied

Lumbar CSF shunting preferentially drains the cerebral subarachnoid over the ventricular spaces: implications for the treatment of slit ventricle syndrome.

Based on a proposed pathophysiology of slit ventricle syndrome (SVS), we have hypothesized that lumboperitoneal shunting exerts effects in SVS patients by increasing the buffering capacity for raised intracranial pressure (ICP) via an increase in cerebrospinal fluid drainage from the cerebral subarachnoid space (SAS). We describe 3 SVS patients with patent lumbar subarachnoid drainage but under-functioning ventriculoperitoneal shunts (VPS) who presented with ventriculomegaly (not SVS), and persistence of shunt malfunction like symptoms. Revision of the VPS resulted in complete resolution of symptoms despite a finding of low pressure in the ventricular space. This supports the hypothesis that lumboperitoneal shunting preferentially drains the SAS over the intraventricular space and in these cases allows the 'SVS' ventricles to enlarge by creating a pressure gradient from ventricles to SAS through the cortical mantle.

Cerebral Ventricles↗