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Joseph R. Madsen and R. Michael Scott

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Joseph R. Madsen, Dora W. Hsu, E. Tessa Hedley-Whyte and William D. Matthew

✓ The monoclonal antibody Hy2D4 was found to label a previously undescribed subset of rat and human anterior pituitary cells. The antibody binding site appears to be a carbohydrate moiety previously named “X hapten.” Double-label immunofluorescence studies in both normal rat and postmortem human pituitaries showed that this antigen is distributed on a subset of adrenocorticotropic hormone (ACTH)-positive cells, but is not detectable in cells immunoreactive for growth hormone, prolactin (PRL), thyroid-stimulating hormone, or luteinizing hormone. Since X hapten labeling revealed a biological subdivision of corticotroph cells, it was expected that some ACTH-positive tumors would be immunoreactive, but that tumors of other hormonal types would be negative. Instead, in 21 surgical specimens examined, tumors of all hormonal types were found to show immunoreactivity. To determine whether experimental proliferative changes in the pituitary could explain the shift in the cell type expressing the antigen, PRL-cell hyperplasia was induced in rats through chronic (8-week) exposure to diethylstilbestrol. The fraction of X-positive cells increased in these hyperplastic glands almost ninefold and, as in human adenomas, many non-corticotroph cells expressed the X marker in this model. However, the non-corticotroph cells expressing X were predominantly growth hormone cells, not the proliferative PRL cells. Thus, expression of the antigen does not necessarily imply that a cell is in a proliferative mode. While it is not known what role an altered expression of this antigen might play, the antibody offers a probe into cellular biology of human and experimental pituitary tumors.

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Daniel T. Ginat, Sanjay P. Prabhu and Joseph R. Madsen

Alterations in the appearance of the corpus callosum occasionally occur following successful ventricular decompression in patients with chronic hydrocephalus. There are certain features on imaging that suggest the diagnosis of what the authors propose be termed “postshunting corpus callosum swelling,” including diffuse high T2 signal predominantly affecting the body of the corpus callosum, with transverse orientation along the crossing white matter tracts and scalloping along the posterior margin of the structure. In this report, the authors demonstrate preservation of the corpus callosum white matter fiber tracts by using diffusion tensor imaging with tractography.

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Subash Lohani, Joseph R. Madsen, Ann M. Bergin and Edward R. Smith

The combination of moyamoya syndrome and symptomatic mesial temporal sclerosis (MTS) has not previously been reported. The authors present the case of a 5-year-old boy with symptomatic MTS who developed progressive moyamoya syndrome. This combination of progressive moyamoya and a structural seizure focus presented a unique clinical problem, with the natural history of MTS predicting a high likelihood of needing resection in the future, which could be challenging following any type of moyamoya-related revascularization surgery. In anticipation of this problem, the patient underwent resection of the right inferior and mesial temporal lobe followed by right pial synangiosis as a 1-day combined operation. Postoperatively he recovered well without any neurological deficits and had an uneventful hospital stay. This case of moyamoya is unique in its association with MTS, and for the simultaneous operations for pial synangiosis and temporal lobectomy, highlighting the importance of surgical planning in patients with dual pathological processes.

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Eun-Hyoung Park, Per Kristian Eide, David Zurakowski and Joseph R. Madsen

Object

The pathophysiology of normal pressure hydrocephalus (NPH), and the related problem of patient selection for treatment of this condition, have been of great interest since the description of this seemingly paradoxical condition nearly 50 years ago. Recently, Eide has reported that measurements of the amplitude of the intracranial pressure (ICP) can both positively and negatively predict response to CSF shunting. Specifically, the fraction of time spent in a “high amplitude” (> 4 mm Hg) state predicted response to shunting, which may represent a marker for hydrocephalic pathophysiology. Increased ICP amplitude might suggest decreased brain compliance, meaning a static measure of a pressure-volume ratio. Recent studies of canine data have shown that the brain compliance can be described as a frequency-dependent function. The normal canine brain seems to show enhanced ability to absorb the pulsations around the heart rate, quantified as a cardiac pulsation absorbance (CPA), with properties like a notch filter in engineering. This frequency dependence of the function is diminished with development of hydrocephalus in dogs. In this pilot study, the authors sought to determine whether frequency dependence could be observed in humans, and whether the frequency dependence would be any different in epochs with high ICP amplitude compared with epochs of low ICP amplitude.

Methods

Systems analysis was applied to arterial blood pressure (ABP) and ICP waveforms recorded from 10 patients undergoing evaluations of idiopathic NPH to calculate a time-varying transfer function that reveals frequency dependence and CPA, the measure of frequency-dependent compliance previously used in animal experiments. The ICP amplitude was also calculated in the same samples, so that epochs with high (> 4 mm Hg) versus low (≤ 4 mm Hg) amplitude could be compared in CPA and transfer functions.

Results

Transfer function analysis for the more “normal” epochs with low amplitude exhibits a dip or notch in the physiological frequency range of the heart rate, confirming in humans the pulsation absorber phenomenon previously observed in canine studies. Under high amplitude, however, the dip in the transfer function is absent. An inverse relationship between CPA index and ICP amplitude is evident and statistically significant. Thus, elevated ICP amplitude indicates decreased performance of the human pulsation absorber.

Conclusions

The results suggest that the human intracranial system shows frequency dependence as seen in animal experiments. There is an inverse relationship between CPA index and ICP amplitude, indicating that higher amplitudes may occur with a reduced performance of the pulsation absorber. Our findings show that frequency dependence can be observed in humans and imply that reduced frequency-dependent compliance may be responsible for elevated ICP amplitude observed in patients who respond to CSF shunting.

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Per K. Eide, Benjamin I. Rapoport, William B. Gormley and Joseph R. Madsen

Object

In the search for optimal monitoring and predictive tools in neurocritical care, the relationship of the pulsatile component of intracranial pressure (ICP) and the pressure itself has long been of great interest. Higher pressure often correlates with a higher pulsatile response to the heartbeat, interpreted as a type of compliance curve. Various mathematical approaches have been used, but regardless of the formula used, it is implicitly assumed that a reproducible curve exists. The authors investigated the stability of the correlation between static and pulsatile ICPs in patients with subarachnoid hemorrhage (SAH) who were observed for several hours by using data sets large enough to allow such calculations to be made.

Methods

The ICP recordings were obtained in 39 patients with SAH and were parsed into 6-second time windows (1,998,944 windows in 197 recordings). The ICP parameters were computed for each window as follows: static ICP was defined as the mean ICP, and pulsatile ICP was characterized by mean ICP wave amplitude, rise time, and rise time coefficient.

Results

The mean ICP and ICP wave amplitudes were simultaneously high or low (the expected correlation) in only ~ 60% of observations. Furthermore, static and pulsatile ICP correlated well only over short intervals; the degree of correlation weakened over periods of hours and was inconsistent across patients and within individual patients over time. Decorrelation originated with abrupt shifting and gradual drifting of mean ICP and ICP wave amplitude over several hours.

Conclusions

The relationship between the static and pulsatile components of ICPs changes over time. It evolves, even in individual patients, over a number of hours. This can be one reason the observation of high pulsatile ICP (indicative of reduced intracranial compliance) despite normal mean ICP that is seen in some patients with SAH. The meaning and potential clinical usefulness of such changes in the curves is uncertain, but it implies that clinical events result not only from moving further out on a compliance curve; in practice, the curve, and the biological system that underlies the curve, may itself change.

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Cormac O. Maher, Lilliana Goumnerova, Joseph R. Madsen, Mark Proctor and R. Michael Scott

Object

Patients who have undergone prior myelomeningocele or lipomyelomeningocele repair may present with symptomatic retethering of the spinal cord. In some cases, symptomatic tethering may recur after previous untethering operations. The expected outcome following repeated untethering in a patient after two or more prior untethering operations is not well described.

Methods

The authors examined surgical indications, techniques, and outcomes for 30 repeated untethering operations in 22 patients who had undergone a previous repair of the primary spinal disorder and at least two subsequent untethering operations.

The mean age at repeated untethering was 12.3 years. Presenting symptoms were pain (70%), weakness (70%), urinary symptoms (57%), and sensory changes (27%). The mean duration of symptoms was 7.5 months, and a longer symptomatic interval correlated with an increased number of prior operations. Total circumferential untethering was accomplished in 11 cases (37%). Postoperative symptomatic improvement was noted most often for pain (81%), and less often for urinary symptoms (53%) and weakness (48%). Complications included postoperative cerebrospinal fluid leakage or pseudomeningocele and new postoperative lower-extremity dysesthesia in five cases (17%). An increasing number of prior untethering operations was associated with a worse result for pain relief and a greater chance of significant morbidity.

Conclusions

Multiple repeated untethering operations offer symptomatic relief to well-selected patients with this condition.

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R. Michael Scott, Jodi L. Smith, Richard L. Robertson, Joseph R. Madsen, Sulpicio G. Soriano and Mark A. Rockoff

Object. Moyamoya syndrome, a narrowing of the basal intracranial vessels accompanied by the development of a cloud of collateral “moyamoya” vasculature, causes cerebral ischemia and stroke. This study was undertaken to determine if a standardized neurosurgical revascularization procedure, pial synangiosis, conferred long-term benefit in pediatric patients.

Methods. The authors reviewed the clinical and radiographic records obtained in a consecutive series of patients with moyamoya syndrome. Patients were 21 years of age or younger and underwent surgery performed by a single neurosurgeon during a 17-year period.

There were 143 patients (89 females and 54 males). Sixteen patients were Asian. Neurofibromatosis was present in 16 patients, 13 had undergone therapeutic cranial irradiation, and Down syndrome was present in 10. In 66 there was no known predisposing condition. Stroke had occurred in 67.8% of the population and transient ischemic attacks (TIAs) in 43.4% prior to surgery. Within the first 30 days following 271 craniotomies for pial synangiosis, there were 11 episodes of stroke (7.7% per patient; 4% per surgically treated hemisphere) and three severe TIAs.

Follow-up evaluation was performed in all but one patient (mean period 5.1 years). In 126 patients followed for more than 1 year, four suffered a late-onset stroke, one suffered a severe reversible TIA without magnetic resonance imaging—documented evidence of stroke, and two experienced persistent TIAs. In 46 patients followed for more than 5 years in whom the major initial presentation was stroke alone, only two late-onset strokes have occurred. Functional status at the time of surgery determined long-term functional status.

Conclusions. Following pial synangiosis, the majority of pediatric patients with moyamoya syndrome stop having strokes and TIAs, and they appear to experience an excellent long-term prognosis.

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Cormac O. Maher, Stuart B. Bauer, Liliana Goumnerova, Mark R. Proctor, Joseph R. Madsen and R. Michael Scott

Object

Patients who have undergone myelomeningocele or lipomyelomeningocele repair may present with symptomatic retethering of the spinal cord. The authors describe the results as well as the utility of urological testing in pediatric patients undergoing multiple repeat untethering operations.

Methods

The authors reviewed the records of 13 patients with lipomyelomeningocele or myelomeningocele who underwent at least 2 untethering procedures after their initial repair and who had urodynamic testing within 6 months prior to and 6 months following each untethering operation. In each case, urological testing included a slow-fill cystometrogram and an external urethral sphincter electromyogram using a concentric needle electrode to analyze individual motor unit action potentials at rest, in response to sacral reflexes, and during bladder filling and emptying.

Results

New urinary symptoms were identified in 7 of 13 cases prior to surgery. Postoperative subjective improvement in urinary symptoms was noted in 5 of these 7 cases. Improvement in bladder function on urodynamic testing correlated with symptomatic improvement. Sphincter electromyography findings did not correlate with changes in preoperative symptoms or postoperative improvement.

Conclusions

In patients undergoing multiple repeat spinal cord untethering operations, measuring bladder function is more useful than sphincter electromyographty when selecting candidates for surgery and for measuring surgical outcomes.

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Eun-Hyoung Park, Stephen Dombrowski, Mark Luciano, David Zurakowski and Joseph R. Madsen

Object

Analysis of waveform data in previous studies suggests that the pulsatile movement of CSF may play a role in attenuating strong arterial pulsations entering the cranium, and its effectiveness in attenuating these pulsations may be altered by changes in intracranial pressure (ICP). These findings were obtained in studies performed in canines with normal anatomy of the CSF spaces. How then would pulsation absorbance respond to changes in CSF movement under obstructive conditions such as the development of hydrocephalus? In the present study, chronic obstructive hydrocephalus was induced by the injection of cyanoacrylate gel into the fourth ventricle of canines, and pulsation absorbance was compared before and after hydrocephalus induction.

Methods

Five animals were evaluated with simultaneous recordings of ICP and arterial blood pressure (ABP) before and at 4 and 12 weeks after fourth ventricle obstruction by cyanoacrylate. To assess how the intracranial system responds to the arterial pulsatile component, ABP and ICP waveforms recorded in a time domain had to be analyzed in a frequency domain. In an earlier study the authors introduced a particular technique that allows characterization of the intracranial system in the frequency domain with sufficient accuracy and efficiency. This same method was used to analyze the relationship between ABP and ICP waveforms recorded during several acute states including hyperventilation as well as CSF withdrawal and infusion under conditions before and after inducing chronic obstructive hydrocephalus. Such a relationship is reflected in terms of a gain, which is a function of frequency. The cardiac pulsation absorbance (CPA) index, which is simply derived from a gain evaluated at the cardiac frequency, was used to quantitatively evaluate the changes in pulsation absorber function associated with the development of hydrocephalus within each of the animals, which did become hydrocephalic. To account for normal and hydrocephalic conditions within the same animal and at multiple time points, statistical analysis was performed by repeated-measures ANOVA.

Results

The performance of the pulsation absorber as assessed by CPA significantly deteriorated after the development of chronic hydrocephalus. In these animals the decrement in CPA was far more significant than other anticipated changes including those in ICP, compliance, or ICP pulse amplitude.

Conclusions

To the extent that the free CSF movement acts as a buffer of arterial pulsation input to flow in microvessels, alterations in the pulsation absorber may play a pathophysiological role. One measure of alterations in the way the brain deals with pulsatile input—the CPA measurement—changes dramatically with the imposition of hydrocephalus. Results in the present study suggest that CPA may serve as a complementary metric to the conventional static measure of intracranial compliance in other experimental and clinical studies.