Biomedical subjects

Robert R Goodman

Publications and source records attributed to Robert R Goodman.

17 recordsLinked to original sources

PubMed2006

Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors.

PURPOSE: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition. EXPERIMENTAL DESIGN: Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m(2)/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen. RESULTS: Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms. CONCLUSIONS: Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Brain Mapping↗

PubMed2006

Tamoxifen paradoxically decreases paclitaxel deposition into cerebrospinal fluid of brain tumor patients.

BACKGROUND: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component of the blood-cerebrospinal fluid barrier (BCSFB). We conducted a prospective, randomized study to assess if Pgp inhibition by TAM alters deposition of paclitaxel in cerebrospinal fluid (CSF). METHODS: Ten patients with either primary or metastatic brain tumors were randomized to: paclitaxel alone (175 mg/m2/IV) or a course of TAM (160 mg/m2 PO BID on Days 1-5) followed by paclitaxel (175 mg/m2/IV on Day 5). CSF and plasma samples were obtained following paclitaxel infusion; paclitaxel and TAM concentrations were measured by high-performance liquid chromatography assays. RESULTS: Paclitaxel was detected in the CSF of six of the 10 patients. Peak CSF paclitaxel concentrations of the paclitaxel and paclitaxel-TAM groups ranged between 3.5-57.4 and 2.3-24.6 nM, respectively. Though there was a 2.4-fold higher mean CSF paclitaxel concentration and a 3.7-fold higher median peak CSF:plasma paclitaxel ratio for those who received paclitaxel alone as compared to combined paclitaxel-TAM, it was not statistically significant (P = 0.22). In one patient enrolled to both arms, higher CSF concentrations of paclitaxel and higher paclitaxel CSF: plasma ratios were observed when given paclitaxel alone. CONCLUSIONS: The trend towards lower paclitaxel CSF concentrations when given with TAM is consistent with the published finding that Pgp's localization in the endothelial cells of the choroid plexus works in an opposite direction and keeps drugs in the CSF. Thus, agents which inhibit Pgp, such as TAM, may increase efflux of Pgp substrates out of the BCSFB and may paradoxically lower CSF concentrations of natural product chemotherapy drugs. Conceptually, this finding implies that the Pgp in the BBB and BCSFB keeps natural toxins such as paclitaxel, from entering the brain (BBB) and, if they do enter the brain, keeps them in the CSF (BCSFB) where they may be less harmful than if they re-entered the brain. Thus, our work supports this novel idea and adds to the understanding of the functions of the BCSFB.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Carcinomatous meningitis from urachal carcinoma: the first reported case.

Carcinomatous meningitis (CM) occurs in less than 10% of cancer patients. Although patients frequently present with a focal complaint, multifocal signs are often found following careful neurological examination. The gold standard for diagnosis remains the demonstration of neoplastic cells in the cerebrospinal fluid. Despite the discouraging prognosis, palliative treatment may improve quality of life and lengthen lifespan. We report a patient with known primary carcinoma of the urachus who presented with headaches, nausea, vomiting and ataxia 1 week following resection of a nodular arachnoidal metastasis (indenting the cerebellum). Lumbar cerebrospinal fluid subsequently confirmed carcinomatous meningitis. This is the first reported case of carcinomatous meningitis resulting from metastatic urachal carcinoma.

Adenocarcinoma↗

PubMed2006

Astrocytoma with pilomyxoid features presenting in an adult.

Pilomyxoid histology is presently considered to occur in pediatric brain tumors. We report an astrocytoma with pilomyxoid features presenting in an adult and discuss its relationship to both the established childhood pilomyxoid astrocytoma (PMA) and recently reported tanycytoma. A 28-year-old man with medically intractable seizures presented for surgical evaluation. MRI revealed a discrete lesion in the right amygdala/uncus region. The patient elected for craniotomy with stereotactic temporal lobe resection and excision of the lesion. Postoperatively, the patient has done well. At 30-month follow up, he is seizure free and without evidence of tumor recurrence. We report an astrocytoma with pilomyxoid features presenting in an adult, illustrating that while this histological pattern is most commonly seen in children, it may also affect older individuals. Recognition of this enigmatic pattern in adult gliomas expands the currently accepted epidemiology for this lesion.

Adult↗

PubMed2006

Facial emotion recognition after curative nondominant temporal lobectomy in patients with mesial temporal sclerosis.

PURPOSE: The right (nondominant) amygdala is crucial for processing facial emotion recognition (FER). Patients with temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS) often incur right amygdalar damage, resulting in impaired FER if TLE onset occurred before age 6 years. Consequently, early right mesiotemporal insult has been hypothesized to impair plasticity, resulting in FER deficits, whereas damage after age 5 years results in no deficit. The authors performed this study to test this hypothesis in a uniformly seizure-free postsurgical population. METHODS: Controls (n=10), early-onset patients (n=7), and late-onset patients (n=5) were recruited. All patients had nondominant anteromedial temporal lobectomy (AMTL), Wada-confirmed left-hemisphere language dominance and memory support, MTS on both preoperative MRI and biopsy, and were Engel class I 5 years postoperatively. By using a standardized (Ekman and Friesen) human face series, subjects were asked to match the affect of one of two faces to that of a simultaneously presented target face. Target faces expressed fear, anger, or happiness. RESULTS: Statistical analysis revealed that the early-onset group had significantly impaired FER (measured by percentage of faces correct) for fear (p=0.036), whereas the FER of the late-onset group for fear was comparable to that of controls. FER for anger and happiness was comparable across all three groups. CONCLUSIONS: Despite seizure control/freedom after AMTL, early TLE onset continues to impair FER for frightened expressions (but not for angry or happy expression), whereas late TLE onset does not impair FER, with no indication that AMTL resulted in FER impairment. These results indicate that proper development of the right amygdala is necessary for optimal fear recognition, with other neural processes unable to compensate for early amygdalar damage.

Adolescent↗

PubMed2006

Radiographic characteristics fail to predict clinical course after subdural electrode placement.

OBJECTIVE: Subdural arrays of grid and strip electrodes are frequently used in epilepsy patients to localize the seizure focus and determine the location of critical brain functions via stimulation mapping. Postoperatively, the majority of patients with implanted subdural electrodes develop subacute extra-axial collections (EACs). Although conservative management is appropriate in most of these cases, occasionally patients manifest neurological symptoms that may necessitate reoperation for collection evacuation. Currently, there is little information available regarding the range of EAC size and the potential correlation between EAC size and symptom development. To facilitate treatment decision-making in postoperative subdural electrode patients, we reviewed and compared the computed tomographic (CT) features of postelectrode placement EACs in asymptomatic and symptomatic patients. METHODS: We retrospectively reviewed the medical records and CT scans of 22 consecutive patients who underwent craniotomy for placement of subdural grid and strip electrodes at Columbia University Medical Center. Medical records were reviewed for neurological complications from the time of grid placement until its removal. Each EAC was measured on CT for volume (% of total cranial volume), maximal thickness, and midline shift. One patient was excluded secondary to the development of an intracerebral hemorrhage. RESULTS: Thirteen of 21 patients remained asymptomatic or minimally symptomatic during their hospitalization, with only mild to moderate, intermittent, postoperative headaches. The remaining eight developed symptoms such as persistent and severe headache, transient motor deficit, or speech impairment. Two of these patients underwent reoperation for hematoma evacuation. EACs in asymptomatic patients had a mean volume, maximal thickness, and midline shift of 5.7%, 1.25 cm, and 0.33 cm, respectively. EACs in symptomatic patients had a mean volume, maximal thickness, and midline shift of 7.7%, 1.46 cm, and 0.5 cm, respectively. Differences between maximal thickness and midline shift did not approach statistical significance. Despite this, the difference between the mean volume of symptomatic and asymptomatic EACs was statistically significant (P = 0.04). CONCLUSION: The conventional methods of midline shift and maximal thickness for assessing EAC size did not adequately differentiate symptomatic and asymptomatic subdural electrode patients with EACs. Although total volume calculation using digital planimetric analysis demonstrated a statistically significant difference, we found no clear threshold volume that correlated with clinical course. Therefore, the appearance of EACs on CT scans is of limited use in predicting the development of symptoms and possible postoperative complications after subdural grid placement. Clinical judgment must guide management and determine the potential need for reoperation.

Adolescent↗

PubMed2006

Ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus increases midbrain size: a potential mechanism for gait improvement.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is characterized by a classic clinical triad of symptoms, including dementia, urinary incontinence, and gait disturbance. Recent work has demonstrated that the maximal midbrain anteroposterior (AP) diameter is significantly smaller in patients with INPH than in healthy, age-matched controls. The current study was undertaken to determine the effect of ventriculoperitoneal shunt placement on midbrain dimensions in INPH patients. METHODS: Twelve consecutive INPH patients undergoing ventriculoperitoneal shunt placement with pre- and postoperative computed tomographic scans at the Columbia University Medical Center were enrolled. Each patient's pre- and postoperative maximum AP and left-to-right diameters of the midbrain at the pontomesencephalic junction were independently measured in a blinded fashion by two of the authors. The average value of each dimension was computed by calculating the mean values of the measurements of the two observers. RESULTS: Both the mean AP diameter (preoperative mean, 2.06 +/- 0.04 cm; postoperative mean, 2.27 +/- 0.05; P = 0.0007) and left-to-right diameter (preoperative mean, 2.80 +/- 0.07; postoperative mean, 3.03 +/- 0.08; P = 0.0029) increased from pre- to postoperative imaging. The approximate cross-sectional area determined as the product of AP and left-to-right diameters also increased from pre- to postoperative images (preoperative mean, 5.79 +/- 0.22 cm; postoperative mean, 6.90 +/- 0.25 cm; P = 0.00049). CONCLUSION: This study provides supportive evidence that midbrain cytoarchitecture may play a role in the pathophysiology and post-ventriculoperitoneal shunt gait improvement of INPH patients.

Aged↗

PubMed2005

Subthalamic stimulation for Parkinson disease: determination of electrode location necessary for clinical efficacy.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. METHODS: The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were "on" and "off" medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging-determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. CONCLUSIONS: The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

Adult↗

PubMed2005

Microelectrode recording-determined subthalamic nucleus length not predictive of stimulation-induced side effects.

OBJECT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a popular treatment for patients with medically refractory Parkinson disease. Many surgeons believe that microelectrode recording (MER) during DBS electrode implantation is needed to optimize placement, whereas stimulation-induced side effects such as paresthesias, dystonic contractions, dyskinesias, and ocular motor signs that become apparent postoperatively may be an indicator of the proximity of the electrode to various boundaries of the STN. This study was performed to evaluate the relationship between mapping of the STN by using MER and postoperative stimulation-induced side effects. METHODS: Eighty-two electrodes implanted in 75 patients between March 1999 and March 2003 were retrospectively examined to evaluate the length of the STN defined by MER, and the number of and threshold for postoperative stimulation-induced side effects. Electrodes were typically tested with increasing stimulation amplitudes (maximum 6 V) by using a monopolar array. The 82 electrodes were associated with 97 stimulation-induced side effects. The mean time between surgery and testing stimulation-induced side effects was 3.9 months. Statistical analysis (two-tailed t-test) revealed no significant difference in the number of stimulation-induced side effects (or the mean threshold for paresthesias, the most common side effect) for electrodes associated with an STN length less than 4.5 mm (13 electrodes) compared with those associated with an STN greater than or equal to 4.5 mm (69 electrodes, p = 0.616). For every electrode, the target adjustment based on MER results was within 2 mm of the image-planned target (usually 1 mm anterior). In the x axis (medial-lateral orientation), there was no systematic difference in adjustments made for the electrodes associated with the shorter compared with the longer STN lengths. In the y axis (anterior-posterior orientation), there was a very small statistically significant difference in the mean adjustment (0.4 mm) between the two groups. CONCLUSIONS: Analysis of these results suggests that a shorter MER-determined STN length alone does not reliably predict the incidence of stimulation-induced side effects.

Chi-Square Distribution↗

PubMed2005

Brain stimulation reveals critical auditory naming cortex.

One challenge in dominant temporal lobe epilepsy surgery is to remove sufficient epileptogenic tissue without compromising post-operative language functioning. Pre-resection electrical stimulation mapping enables identification of language areas that can be spared from resection, and also provides a unique opportunity to investigate brain-language relationships. Visual object naming is the gold standard for identifying 'essential' language cortex; however, sparing visual naming (VN) sites has not reliably prevented post-operative language decline. In addition to visual object naming, we included a more 'ecologically valid' auditory description naming task in our pre-resection cortical mapping protocol. Of the seven patients who had auditory naming (AN) sites removed, six declined post-operatively, whereas of the 12 patients who did not have AN sites removed, only 3 declined post-operatively (P = 0.02), suggesting an association between AN site removal and post-operative naming decline. Interestingly, although VN sites were preserved in all patients, AN site removal resulted in decline in both auditory and VN tasks. These findings not only have potentially critical clinical significance, but also argue for modality specificity, with considerable integration within the semantic system.

Adolescent↗

PubMed2005

Unusual findings in brain biopsies of two patients with acute magnetic resonance imaging lesions associated with focal seizures.

PURPOSE: Patients with focal seizures often have magnetic resonance imaging (MRI) abnormalities in the brain region of their presumed seizure focus. Neoplasms, ischemic infarctions, inflammatory processes, and other specific pathologic entities have been diagnosed by biopsies of such MRI abnormalities. Two patients with this presentation had brain lesion biopsies with a leading presumptive diagnosis of glial neoplasm but were found to have indistinct histopathology. METHODS: Each patient was initially seen with focal seizures (right parietal region, right hippocampus) corresponding with focally increased T2 signal on MRI. In both patients, the preoperative clinical suspicion was for neoplastic or inflammatory processes. RESULTS: Several weeks after seizure onset, craniotomy in patient 1 and stereotactic needle biopsy in patient 2 revealed mild gliosis with reactive vascular changes and perivascular hemosiderin deposition, not diagnostic of but compatible with venous congestion (or possibly venous thrombosis). Postoperatively, patient 1 had brief sensory seizures that stopped 5 months after surgery, whereas subsequent seizures did not develop in patient 2. Both patients had normalization of their MRI (except for postoperative changes) and have remained seizure free. CONCLUSIONS: We describe two patients who had brain biopsies of striking focal increased T2 signal MRI abnormalities associated with seizures. Pathologic findings contradicted our preoperative suspicions (neoplasm or inflammatory process), compatible with (but not conclusive for) subacute venous congestion/thrombosis. These findings indicate that patients with seizures may have an associated discrete intraaxial MRI lesion that is not neoplastic. To our knowledge, this is the first report of focal seizure-associated MRI lesions with biopsy findings compatible with venous congestion/thrombosis.

Adult↗

PubMed2004

Implantation of bilateral deep brain stimulators in patients with Parkinson disease and preexisting cardiac pacemakers. Report of two cases.

Deep brain stimulation (DBS) has become an important modality in the treatment of refractory Parkinson disease (PD). In patients with comorbid arrhythmias requiring cardiac pacemakers, DBS therapy is complicated by concerns over a possible electrical interaction between the devices (or with device programming) and the inability to use magnetic resonance imaging guidance for implantation. The authors report two cases of PD in which patients with preexisting cardiac pacemakers underwent successful implantation of bilateral DBS electrodes in the subthalamic nucleus (STN). Each patient underwent computerized tomography-guided stereotactic frame-based placement of DBS electrodes with microelectrode recording. Both extension wires were passed from the right side of the head and neck (contralateral to the pacemaker) to place the cranial pulse generators subcutaneously in the left and right abdomen. The cranial pulse generators were placed farther than 6 in from the cardiac pacemaker and from each other to decrease the chance of interference between the devices during telemetry reprogramming. Postoperative management involved brain stimulator programming sessions with simultaneous cardiological monitoring of pacemaker function and cardiac rhythm. No interference was noted at any time, and proper pacemaker function was maintained throughout the follow-up period. With bilateral STN stimulation, both patients experienced a dramatic improvement in their PD symptoms, including elimination of dyskinesias, reduction of "off" severity, and increase of "on" duration. With some modifications of implantation strategy, two patients with cardiac pacemakers were successfully treated with bilateral DBS STN therapy for refractory PD. To our knowledge, this is the first report on patients with cardiac pacemakers undergoing brain stimulator implantation.

Aged↗

PubMed2003

Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain.

The subcortical white matter of the adult human brain harbors a pool of glial progenitor cells. These cells can be isolated by fluorescence-activated cell sorting (FACS) after either transfection with green fluorescent protein (GFP) under the control of the CNP2 promoter, or A2B5-targeted immunotagging. Although these cells give rise largely to oligodendrocytes, in low-density culture we observed that some also generated neurons. We thus asked whether these nominally glial progenitors might include multipotential progenitor cells capable of neurogenesis. We found that adult human white-matter progenitor cells (WMPCs) could be passaged as neurospheres in vitro and that these cells generated functionally competent neurons and glia both in vitro and after xenograft to the fetal rat brain. WMPCs were able to produce neurons after their initial isolation and did not require in vitro expansion or reprogramming to do so. These experiments indicate that an abundant pool of mitotically competent neurogenic progenitor cells resides in the adult human white matter.

Adolescent↗

PubMed2002

Epilepsy surgery: indications, approaches, and results.

The surgical treatment of epilepsy is divided into procedures with curative or palliative goals. Curative procedures are highly effective in rendering the majority of patients seizure free, and palliative procedures often result in marked improvement in seizure frequency, quality of life, or both. This brief overview of epilepsy surgery outlines the goals of surgery, criteria used to determine patient eligibility, the various types of epilepsy surgery, and anticipated outcomes of these approaches. Newer surgical techniques including vagus nerve and deep brain stimulation and gamma knife radiosurgery are also discussed.

Animals↗

PubMed2002

Volumetric measurements in the detection of reduced ventricular volume in patients with normal-pressure hydrocephalus whose clinical condition improved after ventriculoperitoneal shunt placement.

OBJECT: The syndrome of normal-pressure hydrocephalus (NPH) refers to the clinical triad of gait disturbance, dementia, and urinary incontinence in association with idiopathic ventriculomegaly and normal intracranial pressure. Ventriculoperitoneal (VP) shunt placement often yields significant clinical improvements, sometimes without apparent reduction of ventricular size. The authors hypothesized that careful volumetric measurements would show a decrease in ventricular volume in these patients. METHODS: Twenty consecutive patients with NPH underwent placement of VP shunts equipped with programmable valves. In 11 patients pre- and postoperative neuroimaging was performed, which allowed volumetric analysis. Volumetric measurements of the lateral ventricles were calculated in triplicate by National Institutes of Health image-processing software to assess standard computerized tomography (CT) scans (eight patients) or magnetic resonance (MR) images (three patients) obtained before and after shunt placement. Ventricular volumes were also assessed by an independent neuroradiologist. Postoperative studies were performed at a time of clinical improvement, between 1 and 9 months postsurgery (mean 5 months). Preoperative and postoperative Unified Parkinson's Disease Rating Scale evaluations were performed in four patients. Significant clinical improvement occurred in all patients after shunt placement (mean follow-up period 17.5 months). Although 10 (91%) of 11 patients demonstrated a calculable decrease in volume in the lateral ventricles (mean decrease 39%), formal interpretation of neuroimages indicated a definite decrease in lateral ventricular volume in only three (27%) of 11 patients. CONCLUSIONS: Volumetric measurements obtained to compare preoperative and postoperative CT or MR studies obtained in patients with NPH in whom clinical improvement was seen after shunt placement surgery show a demonstrable decrease in ventricular size. Volumetric measurements may be helpful in clinical assessment postoperatively and in guiding programmable valve pressure settings.

Aged↗

PubMedDate not supplied

"Tectonic" hippocampal malformations in patients with temporal lobe epilepsy.

Histological analysis of hippocampi removed en bloc during surgical treatment of temporal lobe epilepsy revealed a subgroup of patients with bulbous expansions of the CA1 pyramidal cell/subicular layers that were consistently accompanied by "tectonic" invaginations of the adjacent dentate gyrus. Most hippocampi containing the CA1/subicular anomaly and the tectonically deformed dentate gyrus exhibited minor cell loss compared to hippocampi with typical hippocampal sclerosis, and retrospective analysis revealed that conventional imaging methods usually failed to detect subtle hippocampal atrophy or abnormal signal characteristics in patients with this anomaly. Cells within the anomaly exhibited the spherical appearance of undifferentiated pyramidal layer neurons, and were immunopositive for the neuronal marker NeuN. Immunostaining for the synaptic marker beta-synuclein suggested abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly, but not in unaffected areas of the same specimens. Despite differences in the extent of neuronal loss between patients with hippocampal sclerosis and those with the CA1/subicular anomaly, the incidence of antecedent febrile seizures was similar in both groups. In a comparison group of hippocampi obtained at autopsy, structural irregularities were evident, but were consistently less disruptive to hippocampal architecture than the anomalies observed in epilepsy patients. We hypothesize that developmental malformation of the CA1 pyramidal cell/subicular layers may adversely influence the subsequent development of the adjacent dentate gyrus, and may render temporal lobe structures hyperexcitable and more vulnerable to relatively innocuous seizures and injuries. Thus, these presumably developmental hippocampal anomalies may serve as substrates for early febrile seizures and subsequent epilepsy.

Adolescent↗