Walter E. Drane

Central Nervous System Structure and Function in Sturge-Weber Syndrome: Evidence of Neurologic and Radiologic Progression

Sturge-Weber syndrome is characterized by the presence of a port-wine nevus, epilepsy, stroke-like episodes, headache, and developmental delay. We studied 20 cases to test the hypothesis that decreased cerebral blood flow alters neurologic function by affecting cellular glucose metabolism. Group A consisted of 10 patients with a mean age of 1.75 years and early seizure onset (6.8 months), whereas group B was composed of older patients (mean age, 15.3 years) with later onset of seizures (3.7 years). Neurologic disease was more severe in group A, but group B had more widespread structural brain defects — shown on computed tomographic scans and magnetic resonance imaging — and metabolic brain defects — shown on hexamethylpropyleneamine oxime and [18F] fluorodeoxyglucose single photon emission computed tomographic scans. Six group A cases had hypoperfusion at baseline and five of nine had worsening of perfusion and glucose metabolism 1 year later. A total of 119 stroke-like episodes occurred in six group A cases and eight group B cases; there were 65% fewer strokes in children treated with aspirin. The data suggest that progressive hypoperfusion and glucose hypometabolism are associated with neurologic deterioration in Sturge-Weber syndrome. Longitudinal studies are needed to better define the natural history of disease and to evaluate the safety and efficacy of aspirin therapy. (J Child Neurol 1998;13:606-618).

Topical Review Article: Brainstem Glioma: I. Pathology, Clinical Features, and Therapy

Gliomas that arise in the brain stem have been associated with a poor prognosis. Diagnostic neuroimaging readily identifies the tumor as it extends between normal brainstem structures. Histologic sampling of tumor with stereotactic methods is notoriously unreliable in establishing a definitive prognosis. Clinical trials that incorporate high-dose chemotherapy, autologous bone marrow rescue, and irradiation hold promise of better tumor control by overcoming the inaccessibility of the central nervous system to standard doses of chemotherapy. We review the pathology, clinical features, neuroimaging features, and current therapeutic concepts relative to brainstem glioma. The pediatric neurologist has a pivotal role in identifying and monitoring children with this malignancy. (J Child Neurol 1993;8:112-128).

Erythromycin enhances gastric emptying in patients with gastroparesis after vagotomy and antrectomy

We studied the effect of erythromycin on gastric emptying in nine patients with gastroparesis following truncal vagotomy and antrectomy, and assessed their clinical response to chronic oral erythromycin. Gastric emptying was evaluated using a solid-phase radio-labeled meal. Patients were studied after erythromycin 200 mg intravenously (N=9) and after an oral suspension of erythromycin 200 mg (N=7) each given 15 min after ingestion of the meal. Three parameters of gastric emptying were analyzed: half-emptying time (T1/2), area under the curve, and percent gastric residual at 2 hr. Nine patients were subsequently placed on oral suspension erythromycin 150 mg three times a day before meals (range 125–250 mg three times a day) and symptoms of nausea, vomiting, postprandial fullness, and abdominal pain were assessed before and after erythromycin. Intravenous erythromycin markedly accelerated the gastric emptying (all three parameters studied) of solids (P<0.01) in seven of nine patients with postsurgical gastroparesis [baselineT1/2 154±15 min; after intravenous erythromycin,T1/2 56±17 min (mean ±sem)]. Oral erythromycin enhanced (P<0.05) the gastric emptying rate (T1/2, area under the curve) in five of seven patients (baselineT1/2 146±16 min; after oral erythromycin,T1/2 87±20 min). Of the nine patients who were placed on oral maintenance erythromycin, three showed clinical improvement after two weeks. In summary, erythromycin significantly enhances gastric emptying in many patients with vagotomy and antrectomy-induced gastroparesis; however, only a small subset of patients respond clinically to chronic oral erythromycin.

Diagnostic value of noninvasive combined fluorine‐18 labeled fluoro‐2‐deoxy‐D‐glucose positron emission tomography and computed tomography enterography in active Crohn's disease

Background: The role of combined localized positron emission tomography (lPET) and computed tomography enterography (CTe) in Crohns disease is unclear. We examined if this imaging modality using fluorine‐18 labeled‐fluoro‐2‐deoxy‐D‐glucose (FDG) could more effectively identify disease activity. Methods: 52 lPET‐CTe scans were analyzed in this retrospective study. CTe scores and FDG uptake were quantified. Correlations of CTe scores and standard uptake value (SUV) with C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), short Inflammatory Bowel Disease Questionnaire (sIBDq), and Harvey–Bradshaw index (HBI) were estimated using Pearson analysis. Imaging scores were compared to medical outcome by logistics regression model. Results: CTe scores correlated with SUV, but additional abnormal segments of small bowel were not identified. In all, 38 (79%) abnormal CTe segments demonstrated increased FDG uptake with mean SUVmax 4.77; 10 (21%) abnormal CTe segments lacked FDG accumulation, with mean SUVmax 1.27. There was no correlation between SUVmax and CRP, ESR, sIBDq, or HBI. There were no significant differences in clinical indices, biochemical parameters, and presence of multiple abnormal segments between medical responders and uptake were associated with failed medical therapy (P = 0.001). Conclusions: PET scanning added to CTe did not identify additional abnormal segments when compared to CTe alone. Abnormal segments with mucosal enhancement on CTe that did not accumulate FDG were significantly associated with failure of medical therapy. A larger trial is warranted to confirm if combined lPET‐CTe has an important role in the clinical management of stricturing Crohns disease. (Inflamm Bowel Dis 2009;)

Clinical and Radiographic Response With Combined BRAF-Targeted Therapy in Stage 4 Ameloblastoma

Affiliations of authors: Department of Medicine (FJK) and Clinical Trials Office (AMI), University of Florida Cancer Center; Department of Radiology (WD), Department of Radiation Oncology (WMM), and Department of Pathology, Immunology, and Laboratory Medicine (RWA), University of Florida College of Medicine, Gainesville, FL. Correspondence to: Frederic J. Kaye, MD, University of Florida College of Medicine, 2033 Mowry Rd, CGRC Rm 364, Gainesville, FL 32610 (e-mail: fkaye@ufl.edu).

Central nervous system perfusion and metabolism abnormalities in Sturge- Weber syndrome

nerve, an ipsilateral leptomeningeal angioma, and an angioma of the choroid membrane of the eye producing glaucoma, buphthalmos, and vision loss.2 The neurologic features in affected patients include progresssive mental retardation, intractable seizures localized contralateral to the nevus flammeus, and an associated hemiparesis or hemiplegia.3>4 Radiologic advances have greatly improved the ability to characterize involvement of the central nervous system in Sturge-Weber syndrome although the pathophysiology is still poorly understood.5 The angioma produces obstruction, stasis, and decreased venous return. This in turn may cause ischemic lesions to the underlying cortical and subcortical areas leading to progressive calcium deposition.6,7 Computed tomography (CT) may demonstrate an enlarged choroid plexus from abnormal venous drainage, cortical atrophy, and calcifications of the angioma and underlying cerebral cortex Magnetic resonance imaging (MRI) demonstrates cortical atrophy, choroid plexus enlargement, prominence of the deep venous system, and the angiomas of the meninges and eye.9>&dquo; We report two cases in which cerebral perfusion abnormalities as detected by technetium99m (~9mTc) hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) were evident prior to structural abnormalities seen on CT or MRI. In both patients, glucose metabolism in the brain, as measured by [ 18F] fluorodeoxyglucose SPECT was significantly reduced despite a previously normal MRI. In Sturge-Weber syndrome, defects in glucose metabolism or cerebral perfusion may precede the appearance of defects on CT or MRI. In both patients, glucose metabolism in the brain, as measured by [18F] fluorodeoxyglucose SPECT was significantly reduced despite a previously normal MRI.

Intraventricular Alpha Interferon Therapy for Rasmussen’s Syndrome

A 4-year-old boy developed Rasmussens syndrome and was treated with alpha interferon intraventricularly. An improvement in the epileptic and neurologic syndrome was noted for several weeks following interferon. No adverse side effects were encountered. Since hemispherectomy is the only established therapy in Rasmussens Syndrome, further studies are needed to establish if intraventricular alpha interferon may halt the clinical progression of the syndrome.

Scintigraphic evaluation of duodenogastric reflux. Problems, pitfalls, and technical review.

Bile reflux has been implicated in the pathogenesis of gastritis, gastric ulcer, and esophagitis. Radionuclide techniques provide the only non-invasive method to detect duodenogastric reflux. To analyze the problems that occur with attempts at quantitation, 55 patients were prospectively evaluated (45 patients with reflux esophagitis or Barretts esophagus and ten patients with clinical symptoms of bile reflux, four of whom had Bilroth II surgery) with Tc-99m DISIDA, using a fasting technique with gallbladder stimulation by sincalide. Visual duodenogastric reflux occurred in 16 of 55 patients. Overlap of small bowel with the stomach is the major problem for accurate quantitation and occurred in 20 of 55 patients (36%). Overlap of left lobe of the liver occurred in 40 of 55 patients (73%), but its contribution to gastric activity was slight and could be easily subtracted. Reflux was intermittent in six of the 16 positive studies (38%), and continuous computer acquisition is needed to detect its maximum value. Primarily because of the problem of small bowel overlap, scintigraphic evaluation of duodenogastric reflux is only, at best, semi-quantitative. A review of the technical variables used in this examination, as well as potential problems that can occur, is provided.

High Prevalence of Bihemispheric Structural and Functional Defects in Sturge-Weber Syndrome

Abnormal cerebral venous drainage is associated with hypoxia and glucose deprivation, which can account for progressive neurologic deterioration in Sturge-Weber syndrome. Although developmental delay is common in Sturge-Weber syndrome, bihemispheric calcification is uncommon. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to study the neuroanatomy, while single photon emission computed tomography (SPECT) was used concurrently to evaluate perfusion and glucose metabolism using 99mTc hexamethylpropyleneamine oxime (HMPAO) and [18F] fluorodeoxyglucose (FDG), respectively. Ten patients (10 to 22 years of age) with previously diagnosed Sturge-Weber syndrome, port-wine nevi, and clinical evidence of seizures or stroke-like episodes were studied. Five children with onset of seizures in the first year of life had overall clinical severity comparable to that of children with later-onset seizures. Calcification was present in both hemispheres in one patient; six additional patients had other radiologic evidence of bihemispheric disease; SPECT studies detected bihemispheric disease in four cases. Our study is the first to concurrently evaluate structure, perfusion, and glucose metabolism in Sturge-Weber syndrome and to show a mismatch between functional and structural brain imaging in both cerebral hemispheres. Widespread abnormalities of cerebral perfusion and glucose metabolism might explain the high prevalence of developmental delay associated with Sturge-Weber syndrome. Longitudinal studies are needed to define better the natural history of neurologic deterioration and radiologic progression that relates to central nervous system circulatory dysfunction in Sturge-Weber syndrome. (J Child Neurol 1998;13:595-605).

Value of thallium-201 SPECT imaging in childhood brain tumors.

Thallium-201 chloride single photon emission computed tomography (201Tl SPECT) has been proposed as a diagnostic tool in the assessment of patients with brain tumors. We performed SPECT scans coupled with magnetic resonance imaging (MRI) in children with brain tumors to determine the sensitivity and potential value of SPECT in neuro-oncology. Each patient was injected with 2.5-3.0 mCi of thallium chloride, followed by technetium-99m HMPAO (5-15 mCi) to assess cerebral perfusion. 201Tl uptake was imaged with triple-headed SPECT in 20/24 (83%) histologically and anatomically diverse neoplasms with MRI-measurable residual disease, including 13/16 (80%) posterior fossa tumors. 201Tl SPECT demonstrated uptake in tumors with MRI volumes ranging from 0.03 to 60 cm3. 201Tl SPECT imaging was not correlated with the following MRI features: gadolinium enhancement, necrosis, exophytic, unicentric and multicentric. 201Tl uptake was not detectable in patients with tumors of maldevelopmental origin or radionecrosis. It is suggested that 201Tl SPECT is an important imaging adjunct in the assessment of children with brain tumors.