Ronald G. Quisling

Cavernous angioma: a review of 126 collected and 12 new clinical cases.

The histopathological, clinical, and radiological features of the intracranial cavernous angioma are reviewed, based on an analysis of 138 symptomatic, histologically verified cases. Twelve of the cases are from our own series and 126 were collected from appropriately documented reports in the modern literature. The analysis indicated that, at the time of diagnosis, one-third of the patients (49 cases) were being evaluated for seizures, one-third (40 cases) for clinical evidence of hemorrhage, and one-third (49 cases) for mass lesions. Unlike the other two groups, the group presenting with clinical evidence of hemorrhage was distinguished by a dominant age at the time of diagnosis (41% were diagnosed during the 4th decade of life), by a high incidence of prior neurological evaluation (43%), by a higher rate of diagnosis at autopsy (28%) than at operation, and by the absence of microscopic calcification within the lesion.

Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children

OBJECTIVE. Open-label studies indicate that oral dichloroacetate (DCA) may be effective in treating patients with congenital lactic acidosis. We tested this hypothesis by conducting the first double-blind, randomized, control trial of DCA in this disease. METHODS. Forty-three patients who ranged in age from 0.9 to 19 years were enrolled. All patients had persistent or intermittent hyperlactatemia, and most had severe psychomotor delay. Eleven patients had pyruvate dehydrogenase deficiency, 25 patients had 1 or more defects in enzymes of the respiratory chain, and 7 patients had a mutation in mitochondrial DNA. Patients were preconditioned on placebo for 6 months and then were randomly assigned to receive an additional 6 months of placebo or DCA, at a dose of 12.5 mg/kg every 12 hours. The primary outcome results were (1) a Global Assessment of Treatment Efficacy, which incorporated tests of neuromuscular and behavioral function and quality of life; (2) linear growth; (3) blood lactate concentration in the fasted state and after a carbohydrate meal; (4) frequency and severity of intercurrent illnesses and hospitalizations; and (5) safety, including tests of liver and peripheral nerve function. OUTCOME. There were no significant differences in Global Assessment of Treatment Efficacy scores, linear growth, or the frequency or severity of intercurrent illnesses. DCA significantly decreased the rise in blood lactate caused by carbohydrate feeding. Chronic DCA administration was associated with a fall in plasma clearance of the drug and with a rise in the urinary excretion of the tyrosine catabolite maleylacetone and the heme precursor δ-aminolevulinate. CONCLUSIONS. In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

Molar Tooth Sign in Joubert Syndrome: Clinical, Radiologic, and Pathologic Significance:

Joubert syndrome is a rare autosomal-recessive condition characterized by early hyperpnea and apnea, developmental delay, and truncal ataxia. We previously described key ocular motor signs in Joubert syndrome and the molar tooth sign resulting from dysplasia of the isthmic segment of the brain stem, superior cerebellar peduncles, and vermis. In this study, we obtained clinical and developmental data in 61 cases, and radiologic data in 46 of these, to determine the prevalence of the molar tooth sign in a large sample, and to ensure that magnetic resonance images obtained for study were representative of the Joubert syndrome population at large. We studied the morphology of the isthmic segment of the pontomesencephalic junction, the segment of the brain stem derived from the primitive isthmus. Portions of the cerebellum analyzed included the superior cerebellar peduncles, the anterior and posterior lobes of the vermis, and the flocculonodular lobe. In one case, autopsy of the brain was performed. The average age at diagnosis was 33 months. All patients were hypo-tonic and developmentally delayed. The molar tooth sign was present in 85% of cases with 13% of these showing additional malformations. All patients without the molar tooth sign had other mimicking conditions such as neocerebellar dysgenesis, isolated vermian atrophy, cerebellar aplasia, and cystic dilation of the cisterna magna. Autopsy showed aplasia of the cerebellar vermis with dysplasia of the dentate nucleus, elongated locus coeruleus, and marked dysplasia of the caudal medulla. A better understanding of the clinical, radiologic, and pathologic features of Joubert syndrome should help uncover the genetic basis for the syndrome. (J Child Neurol 1999;14:368-376).

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).

Can standard magnetic resonance imaging reliably distinguish recurrent tumor from radiation necrosis after radiosurgery for brain metastases? A radiographic-pathological study.

OBJECTIVEStereotactic radiosurgery is a commonly used treatment method in the management of metastatic brain tumors. When lesions enlarge after radiosurgery, it may represent tumor regrowth, radiation necrosis, or both. The purpose of this study was to determine whether standard magnetic resonance imaging (MRI) sequences could reliably distinguish between these pathological possibilities. METHODSA total of 619 patients, reported in a previous study, were treated with radiosurgery for metastatic brain tumors. Of those patients, 59 underwent subsequent craniotomy for symptomatic lesion enlargement. Of those 59 patients, 32 had complete preoperative MRI studies as well as surgical pathology reports. The following MRI features were analyzed in this subset of patients: arteriovenous shunting, gyriform lesion or edema distribution, perilesional edema, cyst formation, and pattern of enhancement. A novel radiographic feature, called the lesion quotient, which is the ratio of the nodule as seen on T2 imaging to the total enhancing area on T1 imaging, was also analyzed. RESULTSSensitivity, specificity, and predictive values were computed for each radiographic characteristic. Lesions containing only radiation necrosis never displayed gyriform lesion/edema distribution, marginal enhancement, or solid enhancement. All lesions exhibited perilesional edema. A lesion quotient of 0.6 or greater was seen in all cases of recurrent tumor, a lesion quotient greater than 0.3 was seen in 19 of 20 cases of combination pathology, and a lesion quotient of 0.3 or less was seen in 4 of 5 cases of radiation necrosis. The lesion quotient correlated with the percentage of tumor identified on pathological specimens. CONCLUSIONThe lesion quotient appears to reliably identify pure radiation necrosis on standard sequence MRI. Other examined radiographic features, including arteriovenous shunting, gyriform lesion/edema distribution, enhancement pattern, and cyst formation, achieved 80% or greater predictive value but had either low sensitivity or low specificity.

Cervical Carotid Dissecting Aneurysms

Thirteen cases of cervical carotid dissecting aneurysm have been seen at the University of Florida during the past 3 years. In our experience, two groups of patients with this disease can be distinguished clearly by either clinical or angiographic criteria. One group of cervical carotid dissecting aneurysms is characterized by spontaneous onset, unilaterality, and the absence of pseudoaneurysm formation. These lesions have a strong tendency to resolve with appropriate medical therapy. The other group is characterized by an association with obvious predisposing factors, such as fibromuscular dysplasia, angiography, or trauma. These lesions are often associated with pseudoaneurysms and rarely resolve spontaneously. These two groups of lesions probably represent a spectrum of the same basic disease process. The natural history of patients who survive a cervical carotid dissection is usually one of stability or improvement. A trial of medical therapy (to prevent embolic symptoms) and repeat arteriography are indicated before the consideration of surgical therapy.

Gadolinium-DTPA-enhanced magnetic resonance imaging in optic neuropathies.

Magnetic resonance imaging (MRI), after intravenous administration of the paramagnetic agent gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), showed enhancement of the optic nerve in 7 of 13 patients with acute optic neuritis. Four of these patients had Gd-DTPA enhancement of the intracranial optic nerve and two had involvement of the optic nerve at the orbital apex, ipsilateral to the eye with visual loss. Gadolinium-DTPA enhancement of both intracranial optic nerves was seen in one of two patients with bilateral retrobulbar neuritis. Two patients with acute radiation-induced optic neuropathy also had Gd-DTPA enhancement of the intracranial optic nerve. The authors recommend MRI with Gd-DTPA as the neuro-diagnostic procedure of choice for visualization of increased permeability of the blood-brain barrier in acute optic neuritis and radiation-induced optic neuropathy.

Intramedullary spinal tuberculoma.

A case report of intramedullary spinal tuberculomas presenting as cervical myelopathy is described. The rarity of these lesions in North America make this case unique. The use of modern neurodiagnostic and microsurgical techniques as well as the use of postoperative antituberculous drugs resulted in a good outcome. The first known description of magnetic resonance imaging of intramedullary spinal tuberculomas is presented. The gross and microscopic appearances of the lesion are given.

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).

Hemorrhage into Pituitary Adenomas

The clinical and pathologic features of pituitary apoplexy were evaluated within the last 100 consecutive pituitary tumors surgically treated at this institution. From this group, ten tumor specimens exhibited pathologically verifiable hemorrhagic necrosis, including six with classic apoplectic onset; the hemorrhage in four patients was asymmetric. The tumors of symptomatic patients were large, with suprasellar and parasellar extension readily identifiable by neuroradiologic examination. All tumors within this group were chromophobic adenomas by light microscopy, and each of these tumors microscopically exhibited a sinusoidal arrangement with very prominent vascularity. Comparatively, those tumors with asymptomatic hemorrhage were all intrasellar and were encountered in younger patients who had exhibited prior endocrine disturbances. By light microscopy, two of these asymptomatic lesions were chromophobic and two were acidophilic adenomas. In contrast with larger tumors, however, increased vascularity or sinusoidal patterns were not a prominent feature within this group. Our experience suggests hemorrhage within pituitary tumors is a common event, but symptomatic bleeding generally occurs in older patients whose larger tumors contain a pathologic vascular predisposition. Urgent surgical decompression (usually transsphenoidal) in symptomatic patients produced great neurologic improvement in each case.