Acute necrotizing encephalopathy of childhood: correlation of MR findings and clinical outcome.

BACKGROUND AND PURPOSE: The clinical outcome of acute necrotizing encephalopathy of childhood (ANEC), an encephalopathy characterized by symmetrical involvement of the thalami, has historically been poor, but recent studies have reported better outcomes. By devising a MR imaging scoring system, we determined the relationship between characteristic MR findings and clinical outcome of patients with ANEC. METHODS: MR studies of 12 patients with ANEC were retrospectively reviewed. A MR imaging score was calculated for each patient according to the presence of hemorrhage, cavitation, and location of lesions. Clinical outcome of the patients was assessed, yielding outcome categories based on health state utility value. Spearman rank test was used to correlate the MR imaging score with clinical outcome of the patients. RESULTS: Statistically significant correlation (r = 0.76, P = .001) was found between the MR score and the outcome category. The thalami were involved in all 12 patients, brain stem in 10, cerebral white matter in 8, and cerebellar white matter in 4. Hemorrhage was present in 5 patients and cavitation in 4. Clinical outcome category was 1 in 2 patients, 2 in 8 patients, and 3 in 2 patients. No patients were in category 4. CONCLUSION: There is a significant and positive correlation between the clinical outcome and the MR imaging score in patients with ANEC. The relation between clinical outcome and each individual MR feature remains to be determined. Patients with ANEC may have a better clinical outcome than has been previously reported.

Vascular risk factors and diabetic neuropathy.

BACKGROUND: Other than glycemic control, there are no treatments for diabetic neuropathy. Thus, identifying potentially modifiable risk factors for neuropathy is crucial. We studied risk factors for the development of distal symmetric neuropathy in 1172 patients with type 1 diabetes mellitus from 31 centers participating in the European Diabetes (EURODIAB) Prospective Complications Study. METHODS: Neuropathy was assessed at baseline (1989 to 1991) and at follow-up (1997 to 1999), with a mean (+/-SD) follow-up of 7.3+/-0.6 years. A standardized protocol included clinical evaluation, quantitative sensory testing, and autonomic-function tests. Serum lipids and lipoproteins, glycosylated hemoglobin, and the urinary albumin excretion rate were measured in a central laboratory. RESULTS: At follow-up, neuropathy had developed in 276 of 1172 patients without neuropathy at baseline (23.5 percent). The cumulative incidence of neuropathy was related to the glycosylated hemoglobin value and the duration of diabetes. After adjustment for these factors, we found that higher levels of total and low-density lipoprotein cholesterol and triglycerides, a higher body-mass index, higher von Willebrand factor levels and urinary albumin excretion rate, hypertension, and smoking were all significantly associated with the cumulative incidence of neuropathy. After adjustment for other risk factors and diabetic complications, we found that duration of diabetes, current glycosylated hemoglobin value, change in glycosylated hemoglobin value during the follow-up period, body-mass index, and smoking remained independently associated with the incidence of neuropathy. Cardiovascular disease at baseline was associated with double the risk of neuropathy, independent of cardiovascular risk factors. CONCLUSIONS: This prospective study indicates that, apart from glycemic control, the incidence of neuropathy is associated with potentially modifiable cardiovascular risk factors, including a raised triglyceride level, body-mass index, smoking, and hypertension.

Magnetic resonance imaging of carotid artery abnormalities in patients with sphenoid sinusitis.

Sphenoid sinusitis is unusual in children, but when it occurs, it can lead to serious intracranial complications. We show the value of MRI in demonstrating intracranial abnormalities due to sphenoid sinus infection, particularly those involving the internal carotid arteries and cavernous sinuses. We reviewed our imaging experience of sphenoid sinusitis and found four patients with ICA narrowing who had undergone MR evaluation including conventional and diffusion imaging. MR angiography was also performed in three patients to determine the extent of ICA narrowing. Narrowing of ICA was found in the cavernous segment in all patients and in the supraclinoid segment in three. Cerebral infarction was found in two patients. In one patient the cavernous sinus showed hyperintensity on diffusion-weighted images and hypointensity on apparent diffusion coefficient map, suggesting reduced diffusion. Although infrequent in children, sphenoid sinus infection should be considered as a possible cause of intracranial infection, particularly in teenagers. Early recognition of cavernous sinus involvement and ICA narrowing may lead to prompt treatment and hence a more favorable outcome.

Diffusion-weighted imaging in acute bacterial meningitis in infancy.

Bacterial meningitis is frequently fatal or leads to severe neurological impairment. Complications such as vasculitis, resulting in infarcts, should be anticipated and dealt with promptly. Our aim was to demonstrate the complications of meningitis by diffusion weighted imaging (DWI) in patients who deteriorated despite therapy. We studied 13 infants between the ages of 1 day and 32 months who presented with symptoms ranging from fever and vomiting to seizures, encephalopathy and coma due to bacterial meningitis, performing MRI, including DWI, 2-5 days after presentation. Multiple infarcts were found on DWI in 12 of the 13, most commonly in the frontal lobes (in 10). Global involvement was seen in four children, three of whom died; the fourth had a very poor outcome. In one case abnormalities on DWI were due to subdural empyemas. We diagnosed vasculitis in three of five patients studied with MRA. We think DWI an important part of an MRI study in infants with meningitis. Small cortical or deep white-matter infarcts due to septic vasculitis can lead to tissue damage not easily recognized on routine imaging and DWI can be used to confirm that extra-axial collections represent empyemas.

Management of type 1 diabetes and perioperative fasting.

Pre and postoperative fasting presents specific problems to patients with type 1 diabetes. Too much insulin can cause hypoglycaemia, whereas too little can lead to ketoacidosis. Simon Eaton explains how avoiding these complications requires use of appropriate treatment regimes and careful monitoring of glucose levels.

Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype.

BACKGROUND: The middle interhemispheric variant (MIH) is a subtype of holoprosencephaly (HPE) in which the posterior frontal and parietal areas lack midline separation, whereas more polar areas of the cerebrum are fully cleaved. While the neuroradiologic features of this subtype have been recently detailed, the clinical features are largely unknown. OBJECTIVE: To present the clinical manifestations of MIH and to compare them with classic subtypes (alobar, semilobar, and lobar) of HPE. METHODS: The authors evaluated 15 patients with MIH in a multicenter study. Neuroimaging and clinical data were collected and correlated. They compared the data with those of 68 patients who had classic HPE. RESULTS: The frequency of endocrinopathy in MIH (0%) was lower compared with the classic subtypes (72%) (p < 0.0001). This correlated with the lack of hypothalamic abnormalities. The percentage of patients with seizures (40%) did not significantly differ from classic HPE. Spasticity was the most common motor abnormality, seen in 86% of MIH patients, similar to other subtypes. The frequency of choreoathetosis in MIH (0%) was lower than that for semilobar HPE (41%) (p < 0.0039). This correlated with the lack of caudate and lentiform nuclei abnormalities. Developmental functions, including mobility, upper-extremity function, and language, of the MIH group were similar to the least severe classic type, lobar HPE. CONCLUSION: MIH is a recognizable variant of HPE with differing clinical prognosis. Similar to the lobar subtype by functional measures, MIH differs from classic HPE by the absence of endocrine dysfunction and choreoathetosis.

MRI shows abnormal white matter maturation in classical holoprosencephaly.

In an attempt to assess white matter maturation in holoprosencephaly (HPE), MRI scans of 47 patients with HPE were retrospectively reviewed. White matter maturation was delayed in 25/47 patients, including 24/29 patients with classic HPE who were

Neuroanatomy of holoprosencephaly as predictor of function: beyond the face predicting the brain.

BACKGROUND: Despite advances in neuroimaging and molecular genetics of holoprosencephaly (HPE), the clinical spectrum of HPE has remained inadequately described. OBJECTIVE: To better characterize the clinical features of HPE and identify specific neuroanatomic abnormalities that may be useful predictors of neurodevelopmental function. METHODS: The authors evaluated 68 children with HPE in a multicenter, prospective study. Neuroimaging studies were assessed for the grade of HPE (lobar, semilobar, and alobar), the degree of nonseparation of the deep gray nuclei, and presence of dorsal cyst or cortical malformation. RESULTS: In general, the severity of clinical problems and neurologic dysfunctions correlated with the degree of hemispheric nonseparation (grade of HPE). Nearly three-quarters of the patients had endocrinopathies, with all having at least diabetes insipidus. The severity of endocrine abnormalities correlated with the degree of hypothalamic nonseparation (p = 0.029). Seizures occurred in approximately half of the children with HPE. The presence of cortical malformations was associated with difficult-to-control seizures. The presence and degree of dystonia correlated with the degree of nonseparation of the caudate and lentiform nuclei and the grade of HPE (p < 0.05). Hypotonia correlated with the grade of HPE (p < 0.05). Mobility, upper extremity function, and language correlated with the degree of nonseparation of the caudate, lentiform and thalamic nuclei, and grade of HPE (p < 0.01). CONCLUSIONS: Patients with HPE manifest a wide spectrum of clinical problems and neurologic dysfunction. The nature and severity of many of these problems can be predicted by specific neuroanatomic abnormalities found in HPE.

The dorsal cyst in holoprosencephaly and the role of the thalamus in its formation.

The dorsal cyst is poorly understood, although it is commonly encountered in holoprosencephaly. We endeavor to establish the role of diencephalic malformations in the formation of the dorsal cyst and speculate on the developmental factors responsible. We reviewed the imaging of 70 patients with holoprosencephaly (MRI of 50 and high-quality CT of 20). The presence or absence of a dorsal cyst, thalamic noncleavage and abnormal thalamic orientation were assessed for statistical association, using Fisher's Exact Test and logistical regression. The presence of a dorsal cyst correlated strongly with the presence of noncleavage of the thalamus (P = 0.0007) and with its degree (P < 0.00005). There was a trend toward an association between abnormalities in the orientation of the thalamus and the dorsal cyst, but this was not statistically significant (P = 0.07). We speculate that the unseparated thalamus physically blocks egress of cerebrospinal fluid from the third ventricle, resulting in expansion of the posterodorsal portion of the ventricle to form the cyst.

Holoprosencephaly: new concepts.

Holoprosencephaly represents a broad spectrum of malformations resulting from a lack of separation of the structures of the forebrain. Recent discoveries in the fields of genetics and developmental neurobiology have advanced our knowledge of this complex disorder. By combining this basic-science knowledge with observations of brain morphology, we can better understand the embryology and genetic factors that influence brain development and, ultimately, form more accurate classification systems and stratification measures for predicting patient outcome.

Callosal agenesis with cyst: a better understanding and new classification.

OBJECTIVE: To analyze imaging studies of 25 cases of agenesis of the corpus callosum with interhemispheric cyst to assess this malformation itself and associated anomalies. METHODS: CT (6 patients) and MRI (19 patients) were retrospectively reviewed. The patients were categorized according to morphologic and clinical characteristics. RESULTS: Based on morphology, the patients were separated into two major types, each with subtypes. Type 1 cysts appear to be an extension or diverticulation of the third or lateral ventricles, whereas Type 2 are loculated and do not communicate with the ventricular system. Type 1a were associated with presumed communicating hydrocephalus but no other cerebral malformations. Type 1b were associated with hydrocephalus secondary to diencephalic malformations prohibiting egress of CSF from the third ventricle into the aqueduct of Sylvius. Type 1c were associated with small head size and apparent cerebral hemispheric dysplasia or hypoplasia. Type 2a (multiloculated cysts) were associated with no abnormalities other than callosal agenesis/hypogenesis. Type 2b were associated with deficiencies of the falx cerebri, subependymal heterotopia, and polymicrogyria (and were almost all in patients diagnosed with Aicardi syndrome). Type 2c were associated with subcortical heterotopia. Type 2d consists of interhemispheric arachnoid cysts. Other than those with Type 2b cysts, gender predominance was overwhelmingly male. CONCLUSION: Agenesis of the corpus callosum with interhemispheric cyst appears to consist of a heterogeneous group of disorders that have in common callosal agenesis and extraparenchymal cysts, both of which are among the commonest CNS malformations. This article proposes a classification system, based primarily on morphology, by which this complex group of disorders might begin to be better understood.

Assessment of the deep gray nuclei in holoprosencephaly.

BACKGROUND AND PURPOSE: Although holoprosencephaly has been known for many years, few detailed analyses have been performed in a large series of patients to outline the range of morphology in this disorder, particularly regarding the deep gray nuclear structures. We reviewed a large patient cohort to elucidate the combinations of morphologic aberrations of the deep gray nuclei and to correlate those findings with recent discoveries in embryology and developmental neurogenetics. METHODS: A retrospective review of the imaging records of 57 patients (43 MR studies and 14 high-quality CT studies) to categorize the spectrum of deep gray nuclear malformations. The hypothalami, caudate nuclei, lentiform nuclei, thalami, and mesencephalon were graded as to their degree of noncleavage. Spatial orientation was also evaluated, as was the relationship of the basal ganglia to the diencephalic structures and mesencephalon. The extent of noncleavage of the various nuclei was then assessed for statistical association. RESULTS: In every study on which it could be accurately assessed, we found some degree of hypothalamic noncleavage. Noncleavage was also common in the caudate nuclei (96%), lentiform nuclei (85%), and thalami (67%). Complete and partial noncleavage were more common in the caudate nuclei than in the lentiform nuclei. The degree of thalamic noncleavage was uniformly less than that in the caudate and lentiform nuclei. Abnormalities in alignment of the long axis of the thalamus were seen in 71% of cases, and were associated with degree of thalamic noncleavage; 27% of patients had some degree of mesencephalic noncleavage. CONCLUSION: The hypothalamus and caudate nuclei are the most severely affected structures in holoprosencephaly, and the mesencephalic structures are more commonly involved than previously thought in this "prosencephalic disorder." These findings suggest the lack of induction of the most rostral aspects of the embryonic floor plate as the cause of this disorder.

Fast MR imaging of fetal CNS anomalies in utero.

BACKGROUND AND PURPOSE: Although sonography is the primary imaging technique for evaluating the developing fetus, significant limitations exist in the sonographic prenatal diagnosis of many brain disorders. Fast MR imaging is increasingly being used to determine the underlying cause of nonspecific fetal CNS abnormalities detected sonographically and to confirm or provide further support for such anomalies. Our goal was to determine the value of MR imaging in establishing the diagnosis of fetal CNS anomalies, to ascertain how this information might be used for patient counseling, and to assess its impact on pregnancy management. METHODS: We prospectively performed MR examinations of 73 fetuses (66 pregnancies) with suspected CNS abnormalities and compared these with available fetal sonograms, postnatal images, and clinical examinations. Retrospectively, the impact on patient counseling and pregnancy management was analyzed. RESULTS: Images of diagnostic quality were routinely obtained with in utero MR imaging, which was particularly valuable in detecting heterotopia, callosal anomalies, and posterior fossa malformations, and for providing excellent anatomic information. We believe that 24 (46%) of 52 clinical cases were managed differently from the way they would have been on the basis of sonographic findings alone. In every case, the referring physicians thought that MR imaging provided a measure of confidence that was not previously available and that was valuable for counseling patients and for making more informed decisions. CONCLUSION: Sonography is the leading technique for fetal assessment and provides reliable, inexpensive diagnostic images. Fast MR imaging is an important adjunctive tool for prenatal imaging in those instances in which a complex anomaly is suspected by sonography, when fetal surgery is contemplated, or when a definitive diagnosis cannot be determined.

Antenatal diagnosis of subependymal heterotopia.

Subependymal heterotopia consist of gray matter nodules along the lateral ventricular walls and are associated with epilepsy and other cerebral malformations. Some cases have an X-linked inheritance, and early antenatal diagnosis of affected fetuses is important for appropriate management. We present a case of heterotopia diagnosed by sonography and MR imaging at 23 weeks' gestation and discuss the differential diagnosis, reviewing the evolution and imaging appearances of the germinal matrix and its implications for detection of heterotopia.

Laboratory and evolutionary history of Tetrahymena thermophila.

An account is given of the early efforts to domesticate tetrahymenas as laboratory instruments for genetics. The rationale for developing a new organismic technology was the comparative leverage provided by a eukaryotic microorganism at a large evolutionary distance from both prokaryotic microbes and multicellular organisms. The tetrahymenine ciliates were considered more favorable materials than paramecia because of their ability to grow on simple media, though in fact their simpler nutritional needs have never been fully exploited. The first task was to sort the large set of phenotypically similar but evolutionarily and molecularly diverse ciliates referred to at the time as T. pyriformis. Then a species amenable to genetic manipulation was identified and its culture and cytogenetics were brought under control. Fortunately, the very first breeding system investigated--that in the species now called T. thermophila--has proved to be suitable for a wide range of studies. A large factor in the program's success was its use of the foundation previously established by studies on paramecia. However, serious unforeseen difficulties were encountered on the way to "domestication." These included inbreeding deterioration associated with their outbreeding life-style and germinal deterioration (mutational erosion) in the unexpressed micronuclear genome after long maintenance in vegetative culture. Cryogenic preservation was an important means of escaping these organismic limitations, and somatic (macronuclear) assortment has proved a valuable supplement to meiotic recombination.

MR artifact mimicking a temporal lobe lesion in an epilepsy patient.

A ten-year-old healthy child presented with a right upper extremity focal seizure which secondarily generalized. Magnetic resonance imaging (MR) revealed a 1-cm area of abnormal signal intensity in the left posterior temporal lobe at the gray-white junction. This did not appear on all imaging sequences, raising the suspicion of an artifact. Repeat MR revealed no intracranial or extracranial pathology. This case illustrates MR 'wrap around' artifact that mimicked a temporal lobe abnormality in an epilepsy patient. The physics of MR are reviewed as they pertain to this artifact.

Superior blowout fracture of the orbit: the blowup fracture.

We describe a patient who sustained a blowout fracture of the superior orbital roof without an orbital rim fracture. The initial CT study (obtained with 10-mm-thick sections) did not show herniation of the intraorbital fat into the anterior cranial fossa; however, thin (3-mm-thick) direct orbital sections showed a fracture of the midportion of the superomedial orbital roof with displacement of the fracture fragment into the anterior cranial fossa.

Systemic sarcoidosis with bilateral orbital involvement: MR findings.

A 43-year-old woman with diplopia had a disconjugate gaze on physical examination. MR images revealed enlarged, abnormally enhancing extraocular muscles and lacrimal glands bilaterally. Biopsy results were consistent with sarcoidosis. Chest radiographs and CT scans were normal. Clinical and MR findings improved after appropriate medical therapy.

Comparison of sequence differences in a variable 23S rRNA domain among sets of cryptic species of ciliated protozoa.

Studies were undertaken to discover the relative molecular distances separating some familiar forms of ciliated protozoa, and the genetic species they include. Sequences of 190 bases of the D2 domain of the large ribosomal nucleic acid molecule were obtained by polymerase chain reaction from protists of three distinctive groups of ciliated protozoa-Colpoda, Paramecium and Tetrahymena. Evolutionary trees were constructed for each set of sequences using the PHYLOGEN 1.0 string programs. All three groups of ciliates manifested large molecular diversity among strains difficult or impossible to distinguish morphologically. The largest single evolutionary distance within a group was the 75 differences separating Tetrahymena paravorax from the other tetrahymenids. The largest mean distance for a group was the 21.2 for the colpodids. In all the protist groups the large molecular diversity is obscured by morphological conservatism associated with constraints of ancient designs. The molecular diversity within morphotypes argues for long evolutionary coexistence of species differentiated from each other in significant physiological, ecological, or nutritional ways.