Development and developmental disorders of the human cerebellum.

The human cerebellum develops over a long time, extending from the early embryonic period until the first postnatal years. This protracted development makes the cerebellum vulnerable to a broad spectrum of developmental disorders. The development of the cerebellum occurs in four basic steps: 1) characterization of the cerebellar territory at the midbrain-hindbrain boundary; 2) formation of two compartments for cell proliferation: first, the Purkinje cells and the deep cerebellar nuclei arise from the ventricular zone of the metencephalic alar plate; second, granule cell precursors are formed from a second compartment of proliferation, i. e. the upper rhombic lip; 3) inward migration of the granule cells: granule precursor cells form the external granular layer, from which (and continuing into the first postnatal year), granule cells migrate inwards to their definite position in the internal granular layer, and 4) formation of cerebellar circuitry and further differentiation. The precerebellar nuclei, i. e. the pontine nuclei and the inferior olive, arise from the lower rhombic lip. Developmental disorders of the cerebellum are often accompanied by malformations of the precerebellar nuclei. In this review the development of the cerebellum and some of its more frequent developmental disorders, such as the Dandy-Walker and related midline malformations, and the pontocerebellar hypoplasias, are discussed.

Retroclival extradural hematoma is a magnetic resonance imaging diagnosis.

An epidural hematoma of the clivus is reported in a 16-year-old boy after a motor vehicle accident. The diagnosis was made by magnetic resonance imaging. Only five similar cases have been reported in the literature. The patient was treated conservatively and recovered without neurological deficits. The mechanism of injury and formation of the hematoma in this region are discussed.

[Development and developmental disorders of the human brain. III. Neuronal migration disorders of the cerebrum]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. III. Neuronale migratiestoornissen van de grote hersenen.

Neuronal migration disorders of the cerebral cortex form a heterogeneous group of abnormalities, characterised by mental retardation, epilepsy and hypotonia. They are prevalent in 1% of the population and in 20-40% of the untreatable forms of epilepsy. Disorders at the start of the migration result in nodular heterotopias. Bilateral periventricular nodular heterotopias are X-linked disorders, in which cortical neurons are unable to leave their position at the ventricular surface due to the absence of filamin 1. The large group of lissencephalies can be divided into a number of syndromes, each of which is characterised by a gene mutation (LIS1, DCX, RELN). These mutations result in agyria and pachygyria, which are characteristic for this group. A number of these abnormalities, especially the smaller nodular heterotopias and focal cortical dysplasia, may be treated by neurosurgical excision.

[Development and developmental disorders of the human brain. II. Development of the cerebral cortex and major tract systems]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. II. Ontwikkeling van de hersenschors en de grote baansystemen.

In the development of the cerebral cortex, two phases can be distinguished: (a) the formation of the preplate, a superficial layer essential for a normal lamination of the cerebral cortex; (b) the formation of the cortical plate. The cortical plate divides the preplate into a superficial marginal zone (the future layer I) and the subplate. The transient subplate is important for the formation of thalamocortical projections. Most cortical neurons arise in the ventricular zone of the pallium and migrate along radial glial cells (radial migration) to the cortical plate. The gamma-aminobutyric acid (GABA)ergic cortical interneurons, however, originate from the ganglionic eminences and reach the cerebral cortex through tangential migration.

[Development and the developmental disorders of human brain. I. Early development of the cerebrum]. / Ontwikkeling en ontwikkelingsstoornissen van het humane brein. I. Vroege ontwikkeling van de grote hersenen.

The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early development of mostly the spinal cord and the brain stem. Regionalization of the brain has been related to genes that play a part in it. A characteristic developmental disorder for this early phase in the development of the forebrain is holoprosencephaly, a brain patterning disorder. Numerous genes play a part in its occurrence; abnormal function of signal factors as well as of transcription factors may lead to holoprosencephaly.

Cerebellar involvement as a rare complication of pneumococcal meningitis.

A 4-year old girl with meningitis, caused by streptococcus pneumoniae, developed a subcoma with respiratory insufficiency, followed by a severe cerebellar syndrome. Cerebellar involvement after regaining consciousness consisted of a symmetrical ataxia and mutism. This mutism changed into dysarthria and finally into normal speech. Magnetic resonance imaging revealed lesions in both cerebellar hemispheres, suggesting cerebellitis. She recovered with prompt antibiotic treatment.

Proton MR spectroscopy in a child with pyruvate dehydrogenase complex deficiency.

The purpose of this study was the non-invasive quantitative determination by proton MR Spectroscopy (1H MRS) of alterations in cerebral metabolism in a 19-month-old male infant with severe global developmental delay caused by a Pyruvate Dehydrogenase Complex (PDHC) deficiency due to a mutation at the thiamine binding site. Two investigations were performed at different CSF thiamine concentrations to assess the effect of thiamine supplementation. 1H MR spectra were collected at different echo times (20-270 ms) from a voxel located in the striatum; spectroscopic imaging was done on a larger region including occipital white matter. The tissue levels of N-acetylaspartate and choline were in the normal range, while creatine appeared elevated. Abnormally high lactate and alanine signals were observed both in and outside the striatum; the levels of these metabolites were higher during the second measurement at a lower thiamine concentration. Abnormal cerebral levels of alanine have only been described once before in PDHC deficiency. The 1H MRS profile of this patient reflects the diversity of brain metabolite alterations in patients with this genetically heterogeneous disease.

Sjögren-Larsson syndrome: clinical and MRI/MRS findings in FALDH-deficient patients.

OBJECTIVE: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty aldehyde dehydrogenase (FALDH) deficiency. BACKGROUND: The Sjogren-Larsson syndrome (SLS) was originally defined as a clinical triad consisting of ichthyosis, spastic di- or tetralegia, and mental retardation, with autosomal recessive inheritance. By now, both the deficiency of the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome. METHODS: The clinical findings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to 1H MRS in six patients. RESULTS: The severity of neurologic symptoms showed considerable variation. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidence of retarded myelination and a variable degree of dysmyelination. 1H MRS showed an accumulation of free lipids in the periventricular white matter, even before the stage of visible dysmyelination. CONCLUSIONS: The neurologic consequences of FALDH deficiency show considerable variation. The characteristic pattern of ichthyosis and retinal degeneration are seen consistently, yet they are not pathognomonic. MRI and 1H MRS findings suggest an accumulation of long-chain fatty alcohol intermediates, resulting in retarded myelination and dysmyelination.

Transalar sphenoidal encephalocele and respiratory distress in a neonate: a case report.

We present a full-term newborn infant who suffered from immediate postpartum severe respiratory distress. The infant had an inspiratory stridor as a result of a swelling of the soft palate, extending from the roof of the nasopharynx. Transoral endotracheal intubation resulted in normal saturation levels. Histologic examination after an open biopsy showed mature neuroglial tissue. Radiology demonstrated the presence of a right parapharyngeal process obstructing the nasopharynx and oropharynx and extending to the right middle and posterior fossa, via the foramen ovale. After transoral debulking, the infant was extubated successfully. After an uneventful period of 5 months, the patient was readmitted at our hospital for treatment of meningitis. Subsequently, the inspiratory stridor recurred, and staged surgery was performed. First, a transcranial approach was used to remove a large intradural part of the process and close the defect at Meckel's cave. Two weeks later the retro- and parapharyngeal part of the process were removed transorally. Given the site of the defect of the skull base and the intradural location of the process, the diagnosis is a transalar sphenoidal encephalocele. This is a rare type of basal encephalocele, and has never been reported in an infant nor known to present with respiratory distress. The pathogenesis, clinical presentation, pathology, and therapeutic implications of basal encephaloceles are discussed.

Activation of the sensorimotor cortex at 1.0 T: comparison of echo-planar and gradient-echo imaging.

PURPOSE: The increasing demand for the clinical application of functional MR imaging raises the question of whether this technique can be routinely performed on 1.0-T MR scanners. To this end, we assessed the feasibility of functional MR imaging at 1.0 T. METHODS: Healthy volunteers were scanned during the performance of a motor task. Functional data were acquired with echo-planar imaging (EPI) and with gradient-echo (GRE) and dual-echo GRE sequences. The signal intensity variations of the EPI and GRE sequences were compared, and the influence of inflow and blood oxygen level-dependent (BOLD) effects on the signal variations was assessed with the dual-echo GRE sequences. RESULTS: In 11 of the 12 subjects we found activation in the primary motor cortex with both the GRE and EPI sequences. Active voxels had a significantly higher mean percentage of signal changes with the EPI sequence than with the GRE sequence (EPI: 1% to 6.1%, mean 2.4%; GRE: 1% to 4.5%, mean 1.9%). The EPI sequence was less sensitive to motion artifacts and enabled imaging of a larger brain volume in a shorter time. With a dual-echo sequence we found an increasing contribution of inflow effect with an increasing percentage of signal changes. CONCLUSION: Functional MR imaging of the sensorimotor cortex can be routinely performed at 1.0 T.

Hemispheric language dominance studied with functional MR: preliminary study in healthy volunteers and patients with epilepsy.

PURPOSE: We used functional MR imaging to compare hemispheric language dominance in healthy volunteers and in patients with epilepsy. METHODS: We retrospectively reviewed the functional MR images of 23 healthy volunteers and 16 patients with epilepsy obtained by using an echo-planar technique designed for whole-brain imaging. The activation paradigm used was a silent word generation task. Hemispheric language dominance was assessed as the percentage of activated pixels in the left hemisphere minus the percentage of activated pixels in the right hemisphere x 100. RESULTS: We found no significant difference in language lateralization between right-handed male and right-handed female volunteers. However, a statistically significant difference in language distribution was found between left- and right-handed female volunteers. The left-handed female volunteers showed a more bilateral hemispheric language lateralization. Language lateralization in right-handed male epilepsy patients with early age at seizure onset and seizure locus in the left temporal lobe was not significantly different from that of healthy right-handed male volunteers. Similarly, we found no difference in language lateralization between right-handed female volunteers and right-handed female epilepsy patients with late age at seizure onset and seizures in the left temporal lobe. CONCLUSION: Handedness has a significant influence on hemispheric language dominance in healthy volunteers. Sex has no influence on hemispheric language dominance, regardless of the task used to assess such dominance, nor does age at seizure onset influence language lateralization in patients with left temporal lobe epilepsy. Therefore, hemispheric language dominance can be assessed and compared effectively with functional MR imaging.

Quantitative gait analysis in patients with vascular parkinsonism.

Until now the clinical criteria for the diagnosis of vascular parkinsonism (VP) have been disputed. The purpose of the present study is to investigate whether quantitative gait analysis can differentiate between the gait pattern of patients with VP and the gait pattern of patients with idiopathic Parkinson's disease (PD). Twelve patients with VP, 12 patients with PD, and 10 neurologically nondiseased controls were examined by quantitative gait analysis. Patients with VP, having a similar gait velocity and stride length, showed relatively preserved arm swing with markedly more anteflexion in the shoulder on the forward sway of the arm swing than patients with PD. Patients with VP also showed less flexion dystonic posture of the elbow, hip, knee, and trunk than did patients with PD. There was no significant difference in the excursions and coordination of arm swing in the patients with VP compared with the control group. Both patient groups showed reduced leg movements, reduced hip extension, and reduced knee flexion and extension as compared with the controls.

Suboccipital surgery for acoustic neuroma.

A retrospective study was performed on 106 consecutive patients with an acoustic neuroma who underwent suboccipital surgery for the first time between 1980 and 1992. Complete follow-up data were available for all the patients, including regular imaging up to 1 January 1994. Incomplete removal of the tumours was chosen in preference to radical surgery in a large proportion of the patients, to avoid the risk of post-operative morbidity. The recurrence rate in this series was 20%. Comparison of the results of suboccipital surgery to those obtained using other surgical approaches, while taking the tumour size into consideration, showed that better results can be obtained after total removal of the tumour without any additional risk to post-operative facial nerve function. The long-term results of subtotal removal using the suboccipital approach were disappointing. It is therefore necessary to review the indications for non-radical surgery in patients with an acoustic neuroma.

Delays in the diagnosis of acoustic neuromas.

From the medical files of 164 consecutive patients who underwent surgical treatment for a unilateral acoustic neuroma between 1980 and 1992, we collected data on the delay until the diagnosis was made. A distinction was made between the patient's and general practitioner's delay (delay 1) and the delay after the specialist's first visit until the radiologic diagnosis (delay 2). The average delay was 35.7 months (SD, 62.2) for delay 1 and 15.2 months (SD, 36.3) for delay 2. Specialist's delay (otolaryngologist or neurologist) was divided into a delay of a maximum of 12 months (134 patients) and a longer delay (30 patients). In 27 of the 30 patients, no specific tests had been performed, and in the remaining three, the test results were inconclusive. Reasons for not conducting further tests included familial hearing impairment, Meniere's disease, otosclerosis, and alcoholism. In cases in which the specialist had not made the diagnosis within 1 year, it took an average of 6 months extra to make the diagnosis of an acoustic neuroma, usually with a fairly short patient delay. The specialist's delay remained constant in the period of investigation, with the possibility of magnetic resonance imaging (MRI) scanning only in the last 2 years. In view of the increasing accessibility of MRI, it is now recommended if possible to perform MRIs in all patients with symptoms suspicious for an acoustic neuroma.

[Functional MRI: imaging of motor cortex function]. / Functionele MRI: het afbeelden van motorische hersenfuncties.

OBJECTIVE: To image the motor cortex with functional MRI (fMRI), and locate the activated area with the proportional grid of Talairach. DESIGN: Descriptive. SETTING: St. Radboud Academic Hospital Nijmegen. METHODS: In ten volunteers functional images of the motor cortex were made during execution of a motor task (finger movements). From the functional images the positions of activated areas were calculated using the 3D Talairach grid system. RESULTS: fMRI of the motor cortex was possible using a 1.5 T MRI scanner. Task activation of the motor cortex gave a signal increase in Brodmann's area 4, the precentral gyrus. CONCLUSION: Imaging of the active motor cortex with fMRI is feasible. The use of the 3D Talairach proportional grid system for the calculation of the position of an activated area in the motor cortex is possible with adequate accuracy.

MRI in patients with suspected vascular parkinsonism.

To determine whether MRI can reveal more vascular lesions in patients clinically suspected of having vascular parkinsonism, we compared 15 such patients with 15 patients who had idiopathic Parkinson's disease and 10 hypertensive controls. Patients with suspected vascular parkinsonism had significantly more subcortical lesions than those with Parkinson's disease or hypertension. The cutoff point that best distinguished patients with suspected vascular parkinsonism from patients with Parkinson's disease was a 0.6% level of lesioned brain tissue volume. There were two types of vascular parkinsonism: one had an acute onset and lesions located in the subcortical gray nuclei (striatum, globus pallidus, thalamus); the other had an insidious onset and lesions diffusely distributed in the watershed areas.

MR volume estimation of subcortical brain lesions and ventricular cerebrospinal fluid: a simple and accurate stereologic method.

PURPOSE: To describe an MR imaging quantification method for estimation of total volumes of both white and gray matter subcortical lesions and ventricular cerebrospinal fluid (CSF) in the living human brain, and to determine the method's reliability. METHODS: In 12 subjects, total subcortical lesion and ventricular CSF volumes were estimated using systematic sampling. Systematic sampling was performed on equidistant MR sections using a counting grid with systematically ordered intersection points. The grid was randomly positioned on each consecutive MR section. Each grid intersection point hitting the structure of interest represents a fixed known volume dependent on grid intersection point distance and the sum of the section thickness and section gap. RESULTS: Total volume estimation of subcortical lesion and ventricular CSF takes 15 and 5 minutes per subject, respectively. Coefficients of error of the individual volume estimates ranged from .01 to .13 and are negligible to the coefficients of the group mean (range, .70 to .89). For subcortical lesion volume, the random intraobserver error yielded .04 and for ventricular CSF .02; the random interobserver error amounted to .11 and .04, respectively; and the systematic interobserver error was .15 and .04, respectively. CONCLUSION: The method described here for subcortical lesion and ventricular CSF volume estimation is accurate, reliable, valid, and fast.

Conventional radiotherapy combined with carbogen breathing and nicotinamide for malignant gliomas.

High grade malignant gliomas are among the most radioresistant human tumors and total doses up to 80 Gy are inadequate to achieve long-term local control in most of the patients. Hypoxia has been demonstrated in primary brain tumors and may be one of the reasons for their radioresistance. In experimental models carbogen breathing and nicotinamide have been shown to act against hypoxia by different mechanisms and both modalities were tested in 16 patients with supratentorial malignant gliomas in combination with a conventional radiotherapy scheme (50 Gy in 25 daily fractions). The present study was performed to determine the feasibility and toxicity of conventional radiotherapy combined with carbogen breathing and nicotinamide. The unexpectedly high incidence of acute liver toxicity, the possible increase of subacute and late CNS toxicity, and the absence of a higher effectivity led us to reconsider this new treatment modality for patients with malignant gliomas.