Glossary in Congenital Malformations

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General:

#Hemimegalencephaly: This is a condition in which there is an abnormal hemisphere that is larger than the other, normal hemisphere, most likely a combination of proliferative and migration disorder.

·         Clinical features: There is variable degree of mental retardation, not infrequently infantile spasms or the so-called Ohtahara syndrome (early infantile epileptic encephalopathy). In the vast majority of caes seizures are severe and cannot be controlled adequately by anticonvulsant medications. The onset of seizures is early, usually in the first days or weeks of life. Hemispherectomy may control the seizures in up to 85% of cases. Affected individuals have variable psychomotor retardation and hemiparesis.

·         Pathology: It may involve only the cerebrum or both cerebellum and cerebrum. The gyral pattern of the enlarged hemisphere is abnormal, resembling pachygyric or polymicrogyric cortex. Cortical architecture may be abnormal. There are considerable numbers of abnormally large neurons, some larger than Betz cells, scattered through the cortex and also in the subcortical white matter. Hippocampal pyramidal cells and granule cells may also be abnormally large. The may be cytoskeletal abnormalities in these giant neurons; silver staining reveals tangle-like formation reminiscent of Alzheimer tangles. Ballon cells with both features of neurons and glia are present; these cells express both GFAP and synaptophysin.

#Heterotopia: Displacement or misplacement of parts; the presence of a normal tissue in an abnormal location.

#Heterotopic gray matter (neuronal heterotopia): Refers to collections of neurons that lie between the ependymoma of the lateral ventricle and the cortex. They come in four major patterns: diffuse, nodular, laminar, and leptomeningeal.

·         Diffuse neuronal heterotopia: Heterotopic neurons scattered haphazardly through the gyral andcentral white matter. They may be associated with nodular heterotopia and other CNS malformation.

·         Subcortical band heterotopia (double cortex): They are frequently seen in female (heterozygous) carrier of X-linked lissencephaly (doublecortin gene on Xq22.3). They may give a so-called "double cortex" on gross section and MRI. Pathologically, there is laminar, or diffuse and symmetrical heterotopia, consists of a single or interrupted nodular band of gray matter that lies between ventricle and cortex, separated from both the cortex and the ventricle by myelin. Extensive involvement is extensive but striate, cingulated, fusiform and medial temporal gyri are spared.

·         Ventricular nodular heterotopia: Nodular heterotopia occurs commonly. Heterotopic grey matter can be seen in anywhere within the brain but most the ventricular surface is the most common site. There is a female predominance. It may consist of a single nodule of gray matter at the ventricular surface or a row of nodules at the ventricular wall creating an irregular ventricular surface. They may not be well demarcated in the myelinating white matter in fetus and infants. These nodules are frequently positive for synaptophysin.

Bilateral periventricular nodular heterotopia may be related to a gene on Xq28. Pathologically, there are bilateral and symmetric subependymal (periventricular) heterotopia. Clinically, most patients have normal intelligence and epilepsy with multiple seizures types that may or may not be difficult to control. Asymptomatic individuals may be seen. Male patients are more severely affected but female patients are more common.

·         Leptomeningeal glial and glioneuronal heterotopias:

·         Infratentorial: Usually takes the form of small round masses, occasionally as sheets, of fibrillar glial tissue beside the brain stem. Rarely, neurons are present.

·         Supratentorial: Can occur with or without the presence of neurons. They can be seen in a variety of malformations. They may be associated with abnormalities in the underlying cortex. One of the possible embryogenesis is that the migrating neurons breache the glia-limitans. In the brain stem, there is no outer rim of neurons analogous to cerebral cortex, which no doubt accounts for the lack of neurons in the subpial-glial nodules in those sites.

#Holoprosencephaly: (holo-, Greek, whole; pro-, Greek, in front)

·         "A median holosphere with a single ventricular cavity instead of two hemispheres with symmetrical lateral ventricles" (Yakovlev 1959). This is a developmental failure of cleavage of the proencephalon with a deficit in midline facial development (Critical event: the evagination of the cerebral hemispheres via sagittal cleavage of the prosencephalon occurs at approximately 35 days of gestation). Timing: Critical event must have happened no later than the 5th and 6th weeks of gestation.

·         The olfactory bulbs and tracts are almost always absent. It is frequently associated with cyclopia in the severe form; sometimes due to trisomy 13-15. The most severe form is aprosencephaly.

·         The cardinal features include a single telencephalic ventricle and continuity of the cerebral hemisphere across the midline. Corpus callosum is usually absent (olfactory bulbs and tracts are not discernible until 42 days in the normal developing brain).

·         Can be further divided into alobar, semilobar and lobar type.

#Hydromyelia: Dilation of the central canal of the spinal cord with an abnormal accumulation of fluid. The hydromyelic cavity is at least partially covered by ependymal cells and connected with the central canal. Pathogenesis: There is an undoubted association between hydromyelia and neural tube malformations.  Hydromyelia may be resulted from incomplete fusion of the posterior columns or as a persistence of the primitive large canal of the embryo. [Ikenouchi J. et al., Acta Neuropathol 2002 103: 248-254]

#Hydranencephaly: Complete destruction of the cerebral hemispheres resulting in fluid filled bubble-like hemispheres. Absence of the cerebral hemispheres, their normal site being occupied by cerebrospinal fluid. The membrane encasing the CSF has an outer connective tissue layer with and inner irregular layer of glial and glial-neuronal tissue admixed with hemosiderin-laden macrophages and mineralized debris. This is regarded as a destructive process and one of the pathogenesis include compromised blood supply by the internal carotid arteries. Depending on the time of onset of the original insult, the preserved cortex may show cytoarchitectonic abnormalities such as polymicrogyria.

#Hydrocephalus: Increased volume of CSF within the head without a definition of its location. However, usually considered synonymous with enlargement of at least the lateral ventricles.

 

Syndromes and SequencesHead

#Hydrolethalus syndrome: Autosomal recessive. There is hydrocephalus, micrognathia, polydactyly, congenital heart defect, abnormalities of the tracheobronchial tree, abnormally lobated lungs, and normal kidneys.

NeuroLearn NeuroHelp Malformations General Syndromes For Comment: KarMing-Fung@ouhsc.edu