The importance of neuroimaging investigations in the diagnosis of cerebral malformations in adults
SUMMARY
Adult congenital cerebral malformations of the adult can be diagnosed late in numerous cases when uninvestigated patients with neurological signs and symptoms manifested from birth or childhood reach the neurology ward, most often with comitial crises, spastic motor defi cits, mental retardation, dysmorphisms of the skull and other. In the following, we exemplify some clinical situations from our personal database, to which the confi rmation of cerebral malformations was made during adulthood, through neuroimaging investigations. Key words: Cerebral malformations, neuroimaging investigations
INTRODUCTION
A multitude of cerebral, asymptomatic or manifest malformations from birth or childhood, with varied neurological semiology (which may include, most often, partial or generalized comitial crises, but also spastic motor deficits, mental retardation, cranial dysmorphism, oculomotor nerves palsy, coreoatherosclerotic syndromes, aphasic or dysarthric language disorders) are slowly diagnosed in adult patients which were not previously investigated through neuroimaging: cerebral computer tomography and magnetic resonance imaging. An explanation for this situation could be the extremely limited access to this group of investigations in previous years. With increasing accessibility to CT and cerebral MRI, a growing number of adult patients were diagnosed with nodular or band heterotopia, hypo / agenesis of the corpus callosum, schizencephaly with / without polymicrogyria, which could thus explain the etiology of chronic neurological suffering . In the following, we exemplify from the personal database some clinical situations in which cerebral CT scan or cerebral MRI allowed the diagnosis of cerebral malformations in adults. Schizencephaly is a rare cerebral cortex malformation defined by Yakovlev and Wadsworth as an alteration in the formation of cerebral fissures, with the occurrence of a cleft with CSF, delimited by the gray matter, which can range from the ventricular ependimus to the the cerebral pial coverage. In the occurrence of this type of malformation, neuronal migraine disturbances might be involved
(the occurrence of gyrus formation and cerebral palsy appears to be due to the fact that during neocortex formation the neurons can not migrate along the glial projections to reach the cortical superficial layers), early focal damage to the gray matter before complete brain formation, genetic factors (the Homebox EMX2 gene), metabolic, vascular, toxic, infectious or environmental factors, ischemic lesions during the first weeks of pregnancy, when the neuronal migration is incomplete. Schizencephaly can present fused margins – type I or open-type II and may be unilateral or bilateral, symmetrical or asymmetrical. Preferably, the changes occur in the perisylvian region. It may be sporadic (most often) but there are also familial cases with dominant autosomal transmission [1]. Clinical symptoms depends on the size of the cerebral cortex defect, the most frequent manifestations being epileptic seizures: focal or generalized (tonic-clonic convulsive), refractory to treatment. Also, spastic motor disorders (hemiparesis), mental retardation may be encountered. Schizencephaly may be a single malformative manifestation, or it may be associated with other types of cerebral cortex malformations, such as polymicrogyria [2], absence of pellucid septum, heterotopia, agenesis of the corpus callosum, microcephaly, ventriculomegaly, diagnosable by neuroimaging. Patients with mild forms, type I, reach adulthood. Polymicrogyria designates a cerebral malformation where cortical gyruses are abnormal, narrowed,crowded, with the appearance of an abnormal circumvolutionary pattern. Polymicrogyria can affect the entire cortex or it can be located, especially in the Silvian region. It can be associated with other types of malformations: heterotopias, agenesis of the corpus callosum. Polymicrogyria is explained by several mechanisms, one of which is genetic damage. More than 30 genes were identified in combination with the polymicrogyria: BiCD2, LIS-1, NDE s.a. It also involves alterations of the cytoskeletal system that govern neuronal migration and peroximal system disorders. Other hypotheses would address the role of rubella or cytomegalovirus [4]. Clinical manifestations are nonspecific and depend on the extent and location of the polymicrogyria, as well as on the existence of other types of associated malformations. Polymicrogyria may be associated with malformations of other internal organs. Heterotopias are cerebral malformations caused by neuronal migratory disorders that arise by stopping groups of white-matter neurons on their way to the cerebral cortex, resulting in islands of gray matter located in the white substance, with band-shaped or nodular appearance. Neurons fail to migrate from the vicinity of the ventricles to the cerebral cortex. Thus, they form periventricular nodules or bands: normal neurons in an abnormal position. Classically, heterotopias are transmitted X-linked, dominant. Periventricular heterotopia is linked to chromosome 5 by mutations ARFGEF2 and FLNA [5]. Also, traumatic and infectious mechanisms are assumed. Heterotopias have a still unclear mechanism of appearance and are considered epileptogenic.
Clinically, borderline intellect or mental retardation may be present, epilepsy, cardiac malformations, coagulopathies, aortic pathology. Agenesis of the corpus callosum occurs in 2-3 months of intrauterine life. Complete absence defines total agenesis of the corpus callosum, and partial forms – partial agenesis. Most often missing
the posterior part, because the development of the corpus callosum is made from the front to the back. It occurs at 3/1000 births due to genetic damage, chromosomal abnormalities, toxic factors (alcohol, maternal hyperglycemia), infections (rubella). It may associate mental retardation, delay in motor development, malformations of the skull, but also cardiac and urinary abnormalities, tongue, fingers, eye, endocrinopathies, and other cerebral anomalies. The diagnosis of these cerebral malformations, single or multiple, is determined by neuroimaging – cerebral computer tomography or, preferably, magnetic resonance imaging, which determines the type of malformation, localization, stretching, association with other malformations, which allows correlation of imaging data with clinical data. It is thus possible to elucidate the diagnoses of cerebral malformations, including those previously untreated in adults. CLINICAL CASES Schizencephaly with polymicrogyria: Clinical case 1: A 61-year-old patient with no personal pathological history was hospitalized in our clinic for two generalized convulsive crises that occurred in the context of a family psychological trauma. The first seizure was followed after 24 hours by a second one. General clinical examination as well as neurological examination were within normal limits. Cerebral MRI examination revealed a schizencephaly aspect in the right parietal region associated with right perisylvianpolymicrogyria, which could have explained the existence of a late epileptogenic outbreak, which appeared to be manifestingin a late stage (fig.1-3). The patient received anticonvulsant treatment and did not repeat the seizures. He remained in neurological dispensary.
Giant nodular heterotopy with posterior corpus callosum agenesis: Clinical case 2: A 40-year-old patient was admitted to our clinic for recurrent generalized convulsive tonic-clonic epileptic seizures associated with left spastic hemiparesis – MRC 3/5 and mental retardation. Anamnestically, the crises started at the age of 20, with a motor and left sensorial focal aspect. The crises had an increasing frequency, with 6 episodes per week. An imaging examination was performed by MRI, which revealed an aspect of nodular heterotopy in the left parietal lobe, with underdeveloped and thin girths in the cortex of the area. Associated, there was also posterior corpus callosum agenesis (Fig. 4-11). Conclusion: right temporal-parietal giant nodular heterotopia with posterior corpus callosum agenesis.
The patient is in the triple combination of anticonvulsants at the maximum allowable dose, which allowed a reduction in the frequency of seizures but without completely controlling them, epilepsy being fractured as refractory to treatment. Schizencephaly with heterotopia: Clinical case 3: A 21-year-old patient diagnosed with infantile encephalopathy presenting unmanaged spastic left hemiparesis, with normal intellect and schooling up to high school level, is hospitalized in neurology for an acute episode of headache. Neuroimaging by angio-IRM evaluates in the right parietal area the supernumerary fissure, bordered by heterotopic gray matter. The right ventricular wall is trailed. No arterial or cerebral venous changes are noted (fig.12-15).
The imaging evaluation allowed the observing of the etiology of spastic, left-sided hemiparesis that has not been established until the adult age of the patient. Periventricular nodular heterotopy with frontal arachnoid cyst: Clinical case 4: The 55-year-old patient with polymorphic epileptic seizures in adolescence, temporal and generalized tonic-clonic type associated with bilateral deafness is neuroimagistically investigated by cerebral MRI which shows nodular gray-cell heterotopia in thelateral left temporal occipital ventricle wall, associated with a sequel lesion (uncertain etiology) in the right parenchymal frontotemporal area and a small left anterior arachnoid cyst (fig. 16-17).
DISCUSSIONS
Previous cerebral malformations seen in medical practice with a higher frequency, e.g. small or partial corpus callosum agenesis (heterotopias and schizencephaly) may explain the occurrence of neurological deficits of the outbreak or epileptic seizures, sometimes refractory to treatment in the child. Their diagnosis in adults after a long period in which the patient had neurological manifestations is less common and can only be justified by the lack of accessibility to medical care or imaging investigations. The ability to perform MRI and cerebral CT evaluations has led to the diagnosis of a large number of cases in our clinic in recent years.
CONCLUSIONS The imaging investigation of an adult with chronic neurological disease is indispensable in establishing the etiology of neurological manifestations present at birth or childhood. Cerebral MRI or cerebral CT allow the detection of cerebral malformations that explain spastic motor deficits, mental retardation, refractory epilepsy to treatment.
ABBREVATIONS CT- computer tomography MRI – magnetic resonance imaging MRS – Medical Research Scale The informed consent for the publication of the patient’s medical data was obtained and recorded in the observation sheets. All authors have an equal contribution to writing this article. The authors did not benefit from sponsorship in the publication of this article.
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