Ignacio Pascual-Castroviejo

Sturge-Weber syndrome: Study of 40 patients

Forty patients with Sturge-Weber syndrome were studied over a 26-year period. The nevus flammeus was unilateral in 27 patients (twice as often on left side) and bilateral in 13 patients. Only 3 of these 13 patients had bilateral cerebral lesions. Seizures, most of which were focal, were present in 32 patients (80%). The percentage of patients in whom the seizures subsequently became generalized was very high. Seizure presentation coincided with febrile episodes in 10 of 32 patients (31%). Total seizure control was obtained in 15 patients (47%). Abnormality of the cerebral parenchyma can be detected from birth in some patients and has a progressive character; at the same time, progressive atrophy and parenchymatous hyperdensity of the affected hemisphere is evident, as well as a decrease in arterial size, especially during the first decade of life. No relationship exists between the size of the facial nevus flammeus or its unilateral or bilateral location and clinical neurologic impairment. Conversely, a direct relationship exists between greater anatomic manifestations (i.e., atrophy, calcification) in the involved hemisphere when the lesion is unilateral as well as the presence of leptomeningeal angiomatosis in both cerebral hemispheres in patients with bilateral facial nevus flammeus and the severity of clinical disorders. Mental retardation was present in 60% of patients and was severe in 32.5% of all patients. Even though computed tomography and T1- and T2-weighted magnetic resonance imaging have great diagnostic value, magnetic resonance imaging enhanced with gadolinium-DTPA discloses the cerebral, leptomeningeal, and ocular lesions before the first evidence of neurologic abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

MLC1 is associated with the Dystrophin-Glycoprotein Complex at astrocytic endfeet

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible association of MLC1 with the DGC. To test this hypothesis, (co)-localization of DGC-proteins and MLC1 was analyzed by immunohistochemical stainings in gliotic brain tissue from a patient with multiple sclerosis, in glioblastoma tissue and in brain tissue from an MLC patient. In control tissue, a direct protein interaction was tested by immunoprecipitation. Results revealed that MLC1 is co-localized with DGC-proteins in gliotic brain tissue. We demonstrated that both MLC1 and aquaporin-4, a member of the DGC, were redistributed in glioblastoma cells. In MLC brain tissue, we showed absence of MLC1 and altered expression of several DGC-proteins. We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet.

Flaccid paraplegia as complication of umbilical artery catheterization

Two patients are described who acquired neonatal flaccid paraplegia associated with umbilical artery catheterization. Neurophysiologic studies demonstrated spinal cord injury at the level of T7 and below in Patient 1 and at the level of L1 and below in Patient 2. Deferred spinal cord magnetic resonance imaging confirmed regional spinal cord atrophy. In Patient 1, the syndrome was presumed to be triggered by a spasm or embolism of the Adamkiewicz artery due to movement of the umbilical artery catheter. In Patient 2, the spinal cord ischemia was probably caused by an embolic mechanism.

Burkitt's lymphoma presenting as Tolosa-Hunt syndrome.

An 11-year-old girl presented with acute, severe symptoms resembling Tolosa-Hunt syndrome. Response to corticosteroids was rapid and satisfactory, but of short duration. Cranial magnetic resonance imaging demonstrated a supra- and parasellar mass and the abdominal ultrasound demonstrated a round tumor. Histopathologic study of the abdominal mass revealed Burkitts lymphoma.

Facial Hemangioma and Hemispheric Migration Disorder: Presentation of 5 Patients

BACKGROUND AND PURPOSE: The association of cortical organization disorders with facial hemangiomas or vascular malformations has been described in only a few reports. The purpose of this study was to show the close association of these cutaneous anomalies with cortical dysplasias and intracranial vascular abnormalities. MATERIALS AND METHODS: Five patients, all women, with cutaneous vascular abnormalities, 4 with hemangioma and 1 with vascular malformation, were studied with MR and MR angiography. RESULTS: All 5 of the patients showed cortical dysplasia. The cutaneous lesions involved the left frontal region, ipsilateral to the cerebral hemisphere with cortical dysplasia, in all of the patients. Four patients had seizures that responded well to antiepileptic drugs. Hemispheric hypoplasia was associated with the cortical dysplasia in all 5 of the patients. Arterial abnormalities were found in all of the patients, consisting of aplasia of the ipsilateral internal carotid artery in 2, persistence of the trigeminal artery in 2, persistence of both proatlantal arteries and double kinking in the internal carotid artery in 1, and origin of both anterior cerebral arteries from the same internal carotid in all 5 of the patients, 1 of whom also showed an intracavernous anterior cerebral artery origin of the same side of the hemispheric hypoplasia and polymicrogyria. Seizures and mild psychomotor delay could be caused by the cortical dysplasia and the hemispheric hypoplasia. CONCLUSIONS: The presence of many congenital vascular abnormalities in this series suggests that facial hemangioma and vascular malformations may be in close relationship with cortical and vascular abnormalities. The reason that the vascular and cortical abnormalities occurred in the left side in all 5 of the patients and the mechanism underlying the association of both malformations are unclear. A genetic origin is suggested.

Congenital disorders of glycosylation syndromes.

‘Jan et al. reply’ SIR–The letter written by Drs Roulet-Perez and Deonna raises some interesting points, but it is the definition of cortical visual impairment which is at the root of the matter. Good and colleagues describe cortical visual impairment as having the following features: decreased acuity, abnormal neurological imaging, and abnormal electrophysiological testing consistent with bilateral damage to posterior pathways including the occipital lobes. This definition focuses on the posterior pathway and does not involve other structures. In our study, the presentation of children with dyskinetic eye movements was similar to that of children with cortical visual impairment, but there were important differences. Patients with dyskinetic eye movements had near normal or normal visual acuity, based on forced choice acuity cards, normal peripheral field testing, and EEG results that were inconsistent with cortical visual impairment. Further, these children’s clinical presentations were different: they could identify targets more easily than cortically impaired children would but dyskinetic eye movements, which arose while attempting to reach or maintain fixation, resulted in a functional inability to use their vision. As neurological damage can be variable, it would not be unusual to see a spectrum of different neurological causes of visual impairment within the same patient. We have seen patients with a combination of cortical visual impairment and dyskinetic eye movements. As cortical visual impairment clinical features increasingly appear, such as poor visual attention, it becomes more difficult to tease these apart from the neurological features of dyskinetic eye movements. Further, patients with ‘combined’ impairments often have other severe neurological problems which make the assessment more difficult. But in our study, the cortical visual impairment features were minimal, so the apparent visual problems were attributed to dyskinetic eye movements. We would advise caution when describing dyskinetic eye movements with other forms of eye movements. In congenital motor nystagmus, there is a minor reduction in acuity, without specific neuroanatomic anomalies and a normal electrophysiologic testing. In ocular motor apraxia, the cerebellar vermis appears to be affected. Patients with dyskinetic eye movements have different features leading to functional visual impairment which is due to erratic fixation and pursuit behaviour. Although patients with dyskinetic cerebral palsy can use assistive devices, our patients required significant adaptations due to their clinical severity. These patients may have ‘central’ or ‘cerebral’ visual impairment. But, in our opinion, ‘cortical’ visual impairment is not the same as a ‘cerebral’ visual impairment, which we feel is a broad term that encompasses issues related to visual acuity, attention, processing, eye movements, and many others. The term ‘cerebral’ is problematic as it encompasses many disease states, some of which are not in the realm of visual impairment. We feel that the term ‘cerebral’ leads to greater misunderstanding.

New 3C Syndrome

SIR-Recently, Goh and Lo ( D M C N , 35, 637-641) reported two cases in which facial angioma, cerebellar hypoplasia and alterations in 1/14 aortic at ch were associated. They consider (his to be a new syndrome that could be different from the one that I described previously in a clinical and neuroradiological studv of seven female cliildren’, in which the niosr important findings were: (a) presence of the disease esclusively in feniales: (b) the facial angiotna usually was of capillary type, with total or partial location in the area of the first sensitive branch of the f i f th cranial nerve: (c) presence of very diverse embryological abnortrialiries of the rtitraand extracranial arteries arid in the aortic arch, the two most inrportant of these being the absence of carotid arteries on the side of the atigiortia and the persistence of intraor extracranial enrbryonic arteries; and (d) a variable degree of cerebellar hypoplasia, ranging front partial defects to severe global hypogenesis of the cerebellutn, sotnetinies associated with DandyWalker syndrome. Later, I went more f d l y inro the embryology and the way in which the type and extent of the facial angionia related to the intraand extracranial arterial abnornialities and cerebellar defect?. This study described the developnrent and disappearance of the different aortic arches and the chronology of the origin of the intraand extracranial arteries in thetn as well as the association of sotire cardiac-and in soltie cases, aortic arch-abnornialities. The oversiriiplified approach of Goh and Lo is understandable, in view of the fact that they have studied only two cases. The greater nuniber of cases presented in ttiy studies ullow a more extensive view of rhe external (facial angioma) and internal alterations (abnortrralities of the extraor intracranial arteries, heart, aortic arch and cerebelluni), as well as the clinical repercussions, especially neurological, that these patients can presenr, which is reflected irt the above-mentioned reports. . I mist also mention a further reporr of this syndrome, that of Mi,-uno et a].‘, who presented the case of a girl esliibiting the main signs of this disorder.

‘Pascual‐Castroviejo replies’

‘Status epilepticus-induced brain damage and opercular syndrome in childhood’ SIR–We are interested in the study by Pascual-Castroviejo et al.1, describing a 5-year-old girl who developed opercular syndrome after partial status epilepticus. Neuroimaging revealed extensive, bilateral destructive changes involving the parietal lobes and corpus callosum. The changes were attributed to ‘prolonged focal ictal activity’. Although the girl was not febrile at the onset of the illness, an alternative explanation could be that she had a destructive encephalitis with secondary partial status epilepticus. Pascual-Castroviejo and colleagues cite a report by Prats et al.2 as being similar to their case. This report describes a 23-month-old child with sudden-onset partial status epilepticus and subsequent development of opercular syndrome. This child was febrile, had a CSF pleiocytosis, periodic lateralised epileptiform discharges on the EEG, and was treated with acyclovir. Prats and colleagues thought the cause was viral encephalitis (CSF serology for herpes simplex was negative). The clinical and radiological features of the girl described by Pascual-Castroviejo et al. are similar to those of reports describing the development of opercular syndrome after herpes simplex encephalitis3–5. In these three reports, two adults and six children were affected. This seems a more likely explanation of the widespread, bilateral destructive changes than partial status epilepticus arising de novo in a previously healthy 5-year-old child. Pascual-Castroviejo and colleagues state that viral investigations including herpes simplex and varicella were normal. The diagnosis of herpes simplex encephalitis can be difficult to confirm and we would be interested to know whether acute and convalescent blood and CSF serology were studied, and/or whether polymerase chain reaction was performed on CSF. We feel it is important to stress the association of herpes simplex encephalitis with opercular syndrome because it is not well recognised and treatment is available. McGrath et al.5 noted a delay in diagnosis in two of their four patients because of a lack of awareness of this association.