Mathematical learning disabilities in children with 22q11.2 deletion syndrome: a review.

Mathematical learning disabilities (MLD) occur frequently in children with specific genetic disorders, like Turner syndrome, fragile X syndrome and neurofibromatosis. This review focuses on MLD in children with chromosome 22q11.2 deletion syndrome (22q11DS). This syndrome is the most common known microdeletion syndrome with a prevalence of at least 1:4000 to 1:6000 live births. Although the clinical presentation of 22q11DS is quite variable, its major characteristics include velopharyngeal abnormalities, congenital cardiac anomalies, mild facial dysmorphism and learning difficulties. Children with 22q11DS show considerable difficulties in mathematics, despite relatively normal reading performance. While fact retrieval seems to be preserved, impairments in procedural calculation and word problem solving are particularly prominent. Children with 22q11DS also have substantial difficulties in understanding and representing numerical quantities, possibly related to poor visuospatial attention, which all might stem from their underlying abnormalities in the inferior parietal cortex. This review ends with a discussion on how research on genetic disorders might aid our understanding of MLD in general.

Bilateral symmetric tonic posturing suggesting propagation to the supplementary motor area in a patient with precuneate cortical dysplasia.

We report a patient manifesting seizures with bilateral symmetric tonic posturing, which were markedly reduced after resection of the left precuneus. A 16-year-old man had sudden onset, complex partial seizures with bilateral symmetric tonic posturing since the age of eight years. Magnetic resonance fluid-attenuated inversion-recovery imaging revealed a hyperintense lesion in left precuneus. In almost all focal seizures recorded during an invasive EEG evaluation, ictal onset was detected from the inferomesial aspect of the lesion, but fast paroxysmal discharges from the ipsilateral supplementary motor area (SMA) were observed just before the clinical onset. After surgical excision of the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%) reduced. By the 20th month after surgery, there were only brief nocturnal seizures involving slight elevation of both shoulders and slight abduction of both arms, with preservation of consciousness occurring once every few days. Invasive EEG findings and surgical outcome suggested that the epileptic activity originating from the epileptogenic zone may have propagated to the symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report an interesting case of bilateral symmetric tonic posturing suggesting propagation to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a precuneate cortical dysplasia lesion.[Published with video sequences].

Tuberous sclerosis with open lipped schizencephaly.

Tuberous sclerosis is a multisystem disorder that is transmitted in an autosomal dominant fashion. It affects approximately 1 in 10,000 live births. A growing body of evidence implicates a defect of cell maturation and migration in the pathogenesis of many of the lesions in tuberous sclerosis affecting the central nervous system. There have been numerous case reports of various abnormalities of neuronal migration associated with tuberous sclerosis. To our knowledge, there has only been one case of schizencephaly reported in a patient with tuberous sclerosis. The present report describes a male with tuberous sclerosis and an extensive open lipped schizencephalic cleft affecting his right frontoparietal lobe. This case supports the hypothesis that the cerebral lesions in tuberous sclerosis are secondary to a defect in neuronal maturation and migration.

Reversal of vision metamorphopsia: a manifestation of focal seizure due to cortical dysplasia.

Upside-down reversal of vision has rarely been reported in the literature. The reported causes are diverse, including posterior circulation stroke, tumors, trauma, and multiple sclerosis. The term seizure has been used in only two cases in the literature, the cause of which was stroke. To our knowledge, this is the first reported case of cortical dysplasia in the posterior parietal cortex as the cause of complex partial seizures beginning with upside-down reversal of vision. As the pathophysiological characteristics of this phenomenon remain unclear, this case implies that the posterior parietal cortex is a possible anatomical localization of the central integrator of visual extra-personal orientation.

Hot water epilepsy and focal malformation of the parietal cortex development.

Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. HWE is considered to be a geographically specific epileptic syndrome since it mainly occurs in the Indian community. Spontaneous seizures may also occur later in life. The seizure pattern includes complex partial attacks. Although the pathogenesis of HWE is still unknown, temporal lobe has been thought to take part in the epileptogenesis. This paper reports on a 4-year-old girl who, at the age of 6 months, experienced complex partial seizures triggered by bathing in hot water. Non-provoked seizures intercritical EEG showed isolated spikes and spike-and-waves in the left parietal region. Brain MRI detected a left parietal focal cortical dysplasia. This is the second patient with HWE in whom a cortical malformation has been observed. The observation present here and data reported in the literature seem to indicate that the sensory cortex might also be involved in triggering seizures precipitated by a bath in hot water. Moreover, the authors believe that MRI examination should be considered for this group of patients.

Surgical treatment of temporoparietooccipital cortical dysplasia in infants: report of two cases.

PURPOSE: Extensive multilobar cortical dysplasia in infants commonly is first seen with catastrophic epilepsy and poses a therapeutic challenge with respect to control of epilepsy, brain development, and psychosocial outcome. Experience with surgical treatment of these lesions is limited, often not very encouraging, and holds a higher operative risk when compared with that in older children and adults. METHODS: Two infants were evaluated for surgical control of catastrophic epilepsy present since birth, along with a significant psychomotor developmental delay. Magnetic resonance imaging showed multilobar cortical dysplasia (temporoparietooccipital) with a good electroclinical correlation. They were treated with a temporal lobectomy and posterior (parietooccipital) disconnection. RESULTS: Both infants had excellent postoperative recovery and at follow-up (1.5 and 3.5 years) evaluation had total control of seizures with a definite "catch up" in their development, both motor and cognitive. No long-term complications have been detected to date. CONCLUSIONS: The incorporation of disconnective techniques in the surgery for extensive multilobar cortical dysplasia in infants has made it possible to achieve excellent seizure results by maximizing the extent of surgical treatment to include the entire epileptogenic zone. These techniques decrease perioperative morbidity, and we believe would decrease the potential for the development of long-term complications associated with large brain excisions.

Electromagnetic function of polymicrogyric cortex in congenital bilateral perisylvian syndrome.

BACKGROUND: Congenital bilateral perisylvian syndrome (CBPS) is characterised by bilateral perisylvian polymicrogyria and suprabulbar paresis. Mild tetraparesis, cognitive impairment, and epilepsy are frequently associated. Sensory deficits are surprisingly rare, even though polymicrogyria often extends to auditory and sensorimotor cortex. OBJECTIVES: To study the sensorimotor and auditory cortex function and location in CBPS patients. METHODS: We mapped the sensory and motor cortex function onto brain magnetic resonance images in six CBPS patients and seven control subjects using sources of somatosensory and auditory evoked magnetic fields, and of rhythmic magnetoencephalographic (MEG) activity phase-locked to surface electromyogram (EMG) during voluntary hand muscle contraction. RESULTS: MEG-EMG coherence in CBPS patients varied from normal (if normal central sulcus anatomy) to absent, and could occur at abnormally low frequency. Coherent MEG activity was generated at the central sulcus or in the polymicrogyric frontoparietal cortex. Somatosensory and auditory evoked responses were preserved and also originated within the polymicrogyric cortex, but the locations of some source components could be grossly shifted. CONCLUSION: Plastic changes of sensory and motor cortex location suggest disturbed cortex organisation in CBPS patients. Because the polymicrogyric cortex of CBPS patients may embed normal functions in unexpected locations, functional mapping should be considered before brain surgery.

Proteus syndrome associated with liver involvement: case report.

We report a patient with proteus syndrome who has epidermal nevus, right-sided asymmetric growth of extremities, pelvis, vertebrae and hemimegalencephaly. This patient also had enlargement of the liver which is not reported before in the proteus syndrome.

Facial hemangioma and cerebral corticovascular dysplasia: a syndrome associated with epilepsy.

The authors performed imaging studies in two children with epilepsy and congenital facial hemangioma. The first patient had dysplastic pericallosal arteries and frontal polymicrogyria. In the second patient, dysplastic arteries and dysplastic cortex lined the interhemispheric fissure, the dysplastic cortex bridging across the midline, which resulted in holoprosencephaly. Abnormal cortical development may underlie epilepsy in children with facial hemangioma.

Successful neurosurgical treatment of childhood complex partial status epilepticus with focal resection.

The treatment of complex partial status epilepticus continues to be controversial, especially with regard to the intensity of the treatment. Medical therapy and drug-induced coma are sometimes required. Rarely this may not be effective. A healthy 4-year old girl was first seen in complex partial status epilepticus. She had a 1-year history of cryptogenic partial-onset seizures. Detailed magnetic resonance imaging (MRI) studies were normal. Her course was refractory to multiple medical therapies and multiple subpial transection (MST). An urgent epilepsy surgery evaluation resulted in a focal cortical resection being performed over the right mesial parietal region with resultant seizure freedom and no significant neurologic deficit 2 years later. This patient illustrates the need to consider occult focal cortical dysplasia as a cause of nonconvulsive status epilepticus (NCSE) in children, and if it is not responsive to medical management, the utility of performing an urgent epilepsy surgery evaluation.

Life-saving epilepsy surgery for status epilepticus caused by cortical dysplasia.

A uniquely successful neurosurgical intervention in a four-month-old child suffering from status epilepticus (SE) caused by focal cortical dysplasia is reported. Seizures appeared at postnatal day 10 and culminated as medically intractable focal motor SE three months later. The first MRI scan at postnatal week 2 was inconclusive; electroclinical features typical of malformations of cortical development led to the repetition of MRI at the age of 3 months that confirmed the correct diagnosis. Since all medical trials including thiopental anaesthesia have been unsuccessful in treatment of SE, urgent resection of the right frontal and parietal lobes was performed at 4 months of age. One month later, the child had become seizure-free and her psychomotor development is proceeding well. Histopathological analysis of the resected brain tissue revealed abnormalities typical of the Taylor's type of focal cortical dysplasia. The aim of the report is to encourage considering surgery in selected patients suffering from medically intractable SE early in life.

Exploring white matter tracts in band heterotopia using diffusion tractography.

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.

Electroencephalographic dipoles of spikes with and without myoclonic jerks caused by epilepsia partialis continua.

We used electroencephalographic (EEG) dipole analysis to investigate the generators of spikes with and without myoclonic jerks in a 12-year-old patient with epilepsia partialis continua secondary to left parietal cortical dysplasia. We recorded EEG and right wrist extensor electromyography (EMG) and collected 42 spikes with jerks (jerking spikes) and 42 spikes without jerks (nonjerking spikes). We applied a single moving dipole model to the individual and averaged spikes. Dipoles at the negative peak of individual jerking and nonjerking spikes were localized in the dysplastic area. At the onset of the averaged jerking spike that preceded the EMG discharges by 20 ms, the dipole was in the motor cortex, whereas for the averaged nonjerking spike, the dipole was in the sensory cortex. The dipole moment at averaged jerking spike onset was twice that of the averaged nonjerking spike. Electroencephalographic dipole analysis of averaged spikes differentiated the generator of jerking and nonjerking spikes in epilepsia partialis continua. Individual dipoles demonstrated the area of epileptogenic cortical dysplasia.

Functional activation of microgyric visual cortex in a human.

We report on the case of a 20-year-old man with bilateral parasagittal parieto-occipital polymicrogyria and epilepsy. Functional magnetic resonance imaging responses to reversing checkerboard and interhemispheric electroencephalogram coherence changes to moving gratings were investigated. Results of both studies indicate that the polymicrogyric cortex was activated by visual stimuli, suggesting preserved function in the dysplastic area.

Widespread anatomical abnormalities of grey and white matter structure in tuberous sclerosis.

BACKGROUND: Neuroimaging studies of tuberous sclerosis complex (TSC) have previously focused mainly on tubers or subependymal nodules. Subtle pathological changes in the structure of the brain have not been studied in detail. Computationally intensive techniques for reliable morphometry of brain structure are useful in disorders like TSC, where there is little prior data to guide selection of regions of interest. METHODS: Dual-echo, fast spin-echo MRI data were acquired from 10 TSC patients of normal intelligence and eight age-matched controls. Between-group differences in grey matter, white matter and cerebrospinal fluid were estimated at each intracerebral voxel after registration of these images in standard space; a permutation test based on spatial statistics was used for inference. CSF-attenuated FLAIR images were acquired for neuroradiological rating of tuber number. RESULTS: Significant deficits were found in patients, relative to comparison subjects, of grey matter volume bilaterally in the medial temporal lobes, posterior cingulate gyrus, thalamus and basal ganglia, and unilaterally in right fronto-parietal cortex (patients -20%). We also found significant and approximately symmetrical deficits of central white matter involving the longitudinal fasciculi and other major intrahemispheric tracts (patients -21%); and a bilateral cerebellar region of relative white matter excess (patients +28%). Within the patient group, grey matter volume in limbic and subcortical regions of deficit was negatively correlated with tuber count. CONCLUSIONS: Neuropathological changes associated with TSC may be more extensive than hitherto suspected, involving radiologically normal parenchymal structures as well as tubers, although these two aspects of the disorder may be correlated.

Klippel-Trenaunay-Weber syndrome with hemimegalencephaly.

There are many documented cases of Klippel-Trenaunay-Weber syndrome characterized by the triad of port wine stain, varicose veins, and hypertrophy of bones and overlying tissue. A few cases have even included the additional findings of hemimegalencephaly. We report a case of Klippel-Trenaunay-Weber syndrome with hemimegalencephaly and calvarial hypertrophy, but no evidence of limb or trunk hypertrophy.

Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities.

PURPOSE: Diagnostic uncertainty may arise in patients with occipitoparietal epilepsy when there is neuroimaging evidence of a posterior quadrant lesion and coexistent hippocampal abnormalities ("dual pathology"). It is not known whether hippocampal atrophy (HA) in these patients results from seizure propagation to temporolimbic structures or whether it is part of the pathological process underlying the occipitoparietal epilepsy. Clarification of this issue may have a significant bearing on the management of these patients. METHODS: We studied 20 patients with occipitoparietal epilepsy and neuroimaging or pathologic evidence of a congenital developmental abnormality. Normalized hippocampal volumes were obtained in all patients. The medical records and video-EEG recordings were analyzed to correlate the MRI findings with clinical data, seizure semiology, and EEG findings. RESULTS: HA was found in seven patients (35%). Neuroimaging abnormalities concordant with the side of HA were seen in all cases. There was clinical or EEG evidence of temporal spread in 12 patients. There was no correlation between the presence of HA and temporal lobe spread. The only clinical factor associated with HA in this series was a younger age of seizure onset. CONCLUSIONS: HA in patients with occipitoparietal epilepsy due to congenital developmental abnormalities is most likely to be a marker of a more widespread process related to a common pathogenesis during prenatal or perinatal development. HA in these patients is unlikely to be the result of secondary spread from an extrahippocampal focus. Surgical treatment should be tailored toward the primary epileptogenic zone rather the site of seizure spread.

Topographical features of the sensory-evoked responses in malformed brains.

To reveal the functional organization of the somatosensory area in the dysgenetic cortex, somatosensory-evoked potentials were examined in seven patients with congenital brain anomalies diagnosed by magnetic resonance imaging, including six patients in whom multichannel recordings over the scalp were used. In four patients with polymicrogyria/pachygyria and two with lissencephaly, the early cortical responses, frontal P20 and parietal N20, were absent in the cortex contralateral to the stimulated side. The first cortical response was a positive wave that appeared predominantly over the centroparietal area in five patients, and in the frontal area in the other patient with polymicrogyria/pachygyria. These findings suggest that the differentiated somatosensory function is distributed normally in the centroparietal cortex in most cases of widespread cortical dysplasia. However, the absence of P20/N20 may indicate a hypoplastic central sulcus or functionally undifferentiated subdivision of the somatosensory cortex in these patients. The absence of cortical responses in the patient with holoprosencephaly may correspond with growth failure of the thalamocortical afferent projections in this disorder.