Functional connectivity of the thalamocortical circuit in patients with seizure relapse after antiseizure medication withdrawal.

OBJECTIVE: To characterize the features of thalamocortical functional connectivity during seizure recurrence at the time of antiseizure medication (ASM) withdrawal. METHODS: Patients with chronic epilepsy who attempted to discontinue medications were prospectively registered and followed up; 19 patients remained seizure-free (SF-group), 18 patients had seizure relapses (SR-group) after ASM withdrawal, and 28 healthy controls were recruited. Resting-state functional magnetic resonance imaging was performed before ASM withdrawal. Thalamus subdivisions were set as seeds to calculate voxelwise functional connectivity. Partial correlation analysis between functional connectivity and clinical variables was performed. A support vector machine was used to assess the predictive ability of the specific functional connectivity for seizure relapse. RESULTS: The within-group comparison indicated that the SR-group had more extensive functional connectivity than the SF-group; the left inferior pulvinar, left medial pulvinar, and right anterior pulvinar showed a significantly stronger functional connection with the precuneus in the SR-group than in the SF-group (Gaussian random field correction, voxel-level p < .001 and cluster-level p < .05). In the SR-group, a positive correlation was found between the left inferior pulvinar-precuneus connectivity and the active period (r = .46, p = .05), seizure-free period (r = .67, p = .002), and disease duration (r = .53, p = .02), and between the left medial pulvinar-precuneus connectivity and the seizure-free period (r = .58, p = .01). The combination of these thalamocortical connections showed a high predictive ability, with an area under the curve of .92 and accuracy of .90 (p = .01). SIGNIFICANCE: This study determined distinct features of thalamocortical functional connectivity at the time of ASM withdrawal in patients with and without seizure relapse, showing a potential for predicting seizure outcomes following ASM withdrawal.

Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase.

BACKGROUND: WARS2 encodes a tryptophanyl tRNA synthetase, which is involved in mitochondrial protein synthesis. Biallelic mutations in WARS2 are rare and have been associated with a spectrum of clinical presentations, including neurodevelopmental disorder with abnormal movements, lactic acidosis with or without seizures (NEMMLAS). CASE PRESENTATION: Here we present the case of an 8-year-old girl with ataxia and parkinsonism with periventricular white matter abnormalities on magnetic resonance imaging (MRI) and global developmental delay. The initial investigations revealed an elevated lactate level. Extensive metabolic testing, including a muscle biopsy, was inconclusive. Cerebrospinal fluid (CSF) neurotransmitter levels were low; however, a trial of levodopa was unremarkable. The chromosomal microarray and initial ataxia gene panel was normal. Zinc supplementation for a heterozygous variant of unknown significance in the CP gene on the ataxia exome panel was not effective in treating her symptoms. Reanalysis of the ataxia exome panel highlighted biallelic mutations in WARS2, which lead to the diagnosis of neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS). This lead to parental genetic testing, redirected therapy, and helped to expand the symptomology of this rare condition. CONCLUSION: Here we emphasize the importance of imminent and repeat expanded genetic testing to ensure early diagnosis and treatment for rare pediatric disorders. The patient is being trialed on a mitochondrial cocktail in an attempt to compensate for defects in mitochondrial protein synthesis associated with this variant. Longitudinal monitoring of disease manifestation will help establish the currently unknown natural history of this condition.

Alterations in the hippocampal-thalamic pathway underlying secondarily generalized tonic-clonic seizures in mesial temporal lobe epilepsy: A diffusion tensor imaging study.

OBJECTIVE: The epileptogenic network underlying secondarily generalized tonic-clonic seizures (sGTCS) in mesial temporal lobe epilepsy (mTLE) is not well understood. Here, we investigated alterations in the probabilistic hippocampal-thalamic pathway (pHTP) underlying sGTCS using diffusion tensor imaging and resting-state functional magnetic resonance imaging in a cohort of TLE patients with hippocampal sclerosis (HS). METHODS: We consecutively recruited 51 unilateral TLE-HS patients (26 with and 25 without sGTCS) and 22 healthy controls. Probabilistic tractography was used to track the pHTP. Raw fractional anisotropy (FA) and mean diffusivity (MD) of the pHTP were corrected by the FA/MD of the hemispheric white matter on the same side. The volume of the thalamic subregion connected to the hippocampus (TSCH) was investigated. Fractional amplitude of low-frequency fluctuations of the hippocampus, the TSCH, and the thalamic subregion unconnected to the hippocampus in resting-state functional magnetic resonance imaging were also calculated. RESULTS: After correction, the sGTCS group showed lower FA than the non-sGTCS group (P = 0.03), and lower FA as well as higher MD than controls in the ipsilateral pHTP. The non-sGTCS group only showed higher corrected MD in the ipsilateral pHTP relative to controls. Corrected FA or MD in the contralateral pHTP did not differ among groups. The TSCH was located in the mesial aspect of the thalamus, and it was atrophied in the sGTCS group compared to the non-sGTCS group and controls. The sGTCS group had lower fractional amplitude of low-frequency fluctuations in the ipsilateral hippocampus and TSCH compared to controls. SIGNIFICANCE: In TLE-HS, sGTCS was associated with impaired integrity of the pHTP as well as structural and functional abnormalities in the medial thalamus. The medial thalamus is important in seizure generalization in mTLE.

Designing Patient-Specific Optimal Neurostimulation Patterns for Seizure Suppression.

Neurostimulation is a promising therapy for abating epileptic seizures. However, it is extremely difficult to identify optimal stimulation patterns experimentally. In this study, human recordings are used to develop a functional 24 neuron network statistical model of hippocampal connectivity and dynamics. Spontaneous seizure-like activity is induced in silico in this reconstructed neuronal network. The network is then used as a testbed to design and validate a wide range of neurostimulation patterns. Commonly used periodic trains were not able to permanently abate seizures at any frequency. A simulated annealing global optimization algorithm was then used to identify an optimal stimulation pattern, which successfully abated 92% of seizures. Finally, in a fully responsive, or closed-loop, neurostimulation paradigm, the optimal stimulation successfully prevented the network from entering the seizure state. We propose that the framework presented here for algorithmically identifying patient-specific neurostimulation patterns can greatly increase the efficacy of neurostimulation devices for seizures.

Infantile hypophosphatasia combined with vitamin B6-responsive seizures and reticular formation lesions on magnetic resonance imaging: A case report.

BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder characterized by rachitic bone manifestations and a low serum alkaline phosphatase (ALP) level. It is caused by mutations in the tissue non-specific alkaline phosphatase (TNSALP) gene, which encodes the tissue non-specific isozyme of ALP. HPP patients exhibit various presentations depending on their age at onset, such as infantile HPP combined with vitamin B6-responsive seizures. CASE PRESENTATION: A newborn with infantile HPP presented with tonic convulsions from day 5 after birth and received intravenous vitamin B6 (10mg/kg/day pyridoxal phosphate). Eleven days later, frequent apneic episodes occurred, and head magnetic resonance imaging (MRI) showed bilateral reticular formation lesions in the brain stem, including the medulla oblongata. After the pyridoxal phosphate dose was increased (to 40mg/kg/day), the patient's seizures and apnea resolved, and her MRI findings also improved. Genetic testing revealed that she was homozygous for the 1559delT mutation of TNSALP. CONCLUSIONS: High-dose pyridoxal phosphate is a useful treatment for HPP-induced seizures and might improve reticular formation lesions.

Electroencephalographic findings in patients with circumscribed thalamic lesions.

INTRODUCTION: Thalamo-cortical networks have mainly been studied in the generation of idiopathic (genetic) epilepsies. The purpose of this study was to analyze EEG patterns and the occurrence of focal (symptomatic) epileptic seizures in patients with acquired circumscribed thalamic lesions. PATIENTS AND METHODS: Among 596 patients with thalamic lesions, we identified 47 patients in whom circumscribed thalamic lesions were detected by MRI and who underwent an EEG examination at the same stay at hospital. EEG findings were divided into normal findings, unspecific pathological changes and epileptiform discharges. The EEG findings were correlated to the localisation of the lesion within the thalamus and to the patients symptoms. RESULTS: In 32 patients (68%) pathological EEG findings were observed. They were heterogeneous and comprised regional and generalized slowing, triphasic waves, generalized periodic and regional epileptiform discharges. However, some characteristic findings were seen: Regional slowing was associated with ipsilateral thalamic lesions independent of the thalamic subarea, epileptiform discharges were related to lesions in the ipsilateral medial thalamus and periodic generalized discharges/triphasic waves with lesions in the anterior-ventromedial thalamus. Epileptic seizures were also more common in patients with medial thalamic lesions. Patients with regional epileptiform discharges responded to antiepileptic treatment whereas patients with triphasic waves and generalized periodic patterns did not. In some cases, it remained difficult to decide whether the thalamic lesion was the cause or consequence of epileptic activity. CONCLUSION: Pathological EEG findings are common in patients with acute and chronic thalamic lesions. EEG patterns associated with circumscribed thalamic lesions were influenced by the affected thalamic subregion. As in idiopathic generalized epilepsy, also in symptomatic epilepsy, the medial thalamus revealed to play a role in the generation of epileptiform discharges. In the patients with generalized periodic discharges and acute lesions in the ventral-anterior-medial thalamus, however, EEG changes were more likely caused by a disinhibition of cortico-thalamic networks than by a status epilepticus and thus risks and benefits of an aggressive antiepileptic treatment must be thoroughly balanced.

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP.

Localized shape abnormalities in the thalamus and pallidum are associated with secondarily generalized seizures in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a common type of drug-resistant epilepsy and secondarily generalized tonic-clonic seizures (sGTCS) have devastating consequences for patients' safety and quality of life. To probe the mechanism underlying the genesis of sGTCS, we investigated the structural differences between patients with and without sGTCS in a cohort of mTLE with radiologically defined unilateral hippocampal sclerosis. We performed voxel-based morphometric analysis of cortex and vertex-wise shape analysis of subcortical structures (the basal ganglia and thalamus) on MRI of 39 patients (21 with and 18 without sGTCS). Comparisons were initially made between sGTCS and non-sGTCS groups, and subsequently made between uncontrolled-sGTCS and controlled-sGTCS subgroups. Regional atrophy of the ipsilateral ventral pallidum (cluster size=450 voxels, corrected p=0.047, Max voxel coordinate=107, 120, 65), medial thalamus (cluster size=1128 voxels, corrected p=0.049, Max voxel coordinate=107, 93, 67), middle frontal gyrus (cluster size=60 voxels, corrected p<0.05, Max voxel coordinate=-30, 49.5, 6), and contralateral posterior cingulate cortex (cluster size=130 voxels, corrected p<0.05, Max voxel coordinate=16.5, -57, 27) was found in the sGTCS group relative to the non-sGTCS group. Furthermore, the uncontrolled-sGTCS subgroup showed more pronounced atrophy of the ipsilateral medial thalamus (cluster size=1240 voxels, corrected p=0.014, Max voxel coordinate=107, 93, 67) than the controlled-sGTCS subgroup. These findings indicate a central role of thalamus and pallidum in the pathophysiology of sGTCS in mTLE.

Epileptic seizures as the first symptom of Wernicke's encephalopathy with cerebral cortical lesions.

Wernicke's encephalopathy (WE) is acute metabolic disease of the central nervous system caused by deficiency of thiamine. Typical imaging findings are bilateral and symmetric signal in mammillary bodies, medial thalamus and periaqueductal gray. We present a 45-year-old man diagnosed for WE with two seizures and unconsciousness. The magnetic resonance imaging showed bilateral and symmetrical signal hyper-intensities in the frontal and parietal cortex, in addition to the classical MRI findings of WE. Cortical damage in WE is rare. The patient was improved significantly from unconsciousness to obeying commands and answering questions after 3days by thiamine supplementation. But the muscle strength and conscious state did not improve after 1year. This case report reminds us that we should take into account the possibility of WE when imaging shows cortical damage.

Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice.

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine's rank standard was employed to classify the stage of behavioral responses (stage 1~5). The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1) High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2) In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats.

The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A), which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni), on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ). Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions.

A case of frontal lobe epilepsy in which amplitude-integrated EEG combined with conventional EEG was useful for evaluating clusters of seizures.

Accurate evaluation of status epilepticus or clusters of seizures in patients with epilepsy is a critical issue in epilepsy care units. Although the need for continuous electroencephalographic monitoring has been recognized, it has been difficult to evaluate the frequency of ictal changes in electroencephalography (EEG) data in real time. Amplitude-integrated EEG (aEEG) has been reported to be useful for neuromonitoring, particularly in newborn infants. However, few reports of the utility of aEEG in older children with epilepsy have been published. We employed aEEG in combination with conventional EEG in an 11-year old boy presenting with clusters of seizures and were able to accurately evaluate the frequency of seizures in real time. The combination of aEEG and conventional EEG may be a useful tool in both neonatal intensive care units and epilepsy care units.

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].

Pathophysiology of altered consciousness during seizures: Subtraction SPECT study.

BACKGROUND: The mechanisms underlying altered consciousness during seizures are poorly understood. Previous clinicopathologic studies suggest a role for the thalamus and upper brainstem in consciousness mechanisms. OBJECTIVE: To examine blood flow changes associated with altered consciousness during seizures. METHODS: Seventy-one patients with epilepsy who underwent video-EEG monitoring and ictal/interictal SPECT were studied. Patients were divided into three groups depending on their conscious state during seizures: 1) complete impairment of consciousness (CI), 2) no impairment of consciousness (NI), or 3) uncertain impairment of consciousness (UI). The distribution of blood flow changes during these seizures was assessed by subtraction (ictal - interictal) SPECT co-registered to MRI. Conscious state was assessed in relation to secondary ictal hyperperfusion in subcortical regions (i.e., thalamus and upper brainstem). RESULTS: Impairment of consciousness showed a strong association with secondary hyperperfusion in the thalamic/upper brainstem region (p = 0.01), occurring in 92% (45/49) of CI, 69% (9/13) of UI, and 11% (1/9) of NI. CONCLUSIONS: These findings are consistent with a role for the thalamus and upper brainstem in consciousness mechanisms. The authors suggest that the spread of epileptic discharges or a trans-synaptic activation (diaschisis) of these structures is an important mechanism in the alteration of consciousness during seizures. Variance in the results may be due to differences in timing of radioisotope injection, sensitivity of the subtraction SPECT technique, and the ability to clinically assess the conscious state.

Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency.

Radiographic contrast agents are associated with a number of adverse effects, including central nervous system effects and seizures. Almost all contrast agents are primarily filtered and excreted by the kidneys, and they accumulate in patients with end-stage renal disease. Brain retention of contrast associated with high doses is a rare event, having been reported only twice in the literature. We report a case of a 49-year-old male on chronic hemodialysis who developed brain retention of contrast resulting in seizures and encephalopathy after receiving large doses of meglumine/sodium diatrizoate during coronary angiography. He was treated successfully with hemodialysis and suffered no permanent neurologic sequelae. Patients with end-stage renal disease may be at increased risk of adverse effects from contrast when administered in high doses.

Sonographic lenticulostriate vasculopathy in infants: some associations and a hypothesis.

PURPOSE: To describe the causes of infantile lenticulostriate vasculopathy (LSV) as demonstrated by sonography and propose the pathogenesis of these findings. METHODS: Five hundred eighty-six infants were examined via echoencephalography because of seizures, psychomotor retardation, dysmorphism, congenital malformation, microcephaly, macrocephaly, bulging of anterior fontanel, consciousness disturbance, or prematurity. We directed our attention on the sonographic study to the basal ganglionic and thalamic areas. Twenty-eight of the 586 patients underwent color Doppler studies. RESULTS: In 34 infants with gray-scale neurosonographic findings of LSV, 16 were associated with various causes that have been reported before. In 8 patients entities not previously associated with LSV were found: neonatal lupus, neonatal hypoglycemia, uncomplicated prematurity, encephalitis, and head injury. In the remaining 10 cases, a specific cause could not be found. The LSV was found in 16 (40%), 5 (14%), and 13 (3%) patients with perinatal, acquired, and nonspecific causes, respectively. Generally, this is an uncommon finding because it was observed in only 34 (5.8%) of the study infants; 24 of these 34 had a documented cause of the vasculopathy. With LSV associated with perinatal causes there was a greater chance of sonographic LSV's developing than with that of acquired causes. CONCLUSIONS: We suggest that sonographic LSV is a nonspecific marker of a previous insult to the developing brain, and the special hemodynamics of the fetal brain plays an important role in its pathogenesis.

Seizures of sleep onset: clinical and therapeutical aspects.

We studied the clinical characteristics and therapeutic response of 10 patients who presented with seizures shortly after falling asleep as the only or main manifestation of their epilepsy. The clinical evaluation was designed to investigate the appearance of seizures during diurnal and nocturnal sleep. The pharmacological response to coffee or amphetamine was investigated after normalization of previous anticonvulsant treatment. Seven of 10 patients (70%) presented with seizures during the siesta, and in 3 of 10, seizures occurred if they fell asleep at any time of the day. Seizures were detected in later hours of the night in five patients as sleep reinitiation seizures or seizures without previous awakening. The response to anticonvulsants alone was disappointing. The addition of coffee or amphetamine suppressed seizures of sleep beginning at night or during the siesta. Neither of them had an influence on sleep diurnal seizures outside of the siesta or on seizures of nocturnal sleep reinitiation. Suppression of coffee or amphetamine was followed by reappearance of the seizures.