Ictal and interictal technetium-99m-bicisate brain SPECT in children with refractory epilepsy

Identification of epileptogenic foci in patients with refractory epilepsy remains a significant diagnostic challenge. Magnetic resonance imaging studies frequently fail to reveal an anatomic origin for the seizures, and scalp electroencephalography is often limited to identification of the involved hemisphere. Functional imaging modalities such as PET and SPECT are more promising tools for this application because they reflect the functional pathology associated with the seizure. These changes are more pronounced ictally, but until recently, no radiopharmaceutical was available that could be used routinely for ictal SPECT. The present study was therefore undertaken to determine whether 99mTc-bicisate could be used in ictal SPECT in pediatric patients with refractory epilepsy, to compare the patterns of ictal and interictal blood flow in these patients and to compare the localization information provided by ictal SPECT with that available from other techniques. METHODS: Technetium-99m-bicisate/SPECT was compared prospectively with scalp EEG for its ability to identify a possible seizure focus in pediatric patients with refractory epilepsy. Ictal and interictal SPECT studies were performed in 10 patients (3-19 yr old, mean age 10.9 +/- 4.3 yr; 7 female, 3 male) in whom MRI scans revealed no lesions that might be responsible for the seizures. RESULTS: Ictal SPECT was performed in all patients, and all ictal studies revealed focal perfusion abnormalities. By comparison, four of the interictal SPECT studies showed regional hypoperfusion that corresponded to the regions of hyperperfusion in the ictal studies, and three showed regional hyperperfusion corresponding to the hyperperfused regions in the ictal studies. Three interictal studies revealed no abnormal perfusion. Scalp EEG provided localization information in five patients. CONCLUSION: These initial results suggest that ictal SPECT with 99mTc-bicisate is a more promising tool for the identification of epileptogenic foci than interictal SPECT or scalp EEG in patients without focal abnormalities on MRI.     

The practical utility of performing peri-ictal SPECT in the evaluation of children with partial epilepsy

The distribution of membrane filipin sterol complexes (FSC) in the plasma membrane of the acrosomal region (PMAR) of rabbit sperm from epididymis and testis, in normal and hypercholesterolaemic rabbits, was examined at ultrastructural level. Membrane FSG were quantitatively analysed on freeze fracture replicas of filipin-treated cells. Cauda epididymal sperm shows a significant increase in filipin sterol complexes concentration in PMAR of hypercholesterolaemic animals compared to normal rabbits. Hypercholesterolaemic animals had 0.53 +/- 0.08 FSC micron-2 in the marginal segment of PMAR and 0.26 +/- 0.03 FSC micron-2 for normal animals. In the principal piece we found 0.70 +/- 0.07 FSC micron-2 for hypercholesterolaemic and 0.43 +/- 0.03 FSC micron-2 for control animals. We also counted 0.58 +/- 0.04 FSC micron-2 in the equatorial segment of PMAR for hypercholesterolaemic and 0.38 +/- 0.03 FSC micron-2 for normal animals respectively. The FSC concentration of testicular sperm, like sperm from corpus and caput of epididymis in hypercholesterolaemic animals, did not differ from the controls. Cholesterol, phospholipids and cholesterol:phospholipid ratio in caudal epididymal sperm from treated males did not differ from controls. Only the sphingomyelin concentration decreases in cauda epididymal sperm from hypercholesterolaemic males compared to controls. The results presented in this paper suggest that the lipidic domains in PMAR of hypercholesterolaemic rabbits changes when the gametes go through the epididymis.     

Benign partial epilepsy with affective symptoms: hyperkinetic behavior during interictal periods

We report a 4-year-old boy with benign partial epilepsy (BPE) with affective symptoms associated with hyperkinetic behavior during interictal periods. He had had hypermobility and restlessness since about age 3. At 4 years, 6 months, he developed episodes consisting of an expression of terror without complete loss of consciousness. Although we first suspected an acute psychic problem, the ictal EEG was abnormal. After carbamazepine (CBZ) therapy, the frequency of the attacks decreased dramatically and the hyperkinetic behavior gradually diminished.     

MFT in complex partial epilepsy: spatio-temporal estimates of interictal activity

Following exposure of CHO-K1 cells to 137Cs irradiation at doses up to 20Gy, a delay in G2 was observed to occur in cells permitted to divide normally, while cells induced to become giants by means of cytochalasin B demonstrated a minimal delay in the transition 2C-8C suggesting that the inhibition of cytokinesis results in modification of one or more cell cycle checkpoints. We postulate that this may occur as a consequence of damage tolerance, or by a feedback loop resulting from the reorganisation of the cytoskeleton that precludes cytokinesis.     

SPECT brain perfusion abnormalities in mild or moderate traumatic brain injury

The accumulation of wild-type p53 protein results in two pathways, cell cycle G1 arrest by p21WAF1/CIP1/SDI1 and apoptosis inhibited by bcl2, which together carry out the tumor suppressor function. Since genetic alterations of p53 are frequently observed in gastric cancers, the expression of p21 and bcl2 may be altered in gastric carcinogenesis. We therefore analyzed normal mucosa, nondysplastic lesions, hyperplastic polyps, adenomas and carcinomas of the human stomach using immuno-histochemistry, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing. In normal gastric mucosa, the expression of p21, bcl2 and p53 was topographically restricted: a) p21 expression was limited to foveolar epithelial cells; b) bcl2 and p53 expression was confined to only a few regenerative epithelial cells of the mucous neck region. In chronic gastritis or intestinal metaplasia, topographic expression became more obvious. This topographic expression was altered in hyperplastic polyps and adenomas. Hyper-plastic polyp showed an increased p21 and p53 expression with no bcl2 expression. Where as bcl2 expression increased and extended up parabasal and superficial dysplastic epithelium, p21 expression increased and was limited to surface dysplastic epithelium. Weak p53 expression was in full thickness of dysplastic epithelium. p21 and bcl2 expression in adenoma was higher than in intestinal type of carcinoma. In carcinomas, this topography was abrogated, but p53 mutation (36%) was present. There was no relationship between p53, p21 and bcl2 expression. As a result, in normal gastric epithelial cells, there was a precisely ordered topographic pattern of p21, bcl2 and wild-type p53 expression that becomes disordered during neoplasia. These results suggest that altered cell cycle and apoptosis control by wild-type p53 and its mediators appears to be an early event in gastric carcinogenesis that may facilitate tumor progression.     

Usefulness of ictal and interictal 99mTc ethyl cysteinate dimer single photon emission computed tomography in patients with refractory partial epilepsy

OBJECTIVE: The aim was to investigate the feasibility of recording the electrical auditory brain stem response (EABR) evoked by electrical stimulation at the promontory (Prom-EABR) as a tool to assist selection of the ear for cochlear implantation in young children. STUDY DESIGN: The study group consisted of young children for whom the decision to proceed with implantation with the Nucleus mini 22-channel cochlear implant (Cochlear (UK) Ltd., London, UK) had already been made. SETTING: The Prom-EABR was recorded after the children had been anesthetised, but before the start of surgery. PATIENTS: A group of 25 children (11 boys and 14 girls), whose age at implantation ranged from 2 years 11 months to 6 years 8 months (mean age, 4 years 5 months), were investigated. INTERVENTION: Recordings of the Prom-EABR were used to determine which ear would receive the cochlear implant, providing there were no preexisting contraindications regarding selection of the ear. MAIN OUTCOME MEASURE: It has been suggested from earlier studies that the characteristics of the amplitude input/output (I/O) function of the EABR are related to neuronal survival. If the ear with the "better" I/O function is chosen for implantation, it might be expected that these children will perform better on average than those in whom the ear has been selected at random. RESULTS: Reliable recordings of the Prom-EABR were achieved in 40 ears (80%) of the 50 ears in the study. In 20 of the 25 children the technique was actively employed for selection of the ear for implantation. CONCLUSIONS: Recording of the Prom-EABR in the operating theater is a viable technique. Future analysis of long-term outcome measures of performance with the implant will confirm or dispute the benefit of ear selection using the Prom-EABR.     

Surgical treatment for partial epilepsy among Norwegian children and adolescents

We conducted a retrospective longitudinal self-controlled study of 64 patients aged 4-19 years treated with resective surgery for partial epilepsy from 1952 to 1988. Approximately 60% of patients experienced > 95% reduction in seizure frequency, and 70% had worthwhile improvement of at least 75% reduction. Seizure relief was more frequent among patients who underwent operation after 1978, and significant differences by time period of operation were noted for those with temporal lobe excisions and patients with normal tissue histology. The region of resection and the age at treatment did not provide significant information with respect to seizure outcome. Postresection electrocorticography (ECoG) and EEG of the first postoperative year predicted later seizure outcome. Small neurologic deficits were more common among patients resected in the temporal lobe than in patients resected in the frontal lobe. Half of the patients with preoperative unilateral focal activity and a third of those with bilateral focal activity had normal EEG postoperatively. One fourth had discontinued antiepileptic drug (AED) therapy. As expected, long-term mortality was significantly higher than the mortality of the general population. Seven patients died during follow-up. Two male patients committed suicide.     

A case of postencephalitic intractable partial epilepsy with multiple brain lesions demonstrated by MRI

The aim of this work was the development of a fluorescent microscopy technique to visualize acid phosphatase activity in living and pre-fixed cells. We have shown that a coupling azo dye method, using naphthol AS-MX phosphate (NP) as substrate and fast red TR (FR) as a diazonium salt coupling agent, gives rise to a fluorescent azo dye reaction product which permits a highly sensitive demonstration of lysosomal acid phosphatase in both living and pre-fixed monolayer cell cultures. The granular staining is prevented by inhibition of acid phosphatase activity using fluoride and/or orthovanadate in both living and pre-fixed preparations. Lysosomal staining in living cells is also abolished by inhibition of fluid-phase endocytosis using low temperatures or inhibition of oxidative phosphorylation. It was shown that whilst NP entered living cells by passive diffusion, occurrence of FR in lysosomes resulted from fluid-phase endocytosis. Spectroscopic analysis of the emission and absorption features of FR, NP, naphthol AS-MX (N), and the N-FR azo dye reaction product in solution corroborated our microscopic results. The differing uptake mechanisms, and the occurrence of lysosomally localized azo dye, were also in keeping with the predictions of quantitative structure-activity relationship models of this system.     

Event-related potentials suggest slowing of brain processes in generalized epilepsy and alterations of visual processing in patients with partial seizures

Diagnostic imaging is frequently used to evaluate the patient who has or may have an infection or other inflammatory lesion in the neck. In fact, these diagnoses and their differentiation from tumor may only be made after a careful radiological evaluation. This review will illustrate the imaging appearance of many of the common inflammatory conditions that may arise in the neck. In most, but not all cases, CT is the imaging study of choice in the initial work-up of this patient population.     

Single photon emission tomography in temporal epilepsy: interictal and ictal studies with visual and semi quantitative analysis

Single photon emission tomography (SPECT) was performed in 27 patients with refractory complex partial seizures from the temporal lobes due to mesial temporal sclerosis. Independent blinded observers assessed the 28 interictal studies and 9 ictal/postictal studies. Visual analysis of interictal studies detected hypoperfusion in 22, ipsilateral to the epileptogenic zone in 19 (67%) and contralateral in 3 (10.7%). Quantified temporal lobe asymmetry, greater than a previously derived normal range, correctly identified the epileptogenic zone in 16 (61.5%) with false lateralization in 4 (15.3%). In all 9 cases in which they were performed, ictal/postictal studies showed hyperperfusion at the region of epileptic focus. In 3 patients with complex partial seizures followed by symmetric generalized tonic-clonic seizures, hyperperfusion restricted to the temporal lobe was demonstrated. In 5 of these patients the interical studies were unable to demonstrate localized changes. There were no significant correlations between SPECT findings and clinical parameters or EEG slowing in the temporal lobes.     

Etiology in complex partial epilepsy. II. Correlation between EEG topography and neuroimaging

Neuro-imaging studies (NI) in patients with complex partial seizures (CPC) demonstrate the epileptogenicity of a more or less localized underlying lesion. Correlation with the topography of the EEG focus permits affirmation of the origin. We analyze anomalies on NI and on the EEG of 151 patients with CPC. The EEG was abnormal in 128 and showed a unilateral epileptic focus in 117. NI was focal and unilateral in 72 of the 102 abnormal cases. Topographic correlation was 78.5%. This close correlation in our series makes us consider the localized lesions to be the probable aetiological factor.     

Language dysfunction in children with Rolandic epilepsy

Rolandic epilepsy is regarded as the classic example of benign focal epilepsy. However, neuropsychological deficits have been noted in affected children. As Rolandic discharges are mainly distributed over the centrotemporal region, specific interference with language function might be suspected. Therefore, we conducted a standardized neuropsychological assessment in children with Rolandic epilepsy which covered all important aspects of language processing. We measured intelligence Quotient, verbal memory, auditory discrimination, vocabulary, grammar and literacy in 20 children with an active Rolandic focus. Information about performance at school was obtained from teachers by means of a questionnaire. Patients with Rolandic epilepsy failed five of the twelve standardized language tests significantly more often than the normative population and consequently showed impairment of the following functions: reading, spelling, auditory verbal learning, auditory discrimination with background noise and expressive grammar. Thirteen of the 20 children showed language dysfunction with difficulties in two or more of the twelve standardized language tests. In eight of these 13 children the Full Scale Intelligence Quotient was within average range, indicating a specific language deficit. Language dysfunction was closely associated with learning difficulties at school. This study documents a consistent pattern of language dysfunction in children with Rolandic epilepsy which suggests interictal dysfunction of perisylvian language areas.     

Clinical experience with the technetium-99 scan in children

A study of 86 bone scans in 79 patients was conducted to determine ways to enhance the usefulness of this test and learn what factors influence its results. While the overall value of the bone scan as we initially used it was not what we had hoped, it could be improved substantially by utilizing all initial clinical information when ordering as well as interpreting the scan. Its main value in suspected sepsis is to localize affected areas in and around the pelvis and spine. The scan is often unnecessary in the diagnosis of long-bone osteomyelitis and is seldom indicated when diagnosing cellulitis or synovitis. In occult trauma it is valuable for further investigation of specific areas with possible nondisplaced fractures. Needle aspiration of the bone or joint does not seem to alter the scan. We conclude that the bone scan is chiefly valuable in locating focal areas of skeletal pathophysiology.     

FDG-PET and volumetric MRI in the evaluation of patients with partial epilepsy

We performed interictal FDG-PET- and MRI-based hippocampal volumetric measurements on 18 adult patients with complex partial epilepsy of temporal lobe origin in whom we had identified their ictal focus by video-telemetry EEG. Sixteen patients (89%) had regional hypometabolism, 11 (61%) had focal 1.5-tesla T2-weighted MRI (two structural abnormalities, nine hippocampal formation [HF] increased T2 signal), and nine (50%) had absolute HF atrophy ipsilateral to the temporal ictal focus. Ten (55%) had abnormal L/R HF ratios, nine ipsilateral to the EEG focus. All patients with abnormal MRI volumetric studies had focal PET abnormalities. Only seven had both abnormal HF volume ratios and T2 MRI (all increased HF T2 signal). There was a significant correlation between hippocampal volume and inferior mesial and lateral temporal lobe cerebral metabolic rate of glucose asymmetry index (p < 0.01), suggesting that hypometabolism may reflect hippocampal atrophy. PET is more sensitive than MRI volumetry in identifying the ictal focus but does not provide additional information when HF atrophy is present.     

Is partial epilepsy progressive? Ten-year follow-up of EEG and neuropsychological changes in adults with partial seizures

PURPOSE: This study was undertaken to determine what changes, if any, occur in the electroencephalogram (EEG) and in neuropsychological test findings of adults with medically intractable complex partial epilepsy over a 10-year period. METHODS: We studied 35 adults, with a mean age of 32 years (range, 16-59 years) at time of initial testing. We compared the distribution of epileptiform patterns documented on the initial pair of waking and sleeping EEGs to those observed on another pair obtained 10 years later. During this same 10-year period, we also examined changes in the Wechsler Adult Intelligence Scale (WAIS) and on the tests from the Neuropsychological Battery for Epilepsy. RESULTS: The EEGs of 28 (80%) of patients at the tenth year were identical to those seen initially. Five (14%) of patients demonstrated EEGs after 10 years with either no discharges or only unilateral discharges, where bilateral discharges were seen a decade earlier. Only two (6%) of patients had EEGs at the tenth year that showed bilateral discharges where only unilateral discharges were seen originally. We found no general change in intelligence or neuropsychological functioning after 10 years, although a few subtle losses were noted on several neuropsychological measures. CONCLUSIONS: For most adults with medically intractable complex partial epilepsy, the EEG and neuropsychological test scores remain reasonably stable over a decade.     

D2 receptor imaging with iodine-123-iodobenzamide brain SPECT in infants with hypoxic-ischemic brain injury

The purpose of this study was to evaluate the striatal dopamine D2 receptor density in infants with perinatal hypoxic-ischemic brain injury (HIBI) using 123I-iodobenzamide (IBZM) brain SPECT and to correlate the findings with the severity of HIBI and neurologic outcome. METHODS: Twenty infants who were diagnosed to have perinatal HIBI were included in this study. They were classified as having mild (n = 6), moderate (n = 10) or severe (n = 4) HIBI according to their neurologic findings at birth using the criteria of Sarnat and Sarnat. Neurologic outcome of these infants was determined by serial neurologic examinations and the Denver developmental screening test; 10 infants recovered without any deficit and the remaining 10 were affected to a degree varying from motor impairment to cerebral palsy. All 20 infants were examined using 123I-IBZM brain SPECT at age 7.8 +/- 2.3 mo. Transaxial slices were obtained 2 hr after intravenous injection of 300 micro ci (11.1 MBq) 123I-IBZM and the activity ratios of striatal to occipital cortex (ST/OC) were calculated. RESULTS: The mean ST/OC ratios in patients with mild, moderate and severe HIBI (1.219 +/- 0.078, 1.097 +/- 0.069 and 0.813 +/- 0.140, respectively) were significantly different from each other (p = 0.001). The infants who recovered from HIBI without any neurologic sequelae had higher mean ST/OC ratios than the others (1.184 +/- 0.010 versus 0.969 +/- 0.160, p = 0.002). CONCLUSION: The results of this study show that in infants with HIBI, striatal D2 receptor density decreases as the severity of injury increases. The D2 receptor density is higher in infants who recover without neurologic deficits compared to those who are affected neurologically. Dopamine D2 receptor imaging can be used to assess the severity of HIBI in children.     

Aggression in children treated with clobazam for epilepsy

Seven of 63 children (11%) treated with clobazam (CLB) for refractory epilepsy developed a severe behavior disorder. This disorder was characterized by aggressive agitation, self injurious behavior, insomnia, and incessant motor activity occurring between 10 and 55 days after initiation of drug therapy. The affected children were relatively young (mean age 6.4 years) and developmentally disabled (four were autistic and two had isolated mental retardation). The disorder occurred with a short latency after initiation of therapy and at a relatively low dosage of CLB. Serum levels of other coadministered antiepileptic drugs were unchanged by the administration of CLB. One child was taking CLB monotherapy. This behavioral deterioration required the discontinuation of CLB, after which patients returned to their previous behavior within 3 weeks. After > 3 years of follow-up all children continue to require multiple antiepileptic drugs but have not had a recurrence of this aggressive agitation. The mechanism of the behavioral change is unclear.     

Clinical value of SPECT scanning in children with neurological disorders

We retrospectively evaluated the clinical value of Tc-99-HMPAO brain single photon emission tomography (SPECT) in 21 children with neurological disorders of varied aetiology. All 21 patients were examined with electroencephalograms (EEGs), 17 with computed tomography (CT) and ten with magnetic resonance imaging (MR). New relevant information was obtained from SPECT in all 21 cases and in four of these cases the investigation directly led to a change in diagnosis and better assessment of the prognosis. It is concluded that SPECT is an important investigational method in children with neurological symptoms of partly or completely unknown aetiology.     

Psychopathology in pediatric complex partial and primary generalized epilepsy

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.     

Grouped crises and status epilepticus in complex partial epilepsy

INTRODUCTION: In complex partial crises (CPC) some characteristics of the way in which they occur may be helpful in localizing the focus of origin in the cerebral cortex. Thus, the appearance of any kind of status epilepticus will not predominate depending on the origin of the epileptic focus, but the complex partial state will be rare when the origin is temporal and more frequent when the origin is frontal. The appearance of CPC in a cluster form is, on the other hand, characteristic of crises originating in the frontal lobe. MATERIAL AND METHODS: We review the clinical history of 151 epileptics with CPC, evaluating the way in which the crises appear, together with other clinical data. We define the start of the crisis in a specific lobe, when this was the site of maximum voltage of the epileptic anomaly or of maximum phase opposition. RESULTS: 10% of the patients showed grouping of their CPC; in the remainder the appearance was isolated, 15% showed status epilepticus at some point in their illness. We found a statistical difference when relating this to the anomalous topography of the EEG; between 15% and 42% more patients with status epilepticus were counted when the topography of the anomaly in the EEG was extratemporal. There was also between 37.2% and 76.4% more patients with cluster crises in the cases with an extratemporal focus.