Ictal SPECT during autonomic crisis in familial dysautonomia.

The authors report results of SPECT cerebral perfusion studies in two patients with familial dysautonomia (FD) during dysautonomic crises and when clinically stable. SPECT imaging studies used 99mTc ethylene cysteine dimer. During dysautonomic crises, regions in the temporoparietal and frontal lobes had increased uptake. Uptake in these areas was less during asymptomatic periods. Episodic asymmetric cerebral perfusion during crises especially affecting the frontal and temporal lobes is suggestive of ictal activity.

Update on epilepsy in pediatric patients.

Epilepsy is a common condition that affects 0.5 to 1% of all children. Although most children with epilepsy have well-controlled seizures with use of one antiepileptic drug (AED), some children have medically refractory seizures. This situation can be the result of inaccurate classification of the paroxysmal event, use of an inappropriate AED, of a truly medically refractory seizure disorder. Paramount to the initial assessment of a child with presumed epilepsy is the appropriate classification of the paroxysmal event. Several nonepileptic conditions, such as motor tics or breath-holding spells, can cause paroxysmal abnormalities in children, which can be confused with epilepsy. The common pediatric epileptic and nonepileptic conditions are reviewed, and the standard and new AEDs and their side effects are discussed. When a child's seizure disorder is intractable despite adequate trials of AEDs, surgical treatment is increasingly becoming an effective option. Such procedures should ideally be performed at centers with extensive experience in this area and with a multidisciplinary team approach. With improved magnetic resonance imaging technology, increasing numbers of children with medically intractable localization-related epilepsy are being found to have underlying focal cortical dysplasia, tumors, or hippocampal atrophy. These abnormalities can often be surgically resected with excellent results. A generalized epilepsy may also be remediable with surgical treatment. Specifically, preliminary data suggest that infantile spasms, when triggered by an underlying focal cortical dysplasia, may be effectively treated by surgical resection. Patients with certain catastrophic seizure disorders, such as Sturge-Weber syndrome or hemimegalencephaly, require prompt intervention with hemispherectomy. The presurgical evaluation relies heavily on the magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography scan data as well as the electroencephalogram in identifying the area of epileptogenic abnormality.

The distribution of somatostatin binding sites in the brain of gymnotiform fish, Apteronotus leptorhynchus.

The neuropeptide somatostatin (SS) and its binding sites display a wide distribution in the central nervous system of vertebrates. By employing semi-quantitative autoradiography, we identified such binding sites in the brain of the weakly electric fish Apteronotus leptorhynchus (Gymnotiformes, Teleostei). Whereas (SS1) binding sites for the octapeptide analogue Tyr3-SMS-201-995 appear to be absent in the gymnotiform brain, (SS2) binding sites for the analogue [Tyr0-D-Trp8]-somatostatin-14 were found in many brain regions and showed a similar distribution to that observed by other authors in the amphibian and mammalian central nervous system. Telencephalon While binding in the ventral telencephalon was typically low, all cell groups of the dorsal portion displayed a high degree of binding. The highest density of binding sites was found in the dorsal and caudal subdivision 2 of the dorsomedial telencephalon. Diencephalon Many cell groups of the diencephalon showed a medium to high degree of binding density. The highest level was seen in the habenula. Mesencephalon All layers of the optic tectum contained a medium number of binding sites, except the stratum marginale. In the torus semicircularis, the different layers displayed distinct binding density. While laminae 7-8 showed the highest degree of binding, the lowest density was found in lamina 6. Rhombencephalon Binding was generally low or absent in the tegmentum. Low levels of binding density were observed in the electrosensory lateral line lobe. Cerebellum Extremely high levels of binding were found in the eminentia granularis medialis and the eminentia granularis posterior. Throughout most regions of the brain, the relative density of binding sites and the relative amount of somatostatin immunoreactivity in fibres, as determined in previous studies, were in good agreement.

In situ hybridization of putative somatostatin mRNA in the brain of electric gymnotiform fish.

The distribution of somatostatin mRNA in the brain of Apteronotus leptorhynchus, a weakly electric gymnotiform fish, has been mapped by employing in situ hybridization with an oligodeoxynucleotide probe corresponding to nucleotides 1-26 of catfish somatostatin mRNA; this probe was end-labelled with digoxigenin. Most labelled cell groups were found in the telencephalon, followed by the diencephalon. This distribution is in good agreement with previous immunohistochemical investigations. In the complex of the diencephalic central-posterior/prepacemaker nucleus, a cluster of neurons controlling electrocommunicatory behavior, somatostatin mRNA could be detected only in lateral aspects, although many medial cells also stain positively with immunohistochemical techniques. This difference may be related to the growth of these neurons during adulthood.

Neuroimaging in the evaluation of children and adolescents with intractable epilepsy: I. Magnetic resonance imaging and the substrates of epilepsy.

Recent advances in neuroimaging, particularly the magnetic resonance imaging (MRI) scan, have greatly enhanced our ability to visualize intraparenchymal anatomy. With the linkage between intracranial pathology and epilepsy now clearly established, the MRI data provides detailed information for the clinician treating patients with epilepsy. This article supplies the reader with an overview of the new techniques in MRI brain imaging that allow us to identify intracranial abnormalities, and a survey of some of the MRI-identified substrates of epilepsy.

Neuroimaging in the evaluation of children and adolescents with intractable epilepsy: II. Neuroimaging and pediatric epilepsy surgery.

The costs of epilepsy encompass all aspects of life, including medical, educational, and psychosocial. Adults with intractable epilepsy who undergo epilepsy surgery and have seizure-free outcomes still have significant barriers in the attainment of improved quality of life. For this reason, there is increasing interest in the recognition of children and adolescents with intractable epilepsy who might be epilepsy surgery candidates. This is Part II of an article on the role of neuroimaging in the evaluation of children and adolescents with intractable epilepsy. Part I addressed the role of MRI in detecting the substrates of epilepsy (Pediatr Neurol 1997;17: 19-26); Part II elaborates on the selection process of pediatric patients who might benefit from epilepsy surgery. Although EEG remains the cornerstone of the evaluation process, MRI, SPECT, and PET can play a pivotal role in the identification of the underlying epileptogenic focus and minimize the need for invasive EEG monitoring. Magnetic resonance spectroscopy and magnetoencephalography are also innovative, noninvasive techniques which may aid in the localization of the epileptogenic focus. Functional MRI scans may soon replace invasive technologies in the identification of eloquent cortex that should not be a part of the surgical resection.

Unusual presentation and MRI findings in Rasmussen's syndrome.

Rasmussen's syndrome is a chronic disorder characterized by uncontrollable focal seizures and eventually epilepsia partialis continua, ipsilateral hemiparesis, developmental arrest, and cerebral inflammation. Viral and autoimmune etiologies have been postulated. A patient is presented who illustrates the wide variability of clinical and radiographic presentations in this disorder. The patient is an 8-year-old female who developed intermittent facial twitching at 2 years of age that eventually progressed to epilepsia partialis continua. Electroencephalography demonstrated clinical seizures that emanated from the right parasagittal area. Cranial magnetic resonance imaging revealed pronounced atrophy of the right caudate nucleus, globus pallidus, and putamen, with mild increased T2-weighted signal in the right striatum, without accompanying cortical atrophy. Ictal single-photon emission computed tomography revealed markedly reduced uptake in the right hemisphere that was maximum in the right basal ganglia. Cerebrospinal fluid, blood, and urine collected for metabolic and immunologic screening and DNA testing for a wide variety of disorders were all unremarkable. Neuropsychologic testing demonstrated difficulties in memory, attention, and calculation. Brain biopsy revealed mild microglial activation, rare glial nodules, and collections of lymphocytes and histiocytes, consistent with the clinical diagnosis of Rasmussen's syndrome. After a modified hemispherectomy, she demonstrated marked clinical improvement.

Alternating hemiplegia of childhood: clinical manifestations and long-term outcome.

We present our analysis of 44 patients with alternating hemiplegia of childhood. The clinical course usually consisted of three phases. The first was dominated by abnormal eye movements and dystonic episodes, the second by hemiplegic spells and psychomotor regression, and the third by persistent developmental delay and fixed neurologic deficits. The age of onset was 0-54 months (mean = 7.9 +/- 13 months). The presenting signs included abnormal ocular movements in 65%, dystonia in 60%, and hemiplegia in 32%. Patients with an early onset of the disorder and an early appearance of hemiplegic spells faired the poorest developmentally. Developmental delay was present in 91%, ataxia in 68%, choreoathetosis in 50%, and seizures in 18%. Laboratory investigations suggested mitochondrial abnormalities and cerebrovascular dysfunction in several patients. Numerous therapies were largely ineffective. Flunarizine reduced the duration, severity, and frequency of the hemiplegic attacks in 78%. Patients who received flunarizine did not differ developmentally from those who did not. Our data suggest that flunarizine does not adversely affect and may favorably influence the outcome in patients with alternating hemiplegia of childhood. Additionally, the occurrence of autosomal-dominant cases of the syndrome, although rare, suggests that, in addition to mitochondrial dysfunction, genetic factors may be important.

123I-iodoamphetamine SPECT brain imaging in alternating hemiplegia.

Alternating hemiplegia of childhood is an unusual disorder characterized by early onset (occurring before 18 months of age); repeated attacks of hemiplegia involving both sides of the body; other paroxysmal phenomena, such as tonic stiffening, dystonic posturing, choreoathetoid movements, ocular motor abnormalities, and autonomic disturbances, in association with bouts of hemiplegia or occurring independently; and evidence of mental or neurologic deficits. A girl was examined because of left hemiplegia at the age of 16 months. The patient had begun exhibiting episodes of alternating hemiplegia at approximately 4 months of age. They consisted of tonic stiffening and dystonia of the right or left extremities, lasting from 30 min to several hours and followed by residual hemiparesis. They were invariably accompanied by ocular motor abnormalities. Magnetic resonance imaging, computed tomography, and angiography all were normal. Single proton emission computed tomography brain images during an acute episode of right hemiplegia demonstrated hypoperfusion of the left cerebral hemisphere. Following improvement of the hemiplegia, the patient was re-evaluated. The uptake of the radiotracer in the left hemisphere was increased. The scan did not demonstrate significant asymmetry in cerebral perfusion.

Osmiophilic deposits in cytosomes in Hallervorden-Spatz syndrome.

A young child with Hallervorden-Spatz syndrome is presented. She was well until 8 years of age when she lost interest in activities and her school performance declined. At age 11 years, she began having episodes of blepharospasm, accompanied by bilateral ptosis and occasional episodes of oculogyric crisis. By age 12 years, her motor coordination had declined and she began to exhibit evidence of dementia, dystonia, dysarthria, and tremor. Motor incoordination, dystonia, and tremor progressed until the patient was wheel-chair-bound. Multiple tests were performed, including metabolic studies, magnetic resonance imaging, bone marrow biopsy, and electron microscopy of the buffy coat. Both bone marrow and buffy coat revealed inclusions in the cytosomes which were granular and osmiophilic. To our knowledge, this is the third case report of inclusion bodies found in patients with manifestations of Hallervorden-Spatz syndrome. These findings suggest that obtaining a buffy coat and bone marrow biopsy may aid in the diagnosis of Hallervorden-Spatz syndrome and ultimately provide information regarding etiology.

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

Peri-ictal brain single-photon emission computed tomography (SPECT) is increasingly being established as a useful test in localizing partial epilepsy in adults. However, obtaining an ictal injection and acquiring the SPECT images poses a greater challenge in pediatric patients, and few reports have specifically addressed the practical use of this technique in children. The Mayo Clinic experience of peri-ictal SPECT in the evaluation of children with partial epilepsy is reported here. Peri-ictal SPECT was attempted during 71 admissions involving 59 patients (median age 12 years, range 1 year 6 months-17 years). A peri-ictal SPECT injection was performed on 48 (67.6%) of these admissions in 43 (72.9%) patients, and only two patients could not be scanned. Of the 46 peri-ictal images successfully obtained, 30 (65.2%) were from ictal injection and 16 (34.8%) from post-ictal injections. Forty-two (91.3%) of the successfully obtained SPECT images, in 38 patients (92.3%), were classified as localizing (15 temporal, 24 extratemporal). We conclude that, with the appropriate unit setup and well-trained staff, peri-ictal SPECT scans can be obtained in most pediatric partial epilepsy patients. Moreover, the procedure provides specific localizing information in a high proportion of these patients.

Rasmussen encephalitis: epilepsia partialis continua secondary to chronic encephalitis.

Rasmussen encephalitis is a disease consisting of chronic encephalitis with progressive neurologic deficits and focal intractable seizure activity. The etiology is unknown, but pathologic specimens revealed changes consistent with viral encephalitis. Even though neuro-imaging techniques, such as positron emission tomography and magnetic resonance imaging, offer the prospect of specific, presurgical diagnostic criteria, the initial diagnosis usually is made on a clinical basis. Treatment modalities, including a wide variety of antiepileptic drug therapies and surgical interventions, may result in significant physical and mental impairments. We summarize the clinical presentation, diagnostic considerations, and different treatment protocols in a patient with this rare and debilitating disorder.

Proteome analysis reveals protein candidates involved in early stages of brain regeneration of teleost fish.

Exploration of the molecular dynamics underlying regeneration in the central nervous system of regeneration-competent organisms has received little attention thus far. By combining a cerebellar lesion paradigm with differential proteome analysis at a post-lesion survival time of 30 min, we screened for protein candidates involved in the early stages of regeneration in the cerebellum of such an organism, the teleost fish Apteronotus leptorhynchus. Out of 769 protein spots, the intensity of 26 spots was significantly increased by a factor of at least 1.5 in the lesioned hemisphere, relative to the intact hemisphere. The intensity of 9 protein spots was significantly reduced by a factor of at least 1.5. The proteins associated with 15 of the spots were identified by peptide mass fingerprinting and/or tandem mass spectrometry, resulting in the identification of a total of 11 proteins. Proteins whose abundance was significantly increased include: erythrocyte membrane protein 4.1N, fibrinogen gamma polypeptide, fructose-biphosphate aldolase C, alpha-internexin neuronal intermediate filament protein, major histocompatibility complex class I heavy chain, 26S proteasome non-ATPase regulatory subunit 8, tubulin alpha-1C chain, and ubiquitin-specific protease 5. Proteins with significantly decreased levels of abundance include: brain glycogen phosphorylase, neuron-specific calcium-binding protein hippocalcin, and spectrin alpha 2. We hypothesize that these proteins are involved in energy metabolism, blood clotting, electron transfer in oxidative reactions, cytoskeleton degradation, apoptotic cell death, synaptic plasticity, axonal regeneration, and promotion of mitotic activity.

Environmental occurrence, fate and transformation of benzodiazepines in water treatment.

Benzodiazepine derivatives are prescribed in large quantities globally and are potentially new emerging environmental contaminants. Unfortunately, a dearth of data exists concerning occurrence, persistence and fate in the environment. This paper redresses this by reviewing existing literature, assessing the occurrence of selected benzodiazepine anxiolytics (diazepam, oxazepam and bromazepam) in wastewater influent and effluent and surface water from Slovenia, evaluating their removal during water treatment and identifying the transformation products formed during water treatment. Their occurrence was monitored in hospital effluent, river water and in wastewater treatment plant influent and effluent. The study reveals the presence of benzodiazepine derivatives in all samples with the highest amounts in hospital effluents: 111 ng L(-1), 158 ng L(-1) and 72 ng L(-1) for diazepam, bromazepam and oxazepam, respectively. Removal efficiencies with respect to biological treatment of diazepam were 16-18% (oxic), 18-32% (anoxic→oxic), 53-76% (oxic→anoxic) and 83% (oxic→anoxic→oxic→anoxic cascade bioreactors), while the removal oxazepam was 20-24% under anoxic conditions. Coupled biological and photochemical treatment followed by the adsorption to activated carbon resulted in a removal efficiency of 99.99%. Results reveal the recalcitrant nature of benzodiazepine derivatives and suggest that only combinational treatment is sufficient to remove them. In addition, eight novel diazepam and four novel oxazepam transformation products are reported.

Theodore H. Bullock: pioneer of integrative and comparative neurobiology.

Theodore H. Bullock (1905-2005) was a pioneer of integrative and comparative neurobiology and one of the founders of neuroethology. His work--distinguished by the tremendous number of different research themes and animal taxa studied--provided the basis for a comprehensive analysis of brain evolution. Among his major achievements are: one of the first physiological analyses of rhythmic central pattern generators; the first simultaneous recording from both the presynaptic and postsynaptic region of a chemical synapse; the demonstration of intercellular communication through graded potentials; and the discovery of two novel sensory organs formed by infrared receptors in pit vipers and electroreceptors in electric fish. He was also one of the first who applied computational tools to the analysis of complex neural signals and to perform a comparative analysis of cognitive events. His two-volume treatise "Structure and function in the nervous system of invertebrates" (with G. Adrian Horridge) remains the most comprehensive, authoritative review of this topic ever written. In addition to his research merits, his legacy is particularly based on his cosmopolitan way of thinking and acting, his large, worldwide school of students, and his committed advocacy for comparative and systems-oriented neurobiology.

Potential pharmacokinetic interaction between felbamate and phenobarbital.

OBJECTIVE: To report a case of a potential pharmacokinetic interaction between felbamate and phenobarbital in a patient with epilepsy. CASE SUMMARY: A patient with a history of a mixed seizure disorder and static encephalopathy who was receiving sodium valproate 750 mg/d and phenobarbital 230 mg/d was initiated on felbamate (as part of a compassionate use program). Upon instituting felbamate, valproate dosage was reduced to 500 mg/d and phenobarbital to 200 mg/d. Felbamate dosage was titrated to approximately 50 mg/kg/d over three weeks. In this patient, plasma phenobarbital concentrations increased from 48 micrograms/mL to 68 micrograms/mL, at which point the patient was hospitalized because of clinically significant neurotoxicity. Phenobarbital dosage was subsequently reduced to 150 mg/d; this resulted in phenobarbital trough concentrations of 60 micrograms/mL. CONCLUSIONS: Felbamate has been shown previously to interact with multiple other anticonvulsant medications, including valproate, phenytoin, and carbamazepine. Felbamate appears to decrease the clearance of valproate, phenytoin, and carbamazepine epoxide to a significant extent, an effect that may be the result of inhibition of the metabolism of these compounds. Carbamazepine plasma concentrations have been demonstrated to decrease following administration of felbamate, suggesting metabolic induction. It is reasonable to suggest that based on these findings and the observations in our patient, felbamate comedication may result in clinically significant increases in plasma phenobarbital concentrations. It would seem prudent, therefore, when initiating or adjusting felbamate therapy in patients receiving this drug combination, to monitor phenobarbital plasma concentrations.

Birth and migration of neurons in the central posterior/prepacemaker nucleus during adulthood in weakly electric knifefish (Eigenmannia sp.).

In contrast to mammals, fish maintain their capacity to generate neurons in the central nervous system even during adulthood for prolonged periods of life. By employing immunohistochemical, autoradiographic, and electron microscopic techniques, we studied such a postnatal neurogenesis within the complex of the central posterior/prepacemaker nucleus (CP/PPn) in knifefish (Eigenmannia sp.), a weakly electric teleost. The CP/PPn is a bilateral cluster of neurons in the thalamus. It controls frequency modulations of the electric organ discharge as they are used during social interactions. In the CP/PPn region adjacent to the wall of the third ventricle ("ventricular zone"), cells are born continuously and at high rates. They undergo multiple cell divisions before differentiating into neurons. Concomitant with this development, the newborn neurons migrate toward lateral regions of the CP/PPn. In the course of this lateral migration, they appear to acquire immunological and morphological characteristics that are typical for mature CP/PPn neurons. We hypothesize that at least some of the newly generated cells develop finally into functional CP/PPn neurons.

Long-term seizure outcome in 74 patients with Lennox-Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup.

PURPOSE: To determine if using more stringent criteria for cryptogenic Lennox-Gastaut syndrome (LGS) would result in an improved prognosis for that group. Cryptogenic, symptomatic, and non-cryptogenic LGS patients without etiology (indeterminate) were compared with respect to seizure and cognitive outcome. METHODS: Retrospective chart review was performed on 245 patients seen at the Mayo Clinic Rochester from 1976 to 1997, with a diagnosis of either LGS or slow spike wave on EEG. LGS was confirmed in 107 (64 male, 43 female) patients. This group was divided into cryptogenic, symptomatic, and indeterminate groups containing 23, 47, and 37 patients, respectively. In this study, cryptogenic patients all had normal development before onset of LGS, absence of dysmorphic features, normal neurologic examination, and normal magnetic resonance (MRI) brain imaging. Of the 107 patients, 74 had >/=3 years of follow-up. RESULTS: LGS onset in the 107 patients occurred at a median age of 4.0 years (range, 0.6-28.9 years). When last seen, 63% of those with symptomatic LGS had more than three seizures a day compared with 50% of cryptogenic and 34% of indeterminate patients. The most common seizure types were tonic (77%), atypical absence (61%), and generalized tonic-clonic (56%). Only three patients, all part of the indeterminate group, were seizure free at last follow-up. CONCLUSIONS: Using stringent criteria in defining the cryptogenic subgroup resulted in no significant difference in seizure outcome. Individuals with a normal cognitive outcome did not segregate into one etiologic subgroup, but did have LGS onset at an older age.