Fragile X syndrome with FMR1 and FMR2 deletion.
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We report a 13 year old boy with fragile X syndrome resulting from a de novo deletion of the FMR1 and FMR2 genes extending from (and including) DXS7536 proximally to FMR2 distally. The patient has severe developmental delay, epilepsy, and behavioural difficulties, including autistic features. He has epicanthic folds, in addition to facial features typical of fragile X syndrome, and marked joint hypermobility. We compare our patient to the three other cases reported in which both FMR1 and FMR2 are deleted. This case has the smallest deletion reported to date. All four patients have epilepsy and a more severe degree of mental retardation than is usual in fragile X syndrome resulting from FMR1 triplet repeat expansion. Three of the patients have joint laxity and two have epicanthic folds. We suggest that these features, in particular severe developmental delay and epilepsy, may form part of the characteristic phenotype resulting from deletion of both FMR1 and FMR2 genes. The diagnosis in this case was delayed because routine cytogenetics showed no abnormality and standard molecular tests for FMR1 triplet repeat expansion (PCR and Southern blotting) failed. Further DNA studies should be undertaken to investigate for a deletion where clinical suspicion of fragile X syndrome is strong and routine laboratory tests fail. (+info)
Injuries and noncommunicable diseases: emerging health problems of children in developing countries.
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The present article identifies, for children living in developing countries, the major causes of ill-health that are inadequately covered by established health programmes. Injuries and noncommunicable diseases, notably asthma, epilepsy, dental caries, diabetes mellitus and rheumatic heart disease, are growing in significance. In countries where resources are scarce it is to be expected that increasing importance will be attached to the development and implementation of measures against these problems. Their control may benefit from the application of elements of programmes directed against infectious, nutritional and perinatal disorders, which continue to predominate. (+info)
Efficacy of statin therapy: possible effect of phenytoin.
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Statins are currently the most widely prescribed lipid-lowering drugs. Individual statins are known to be metabolised by the CYP3A4 isoform of the cytochrome P450 system. The effect of CYP3A4 inducers such as phenytoin on the metabolism and efficacy of these agents is unknown. We report a patient with familial hypercholesterolaemia and epilepsy in whom the introduction and subsequent discontinuation of phenytoin were associated with marked changes in the lipid response to treatment with simvastatin and atorvastatin. The serum activity of gamma-glutamyl transpeptidase may have acted as a marker of microsomal induction by phenytoin, since it rose markedly when phenytoin was introduced and returned to normal after it was discontinued. (+info)
Experience with vagus nerve stimulation for intractable epilepsy: some questions and answers.
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Vagus nerve stimulation (VNS) is gaining increasing popularity and credibility as a treatment option for patients with intractable epilepsy. VNS is a relatively recent innovation, however, and like many other incipient developments, it has engendered a number of unresolved controversies and perplexities. Limitations in our current understanding of how VNS works lie at the crux of these uncertainties. In this article, we present our clinical experience with VNS and review the fundamental issue which remain unsettled, such as the mechanism of VNS action, the factors underlying variability in patient outcome, and the selection of ideal candidates for VNS therapy. Although many enigmas persist, VNS has proven to be a safe, feasible, and potentially effective method of reducing seizures in select patient populations. It offers several advantages over extant treatments and, as a result, holds much promise for future therapy of medically refractory epilepsy. (+info)
Group I mGluR-mediated silent induction of long-lasting epileptiform discharges.
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Picrotoxin, an antagonist of GABA(A) receptor-mediated activity, elicited 320- to 475-ms synchronized bursts from the CA3 region of the guinea pig hippocampal slice. The addition of the selective group I metabotropic glutamate receptor (mGluR) agonist (S)-3, 5-dihydroxyphenylglycine (DHPG, 50 microM; 20- to 45-min application) gradually increased the burst duration to 1-4 s; this effect persisted 2-3 h after agonist removal. To determine whether the induction of this long-lasting effect required ongoing synchronized activity during mGluR activation, DHPG application in a second set of experiments took place in the presence of CNQX and (R, S)-CPP, antagonists of AMPA/kainate and NMDA receptors, respectively. In these experiments, synchronized bursting was silenced during the mGluR agonist application, yet after wash out of the DHPG and the ionotropic glutamate receptor (iGluR) blockers, epileptiform discharges 1-10 s in duration appeared and persisted at least 2 h after wash out of the mGluR agonist. The potentiated bursts were reversibly shortened by application of 500-1,000 microM (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) or (S)-4-carboxyphenylglycine (4CPG), agents with group I mGluR antagonist activity. These data suggest that transient activation of group I mGluRs, even during silencing of synchronized epileptiform activity, may have an epileptogenic effect, converting brief interictal-length discharges into persistent seizure-length events. The induction process is iGluR independent, and the maintenance is largely mediated by the action of endogenous glutamate on group I mGluRs, suggesting that autopotentiation of the group I mGluR-mediated response may underlie the epileptogenesis seen here. (+info)
Triple-technique (MR imaging, single-photon emission CT, and CT) coregistration for image-guided surgical evaluation of patients with intractable epilepsy.
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Ictal and interictal single-photon emission CT (SPECT) play an increasingly important role in the surgical evaluation of patients with epilepsy. We present a method of coregistration of MR, SPECT, and CT images to correlate structural data (MR imaging), blood flow changes (SPECT), and location of subdural electrodes (CT) for patients undergoing image-guided surgical treatment of epilepsy. MR-SPECT root mean square (rms) mismatch distances were 2.1 to 2.5 mm, and MR-CT rms mismatch distances were 1.0 to 4.5 mm. Coregistration assisted in image-guided placement of subdural electrodes and in surgical resection of the suspected epileptogenic focus. (+info)
Pyridoxine dependent epilepsy: a suggestive electroclinical pattern.
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AIMS: To determine if there is an electroencephalographic pattern suggestive of pyridoxine dependent epilepsy that could be used to improve the chances of early diagnosis. METHODS: A retrospective study was made of all the clinical records and electroencephalograms of neonates identified with pyridoxine dependent seizures between 1983 and 1994, at this hospital. Neonates whose seizures began after more than 28 days of life were excluded; in all, five patients from four families were studied. Follow up ranged from 2 to 10 years. RESULTS: A history of miscarriage and neonatal death during an epileptic seizure had occurred in the siblings of two families. One mother reported rhythmic movements of her child during the last month of pregnancy. At birth, all babies were hypotonic; four had decreased visual alertness. All babies were agitated, irritable, jittery, hyperalert, and exhibited sleeplessness and a startle reaction to touch and sound. Age of onset of seizures varied from 30 minutes to 3 days. Seizures of various types were recorded in all cases on EEG tracings, including spasms, myoclonic seizures, partial clonic, and secondary generalised seizures. Burst-suppression patterns occurred in three cases, and a combination of continuous and discontinuous patterns in two others. Bilateral high voltage delta slow wave activity was observed in four patients. Psychomotor delay was severe in three patients, moderate in one, and mild in one. CONCLUSIONS: There is an identifiable EEG pattern that is highly suggestive of pyridoxine dependent epilepsy. Pyridoxine dependent epilepsy is probably underdiagnosed. (+info)
Electrophysiological studies of human face perception. I: Potentials generated in occipitotemporal cortex by face and non-face stimuli.
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This and the following two papers describe event-related potentials (ERPs) evoked by visual stimuli in 98 patients in whom electrodes were placed directly upon the cortical surface to monitor medically intractable seizures. Patients viewed pictures of faces, scrambled faces, letter-strings, number-strings, and animate and inanimate objects. This paper describes ERPs generated in striate and peristriate cortex, evoked by faces, and evoked by sinusoidal gratings, objects and letter-strings. Short-latency ERPs generated in striate and peristriate cortex were sensitive to elementary stimulus features such as luminance. Three types of face-specific ERPs were found: (i) a surface-negative potential with a peak latency of approximately 200 ms (N200) recorded from ventral occipitotemporal cortex, (ii) a lateral surface N200 recorded primarily from the middle temporal gyrus, and (iii) a late positive potential (P350) recorded from posterior ventral occipitotemporal, posterior lateral temporal and anterior ventral temporal cortex. Face-specific N200s were preceded by P150 and followed by P290 and N700 ERPs. N200 reflects initial face-specific processing, while P290, N700 and P350 reflect later face processing at or near N200 sites and in anterior ventral temporal cortex. Face-specific N200 amplitude was not significantly different in males and females, in the normal and abnormal hemisphere, or in the right and left hemisphere. However, cortical patches generating ventral face-specific N200s were larger in the right hemisphere. Other cortical patches in the same region of extrastriate cortex generated grating-sensitive N180s and object-specific or letter-string-specific N200s, suggesting that the human ventral object recognition system is segregated into functionally discrete regions. (+info)