Spike-triggered fMRI in reading epilepsy: involvement of left frontal cortex working memory area.

OBJECTIVE: To determine the origin of epileptiform activity in reading epilepsy (RE) and the association between these regions and regions activated by reading, and to assess brain morphometry in these areas. METHODS: In two subjects with RE, EEG was recorded inside the three tesla MRI while subjects read silently. Spike-triggered fMRI images were compared to baseline. In a second fMRI study, 30 seconds of silent reading was compared to visual fixation. Morphometry of these areas was assessed using curvilinear surface reconstruction. Left central sulcal patterns in three subjects with RE were compared to three subjects with idiopathic generalized epilepsy (IGE) and 12 normal controls. RESULTS: One subject with RE showed spike-related activity (17 spikes) in the left precentral gyrus, and bilaterally in the central sulcus and globus pallidus. The other showed no definite activation owing to low spike numbers (4 spikes). In both subjects, the block reading task recruited normal visual and language areas including the left posterior middle frontal gyrus. Two subjects with RE showed an unusual gyrus branching anteriorly off the left central sulcus. A similar sulcal pattern was seen in none of the subjects with IGE and only 1 of 12 controls. CONCLUSION: Spike activity overlapped with reading activity in the left middle frontal gyrus, a structure recruited during working memory cognitive tasks. The authors postulate that, because of a local structural anomaly, the spikes of reading epilepsy spread from working memory areas into adjacent motor cortex, activating a cortical subcortical circuit.

Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics.

OBJECTIVE: To study the clinical features and genetics of idiopathic generalised epilepsy (IGE) beginning in adult life. METHODS: Consecutive patients with IGE, defined as generalised seizures with spike or polyspike and wave on EEG, were studied in the setting of a first seizure clinic where an early postictal EEG record is part of the protocol. Patients were divided into two groups: "classical IGE" with onset before 20 years and inclusive of all the IGE subsyndromes recognised by the international classification; and "adult onset IGE", when seizure onset was at age 20 years or later. Seizure patterns, clinical features, and genetics of the adult onset group were examined. RESULTS: Of 121 patients with an electro-clinical diagnosis of IGE, 34 (28%) were diagnosed as adult onset IGE. The seizure patterns in these 34 cases were tonic-clonic seizures + absences (3), tonic-clonic seizures + myoclonus (6), and tonic-clonic seizures alone (25). Tonic-clonic seizures were often precipitated by alcohol or sleep deprivation. The proportion of affected first and second degree relatives did not differ between the classical and adult onset IGE groups. Twenty adult onset cases were treated with sodium valproate, four with other antiepileptic drugs, and 10 were untreated. Follow up of 32 of the 34 cases (for 31 (22) months (mean (SD)) showed that tonic-clonic seizures recurred in eight patients: five with identified provocative factors and three without. CONCLUSIONS: Adult onset IGE is a relatively frequent and benign disorder. Seizures are usually provoked and are easy to control. Patients in this age group may often be misdiagnosed as having non-lesional partial epilepsy. Early postictal EEG and sleep deprivation studies may improve the detection of these patients. Pedigree analysis suggests that adult onset IGE, like classical IGE, has a genetic aetiology.

Brain reorganisation in cerebral palsy: a high-field functional MRI study.

Early brain damage may induce alternative organisation of cortical brain functions. This may happen even if there is no damage to the cortex. We assessed a 15-year-old girl with a perinatal left-sided subcortical lesion without cortical damage by functional MRI at 3 Tesla. The patient had congenital hemiparesis, mirrored limb movements and normal language function. Functional MRI was used to assess language using orthographic-lexical retrieval and noun-verb generation tasks, and demonstrated right-sided language dominance. Functional MRI of motor function was assessed for both hands separately, by squeezing a rubber balloon. Both hand movements induced asymmetric bilateral activation of the motor cortex, with a predominance of contralateral activation. Language-associated activity is usually left-hemispheric, but was found in the undamaged right-sided hemisphere. Motor function was associated with the unusual pattern of bilateral cortical activation. The MR findings explain the clinical features and suggest widespread alternative cortical organisation in the presence of a focal lesion confined to subcortical structures.

Acute liver failure in pregnancy. A case report.

BACKGROUND: Liver disease in pregnancy can be grossly divided into those disorders coincidentally occurring during the pregnant state and hepatic diseases limited to pregnancy. Numerous infectious agents can result in acute hepatitis and include not only the hepatitis viruses--A, B, C and E--but herpesvirus and cytomegalovirus as well. Coxsackie B viruses can cause several clinical presentations, ranging from asymptomatic to mild febrile illness to myocarditis and meningitis. Rarely has coxsackievirus infection been associated with fulminant hepatic failure. CASE: A Coxsackie B virus infection resulted in acute liver failure in a gravid woman. The patient was managed expectantly, with resolution of the liver disease and delivery five weeks after discharge. CONCLUSION: The onset of hepatic disease is insidious, with only vague symptoms or minor complaints often heralding the progression to liver failure. A careful history, physical examination and appropriate diagnostic tests can help determine the etiology of hepatic disease and help decide whether expectant management of the gravid patient or immediate delivery is appropriate.

NAMS/Solvay Resident Essay Award. Relationship between estrogen, serotonin, and depression.

OBJECTIVE: A limited review of the medical literature was performed to determine whether there is an increase in the prevalence of depressive symptomatology in women undergoing menopause and whether this increase can be related to fluctuating levels of estrogen. In addition, we evaluate the possible effect that estrogen has on the concentrations of neurotransmitters, specifically serotonin, in the central nervous system and the subsequent impact on mood in peri- and postmenopausal women. Finally, we examine whether estrogen replacement therapy is efficacious in the treatment of depression during the climacteric. DESIGN: Limited MEDLINE review of the medical literature on depression in women, the evidence for a serotonergic role in depression, evidence linking estrogen to changes in serotonergic activity and evidence that estrogen therapy can improve depression. RESULTS: Depression is more common in women than in men and seems to be increased at times of changing hormone levels in women. The serotonergic system seems to play a major role in depression, although other neurotransmitters are also involved. Estrogen can alter not just serotonergic activity but also has an impact on the activity of several other neurotransmitters that might result in an antidepressant effect. At this time, estrogen therapy for the treatment of depression in peri- and postmenopausal women may be useful, but confirmatory studies are still lacking. CONCLUSIONS: There is suggestive evidence that estrogen therapy is appropriate treatment for mid-to-moderate depression in peri- and postmenopausal women.

Bilateral optic disk pallor after unilateral internal carotid artery occlusion.

Bilateral pallor of the optic disks was observed in a 52-year-old man after dissection of an internal carotid artery. Diffuse pallor of the ipsilateral optic disk reflected infarction of the ipsilateral optic nerve and "bow-tie" atrophy of the contralateral optic disk reflected infarction of the ipsilateral optic tract. The findings were due to an occlusion of the internal carotid artery proximal to the origin of the ophthalmic artery, resulting also in insufficiency in the area of supply of the anterior choroidal artery.

Use of ileocecal continent urinary reservoir in patients with previous pelvic irradiation.

OBJECTIVE: To assess the results of the use of ileocecal continent urinary reservoirs in patients with previous pelvic irradiation. METHODS: A retrospective analysis for morbidity and clinical outcome was undertaken for 37 female patients with prior therapeutic pelvic irradiation who underwent continent urinary diversion with a detubularized right colonic segment as the urinary reservoir, a plicated ileocecal valve as the continence mechanism, and a tapered distal ileum for efferent catheterization. RESULTS: Thirty-one patients had persistent or recurrent pelvic malignancies, 17 of whom had total pelvic exenteration and 14 had anterior exenteration. The remaining 6 patients had radiation-induced vesicovaginal fistulas without evidence of recurrence and underwent urinary diversion alone. Follow-up ranged from 2 to 33 months (median 11 months). Postoperative radiographic evaluation revealed no evidence of urinary extravasation. Of the 74 implanted ureters, 4 had reflux (5%), 2 developed stricture (3%), and 5 had mild to moderate hydronephrosis (7%). All patients achieved daytime continence with catheterization intervals of 3-8 hr (median 4 hr) and capacities of 200-1000 cc (median 500 cc). Nighttime continence was reported by 33 of 37 patients (89%). Reoperation was required in 3 patients (8%), 2 with stoma stenosis and 1 with difficulty in catheterization. CONCLUSIONS: The use of the ileocecal continent urinary reservoir in patients with previous pelvic irradiation achieves results comparable to those reported for nonirradiated patients, thus supporting its use in this select group of patients.

Human growth hormone (hGH) secretion in milk of goats after direct transfer of the hGH gene into the mammary gland by using replication-defective retrovirus vectors.

Mammary-specific promoters have been used in transgenic animals to limit transgene expression to the mammary gland. Gene therapy techniques to target just one organ for introduction of a foreign gene have also been demonstrated. We have directly infused replication-defective retroviruses encoding hGH into the mammary gland of goats via the teat canal during a period of hormone-induced mammogenesis. This resulted in the secretion of hGH into the milk when lactation commenced on day 14 of the regime. Levels of hGH in the milk were highest on the first day of lactation, averaging approximately 60 ng/ml, and declined to a plateau of 12 ng/ml from day 9 to day 15 of lactation. Thus we report targeting of replication-defective retroviruses to the mammary secretory epithelial cells to produce foreign proteins in the milk of ruminants.

A method for the generation of complex vibrotactile stimuli.

A method is described utilizing computer-generated sine wave data and purpose-built hardware to generate a complex vibrotactile stimulus. Two sine waves of different frequency were summed to produce a complex waveform with two temporal components, a high frequency component and a low frequency beat component. The computer-generated data points for each of the two component sine waves were downloaded to two banks of static memory in a dual synchronous arbitrary function generator. The data points in memory were fed to two 12-bit digital-to-analogue converters which sent the two analogue sine wave signals to a summing amplifier where the two sine waves were added. This method provides a complex waveform that can be gated on and off, has a fixed frequency ratio of the component sine waves and no phase drift between the component waves. Addition of the separate sine waves in a summing amplifier allows for easy alteration of the amplitude ratio of the sine waves. The output of the summing amplifier is sent to a feedback controlled mechanical stimulator, thereby allowing the stimulus to be presented to the skin of human subjects and experimental animals.

Dissemination of disease following transurethral resection for locally advanced prostate cancer.

Between 1974 and 1978, 258 patients with clinical Stage C adenocarcinoma of the prostate were treated at the U.T. M.D. Anderson Hospital in Houston. Of these, 208 were considered evaluable for a review of the impact of transurethral resection (TUR) on the dissemination of disease. After TUR, the incidence of disease progression was 38.9 per cent, compared with 36.4 per cent for patients who did not undergo TUR. There were significant differences in both incidence of progression (31.2% versus 55.6%, p = 0.002) and time to progression (p less than 0.001) when patients were divided into Stages C1 and C2 (presence or absence of pelvic side wall fixation) irrespective of their TUR status. Therefore, it appears that for patients with locally advanced prostate cancer, the degree of tumor burden and not the TUR status has a significant influence on disease progression.