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Biomedical subjects

H Cross

Publications and source records attributed to H Cross.

At least 19 recordsLinked to original sources

Posterior quadrantic dysplasia or hemi-hemimegalencephaly: a characteristic brain malformation.

INTRODUCTION: Posterior quadrantic dysplasia (PQD), a developmental malformation involving the temporal, parietal, and occipital lobes of one cerebral hemisphere, leads to intractable epilepsy. OBJECTIVE: To characterize the clinical features of 19 patients with PQD and analyze the postsurgical outcome of those who underwent resection of dysplastic tissue. METHODS: The extent and nature of the malformation were primarily assessed with high-resolution brain imaging. Fourteen patients underwent complete or partial temporoparieto-occipital resection or temporal resection associated with parieto-occipital disconnection. Postoperative follow-up period ranged from 8 months to 7 years. The authors used the Engel classification for postoperative outcome. RESULTS: All patients were sporadic. Clinical features included infantile spasms, partial seizures, mental retardation, mild hemiparesis, and visual field defects. Neuroimaging localized the malformation within the posterior cerebral quadrant contralateral to the neurologic deficit and demonstrated hemi-hemimegalencephaly in 14 of 19 patients and multilobar cortical dysplasia in 5 of 19 patients. The authors observed class I outcome in six patients. Two patients had class II and four patients had class III outcome. Class IV outcome was seen in two patients. After surgery, two patients developed mild hemiparesis, and two developed a visual field defect. CONCLUSIONS: Widespread cortical dysplasia is more frequent in the posterior quadrant. In our series, posterior quadrantic dysplasia represents either hemi-hemimegalencephaly or multilobar cortical dysplasia. Individuals with posterior quadrantic dysplasia share a spectrum of clinical features. The intractable epilepsy in these patients may be alleviated by a large quadrantic temporoparieto-occipital resection.

Adolescent↗

Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis.

Focal cortical dysplasia (FCD) and microdysgenesis (MD) are likely to represent abnormalities of radial neuronal migration during cortical development. We investigated the distribution of reelin-positive Cajal-Retzius cells, known to be important in the later stages of radial neuronal migration and cortical organization, in 12 surgical cases of both MD and FCD. Quantitation revealed significantly higher numbers of these cells in MD cases compared to controls. As the majority of cortical interneurones arise via tangential rather than radial migration, we studied the distribution and morphology of inhibitory interneuronal subsets immunolabelled for calbindin, parvalbumin and calretinin within these malformations. Frequent findings were a reduction of inhibitory interneurones in the region of FCD and abnormally localised hypertrophic or multipolar calbindin-positive interneurones in both FCD and MD. Neuropeptide Y immunostaining showed a striking increase in the density of the superficial plexus of fibres in both MD and FCD cases in addition to labelling of dysplastic neurones, which may represent an adaptive anti-convulsant mechanism to dampen down seizure propagation.

Adolescent↗

Treatment of Lennox-Gastaut syndrome.

BACKGROUND: The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and personality disorders. It occurs more frequently in males and onset is usually before the age of eight with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (for example hyperactivity, aggressiveness and autistic tendencies)and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time. OBJECTIVES: To compare the effects of pharmaceutical therapies used to treat Lennox-Gastaut syndrome in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialed (often as add-on therapy). SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (March 2003), MEDLINE (1966 to March 2003) and EMBASE (1980 to March 2003). In addition, we contacted pharmaceutical companies and colleagues in the field to ascertain any unpublished/ongoing studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) of the administration of drug therapy to patients with Lennox-Gastaut syndrome. DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (eg drop attacks), adverse effects and mortality. MAIN RESULTS: We found five RCTs, but were unable to perform any sort of meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes. REVIEWER'S CONCLUSIONS: The optimum treatment for Lennox-Gastaut syndrome remains uncertain and no study to date has shown any one drug to be highly efficacious; lamotrigine, topiramate and felbamate may be helpful as add-on therapy. Until further research has been undertaken clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects.

Age of Onset↗

A possible role for gap junctions in generation of very fast EEG oscillations preceding the onset of, and perhaps initiating, seizures.

PURPOSE: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. METHODS: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon-axon gap junctions between principal neurons, as supported by recent experimental data. RESULTS: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30-70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. CONCLUSIONS: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.

Animals↗

An intensive self care training programme reduces admissions for the treatment of plantar ulcers.

This paper describes, in detail, an intensive 14 day Self Care Training Programme that is conducted at Lalgadh Leprosy Services Centre in Nepal. An evaluation of the programme was undertaken in which hospital admission for infected plantar ulceration was the outcome measure. It was found that those who had undertaken the programme were less likely to have been admitted for hospital treatment in a 3-month follow-up period (chi 2 = 5.1, P = 0.02). An odds ratio of 1:1.8 (95% CI = 0.15-0.01) was also calculated. This paper presents an overview of the issues related to impairment, a description of the Self Care Training Programme, an analysis of the evaluation results and a discussion of the findings.

Adult↗

The mitosis of fibroblasts in cell culture is enhanced by binding GP IIb-IIIa of activated platelets on fibrinogen.

A fibroblast cell culture model enables us to measure the mitogenic ability mediated by growth factors released from stimulated platelets under different conditions. Simultaneously the growth factors secreted in the culture medium were determined. Cell mitotic rate was measured by incorporation of 3H-thymidine on days 3, 5 and 7 of culture. PDGF, TGF-beta, EGF and IGF-I were determined by Western blot. When fibroblasts were grown on surfaces precoated with a mixture of fibrinogen and thrombin-stimulated platelets, the 3H-thymidine uptake (196,645 +/- 56,864 cpm/ml) was increased, in comparison to fibroblasts grown on uncoated surfaces, in medium supplemented with FBS (28,855 +/- 7329 cpm/ml). Neither thrombin-stimulated platelets without fibrinogen nor fibrinogen alone had positive effects on the mitogenic activity of fibroblast. Growth factors were identified only in a culture medium in which the cells were grown on surfaces precoated with fibrinogen and thrombin-stimulated platelets. Blocking the platelet integrin GP IIb-IIIa inhibited the release of growth factors from thrombin-stimulated platelets and consecutively the stimulation of mitosis by fibrinogen and activated platelets was absent. Antibodies against the growth factors added to the medium suppressed the stimulation of cell mitosis. These results show that delivery of growth factors from platelets' secretory granules is dependent on binding of fibrinogen to GP IIb-IIIa.

Antibodies↗

The significance of bilateral EEG abnormalities before and after hemispherectomy in children with unilateral major hemisphere lesions.

The rate of seizure relief following hemispherectomy varies between 50 and more than 80%. There has been particular debate concerning the significance of bilateral electroencephalography (EEG) abnormalities in influencing prognosis. This study was set out to determine the frequency of bilateral EEG abnormalities and their relationship to underlying pathology and outcome. We investigated 28 children with unilateral hemisphere lesions, who underwent hemispherectomy. Interictal and ictal EEGs before and after hemispherectomy were reviewed. Post-operative outcome with respect to seizures was noted. Bilateral EEG abnormalities were seen in 75%, but were more common in children with malformations of cortical development than in patients with acquired cerebral lesions, and were found more often in interictal than in ictal records. Post-operative EEG abnormalities were variable and did not consistently predict outcome. Short-term outcome was similar, irrespective of aetiology. With longer term follow-up, only 47% of children with developmental abnormalities were still seizure-free in contrast to 77% of children with acquired abnormalities. Although the incidence of bilateral EEG abnormalities in patients with major unilateral hemisphere lesions is high, these findings alone should not preclude further consideration for hemispherectomy. Our findings emphasise that the aetiology of the lesion plays a major role in determining outcome.

Adolescent↗

Paradoxic reaction to lamotrigine in a child with benign focal epilepsy of childhood with centrotemporal spikes.

UNLABELLED: A girl aged 5 years developed nocturnal seizures (mouth twitching, salivation, anarthria, with right arm jerking and occasional secondary generalisation), with frequent focal sharp waves over the left centrotemporal region in her EEG, suggesting benign childhood epilepsy with centrotemporal spikes (BECTS). Seizures became diurnal and frequent, not modified by carbamazepine (CBZ) or valproate (VPA) but responding to VPA and lamotrigine (LTG) with recommended dosage schedules for this combination. Her school performance then deteriorated insidiously, with poor memory and concentration, clumsiness, stuttering, and emotional lability. After 4 months, new episodes, < or =10 per day, occurred. These lasted a few seconds; she stared into space, her jaw dropped, her head dropped to the right, and her eyelids flickered. She usually maintained awareness. Attacks were often provoked by blowing or sneezing. Ictal EEG showed anterior-predominant 3/s sharp-slow wave complexes lasting < or =8 s, with bilateral rolandic discharges interictally. Withdrawal of LTG resulted in rapid improvement in cognitive function and gradual remission of the new attacks. CONCLUSIONS: This appears to be a paradoxic reaction to LTG in the setting of BECTS.

Acute Disease↗

Bilateral parasagittal parietooccipital polymicrogyria and epilepsy.

We describe 9 patients with a bilateral malformation of cortical development, centered around the parasagittal and mesial aspects of the parietooccipital cortex, with magnetic resonance imaging findings suggestive of polymicrogyria. No familial distribution or etiologic factors were identified. Location in a watershed area between anterior and posterior cerebral arteries suggests postmigratory perfusion failure as the underlying cause. In most patients the malformation was detected by magnetic resonance imaging after computed tomography scans with 10-mm-thick sections were considered normal. Seizures, present in all, had started between the ages of 20 months and 15 years (mean, 9 years) and were intractable in 7. Complex partial seizures with or without minor automatisms were the most frequent ictal pattern. In only 4 patients these were preceded by symptoms indicating posterior onset. Interictal electroencephalograms showed both diffuse and bilateral parietooccipital or temporal abnormalities. The range of IQ scores indicated average intelligence to mild retardation. Several patients presented deficits on neuropsychological tasks requiring performance under time constraints, suggesting that the malformation may result in cognitive slowing. Early diagnosis of this malformation may be difficult because of the lack of neurological signs, relatively late seizure onset, difficulty in localizing seizure onset, and inability to recognize the cortical abnormality on computed tomography scans.

Adolescent↗

Plantar ulceration in patients with leprosy.

A controlled trial was implemented to investigate the hypothesis that plantar ulcer sites associated with leprosy, in subjects who were supplied with foot orthoses, would heal more quickly than those in a control group. The population was comprised of individuals with impairments associated with leprosy, living near a leprosy hospital in India. Ulcer area was compared in the two groups and assessed at three-monthly intervals from July 1993 to March 1994. At the March 1994 assessment 58% of ulcers in the experimental group had healed but only 14% in the control group. At this point patients in the control group were supplied with orthoses and three months later, in June 1994, 60% of the ulcers in the experimental group and 62% of ulcers in the control group had healed. The results of this study demonstrate that orthotic intervention can significantly reduce the duration of ulceration.

Adult↗

The efficacy of podiatric orthoses as an adjunct to the treatment of plantar ulceration in leprosy.

This study examines the outcome of a management approach to plantar ulceration secondary to leprotic neuropathy. Locally-available resources were used to produce podiatric orthoses which were supplied to an experimental group. The effects on healing time and quality of healing were compared with a control group. Both groups were ambulant (the programme sought not to interfere with socioeconomic independence). Using standard nonparametric methods of analysis, it was demonstrated that the effects on healing rate, attributed to the experimental intervention, were highly significant. Over a 7-month period, 57% of the experimental group ulcers healed, while only 12.5% of the control group ulcers healed. The experimental intervention also demonstrated a positive effect on the quality of ulcer healing. This effect was not reflected in the control group.

Foot Ulcer↗