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Biomedical subjects

W Harkness

Publications and source records attributed to W Harkness.

At least 19 recordsLinked to original sources
PubMed2005

Psychopathology in children with epilepsy before and after temporal lobe resection.

The aim of this study was to establish the rate and spectrum of psychiatric disorder among children before and after temporal lobe surgery for epilepsy. Data were examined for associations between psychopathology and seizure outcome following surgery, or association between psychopathology and other variables, such as laterality of lesion, sex, cognitive level, and underlying pathology. Participants were 60 children (35 males, 25 females) who had focal seizures of temporal lobe origin and who had undergone temporal lobe resection between 1992 and 1998; mean age at time of operation 10 y 7 mo, (SD 4 y 11 mo) range 7 mo to 17 y 11 mo. Mean length of follow-up was 5.1 years (SD 2.3, range 2 to 10 y). Twenty-eight (47%) children had undergone right temporal lobectomy. Diagnosis of a psychiatric disorder was present in 50/60 (83%) children at some point, with high rates of psychiatric comorbidity. Common childhood psychiatric disorders of attention-deficit-hyperactivity disorder, oppositional defiant disorder/conduct disorder, and emotional disorders were present in about 25% of children. Disorders rarely seen in the general child population were over-represented: disruptive behaviour disorder--not otherwise specified (30/60 [50%]), and pervasive developmental disorder (autistic spectrum disorder; 23/60 [38%]). there was no significant relationship between pathology, sex, seizure frequency, or postoperative seizure outcome and psychiatric disorder, other than for pervasive developmental disorder. The same proportion of children had psychiatric diagnoses pre- and postoperatively (43/60 [72%] and 41/57 [72%] respectively). Although mental health problems are common in children undergoing temporal lobe resection, there are few predictors of psychiatric outcome following epilepsy surgery. Parents require counselling on these issues in the preoperative work-up.

Adolescent↗
PubMed2005

Mcm2 labelling of balloon cells in focal cortical dysplasia.

Balloon cells (BC) are the prominent and defining cellular component of type IIB Focal Cortical Dysplasia (FCD), a common cause of focal epilepsy in patients undergoing surgical treatment. BC are considered immature cells of uncommitted cellular differentiation having immunophenotypical characteristics of both neurones and glia. They are often located in the lower cortical layers and white matter underlying the dysplastic cortex, suggesting migratory arrest during development. We investigated the proliferative potential of BC in 15 cases of FCD from patients with a wide range of ages using immunohistochemistry for Mcm2 (mini chromosome maintenance protein) and Ki67. In the majority of cases, BC showed Mcm2 nuclear positivity. In addition, cells with intermediate neuronal-glial characteristics were labelled whilst the dysmorphic or hypertrophic pyramidal neuronal components of FCD were not. Ki67 labelled only occasional BC. These findings support the view that BC cells represent a pool of less differentiated glial cells with proliferative capacity which may have potential for delayed neuronal differentiation. Furthermore, as Mcm2 specifically identifies BC populations, this marker may be of diagnostic value in the subtyping of FCD lesions in patients with epilepsy.

Adolescent↗
PubMed2003

MRI study of the natural history and risk factors for pseudomeningocoele formation following postfossa surgery in children.

Surgical approaches to the posterior fossa may be complicated by pseudomeningocoele formation. We report on its natural history and risk factors for its formation, as seen on serial MRI postoperatively in children with posterior fossa tumours. In a retrospective study of 84 children undergoing surgery for posterior fossa tumours, 13 (16%) developed clinically apparent pseudomeningocoeles. On postoperative MRI, pseudomeningocoeles were apparent in 34 (41%) patients at 1-5 days, but in only four patients at 10-15 months postsurgery. There was a progressive decrease in the mean depth of pseudomeningocoele measured from the MRI scans postoperatively. Patients with pseudomeningocoeles were more likely to have a postoperative CSF leak from the wound (39 v. 13%), lumbar punctures or lumbar drains (54 v. 25%), wound re-closures (23 v. 1%) and prolonged hospital stay (19.9 v. 14.5 days). On multivariate analysis, patients with pseudomeningocoeles were also more likely to have undergone a suboccipital craniectomy than those without pseudomeningocoeles (69 v. 38%). Postoperative pseudomeningocoele formation following posterior fossa surgery is more apparent radiologically than clinically, but there is clinical and radiological evidence that pseudomeningocoeles gradually resolve over the postoperative period. The risk of pseudomeningocoele formation is increased by performing a suboccipital craniectomy and there is an association with increased CSF leaks, needing re-closure of the wounds.

Adolescent↗
PubMed2003

Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence.

Hemispherectomy has been performed in the treatment of epilepsy in association with hemiplegia for over 50 years. However, the optimal timing of surgery with respect to age at presentation and the influence of underlying pathology on outcome is only slowly emerging. This study reports on the clinical course and outcomes of 33 children who underwent hemispherectomy at Great Ormond Street Hospital, London, between 1991 and 1997. Age at surgery was 0.33-17 years (median 4.25) with 1-8 years follow-up (median 3.4). The underlying pathology was developmental in 16 (10 hemimegalencephaly, two polymicrogyria, two focal cortical dysplasia, one diffuse cortical dysplasia and one microdysgenesis), acquired in 11 (six middle cerebral artery infarct, three post encephalitis/trauma, and one each of hemiconvulsion-hemiplegia epilepsy and perinatal ischaemic insult) and progressive in six children (four Rasmussen encephalitis, two Sturge-Weber syndrome). At follow-up, 52% were seizure free, 9% experienced rare seizures, 30% showed >75% reduction in seizures and 9% showed <75% seizure reduction or no improvement. Seizure freedom was highest in those with acquired pathology (82%), followed by those with progressive pathology (50%) and those with developmental pathology (31%). However, seizure freedom, rare seizures or >75% reduction in seizures occurred in 100% of those with progressive pathology, 91% of those with acquired and 88% of those with developmental pathology, indicating a worthwhile seizure outcome in all groups. Hemiplegia remained unchanged following surgery in 22 out of 33 children, improved in five and was worse in six. No significant cognitive deterioration or loss of language occurred, and four children showed significant cognitive improvement. Behavioural improvement was reported in 92% of those who had behaviour problems pre-operatively.

Adolescent↗
PubMed2002

Correlation of SPECT with pathology and seizure outcome in children undergoing epilepsy surgery.

SPECT can be used to image regional cerebral blood flow (rCBF) and has been shown to help localize the seizure focus in partial epilepsies as part of the presurgical evaluation. Few studies have explored the possible relation between preoperative SPECT and underlying pathology, or any relation to postsurgical outcome. In this study preoperative ictal and interictal rCBF in relation to the histopathological diagnosis and outcome in a series of 35 children (24 females, 11 males; mean age 9.6 years, age range 11 months to 18 years) who had undergone resective surgery for epilepsy were retrospectively evaluated. A correlation between ictal hyperperfusion and the underlying responsible pathology was shown, with a consistent ictal increase in perfusion in developmental pathologies and Rasmussen's encephalitis, and consistent interictal hypoperfusion in hippocampal sclerosis (HS). No rCBF study parameter appeared to relate to outcome but in the group with HS the best outcome was seen in those with localizing ictal rCBF. The varied group of pathologies from hemispherectomy had excellent outcome but the SPECT findings had little to contribute over the abnormalities detected on MRI. In conclusion, rCBF studies remain a useful presurgical investigation in children with partial epilepsy, especially where HS, cortical dysplasia, or inflammatory disease are the underlying pathology. However, rCBF studies add little to the investigation of children with seizures secondary to benign tumours or cerebral infarcts, or where hemispherectomy is the likely preferred surgical option.

Adolescent↗
PubMed2002

Metastatic infiltration of the dental pulp by medulloblastoma.

Medulloblastoma is an infratentorial primitive neuroectodermal tumour. It is the most commonly occurring brain tumour of childhood, accounting for 15-20% of all paediatric tumours. Extracranial metastasis is rare, but may involve the skeleton. Jaw lesions, however, have never been described. A case is reported of metastases of a medulloblastoma to the jaw including the dental pulp.

Bone Neoplasms↗
PubMed2001

Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults.

Although astrocytomas are the most common central nervous system tumours in all age groups, there is substantial evidence that tumours arising in young patients (< 25 years of age) do not have the same genetic abnormalities that are characteristic of tumours in older patients. Furthermore, novel, consistent changes have not been identified in astrocytomas in children and young adults. We analysed 13 malignant astrocytomas from young patients using comparative genomic hybridisation. Regions of genomic imbalance were identified in 10 cases. The most common recurrent copy number aberrations were loss of 16p (54% of cases), 17p (38%), 19p (38%), and 22 (38%) and gain on 2q (38%), 12q (38%), 13 (38%), 4q (31%), 5q (31%), and 8q (31%). Seven regions of high copy number amplification were observed at 8q21-22 (three cases), 7q22-23 (two cases), and 1p21-22, 2q22, 12q13-pter, 12q15-21, and 13q11-14 (one case each). This study provides evidence of new characteristic chromosomal imbalances from which potential candidate genes involved in the development of malignant astrocytoma in children and young adults may be identified.

Adolescent↗
PubMed2001

Gain of 1q and loss of 22 are the most common changes detected by comparative genomic hybridisation in paediatric ependymoma.

Ependymomas are the third most common brain tumour in the paediatric population. Although cytogenetic and molecular analyses have pinpointed deletions of chromosomes 6q, 17, and 22 in a subset of tumours, definitive patterns of genetic aberrations have not been determined. In the present study, we analysed 40 ependymomas from paediatric patients for genomic loss or gain using comparative genomic hybridisation (CGH). Eighteen of the tumours (45%) had no detectable regions of imbalance. In the remaining cases, the most common copy number aberrations were loss of 22 (25% of tumours) and gain of 1q (20%). Three regions of high copy number amplification were noted at 1q24-31 (three cases), 8q21-23 (two cases), and 9p (one case). Although there was no association with the loss or gain of any chromosome arm or with benign versus anaplastic histologic characteristics, the incidence of gain of 7q and 9p and loss of 17 and 22 was significantly higher in recurrent versus primary tumours. This study has identified a number of chromosomal regions that may contain candidate genes involved in the development of different subgroups of ependymoma.

Adolescent↗
PubMed2001

Microdysgenesis in temporal lobe epilepsy. A quantitative and immunohistochemical study of white matter neurones.

Microdysgenesis is a microscopic cortical malformation considered to act as a substrate for seizures in some patients with generalized epilepsy. It is also recognized to involve the temporal lobe in a proportion of patients with intractable temporal lobe epilepsy, but the incidence of this abnormality, its relationship to mesial temporal lobe sclerosis and relevance to epileptogenesis remain unknown. This is partly due to a lack of well-defined quantitative pathological diagnostic criteria. To begin to address these issues, we have carried out a rigorous quantitative analysis, using three-dimensional cell counting methods, of several components of microdysgenesis in temporal lobectomy specimens. White matter, cortical and layer I neuronal densities (NDs) were measured using immunohistochemistry for the neuronal markers neuronal nuclear antigen and calbindin D-28-K. Patients with a seizure-free outcome (Class I) showed significantly more microdysgenetic features including higher white matter ND (P < 0.05), particularly of small (<10 microm diameter) neurones (P < 0.01), higher layer I ND (P < 0.05) and increased numbers of Cajal-Retzius-like calbindin-positive neurones (P < 0.05). We also demonstrated that white matter ND was independent of the degree of temporal lobe gliosis as assessed by quantitation of glial fibrillary acidic protein-immunoreactive cells. These findings suggest that microdysgenesis may be a significant lesion in temporal lobe epilepsy in terms of post-surgical prognosis.

Adult↗
PubMed2000

Chemosensitivity in childhood brain tumours in vitro: evidence of differential sensitivity to lomustine (CCNU) and vincristine.

The aim of this study was to examine the range of sensitivity of a panel of short-term cultures derived from different types of malignant childhood brain tumours including medulloblastoma, ependymoma and glioblastoma multiforme to three cytotoxic drugs, lomustine (CCNU), vincristine (VCR) and procarbazine (PCB). Sensitivity was assessed using a modification of the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. Short-term cell lines derived from ependymomas were considerably more resistant to VCR than other types of childhood brain tumours, while cultures derived from supratentorial primitive neuroectodermal tumour (PNET) displayed marked sensitivity to both lomustine and VCR. Cultures from ependymomas, medulloblastoma and astrocytic gliomas had similar sensitivity to lomustine and PCB as cultures derived from adult malignant astrocytoma.

Adult↗
PubMed2000

Management of choroid plexus tumours in children: 20 years experience at a single neurosurgical centre.

OBJECTIVE: Tumours of the choroid plexus are rare tumours of neuro-ectodermal origin, accounting for less than 1% of all intracranial tumours. Most cases present in children less than 2 years of age. While choroid plexus carcinomas (CPC) are reported to have an extremely poor prognosis, choroid plexus papillomas (CPP) are generally regarded as benign tumours with a very favourable long-term outcome. Management dilemmas are associated with the choice of surgical procedure, tumour vascularity, the treatment of hydrocephalus and the value of adjuvant therapy. The objective of this study was to review our experience with this rare tumour over a 20-year period. METHODS: Patients were identified from the Great Ormond Street Neurosurgical Brain Tumour Database. Over a 20-year period (1979-1999), 34 children were identified with a choroid plexus tumour. There were 25 cases of CPP and 9 cases of CPC. A retrospective review of case notes, radiological imaging, operation reports and pathology was performed. RESULTS: The median age at presentation was 17 months (1-138) for CPP and 13 months (2-102) for CPC. There was no sex difference for CPP. However, 8 of the 9 CPCs were male (89%). A complete surgical resection was achieved in all 25 cases of CPP and in 3 cases of CPC (33%). The median survival for CPPs was 75.5 months (2-228), with a median follow-up of 73.5 months (2-228). The median survival for CPCs was 6 months (1-90), with a median follow-up of 6 months (1-90). CONCLUSION: With modern neurosurgical practise, a cure should be the aim for all children with CPP. There is no evidence that adjuvant therapy has any role in the primary management of these children. However, CPC still has an extremely poor prognosis, and the efficacy of adjuvant therapy remains to be established.

Age of Onset↗
PubMed2000

A sequential sampling scheme for detecting infestation levels of tracheal mites (Heterostigmata: Tarsonemidae) in honey bee (Hymenoptera: Apidae) colonies.

The introduction of parasitic honey bee mites, the tracheal mite, Acarapis woodi (Rennie) in 1984 and the Varroa mite, Varroa jacobsoni, in 1987, has dramatically increased the winter mortality of honey bee, Apis mellifera L., colonies in many areas of the United States. Some beekeepers have minimized their losses by routinely treating their colonies with menthol, currently the only Environmental Protection Agency-approved and available chemical for tracheal mite control. Menthol is also expensive and can interfere with honey harvesting. Because of inadequate sampling techniques and a lack of information concerning treatment, this routine treatment strategy has increased the possibility that tracheal mites will develop resistance to menthol. It is important to establish economic thresholds and treat colonies with menthol only when treatment is warranted rather than treating all colonies regardless of infestation level. The use of sequential sampling may reduce the amount of time and effort expended in examining individual colonies and determining if treatment is necessary. Sequential sampling also allows statistically based estimates of the percentage of bees in standard Langstroth hives infested with mites while controlling for the possibility of incorrectly assessing the amount of infestation. On the average, sequential sampling plans require fewer observations (bees) to reach a decision for specified probabilities of type I and type II errors than are required for fixed sampling plans, especially when the proportion of infested bees is either very low or very high. We developed a sequential sampling decision plan to allow the user to choose specific economic injury levels and the probability of making type I and type II errors which can result inconsiderable savings in time, labor and expense.

Animals↗
PubMed1999

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↗
PubMed1999

Surgical outcome in patients with epilepsy and dual pathology.

High-resolution MRI can detect dual pathology (an extrahippocampal lesion plus hippocampal atrophy) in about 5-20% of patients with refractory partial epilepsy referred for surgical evaluation. We report the results of 41 surgical interventions in 38 adults (mean age 31 years, range 14-63 years) with dual pathology. Three patients had two operations. The mean postoperative follow-up was 37 months (range 12-180 months). The extrahippocampal lesions were cortical dysgenesis in 15, tumour in 10, contusion/infarct in eight and vascular malformation in five patients. The surgical approach aimed to remove what was considered to be the most epileptogenic lesion, and the 41 operations were classified into lesionectomy (removal of an extrahippocampal lesion); mesial temporal resection (removal of an atrophic hippocampus); and lesionectomy plus mesial temporal resection (removal of both the lesion and the atrophic hippocampus). Lesionectomy plus mesial temporal resection resulted in complete freedom from seizures in 11/15 (73%) patients, while only 2/10 (20%) patients who had mesial temporal resection alone and 2/16 (12.5%) who had a lesionectomy alone were seizure-free (P < 0.001). When classes I and II were considered together results improved to 86, 30 and 31%, respectively. Our findings indicate that in patients with dual pathology removal of both the lesion and the atrophic hippocampus is the best surgical approach and should be considered whenever possible.

Adolescent↗
PubMed1999

Spontaneous intralesional haemorrhage in dysembryoplastic neuroepithelial tumours: a series of five cases.

Five patients with dysembryoplastic neuroepithelial tumour (DNT) showing extensive secondary haemorrhage, a finding not previously associated with these neoplasms, are described. The clinical presentations, neuroimaging findings, and histopathological features of these patients are reviewed. One patient, a previously asymptomatic 12 year old girl, presented with an acute intracerebral haemorrhage into a DNT. A further four young adults with histories of intractable partial and generalised seizures dating from childhood showed significant chronic haemorrhages within DNT, the MRI appearances in one patient giving a false impression of a cavernoma. Histopathology disclosed vascular abnormalities within these tumours which, together with other factors discussed, may have predisposed these tumours to haemorrhage.

Brain Neoplasms↗