Liliequist's membrane in minimally invasive endoscopic neurosurgery

Liliequist's membrane, an arachnoid condensation extending from the upper border of the dorsum sellae to the anterior edge of the mammillary bodies and formerly a relatively insignificant structure, has been found to be extremely important in the neuroendoscopic management of hydrocephalus. Failure to open this membrane can lead to the failure of third ventriculostomies. Clin. Anat. 11:187–190, 1998. © 1998 Wiley-Liss, Inc.     

Medulloblastoma in childhood: revisiting intrathecal therapy in infants and children

Introduction

Intrathecal chemotherapy is being explored in medulloblastoma in pre-school children as part of brain-sparing strategies and as an alternative to unacceptably neurotoxic cranio-spinal radiotherapy. The range of drugs suitable for this route of administration is restricted by the lack of research evidence of pharmacological suitability and efficacy of other drugs in medulloblastoma.

Methods

Ideal clinical, biological, physicochemical and pharmaceutical properties for intrathecal administration were defined through literature review of pharmaceutical texts, Medline, Embase and consulting the manufacturers. A total of 126 chemotherapy agents were assessed against these criteria by searching the academic domain of pharmaceutical texts, computer databases and consultation with manufacturers.

Results

Of the 126 candidate drugs, 99 were rejected because of documentation of their irritant nature, neurotoxicity and requirement for hepatic activation in standard pharmaceutical texts. Fifty were rejected for a single identifiable reason including, neurotoxicity (n = 24), irritant (n = 15), needs enzyme activation (n = 5), clinical evidence of intrathecal neurotoxicity (n = 4) and no evidence of tumour-specific efficacy (n = 2). Where two reasons were cited the justifications were: neurotoxic and irritant (n = 3) and needs activation and systemic administration results in equivalent concentration (n = 1). Twenty-seven drugs remained of which 12 were selected as eligible for further clinical investigation, and 15 were selected for further pre-clinical investigation.

Conclusions

The pre-determined criteria were not applicable, in their entirety, in the majority of drugs, due to lack of information in the academic domain, emphasising the importance of a more open approach for sharing basic drug information. The prioritised list of 12 candidate drugs for clinical trial and 15 for pre-clinical investigation justify that a concerted research effort in this area of practice is made.     

Neuroendoscopy in the premature population

The population born prematurely is particularly prone to hydrocephalus. Shunting techniques, whilst still the gold standard, have considerable failure rates and contribute significant morbidity and mortality. The role of neuroendoscopic techniques in the treatment of such patients is explored, and a series of 19 patients born prematurely and operated on neuroendoscopically before their 1st birthdays is described. Received: 8 May 1998     

ERBB-2 gene overexpression and amplification in uterine sarcomas

BACKGROUND: The aim of this study was to determine ERBB-2 (HER-2/neu) gene alterations in different subtypes of uterine sarcomas. METHODS: After central review, representative biopsies were immunohistochemically stained and semiquantitatively scored as negative, weakly (1+), moderately (2+), or strongly (3+) positive. Subsequently, fluorescence in situ hybridization (FISH) was performed on cases with 2+ and 3+ expression. RESULTS: Seventy tumors (52 primaries and 18 recurrent) were evaluated. All 10 adenosarcomas, 21 endometrial stromal sarcomas, and 10 leiomyosarcomas were negative both in the primary and recurrent setting. Twenty-two primary carcinosarcomas were scored. The epithelial component was negative/1+ in 16 (73%), 2+/3+ in five (22.5%) tumors, and could not be evaluated in one case (4.5%), whereas the sarcoma component stained negative/1+ in 21 cases (95.5%) and 3+ (4.5%) in one case. In two recurrent carcinosarcomas, the epithelial component stained 3+ in both cases, whereas the sarcoma component scored negative and 1+. Amplification of the ERBB-2 gene as determined by FISH was observed in 3/7 (43%) carcinosarcomas with 2+ or 3+ overexpression, resulting in an overall 3/22 (14%) amplification rate. One out of four undifferentiated uterine sarcomas stained 2+. ERBB-2 immunopositivity (3+) and ERBB-2 amplification by FISH were confirmed in the recurrent tumor, resulting in a gene amplification rate of 1/4 in undifferentiated uterine sarcomas. CONCLUSION: The current results suggest absence of ERBB-2 overexpression in uterine leiomyosarcoma, uterine adenosarcoma, and endometrial stromal sarcoma, whereas the ERBB-2 gene might have a biologic role in uterine carcinosarcoma and undifferentiated uterine sarcomas.     

Selective dorsal rhizotomy as an alternative to intrathecal baclofen pump replacement in GMFCS grades 4 and 5 children

Background

Conventionally, selective dorsal rhizotomy (SDR) has been reserved for ambulant children and implantation of intrathecal baclofen (ITB) pump for non-ambulant children with cerebral palsy. Rather than replacing the ITB pump in selected Gross Motor Function Classification System (GMFCS) grades 4 and 5 children, we elected to undertake SDR instead. We discuss the rationale and outcomes.

Objectives

To assess if children with severe spasticity treated with long-term ITB pump would benefit from SDR as alternative procedure to replacement of ITB pump.

Method

This study is a prospective review of ten children with severe spasticity. Indications for ITB pump replacement in 3/10 children were previous ITB pump infection and the remaining seven were nearing depletion of drug delivery system. Pre- and post-SDR mean modified Ashworth scores, assessment of urological function and survey of parent/carer satisfaction were undertaken.

Result

Mean Ashworth score reductions post-SDR in the lower limbs and upper limbs were 2.4 and 1.70, respectively. An improvement in urological function was also noticed in 27 % of patients. Overall, 90 % of parents/carers felt that functional outcome with SDR was improved compared with that of ITB.

Conclusion

SDR in comparison to ITB in this subgroup is cheaper, less intrusive by avoiding refills/replacement and found to be more effective than ITB in reducing spasticity and providing ease for nursing care. We therefore suggest that consideration should be given to SDR as an alternative in patients previously implanted with ITB systems complicated by infection or nearing end of battery life.

     

Aggressive male APP23 mice modeling behavioral alterations in dementia

In addition to cognitive deterioration, Alzheimer's disease patients exhibit behavioral and psychological signs and symptoms of dementia. Behavioral alterations are a major source of caregiver stress and an important contributor in the decision to institutionalize patients. The amyloid precursor protein (APP) 23 transgenic mouse model develops amyloid plaques from the age of 6 months onward and exhibits tau pathology, which is absent in most other amyloid-based models. Besides mimicking the demented patients' memory deficits, these transgenic mice present with various behavioral disturbances, thereby approximating the clinical situation remarkably well. Using an isolation-induced/resident-intruder paradigm of aggression, the authors revealed increased aggressiveness in male APP23 mice at the ages of 6 and 12 months. The presence of aggressive disturbances in this valuable mouse model opens perspectives to evaluate aggression-modulating therapies.     

Mood and male sexual behaviour in the APP23 model of Alzheimer's disease

Alzheimer's disease is characterised by both cognitive deterioration and the development of a wide range of neuropsychiatric disturbances, among which affective disturbances, stereotyped behaviour, dietary hyperactivity and changes in sexual behaviour. The transgenic APP23 mouse models Alzheimer's disease and has shown to be a unique tool in the study of this condition. APP23 mice develop, next to the age-dependent cognitive decline, also a range of behavioural problems, such as circadian activity disturbances and increased aggression, in analogy with the dementing patients. The present study aimed to investigate whether this model also develops mood disturbances and changes in sexual behaviour. Using two behavioural despair paradigms and the sucrose preference test, we did not find evidence for the development of depression-related behaviours. A sophisticated protocol was neither able to unravel changes in male sexual behaviour between APP23 and WT mice. The present study nevertheless provides evidence that the APP23 mice are more anxious and fearful in comparison with control littermates, which opens perspectives to future treatment studies.     

Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study

OBJECTIVE: Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n = 205), frontotemporal dementia (FTD) (n = 29), mixed dementia (MXD) (n = 39) and dementia with Lewy bodies (DLB) (n = 23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). RESULTS: In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. CONCLUSIONS: Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology.     

The role of neuroendoscopy in the management of brain tumours

Neuroendoscopy is increasingly used in the management of brain tumours and tumour related hydrocephalus and this study reviews the efficacy of neuroendoscopic interventions in this unit in patients with brain tumours. A series of 87 neuroendoscopic operations carried out in 77 patients with brain tumours over a 6-year period is reported. The age range of the patients was from 5 months to 70 years (median 13 years). In 56 cases (64%) presentation was with a newly-diagnosed tumour and hydrocephalus. The majority of the remaining patients had varying degrees of worsening hydrocephalus on the background of a previously diagnosed tumour. Neuroendoscopic third ventriculostomy (NTV) was successful in relieving hydrocephalus in the short term in 63/66 cases (95%) and in the longer term in 55/66 cases (83%). Neuroendoscopic tumour biopsies were successful in providing a tissue diagnosis in 17/28 cases (61%) and four extensive and three partial resections of tumour were carried out. There were two deaths within 30 days of the procedure with only one of these, secondary to intraventricular haemorrhage, directly related to neuroendoscopy. Few significant complications were noted otherwise. For selected intraventricular and paraventricular tumours neuroendoscopy offers the opportunity to combine relief of hydrocephalus with tumour biopsy and sampling of CSF in a single procedure.