Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

Chiari Malformation Presenting as Headaches Associated with Laughter.

Presentation We describe the case of a 5 year old boy, referred to our outpatient department with a one year history of headaches associated with laughter. Diagnosis Investigation with MRI Brain revealed Chiari Type 1 Malformation (CM-1), with cerebellar tonsillar descent of 19mm below the foramen magnum. Treatment He is being managed conservatively with serial neuroimaging and symptom monitoring. Discussion CM-1 is a hindbrain malformation characterised by ≥5mm herniation of the cerebellar tonsils.1,2 It is diagnosed radiographically, and is increasingly being detected incidentally.3,4 The natural history of asymptomatic patients is usually to remain asymptomatic, and symptomatic patients often show symptom improvement, particularly in paediatric populations.3,5 Neurosurgical interventions may be offered based on symptoms and radiographic findings, but carries a complication rate of 8.2%.6.

Concurrent management of suppurative intracranial complications of sinusitis and acute otitis media in children.

OBJECTIVE: Intracranial complications of sinusitis and acute otitis media (AOM) are rare but life-threatening events. In children with suppurative intracranial complications, concurrent neurosurgical and otolaryngological (ORL) intervention has been recommended to optimize outcomes. The aim of this study was to investigate outcomes following concurrent neurosurgical and ORL intervention. METHODS: A retrospective cohort study of children undergoing neurosurgical intervention for intracranial complications of sinusitis or AOM in two neurosurgical centres in Ireland was conducted. RESULTS: 65 children were identified. Mean age was 11.9 years. The most prevalent symptoms were headache, pyrexia, altered level of consciousness, facial swelling, and vomiting. Subdural empyema (n = 24, 36.9%) and extradural abscess (n = 17, 26.2%) were the most common complications. 54 underwent same admission ORL intervention; 47 (87%) were performed concurrently or earlier. For rhinogenic infections, 35 (64.8%) underwent endoscopic sinus surgery (ESS), 13 (24.1%) underwent frontal sinus trephine, and 5 (9.3%) underwent maxillary sinus washout alone. For otogenic infections, 10 (90.9%) underwent mastoidectomy and 7 (63.6%) underwent tympanostomy tube placement. 19 (29.2%) had post-operative neurological deficits, of which 2 (3.1%) were permanent. Streptococcus intermedius was the most common pathogen (n = 30, 46.2%). Concurrent intervention reduced the prevalence of residual collection (p = 0.018) and the need for revision neurosurgical intervention (p = 0.039) for sinogenic complications. The same trends did not achieve statistical significance for the otogenic group. Mortality was 0%. CONCLUSION: Intracranial complications of sinusitis and AOM are best managed in a specialist centre with multidisciplinary input. Concurrent ORL and neurosurgical intervention reduces abscess recurrence and requirement for revision neurosurgery in sinogenic complications and should represent the standard of care. ESS is the ORL modality of choice in experienced hands.

Primary External Ventricular Drains in the Management of Open Myelomeningocele Repairs in the Neonatal Setting in Ireland

Aim The aim of this study is to outline the role of primary external ventricular drains (EVD) in the management of open myelomeningoceles in the neonatal setting in Ireland. Methods Retrospective cohort study involving all infants who underwent open myelomeningocele repair in a teritary centre in Ireland between January 2009 and April 2016. Medical charts and laboratory data was reviewed on all infants meeting the inclusion criteria. Results One hundred and forty-three neonates underwent open myelomeningocele repair in the 6.5 year period. EVD were inserted at the time of primary wound closure in 19 cases (13%). EVD were used to aid in wound closure and as a primary method of cerebrospinal fluid (CSF) diversion. They remained in place for a median of 8 days, ranging from 1-22 days. All EVD, apart from one, in our series were replaced by a ventricular-peritoneal (VP) shunt at some stage. Conclusion EVD were used in 13% of cases of open myelomeningocele repairs from Jan 2009-Apr 2016 as a primary measure to aid in management. Compared to the cohort in whom an EVD was not inserted at the time of surgery, there was a decrease in the rate of infections. However, there was an increased rate of wound dehiscence/leak and a later need for VP shunt insertion.

Pre-operative neutrophil count and neutrophil-lymphocyte count ratio (NLCR) in predicting the histological grade of paediatric brain tumours: a preliminary study.

INTRODUCTION: The neutrophil-lymphocyte count ratio (NLCR) is an established prognostic marker for renal, lung and colorectal carcinomas and has been suggested to be predictive of histological grade and outcome in adult intracranial tumours. The purpose of this study was to determine whether a correlation of the pre-operative neutrophil count (NC) and NLCR with the final histological grade exists in paediatric intracranial tumours. METHODS: A retrospective analysis was undertaken at a single centre. Patients less than 18 years old at the time of surgery who underwent tumour-related procedures from 2006 to 2015 were included. Patients with recurrent tumours, previous bone marrow transplant and metastases were excluded. Pre-operative full blood counts (FBC), collected before the diagnosis of intracranial pathology and before administration of steroids, were matched with histological diagnosis for each patient. Post-operative FBC was also recorded, together with survival data where applicable. RESULTS: A total of 116 patients (74 male, 42 female; mean age, 8 ± 0.9 years) with a diagnosis of primary intracranial tumours had pre-operative FBC that could be matched to final histological grade. Pre-operative NC and NLCR were higher with increasing grade of tumour: grade 1 (NC 4.29 109/l, NLCR 2.26), grade 2 (NC 4.59 109/l, NLCR 2.38), grade 3 (NC 5.67 109/l, NLCR 2.72) and grade 4 (NC 6.59 109/l, NLCR 3.31). Patients with WHO grade 1 and 2 tumours pooled together had a lower NC (4.37 95% CI ± 0.67 109/l) compared to WHO grade 3 and 4 patients (6.41 95% CI ± 0.99 109/l, p = 0.0013). The NLCR was lower in grade 1 and 2 tumours (2.29 ± 0.59) (compared to grade 3 and 4 tumours; 3.20 ± 0.76) but this did not reach significance (p = 0.069). The subgroup of patients with pilocytic astrocytoma had a significantly lower NC when compared to patients with high-grade tumours (p = 0.005). Medulloblastoma and supratentorial PNET subgroups had significantly higher NC compared to the low-grade group (p = 0.033, p = 0.002). Post-operative NC was significantly higher in the high-grade tumours (p = 0.034), but no difference was observed for NLCR (p = 0.28). CONCLUSIONS: No evidence exists to support the correlation of pre-operative NC or NLCR to histological diagnosis in paediatric intracranial tumours. Our results indicate that a higher pre-operative NC/NLCR correlates with a higher histological grade of tumour. This suggests that immunological mechanisms may be involved in the pathogenesis of paediatric brain tumours, and a further prospective study is required to substantiate and expand these findings.

Is the endoscopic third ventriculostomy success score an appropriate tool to inform clinical decision-making?

INTRODUCTION: The endoscopic third ventriculostomy success score (ETVSS) is a model, which provides each patient with a prediction of the outcome of endoscopic third ventriculostomy. The objective of this study was to determine if there is clinical value to the use of the ETVSS in the decision for ETV. METHODS: Prospectively collected data on all ETV procedures with the Republic of Ireland in children ≤16 years of age, totalling 112, from 2008 to 2014 was analysed. The percentage chance of success at six months was retrospectively calculated according to the ETVSS. A multivariable model, comprising the risk factors from the ETVSS - age, aetiology and previous shunt - was created and its performance compared to that of the ETVSS. RESULTS: The ETVSS achieved an AUC of 0.61 (95% CI: 0.49-0.71) with a sensitivity and specificity of 50% and 76%, respectively, at its optimal cutoff. The ETVSS was not significantly well calibrated in this cohort and there was a limited net benefit on decision curve analysis in comparison with the strategy of performing ETV in all patients. The multivariable model achieved an AUC of 0.67 (95% CI: 0.56-0.78), was well calibrated and was associated with a superior net benefit over that of the ETVSS. CONCLUSION: The ETVSS represents the future of patient risk stratification with an easy to use, individualised approach for each patient. The ETVSS has performed adequately in this study. However, through the addition of novel risk factors, the continuous updating of the model and recalibration where needed, the ETVSS can become a tool that the paediatric neurosurgeon cannot do without.

Group B Streptoccocal Meningitis and Ventriculo-peritoneal Shunts.

There is no available Irish data on the rate of Ventriculo-peritoneal (VP) shunt insertion in infants with group B streptococcus (GBS) meningitis. We performed a retrospective case series of 40 infants with GBS meningitis over 6 years. Four (10%) infants required insertion of VP shunt for hydrocephalus. Those infants who required a VP shunt initially presented with seizures, lethargy and a low serum white cell count.

Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature.

INTRODUCTION: Ventriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt. OBJECTIVE: The authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction. CONCLUSION: CSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort.

Can lower risk patients presenting with transient ischaemic attack be safely managed as outpatients?

This study aimed to examine outcome in low risk transient ischaemic attack (TIA) patients presenting to emergency departments (ED) in a regional Australian setting discharged on antiplatelet therapy with expedited neurology review. All patients presenting to Gosford or Wyong Hospital ED with TIA, for whom faxed referrals to the neurology department were received between October 2008 and July 2010, were included in this prospective cohort study. Classification of low risk was based on an age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score <4 and the absence of high risk features, including known carotid disease, crescendo TIA, or atrial fibrillation. Patients with ABCD2 scores > or =4 or with high risk features were discussed with the neurologist on call (a decision regarding discharge or admission was then made at the neurologist's discretion). Patients were investigated with a brain CT scan and/or CT angiography, routine pathology, and an electrocardiogram. All discharged patients were commenced on antiplatelet therapy and asked to follow up with their local medical officer within 7 days. The patients were contacted by the neurology department to arrange follow-up. Our primary outcome was the number of subsequent strokes occurring within 90 days. Of 200 discharged patients for whom referrals were received, three patients had a stroke within 90 days. None of these would have been prevented through hospitalisation. In conclusion, medical assessment, expedited investigation with immediate commencement of secondary prevention and outpatient neurology review may be a reasonable alternative to admission for low risk patients presenting to the ED with TIA.

Occurrence and distribution of pilomyxoid astrocytoma.

PURPOSE: To know the occurrence and distribution of Pilomyxoid Astrocytomas amongst tumours previously diagnosed histologically as Pilocytic Astrocytoma and to assess the clinical impact of this new entity. METHODS: Retrospective Diagnostic review of all cases histologically diagnosed as WHO Grade I Astrocytoma at a single Neurosurgical unit between 1990 and 2003. RESULTS: Of a total of 91 cases identified, 9 were found to have Pilomyxoid histology. Of these, 8 were children (mean age 3.33 years) and 1 adult. 6 tumours were hypothalamochiasmatic in location. The clinical course of Pilomyxoid tumours was aggressive marked by maturation, multiple recurrences and disease control was rarely achieved with single treatment modality as opposed to typical pilocytics. The overall survival of the pilomyxoid group was not statistically different from the pilocytic tumours. CONCLUSIONS: Encompassing all age-groups and locations, Pilomyxoid Astrocytomas constitute about 10% of all tumours previously diagnosed as Pilocytic Astrocytoma. Nearly two-thirds are hypothalamo-chiasmatic in location. Knowledge of this entity is essential for appropriate aggressive treatment and follow-up.

FASTER (Face, Arm, Speech, Time, Emergency Response): experience of Central Coast Stroke Services implementation of a pre-hospital notification system for expedient management of acute stroke.

Despite benefit in acute ischaemic stroke, less than 3% of patients receive tissue plasminogen activator (tPA) in Australia. The FASTER (Face, Arm, Speech, Time, Emergency Response) protocol was constructed to reduce pre-hospital and Emergency Department (ED) delays and improve access to thrombolysis. This study aimed to determine if introduction of the FASTER protocol increases use of tPA using a prospective pre- and post-intervention cohort design in a metropolitan hospital. A pre-hospital assessment tool was used by ambulance services to screen potential tPA candidates. The acute stroke team was contacted, hospital bypass allowed, triage and CT radiology alerted, and the patient rapidly assessed on arrival to ED. Data were collected prospectively during the first 6 months of the new pathway and compared to a 6-month period 12 months prior to protocol initiation. In the 6 months following protocol introduction, 115 patients presented within 24 hours of onset of an ischaemic stroke: 22 (19%) received thrombolysis, significantly greater than five (7%) of 67 patients over the control period, p=0.03. Overall, 42 patients were referred via the FASTER pathway, with 21 of these receiving tPA (50%). One inpatient stroke was also treated. Only two referrals (<5%) were stroke mimics. Introduction of the FASTER pathway also significantly reduced time to thrombolysis and time to admission to the stroke unit. Therefore, fast-track referral of potential tPA patients involving the ambulance services and streamlined hospital assessment is effective and efficient in improving patient access to thrombolysis.

The MRI appearances of early vertebral osteomyelitis and discitis.

AIM: To describe the magnetic resonance imaging (MRI) appearances in patients with a clinical history suggestive of vertebral osteomyelitis and discitis who underwent MRI very early in their clinical course. MATERIALS AND METHODS: A retrospective review of the database of spinal infections from a spinal microbiological liaison team was performed over a 2 year period to identify cases with clinical features suggestive of spinal infection and an MRI that did not show features typical of vertebral osteomyelitis and discitis. All patients had positive microbiology and a follow up MRI showing typical features of spinal infection. RESULTS: In four cases the features typical of spinal infection were not evident at the initial MRI. In three cases there was very subtle endplate oedema associated with disc degeneration, which was interpreted as Modic type I degenerative endplate change. Intravenous antibiotic therapy was continued prior to repeat MRI examinations. The mean time to the repeat examination was 17 days with a range of 8-22 days. The second examinations clearly demonstrated vertebral osteomyelitis and discitis. CONCLUSION: Although MRI is the imaging method of choice for vertebral osteomyelitis and discitis in the early stages, it may show subtle, non-specific endplate subchondral changes; a repeat examination may be required to show the typical features.

imProving Outcomes after STroke clinical pilot trial protocol.

RATIONALE: One in three patients experience depression after stroke and this risk is consistent over time. A strategy to prevent depression that could be economically delivered to most stroke patients and ideally which also has a low likelihood of adverse events needs to be developed and evaluated. Aims POST aims to determine whether a simple intervention (postcards) prevents depression (Hospital Anxiety and Depression rating Scale, HADS depression subscale score > or =8) in patients with a recent stroke. Secondary end-points include reduced anxiety (HADS anxiety subscale score > or =8) and improved health-related quality of life in patients with a recent stroke. DESIGN: A single-centre randomised, double-blind, pilot trial to prevent depression in patients with a recent (within 8 weeks) stroke presenting to hospital. Patients will be enrolled over 12 months and randomised to receive three trial-specific assessments (baseline, 3- and 6-month assessments of mood, HRQoL and social functioning), or three trial-specific assessments plus a postcard sent centrally in a sealed envelope at 1, 2, 3, 4 and 5 months after discharge from hospital. Blinded follow-up telephone assessments will be conducted for both groups. STUDY OUTCOMES AND SAMPLE SIZE: For the primary end-point the POST trial will have 80% power to detect a relative risk of 0.4 given an incidence of depression of 30%. For the secondary aims POST has 90% power to detect a difference of 3 points on the HADS depression subscale (assuming a standard deviation of 6 points) between randomised groups. This includes an inflation factor of 15% to account for patients lost to follow-up. DISCUSSION: Evidence of efficacy will determine whether a multi-centre, international trial is warranted.

The use of zolpidem in the treatment of progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a debilitating progressive neurodegenerative disorder for which there is no proven pharmacological treatment. Zolpidem immediate release formulation has been reported to show short-term improvements in motor function and voluntary saccadic eye movements, but the benefits were not sustained. A 61-year-old man with a 4-year history of PSP was observed over 6 months to have sustained improvement in motor function, pseudobulbar symptoms and ocular motility 2 months after commencing zolpidem controlled release (CR) formulation. He was admitted to hospital and a detailed neurological and functional assessment recorded on video after withdrawal of zolpidem CR, and again following re-introduction of the medication. Within 1 hour of administration of 25mg zolpidem CR the patient had a dramatic improvement in fine motor skills, dexterity, speed and fluidity of movement, facial and vocal expression, oropharyngeal coordination and function and pursuit, and voluntary saccadic eye movements. These improvements were observed for 4 hours to 5 hours post-dose and were reproducible on subsequent withdrawal and re-challenging. We found that zolpidem CR, a gamma aminobutryic acid (GABA)ergic agonist of the benzodiazepine type 1 receptor, caused sustained improvement in motor and ocular symptoms in a patient with PSP over 6 months. Further studies are needed to determine the potential roles of GABA neurotransmission in PSP.

Extradural haematomas in children: a 10-year review.

Extradural haematomas are a significant consequence of head injuries in children. The aim of this study was to evaluate the demographics, symptoms and signs, management and outcome of patients less than 18 years of age with extradural haematomas in our unit. We also specifically looked at repeat imaging performed, indications for this and its effect on further management. No previous reviews have included this. Fifty-six patients were identified from 01/01/1997 to 01/01/2007 for inclusion in this study. Their imaging was then reviewed as were the case notes. Of the patients studied, 70% were male. The average age was 10 years and 2 months with an average length of stay of one week. The commonest mechanisms of injury were a fall from height and an accident involving a bike. Presenting symptoms were documented in 40% of cases. 32% of patients had associated skull fractures. Six patients had other injuries, including long bone fractures and maxillofacial injuries. Glasgow Coma Scale was generally better on admission than pre-operatively and post-operatively was generally better than prior to surgery. Eight patients had neurological signs on admission, 11 had pre-operatively, and nine had post-operatively. 71% underwent a craniotomy with evacuation of the haematoma. Complications were reported in 16% with no mortality. 66% were seen in a neurosurgical clinic, with 46% seen in a Paediatric Head Injury Clinic after discharge. 66% had further imaging after their initial scan of which 52% had no clinical indication. Eight patients were operated on following re-imaging. Most extradural haematomas in children are caused by falls or vehicle accidents. The majority are treated surgically and do well. Indications for further scanning are often not present and in most, management is unchanged. The follow up of these patients also appears to be suboptimal.

Acute stroke and transient ischaemic attack management--time to act fast.

Stroke is Australia's second single greatest killer with 53 000 new events each year at a rate of 1 every 10 min. Stroke services should be organized to enable people to access proven therapies, such as stroke unit care and thrombolysis, to reduce the impact of stroke. Timely, efficient and coordinated care from ambulance services, emergency services and stroke services will maximize recovery and prevent costly complications and subsequent strokes. Efficient management of patients with transient ischaemic attack can produce significant reductions in subsequent stroke events and risk stratification using the ABCD2 tool can aid management decisions. Evidence for acute stroke care continues to evolve and it is crucial that health professionals are aware of, and implement, best practice clinical guidelines for stroke care.

Venous and arterial thrombo-embolic complications of hormonal treatment in a male-to-female transgender patient.

We present a male-to-female (MTF) transgender patient admitted with a pulmonary embolism. The patient had been treated with high-dose oestrogens since the age of 16. Following a prolonged period of hypotension, our patient sustained cerebral border zone infarcts. There was evidence of bilateral carotid stenosis on Doppler ultrasound. We discuss the treatment and vascular complications of gender dysphoria.

Osmotic demyelination syndromes: central and extrapontine myelinolysis.

Osmotic demyelination syndromes are often progressive disorders, with clinical features ranging from a mild tremor or dysarthria to a progressive quadraparesis. Although rapid correction of serum sodium is known to be a potent causative factor, additional pathogenic factors exist, which appear critical in predisposing pontine and extrapontine glia to osmotic stress. Interestingly, several cases of osmotic demyelination have emerged where serum sodium was found to be within normal limits and minimal or no correction of a hypo or hypernatraemic state was implemented. We describe two cases--one of extra pontine and another of central-pontine myelinolysis, both of which have occurred in the context of relatively normal serum sodium. The first case illustrates the association of extrapontine myelinolysis with the traditional risk factor of alcoholic cirrhosis and intravenous fluid resuscitation, while the second, more unusual case, describes a patient who developed central pontine myelinolysis possibly in association with alpha interferon therapy.

Longitudinal prevalence and determinants of early mood disorder post-stroke.

BACKGROUND: Early identification of mood disorder post-stroke (MDPS) or its determinants could improve stroke outcomes. However, the natural history, prevalence and determinants of MDPS within the first weeks post-stroke require further investigation. METHODS: Consecutive hospitalised stroke survivors were assessed within 2-5 days of stroke, and at 1 and 3 months post-stroke. Baseline data included demographics, co-morbidities, stroke subtype, pre-stroke disability and cognition. At baseline, 1- and 3-month interviews physical impairment, disability, cognition and social support were assessed. MDPS was defined as a score of >8 on the depression subscale of the Hospital Anxiety Depression Scale. Factors independently associated with MDPS at each time-point were determined using regression analyses. RESULTS: One hundred and twenty-five subjects were included. The prevalence of MDPS within 5 days and at 1 and 3 months post-stroke was 5%, 16% and 21% respectively. The independent determinants for MDPS at 1 month were disability, social support and change in impairment score between initial and 1-month assessments; and at 3 months were disability, social support and institutionalisation. Individuals moved in and out of the subset of depressed patients over time. MDPS was independently associated with mortality at 3 months post-stroke. CONCLUSION: Mood disorder post-stroke increases in prevalence over the initial weeks post-stroke despite an improvement in disability, and is associated with mortality. Patients with MDPS at 1 month were not necessarily affected at 3 months and vice versa, indicating the dynamic nature of MDPS in the early stages.

Subtypes of oligodendroglioma defined by 1p,19q deletions, differ in the proportion of apoptotic cells but not in replication-licensed non-proliferating cells.

Oligodendrogliomas may be divided into those with deletion of chromosomes 1p and 19q (Del+), and those without (Del-). Del+ tumours show better survival and chemoresponsiveness but the reason for this difference is unknown. We have investigated whether these subgroups differ in (a) apoptotic index, (b) the proportion of cells licensed for DNA replication but not in-cycle, and (c) the relative length of G1-phase. Fluorescence in situ hybridisation with probes to 1p and 19q was used to determine the deletion status of 54 oligodendrogliomas, including WHO grades II and III. The apoptotic index was determined using counts of apoptotic bodies. Replication-licensed non-proliferating cells were determined from the Mcm2 minus Ki67 labelling index, whilst the geminin to Ki67 ratio was used as a measure of the relative length of G1. Del+ oligodendrogliomas showed a higher apoptotic index than Del- tumours (P=0.037); this was not accounted for by differences in tumour grade or in proliferation. There were no differences in the Mcm2-Ki67 index or in the geminin/Ki67 ratio between the subgroups, but grade III tumours showed a higher proportion of licensed non-proliferating cells than grade II tumours (P=0.001). An increased susceptibility to apoptosis in oligodendrogliomas with 1p+/-19q deletion may be important in their improved clinical outcome compared to Del- tumours.