Kanna K. Gnanalingham

The impact of the international subarachnoid aneurysm trial (ISAT) on the management of aneurysmal subarachnoid haemorrhage in a neurosurgical unit in the UK

OBJECTIVE To review the changes in the management of aneurysmal subarachnoid haemorrhage (SAH) in a single neurosurgical unit in the UK, following the publication of the international subarachnoid aneurysm trial (ISAT). METHODS The presentation, investigations, treatments and outcome data of all patients admitted with SAH to the neurosurgical unit between February 2001 and May 2003 were prospectively recorded in a database. The total period studied was split in to three blocks, around the time of publication of the ISAT in October 2002 (period 1=February-December, 2001; period 2=January-September, 2002 and period 3=October 2002 to May 2003). RESULTS Of the 177 patients admitted with presumed SAH, 130 patients with evidence of an aneurysm on angiograms were included in the study. The mean age was 53+/-1 years, 92 (71%) patients were WFNS grade 1 or 2 and 77 (60%) were Fischer grade 2 or 3. These parameters were unchanged over the study period. Overall, 60 patients (46%) underwent a craniotomy for clipping or wrapping of aneurysm, 60 (46%) underwent endovascular embolisation of the aneurysm and 10 patients (8%) were managed conservatively. Over the study periods 1-3, the proportion of patients undergoing open surgery decreased (from 51 to 31%) while endovascular treatment of aneurysms increased (35-68%; p<0.01). Over the same time points there was a non-significant trend towards better Glasgow outcome scores at 6 months follow-up. The management mortality for all WFNS grades of patients with SAH was eight deaths (14%). The mortality in the surgical group was 3 patients (5%) and there were no deaths in the endovascular group. Over the study periods 1-3, there was a decrease in the mean total duration of hospital stay (from 23.6 to 15.5 days; p<0.05) in WFNS grade 1 and 2 patients and this was related to a shorter duration of hospital stay in the endovascular than surgical group of patients (p<0.05). The mean delay in obtaining an angiogram increased over the study periods 1-3 (1.1-2.3 days; p<0.05). CONCLUSIONS This observational study highlights the changing pattern of management of SAH and the potential difficulties that could be encountered. The proportion of patients undergoing endovascular treatment of aneurysms has increased following the publication of the ISAT study. The associated increase in the delay in obtaining an angiogram may reflect the increased workload encountered by the neuroradiologists.

Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc

IntroductionMatrix metalloproteinases (MMPs) are known to be involved in the degradation of the nucleus pulposus (NP) during intervertebral disc (IVD) degeneration. This study investigated MMP-10 (stromelysin-2) expression in the NP during IVD degeneration and correlated its expression with pro-inflammatory cytokines and molecules involved in innervation and nociception during degeneration which results in low back pain (LBP).MethodsHuman NP tissue was obtained at postmortem (PM) from patients without a history of back pain and graded as histologically normal or degenerate. Symptomatic degenerate NP samples were also obtained at surgery for LBP. Expression of MMP-10 mRNA and protein was analysed using real-time polymerase chain reaction and immunohistochemistry. Gene expression for pro-inflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-α), nerve growth factor (NGF) and the pain-associated neuropeptide substance P were also analysed. Correlations between MMP-10 and IL-1, TNF-α and NGF were assessed along with NGF with substance P.ResultsMMP-10 mRNA was significantly increased in surgical degenerate NP when compared to PM normal and PM degenerate samples. MMP-10 protein was also significantly higher in degenerate surgical NP samples compared to PM normal. IL-1 and MMP-10 mRNA demonstrated a significant correlation in surgical degenerate samples, while TNF-α was not correlated with MMP-10 mRNA. NGF was significantly correlated with both MMP-10 and substance P mRNA in surgical degenerate NP samples.ConclusionsMMP-10 expression is increased in the symptomatic degenerate IVD, where it may contribute to matrix degradation and initiation of nociception. Importantly, this study suggests differences in the pathways involved in matrix degradation between painful and pain-free IVD degeneration.

Endoscopic transsphenoidal pituitary surgery: evidence of an operative learning curve.

BACKGROUND:The use of the fiberoptic endoscope is a recent innovation in pituitary surgery. OBJECTIVE:To investigate the evidence of an operative learning curve after the introduction of endoscopic transsphenoidal surgery in our unit. METHODS:The first 125 patients who underwent endoscopic transnasal transsphenoidal surgery for pituitary fossa lesions between 2005 and 2007 performed by 1 surgeon were studied. Changes in a number of parameters were assessed between 2 equal 15-month time periods: period 1 (53 patients) and period 2 (72 patients). RESULTS:There were 67 patients (54%) with nonfunctioning adenomas, 22 (18%) with acromegaly, and 10 (8%) with Cushings disease. Between study periods 1 and 2, there was a decrease in the mean duration of surgery for nonfunctioning adenomas (from 120 minutes to 91 minutes; P < .01). This learning effect was not apparent for functioning adenomas, the surgery for which also took longer to perform. The proportion of patients with an improvement in their preoperative visual field deficits increased over the study period (from 80% to 93%; P < .05). There were nonsignificant trends toward improved endocrine remission rates for patients with Cushings disease (from 50% to 83%), but operative complications, notably the rates of hypopituitarism, did not change. Overall length of hospital stay decreased between time periods 1 and 2 (from 7 to 4 days median; P < .01). CONCLUSION:The improvements in the duration of surgery and visual outcome noted after about 50 endoscopic procedures would favor the existence of an operative learning curve for these parameters. This further highlights the benefits of subspecialization in pituitary surgery.

Quality of life assessment using the Short Form-12 (SF-12) questionnaire in patients with cervical spondylotic myelopathy: Comparison with SF-36

Study Design. Clinical outcome study comparing the Short Form-36 (SF-36) and Short Form-12 (SF-12) assessment scales in patients with cervical spondylotic myelopathy (CSM). Objectives. To compare the validity, reliability, and sensitivity to change of the SF-12 and SF-36 scales in CSM patients undergoing decompressive surgery. Summary of Background Data. The SF-36 is a generic Health Related Quality of Life (HRQoL) questionnaire, consisting of 36 questions that can be reported as a Physical (PCS) and Mental Component Summary (MCS). Recently, an abbreviated version of SF-36, the SF-12, which uses only 12 questions drawn from the SF-36, has been described. Methods. In this prospective study, patients with CSM undergoing decompressive surgery, self-completed the SF-36 questionnaire before surgery and at 6 months after surgery. SF-12 item responses were abstracted from the responses given to the SF-36 questionnaire. The validity, reliability, and sensitivity to change of the PCS and MCS components of SF-12 and SF-36 scales were compared. Results. Overall, 105 patients underwent anterior (N = 58) or posterior (N = 47) decompressive surgery. After surgery, there were improvements in the PCS components of both the SF-36 (40 ± 2 to 54 ± 2) and SF-12 (34 ± 2 to 48 ± 3), as well as in the MCS component of the SF-36 (48 ± 2 to 63 ± 2) and SF-12 (43 ± 2 to 59 ± 2) (P < 0.001). The sensitivity to change and absolute sensitivity for both SF-12 and SF-36 were comparable, but the reliability of SF-36 was marginally greater. There were close and linear correlations between the SF-36 and SF-12 scores for both the PCS and MCS components, before and after surgery (R = 0.86 to 0.93; P < 0.0001). Conclusions. Both the SF-12 and SF-36 scales are valid and sensitive to changes in physical and mental health status in CSM patients, undergoing decompressive surgery. Despite its abbreviated nature, the SF-12 appears to be an adequate substitute for SF-36, and its brevity should increase its attractiveness to both clinicians and patients.

Differential anti-parkinsonian effects of benzazepine D1 dopamine agonists with varying efficacies in the MPTP-treated common marmoset

In common marmosets systemically treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the behavioural effects of benzazepine D1 dopamine (DA) agonists with full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393, SKF 75670 and SKF 83565) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) activity were investigated. The benzazepine derivatives, with the exception of SKF 82958 (8 fold D1 DA receptor selectivity), demonstrated high D1 DA receptor affinity and selectivity (approximately 100 fold or more) in rat striatal homogenates. Administration of MPTP in marmosets induced locomotor hypoactivity, rigidity and motor disability. SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and SKF 75670 (3-CH3 analogue) further reduced locomotor activity (by −70 to −80%) and increased motor disability (by +22 to +67%) in these animals. SKF 83565 (6-Cl, 3-CH3, 3′-Cl analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) had only a slight effect on locomotor activity but decreased motor disability at high doses (−46 to −60%). In contrast, SKF 83959 (6-Cl, 3-CH3, 3′-CH3 analogue) and SKF 80723 (6-Br analogue) produced pronounced increases in locomotion (6–10 fold) and a reversal in motor disability (by −64 to −77%). Oral activity, consisting largely of abnormal, ‘dyskinetic’ tongue protrusions and vacuous chews, was increased in animals treated with SKF 38393, SKF 83565, SKF 82958 and more especially with SKF 80723 and SKF 83959. Grooming was increased with SKF 82958 and more especially with SKF 80723 and SKF 83959. In contrast, quinpirole (D2 DA agonist), reversed the MPTP-induced motor deficits in the marmoset, with no effect on grooming and oral activity. The present findings further demonstrate the antiparkinsonian actions of some D1 DA agonists in MPTP-treated primates. However, in general the behavioural effects of benzazepines failed to correlate with either their D1 DA receptor affinity/selectivity or their efficacy in stimulating adenylate cyclase (AC) activity. These observations further implicate a behavioural role for D1 DA receptors uncoupled to AC and/or a role for extrastriatal D1 DA receptors in mediating the behavioural response to D1 DA agonists.

The differential behavioural effects of benzazepine D1 dopamine agonists with varying efficacies, co-administered with quinpirole in primate and rodent models of Parkinson's disease

The effects of co-administration of quinpirole with benzazepine D1 dopamine (DA) agonists possessing full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393 and SKF 75670) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) were investigated in rodent and primate models of Parkinsons disease (PD). In rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle, co-administration of SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3′-CH3 analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) strongly potentiated the contralateral circling induced by quinpirole. In MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated common marmosets, administration of quinpirole alone increased locomotor activity and reversed motor deficits. Grooming and oral activity were unaltered. Co-administration of SKF 38393 and SKF 75670 inhibited the quinpirole-induced changes in locomotor activity and motor disability. The combined treatment of SKF 80723 or SKF 82958 with quinpirole had no overall effect on locomotor activity or motor disability. In contrast, SKF 83959 extended the duration of the quinpirole-induced increase in locomotor activity with corresponding decreases in motor disability. Co-administration of high doses of SKF 82958 and more especially SKF 83959 and SKF 80723, with quinpirole induced hyperexcitability and seizures. Oral activity and grooming were unaltered following the co-administration of benzazepine derivatives with quinpirole. The ability of some benzazepine D1 DA agonists to prolong the antiparkinsonian effects of quinpirole in the MPTP-treated marmoset may indicate a role for certain D1 DA agonists in the clinical treatment of PD. In general, the behavioural responses to the combined administration of benzazepines with quinpirole in the 6-OHDA lesioned rat and more especially the MPTP-treated marmoset failed to correlate with their ability to stimulate AC. These observations further implicate a behavioural role for D1 DA receptors not linked to AC.

Acromegaly surgery in Manchester revisited - The impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission.

Introduction  Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remission rate of 27% using accepted criteria for biochemical remission at the time. The establishment of the 2010 Consensus guidelines further tightens biochemical criteria for remission. This report aims to assess the impact of establishing a specialist pituitary surgery service in Manchester in 2005, with reduced surgeon numbers on the remission rates for acromegaly surgery.

Attitudes to the use of prophylaxis for thrombo-embolism in neurosurgical patients.

Neurosurgical patients are at significant risk of thromboembolic complications. A survey of 58 consultant neurosurgeons in United Kingdom confirmed that 84.5% regularly used some form of prophylaxis. For all forms of neurosurgery, the most preferred method of prophylaxis was mechanical (graduated compression stockings-TEDS and intra-operative pneumatic calf compressors-IPC) or in the post-operative period a combination of mechanical methods and low molecular weight heparin (LMWH). LMWH was rarely administered in the perioperative period. The majority of neurosurgeons believed that TEDS and LMWH reduced post-operative DVT (79% and 90%, respectively) and PE (43% and 67%), but 29% associated LMWH with bleeding complications. A review of current literature revealed that TEDS, IPC, and LMWH are effective in reducing the incidence of DVT, but the evidence over the safety of heparin is inconclusive in neurosurgical patients. There is still room for improvement as a minority of neurosurgeons continue to ignore the importance of prophylaxis against thrombo-embolism in neurosurgery.

Pituicytoma: A misdiagnosed benign tumour of the posterior pituitary

A 77-year-old man presented with hypogonadism and bitemporal inferior quadrantonopia. Endocrine testing revealed decreased levels of gonadotrophins and testosterone. The prolactin levels were slightly raised at 586, suggesting a stalk effect. A magnetic resonance scan revealed a 2-cm suprasellar lesion, above a normally sited pituitary gland (Fig. 1a). There was uniform enhancement with gadolinium (Fig. 1b). The lesion was clinically and radiologically presumed to be a craniopharyngioma. Given his significant co-morbidity (ischaemic heart disease, hypertension and diabetes mellitus), an extended transnasal transphenoidal subtotal resection of the tumour was undertaken. The tumour was fibrous and vascular, and only the anterior part of the tumour was resected to decompress the optic chiasm. Histopathology revealed spindle shaped cells with little nuclear pleomorphism and no mitoses (Fig. 2a). The proliferation index with Ki-67 was less than 2%. The tumour showed GFAP-immunoreactivity with some positivity for S-100 (Fig. 2b). These findings met the criteria proposed by Brat et al. for the diagnosis of pituicytoma. Pituicytomas are rare benign primary astrocytic tumours of the neurohypophysis. – 3 Their rarity has led to these tumours in the suprasellar region being confused with more common neoplasms, such as craniopharyngiomas, germ cell tumours, granular cell tumours or rarely a suprasellar meningioma. Although there are no pathognomonic radiological features, a dynamic MR after gadoliniuim injection can show a rapid early phase enhancement of the tumour, which may reflect well developed capillary network. The diagnosis is usually histological with

Short and long-term changes in cerebral [14C]-2-deoxyglucose uptake in the MPTP-treated marmoset: relationship to locomotor activity

The “short-term” (0.7 ± 0.1 months post-MPTP) and “long-term” effects (36.7 ± 4.4 months) of MPTP treatment on motor behaviour and [14C]-2DG uptake were investigated in the common marmoset. The subcutaneous administration of MPTP greatly reduced locomotor activity (−94% with respect to controls) and induced motor disability in the “short-term” MPTP-treated marmoset group. In the “long-term” MPTP group, MPTP treatment did not significantly affect locomotor activity (−27% with respect to controls) and there was partial recovery of motor disability. In the “short-term” MPTP group, there were increases in [14C]-2DG uptake in the GP1 (+31 to +37%), SNc (+34 to +42%), VTA (+35%), LC (+23%), PPN (+19%) and in the VA (+19%), VL (+20%) and AM (+17%) thalamic nuclei. [14C]-2DG uptake was decreased in the STN (−15%). In the “long-term” MPTP group, [14C]-2DG uptake was increased in the GP1 (+18%), SNc (+27%), VTA (+25%), PPN (+19%), ventral caudate nucleus (+18 to +23%), NAc (+22%), F.Ctx (+18%) and in the VA (+34%), VL (+28%), AV (+33%) and AM (+24%) thalamic nuclei. [14C]-2DG uptake was unchanged in the STN. The increase in metabolic activity of the surviving DA neurones and/or the reactive gliosis may account for the initial increase in [14C]-2DG uptake in the SNc and VTA. On the other hand, in the “long-term” MPTP-treated animals the increase in [14C]-2DG uptake in the SNc (though less than in the “short-term” MPTP group), ventral caudate and NAc may reflect the regenerative changes in the dopaminergic system in these areas. Despite the behavioural recovery, [14C]-2DG uptake remained elevated in the target areas for medial paludal output (the thalamic nuclei and PPN). However, the attenuation of the changes in [14C]-2DG uptake in the GP1 and STN of “longterm” MPTP-treated marmosets suggest that the striato-GPl and GP1-STN outputs closely reflect motor function in this primate model of Parkinsons disease.