Crystal structures of 3/4-pyridyl-based thiosemicarbazones and related Cu and Ni coordination compounds.

In this investigation, the crystal structures of the thio-ligands 3-formylpyridine 4-phenylthiosemicarbazone (C13H12N4S, 1) and 4-benzoylpyridine 4-ethylthiosemicarbazone (C15H16N4S, 2), and of two new coordination compounds, chlorido(3-formylpyridine 4-phenylthiosemicarbazone-κS)bis(triphenylphosphane-κP)copper(I) acetonitrile monosolvate, [CuCl(C13H12N4S)(C18H15P)2]·CH3CN, 3, and bis(3-formylpyridine 4-ethylthiosemicarbazonato-κ2N1,S)nickel(II), [Ni(C9H11N4S)2], 4, are reported. In complex 3, the thio-ligand coordinates in a neutral form to the Cu atom through its S-donor atom, and in complex 4, the anionic thio-ligand chelates to the Ni atom through N- and S-donor atoms. The geometry of complex 3 is distorted tetrahedral [bond angles 99.70 (5)-123.23 (5)°], with the P-Cu-P bond angle being the largest, while that of complex 4 is square planar, with trans-S-Ni-S and N-Ni-N bond angles of 180°.

Pulmonary embolism with coexistent incidental pulmonary cement embolism post vertebroplasty.

A 46-year-old woman presented with sudden onset of shortness of breath and pleuritic chest pain. A CT pulmonary angiogram identified a 5 cm cement pulmonary embolus within the right main pulmonary artery with a surrounding thrombus. She had undergone an L4 vertebroplasty 3 years prior to presentation for a benign lytic lesion. Cement embolus is a known complication of cement vertebroplasty with incidence rates of approximately 0.9%. Management is usually conservative and associated morbidity and mortality rates are low. It is not known whether a previous cement embolus could provide a nidus for thrombus formation.

Spinal cord herniation as a complication of en bloc, multilevel, anterior thoracic vertebrectomy for a giant cell tumor: success of posterior cord reduction and dural repair.

Iatrogenic spinal cord herniation is a rare complication following spinal stabilization surgery. The authors present a case of circumferential thoracic tumor decompression and fixation by anterior instrumentation complicated by delayed anterior spinal cord herniation. This complication resulted in progressive paraparesis 5 years after the original procedure. The patient underwent reexploration and repair of the dural defect, resulting in the reduction of the spinal cord to its normal position. The patient's paraparesis improved significantly after dural repair. Although progression of neurological deficit can be very slow, repair of the dural defect can restore normal spinal cord alignment and improve neurological deficit. To the best of the authors' knowledge, this is the first reported case of spinal cord herniation following an anterior thoracic vertebrectomy.

The surgical management of the rheumatoid spine: Has the evolution of surgical intervention changed outcomes?

CONTEXT: Surgery for the rheumatoid cervical spine has been shown to stabilize the unstable spine; arrest/improve the progression of neurological deficit, help neck pain, and possibly decelerate the degenerative disease process. Operative intervention for the rheumatoid spine has significantly changed over the last 30 years. AIMS: The purpose of this study was to review all cases of cervical rheumatoid spine requiring surgical intervention in a single unit over the last 30 years. MATERIALS AND METHODS: A prospectively-maintained spine database was retrospectively searched for all cases of rheumatoid spine, leading to a review of indications, imaging, Ranawat and Myelopathy Disability Index measures, surgical morbidity, and survival curve analysis. RESULTS: A total of 224 cases were identified between 1981 and 2011. Dividing the data into three time-epochs, there has been a significant increase in the ratio of segment-saving Goel-Harms C1-C2: Occipitocervical fixation (OCF) surgery and survival has increased between 1981 and 2011 from 30% to 51%. Patients undergoing C1-C2 fixation were comparatively less myelopathic and in a better Ranawat class preoperatively, but postoperative outcome measures were well-preserved with favorable mortality rates over mean 39.6 months of follow-up. However, 11% of cases required OCF at mean 28 months post-C1-C2 fixation, largely due to instrumentation failure (80%). CONCLUSION: We present the largest series of surgically managed rheumatoid spines, revealing comparative data on OCF and C1-C2 fixation. Although survival has improved over the last 30 years, there have been changes in medical, surgical and perioperative management over that period of time too confounding the interpretation; however, the analysis presented suggests that rheumatoid patients presenting early in the disease process may benefit from C1 to C2 fixation, albeit with a proportion requiring OCF at a later time.

Osteosarcoma of the spine: dismal past, any hope for the future?

PURPOSE: The purpose of this study was to analyse all cases of spinal osteosarcoma (OS) treated in a regional bone tumour unit over the last 27 years. We were primarily interested in overall survival following tumour surgery, and if there is a difference in the survival of patients undergoing en bloc resection versus non-en bloc surgery. METHODS: Prospectively maintained tumour databases were searched in a regional bone tumour unit. All cases of surgically managed spinal OS were extracted and inpatient notes, imaging (including staging), histological margin status, and outcomes (neurological deficit and survival curves) were reviewed. RESULTS: Twenty-six patients were identified between 1985 and 2012. The median age was 26.5 years (range 6-78 y). Overall Kaplan-Meier survival was 69.5% (95% CI: 46.3-84.2%) and 10.8% (95% CI: 1.8-29.0%) at 1 and 5 years, respectively. There appears to be improved survival associated with primary spinal OS compared to that of metastatic disease, but this does not reach statistical significance (p = 0.29, Cox proportional hazards analysis). En bloc resection results in a significantly improved survival time compared to non-en bloc (biopsy and debulking): 44.1% alive at 2 years compared to 9.4%, respectively, p = 0.009. CONCLUSIONS: En bloc resection for primary spinal OS is associated with improved survival; there have been major changes in both surgical treatment and chemo/radiotherapy regimens over the period studied, potentially confounding the interpretation.

Rigid occipitocervical fixation: indications, outcomes, and complications in the modern era.

OBJECT: Over the past 40 years, various methods and instrumentation types have been developed for occipitocervical fixation (OCF) in the management of occipitocervical instability. This study reports indications, outcomes, and complications with rigid OCF using screw-rod and screw-plate instrumentation, which has comparatively less long-term data. METHODS: A prospectively maintained database identified 100 consecutive patients who underwent rigid OCF in a single unit over a period of 13 years. Patient demographics, clinical indications, pre- and postoperative radiographic findings, neck disability indices (NDIs), myelopathy disability indices (MDIs), visual analog scale (VAS) scores, and Ranawat scores were recorded. Complications including instrumentation failure were also documented. RESULTS: Underlying etiologies included rheumatoid arthritis (RA; 41%), tumor (16%), trauma (15%), congenital etiologies (14%), metabolic (6%) and inflammatory (6%) conditions, and infection (2%). The pre- and postoperative MDI and VAS scores for neck pain showed significant improvements in the RA group (MDI 64.5% vs 42.5%, p = 0.02; mean VAS 7.5 of 10 vs 3.7 of 10, p < 0.001). Improvements in MDI and NDI outcome measures were also seen in the trauma and tumor categories. Overall, there were 4 cases of instrumentation failure; all included broken rods in the stress riser region of occipitocervical rod curvature, and 1 patient also had occipital plate screw pullout. Other complications included 5 wound infections requiring wound washout, 1 vertebral artery injury (no clinical sequelae), and 1 perioperative death due to myocardial infarction. CONCLUSIONS: Rigid OCF is a safe and effective method of managing occipitocervical instability due to a variety of causes. Outcome measures are favorable, and patients with chronically debilitating diseases such as RA may benefit in terms of improvements in neurological deficit and neck pain. The complication profile is comparable to that reported in other series of OCF in the literature, as well as to the previously used semirigid type of rod/sublaminar wire fixation.

The incidence of deep brain stimulator hardware infection: the effect of change in antibiotic prophylaxis regimen and review of the literature.

The complication of hardware infection related to deep brain stimulator implantation (or revision) varies between 0 and 15.2% in the literature. However, no national guidelines exist at present to define an average or acceptable rate of infection associated with, nor the preferred antibiotic prophylaxis required for, this procedure. The aim of this study was to examine the effect of changing the antibiotic prophylaxis regimen used in a single neurosurgical centre on the incidence and outcome of hardware infection. A prospective cohort of 38 patients undergoing deep brain stimulation (DBS) implantation or internal pulse generator (IPG) replacement and receiving perioperative vancomycin (including intravenous gentamicin on induction) and pouch-installed gentamicin, was compared to a historical cohort of 35 patients receiving perioperative cefuroxime in the same unit. The infection rate over 2 years in the prospective group for DBS surgery was 0 compared to 1 (5.6%) in the historical cohort (p = 0.11, χ(2)); the infection rate for IPG replacements was 1(3.6%) in the prospective cohort, versus 3 (17.6%) in the historical (p = 0.44, χ(2)). In this article, we have also systematically reviewed the literature to date and derived an average infection rate of 4.7% (PI 0.9-22%, Random Effects Meta-analysis, Stata) for 35 studies comprising 3550 patients. There is no significant difference in infection rates between DBS procedures that are primarily internalised (n = 9) compared to those in which there is a period of electrode externalisation (n = 23) (p = 0.9, Meta-regression analysis, Stata).

Spreading depolarizations cycle around and enlarge focal ischaemic brain lesions.

How does infarction in victims of stroke and other types of acute brain injury expand to its definitive size in subsequent days? Spontaneous depolarizations that repeatedly spread across the cerebral cortex, sometimes at remarkably regular intervals, occur in patients with all types of injury. Here, we show experimentally with in vivo real-time imaging that similar, spontaneous depolarizations cycle repeatedly around ischaemic lesions in the cerebral cortex, and enlarge the lesion in step with each cycle. This behaviour results in regular periodicity of depolarization when monitored at a single point in the lesion periphery. We present evidence from clinical monitoring to suggest that depolarizations may cycle in the ischaemic human brain, perhaps explaining progressive growth of infarction. Despite their apparent detrimental role in infarct growth, we argue that cycling of depolarizations around lesions might also initiate upregulation of the neurobiological responses involved in repair and remodelling.

Dynamic metabolic response to multiple spreading depolarizations in patients with acute brain injury: an online microdialysis study.

Spreading depolarizations (SDs) occur spontaneously with high incidence in patients with acute brain injury. They can be detected by subdural electrocorticographic recordings. We here characterize the dynamic metabolic response to these events. A microdialysis catheter was inserted into perilesional cortical tissue adjacent to a strip for electrocorticography following craniotomy in 10 patients. The microdialysis catheter was connected to an online microdialysis assay measuring glucose and lactate concentrations every 30 to 60 secs. Spontaneously occurring SDs systematically caused a reduction in dialysate glucose by -32.0 micromol/L (range: -92.3 to -18.4 micromol/L, n=90) and increase in lactate by +23.1 micromol/L (range: +5.5 to +93.6 micromol/L, n=49). The changes were sustained at 20 mins after the SD events and highly significant using an area under the curve analysis (P<0.0001). Multiple and frequent SDs led to a progressive stepwise depletion of brain glucose. Hence, SD events cause a massive energy imbalance and their frequent occurrence leads to a local insufficiency of glucose supply. Such a failure would compromise cellular repolarization and hence tissue viability. The findings offer a new mechanism to account for otherwise unexplained instances of depletion of brain microdialysate glucose.

A case of primary leptomeningeal gliomatosis confined to the spinal cord.

We report a case of primary leptomeningeal gliomatosis limited to the spinal cord occurring in a 52 years-old patient, who presented with back pain and leg weakness. MRI-scan of the craniospinal axis revealed an enhancing cervicothoracic lesion confined to the leptomeninges. A diagnostic biopsy was taken followed by a six level cervicothoracic laminoplasty with the aim of debulking of the dorsal portion of the tumour and relieving cord compression. Two weeks following surgery, the patient developed bilateral arm weakness. Repeat imaging revealed extension of the lesion to the level of the lower medulla. This patient underwent spinal radiotherapy and concomitant chemotherapy with Temozolomide, but she died of pneumonia 8.5 months after the time of diagnosis. No post-mortem was performed. Primary leptomeningeal gliomatosis exclusively involving the spinal cord is an extremely rare condition bearing a dismal prognosis. It can be suspected on neuroimaging, but histopathological examination is required for the final diagnosis. No current treatment protocols are available. Decompressive surgery may have a role in relieving symptoms, but no substantial benefit has been proven in administering radio-chemotherapy.

Spreading depolarizations and late secondary insults after traumatic brain injury.

Here we investigated the incidence of cortical spreading depolarizations (spreading depression and peri-infarct depolarization) after traumatic brain injury (TBI) and their relationship to systemic physiologic values during neurointensive care. Subdural electrode strips were placed on peri-contusional cortex in 32 patients who underwent surgical treatment for TBI. Prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly nursing chart data. Recordings were 84 hr (median) per patient and 2,503 hr in total. In 17 patients (53%), 280 spreading depolarizations (spreading depressions and peri-infarct depolarizations) were observed. Depolarizations occurred in a bimodal pattern with peak incidence on days 1 and 7. The probability of a depolarization occurring increased significantly as a function of declining mean arterial pressure (MAP; R(2) = 0.78; p < 0.001) and cerebral perfusion pressure (R(2) = 0.85; p < 0.01), and increasing core temperature (R(2) = 0.44; p < 0.05). Depolarization probability was 7% for MAP values of >100 mm Hg but 33% for MAP of < or =70 mm Hg. Temperatures of < or =38.4 degrees C were associated with a 21% depolarization risk, compared to 63% for >38.4 degrees C. Intracranial pressures were higher in patients with depolarizations (18.3 +/- 9.3 vs. 13.5 +/- 6.7 mm Hg; p < 0.001). We conclude that depolarization phenomena are a common cortical pathology in TBI. Their association with lower perfusion levels and higher temperatures suggests that the labile balance of energy supply and demand is an important determinant of their occurrence. Monitoring of depolarizations might serve as a functional measure to guide therapeutic efforts and their blockade may provide an additional line of defense against the effects of secondary insults.

The management of hydrocephalus in children with posterior fossa tumours: the role of pre-resectional endoscopic third ventriculostomy.

AIMS: The purpose of this retrospective case series was to determine the incidence of complications and outcomes associated with a primary management policy of endoscopic third ventriculostomy (ETV) prior to posterior fossa tumour resection in a single paediatric neurosurgical unit. METHODS: Between July 1999 and August 2007, 59 children with posterior fossa tumours were surgically managed. Based on presenting neurology, imaging criteria and cerebrospinal fluid (CSF) pressure during ventriculostomy, patients were categorised into no (n = 16), mild (6), moderate (22) or severe (15) hydrocephalus on admission. RESULTS: Thirty-seven (63%) patients underwent ETV within (mean) 1.5 days of admission, and of those, 32 (87.1%) exhibited significant improvement in presenting symptomology immediately after ETV. Complications arising after ETV included CSF infection/meningitis (n = 2) and bleeding (n = 1). ETV failed in 5/37 patients over the follow-up period. There was a significant association between increasing severity of hydrocephalus before ETV and increased number of complications (p = 0.03). CONCLUSIONS: The use of pre-resectional ETV at this institution is an effective and safe procedure with a high success rate at up to 7.5 years of follow-up. We believe that all paediatric neurosurgical institutions should review their practice regarding hydrocephalus associated with posterior fossa tumours in the light of the controversy surrounding perioperative CSF diversion.

Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leão's spreading depression.

Rapid sampling microdialysis (rsMD) directed towards the cerebral cortex has allowed identification of a combined time-series signature for glucose and lactate that characterizes peri-infarct depolarization in experimental focal ischaemia, but no comparable data exist for 'classical' cortical spreading depression (CSD) associated with hyperaemia in the normally perfused brain. Here, we examined the rsMD responses of dialysate glucose and lactate to five hyperaemic spreading depressions induced with intracortical microinjections, typically of 1 mol/L KCl, in open-skull preparations in five cats under chloralose anaesthesia. Depolarization was verified with microelectrodes, and laser speckle flowmetry was used to examine propagation of the events and perfusion responses near the MD probe. Ten minutes after depolarization, dialysate glucose fell and lactate rose by 28% and 58% respectively. There was no recovery of dialysate glucose 30 mins after depolarization. Mean baseline indicative cerebral blood flow was 25.5+/-4.1 mL/100 g/min and mean maximum hyperaemic increase was by 29.6+/-6 mL/100 g/min; hyperaemia remained present 30 mins after CSD. As CSD events are repetitive, frequent, and often clustered temporally in human acute brain injury, these results indicate a high risk of depletion of extracellular glucose in association with depolarization events of a pattern previously thought to be largely benign.

Neuropsychological profiling of ischemic deficit secondary to ruptured dermoid cyst: a case report.

This report presents a case of a 39-year-old male with a spontaneously ruptured frontotemporal dermoid cyst. Intraoperatively, during surgical resection of the cyst, significant fat spillage occurred associated with a profound anterior circulation vasospasm. The patient underwent serial neuropsychological evaluation over five months, revealing a profile of initial deterioration, followed by delayed recovery of cognitive function. A review of the literature reveals three other case reports describing ischemic deficit after dermoid rupture, but the cognitive impairment associated with this pathology has never been formally profiled before, and it may be possible to draw analogies to the well-established ischemic deficit post-subarachnoid hemorrhage found in the literature. Neuropsychological profiling additionally informs us about the nature and progression of this entity from a cognitive perspective and whether the etiology of deficit caused by dermoid rupture could be localized, or global, secondary to diffuse fatty dissemination in the CSF.

Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain.

OBJECTIVE: To test the co-occurrence and interrelation of ictal activity and cortical spreading depressions (CSDs) - including the related periinfarct depolarisations in acute brain injury caused by trauma, and spontaneous subarachnoid and/or intracerebral haemorrhage. METHODS: 63 patients underwent craniotomy and electrocorticographic (ECoG) recordings were taken near foci of damaged cortical tissue for up to 10 days. RESULTS: 32 of 63 patients exhibited CSDs (5-75 episodes) and 11 had ECoGraphic seizure activity (1-81 episodes). Occurrence of seizures was significantly associated with CSD, as 10 of 11 patients with seizures also had CSD (p=0.007, 2-tailed Fishers exact test). Clinically overt seizures were only observed in one patient. Each patient with CSD and seizures displayed one of four different patterns of interaction between CSD and seizures. In four patients CSD was immediately preceded by prolonged seizure activity. In three patients the two phenomena were separated in time: multiple CSDs were replaced by ictal activity. In one patient seizures appeared to trigger repeated CSDs at the adjacent electrode. In 2 patients ongoing repeated seizures were interrupted each time CSD occurred. CONCLUSIONS: Seizure activity occurs in association with CSD in the injured human brain. SIGNIFICANCE: ECoG recordings in brain injury patients provide insight into pathophysiological mechanisms, which are not accessible by scalp EEG recordings.

The application of near-infrared oximetry to cerebral monitoring during aneurysm embolization: a comparison with intraprocedural angiography.

Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rSO2) in patients at risk of cerebral desaturation during surgical and neurointerventional procedures. However, the quantitative capabilities of the method have been questioned, as has its validation compared with jugular bulb oximetry. Here, we compare NIRS data acquired during coil embolization procedures with incidence of vasospasm as detected from angiography. Thirty-two subarachnoid hemorrhage patients underwent embolization. Bilateral SomaSensor strips (Invos 4100, Somanetics) were affixed to the forehead at constant anatomic positions, avoiding frontal sinuses and scalp hair. Mean arterial pressure, SaO2, end-tidal pCO2, temperature and Hb were held within a narrow range during the procedure. Ipsilateral angiography was performed every 10 to 15 minutes. An independent neuroradiologist classified any vasospasm in the parent vessel as mild (25% baseline), moderate (50%), severe (75%), or total (100%). Of all, 15/32 (46.9%) patients developed spasm; in 2 it was severe or total. There was no significant association between World Federation of Neurological Surgeons grade and baseline rSO2 signal (either ipsilateral or contralateral to the side of the aneurysm) (P=0.598). There was no significant association between side of aneurysm and baseline rSO2 signal (P=0.243). However, episodes of angiographic spasm were strongly associated with reduction in trend ipsilateral NIRS signal (P<0.001); furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal (P<0.001) (2-level random effects regression model, Stata 8.2, Stata Corp, TX). NIRS may have a useful role to play in the detection of cerebral desaturation secondary to vasospasm during neuroendovascular procedures.

Delayed ischaemic neurological deficits after subarachnoid haemorrhage are associated with clusters of spreading depolarizations.

Progressive ischaemic damage in animals is associated with spreading mass depolarizations of neurons and astrocytes, detected as spreading negative slow voltage variations. Speculation on whether spreading depolarizations occur in human ischaemic stroke has continued for the past 60 years. Therefore, we performed a prospective multicentre study assessing incidence and timing of spreading depolarizations and delayed ischaemic neurological deficit (DIND) in patients with major subarachnoid haemorrhage (SAH) requiring aneurysm surgery. Spreading depolarizations were recorded by electrocorticography with a subdural electrode strip placed on cerebral cortex for up to 10 days. A total of 2110 h recording time was analysed. The clinical state was monitored every 6 h. Delayed infarcts after SAH were verified by serial CT scans and/or MRI. Electrocorticography revealed 298 spreading depolarizations in 13 of the 18 patients (72%). A clinical DIND was observed in seven patients 7.8 days (7.3, 8.2) after SAH. DIND was time-locked to a sequence of recurrent spreading depolarizations in every single case (positive and negative predictive values: 86 and 100%, respectively). In four patients delayed infarcts developed in the recording area. As in the ischaemic penumbra of animals, delayed infarction was preceded by progressive prolongation of the electrocorticographic depression periods associated with spreading depolarizations to >60 min in each case. This study demonstrates that spreading depolarizations have a high incidence in major SAH and occur in ischaemic stroke. Repeated spreading depolarizations with prolonged depression periods are an early indicator of delayed ischaemic brain damage after SAH. In view of experimental evidence and the present clinical results, we suggest that spreading depolarizations with prolonged depressions are a promising target for treatment development in SAH and ischaemic stroke.