Hemorrhage due to a pseudoaneurysm on a dural-pial anastomosis after decompression for Chiari malformation type I: case report.

While intracranial aneurysms rarely develop after neurosurgical procedures, delayed pseudoaneurysm formation after foramen magnum decompression (FMD) has never been reported. A 52-year-old woman presented with an atypical subarachnoid hemorrhage in the posterior fossa 12 years after a FMD for symptomatic Chiari malformation type I was performed. A pseudoaneurysm on a dural-pial anastomosis was identified as the bleeding source and successfully occluded by endovascular means with full clinical recovery of the patient. Injury to the distal posterior inferior cerebellar artery related to surgery and postoperative infection likely caused formation of a dural-pial anastomosis. Additionally, hemodynamic stress or dissection may have contributed to delayed pseudoaneurysm formation and rupture.

Intracranial pressure during hemodialysis in patients with acute brain injury.

BACKGROUND: Because osmotic fluid shifts may occur over the blood-brain barrier, patients with acute brain injury are theoretically at risk of surges in intracranial pressure (ICP) during hemodialysis. However, this remains poorly investigated. We studied changes in ICP during hemodialysis in such patients. METHODS: We performed a retrospective study of patients with acute brain injury admitted to Rigshospitalet (Copenhagen, Denmark) from 2012 to 2016 who received intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT) while undergoing ICP monitoring. Data from each patient's first dialysis session were collected. Area under the curve divided by time (AUC/t) for ICP was calculated separately before and during dialysis. RESULTS: Thirteen patients were included. During dialysis, ICP increased from a baseline of 11.9 mm Hg (median; interquartile range 6.3-14.7) to a maximum of 21 mm Hg (18-27) (P = 0.0024), and AUC/t for ICP was greater during dialysis (15.2 (13.4-18.8) vs 11.7 mm Hg (6.4-15.1), P = 0.042). The maximum ICP increase was independent of dialysis modality, but peak values were reached earlier in patients treated with IHD (N = 4) compared to CRRT (N = 9) (75 [30-90] vs 375 min [180-420] after start of treatment, P = 0.0095). The maximum ICP increase correlated positively to the baseline plasma urea concentration (Spearman's r = 0.69, P = 0.017). CONCLUSION: Hemodialysis is associated with increased ICP in neurocritically ill patients, and the magnitude of the increase may be related to initial plasma urea levels.

Criteria for brain death in Denmark.

In 1990, the Danish brain death legislation was adopted by the Danish Parliament. Each year, around 100 patients in Denmark fulfil criteria for brain death/death by neurological criteria (BD/DNC). In this review of current Danish criteria including the indication for ancillary investigation, which in Denmark is digital subtraction angiography (DSA), we conclude that the time has come to revise the national BD/DNC criteria. We propose that visible anoxic-ischaemic encephalopathy on brain CT after cardiac arrest does not require evaluation by ancillary testing, and that CT-angiography can be used instead of DSA.

Confirmatory digital subtraction angiography after clinical brain death/death by neurological criteria: impact on number of donors and organ transplants.

Background: Demand for organs exceeds the number of transplants available, underscoring the need to optimize organ donation procedures. However, protocols for determining brain death (BD)/death by neurological criteria (DNC) vary considerably worldwide. In Denmark, digital subtraction angiography (DSA) is the only legally approved confirmatory test for diagnosing BD/DNC. We investigated the effect of the time delay caused by (repeat) confirmatory DSA on the number of organs donated by patients meeting clinical criteria for BD/DNC. We hypothesized that, first, patients investigated with ≥2 DSAs donate fewer organs than those investigated with a single DSA; second, radiological interpretation of DSA is subject to interrater variability; and third, residual intracranial circulation is inversely correlated with inotropic blood pressure support. Methods: All DSAs performed over a 7-year period as part of BD/DNC protocols at Rigshospitalet, Copenhagen University Hospital, Denmark, were included. Clinical data were extracted from electronic health records. DSAs were reinterpreted by an independent neurinterventionist blinded to the original radiological reports. Results: We identified 130 DSAs in 100 eligible patients. Patients with ≥2 DSAs (n = 20) donated fewer organs (1.7 +/- 1.6 SD) than patients undergoing a single DSA (n = 80, 2.6 +/- 1.7 organs, p = 0.03), and they became less often donors (n = 12, 60%) than patients with just 1 DSA (n = 65, 81.3%; p = 0.04). Interrater agreement of radiological DSA interpretation was 88.5% (Cohen's kappa = 0.76). Patients with self-maintained blood pressure had more often residual intracranial circulation (n = 13/26, 50%) than patients requiring inotropic support (n = 14/74, 18.9%; OR = 0.23, 95% CI [0.09-0.61]; p = 0.002). Discussion: In potential donors who fulfill clinical BD/DNC criteria, delays caused by repetition of confirmatory DSA result in lost donors and organ transplants. Self-maintained blood pressure at the time of clinical BD/DNC increases the odds for residual intracranial circulation, creating diagnostic uncertainty because radiological DSA interpretation is not uniform. We suggest that avoiding unnecessary repetition of confirmatory investigations like DSA may result in more organs donated.

Diagnostics with clinical microbiome-based identification of microorganisms in patients with brain abscesses-a prospective cohort study.

Brain abscesses are often polymicrobial and of unclear primary origin. Here, we compare the use of next-generation sequencing (NGS) technology with classical microbiological diagnostics for identification of clinically relevant microorganisms and describe the microbiome profiling with respect to the primary source of brain abscess. Thirty-six samples from 36 patients, with primary brain abscesses, were subjected to both culture- and 16S/18S rRNA Sanger sequencing-based diagnostics ("standard methods") and compared to a 16S/18S amplicon-based NGS, which were also subjected to a microbiome diversity analyses. Forty-seven species were identified with "standard methods" compared to 96 species with NGS, both confirming and adding to the number of species identified (p < 0.05). The variation of the brain abscess microbiome diversity was not continuous but could be stratified comparing the presumable origin of infection ("dental," "sinus," "disseminated," or "unknown"). Alpha diversity did not differ (p > 0.05) between groups while beta diversity differed significantly (p = 0.003) comparing disseminated vs the other presumable origin of infection. Interesting, clustering was also detected between "dental" and "sinusitis," although not significantly (p = 0.07). Microbiome-based diagnostics can increase sensitivity without losing specificity. The bacterial beta diversity differed between the presumably origin of the brain abscess and might help to clarify the primary source of infection.

[Treatment of metastatic spinal cord compression].

Metastatic spinal cord compression is an oncologic emergency, and the most frequent initial symptom is radicular backpain. Urgent diagnostics with acute MRI and early treatment is essential to prevent permanent neurologic damage. Treatment is mainly palliative. For patients who have a good prognosis, the treatment of choice is decompressive surgery followed by radiotherapy, but only few patients are candidates to surgery due to significant comorbidities and poor performance status. Optimal therapy is required to maintain high quality of life at an acceptable risk, as argued in this review.

[Spinefractures - diagnosis and treatment].

Acute onset back pain is a common reason for referral to primary health care or emergency departments. In this review, the different spine fracture types are highlighted, and a treatment algorithm is proposed. CT is the modality of choice when a spine fracture is suspected. MRI should be performed when disc or ligamentous lesions are suspected or in patients with known ankylosis or diffuse idiopathic skeletal hyperostosis. Treatment is mainly conservative with bracing, but unstable fractures and patients with neurological deficits should be treated surgically.

Delayed Iatrogenic Intracranial Hypotension After Thoracotomy.

We report a case of intracranial hypotension (IH) after thoracotomy. A 56-year-old woman presented 10 days after a left upper lobectomy with severe headache due to pneumocephalus and pneumorrhachis, which resolved on conservative treatment. Two months later, the patient was readmitted in an unconscious state with characteristics of IH and "sagging brain." Subsequent magnetic resonance imaging revealed a fistula at the level of the left Th5 pedicle. The patient underwent operation with closure of the fistula and recovered without complications. The presence of pneumocephalus and pneumorrhachis after thoracotomy should raise the suspicion of a persistent subarachnoid-pleural fistula to prevent IH and "sagging brain."

Long-Term Effect of Decompressive Craniectomy on Intracranial Pressure and Possible Implications for Intracranial Fluid Movements.

BACKGROUND: Decompressive craniectomy (DC) is used in cases of severe intracranial hypertension or impending intracranial herniation. DC effectively lowers intracranial pressure (ICP) but carries a risk of severe complications related to abnormal ICP and/or cerebrospinal fluid (CSF) circulation, eg, hygroma formation, hydrocephalus, and "syndrome of the trephined." OBJECTIVE: To study the long-term effect of DC on ICP, postural ICP regulation, and intracranial pulse wave amplitude (PWA). METHODS: Prospective observational study including patients undergoing DC during a 12-mo period. Telemetric ICP sensors (Neurovent-P-tel; Raumedic, Helmbrechts, Germany) were implanted in all patients. Following discharge from the neuro intensive care unit (NICU), scheduled weekly ICP monitoring sessions were performed during the rehabilitation phase. RESULTS: A total of 16 patients (traumatic brain injury: 7, stroke: 9) were included (median age: 55 yr, range: 19-71 yr). Median time from NICU discharge to cranioplasty was 48 d (range: 16-98 d) and during this period, mean ICP gradually decreased from 7.8 ± 2.0 mm Hg to -1.8 ± 3.3 mm Hg (P = .02). The most pronounced decrease occurred during the first month. Normal postural ICP change was abolished after DC for the entire follow-up period, ie, there was no difference between ICP in supine and sitting position (P = .67). PWA was markedly reduced and decreased from initially 1.2 ± 0.7 mm Hg to 0.4 ± 0.3 mm Hg (P = .05). CONCLUSION: Following NICU discharge, ICP decreases to negative values within 4 wk, normal postural ICP regulation is lost and intracranial PWA is diminished significantly. These abnormalities might have implications for intracranial fluid movements (eg, CSF and/or glymphatic flow) following DC and warrants further investigations.

Long-term functional outcome after decompressive suboccipital craniectomy for space-occupying cerebellar infarction.

OBJECTIVES: Suboccipital decompressive craniectomy (SDC) is considered the best treatment option in patients with space-occupying cerebellar infarction and clinical signs of deterioration. The primary purpose of this study was to evaluate long-term functional outcome in patients one year after SDC for space-occupying cerebellar infarction, and secondly, to determine factors associated with outcome. PATIENTS AND METHODS: All patients treated with SDC due to space-occupying cerebellar infarction between January 2009 and October 2015 were included in the study. Data was retrospectively collected from patient records, CT/MRI scans and surgical protocols. Long-term functional outcome was determined by the modified Rankin Scale (mRS) and mRS ≥ 4 was defined as unfavorable outcome. RESULTS: Twenty-two patients (16 male, 6 female) were included in the study. Median age was 53 years. Nine patients were treated with external ventricular drainage as an initial treatment attempt prior to SDC. Median time from symptom onset (stroke ictus) to initiation of the SDC surgery was 48 h (IQR 28-99 hours) and median GCS before SDC was 8 (IQR 5-10). At follow up, median mRS was 3 (IQR 2-6). Outcome was favorable (mRS 0-3) in 12 patients and unfavorable in 10 (3 with major disability, 7 dead). Brainstem infarction and bilateral cerebellar infarction were associated with unfavorable outcome. CONCLUSIONS: In this small study, functional long-term outcome in patients with space-occupying cerebellar infarction treated by SDC was acceptable and comparable to previously published results (favorable outcome in 54% of patients). Brainstem infarction and bilateral cerebellar infarction were associated with unfavorable outcome.

Intracranial pressure before and after cranioplasty: insights into intracranial physiology.

OBJECTIVE: Decompressive craniectomy (DC) is an emergency neurosurgical procedure used in cases of severe intracranial hypertension or impending intracranial herniation. The procedure is often lifesaving, but it exposes the brain to atmospheric pressure in the subsequent rehabilitation period, which changes intracranial physiology and probably leads to complications such as hydrocephalus, hygromas, and "syndrome of the trephined." The objective of the study was to study the effect of cranioplasty on intracranial pressure (ICP), postural ICP changes, and intracranial pulse wave amplitude (PWA). METHODS: The authors performed a prospective observational study including patients who underwent DC during a 12-month period. Telemetric ICP sensors were implanted in all patients at the time of DC. ICP was evaluated before and after cranioplasty during weekly measurement sessions including a standardized postural change program. RESULTS: Twelve of the 17 patients enrolled in the study had cranioplasty performed and were included in the present investigation. Their mean ICP in the supine position increased from -0.5 ± 4.8 mm Hg the week before cranioplasty to 6.3 ± 2.5 mm Hg the week after cranioplasty (p < 0.0001), whereas the mean ICP in the sitting position was unchanged (-1.2 ± 4.8 vs -1.1 ± 3.6 mm Hg, p = 0.90). The difference in ICP between the supine and sitting positions was minimal before cranioplasty (1.1 ± 1.8 mm Hg) and increased to 7.4 ± 3.6 mm Hg in the week following cranioplasty (p < 0.0001). During the succeeding 2 weeks of the follow-up period, the mean ICP in the supine and sitting positions decreased in parallel to, respectively, 4.6 ± 3.0 mm Hg (p = 0.0003) and -3.9 ± 2.7 mm Hg (p = 0.040), meaning that the postural ICP difference remained constant at around 8 mm Hg. The mean intracranial PWA increased from 0.7 ± 0.7 mm Hg to 2.9 ± 0.8 mm Hg after cranioplasty (p < 0.0001) and remained around 3 mm Hg throughout the following weeks. CONCLUSIONS: Cranioplasty restores normal intracranial physiology regarding postural ICP changes and intracranial PWA. These findings complement those of previous investigations on cerebral blood flow and cerebral metabolism in patients after decompressive craniectomy.

Copenhagen Head Injury Ciclosporin Study: A Phase IIa Safety, Pharmacokinetics, and Biomarker Study of Ciclosporin in Severe Traumatic Brain Injury Patients.

Traumatic brain injury (TBI) contributes to almost one third of all trauma-related deaths, and those that survive often suffer from long-term physical and cognitive deficits. Ciclosporin (cyclosporine, cyclosporin A) has shown promising neuroprotective properties in pre-clinical TBI models. The Copenhagen Head Injury Ciclosporin (CHIC) study was initiated to establish the safety profile and pharmacokinetics of ciclosporin in patients with severe TBI, using a novel parenteral lipid emulsion formulation. Exploratory pharmacodynamic study measures included microdialysis in brain parenchyma and protein biomarkers of brain injury in the cerebrospinal fluid (CSF). Sixteen adult patients with severe TBI (Glasgow Coma Scale 4-8) were included, and all patients received an initial loading dose of 2.5 mg/kg followed by a continuous infusion for 5 days. The first 10 patients received an infusion dosage of 5 mg/kg/day whereas the subsequent 6 patients received 10 mg/kg/day. No mortality was registered within the study duration, and the distribution of adverse events was similar between the two treatment groups. Pharmacokinetic analysis of CSF confirmed dose-dependent brain exposure. Between- and within-patient variability in blood concentrations was limited, whereas CSF concentrations were more variable. The four biomarkers, glial fibrillary acidic protein, neurofilament light, tau, and ubiquitin carboxy-terminal hydrolase L1, showed consistent trends to decrease during the 5-day treatment period, whereas the samples taken on the days after the treatment period showed higher values in the majority of patients. In conclusion, ciclosporin, as administered in this study, is safe and well tolerated. The study confirmed that ciclosporin is able to pass the blood-brain barrier in a TBI population and provided an initial biomarker-based signal of efficacy.

Neuroglobin in the rat brain (II): co-localisation with neurotransmitters.

In an accompanying article, we found that neuroglobin (Ngb) was expressed in a few well-defined nuclei in the rat brain. Here, we show by use of immunohistochemistry and in situ hybridisation (ISH) that Ngb co-localise with several specific neurotransmitters. Ngb co-localise consistently with tyrosine hydroxylase (TH) in the noradrenergic/adrenergic A1/C1 and A2/C2; the noradrenergic A5, A6 and A7. Ngb were not observed to co-localise TH in the dopaminergic A8-A16 cell populations. Ngb were only seen to co-localise with choline acetyltransferase (ChAT) in the laterodorsal tegmental nucleus (LDTg) and in the pontine tegmental nucleus (PPTg). Many Ngb-ir neurones co-localised with neuronal nitric oxide synthase (nNOS) in the LDTg, whereas fewer Ngb-ir neurones co-localise nNOS in the anterior basomedial (BMA) and the posterodorsal medial (MePD) amygdaloid nucleus, in the medial preoptic area (MPA) and in part of the lateral hypothalamus (LH). Ngb-ir neurones co-localise heme oxygenase 1 (HO-1) in the LDTg and locus coeruleus. Ngb-ir neurones co-localise hypocretin-1 (Hcrt1) in the perifornical (PeF) and perifornical lateral hypothalamus (PeFLH). Within the LH, Ngb-ir neurones co-localised melanin concentration hormone (MCH). A few Ngb-ir perikarya in the paraventricular hypothalamic nucleus (PVN) co-localised arginine vasopressin (aVP). Ngb were not observed to co-localise with serotonin, vasointestinal peptide (VIP), or cocaine amphetamine-regulated transcript (CART) at any places. In the present study, we found no evidence that one or more particular neurotransmitters are coupled 100% to Ngb or that Ngb is coupled 100% to a specific neurotransmitter. Based on these findings, we suggest that Ngb could be involved in some sort of regulation of the sleep-wake cycle. Secondly, that Ngb in some neurones is involved in regulation of gaseous neurotransmission, and that this in any given case only involves a subset of neurones. To us this indicates that the cellular and physiological function of Ngb in different subsets of neurones might not be identical, or that all neurones containing Ngb has one thing in common that we at presently not are aware of.

Neuroglobin in the rat brain: localization.

Neuroglobin (Ngb) is a neuronal hemeprotein similar to myoglobin and hemoglobin and shares their capability for oxygen binding. It has thus been proposed that Ngb acts as an oxygen reservoir or combats reactive oxygen species. In the present study, we investigated the Ngb expression pattern in the rat brain using immunohistochemistry, in situ hybridization, and quantitative real-time PCR (qRT-PCR). This revealed the interesting finding that Ngb expression is restricted to a few neurone populations, many of which are involved in the sleep-wake cycle, circadian regulation or food regulation. In the forebrain we found intense Ngb expression in neurones in the piriform cortex, the central and medial amygdala, the medial preoptic area, the suprachiasmatic nucleus (SCN), the hypothalamic paraventricular nucleus, the perifornical nucleus, the lateral hypothalamus. Within the mid- and hindbrain Ngb expressing neurones were found in the laterodorsal tegmental nucleus, the pedunculo pontine tegmental nucleus, the locus coeruleus, and the lateral parabrachial nucleus. In the medulla oblongata Ngb expressing neurones were found in the nucleus of the solitary tract. The qRT-PCR data showed a diurnal variation of Ngb mRNA in the SCN, having a peak in the day time (light-period) and nadir during night (dark-period).

[Successful treatment and rehabilitation of severe, penetrating brain injury].

Penetrating brain injuries due to gunshots are rare in Denmark. This is a case report of the successful treatment of a 31-year-old man who was shot in the right frontal region of the head. The bullet went through his brain without damaging the large intracranial vessels. On admission he had a GCS of 9. Haematoma removal and bifrontal craniectomy was performed to obtain lowering of the intracranial pressure. One year after the incidence the patient was able return to work. This case report illustrates the importance of early prehospital and neurointensive treatment with lowering of the intracranial pressure and highly specialised rehabilitation.

Feasibility of Telemetric Intracranial Pressure Monitoring in the Neuro Intensive Care Unit.

Intracranial pressure (ICP) monitoring is crucial in the management of acute neurosurgical conditions such as traumatic brain injury (TBI). However, pathological ICP may persist beyond the admission to the neuro intensive care unit (NICU). We investigated the feasibility of telemetric ICP monitoring in the NICU, as this technology provides the possibility of long-term ICP assessment beyond NICU discharge. In this prospective investigation, we implanted telemetric ICP sensors (Raumedic Neurovent-P-tel) instead of conventional, cabled ICP sensors in patients undergoing decompressive craniectomy. We recorded ICP curves, duration of ICP monitoring, signal quality, and complications. Seventeen patients were included (median age 55 years) and diagnoses were: severe TBI (8), malignant middle cerebral artery infarction (8), and spontaneous intracerebral hemorrhage (1). In total, 3015 h of ICP monitoring were performed, and the median duration of ICP monitoring was 188 h (interquartile range [IQR] 54-259). The ICP signal was lost 613 times (displacement of the reader unit on the skin) for a median of 1.5 min, corresponding to 0.8% of the total monitoring period. When the signal was lost, it could always be restored by realignment of the reader unit on the skin above the telemetric sensor. Sixteen of 17 patients survived the NICU admission, and ICP gradually decreased from 10.7 mm Hg (IQR 7.5-13.6) during the first postoperative day to 6.3 mm Hg (IQR 4.0-8.3) after 1 week in the NICU. All 17 implanted telemetric sensors functioned throughout the NICU admission, and no wound infections were observed. Therefore, telemetric ICP monitoring in an acute neurosurgical setting is feasible. Signal quality and stability are sufficient for clinical decision making based on mean ICP. The low sampling frequency (5 Hz) does not permit analysis of intracranial pulse wave morphology, but resolution is sufficient for calculation of derived indices such as the pressure reactivity index (PRx).

[Traumatic penetrating brain injury].

Penetrating brain injury is a severe form of traumatic brain injury. It is significantly less prevalent than closed head injury but carries a much worse prognosis. The experience with traumatic penetrating brain injury in Denmark is limited. The most common causes in penetrating brain injury in Denmark are: violence, accidents and suicidal behaviour. The aim of this review is to give a brief update on historical background, mechanisms of disease, recommended medical and surgical treatment, and complications. Clinical examples and a treatment algorithm are discussed.

[Rapid resolution of acute subdural haematoma with significant impact on clinical outcome].

A 73-year-old woman was admitted to hospital due to anaemia. She suffered a minor head trauma and deteriorated to deep unconsciousness. A CT revealed an acute subdural haematoma (ASDH). Initially, she was not found to be a candidate for neurosurgical intervention, but within 24 hours her level of consciousness improved dramatically, and a renewed CT showed resolution of the ASDH. She underwent acute craniotomy with good outcome. This illustrates the importance of re-evaluation of patients with intracranial haemorrhage.

Increased Intracranial Pressure during Hemodialysis in a Patient with Anoxic Brain Injury.

Dialysis disequilibrium syndrome (DDS) is a serious neurological complication of hemodialysis, and patients with acute brain injury are at increased risk. We report a case of DDS leading to intracranial hypertension in a patient with anoxic brain injury and discuss the subsequent dialysis strategy. A 13-year-old girl was admitted after prolonged resuscitation from cardiac arrest. Computed tomography (CT) revealed an inferior vena cava aneurysm and multiple pulmonary emboli as the likely cause. An intracranial pressure (ICP) monitor was inserted, and, on day 3, continuous renal replacement therapy (CRRT) was initiated due to acute kidney injury, during which the patient developed severe intracranial hypertension. CT of the brain showed diffuse cerebral edema. CRRT was discontinued, sedation was increased, and hypertonic saline was administered, upon which ICP normalized. Due to persistent hyperkalemia and overhydration, ultrafiltration and intermittent hemodialysis were performed separately on day 4 with a small dialyzer, low blood and dialysate flow, and high dialysate sodium content. During subsequent treatments, isolated ultrafiltration was well tolerated, whereas hemodialysis was associated with increased ICP necessitating frequent pauses or early cessation of dialysis. In patients at risk of DDS, hemodialysis should be performed with utmost care and continuous monitoring of ICP should be considered.