Showing papers by "Karol P. Budohoski published in 2019"

Twenty-Five Years of Intracranial Pressure Monitoring After Severe Traumatic Brain Injury: A Retrospective, Single-Center Analysis.

Abstract: BACKGROUND Intracranial pressure (ICP) is a clinically important variable after severe traumatic brain injury (TBI) and has been monitored, along with clinical outcome, for over 25 yr in Addenbrooke's hospital, Cambridge, United Kingdom. This time period has also seen changes in management strategies with the implementation of protocolled specialist neurocritical care, expansion of neuromonitoring techniques, and adjustments of clinical treatment targets. OBJECTIVE To describe the changes in intracranial monitoring variables over the past 25 yr. METHODS Data from 1146 TBI patients requiring ICP monitoring were analyzed. Monitored variables included ICP, cerebral perfusion pressure (CPP), and the cerebral pressure reactivity index (PRx). Data were stratified into 5-yr epochs spanning the 25 yr from 1992 to 2017. RESULTS CPP increased sharply with specialist neurocritical care management (P < 0.0001) (introduction of a specific TBI management algorithm) before stabilizing from 2000 onwards. ICP decreased significantly over the 25 yr of monitoring from an average of 19 to 12 mmHg (P < 0.0001) but PRx remained unchanged. The mean number of ICP plateau waves and the number of patients developing refractory intracranial hypertension both decreased significantly. Mortality did not significantly change in the cohort (22%). CONCLUSION We demonstrate the evolving trends in neurophysiological monitoring over the past 25 yr from a single, academic neurocritical care unit. ICP and CPP were responsive to the introduction of an ICP/CPP protocol while PRx has remained unchanged.

A map of transcriptional heterogeneity and regulatory variation in human microglia

Abstract: Microglia, the tissue resident macrophages of the CNS, are implicated in a broad range of neurological pathologies, from acute brain injury to dementia. Here, we profiled gene expression variation in primary human microglia isolated from 141 patients undergoing neurosurgery. Using single cell and bulk RNA sequencing, we defined distinct cellular populations of acutely in vivo-activated microglia, and characterised a dramatic switch in microglial population composition in patients suffering from acute brain injury. We mapped expression quantitative trait loci (eQTLs) in human microglia and show that many disease-associated eQTLs in microglia replicate well in a human induced pluripotent stem cell (hIPSC) derived macrophage model system. Using ATAC-seq from 95 individuals in this hIPSC model we fine-map candidate causal variants at risk loci for Alzheimer9s disease, the most prevalent neurodegenerative condition in acute brain injury patients. Our study provides the first population-scale transcriptional map of a critically important cell for neurodegenerative disorders.

Awake Craniotomy for Resection of Left Temporal Cavernoma: 3-Dimensional Operative Video.

Abstract: Cavernomas presenting with seizures refractory to medical treatment may require surgical excision for seizure control. If superficial, they can be surgically accessible but can pose additional risks when located in or near eloquent cortex. In this 3D operative video we illustrate the technique for the resection of a left temporal cavernoma located near eloquent cortex for speech with awake surgery and cortical mapping to avoid a speech deficit postoperatively. Informed consent was obtained for this procedure. Navigation is used to localize the cavernoma following which a large craniotomy is performed exposing the temporal lobe, frontal lobe, and sylvian vein. Bipolar stimulation is used to localize speech with the patient awake until speech arrest occurs. The cavernoma is situated immediately inferior to the sulcus over which speech arrest occurs. The sulcus immediately above the cavernoma is opened and adjacent arteries are carefully preserved. The glial plane around the cavernoma is used to dissect the cavernoma from the surrounding cortex. Care is taken to remove the haemosiderin as this can act as a precipitant for ongoing seizures. In this case the patient had no neurological deficits following surgery and was seizure free.

Infratentorial Supracerebellar Approach for Resection of Midbrain Cavernous Malformation: 3-Dimensional Operative Video.

Abstract: Cavernous malformations (cavernomas) of the brain stem with recurrent hemorrhage may be amenable to microsurgical resection if they are present close to the surface. The risks of surgery need to be balanced with the natural history of the lesion and the accumulation of neurological deficits and risk to life with multiple hemorrhages. In this 3D operative video, we illustrate the technique for the resection of a dorsally located midbrain cavernous malformation. Informed consent was obtained for this procedure. The cavernoma is accessed with the use of a supracerebellar infratentorial approach. The infratentorial craniotomy and coagulation of the superior vermian veins is shown. A description is provided of the use of hemosiderin staining and the intercollicular relative "safe zone"1 as landmarks for the neurotomy. The technique of cavernoma dissection from the surrounding gliotic plane is shown and described. In this case, the patient required prolonged rehabilitation but fully recovered without residual deficit 1 yr following surgery.

Management Evaluation of Metastasis in the Brain (MEMBRAIN) – A UK & Ireland prospective, multicentre observational study

Abstract: Over the recent years an increasing number of patients with brain metastasis are being referred to the neuro-oncology multi-disciplinary team (NMDT). Our aim was to determine if referrals of this group of patients to the NMDT in the UK & Ireland comply with NICE guidelines and to assess referral volume, quality of information provided and its impact on NMDT decision-making. Prospective multicentre oberservational study including all adult patients referred with ≥1 cerebral metastasis. Data was collected in neurosurgical units from 11/2017 to 02/2018. Demographics, primary disease, Karnofsky performance status (KPS), imaging and treatment recommendation were entered into an online database. 1049 patients were analysed from 24 neurosurgical units. Median age was 63[range 21–93] years with a median number of 3[range 1–17] referrals per NMDT. The most common primary malignancies were lung (36.5%, n=383), breast (18.5%, n=194) and melanoma (12.0%, n=126). 51.6% (n=541) of the referrals to the NMDT were within the NICE 2006 guidelines, and resulted in specialist intervention being offered in 68.8%. 41.2% (n=197) of patients being referred outside of the NICE 2006 guidelines were offered specialist treatment. NMDT decision-making was influenced by number of metastases, age, KPS, primary disease status and extent of extracranial disease (univariate logistic regression, p<0.0001) as well as metastasis location/histology (p<0.05). This study confirmed a national change in culture of referral patterns. We identified a delay in NMDT decision-making in ~20%, contributing to increased NMDT workload. New stratification tools may be needed to reflect advancements in diagnostics and treatment modalities.