Middle cerebral artery occlusion treatment
Zang et al. reported the protective effects of Trelagliptin against blood brain barrier disruption and macrophage infiltration. The results indicate that the infarction volume, the neurological score, and macrophage infiltration staining with CD68 were increased in middle cerebral artery occlusion (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction zonula occludens protein-1 (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of ZO-1, and elevated expression level of CXCL1 by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. The results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood-brain barrier in the brains of MCAO mice 1).
Osmotherapy, buffers, sedation, mannitol, hyperventilation 2) 3) , and more recently hypothermia 4) 5) 6) are the intensive care treatments which can be applied in patients with clinical worsening due to ischemic tissue swelling. Unfortunately, they represent only short-lived interventions and temporizing measures which just slow the inexorable development of further deterioration from tissue displacement and brain stem shift 7) 8) 9) 10).
Surgery conversely can be very effective with adequate indications; the reasonable operative treatment in massive cerebral infarction is decompressive hemicraniectomy. The goal of such removing of a part of the cranial vault is to reduce the pressure of the swollen ischemic tissue and to save the brain that is still viable. Several animal studies demonstrated the biological effects of this surgical procedure, as the improvement of the overall cortical perfusion 11) 12) and the reduction of apoptosis in the ischemic border zone 13). To not consider the surgical option leads to missed opportunities of successful treatment 14) , but on the other hand not all the patients with the above requisite may really benefit from the intervention.
Decompressive hemicraniectomy should be performed within 48 h of stroke 15) 16) before brainstem dysfunction is patent. The requisite for the surgical indication is an even initial worsening in patients with verified massive cerebral infarction, and clinical trials failed to demonstrate benefits by prophylactic ultra-early surgery as no differences were found between patients treated at 24 and 48 hours from stroke onset 17) 18) 19). Anyway the possible occurrence of a radiological worsening despite a stable clinical status keeps being an unresolved issue for indication to decompress.
The second factor that the neurosurgeon has to consider is the patient prestroke condition, which is a good predictor of the chance of survive and mostly of the quality of life in case of surgical intervention 20) 21). In the available clinical trials the patient age resulted in one of the most reliable outcome indicators. Generally, patients older than 60 years are not ideal candidates for surgical decompression 22) 23), as they possess a lower neuronal plasticity and also frequently have more vascular risk factors and comorbidities. Even in young patients with severe hypertension, cardiac failure, pulmonary embolism, and other analogous unfavorable diseases the hemicraniectomy might result highly risky and less effective. Conversely also in older patients with a good antecedent condition hemicraniectomy seems somehow to improve the prognosis 24). As not univocal data result from literature it is suggested to not routinely perform surgical decompression in stroke patients older than 60 years at least in really well-selected cases. The effects of hemicraniectomy in patients aged over 65 years will be anyway assessed in the ongoing Destiny II trial.
Surgery can be safely performed even after intravenous tissue plasminogen activator administration for thrombolysis 25) 26). The side of the stroke does not seem to affect the vital status after surgical decompression, so it should not influence the choice to operate 27) 28). However, the family should be informed about the likely chance for the patient to survive but with severe speech disturbances. Family in turn may provide useful information concerning the patient's wishes 29).
The skin incision can be made as a big question mark or a midline leaf-spring. Some surgeons advocate resection of the temporal muscle and fascia to allow a maximum decompression 30) , but this is not commonly performed. The craniotomy should include the frontal, parietal, and temporal bones and its anteroposterior length should not be inferior to 12 cm; larger openings up to 14 cm or more are thought to allow an even better pressure relieve 31). Particular attention has to be paid to decompression of the basal temporal area, as it represents a critical compartment with close relationship with the brainstem. In order to gain additional room, the dura mater is commonly opened as well. It can then be enlarged with a biological or synthetic substitute or left patent, just covered by hemostatic material for a faster closure 32). The cerebral tissue itself should be completely preserved at surgery for recovery of the not deadly damaged areas, which may be not distinguishable from the infarction itself.
The bone flap can be preserved in a subcutaneous pocket overlying the abdomen, but this leads to partial reabsorption in the following weeks, longer operation times, and additional risks related to the additional wound. A valid and currently prevailing alternative is to store the bone frozen (−80°C) in a sterile box. The possible complications of decompressive craniectomy are surgical site infections, hemorrhagic troubles and extra-axial fluid collections, hydrocephalus, and the so-called sinking flap syndrome 33)
Cranioplasty
It is not exceptional that after cranioplasty the patients show some clinical improvement 34) 35). The need to primarily use different materials than the autologous bone to cover the skull defect is uncommon in patients decompressed for ischemic stroke. The perfect timing for cranioplasty after hemicraniectomy is debated, and in the literature do articles specific for patients who underwent surgery for malignant cerebral infarction not exist. It can anyway be deduced from more general studies that the bone flap can be usually repositioned within 5 to 12 weeks 36) 37) 38) 39).