Overview
Primary intracerebral hemorrhage (PICH, abbreviated as cerebral hemorrhage – ICH) refers to the rupture of blood vessels in the brain and the direct entry of blood into the brain parenchyma, which is different from subarachnoid hemorrhage. In the United States, ICH accounts for about 9% of all strokes; in China, it accounts for about 15% to 30% of strokes.
The incidence of ICH increases exponentially with age, with the incidence of ICH increasing exponentially every 10 years after the age of 35. ICH is extremely fatal and disabling, with a 30-40% death rate within 30 days (based on inpatient studies) and even up to 52% (based on community studies). Survivors have an annual mortality rate of about 8% for the next 5 years. Almost half of the annual deaths are attributed to complications of the initial bleeding (e.g., myocardial infarction, sudden death, extracranial hemorrhage, and pneumonia).
Etiology
Causes of ICH include hypertension, cerebral amyloid angiopathy, use of anticoagulant, fibrinolytic, and antiplatelet drugs, use of prohibited drugs, and other bleeding disorders; hypertension is the most common. Secondary causes of ICH include vascular malformations (arteriovenous malformations, dural arteriovenous fistulas, and cavernous vascular malformations), aneurysms, brain tumors (primary and secondary), hemorrhagic transformation of cerebral infarction, cerebral venous tract thrombosis with hemorrhage, and smoker’s disease.
Hypertensive ICH accounts for about 75% of cases, and hypertension is both the most common cause of ICH and a modifiable risk factor. Thrombolytic therapy, age >70 years, blood glucose over 300 mg/dL, NIHSS score >20, and early demonstration of ischemic changes on CT are risk factors predisposing to ICH. Therefore, clinicians should strictly control the timing and indications of thrombolytic therapy, and blind thrombolysis is not advisable in patients of advanced age, critical condition, high blood glucose plus obvious ischemic changes already seen on CT brain scan.
Pathophysiology of ICH
The pathophysiology of ICH is based on cerebral microaneurysm, which is similar to a waterfall effect, and once it occurs, many cerebral microaneurysms may rupture and bleed at the same time, or combined with venous bleeding, sometimes with more than 100 Sometimes the bleeding volume is more than a hundred milliliters. The posthemorrhagic occupancy effect is only one factor, and the subsequent cerebral edema is not due to occupancy alone.
Within 72 h of hemorrhage, cerebral edema increases rapidly with progressive deterioration of neurological function, followed by a slow increase in cerebral edema over the next 10-14 d, after which it gradually subsides. The cerebral edema is related to the amount of hematoma, perhaps due to the plasma exuded from the hematoma. The precipitation of plasma components within the hematoma and hemoglobin degradation products are contributing factors to the formation of edema in the surrounding brain tissue. The release of methemoglobin from hemoglobin degradation produces iron-dependent oxidative damage and causes cell necrosis, i.e., the iron toxicity theory.
The release of thrombin into the brain tissue after ICH is a very harmful factor that can cause secondary brain injury, and the late formation of thrombin can directly cause neuronal toxic effects and blood-brain barrier damage, aggravating vasogenic edema.
Many pro-inflammatory response transcription factors are upregulated after ICH, activating extracellular matrix degrading protein hydrolases, one of which is matrix metalloprotein hydrolases class (MMPs), the latter may have many destructive effects such as blood-brain barrier disruption, hemorrhage, edema, apoptosis and disruption of some cellular signals.
Activation of the inflammatory waterfall response after ICH can increase some cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (NGF-α), which may be involved in the pathophysiological process of vascular rupture and hematoma enlargement, which is associated with factors such as increased blood glucose, fibrin and enlarged hemorrhagic vesicles.
Early hematoma enlargement in ICH is often accompanied by increased leukocytes and fibrinogen, thrombocytopenia and intracerebroventricular accumulation of blood, and markedly elevated plasma IL-6, NGF-α and MMP9. The local oxygen uptake ratio of the brain tissue surrounding the hematoma was shown to be normal by PET studies, suggesting not ischemia but decreased perfusion due to reduced cerebral metabolism.
Classification of shell nucleus hemorrhage
ICH is most frequent in the nucleus accumbens and is classified as limited, involving the internal capsule (anterior and posterior limbs), breaking into the ventricles, downward involving the midbrain, and mixed (both medial and lateral involvement of the internal capsule).ICH should be differentiated from cerebral infarction, craniocerebral trauma, subdural hematoma, encephalitis, and other causes of coma.
Diagnosis
CT scan of the head is the most important tool for the diagnosis of ICH, as it is difficult to distinguish between hemorrhage and ischemia in the absence of CT equipment. CT can immediately confirm the diagnosis of ICH and can provide more accurate and intuitive information about the site and size of the hematoma, whether it has broken into the ventricles, whether there is edema, and whether there are any occupying effects, providing more accurate and intuitive information for medical and surgical treatment options. However, CT also has its limitations; it is difficult to distinguish old ICH from cerebral infarction; it cannot detect microhemorrhagic lesions; and it is likely to show isointense and hypointense lesions or even normal in patients with severe anemia.
Therefore, the CT examination results should not be overly trusted in isolation from the clinic. If the edematous band around the high density is large and irregular at the early onset, not at the common site of hemorrhage, and the high density foci are very round and close to the meninges, brain tumor should be alerted and further examination by CT-enhanced scan or MRI is needed. MRI is still not the main means of detection for acute ICH, but it can still provide many information that CT cannot reveal for the subacute and chronic phases of ICH.
MRI gradient-echo sequences (T2*) can detect microhemorrhagic foci, and anticoagulation and antiplatelet agents (including blood-activating drugs) should be used with caution when more microhemorrhagic foci are found.
Treatment
The medical and surgical consultation and treatment process for ICH is basically similar, starting with careful history taking, necessary laboratory tests, urgent cranial CT scan and neurological function assessment. In cases of coma, deteriorating neurological function, or respiratory insufficiency, emergency tracheal intubation should be performed to address ventilation.
ICH due to coagulation dysfunction should be promptly given lyophilized plasma and vitamin K. Lobar hemorrhage with epileptic seizures should be given a loading dose of antiepileptic drugs; those with increased blood pressure (systolic blood pressure over 200-220 mmHg and diastolic blood pressure over 110-120 mmHg) should consider appropriate application of antihypertensive drug therapy, and generally do not easily lower blood pressure or use drastic antihypertensive drugs, preferably not given orally . However, lowering the systolic blood pressure below 140 to 160 mmHg has also been advocated as beneficial in preventing early expansion of the hematoma (INTERACT study).
Supportive therapy is crucial and includes regular neurological assessment, maintenance of vital signs, intensive care, oxygenation via nasal or mask to ensure normal oxygen saturation, maintenance of water and electrolyte balance, reduction of body temperature to normal range with antipyretic drugs, ice blankets or intravascular subhypothermia (hypothermia should not be used in the acute phase to avoid hypertension), wearing elastic stockings to prevent venous thrombosis of the lower extremities, and prevention of stress ulcers.
If the patient’s coma deepens or neurological function continues to deteriorate, intracranial pressure monitoring should be performed promptly, and cranial pressure-lowering drugs and methods (such as hyperventilation, elevation of the head of the bed, appropriate sedation, cranial pressure-lowering drugs [tachypnea, hypertonic saline, mannitol and glycerol fructose, etc.], and finally cranial open flap decompression surgery should be considered for ICH patients with moderate amount of hematoma) should be selected appropriately according to the condition. The use of hormones remains controversial (effective only for moderate-sized hematomas) Hormonal therapy may be effective.
Application of standardized and evaluated precise stereotactic minimally invasive surgery followed by local administration of local combination therapy drugs may improve patient prognosis. local combination therapy drugs include rt-PA, dexamethasone, nerve growth factor (NGF), NGF+dexamethasone, etc.
Cerebellar hemorrhage >75px in diameter, regardless of size, should be treated with immediate surgical removal of the hematoma as long as there is neurological deterioration and signs of brainstem compression; surgical removal of the hematoma should be considered in young patients with easily accessible large cortical hematoma or secondary neurological deterioration. enlargement, reduced morbidity and mortality, and improved neurological function as judged at 90 days.
However, there was a small increase in thromboembolic adverse events. However, the final results of the FAST phase III trial were negative, and there was no benefit from recombinant activated factor VII treatment, probably due to severe impaired consciousness, intraventricular blood accumulation, ventricular enlargement, and older age in the treated group. Cone-cranial hematoma fragmentation (minimally invasive surgery) is a life-saving method that requires good timing (indication for surgery). Minimally invasive intracranial hematoma aspiration and drainage (minimally invasive surgery) for ICH requires standardized clinical procedures and a larger sample of evidence-based medicine.
Prognostic factors
In general, the prognosis of ICH depends on the magnitude of the bleeding, the Glasgow Coma Scale score (GCS, or other neurological rating scale), the presence of intracerebroventricular blood, and the amount of accumulated blood. Poor prognostic factors include advanced age, hydrocephalus, deep brain hemorrhage, high blood pressure on admission, and those requiring mechanical ventilation. Patients with ICH who have more than 40 mL of hemorrhage, a GCS score of 7 or less, a blood glucose higher than 8 mmol/L and a midline structure displaced more than 5 mm to the contralateral side tend to die within 24 h, and medical management is difficult to be successful.
The prognostic factors for death within 30d included impairment of consciousness (5 points), urinary incontinence (4 points), dysphagia (3 points), temperature over 36.5oC on admission (2 points) and those with no history of diabetes mellitus with elevated blood glucose (2 points), with a maximum of 16 points, and the risk of death within 30d was about 75% for those with more than 11 points.
Outlook
In the future, we will continue to work on the stratified treatment of cerebral hemorrhage (surgery, minimally invasive interventions), stem cell transplantation (still in animal experimental stage), development of rehabilitation medicine, early control of hematoma expansion (hypotension, hemostatic drugs, neuroprotective agents), and new therapeutic targets. In the face of opportunities and challenges, we neurologists have a long way to go, and we hope that there will be new methods to play a positive role in the diagnosis and treatment of cerebral hemorrhage.