Intraparenchymal hemorrhage
Synonyms and keywords:Intracerebral Hemorrhage, Intraparencymal Hematoma, Intracerebral Hematoma, Parenchymal Hemorrhages, Cerebral Brain Hemorrhages; Hemorrhage, Cerebral Brain Hemorrhage, Cerebral Hemorrhage, Cerebrum Parenchymal Hemorrhage, Cerebral Hemorrhages, Cerebrum Hemorrhages;, Cerebral Hemorrhages.

# Overview
Intraparenchymal hemorrhage is one of the common causes of stroke. Although less prevalent than ischemia, intraparenchymal hemorrhage has the highest mortality rate among all the causes of stroke. It is associated with multiple risk factors, with hypertension being the most common among them. It can be classified into primary or secondary type depending upon the underlying etiology. Intraparenchymal hemorrhage occurs more commonly in the older population. Diagnosis is made using Ct-scan or MRI brain. Owing to its poor prognosis, early diagnosis and management are of paradigm importance.

# Historical prespective
- There is no available historical data regarding intraparenchymal hemorrhage.

# Classification
- Intraparenchymal hemorrhage may be classified according to etiology into primary and secondary intraparenchymal hemorrhage. Intraparenchymal hemorrhage occurring as a consequence of hypertension or cerebral amyloid angiopathy is termed as primary intraparenchymal hemorrhage. If the etiology is other than hypertension or cerebral amyloid angiopathy then intraparenchymal hemorrhage is termed as secondary intraparenchymal hemorrhage.

# Pathophysiology
- Intraparenchymal hemorrhages are caused by small bleeds that occur when parenchymal arterioles rupture. Hypertension is the major risk factor for development of intraparenchymal hemorrhage. Hypertension increases the risk of intraparenchymal hemorrhage by inducing certain degenerative changes in small arterioles. Sometimes aneurysms form as a consequence and eventually rupture. Hypertensive hemorrhages usually occur in deep brain structures like basal ganglia, pons, thalamus and cerebellum.
- Cerebral amyloid angiopathy is another risk factor that contributes to a large number of intraparenchymal hemorrhages. It involves deposition of -amyloid in cortical blood vessels, which results in weakened blood vessels and hence increased risk of rupture. 
- Certain vascular malformations are also at increased risk of rupture and causing intraparenchymal hemorrhage. Arteriovenous malformations consist of dysplastic arteries that form a web and drain into veins. These Av malformations may rupture leading to intraparenchymal hemorrhage.
- Dural arteriovenous fistulae are abnormal connections between arteries and veins inside dura matter. If the drainage occurs into a pressurized vein then there is an increased chance of hemorrhage as a result of venous hypertension.
- Cerebral venous thrombosis may lead to intraparenchymal hemorrhage as there is poor cerebral venous drainage causing increased pressure in vein and eventually venous rupture. *Saccular aneurysm when ruptures may lead to intraparenchymal hemorrhage, although it mostly results in subarachnoid hemorrhage. Moyamoya disease involves the narrowing of intracranial arteries. Collateral blood vessels form as a consequence. These collaterals have fragile walls and are prone to rupture leading to intraparenchymal hemorrhage.

# Causes
- The most common cause of spontaneous intra parenchymal hemorrhage is hypertensive angiopathy. In older adults, most common cause of lobar intra-parenchymal hemorrhage is cerebral amyloid angiopathy. For intra-parenchymal hemorrhages in children, vascular malformations are the most common cause.  Less common causes of spontaneous intra-parenchymal hemorrhage include vasculitis, CNS infection, rupture of dural AV fistula, septic embolism, mycotic aneurysm rupture, tumors, Av malformation rupture, cerebral hyperperfusion syndrome, rupture of saccular aneursym, dural sinus thrombosis, moyamoya disease, reversible cerebral vasoconstriction syndromes, transformation of ischemic stroke into hemorrhagic stroke, , systemic illnesses like cirrhosis of liver and thrombocytopenia, medications for anticoagulation, drugs like amphetamines and cocaine. 

# Differentiating intraparenchymal hemorrhage from other Diseases
- Intraparenchymal hemorrhage must be differentiated from ischemic stroke. But it is difficult to differentiate between the 2 based on clinical features. Therefore, neuroimaging should always be used to confirm the diagnosis.

# Epidemiology and Demographics
- The incidence of intra-parenchymal hemorrhage is approximately  per 100,000 person years. 

## Age
- Intraparenchymal hemorrhage is more commonly observed among elderly patients. Risk doubles every 10 years after 35 years of age. 

## Gender
- Intraparenchymal hemorrhage affects men and women equally. 

## Race
- Intraparenchymal hemorrhage usually affects individuals of asian race more than other races.

# Risk Factors
- The most potent risk factor in the development of intraparenchymal hemorrhage is hypertension.  Other risk factors include presence of amyloid angiopathy, old age, use of anti-coagulants, alcohol intake, smoking, low LDL and total cholesterol, increased HDL cholesterol, presence of apolipoprotein E with E2 and E4 alleles.

# Natural History, Complications, and Prognosis
- Common complications of intraparenchymal hemorrhage include raised ICP, seizures, focal neurologic deficits, functional decline of patients, post hemorrhage dementia, post hemorrhage depression. 
- Prognosis of intraparenchymal hemorrhage is generally poor.  30 day case fatality rate of IPH is reported to be around 40%. IPH has the highest mortality rate among all the causes of stroke with the 1-year and 10-year survival rates of 40% and 24% respectively.  Annually, it is responsible for over 20,000 deaths in US.

# Diagnosis

## Diagnostic criteria
- There are no specific diagnostic criteria.

## History and symptoms
Common symptoms of intraparenchymal hemorrhage include:
- acute onset focal neurological deficit
- altered sensorium
- vomiting
- headache
- seizures.
- Nausea, vomiting, headache and decreased level of consciousness when present point more towards hemorrhage rather than ischemic stroke.  Seizures occur more commonly in IPH secondary to venous sinus thrombosis or cavernous malformation as compared to other causes of IPH.   Secondary IPH, specially due to venous sinus thrombosis and vascular malformations usually presents at younger age and patients usually have no history of hypertension.

## Physical examination
Physical examination may be remarkable for:.   
- lower than normal GCS
- hemiplegia
- hemisensory loss
- bradycardia or tachycardia
- gaze palsy
- dysarthria
- facial palsy
- Dysphasia

## Laboratory findings
- There are no specific laboratory findings associated with intraparenchymal hemorrhage.

## Electrocardiogram
- Findings on ECG associated with intraparenchymal hemorrhage include, ST-T wave changes and prolonged QT interval. It is suspected to be caused by excess catecholamine release as a consequence of brain injury. 

## X-ray
- There are no x-ray findings associated with intraparenchymal hemorrhage.

## Echocardiography or Ultrasound
- Findings on electrocardiography associated with intraparnechymal hemorrhage include, decreased ejection fraction and wall motion abnormalities.  

## CT scan
- Non-contrast Ct scan is the gold standard for diagnosing intraparenchymal hemorrhage in Emergency, as it is readily available and highly sensitive for intraparenchymal hemorrhage. Moreover, it can provide valuable information regarding location and extension of intra-parenchymal hemorrhage, hydrocephalus and compression of the brainstem by hematoma.
- CT-angiography is a very useful technique for identifying vascular abnormalities like Av shunts, aneurysms, and venous sinus thrombosis that could have lead to intraparenchymal hemorrhage.  Though Ct-angiography is very helpful for diagnosing vascular malformations but digital subtraction angiography is the gold standard for this purpose. The presence of "spot sign" on CTA, i.e, extravasation of contrast within hematoma predicts hematoma expansion and adverse outcome.

## MRI
- Owing to its high sensitivity and specificity, MRI is another suitable modality for diagnosis of intraparenchymal hemorrhage. Secondary causes of intraparenchymal hemorrhage like tumor, ischemic stroke or cavernous malformation can be better identified by MRI. Microbleed patterns indicative of hypertensive angiopathy or cerebral amyloid angiopathy may also be detected in a better fashion through MRI.

## Other imaging findings
- There are no other imaging findings associated with intraparenchymal hemorrhage.

## Other diagnostic studies
- There are no other diagnostic studies associated with intraparenchymal hemorrhage.

# Treatment

## Medical Therapy
- Intraparenchymal hemorrhage is a medical emergency and requires prompt treatment.  Special attention should be given to airway support as these patients may be unable to protect their airways. Blood pressure control is an important feature of IPH management as raised blood pressure is associated with hematoma expansion and poor outcome. According to American Heart Association/American Stroke Association guidelines, for IPH patients presenting with systolic blood pressure of 150 to 220mmHg, the goal should be to keep the systolic blood pressure below 140mmHg if there is no contraindication.  Short acting anti hypertensives like nicardipine and labetalol are recommended while drugs like nitrates and hydralazine should not be used.
- Specific coagulation factor therapy or platelet transfusion is recommended for patients with coagulation factor deficiency or thrombocytopenia respectively. Platelet transfusion is not recommended for patients on antiplatelet drugs. Patients who are taking warfarin or any other Vitamin K antagonist and have high INR should be given Vitamin K and prothrombin complex concentrate. Idarucizumab should be administered to patients on dabigatran while adexanet alfa should be given to patients taking factor Xa inhibitors.  . For reversal of heparin induced coagulopathy, protamine sulphate should be administered.
- Antiepileptics should be given to patients who present with seizures. Prophylactic use of antiepileptic is not recommended. Intermittent pneumatic compression for Dvt prophylaxis should also be done. 1 day after the bleeding cessation, low molecular weight heparin or subcutaneous heparin can also be used for Dvt prophylaxis.

## Surgery
- Urgent neurosurgical assessment of IPH patients should be done. IPH patients who are comatose, have substantial intraventricular hemorrhage and hydrocephalus should undergo external ventricular drain placement.  Benefit of surgical evacuation of hematomas over conservative management is still unproven. Surgical evacuation of hematomas is recommended in case of cerebellar hematomas with evidence of hydrocephalus or/and brainstem compression. 

## Prevention
- Long term blood pressure control is the most important measure in preventing recurrent intraparenchymal hemorrhage. Target blood pressure of less than 130/80mmHg is recommended.  In addition to blood pressure control certain other measures like smoking cessation, avoiding illicit drug use as well as alcohol intake can have beneficial effects in this regard.