History

Fact Explanation
Confusion Cerebral oedema is due to abnormal accumulation of fluid within the brain parenchyma. Which can occur by two methods: vasogenic and cytotoxic. Main areas of fluid accumulation inside the brain are blood in the cerebral blood vessels, the cerebrospinal fluid in the ventricular system and subarachnoid space, the interstitial fluid of the brain parenchyma, and the intracellular fluid of the neurons and glia. [6] Vasogenic oedema occurs when the fluid from the vessels accumulate extracellularly and intracellular fluid accumulation as in the case of ischaemia/ infarction referred to cytotoxic oedema. Vasogenic edema, occurs due to the protein extravasation secondary to damaging the vessel wall, that creates an increased osmotic gradient. During the cytotoxic damage,the releasing mediators such as bradykinin, glutamate, arachidonic acid, and leukotrienes are responsible for the swelling of the parenchyma. Volume of the rigid skull is fixed. Brain swelling may be compensated by displacement of CSF (and blood) at initial phase. [2] Effect of swelling may cause secondary neuronal injury. [6]
Headache Small changes in percentage of brain water content can reflect large changes in the absolute water content of the brain. These may alter the intracranial pressure and blood flow. Cerebral perfusion pressure may depend on intracranial pressure and the mean arterial pressure. The brain has an autoregulatory mechanism to maintain perfusion at nearly normal level. [9] Cerebral oedema will lead to increased intracranial pressure and it is associated with high mortality when the perfusion pressure is less than 50 mmHg.
Focal neurological symptoms: motor weakness, abnormalities in gait etc. Cerebral tumours can be the cause for cerebral edema. [7]
History of stroke Infarction of the parenchyma causes cytotoxic cerebral oedema. Ischemic and hemorrhagic stroke will have poor outcome when complicate with cerebral oedema. [2]
High altitude This is a rare aetiology. Hypoxia is the contributory factor. [8]
Head trauma May damage the brain cells. [5]
History of diabetes Osmotic fluctuations during the treatment of diabetic ketoacidosis is a potentially life-threatening complication. [3]
History of liver failre Associated with high risk of encephalopathy and cerebral oedema. When plasma glucose is rapidly lowered with insulin, an osmotic gradient develops from brain to plasma. Therefore hypoglycaemia is also a cause for the cerebral oedema. [1]
History of high blood pressure Hypertensive patients have higher chance of getting cerebral oedema following cerebral injury like infarction/haemorrhage than normotensive people. [4]
Fever, pain on neck retraction Meningitis/ meningoencephalitis like infection [5] may be an aetiology.
References
  1. ARIEFF AI, KLEEMAN CR. Studies on Mechanisms of Cerebral Edema in Diabetic Comas. EFFECTS OF HYPERGLYCEMIA AND RAPID LOWERING OF PLASMA GLUCOSE IN NORMAL RABBITS J Clin Invest [online] 1973 Mar, 52(3):571-583 [viewed 12 August 2014] Available from: doi:10.1172/JCI107218
  2. KEEP RF, HUA Y, XI G. Brain water content. A misunderstood measurement? Transl Stroke Res [online] 2012 Jun 1, 3(2):263-265 [viewed 12 August 2014] Available from: doi:10.1007/s12975-012-0152-2
  3. YUEN N, ANDERSON SE, GLASER N, TANCREDI DJ, O'DONNELL ME. Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis Diabetes [online] 2008 Oct, 57(10):2588-2594 [viewed 12 August 2014] Available from: doi:10.2337/db07-1410
  4. ADACHI M, ROSENBLUM WI, FEIGIN I. Hypertensive disease and cerebral oedema. J Neurol Neurosurg Psychiatry [online] 1966 Oct, 29(5):451-455 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC49607
  5. ROSENBERG RN. Treatment of Cerebral Edema Calif Med [online] 1971 Sep, 115(3):49 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518083
  6. WALCOTT BP, KAHLE KT, SIMARD JM. Novel Treatment Targets for Cerebral Edema Neurotherapeutics [online] 2012 Jan, 9(1):65-72 [viewed 12 August 2014] Available from: doi:10.1007/s13311-011-0087-4
  7. COLLINS V. BRAIN TUMOURS: CLASSIFICATION AND GENES J Neurol Neurosurg Psychiatry [online] 2004 Jun, 75(Suppl 2):ii2-ii11 [viewed 18 September 2014] Available from: doi:10.1136/jnnp.2004.040337
  8. BHUTIA M, GOYAL K, RAI A, KEDIA S, KUMAR N, MITRA R. High altitude cerebral edema with a fatal outcome within 24 h of its onset: Shall acclimatization be made compulsory? Saudi J Anaesth [online] 2013, 7(4):488-489 [viewed 18 September 2014] Available from: doi:10.4103/1658-354X.121070
  9. ATKINSON WJ. Cerebral Swelling: Its Physiology, Pathology, Clinical Symptoms and Signs, Differential Diagnosis and Treatment Ann R Coll Surg Engl [online] 1952 Dec, 11(6):367-394 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377587

Examination

Fact Explanation
Febrile Infections may be the cause. [1]
Reduced heart rate (bradycardia) Cushing's reflex is a triad of signs comprised of hypertension, bradycardia and apnea. It is occurred as a response to raised intracranial pressure. It is an autonomic response to maintain an adequate cerebral perfusion pressure despite an elevated ICP. It may be a feature of impending herniation. It is mainly seen in intrinsic brainstem lesions, especially at the ponto-medullary junction. [4]
Tachypnea Increased respiratory rate and hyperventilation is seen due to cerebral herniation and pressure on the brain stem. [4]
Hypertension Cushing's reflex is bradycardia with high blood pressure. [4]
Loss of consciousness or coma Cerebral herniation [6] (subfalcine, transtentorial. tonsillar) may lead to conning, and later coma.Reticular activating system is situated at the brainstem, which gets compressed during cerebral herniation.
Focal neurological signs: motor weakness, sensory impaiment, extensor plantar, increased tone, clonus etc. Cerebral tumours can be the cause for cerebral edema. [1] Ischemic and hemorrhagic stroke will be another causes for cerebral oedema. [2]
Decerebrate posture Secondary neuronal damage may occurred due to the cerebral oedema. [3]
Papilloedema Due to increased intracranial pressure. [7]
Pupilary changes Ipsilateral pupillary dilatation occurs in cerebral herniation. [4]
Neck stiffness Meningitis/ meningoencephalitis may be an aetiology. [5]
References
  1. ROSENBERG RN. Treatment of Cerebral Edema Calif Med [online] 1971 Sep, 115(3):49 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151808
  2. KEEP RF, HUA Y, XI G. Brain water content. A misunderstood measurement? Transl Stroke Res [online] 2012 Jun 1, 3(2):263-265 [viewed 12 August 2014] Available from: doi:10.1007/s12975-012-0152-2
  3. WALCOTT BP, KAHLE KT, SIMARD JM. Novel Treatment Targets for Cerebral Edema Neurotherapeutics [online] 2012 Jan, 9(1):65-72 [viewed 12 August 2014] Available from: doi:10.1007/s13311-011-0087-4
  4. DADLANI R, CHALLAM K, GARG A, HEGDE AS. Can bradycardia pose as a "red herring" in neurosurgery? Surgical stress exposes an asymptomatic sick sinus syndrome: Diagnostic and management dilemmas Indian J Crit Care Med [online] 2010, 14(4):212-216 [viewed 13 August 2014] Available from: doi:10.4103/0972-5229.76088
  5. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 26 August 2014] Available from: doi:10.1177/1756285609337975
  6. JONES SW, WEBB D. Cerebral herniation in bacterial meningitis. BMJ [online] 1993 May 22, 306(6889):1413 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677831
  7. CAMERON AJ. MARKED PAPILLOEDEMA IN PULMONARY EMPHYSEMA Br J Ophthalmol [online] 1933 Mar, 17(3):167-169 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC511527

Differential Diagnoses

Fact Explanation
Stroke Patient presents with sudden onset weakness of one side of the body, may be associated with sensory impairment, dysarthria, dysphagia, facial nerve palsy, vertigo, etc depend on the area of infarction. May have a history of predisposing factors such as diabetes mellitus, hypertension, ischaemic heart disease, past history of stroke and anticoagulant therapy. Infarction of the parenchyma causes cytotoxic cerebral oedema. Ischemic and hemorrhagic stroke will have poor outcome when complicate with cerebral oedema. [1]
Cerebral tumours [4] Space occupying lesions may present with focal neurological symptoms [5] and signs. Early morning headache relieved by vomiting may present.
Central nervous system infections May be acute or chronic. [2] Headache, neck stiffness, fever, positive Kernig's and Brudzinski's sign are the differentiating features. Cerebrospinal fluid analysis will helpful to determine the cause of infection.
Head injury Head trauma [3] may be a cause for the cerebral haematomas like extradural, subdural and intracranial hemorrhages. Neuronal cell injury, compression of the surrounding structures will cause the symptoms. Alcoholics are more prone to these types of injuries.
References
  1. KEEP RF, HUA Y, XI G. Brain water content. A misunderstood measurement? Transl Stroke Res [online] 2012 Jun 1, 3(2):263-265 [viewed 12 August 2014] Available from: doi:10.1007/s12975-012-0152-2
  2. 1) LEE CH, CHANG TY, LIU JW, CHEN FJ, CHIEN CC, TANG YF, LU CH. Correlation of anti-fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis BMC Infect Dis [online] :361 [viewed 11 August 2014] Available from: doi:10.1186/1471-2334-12-361
  3. LEININGER BE, GRAMLING SE, FARRELL AD, KREUTZER JS, PECK EA 3RD. Neuropsychological deficits in symptomatic minor head injury patients after concussion and mild concussion. J Neurol Neurosurg Psychiatry [online] 1990 Apr, 53(4):293-296 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1014166
  4. COLLINS V. BRAIN TUMOURS: CLASSIFICATION AND GENES J Neurol Neurosurg Psychiatry [online] 2004 Jun, 75(Suppl 2):ii2-ii11 [viewed 18 September 2014] Available from: doi:10.1136/jnnp.2004.040337
  5. BENNETT AH. Case of Cerebral Tumour Med Chir Trans [online] 1885:243-275 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121420

Investigations - for Diagnosis

Fact Explanation
Computer tomography In vasogenic edema, CT reveals hypodense frond-like regions located within the white matter with massive edema in relation to the size of the lesion. In cytotoxic edema, there is diffuse hypodense subcortical regions. with a hypodense region in a specific arterial vascular distribution. There will be mass effect causing compression of the sulci, ipsilateral ventricles, cerebral herniation and midline shift. [2]
Magnetic Resonance Imaging Infarctions will manifest as low attenuation with intracellular oedema involving both the gray and white matter. Vasogenic oedema only involves the white matter and occurs in tumours and abscesses. [1] perihematomal edema may be associated with intracerebral hemorrhage. [2]
Serum electrolytes Low serum sodium (hyponatremia) is a cause for the cerebral oedema. [3]
References
  1. HOWELL DA, EMBREE G, TATLOW WF. Observations on Strokes and Cerebral Edema with Intracranial Tumours Can Med Assoc J [online] 1963 Oct 26, 89(17):866-870 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1921916
  2. VENKATASUBRAMANIAN C, MLYNASH M, FINLEY-CAULFIELD A, EYNGORN I, KALIMUTHU R, SNIDER RW, WIJMAN CA. Natural history of perihematomal edema following intracerebral hemorrhage measured by serial magnetic resonance imaging Stroke [online] 2011 Jan, 42(1):73-80 [viewed 13 August 2014] Available from: doi:10.1161/STROKEAHA.110.590646
  3. ATKINSON WJ. Cerebral Swelling: Its Physiology, Pathology, Clinical Symptoms and Signs, Differential Diagnosis and Treatment Ann R Coll Surg Engl [online] 1952 Dec, 11(6):367-394 [viewed 18 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377587

Investigations - Fitness for Management

Fact Explanation
Random blood sugar In diabetic ketoacidosis there is hyperglycaemia with an elevation of blood sugar level. Hypoglycaemia can also be a cause for cerebral oedema. [1] Low plasma glucose less than 60 mg/dl will be there in hypoglycaemia. [2]
References
  1. YUEN N, ANDERSON SE, GLASER N, TANCREDI DJ, O'DONNELL ME. Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis Diabetes [online] 2008 Oct, 57(10):2588-2594 [viewed 12 August 2014] Available from: doi:10.2337/db07-1410
  2. PERLMUTER LC, FLANAGAN BP, SHAH PH, SINGH SP. Glycemic Control and Hypoglycemia: Is the loser the winner? Diabetes Care [online] 2008 Oct, 31(10):2072-2076 [viewed 13 August 2014] Available from: doi:10.2337/dc08-1441

Investigations - Followup

Fact Explanation
Serum osmolality Monitored during mannitol treatment and maintained less than 32 mosmol/kg. Hypo-osmolality (plasma osmolality [P Osm] < 290 mOsm/Kg H2O) can cause further brain damage. [2]
Serum electrolytes Serum electrolyte imbalances are potential causes for secondary brain insult. Eg;- hyponatremia (serum sodium < 142 mEq/L. [2] ). may induce seizures. In addition serum electrolytes may be altered during treatment. eg:- Serum sodium elevation after hypertonic saline therapy. [1]
References
  1. WALCOTT BP, KAHLE KT, SIMARD JM. Novel Treatment Targets for Cerebral Edema Neurotherapeutics [online] 2012 Jan, 9(1):65-72 [viewed 12 August 2014] Available from: doi:10.1007/s13311-011-0087-

Investigations - Screening/Staging

Fact Explanation
Magnetic Resonance Imaging Causative factors such as brain tumors, [1] infatction of the brain, cerebral abscesses or an obstruction to fluid drainage (hydrocephalus) with enlarged ventricles can be seen on MRI.
Computer tomography CT findings, enable to determine the type of edema present and the nature of the underlying pathological process. Cerebral tumours, haemorrhages are evident on CT. [2]
References
  1. HOWELL DA, EMBREE G, TATLOW WF. Observations on Strokes and Cerebral Edema with Intracranial Tumours Can Med Assoc J [online] 1963 Oct 26, 89(17):866-870 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1921916
  2. COLLINS V. BRAIN TUMOURS: CLASSIFICATION AND GENES J Neurol Neurosurg Psychiatry [online] 2004 Jun, 75(Suppl 2):ii2-ii11 [viewed 18 September 2014] Available from: doi:10.1136/jnnp.2004.040337

Management - General Measures

Fact Explanation
Management of fever Infections may be the cause for the cerebral oedema. [1] High fever increases the uptake of ammonia into the brain causing worsening of cerebral oedema , therefore antipyretics should be used to control the fever.
Monitoring the vital signs Heart rate, respiratory rate, blood pressure, level of consciouness and neurological parameters [2] like pupils, motor response need to be monitored. Glasgow Coma Scale (GCS) is of value in checking level of consciousness.
Monitoring the intracranial pressure Not needed in every patient. Important in patients with hypotension, renal and liver failure, and in those with reduced oxygen saturation. [1]
Correct the underlying pathlogy Hypotension, hypoglycemia, malnutrition, alcoholism, renal and liver failure [3] etc need specific attention as these may aggravate the cerebral oedema causing further brain damage.
References
  1. ROSENBERG RN. Treatment of Cerebral Edema Calif Med [online] 1971 Sep, 115(3):49 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518083
  2. ZADOR Z, STIVER S, WANG V, MANLEY GT. Role of Aquaporin-4 in Cerebral Edema and Stroke Handb Exp Pharmacol [online] 2009:159-170 [viewed 18 September 2014] Available from: doi:10.1007/978-3-540-79885-9_7
  3. RAMA RAO KV, REDDY PV, TONG X, NORENBERG MD. Brain Edema in Acute Liver Failure: Inhibition by L-Histidine Am J Pathol [online] 2010 Mar, 176(3):1400-1408 [viewed 18 September 2014] Available from: doi:10.2353/ajpath.2010.090756

Management - Specific Treatments

Fact Explanation
Type of treatment Treatment will depend on the major type of edema contributing to the swelling process: cytotoxic or vasogenic. [1]
Manitol 20% mannitol solution is used to lower the fluid in the cerebral parenchyma. [1] This draws fluid into the intravascular space via an osmotic gradient. Mannitol is administered rapidly in a 1 gm/kg bolus. [2] This may cause systemic hypotension, decreased cerebral perfusion, acute renal failure, and delayed accumulation within the extravascular compartment. Ultimately this leads to a paradoxical rebound elevation in intracranial pressure.
Hypertonic saline This is a type of hyperosmotic therapy to bring fluid into the intravascular space given as 30 mL boluses of 23.4% saline in a single dose. [2] This is used for the treatment of cerebral edema, intracranial hypertension and elevated ICP resulting from ischemic stroke. [3]
Hyperventilation Passive hyperventilation reduces PaCO2 level and causes vasoconstriction. [1]
Corticosteroids High doses are used in the treatment of cerebral oedema due to high altitude. Dexamethasone 4mg 6 hourly is used to reduce subacute or chronic cerebral oedema. [1]
Surgery When there is a mass effect and it is difficult to manage by osmotherapy alone, decompressive craniectomy is considered. [2]
Barbiturates, such as pentobarbital Used when the osmotherapy has failed. It has the ability to lower the cerebral metabolic demand, thereby reducing intracranial blood volume. [2]
References
  1. ROSENBERG RN. Treatment of Cerebral Edema Calif Med [online] 1971 Sep, 115(3):49 [viewed 12 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518083
  2. WALCOTT BP, KAHLE KT, SIMARD JM. Novel Treatment Targets for Cerebral Edema Neurotherapeutics [online] 2012 Jan, 9(1):65-72 [viewed 12 August 2014] Available from: doi:10.1007/s13311-011-0087-4
  3. HUANG LQ, ZHU GF, DENG YY, JIANG WQ, FANG M, CHEN CB, CAO W, WEN MY, HAN YL, ZENG HK. Hypertonic saline alleviates cerebral edema by inhibiting microglia-derived TNF-? and IL-1?-induced Na-K-Cl Cotransporter up-regulation J Neuroinflammation [online] :102 [viewed 13 August 2014] Available from: doi:10.1186/1742-2094-11-102