In the UK, the formal rules for the diagnosis of brainstem death have undergone only minor modifications since they were first published in 1976. The most recent revision of the UK's Department of Health Code of Practice governing use of that procedure for the diagnosis of death reaffirms the preconditions for its consideration. These are:

1. There should be no doubt that the patient’s condition – deeply comatose, unresponsive and requiring artificial ventilation—is due to irreversible brain damage of known cause.

2. There should be no evidence that this state is due to depressant drugs.

3. Primary hypothermia as the cause of unconsciousness must have been excluded, and

4. Potentially reversible circulatory, metabolic and endocrine disturbances likewise.

5. Potentially reversible causes of apnoea (dependence on the ventilator), such as muscle relaxants and cervical cord injury, must be excluded.

With these pre-conditions satisfied, the definitive criteria are:

1. Fixed pupils which do not respond to sharp changes in the intensity of incident light.

2. No corneal reflex.

3. Absent oculovestibular reflexes – no eye movements following the slow injection of at least 50ml of ice-cold water into each ear in turn (the caloric reflex test).

4. No response to supraorbital pressure.

5. No cough reflex to bronchial stimulation or gagging response to pharyngeal stimulation.

6. No observed respiratory effort in response to disconnection of the ventilator for long enough (typically 5 minutes) to ensure elevation of the arterial partial pressure of carbon dioxide to at least 6.0 kPa (6.5 kPa in patients with chronic carbon dioxide retention). Adequate oxygenation is ensured by pre-oxygenation and diffusion oxygenation during the disconnection (so the brainstem respiratory centre is not challenged by the ultimate, anoxic, drive stimulus). This test—the apnoea test—is dangerous – and may prove lethal.

Two doctors, of specified status and experience, are required to act together to diagnose death on these criteria and the tests must be repeated after “a short period of time ... to allow return of the patient’s arterial blood gases and baseline parameters to the pre-test state”. These criteria for the diagnosis of death are not applicable to infants below the age of two months.

Brainstem death is a clinical syndrome defined by the absence of reflexes with pathways through the brainstem—the “stalk” of the brain, which connects the spinal cord to the mid-brain, cerebellum and cerebral hemispheres—in a deeply comatose, ventilator-dependent patient.

Identification of this state carries a very grave prognosis for survival; cessation of heartbeat often occurs within a few days although it may continue for weeks or even months if intensive support is maintained.

In the United Kingdom, the formal diagnosis of brainstem death by the procedure laid down in the official Code of Practice permits the diagnosis and certification of death on the premise that a person is dead when consciousness and the ability to breathe are permanently lost, regardless of continuing life in the body and parts of the brain, and that death of the brainstem alone is sufficient to produce this state.

This concept of brainstem death is also accepted as grounds for pronouncing death for legal purposes in India and Trinidad & Tobago. Elsewhere in the world the concept upon which the certification of death on neurological grounds is based is that of permanent cessation of all function in all parts of the brain—whole brain death—with which the reductionist United Kingdom concept should not be confused. The United States' President's Council on Bioethics made it clear, in its White Paper of December 2008, that the United Kingdom concept and clinical criteria are not considered sufficient for the diagnosis of death in the United States of America.

Brain death is the complete loss of brain function (including involuntary activity necessary to sustain life). It differs from persistent vegetative state, in which the person is alive and some autonomic functions remain.

Brain death is used as an indicator of legal death in many jurisdictions, but it is defined inconsistently. Various parts of the brain may keep functioning when others do not anymore, and the term "brain death" has been used to refer to various combinations. For example, although a major medical dictionary says that "brain death" is synonymous with "cerebral death" (death of the cerebrum), the US National Library of Medicine Medical Subject Headings (MeSH) system defines brain death as including the brainstem. The distinctions can be important because, for example, in someone with a dead cerebrum but a living brainstem, the heartbeat and ventilation can continue unaided, whereas in whole-brain death (which includes brain stem death), only life support equipment would keep those functions going. Patients classified as brain-dead can have their organs surgically removed for organ donation.

Cerebral hypoxia can be caused by any event that severely interferes with the brain's ability to receive or process oxygen. This event may be internal or external to the body. Mild and moderate forms of cerebral hypoxia may be caused by various diseases that interfere with breathing and blood oxygenation. Severe asthma and various sorts of anemia can cause some degree of diffuse cerebral hypoxia. Other causes include status epilepticus, work in nitrogen-rich environments, ascent from a deep-water dive, flying at high altitudes in an unpressurized cabin without supplemental oxygen, and intense exercise at high altitudes prior to acclimatization.

Severe cerebral hypoxia and anoxia is usually caused by traumatic events such as choking, drowning, strangulation, smoke inhalation, drug overdoses, crushing of the trachea, status asthmaticus, and shock. It is also recreationally self-induced in the fainting game and in erotic asphyxiation.

- Transient ischemic attack (TIA), is often referred to as a "mini-stroke". The American Heart Association and American Stroke Association (AHA/ASA) refined the definition of transient ischemic attack. TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. The symptoms of a TIA can resolve within a few minutes, unlike a stroke. TIAs share the same underlying etiology as strokes; a disruption of cerebral blood flow. TIAs and strokes present with the same symptoms such as contralateral paralysis (opposite side of body from affected brain hemisphere), or sudden weakness or numbness. A TIA may cause sudden dimming or loss of vision, aphasia, slurred speech, and mental confusion. The symptoms of a TIA typically resolve within 24 hours, unlike a stroke. Brain injury may still occur in a TIA lasting only a few minutes. Having a TIA is a risk factor for eventually having a stroke.

- Silent stroke is a stroke which does not have any outward symptoms, and the patient is typically unaware they have suffered a stroke. Despite its lack of identifiable symptoms, a silent stroke still causes brain damage and places the patient at increased risk for a major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as fMRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being predisposing factors.

It is very important for family members and health care professionals to be aware of natural movements also known as Lazarus sign or Lazarus reflex that can occur on a brain-dead person whose organs have been kept functioning by life support. The living cells that can cause these movements are not living cells from the brain or brain stem, these cells come from the spinal cord. Sometimes these body movements can cause false hope for the family members.

A brain-dead individual has no clinical evidence of brain function upon physical examination. This includes no response to pain and no cranial nerve reflexes. Reflexes include pupillary response (fixed pupils), oculocephalic reflex, corneal reflex, no response to the caloric reflex test, and no spontaneous respirations.

It is important to distinguish between brain death and states that may be difficult to differentiate from brain death, (such as barbiturate overdose, alcohol intoxication, sedative overdose, hypothermia, hypoglycemia, coma, and chronic vegetative states). Some comatose patients can recover to pre-coma or near pre-coma level of functioning, and some patients with severe irreversible neurological dysfunction will nonetheless retain some lower brain functions, such as spontaneous respiration, despite the losses of both cortex and brain stem functionality. Such is the case with anencephaly.

Note that brain electrical activity can stop completely, or drop to such a low level as to be undetectable with most equipment. An EEG will therefore be flat, though this is sometimes also observed during deep anesthesia or cardiac arrest. Although in the United States a flat EEG test is not required to certify death, it is considered to have confirmatory value. In the UK it is not considered to be of value because any continuing activity it might reveal in parts of the brain above the brain stem is held to be irrelevant to the diagnosis of death on the Code of Practice criteria.

The diagnosis of brain death needs to be rigorous, in order to be certain that the condition is irreversible. Legal criteria vary, but in general they require neurological examinations by two independent physicians. The exams must show complete and irreversible absence of brain function (brain stem function in UK), and may include two isoelectric (flat-line) EEGs 24 hours apart (less in other countries where it is accepted that if the cause of the dysfunction is a clear physical trauma there is no need to wait that long to establish irreversibility). The patient should have a normal temperature and be free of drugs that can suppress brain activity if the diagnosis is to be made on EEG criteria.

Also, a radionuclide cerebral blood flow scan that shows complete absence of intracranial blood flow must be considered with other exams – temporary swelling of the brain, particularly within the first 72 hours, can lead to a false positive test on a patient that may recover with more time.

CT angiography is neither required nor sufficient test to make the diagnosis.

Like coma, chronic coma results mostly from cortical or white-matter damage after neuronal or axonal injury, or from focal brainstem lesions.Usually the metabolism in the grey matter decreases to 50-70% of the normal range. The patient lacks awareness and arousal. The patient lies with eyes closed and is not aware of self or surroundings. Stimulation cannot produce spontaneous periods of wakefulness and eye-opening, unlike patients in vegetative state. In medicine, a coma (from the Greek κῶμα koma, meaning deep sleep) is a state of unconsciousness, lasting more than six hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light, sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. Although, according to the Glasgow Coma Scale, a person with confusion is considered to be in the mildest coma. But cerebral metabolism has been shown to correlate poorly with the level of consciousness in patients with mild to severe injury within the first month after traumatic brain injury (TBI).

A person in a state of coma is described as comatose. In general patients surviving a coma recover gradually within 2–4 weeks. But recovery to full awareness and arousal is not always possible. Some patients do not progress further than vegetative state or minimally conscious state and sometimes this also results in prolonged stages before further recovery to complete consciousness.

Although a coma patient may appear to be awake, they are unable to consciously feel, speak, hear, or move. For a patient to maintain consciousness, two important neurological components must function impeccably. The first is the cerebral cortex which is the gray matter covering the outer layer of the brain. The other is a structure located in the brainstem, called reticular activating system (RAS or ARAS). Injury to either or both of these components is sufficient to cause a patient to experience a coma.

The brain requires approximately 3.3 ml of oxygen per 100 g of brain tissue per minute. Initially the body responds to lowered blood oxygen by redirecting blood to the brain and increasing cerebral blood flow. Blood flow may increase up to twice the normal flow but no more. If the increased blood flow is sufficient to supply the brain's oxygen needs then no symptoms will result.

However, if blood flow cannot be increased or if doubled blood flow does not correct the problem, symptoms of cerebral hypoxia will begin to appear. Mild symptoms include difficulties with complex learning tasks and reductions in short-term memory. If oxygen deprivation continues, cognitive disturbances, and decreased motor control will result. The skin may also appear bluish (cyanosis) and heart rate increases. Continued oxygen deprivation results in fainting, long-term loss of consciousness, coma, seizures, cessation of brain stem reflexes, and brain death.

Objective measurements of the severity of cerebral hypoxia depend on the cause. Blood oxygen saturation may be used for hypoxic hypoxia, but is generally meaningless in other forms of hypoxia. In hypoxic hypoxia 95–100% saturation is considered normal; 91–94% is considered mild and 86–90% moderate. Anything below 86% is considered severe.

It should be noted that cerebral hypoxia refers to oxygen levels in brain tissue, not blood. Blood oxygenation will usually appear normal in cases of hypemic, ischemic, and hystoxic cerebral hypoxia. Even in hypoxic hypoxia blood measures are only an approximate guide; the oxygen level in the brain tissue will depend on how the body deals with the reduced oxygen content of the blood.

In locked-in syndrome the patient has awareness, sleep-wake cycles, and meaningful behavior (viz., eye-movement), but is isolated due to quadriplegia and pseudobulbar palsy, resulting from the disruption of corticospinal and corticobulbar pathways. Locked-in syndrome is a condition in which a patient is aware and awake but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for the eyes. Eye or eyelid movements are the main method of communication. Total locked-in syndrome is a version of locked-in syndrome where the eyes are paralyzed as well.

A neonatal stroke is one that occurs in the first 28 days of life, though a late presentation is not uncommon (as contrasted with perinatal stroke, which occurs from 28 weeks gestation through the first 7 days of life). 80% of neonatal strokes are ischemic, and their presentation is varied, making diagnosis very difficult. The most common manifestation of neonatal strokes are seizures, but other manifestations include lethargy, hypotonia, apnoea, and hemiparesis. Seizures can be focal or generalized in nature. Stroke accounts for about 10% of seizures in term neonates.

Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy. It is defined as the sudden and unexpected, non-traumatic and non-drowning death of a person with epilepsy, without a toxicological or anatomical cause of death detected during the post-mortem examination.

While the mechanisms underlying SUDEP are still poorly understood, it is possibly the most common cause of death as a result of complications from epilepsy, accounting for between 7.5 and 17% of all epilepsy-related deaths and 50% of all deaths in refractory epilepsy. The causes of SUDEP seem to be multifactorial and include respiratory, cardiac and cerebral factors, as well as the severity of epilepsy and seizures. Proposed pathophysiological mechanisms include seizure-induced cardiac and respiratory arrests.

SUDEP occurs in about 1 in 1,000 adults and 1 in 4,500 children with epilepsy a year. Rates of death as a result of prolonged seizures (status epilepticus) are not classified as SUDEP.

Neonatal Stroke, similar to a stroke which occurs in adults, is defined as a disturbance to the blood supply of the developing brain in the first 28 days of life. This description includes both ischemic events, which results from a blockage of vessels, and hypoxic events, which results from a lack of oxygen to the brain tissue, as well as some combination of the two. A neonatal stroke occurs in approximately 1 in 4000 births, but is likely much higher due to the lack of noticeable symptoms. One treatment with some proven benefits is hypothermia, but may be most beneficial in conjunction with pharmacological agents. Neonatal strokes may lead to cerebral palsy, learning difficulties, or other disabilities. Well-designed clinical trials for stroke treatment in neonates are lacking, but some current studies involve the transplantation of neural stem cells and umbilical cord stem cells; it is not yet known if this therapy is likely to be successful.

Diffuse axonal injury (DAI) is a brain injury in which damage in the form of extensive lesions in white matter tracts occurs over a widespread area. DAI is one of the most common and devastating types of traumatic brain injury, and is a major cause of unconsciousness and persistent vegetative state after severe head trauma. It occurs in about half of all cases of severe head trauma and may be the primary damage that occurs in concussion. The outcome is frequently coma, with over 90% of patients with severe DAI never regaining consciousness. Those who do wake up often remain significantly impaired.

DAI can occur in every degree of severity from very mild or moderate to very severe. Concussion may be a milder type of diffuse axonal injury.

Occipital epilepsy is a neurological disorder that arises from excessive neural activity in the occipital lobe of the brain that may or may not be symptomatic. Occipital lobe epilepsy is fairly rare, and may sometimes be misdiagnosed as migraine when symptomatic. Epileptic seizures are the result of synchronized neural activity that is excessive, and may stem from a failure of inhibitory neurons to regulate properly.

Locked-in syndrome usually results from quadriplegia and the inability to speak in otherwise cognitively intact individuals. Those with locked-in syndrome may be able to communicate with others through coded messages by blinking or moving their eyes, which are often not affected by the paralysis. The symptoms are similar to those of sleep paralysis. Patients who have locked-in syndrome are conscious and aware, with no loss of cognitive function. They can sometimes retain proprioception and sensation throughout their bodies. Some patients may have the ability to move certain facial muscles, and most often some or all of the extraocular muscles. Individuals with the syndrome lack coordination between breathing and voice. This prevents them producing voluntary sounds, though the vocal cords are not paralysed.

The most frequently reported symptoms are elementary "visual hallucinations" characterized by basic irritations to perception of sight. Scotomas and aumarosis also occur and are predictors of poor medication response Hallucinations may be described as flashing small circular patterns or zigzags. Vomiting or temporary blindness may occur and visual seizures may be followed by a headache leading to a frequent misdiagnosis as migraine. Seizures may become generalized.

Brain herniation frequently presents with abnormal posturing a characteristic positioning of the limbs indicative of severe brain damage. These patients have a lowered level of consciousness, with Glasgow Coma Scores of three to five. One or both pupils may be dilated and fail to constrict in response to light. Vomiting can also occur due to compression of the vomiting center in the medulla oblongata.

Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the tentorium cerebelli, and even through the foramen magnum (the hole in the base of the skull through which the spinal cord connects with the brain). Herniation can be caused by a number of factors that cause a mass effect and increase intracranial pressure (ICP): these include traumatic brain injury, intracranial hemorrhage, or brain tumor.

Herniation can also occur in the absence of high ICP when mass lesions such as hematomas occur at the borders of brain compartments. In such cases local pressure is increased at the place where the herniation occurs, but this pressure is not transmitted to the rest of the brain, and therefore does not register as an increase in ICP.

Because herniation puts extreme pressure on parts of the brain and thereby cuts off the blood supply to various parts of the brain, it is often fatal. Therefore, extreme measures are taken in hospital settings to prevent the condition by reducing intracranial pressure, or decompressing (draining) a hematoma which is putting local pressure on a part of the brain.

DAI is the result of traumatic shearing forces that occur when the head is rapidly accelerated or decelerated, as may occur in car accidents, falls, and assaults. Vehicle accidents are the most frequent cause of DAI; it can also occur as the result of child abuse such as in shaken baby syndrome.

Immediate disconnection of axons could be observed in severe brain injury, but the major damage of DAI is delayed secondary axon disconnections slowly developed over an extended time course. Tracts of axons, which appear white due to myelination, are referred to as white matter. Lesions in both grey and white matters are found in postmortem brains in CT and MRI exams.

Besides mechanical breaking of the axonal cytoskeleton, DAI pathology also includes secondary physiological changes such as interrupted axonal transport, progressive swellings and degeneration. Recent studies have linked these changes to twisting and misalignment of broken axon microtubules, as well as tau and APP deposition.

Locked-in syndrome (LIS), also known as pseudocoma, is a condition in which a patient is aware but cannot move or communicate verbally due to complete paralysis of nearly all voluntary muscles in the body except for vertical eye movements and blinking. The individual is conscious and sufficiently intact cognitively to be able to communicate with eye movements.

The EEG is "normal" in locked-in syndrome.

Total locked-in syndrome, or completely locked-in state (CLIS), is a version of locked-in syndrome wherein the eyes are paralyzed as well. Fred Plum and Jerome Posner coined the term for this disorder in 1966.

The most common presentation of cerebrovascular diseases is an acute stroke, which occurs when blood supply to the brain is compromised. Symptoms of stroke are usually rapid in onset, and may include weakness of one side of the face or body, numbness on one side of the face or body, inability to produce or understand speech, vision changes, and balance difficulties. Hemorrhagic strokes can present with a very severe, sudden headache associated with vomiting, neck stiffness, and decreased consciousness. Symptoms vary depending on the location and the size of the area of involvement of the stroke. Edema, or swelling, of the brain may occur which increases intracranial pressure and may result in brain herniation. A stroke may result in coma or death if it involves key areas of the brain.

Other symptoms of cerebrovascular disease include migraines, seizures, epilepsy, or cognitive decline. However, cerebrovascular disease may go undetected for years until an acute stroke occurs. In addition, patients with some rare congenital cerebrovascular diseases may begin to have these symptoms in childhood.

Signs and symptoms of CBPS typically appear in infancy or at birth, but can appear later in childhood. These include facial diplegia (paralysis on both sides), facial muscle spasms, pseudobulbar palsy, dysarthria (difficulty speaking), difficulty chewing, dysphagia (difficulty swallowing), epilepsy, and intellectual disability. Epileptic seizures in individuals with CBPS are different between individuals and can vary between episodes.

Consistent risk factors include:

- Severity of seizures, increased refractoriness of epilepsy and presence of generalized tonic-clonic seizures: the most consistent risk factor is an increased frequency of tonic–clonic seizures.

- Poor compliance. Lack of therapeutic levels of anti-epileptic drugs, non-adherence to treatment regimens, and frequent changes in regimens are risk factors for sudden death.

- Young age, and early age of seizures onset.

- Male gender

- Poly-therapy of epilepsy. It remains unclear whether this is an independent risk factor or a surrogate marker for severity of epilepsy.

- Being asleep during a seizure is likely to favour SUDEP occurrence.

CBE is a chronic state of severe bilirubin-induced neurological lesions. Reduction of bilirubin in this state will not reverse the sequelae. Clinically, manifestations of CBE include:

1. movement disorders - athetoid cerebral palsy and or dystonia, 60% have severe motor disability(unable to walk).

2. auditory dysfunction - auditory neuropathy (ANSD)

3. oculomotor impairments (nystagmus, strabismus, Impaired upward or downward gaze, and/or cortical visual impairment),

4. dental enamel hypoplasia/dysplasia of the deciduous teeth,

5. Gastroesophageal reflux,

6. impaired digestive function.

Intellectual disability occur in 25% of cases. But they are often look like intellectually disabled because their severe motor handicaps.

Epilepsy occur in 20% of cases.

These impairments are associated with lesions in the basal ganglia, auditory nuclei of the brain stem, and oculomotor nuclei of the brain stem. Cortex and white matter are mildly involved. Cerebellum may be involved.

Clinical manifestations of intraparenchymal hemorrhage are determined by the size and location of hemorrhage, but may include the following:

- Hypertension, fever, or cardiac arrhythmias

- Nuchal rigidity

- Subhyaloid retinal hemorrhages

- Altered level of consciousness

- Anisocoria, Nystagmus

- Focal neurological deficits

- Putamen - Contralateral hemiparesis, contralateral sensory loss, contralateral conjugate gaze paresis, homonymous hemianopsia, aphasia, neglect, or apraxia

- Thalamus - Contralateral sensory loss, contralateral hemiparesis, gaze paresis, homonymous hemianopia, miosis, aphasia, or confusion

- Lobar - Contralateral hemiparesis or sensory loss, contralateral conjugate gaze paresis, homonymous hemianopia, abulia, aphasia, neglect, or apraxia

- Caudate nucleus - Contralateral hemiparesis, contralateral conjugate gaze paresis, or confusion

- Brain stem - Tetraparesis, facial weakness, decreased level of consciousness, gaze paresis, ocular bobbing, miosis, or autonomic instability

- Cerebellum - Ataxia, usually beginning in the trunk, ipsilateral facial weakness, ipsilateral sensory loss, gaze paresis, skew deviation, miosis, or decreased level of consciousness

Myoclonus can be described as brief jerks of the body; it can involve any part of the body, but it is mostly seen in limbs or facial muscles. The jerks are usually involuntary and can lead to falls. EEG is used to read brain wave activity. Spike activity produced from the brain is usually correlated with brief jerks seen on EMG or excessive muscle artifact. They usually occur without detectable loss of consciousness and may be generalized, regional or focal on the EEG tracing. Myclonus jerks can be epileptic or not epileptic. Epileptic myoclonus is an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity.