Encephalopathy

Refers to an alteration in mental status that affects the patients cognition or level of arousal.

It describes a clinical syndrome rather than a diagnosis and has many potential causes.

Broadly includes mental status changes due to focal or global brain insults, but the term most commonly is used to describe the latter.

Focal cognitive desert deficits such as aphasia or amnesia can mimic global encephalopathy syndrome.

A subtype of a cephalopathy includes delirium in which the patient has a cute altered mental status with waxing and waning attention.

The etiology and differential diagnosis of encephalopathic syndromes is determined by history of onset, progression of symptomatology, its total duration, physical examination including mental status examination, and laboratory/radiologic tests.

Encephalopathy time of onset includes categories: hyperacute, acute, subacute, chronic.

Encephalopathy occurring over anytime course can be due to systemic disease, or toxic-metabolic insult.

Hyperacute-onset encephalopathy leads to consideration of cerebrovascular disease, seizures, trauma, or migraines.

Hyper acute causes of encephalopathy includes intracranial hemorrhage, which is characterized by the compartment where the bleeding occurs: intracerebral, subarachnoid, subdural, or epidural spaces.

Subarachnoid hemorrhage, particularly when caused by ruptured cerebral aneurysm, is often associated with a sudden, severe headache, which can be accompanied by meningeal signs such as meningismus, photophobia, nausea, seizures and decreased level of arousal.

Intraparenchymal hemorrhage causes include: hypertension, cerebral amyloid angiopathy, head trauma, coagulopathy, brain metastases, and dural sinus thrombosis.

Epidural Hematoma and subdural hematoma are almost always associated with head trauma.

Epidural hematoma often occurs from damage to the middle meningeal artery, allowing arterial blood to collect in the epidural space leading to increased intracranial pressure and brain shift.

Acute-onset encephalopathy is considered for neurologic infections such as bacterial or viral meningitis or encephalitis, or acute demyelination.

Subacute-onset encephalopathy leads to consideration of neoplastic disease or metastases, autoimmune conditions, and infections.


Subacute infectious meningoencephalitis can occur with fungal, tuberculosis, or syphilis infections.

Prion disease is rare but important causing rapidly progressive dementia in adults and can present as cognitive impairment, behavioral changes, movement disorders, sensory changes, and altered sleep-wake cycles.

Subdural hematoma can produce cognitive symptoms that emerge slowly, sometimes taking weeks after onset.

Brain tumors can cause encephalopathy as a result of direct infiltrative damage to local tissue, edema, mass effect, and intra-cranial shifts, with effects on intracranial pressure, seizures or hemorrhages.

Chronic-onset encephalopathy considers neurodegenerative conditions such as dementia.

Toxic and metabolic insults can cause variable onset of insult encephalopathy, dependent on the toxin/metabolite.

Ischemic stroke caused by lack of blood flow to one or more regions of the brain, leads to cerebral infarction.

Ischemic stroke clinical findings are related to the location of the ischemia/infarction, most patients present with focal defects.

Embolic strokes typically have an acute presentation with maximum symptoms at onset, whereas small vessel strokes, lacunar strokes, may have a stuttering pace over minutes to hours.

Global encephalopathy can occur with infarctions to certain regions of the brain including bilateral thalami, territories of the right middle and anterior cerebral arteries, and diffuse and bilaterally located small emboli.

Seizures are caused by abnormal, excessive, rhythmic electrical discharges in the brain.

Seizures usually occur as discreet events with a rapid onset, although clinical presentation is variable and depends on where in the brain the aberrant electrical activity originates and whether it remains in one location-that is partial, or becomes more widespread, that is generalized.

Generalized seizures Lead to a loss of consciousness and are followed by a period of global encephalopathy, known as a postictal state.

Partial seizures produce focal symptoms reflecting the function of the area where the aberrant electrical activity occurs-motor, sensory, autonomic-and can cause encephalopathy when the cognitive networks are involved.

Migraine is characterized by unilateral and throbbing headaches that last several hours and is often accompanied by nausea, photophobia, and phonophobia.

Migraine headaches tend to build over a course of minutes and maybe preceded by an aura that is often visual or somatosensory.

Migraine can produce symptoms of confusion in rare instances.

Traumatic brain injury is a common cause of hyperacute encephalopathy.

Concussion refers to mild Traumatic brain injury associated with altered mental status.

Patient with concussion can experience a posttraumatic encephalopathy as part of a broader postconcussive syndrome of headaches, dizziness, mental fogginess, intolerance of loud noises or bright lights, and the onset of symptoms may be delayed by hours or days following impact.

Neuropsychiatric symptoms may accompany the syndrome and include fatigue, sleepiness, insomnia, personality changes and slow processing speed.

Sudden onset encephalopathy can occur with hypertensive emergencies, metabolic derangement, medications, drug withdrawal, and other toxic exposures.

Psychiatric processes such as panic attacks, nonepileptic seizures, fugue state, and psychosis can also present as a sudden onset encephalopathy.

Psychiatric illness may cause acute mania, psychosis, panic, anxiety, and depression along with cognitive impairment, Catalonia, psychomotor agitation, or slowing.

Subdural hematoma, the slow accumulation of blood which may take days or even weeks can occur as a clinically significant mass effect and result in encephalopathy.

Subdural hematoma symptoms include: headache, impaired arousal, focal deficits, cognitive impairment, and seizures.

Subdural hematoma may be caused by head trauma, coagulopathies, anticoagulants, and intracranial hypotension.

Demyelinating disease of the CNS include multiple sclerosis and acute disseminated encephalitis and they may manifest as an encephalopathy.

CNS infection such as meningitis and encephalitis can present with acute encephalopathy, usually accompanied by headache and fever.

In transient global amnesia temporary loss of ability to form new memories and patients present with disorientation.

In transientt global amnesia the mental status exam is normal outside of short-term recall.

The process resolves within 24 hours and may be triggered by intense physiological or emotional stimuli.

Systemic conditions associated with acute encephalopathy include: systemic infections, systemic autoimmune diseases, metabolic disturbances, drugs or drug withdrawal, and toxin ingestions.


Subacute to chronic changes in cognition may be a result of the side effects of treatments used for intracranial tumors such as tissue resection, radiation, and chemotherapy.

Radiation is associated with tissue necrosis and vascular changes. 

Leukoencephalopathy may occur with some chemotherapy agents. 

Episodic headaches seizures and other focal defects that affect cognition can occur after radiation therapy.

Antibody mediated autoimmune conditions can affect the CNS and cause changes in cognition, emotion, and behavior as antibodies have affinity for limbic brain regions.

Auto antibody mediated encephalopathies can be it idiopathic or part of a paraneoplastic phenomenon.

CNS vasculitis can present is subacute progressive cognitive decline.

CNS vasculitis with neural imaging shows sub cortical infarction of different age, and it may be isolated to the brain or spinal cord.

Hashimoto’s autoimmune thyroiditis can be associated with encephalopathy presenting with focal or global symptomatology and at times a rapidly progressive dementia.

Neurosarcoidosis is a granulomatous inflammatory process that can affect the neurological system and commonly causes cranial nerve palsy, meningitis, cognitive and behavioral changes and seizures.

The most common causes of chronic and cephalopathy in older adults relate to the degenerative diseases that lead to dementia.

These type of encephalopathies related to degenerative disease include: Alzheimer’s disease, Lewy body disease, frontotemporal lobar degeneration.

Vascular cognitive impairment is a common cause of chronic encephalopathy among older individuals. 

Cerebrovascular disease that can produce cognitive decline in several ways: progressive accumulation of precisely located symptomatic strokes that leads to reduction in function with each episode, or slowly progressive accumulation of silent microinfarcts often within the white matter, microhemorrhages, and other damage.

Normal pressure hydrocephalus with the typical triad of gait unsteadiness with falls, urinary incontinence and cognitive impairment can a manifest as encephalopathy. 

Multiple sclerosis with chronic symptoms of chronic cognitive impairment and fatigue can affect attention, processing speed, executive functions, and episodic memory.

Chronic, small infections can lead to cognitive symptoms as seen with long-standing HIV, syphilis, progressive multifocal leukoencephalopathy.

Repetitive head trauma that occurs with contact sports such as football boxing and soccer is associated with delayed onset neurodegenerative disease.

Leukodystrophies, metabolic pathway abnormalities for myelin development, and maintenance and destruction may be related to encephalopathy.

Mitochondrial diseases may manifest as a leukoencephalopathy.

Systemic conditions associated with  encephalopathy include vitamin B 12, thiamine, niacin deficiencies, obstructive sleep apnea, adrenal and thyroid endocrinopathies, metabolic disease is such as liver or renal failure, systemic autoimmune disease and porphyrias, alcohol exposure, heavy-metal exposure, celiac disease, Wilson’s disease, fragile X and chronic psychiatric disorders.




Leave a Reply

Your email address will not be published. Required fields are marked *