Systemic organ failure
Liver failure: acute, chronic
Renal failure: acute, chronic
Cardiac failure
Pulmonary disease: hypoxemia and hypercarbia/hypercapnia
Nutritional deficiency
Vitamin B1 deficiency (Wernicke’s encephalopathy, Korsakoff’s syndrome, Marchiafava-Bignami disease)
Vitamin B12 deficiency
Folate deficiency
Niacin deficiency
Drugs and toxins
Drugs of abuse (e.g., ethanol, heroin, hallucinogens)
Prescription medications (e.g., opioids, sedative-hypnotics, antipsychotics, skeletal muscle relaxers)
Withdrawal states (e.g., ethanol, benzodiazepines)
Inhaled toxins (carbon monoxide, cyanide, hydrogen sulfide)
Infections
Sepsis
Systemic infections
Fever-related delirium
18.2 Clinical Features
The commonest clinical features of TDE are nonspecific and do not reliably identify a particular etiology; they include [1]: (1) mental status abnormalities; (2) motor system abnormalities; (3) seizures; (4) cranial nerve abnormalities
1.
Mental status abnormalities are always present and range from subtle abnormalities to confusional state, delirium, stupor, or coma [2].
2.
Motor system abnormalities include: tremor, asterixis, multifocal myoclonus, paratonia, alterations of deep reflexes, and Babinski.
3.
Seizures: usually generalized tonic-clonic; sometimes focal, multifocal, and partial complex.
4.
Cranial nerve abnormalities. The pupillary light reflex and vestibular responses are almost always present in patients with TDE, even in patients in deep coma, but can be blunted. In cases with more severe encephalopathy, dysconjugate roving eyes movement may occur [2].
18.3 Diagnostic Markers
Detailed analysis of clinical history and use of medications are imperative.
A complete laboratory screening is necessary [3].
Blood gas determination: In hyperventilating patients respiratory alkalosis is most commonly due to early sepsis, hepatic failure, early salicylate intoxication. Metabolic acidosis usually reflects uremia, diabetic ketoacidosis, lactic acidosis, methanol and ethylene glycol intoxication, late phases of sepsis
Urine, blood, and cerebrospinal fluid (CSF) culture are indicated if fever is present
Toxicological screening should be performed for suspected intoxications
CSF – Mandatory when the cause of confusional state/delirium is not obvious
EEG – To exclude seizures and to confirm global cerebral dysfunction. Triphasic waves are detectable in hepatic, uremic, and septic encephalopathy. The degree of abnormalities usually correlates with the severity of TDE [4].
TC/MRI – Can show a widespread, symmetric pattern of injury of the deep gray nuclei and cerebral cortex.
18.4 Top Differential Diagnosis
Cerebrovascular disease, central nervous system infection, nonconvulsive status epilepticus, traumatic brain injury, dementia, psychiatric disorders.
18.5 Prognosis
18.5.1 Principles of Treatment
The treatment of TDE is related to the underlying condition (see below specific etiology). However, regardless of the cause, some general measures should be considered, in particular [3]: discontinuation, if possible, of all drugs with potential toxicity to the central nervous system and avoidance of physical restraints. Restraint in a medical inpatient unit is associated with a threefold increased odds of persistent delirium.
Haloperidol: To treat severe agitation except in cases of alcohol withdrawal, anticolinergic toxicity, and benzodiazepine withdrawal.
Thiamine: For patients with a history of alcoholism, malnutrition, renal failure on hemodialysis, cancer.
18.5.2 Disability
TDE is common among patients admitted to intensive care units (ICU); older patients and those with underlying dementia are at greatest risk. Other possible risk factors for TDE include nutritional deficiency, infection, temperature dysregulation, and failure of multiple organ systems. The presence of delirium is an independent risk factor for mortality and prolonged hospitalization in patients receiving mechanical ventilation [5]. TDE is generally considered a reversible condition. However, severe TDE, particularly if causing coma, is a marker for significant morbidity and mortality. Underlying etiology, severity, and duration of coma were found to be independently associated with outcome in a series of 500 patients with medical causes of coma [6–8]. Hypoxic-ischemic coma was associated with a 58 % mortality (see Chap. 3) and a 31 % incidence of persistent vegetative state or severe disability, while other metabolic causes were associated with 47 % mortality and 21 % incidence of persistent vegetative state. Clinical signs predictive of these poor outcomes [7] included: (1) absent corneal or pupillary response at 24 h, (2) motor response poorer than withdrawal at 3 days, and (3) absent roving eye movements at 7 days.
Patients with so-called good outcomes may not be unaffected. Persistent neurological and psychiatric disturbances are reported in up to 32 % of patients with TDE after discharge from ICU [9]. Cognitive impairment is usually diffuse but more prominent in the areas of verbal fluency, working and visual memory, psycho-motor speed, and visual construction abilities. Depression is common, affecting 36 % of patients. Duration of delirium during the acute phase of hospitalization is longer among patients who develop neuropsychological impairment. Advanced age, low premorbid intelligence, hypoxia, cerebrovascular and peripheral vascular disease are also negative prognostic factors [10].
18.6 Hepatic Encephalopathy (HE)
18.6.1 Terminology and Definitions
HE is the result of hepatic insufficiency from acute liver failure or cirrhosis or from portosystemic shunting, even in the absence of intrinsic liver disease. Overt HE consists of neurological and psychiatric abnormalities that can be detected by bedside clinical tests, whereas minimal HE can only be distinguished by specific psychometric tests [11]
18.6.2 Clinical Features
Impaired mental status and impaired neuromotor function such as hyperreflexia, hypertonicity, and asterixis [11].
18.6.3 Diagnostic Markers
Blood – Usually elevated arterial and venous ammonia, abnormal liver function and coagulation, decreased albumin, mild respiratory alkalosis, and hypoxemia
CSF – Increased glutamine
CT – To exclude other causes, diffuse cerebral edema in acute HE
MRI – Bilateral T1WI hyperintensity in basal ganglia, particularly globus pallidus [12].
EEG – (see above)
Psychometric tests – Disturbances in attention, visuospatial abilities, fine motors kills, and memory [13].
18.6.4 Prognosis
18.6.4.1 Principles of Treatment
The management of acute HE should focus on providing supportive care, identifying and treating any precipitating causes, reducing blood ammonia concentration, and assessing the need for long-term therapy and liver transplant evaluation [14]
18.6.4.2 Disability
Approximately 70–80 % of patients with overt HE improve after identification and correction of precipitating factors. Rapid response to first-line medical therapy is usually observed within 24–48 h of initiation of treatment. Once patients show clinical improvement, then the prevention of recurrent HE becomes important, including reinforcement of compliance with treatment [15]. Patients with overt HE may have persistent and cumulative neurological deficits despite an apparent normalization of mental status after treatment. The number of episodes of overt HE correlates with the severity of residual impairment [16]. Fulminant hepatic failure is usually the result of massive necrosis of hepatocytes and is defined as a syndrome in which the sign of encephalopathy develops within 8 weeks from the onset of liver disease in a patient with a previously normal liver. In this condition, despite intensive treatment, patients who become comatose have an 80–85 % mortality [15].
18.7 Uremic Encephalopathy
18.7.1 Terminology and Definitions
Encephalopathy associated with acute or chronic renal failure.
18.7.2 Clinical Features
Lethargy, irritability, disorientation, hallucinations, rambling speech. Tremor, myoclonus, and asterixis are common, tetany may be present. Generalized, focal motor seizures or epilepsia partialis continua may occur. Coma may occur especially in acute renal failure [17].
18.7.3 Diagnostic Markers
Blood – Abnormal renal tests
Neuroimaging – May be required to exclude other diagnosesRelated posts:
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