Toxic & Metabolic Encephalopathies Flashcards
Toxic and Metabolic Encephalopathies: Etiologies and Pathophysiology?
Toxic and metabolic encephalopathies are acute or subacute disturbances in consciousness, attention, and cognition due to diffuse or global brain dysfunction caused by impaired cerebral metabolism. Unlike focal neurological conditions, these encephalopathies result from generalized cortical dysfunction, often reversible if the underlying cause is identified and treated.
Metabolic encephalopathies can be caused by : hypo/hyperglycemia, hypo/hyperantremia, hypo/hypercalcemia, hypoxia/hypercapnia, hyperammonemia, uremia, B1 and B12 deficiency.
Toxic encephalopathies can be caused by :
- exogenous toxins —> alcohol withdrawal, opioid overdose, benzodiazepine overdose, cocaine/amphetamines, CO poisoning, heavy metals.
- endogenous toxins —> hepatic, uremic and sepsis associated encephalopathy.
Infectious causes : meningitis, encephalitis and cerebral malaria.
Endocrine and autoimmune causes : hypothyroidism, adrenal insufficiency, paraneoplastic limbic encephalitis.
Hepatic encephalopathy? Pathophysiology? Clinical features?
Hepatic encephalopathy encompasses a range of neuropsychiatric abnormalities that occur in patients with liver dysfunction, after excluding other brain diseases. It results from hepatic failure or portosystemic shunting, leading to the accumulation of neurotoxic metabolites, particularly ammonia, which impairs brain function.
Mechanisms of Hyperammonemia in the CNS
1. Ammonia crosses the blood-brain barrier (BBB) and accumulates in astrocytes.
2. Astrocytic conversion of ammonia into glutamine increases osmotic pressure, causing cerebral edema and increased intracranial volume.
3. Neurotransmitter imbalances:
• Increased GABAergic inhibition (enhanced sensitivity to GABA).
• Impaired glutamatergic and dopaminergic neurotransmission.
4. Inflammatory activation increases oxidative stress, leading to neuronal dysfunction.
Etiologies of HE include acute causes like acute hepatitis, toxic liver disease and chronic causes like cirrhosis (most common cause) and HCC.
Clinical features include : cognitive and consciousness disturbances, behavioral and personality changes, neurological signs.
HE severity scale? Diagnosis and treatment?
Two most common scales used are FOUR score similar to the Glasgow coma scale and the west haven criteria (0 no changes to 4 coma).
Diagnosis is based on key biomarker elevation like serum ammonia, liver function test, renal test etc, EEG, brain MRI used in severe cases.
Treatment is lactulose + rifaximin. Lactulose being a non absorbable disaccharide which lowers colonic pH, promoted ammonia excretion via diarrhea. Rifaximin being a non absorbable antibiotic which reduces ammonia producing gut bacteria.
Second line treatments include IV ornithine and aspartate which stimulate urea cycle, reducing ammonia.
Liver transplantation is indicated in refractory cases, cirrhosis with end stage liver disease or fulminant hepatic failure.
Uremic encephalopathy pathogenesis, clinical features and management?
Uremic encephalopathy is a neurological syndrome that occurs as a result of advanced renal failure, leading to the accumulation of uremic toxins in the bloodstream. The severity of encephalopathy correlates with hyperazotemia (elevated blood urea nitrogen and creatinine). It is less common than hepatic encephalopathy but still a frequent metabolic disorder.
Pathogenesis : accumulation of uremic toxins which cause neurotransmitter dysfunction leading to cerebral edema and vascular dysfunction. Key neurotoxins include : urea, creatinine, PTH.
Clinical features include :
- early symptoms such as anorexia, nausea, vomiting, fatigue, drowsiness.
- moderate symptoms such as disorientation, confusion, impaired short term memory, mood disturbances and asterixis.
- severe symptoms such as myoclonus, seizures, stupor and coma.
Diagnosis is based on lab rest, EEG, brain MRI if needed.
Management : definitive treatment is dialysis to remove uremic toxins and restore electrolyte balance.
Hyponatremic encephalopathy?
Hyponatremia is defined as a serum Na+ concentration <135 mEq/L, and it is the most common electrolyte abnormality in hospitalized patients. Hyponatremia is caused by a relative excess of water in relation to Na+ and the two main causes of it are the Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) or Cerebral Salt Wasting Syndrome (CSws). Distinguishing these two conditions is important because the clinical manifestations can be identical, but the treatment is different.
SIADH —> due to tumors, pulmonary diseases, infections.
CSws —> rare condition usually occurring in case of subarachnoid hemorrhage.
The main distinguishing factor is that in CSws the patient is hypovolemic so we can give fluids to increase the volume of blood within the brain while in SIADH the patient is hypervolemic or euvolemic and the main indication is fluid restriction.
Clinical manifestations are the same as other metabolic conditions.
Management is IV hypertonic sodium chloride.
Wernicke’s encephalopathy?
Neurological disorder induced by exhaustion of B-vitamin reserves, in particular thiamine (vitamin B1). It has different phases of evolution related to sufferance and damage of neurons and this tends to occur after 2 weeks from the onset of thiamine deficiency.
Causes —> malnutrition, alcoholism, prolonged starvation.
Clinical features —> The typical clinical triad of manifestation is: ocular abnormalities, encephalopathy, and gait ataxia.
Management : It is considered a medical emergency associated with significant morbidity and mortality. The emergency care consists of parental Thiamine (from single to multiple daily doses), alcohol withdrawal, and parental magnesium sulfate in case of hypomagnesemia. A balanced diet with high thiamine-containing foods must be considered too.
What is posterior reversible encephalopathy syndrome?
It is a clinical-radiological syndrome characterized by headache, seizures, altered mental status, and visual loss and by reversible subcortical vasogenic edema affecting the posterior occipital and parietal lobes of the brain, predominantly occipital lobes (primary visual cortex and not the optic pathway). On MRI the patient has signs of vasogenic edema which are reversible after proper treatment.
Pathophysiology : has not been understood yet but is probably due to factors like endothelial damage, impaired auto regulation, increased cerebral perfusion.
Etiologies : pre-eclampsia, infection, autoimmune diseases, cancer.
Clinical features include encephalopathy, seizures, visual abnormalities, focal neurological signs.
Management : maintain patients ABC, symptomatic therapy, correction/removal of underlying cause.
