Hypoxic Ischemic Encephalopathy

1. Hypoxic Ischemic Encephalopathy

2. Electrolyte and Acid-base Disturbances • Sodium • Hypernatremia and hyponatremia • Impaired arousal and cognition • Seizures • Myoclonus • Tremor • Hyponatremia • May have focal deficits • Correct for hyperglycemia and pseudohyponatremia (high triglycerides) • Rapid correction predisposes to osmotic demyelination syndrome (ODS) • Obtundation • Conjugate gaze palsy • Corticospinal tract signs • Pseudobulbar palsy • Potentially fatal • Hypernatremia • Rapid correction may cause cerebral edema (idiogenic osmoles)

3. Osmotic Demyelination Syndrome

4. Electrolyte and Acid-base Disturbances (cont.) • Calcium disorders • Impaired sensorium (agitation, delusions, hallucinations) • Seizures (more common with hypocalcemia) • Hypercalcemia • Hyperparathyroidism (usual cause) • Anorexia, vomiting, osmotic diuresis • Impaired neuromuscular transmission (generalized weakness and hyporeflexia) • Fluid resuscitation • Furosemide, calcitonin, corticosteroids, bisphosphonates, plicamycin, and hemodialysis as adjunctive therapy • Hypocalcemia • Tetany and extrapyradamidal signs when severe • Magnesium • Calcium channel blockade • Symptoms uncommon • Hypermagnesemia (typically during IV infusion for eclampsia) • Impaired arousal, hypotension, decreased neuromuscular transmission, respiratory depression • Hypomagnesemia • Coexists and similar to hypocalcemia • Hypophosphatemia • Rarely symptomatic (when severe—depressed consciousness and seizures)

5. Electrolyte and Acid-base Disturbances (cont.) • Respiratory acidosis • CO2 narcosis • Hypoxemia and hypotension • Respiratory alkalosis • Transient confusion and lightheadedness • Perioral and acralparesthesias (decreased ionized calcium) • Metabolic acid-base disorders • Acute encephalopathy typically due to the underlying metabolic abnormality rather than the acid-base disturbance

6. End Organ Failure • Hepatic encephalopathy • Acetaminophen, viral hepatitis, and toxin-mediated injury can cause acute hepatic failure • GI bleeding, high protein intake, meds, infections may trigger encephalopathy with chronic liver disease • Clinical findings • Depressed consciousness, agitation, asterixis, posturing, extensor plantar reflexes • EEG shows triphasic waves • Ammonia elevated in 90% • Pathophysiology • Decreased clearance of metabolic toxins and meds • Blood-brain barrier permeability (cerebral edema) • Treatment • Lactulose, rifaximin, transplantation

7. End Organ Failure (cont.) • Uremic encephalopathy • Clinical manifestations • Confusion >> coma • Myoclonus, asterixis • EEG may show triphasic waves • Pathophysiology • Decreased clearance of neurotoxins • Treatment • Renal replacement therapy • Dialysis dysequilibrium • During or after dialysis in those recently started on dialysis • Headache, seizures, lethargy, elevated intracranial pressure • Treatment • Stop/slow dialysis • Osmotherapy may be required

8. Generalized Slowing and Triphasic Waves on EEG

9. Nutritional • Thiamine deficiency • Wernicke encephalopathy • Affects mammillary bodies, medial dorsal thalamus, and periaqueductal gray • Triad (mental status changes, ataxia and opthalmoplegia) seldom all present • Occasionally postural hypotension, cardiac failure, and GI symptoms • Treatment • IV thiamine • Korsakoff syndrome • Chronic disorder (often transition from Wernicke encephalopathy) • Impaired memory and learning out of proportion to other cognitive domains • Profound anterograde and retrograde amnesia • Confabulation, anxiety, apathy • Infrequent recovery

10. Nutritional (cont.) • Niacin deficiency • Pellagra (pelleagra “rough skin”) • Seen in ETOH use disorder, anorexia nervosa, INH use • Irritability, insomnia, confusion, and cognitive impairment • Startle myoclonus • Photosensitive dermatitis, diarrhea • Nicotinic acid metabolites in urine • Treatment • IV niacin 25-250 mg 2-3 times daily • Lead toxicity • Altered mental status, neuropathy (rare in isolation), dementia • Intractable colic, weakness including wrist/foot drop, thin blue-gray line at gums (Burton line) • Microcytic, hypochromic anemia with basophilic stippling or RBCs • Arsenic toxicity • Painful neuropathy • Hair and nail changes (Mees lines) • Liver and renal dysfunction • Mercury toxicity • Color vision changes, neuropathy • Pulmonary and renal dysfunction • Bismuth toxicity • Apathy, ataxia, headaches, myoclonus, hallucinations and seizures • Manganese toxicity • Parkinsonism, gait abnormalities, tremor, and psychiatric disturbances • Can occur with TPN containing trace elements

11. Endocrine Disorders • Thyrotoxicosis (Graves’ disease or toxic multinodular goiter) • Precipitating factors • Trauma, obstetric labor, lithium, iodinated contrast, non-thyroid surgery • Agitation, restlessness, emotional lability, confusion, psychosis, coma • Tachycardia, fever • Hypercoagulability (high index of suspicion for cerebral venous sinus thrombosis) • Elevated thyroid levels, decreased TSH, high calcium, mild leukocytosis, hyperglycemia, elevated serum LDH and aminotransferase • Treatment • PTU or methimazole followed by iodine • Supportive management with propranolol, antipyretics, and fluids • 75% mortality with thyrotoxic storm • Myxedema coma (rare, mortality 70%) • Precipitating factors • Infection, heart failure, trauma, cold exposure, anesthesia, and medication non-adherence superimposed on underlying hypothyroidism • Cognitive dysfunction, depression, lethargy, somnolence, coma, hallucinations (“myxedema madness”), seizures • Hypoventilation, bradycardia, cardiomegaly, decreased contractility • Hyponatremia, decreased GFR • Hypothermia • Dry skin, sparse hair, macroglossia • Periorbital, foot, and hand edema • Decreased thyroid levels, elevated TSH (no correlation with severity), elevated CK, normocytic anemia, elevated CSF protein and opening pressure • Treatment • Thyroid hormone replacement and supportive

12. Endocrine Disorders (cont.) • Hashimoto encephalopathy (controversial) • “Steroid responsive encephalopathy with autoimmune thyroiditis” (SREAT) and “non-vasculitic autoimmune meningoencephalitis” (NAIM) • Common—Clouding of consciousnes with reduced wakefulness, attention, or cognitive function • Reported—stroke-like episodes, coma, seizures, subacute cognitive decline, tremor, myoclonus, transient aphasia, sleep abnormalities, gait dysfunction, hallucinations • High titers of antithyroid antibodies (ATG, TPO, antithyroid microsomal) • MRI may show leukoencephalopathy • Often prompt response to IVMP 1 gm daily 3-5 days followed by prednisone 60-100 mg daily up to 30 days • Acute adrenal insufficiency • Causes • Primary injury to adrenal gland • Secondary—interference with ACTH release by the pituitary gland • Tertiary—interference with corticotropin releasing hormone by the hypothalamus • Iatrogenic—suppression of HPA axis due to chronic corticosteroid use • Relative—inappropriately low cortisol production and adrenal suppression associated with sepsis (incidence 20-60%) • Manifestations • Confusion, lethargy, coma, convulsions • Circulatory failure, abdominal pain, vomiting, fever, hypoglycemia, hyperkalemia, hyponatremia • Treatment • Circulatory support • Stress-dose steroids

13. Autoimmune Encephalitis

14. Autoimmune Encephalitis

15. Initial Management and Assessment • ABCs • Consider the following lab studies: • Serum glucose and electrolytes • Complete blood count, lactate, procalcitonin • Liver and kidney function studies • Urine toxicology screen • Arterial blood gas • Carboxyhemoglobin level (if carbon monoxide exposure suspected) • For coma of acute onset and unknown cause administer: • Dextrose, 25 g IV (to treat possible hypoglycemia) • Thiamine, 100 mg IV (to prevent or treat Wernicke encephalopathy) • Naloxone, 1 mg IV (to treat possible opiate overdose) • Treat ongoing seizures • Brain imaging (CT or MRI) if focal intracranial lesion is suspected • CSF analysis if meningitis or SAH is suspected