Metabolic Encephalopathies Flashcards
Encephalopathy, whether caused by metabolic etiology or otherwise, is defined as:
a subacute onset of a confusional state that is marked by fluctuating alterations of consciousness and that progressively worsens if untreated.
The pathophysiology in metabolic encephalopathies involves diverse mechanisms that lead to diffuse involvement of all brain structures. Permanent brain injury can usually be avoided by prompt diagnosis and treatment. The evaluation strategy is first to identify that the patient suffers from a metabolic encephalopathy, and secondly, identify and treat the etiologic diagnosis.
The signs and symptoms of encephalopathy are diverse. Describe them.
There‘s always an acute or subacute alteration of consciousness and mental status with changes in arousal that may be either increased and manifested as delirium or decreased and manifested as lethargy, stupor or coma. The content of thought may also be altered with reduced attention, disorientation, memory impairment, decreased cognitive functions, hallucinations, usually visual, and delusional thinking. There may be seizures, and there is a frequent alteration in respiratory effort that may be decreased or increased.
More signs/symptoms of encephalopathy
The reactivity of the pupil to light is frequently altered. There is usually a symmetric but sluggishly reactive response to light in metabolic encephalopathies. With a few specific exceptions, an asymmetric or a nonreactive pupil response in one or both pupils indicates a structural lesion rather than a metabolic process.
Ocular movements may be conjugate and roving (disconnected from higher centers of volitional control) or worse, dysconjugate and limited in their excursion, or they may be entirely absent.
There is frequent altered motor activity affecting strength, muscle tone, and muscle stretch reflexes, the latter two being increased or decreased depending on the etiology.
Commonly present in metabolic encephalopathy are:
tremor, multifocal myoclonus and asterixis, also known as negative myoclonus.
What is negative myoclonus?
Negative myoclonus involves a sudden lapse in muscle tone best shown by the outstretched arms and hands producing a “liver flap” of the hands.
What is Multifocal myoclonus?
involves the chaotic contraction of small and large groups of muscles to produce sporadic involuntary individual recurrent twitches of a thumb, an eyelid, an arm or even of the entire body when the axial musculature is involved. This is common in hepatic and renal failure, hypoxia and drug overdose.
Encephalopathies may be broadly categorized as either chemical or non-chemical in their pathogenesis. Head trauma, infection, vascular events, and seizures (non-chemical) usually have major focal features but they may present as a diffuse process mimicking a chemical encephalopathy.
An important distinguishing feature of the non-chemical encephalopathies is:
that they more commonly lead to permanent brain injury compared to the chemical encephalopathies. The latter disorders are more likely to be completely reversible if treated appropriately and in a timely manner.
An important clinical point: all encephalopathies present clinically in a similar manner and distinguishing between the various pathogenic etiologies requires a careful history, examination, and an extensive laboratory evaluation.
For example, it is not possible to distinguish between an encephalopathic patient with an underlying cause from a CNS infection versus an abnormality in electrolytes without obtaining the appropriate laboratory tests.
This is a list of the water soluble vitamins that may cause a metabolic encephalopathy.
Other vitamin deficiencies, including vitamins that are water or fat soluble, do cause neurologic disorders but not encephalopathy. For example Vitamin A deficiency leads to night blindness and Vitamin E deficiency leads to myelopathy and polyneuropa
Who commonly gets (B1) Wernicke Korsakoff syndrome?
It is seen primarily in patients with severe alcohol abuse but can complicate any disorder associated with severe nutritional deficiencies (ie. malnutrition due to cancer, bariatric surgery, anoerexia, hyperemesis).
How does Wernicke/Korsakoff Encephalopathy present?
Wernicke patients present with ophthalmoparesis, gait ataxia and a confused state, the so-called classic “Triad” of Wernicke’s encephalopathy.
Korsakoff syndrome, that occurs with and/or follows Wernicke disease, is characterized by amnesia, primarily for recent memories, meaning patients can no longer lay down new memories.
More on WKE presentation
There may be a peripheral neuropathy from chronic alcohol or nutritional deficiency.
What is the prognosis of WKE?
Wernicke signs and symptoms are largely reversible if treated promptly but repeated episodes or inappropriate treatment leads to damage and petechial hemorrhage to several areas of the brain including the dorsomedial thalamus, mamillary bodies, and periaquductal grey.
Brain imaging with MRI can detect these damaged areas antemortem
How is WKE tx?
Treatment with IV thiamine should be prompt and in all instances precede any IV glucose infusion.
The metabolism of glucose requires thiamine and a glucose load in the face of a thiamine deficiency will precipitate brain damage in the areas listed above.
How is WKE diagnosed?
Diagnosis of Wernicke’s is made on clinical grounds. Blood tests for transketolase activity reveal reduced levels but the test is not readily available. The key is to treat patients immediately. In fact, alcoholics and other malnourished patients in the ED, are often supplemented with vitamins, including thiamine, whether they exhibit symptoms of thiamine deficiency or not.
The upper two images present the post-mortem pathology of Wernicke’s disease. Note the periventricular microhemorrhages, resulting in cranial nerve nuclei involvement. There is mammillary body atrophy and hemorrhage in the top right photo and similar pathology in the midbrain periaqueductal gray area in the top left image. The medial dorsal nucleus of the thalamus is also frequently affected.
Note the eye findings with incomplete, asymmetric ocular movement on attempting to look to the right (left lower photo) and even worse on attempting to look to the left (right lower photo) indicating involvement of not only the abducens nuclei but of the PPRF and/or the oculomotor nuclei.
Other presentations for thiamine deficiency include either “wet” or “dry” Beriberi. Describe Wet beriberi. Dry?
Wet: high output cardiac failure
Dry: Polyneuropathy (Lower limbs > upper limbs), Pain & touch decrease/ paresthesia, Loss of ankle & knee reflex (Pathology- axonal degeneration)
Note that niacin deficiency is uncommon but when present may cause:
dementia or polyneuropathy (pathology: diffuse involvement of the CNS and PNS neurons).
Pyridoxine deficiency does not cause encephalopathy but may cause:
a polyneuropathy and seizures particularly in infants.
The top slide shows the subacute combined degeneration of the spinal cord with lateral and posterior columns lesions in B12 deficiency.
On the right side, note the spinal cord findings in the MRI of the spine showing demyelination from B12 deficiency. In the bottom slides, note the lemon yellow complexion of the woman with paleness from anemia; the tongue often shows atrophy of the papillae.
This slide presents the relevant metabolic pathways involving cobalamin as a cofactor.
With B12 deficiency homocysteine and methylmalonic acid levels rise and both can be tested to confirm the diagnosis of B12 deficiency, especially if the B12 level is in the low normal range.
Note that Folate deficiency is associated with normal methylmalonic acid levels but elevated homocysteine levels. Importantly, a normal folate level may suppress the changes seen on peripheral blood smear and thereby mislead the physician from a diagnosis of B12 deficiency.
Vitamin B deficiency can cause optic nerve disease. Describe the findings
There is decreased visual acuity and development of a central scotoma or blind spot in the macular area. Sometimes the central scotoma merges with the physiological blind spot to cause a centrocecal scotoma.
These complications are more common when associated with alcohol abuse and tobacco abuse.
In the upper right inset are shown the differences between hypoglycemia and hyperglycemia, both of which cause encephalopathy. How does the hypoglycemic state present?
In the hypoglycemic state, there is confusion, often complicated by seizures, and one sees the effects of an activated sympathetic system including tachycardia, hypertension, sweating and dilated pupils.
Reflexes are brisk and plantar responses are extensor.
Rapid improvement occurs with prompt IV glucose infusion. This should be given rapidly after drawing a blood glucose level for diagnosis and empirically treating with thiamine in the event thiamine deficiency is present as well.
In contrast, hyperglycemic encephalopathy is characterized by:
very high blood glucose levels with or without an associated ketoacidosis.
Pupils are small, seizures less common, and reflexes are not brisk. Treatment includes insulin and hydration with intravenous saline.
Cerebral hypoxia is most commonly caused by:
respiratory arrest, cardiac arrest or combined cardiorespiratory arrest.
Patients recovering from a severe hypoxic insult may proceed into a vegetative state giving the appearance of being “awake but unaware”; recovery may be associated with severe memory deficits and dementia. A Parkinson like state can sometimes result from basal ganglia involvement. Hypoxia can also result in severe myoclonus that will persist
Acute hepatic encephalopathy with hepatic failure can be caused by acetaminophen overdose. Serum ammonia levels are high with liver failure. Slides on the left show constructional apraxia with difficulty drawing a figure; connecting the numbers in sequence is difficult (this is called the Trails Making Test). Note the asterixis or flapping tremor in the bottom slide.
This slide calls your attention to the general group of toxins that may cause encephalopathy. The offending agents are much more extensive than included on this list.
All of these endocrine disorders may cause encephalopathy.
Elevated or depressed levels of serum sodium, calcium, magnesium or phosphate may cause encephalopathy.
An important clinical note: severe hyponatremia must be corrected SLOWLY, that is not faster than 8 mEq/l/24 hour. Faster correction of hyponatremia may cause what?
Central Pontine Myelinolysis, resulting in severe brain stem injury with impaired cognition and/or coma.
This is a partial list of therapeutic drugs that have been associated with encephalopathy. This information is FYI. When you actually deal with a patient with an altered mental status, it will be important that you review the possibility that the drug causes mental alterations as an adverse effect. Virtually all drugs do so given a high enough dose, but it will be your job to determine first, if there is drug intoxication, and second, if not, what is the probability that a specific drug is responsible for the mental changes. Some, like the ones listed here, are frequent offenders while others much less so, but it will be your job to figure it out.
The laboratory evaluation of a patient who presents with encephalopathy is usually quite extensive, unless the etiology is clear from the outset, for example, the patient’s roommate tells you he saw the patient ingest a bottle of phenobarbital a hour prior to his presentation in coma. What is included?
Blood is drawn quickly for screening of the items listed on the slide.
Blood glucose should be checked, and prior to giving any IV glucose, recall the importance of thiamine administration to avoid precipitating Wernicke’s encephalopathy.
Brain imaging is important to evaluate for focal brain injury and a lumbar puncture is necessary, unless there are contraindications, to rule out a CNS infection.
The EEG will determine whether there is generalized slowing consistent with a metabolic encephalopathy or whether the patient is actually experiencing nonconvulsive status epilepticus.
