Jacewicz - Metabolic Encephalopathies Flashcards
1
Q
What is metabolic encephalopathy (ME)? Describe the pathophys and evaluation strategy.
A
- DEFINITION: subacute onset of confusional state marked by fluctuating alterations of consciousness that progressively worsen if untreated
- PATHOPHYS: diverse mechs lead to diffuse involvement of all brain structures -> permanent brain injury can usually be avoided by prompt dx and tx
- EVALUATION: first, identify that pt suffers from ME, then clarify and tx the etiologic dx
2
Q
What are the signs/symptoms of ME?
A
-
Acute alteration of consciousness/mental status:
1. Arousal: INC = delirium, DEC = lethargy, stupor, coma
2. Content: DEC attention, DEC orientation and memory, DEC cognition, INC hallucinations (visual) and delusions - Seizures
- Altered respiration: hypo/hyperventilation
- Altered pupil light reactivity: usually symmetric and sluggishly reactive; asymmetric/non-reactive pupils, with specific exceptions, indicate structural lesion
- Altered ocular motility: may be roving, dysconjugate, or absent
- Altered motor activity: diffuse alteration of strength, tone, and reflexes; tremor, asterixis (hand tremor when wrist is extended), multifocal myoclonus (spasmodic jerky contraction of groups of muscles)
3
Q
What is the categorical differential of encephalopathy? Sub-categories?
A
- CHEMICAL: vitamin, endocrine, toxin, metabolic, electrolyte, drug
1. More likely to be completely reversible if treated appropriately and in a timely manner - NON-CHEMICAL: trauma, infection, vascular, seizures
1. Usually have major focal features, but may present as diffuse process mimicking chemical encephalopathy
2. More commonly lead to permanent brain injury compared to the chemical encephalopathies
4
Q
Why is a careful history, exam, and lab eval critical to the evaluation of ME’s?
A
- All encephalopathies present clinically in a similar manner, and distinguishing bt the various pathogenic etiologies requires a careful history, examination, and an extensive laboratory evaluation
- It is not possible to distinguish bt an encephalopathic patient with an underlying cause from a CNS infection versus an abnormality in electrolytes without obtaining the appropriate laboratory tests
5
Q
What water-soluble vitamins may cause ME?
A
- B1 (thiamine) deficiency
- Nicotinic (niacin) deficiency
- B12 deficiency
- NOTE: other vitamin deficiencies may cause neuro disorders, but NOT encephalopathies
6
Q
What are the key clinical features of Wernicke/Korsakoff encephalopathy (B1)? Describe population, presentation, dx, and tx.
A
- POPULATION: alcoholics, malnutrition (cancer, bariatric sx, anorexia, hyperemesis gravidarum)
-
WERNICKE TRIAD of opthalmoparesis (horizontal & vertical), ataxia (central, heel-shin), and confusion (poor recall, orientation)
1. Largely reversible if tx’d promptly, but repeated episodes or inappropriate tx leads to atrophy and petechial hemorrhage to several areas of the brain (thalamus, mamillary bodies, PAG) -> CT or MRI scans can detect damaged areas antemortem - AMNESIA (KORSAKOFF): anterograde, retrograde, recent > remote memory, confabulation (occurs w/and usually follows Wernicke’s)
- PERIPHERAL NEUROPATHY: 80% of cases
- PATHOLOGY: dorsomedial thalamus, mammilary body, & periaqueductal gray atrophy + petechial hemorrhage
- LAB: transkeletolase DEC (90-140 mgm), but this test not readily available, and pts must be tx’d immediately
1. Wernicke’s dx made on clinical grounds - TX: prompt IV thiamine BEFORE a glucose load -> metabolism of glu requires thiamine, and glu loads in face of deficiency rapidly leads to permanent brain damage in the areas listed above
7
Q
What do you see here?
A
- Wernicke/Korsakoff encephalopathy w/periventricular microhemorrhages, resulting in CN involvement
- LEFT: midbrain periaqueductal gray atrophy and hemorrhage
- RIGHT: mammillary body atrophy and hemorrhage
8
Q
What may have happened here?
A
- Wernicke/Korsakoff encephalopathy eye findings
- Weakness of right lateral and left lateral rectus fields
9
Q
What is the presentation of beri-beri (wet vs. dry)?
A
- B1 deficiency
- WET: high output cardiac failure, incl. INC HR, INC JVP, dyspnea, and peripheral edema
- DRY: polyneuropathy, lower limbs > upper limbs, pain and touch DEC/paresthesia, loss of ankle/knee reflex
1. Pathology: axonal degeneration
10
Q
What is the presentation and pathology of niacin deficiency?
A
- Pellagra
- Uncommon today
- Causes dementia and polyneuropathy
- Pathology: diffuse involvement of CNS/PNS neurons
11
Q
What is the presentation of pyridoxine deficiency?
A
- B6 deficiency
- Does NOT cause encephalopathy
- Polyneuropathy in adults
- Seizures during infancy
12
Q
What are the causes, syndrome, and signs/symptoms of B12 deficiency?
A
- CAUSES: pernicious anemia (MCC), fish tapeworm, gastric cancer, extreme vegetarian diet, bariatric surgery, sprue, nitrous oxide (N2O) abuse in dental practice, Crohn’s, hyperemesis gravidarum
- SYNDROME: subacute combined degeneration -> spinal cord syndrome w/lesions of dorsal columns and lateral corticospinal tracts
- NEURO SIGNS/SYMPTOMS: DEC vibration/position sense (+ Romberg sign: standing pt loses balance when asked to close eyes)
1. Lhermitte’s sign: electric-like sensation upon neck flexion
2. Distal paresthesias
3. Weakness
4. Spastic gait w/hyper- or hyporeflexia
5. Visual impairment: optic N atrophy
6. Confusion, dementia, depression (COGNITIVE DEFICITS)
7. Peripheral neuropathy - NOTE: B12 deficiency is NOT uncommon
13
Q
What are the pathology, labs, and tx of B12 deficiency?
A
- PATHOLOGY: demyelination of dorsal columns, corticospinal tracts, cerebral white matter, optic NN, and peripheral NN
- LABS: blood smear -> macrocytic anemia w/hyper-segmented neutrophils, low B12 level
1. Borderline low or low-normal B12, check MMA and homocysteine levels -> elevated in B12 def - TX: tx underlying etiology
1. IM cyanocobalamin weekly, then monthly
14
Q
What is going on here?
A
- B12 deficiency
- Subacute combined degeneration of spinal cord, with lateral and posterior column lesions
15
Q
What happened here?
A
- B12 deficiency
- Spinal cord findings in MRI -> demyelination
16
Q
What is going on here?
A
- B12 deficiency
Lemon yellow complexion of the woman with paleness from anemia
- Tongue often shows atrophy of the papillae (glossitis)
17
Q
For what molecular pathways is Vit. B12 important? How can this help you in dx?
A
- With B12 deficiency, both homocysteine and methyl-malonic acid (MMA) levels rise -> both can be tested for to confirm the diagnosis of B12 deficiency, esp. if the B12 level is in the low normal range
- NOTE: folate deficiency is assoc with normal methyl-malonic acid levels, but elevated homocysteine levels
19
Q
What neuro signs/symptoms are associated with diabetes (disorders of glu metabolism)?
A
- Small vessel disease in brain with lacunar infarctions (stroke from occlusion of one of the penetrating arteries that provides blood to the brain’s deep structures)
- Pupillary abnormalities w/preserved accommodation reflex and absent light reflex, suggestive of Argyll Robertson pupil, similar to that seen in neurosyphilis
- Diabetic mononeuritis of extraocular muscles cause ophthalmoparesis and diplopia
- Diabetic neuropathy associated w/hypo- or areflexia, autonomic fxs w/neurogenic bladder, mononeuritis multiplex, trophic changes in feet, and Charcot’s joints
- Diabetic amyotrophy (muscular atrophy) can occur
- Compressive nerve syndromes common in diabetes
20
Q
What are the differences bt the presentations of hypo- and hyperglycemia?
A
- Both cause encephalopathies
- HYPO: INC SYM response to low blood sugar, leading to confusion, seizures, dilated pupils, brisk reflexes, and extensor plantar responses (+ Babinski’s)
1. Rapid improvement w/IV glu, which should only be given after drawing blood glu level for dx - HYPER: acidosis with high sugar levels; pupils are small, seizures less common, reflexes NOT brisk, high blood sugar level is seen -> NO improvement w/IV glu
21
Q
What are the different types of diabetic neuropathy?
A
- SENSORY neuropathy: symmetrical, painful, more often seen in lower than upper limbs initially, disturbing the night sleep
- AUTONOMIC neuropathy: neurogenic atonic bladder
- DIABETIC OPTHALMOPLEGIA: from infarction of N with vascular insufficiency, and causes diplopia -> pain, ocular mm weakness (most common involves the 6th or 3rd cranial nerve)
- MONONEURITIS MULTIPLEX: caused by simultaneous infarction and ischemia of different peripheral nerves
- DIABETIC AMYOTROPHY: caused by involvement of NN roots, with proximal weakness seen in lower limbs
22
Q
What is hypoxic encephalopathy? Describe the most affected areas of the brain, clinical features, common causes, and lasting consequences.
A
- Affects certain parts of brain > others: hippocampus, watershed areas bt vascular territories of major arteries, deep folia of cerebellum
- CLINICAL FXS: stupor or coma, seizures, myoclonus, and if pt recovers, amnesia bc hippocampal damage
- Cerebral hypoxia MCC by cardiac arrest
-
CO poisoning from CO competing w/O2 binding to Hb, w/resultant hypoxia -> cherry red color of skin with cyanotic hue, and carboxyHb level INC in blood
1. Tx is to give hyperbaric O2 - High altitude sickness results in chronic hypoxia with compensated red cell counts
- Chronic bronchitis with resultant CO2 narcosis results in chronic hypoxia and hypercarbia
- NOTE: pts recovering from severe hypoxic insult may proceed to vegetative state, giving appearance of “awake but unaware,” and recovery may be associated with severe memory deficits and dementia
1. Parkinson’s-like state can sometimes result from basal ganglia involvement, and diffuse cortical ischemia can lead myoclonus on a chronic basis
23
Q
What are the causes and neuro signs of hepatic failure and hepatic encephalopathy?
A
- CLINICAL FEATURES: confusion, seizures, slow EEG with triphasic waves, peripheral asterixis (tremor in extended hand), myoclonus (spasmodic, jerky mvmts of group of mm), constructional apraxia (difficulty drawing a figure)
- Reflexes brisk with hepatic failure, but cause of this is not very clear -> differentiates hepatic from uremic encephalopathy, where reflexes are DEC
- Occasionally, spinal cord disease with myelopathy can result but it is not common
- Acute hepatic encephalopathy w/hepatic failure can be caused by acetaminophen OD (chronic cirrhosis, infections, metabolic can also cause liver failure)
1. Serum ammonia levels are high with liver failure - NOTE: polyneuropathy in hepatic disease often associated with alcoholic liver disease
24
Q
What are these 3 images features of? Describe their significance.
A
- Hepatic encephalopathy
- Constructional apraxia with difficulty drawing a figure
- Connecting the numbers in sequence is difficult (Trails Making Test)
- Asterixis, or flapping tremor, in the bottom image
25
Q
What are the systemic complications of uremic encephalopathy?
A
- Systemic complications similar to the ones seen in hepatic encephalopathy, with minor differences (i.e., reflexes DEC)
- Memory deficits, dementia, confusion, INC incidence of seizures, myoclonus, dysequilibrium syndrome with dialysis (DDS: neuro signs and symptoms, attributed to cerebral edema, during or shortly after intermittent hemodialysis), INC tendency for bleeds intracranially, incl subdural hemorrhages
- Peripherally, asterixis with flapping tremor
- Evidence of peripheral neuropathy and proximal mm weakness often associated with low Ca levels seen with chronic renal disease
29
Q
What should the lab workup be for a pt with ME?
A
- Lab eval of pt who presents with ME usually quite extensive unless there is immediate clear etiology
- Blood drawn quickly for screening (items in image)
- Blood glu should be checked prior to giving IV glu, and thiamine should always be given b4 glucose
- Brain imaging is important to evaluate for focal brain injury and LP is necessary (unless contraindications) to rule out a CNS infection
- EEG will determine whether there is generalized slowing consistent with a ME, or in comatose pt, whether pt is experiencing subclinical status epilepticus
