Encephalopathic Disorders and Hydrocephalus

Question 1

Encephalopathy

Answer 1

Encephalopathy is a fairly vague diagnosis that simply means a disorder of
the brain that can be caused by disease, injury, drugs, or chemicals.
● The word is often used to group several different conditions that cause some
degree of brain dysfunction

Question 2

Encephalopathic disorders

Answer 2

○ Toxic-metabolic encephalopathy (TME; an umbrella diagnosis)
○ Wernicke encephalopathy (a specific type of TME)
○ Hepatic encephalopathy (a specific type of TME)
○ Hashimoto encephalopathy (a specific type of TME)
○ Hypoxic-ischemic (Anoxic) encephalopathy (a specific type of TME)
○ Chronic traumatic encephalopathy (due to repeated TBI)
○ Hypertensive encephalopathy (due to uncontrolled high blood pressure)
○ Spongiform encephalopathy (due to prion disease)

Question 3

No matter the cause, the common signs and symptoms of encephalopathy
generally include the following:

Answer 3

○ Confusion, disorientation, or altered mental status
○ Fatigue or sleepiness
○ Behavior or personality changes (agitation or irritability)
○ Depression or apathy
● Other common symptoms may include hallucinations, poor balance,
amnesia, involuntary movements or tremors, seizures, and stupor.
○ In severe cases, patients present in a comatose state

Question 4

Toxic-Metabolic Encephalopathy

Answer 4

● Acute Toxic-Metabolic Encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease
○ Common among critically ill patients and
usually a consequence of systemic illness.

Question 5

This encephalopathy is Generally considered reversible, making
prompt recognition and treatment
important

Answer 5

Toxic-Metabolic Encephalopathy

Question 6

Toxic-Metabolic Encephalopathy pathophysiology

Answer 6

○ Normal neuronal activity requires a balanced environment of electrolytes, water,
amino acids, excitatory and inhibitory neurotransmitters, and metabolic
substrates (glucose, oxygen, protons, etc.).
○ In TME, there is interruption of polysynaptic pathways, alteration of excitatory-
inhibitory amino acid balance, and/or disruption of the blood-brain barrier.
■ Exact pathophysiology varies according to underlying etiology.

Question 7

Toxic-Metabolic Encephalopathy S/S

Answer 7

○ TME presents with a nonspecific combination of the common signs and symptoms of encephalopathy presented on slide 5.
■ The level of alertness reflects the severity of the underlying condition, so severely affected patients are comatose.
■ In comatose patients with TME, brainstem reflexes may even be
affected, mimicking some brain death criteria.
■ In severely obtunded patients, decorticate and decerebrate
posturing can occur.
○ Autonomic instability (with tachycardia, hypertension, fever, sweating)
and respiratory abnormalities (Cheyne-Stokes) may also occur

Question 8

Septic encephalopathy

Answer 8

The most common cause of acute TME.
■ Its presence in sepsis correlates with increased mortality.
■ Treatment is focused on supporting vitals while treating for infection.

Question 9

Uremic encephalopathy

Answer 9

A sign of advanced renal failure.
■ If acute, often reverses with dialysis, although a lag time of 1-2 days usually
occurs before mental status clear.

Question 10

Hypoxic-ischemic encephalopathy

Answer 10

Sometimes called Anoxic encephalopathy.
■ Usually a straightforward diagnosis as it follows an obvious precipitating
event, such as cardiac arrest, or severe hypotension or hypoxemia.

Question 11

Hypoglycemia

Answer 11

Usually preceded by tremor and diaphoresis
■ May progress to seizures, bizarre behavior, coma, and focal neuro deficits

Question 12

Hyperosmolar hyperglycemic state (HHS) and DKA

Answer 12

Diabetic complications.
■ Neurologic deterioration is more common in HHS than DKA alone.

Question 13

Hyponatremia

Answer 13

common cause of TME, most often due to SIADH.
■ Tonic-clonic seizures and coma can occur with advancing hyponatremia.
■ Correcting too quickly can cause Osmotic Demyelination Syndrome (ODS)

Question 14

Hypernatremia

Answer 14

Results in osmotic dehydration of the brain.
■ Correcting too quickly can result in fatal cerebral edema.

Question 15

Toxic-Metabolic Encephalopathy diagnosis

Answer 15

○ The initial workup should focus on excluding other conditions that may
cause acute confusion or altered mental status, as well as identifying
potential etiologies of TME.
■ Imaging: CT head, possibly eventual MRI
■ Labs: CBC, CMP, PT/INR, PTT, TSH, magnesium, ammonia, and ABGs
■ Toxicology and ETOH screening for suspected intoxication
■ Blood and CSF cultures if infection is a possibility
■ EEG in more obtunded or comatose patients

Question 16

Toxic-Metabolic Encephalopathy treatment

Answer 16

○ The treatment of TME should focus primarily on correcting the underlying condition that caused the encephalopathy.
○ Regardless of the cause, several general measures should be initiated:
■ Discontinue all drugs with potential CNS toxicity
■ One-on-one observation for confused/disoriented patients
■ Haloperidol may be given IM/IV to treat severe agitation
● Small doses in elderly are effective
● Avoid in QT prolongation, alcohol or benzodiazepine withdrawal, anticholinergic toxicity, or Parkinson disease
■ Thiamine IM/IV should be given to patients with history of alcoholism, malnutrition, cancer, hyperemesis gravidarum, or on dialysis

Question 17

Toxic-Metabolic Encephalopathy prognosis

Answer 17

○ While TME is a treatable condition, the clinical course can be tedious.
○ Neurologic recovery often lags behind recovery of the underlying
condition, especially in older patients.
○ Hypoxic-ischemic coma is associated with a 58% mortality and a 31%
incidence of persistent vegetative state/severe disability

Question 18

Wernicke Encephalopathy

Answer 18

● Wernicke Encephalopathy (WE), a type of TME, specifically occurs due to an
inadequate intake or poor absorption of Thiamine.
○ Thiamine is Vitamin B1, a water-soluble vitamin that is essential for
glucose metabolism and neuronal function.
○ Found in meat, nuts, eggs, legumes, many vegetables, whole grains, and a
wide variety of fortified foods (cereal, bread, etc.)

Question 19

More commonly than WE, Thiamine deficiency can present as _____

Answer 19

Beriberi.

Question 20

Significant Thiamine deficiency can result in ____

Answer 20

encephalopathy, called
Wernicke, which is most commonly seen in severe alcoholism in the US.

Question 21

Wernicke Encephalopathy etiology

Answer 21

○ Severe alcoholism is a main cause of prolonged Thiamine deficiency because excessive alcohol intake interferes with Thiamine absorption from the GI tract, as well as hepatic storage of the vitamin.
○ Other than people with a history of heavy alcohol use, WE can occur in people who are fasting/starving, receiving parenteral nutrition, recovering from extensive GI surgery, being fed after a period of starvation, undergoing hemodialysis, or suffering from advanced cancer

Question 22

Wernicke Encephalopathy pathophysiology

Answer 22

○ Thiamine deficiency is particularly detrimental to cells in the CNS, as neuronal
cells require large amounts of Thiamine for cellular function (more than other
cell types in the body)
○ Interestingly, giving a carbohydrate load to patients with Thiamine deficiency
can trigger acute Wernicke Encephalopathy.
■ Example- Refeeding after starvation or IV dextrose to high-risk patients.
○ In WE, abnormal CNS lesions caused by petechial hemorrhagic necrosis form
symmetrically around the third ventricle, aqueduct, and fourth ventricle, as well
as other internal brain structures

Question 23

Wernicke Encephalopathy S/S

Answer 23

○ The common signs and symptoms of encephalopathy presented on slide
5 apply here as well.
■ Oculomotor abnormalities, such as nystagmus and/or palsies of
conjugate gaze. Sluggish pupil reaction is common, too.
■ Vestibular dysfunction with gait ataxia. Gait is wide-based, slow,
with short-spaced steps

Question 24

Wernicke Encephalopathy diagnosis

Answer 24

○ Wernicke Encephalopathy is considered a clinical diagnosis, based on the recognition of underlying malnutrition or vitamin deficiency in a Pt with the characteristic triad of signs and symptoms:
■ Confusion, eye movement abnormalities, and gait ataxia
○ No specific tests are diagnostic, and no abnormalities on available tests are considered characteristic.
■ Labs and imaging are largely to rule out other causes of encephalopathy or to identify concomitant disease.
■ Even serum Thiamine levels do not always reflect CSF Thiamine levels, and normal values don’t exclude the diagnosis

Question 25

Wernicke Encephalopathy treatment

Answer 25

○ The first imperative is to administer Thiamine rather than spend time trying to confirm the diagnosis with lab. Treat when suspected.
○ Treatment involves immediate administration of Thiamine IV or IM.
○ Magnesium is a necessary cofactor in Thiamine-dependent metabolism, and hypomagnesemia should be corrected, too, if present.
○ Alcohol cessation is also mandatory in patients with WE, but can be obviously difficult. Refer to GI/Hepatology

Question 26

Is Wernicke Encephalopathy preventable?

Answer 26

Yes
○ Importantly, Wernicke Encephalopathy is preventable.
■ Thiamine supplementation is recommended for Pts at risk for deficiency.
■ WE can be acutely triggered by administration of IV glucose solutions (like
those with dextrose) to Pts with Thiamine deficiency. In susceptible Pts,
precede or accompany IV glucose with Thiamine 100 mg IV

Question 27

What is wernicke-korsakoff syndrome?

Answer 27

Of those untreated who survive, 80% develop “Korsakoff psychosis” with major
memory dysfunction (Wernicke-Korsakoff Syndrome).
■ Korsakoff psychosis- Retrograde and anterograde amnesia, confabulation
■ Wernicke Encephalopathy = the Acute, Korsakoff Syndrome = the Chronic

Question 28

Hepatic Encephalopathy

Answer 28

● Also known as Portosystemic Encephalopathy, this is a serious complication
of chronic liver disease defined as an alteration in mental status and
cognitive function occurring in the presence of liver failure

Question 29

Hepatic Encephalopathy pathophysiology

Answer 29

○ Encephalopathy occurs due to the accumulation of substances normally metabolized by the liver.
○ Liver insufficiency secondary to either hepatocellular dysfunction or portal systemic shunting.
○ Gut-derived neurotoxins that are not removed by the diseased liver build up in the blood, reach the brain, and cause the symptoms.
■ Short-chain fatty acids, phenols, mercaptans, tryptophan, etc.
○ Ammonia levels are typically elevated due to poor hepatic clearance in the feces, and may play a role in some symptomatology.

Question 30

Hepatic Encephalopathy S/S

Answer 30

○ The common signs and symptoms of encephalopathy presented on slide
5 apply here as well.
○ Asterixis may be present, elicited by having
the patient extend their arms and bend their
wrists back (“liver flap”).
○ In addition, patients with hepatic encephalopathy may show signs of
chronic liver disease, portal hypertension, or fulminant hepatic failure,
such as ascites, easy bruising, gynecomastia, caput medusa, etc
○ May have fetor hepaticus, a musty, sweet,
pungent, peculiar smelling breath odor

Question 31

Hepatic Encephalopathy treatment

Answer 31

○ Treatment is multifactorial and may involve treatment of precipitating factors, such as hypokalemia, infection, volume depletion, etc.
○ The mainstay of treatment is Lactulose, a nonabsorbable laxative.
■ Results in colonic acidification that causes bowel movements, facilitating the
elimination of nitrogenous products in the gut.
■ The goal is to promote 2-3 soft stools per day, titrating Lactulose as needed.
■ Poorly absorbed antibiotics may be an alternative to Lactulose.
○ Development of encephalopathy in chronic liver disease is considered a poor prognostic sign, but can be managed in most (GI referral!)

Question 32

Hashimoto Encephalopathy

Answer 32

Hashimoto Encephalopathy (HE) is an uncommon, rare form of acute or
subacute encephalopathy associated with Hashimoto Thyroiditis.
○ Controversial with an unclear mechanism

Question 33

Hashimoto Encephalopathy pathophysiology

Answer 33

○ While not completely clear, the bulk of evidence suggests HE is actually
an autoimmune disorder and is not due to thyroid disease.
○ HE may represent an autoimmune CNS vasculitis occurring from either
endothelial inflammation or immune complex deposition.

Question 34

Hashimoto Encephalopathy S/S

Answer 34

○ The common signs and symptoms of encephalopathy presented on slide
5 apply here as well.
○ Patients with HE can present with a fulminant, subacute, or more
chronic course of declining mental status with no fever.
■ Many patients present with slowly progressing cognitive impairment
with dementia, confusion, hallucinations, or somnolence
○ Other common neurological signs in HE include…
■ Seizures (50-66%)
■ Myoclonus or tremor (38%)
■ Upper Motor Neuron signs (85%)

Question 35

Hashimoto Encephalopathy diagnosis

Answer 35

○ Elevated serum antithyroid peroxidase antibodies (anti-TPO) and/or antithyroglobulin antibodies (anti-TG) is an essential lab finding
○ CSF analysis reveals abnormalities in 80%, with elevated protein being the most common abnormality (with normal glucose level).
○ Thyroid status varies in HE, with patients ranging from overt hypothyroidism to overt hypothyroidism, and even euthyroid
○ EEG generally shows nonspecific slowing of background activity.
○ MRI in HE is usually normal

Question 36

Hashimoto Encephalopathy treatment

Answer 36

○ In a patient with encephalopathy and elevated anti-TPO/anti-TG antibody levels in whom other causes of encephalopathy are ruled out,
an initial trial of a corticosteroid should be attempted
○ Temporary treatment of seizures with an anticonvulsant medication may be necessary for some.
○ Neurology referral is strongly advised and prognosis is generally good.

Question 37

What is Hydrocephalus

Answer 37

● Hydrocephalus is when an accumulation of CSF occurs within the brain,
usually causing an increase in intracranial pressure (ICP).
● Hydrocephalus can occur due to birth defects or
can be acquired later in life.

Question 38

_____ is the most common cause of abnormally large heads in neonates

Answer 38

Hydrocephalus

Question 39

When the hydrocephalus develops before the
fontanelles have closed, ____

Answer 39

he head can enlarge
significantly and the fontanelles can bulge.

Question 40

When the hydrocephalus develops after the
fontanelles have closed, _____

Answer 40

the head circumference does not increase but can cause severe and rapidly increasing ICP

Question 41

Obstructive Hydrocephalus

Answer 41

● As the name implies, Obstructive
Hydrocephalus results from
obstruction of normal CSF flow.
● The obstruction is most commonly
at the Cerebral Aqueduct in the
midbrain (aqueduct of Sylvius)
○ Sometimes the obstruction is at the median
or lateral outlets of the fourth ventricle
(Magendie and Luschka foramen).

Question 42

Obstructive Hydrocephalus pathophysiology

Answer 42

○ Aqueductal stenosis- Narrowing of the aqueduct between the 3rd and 4th
ventricles, either due to congenital deformity or secondary to scarring or narrowing from a tumor, subarachnoid/intraventricular hemorrhage, or infection
○ Dandy-Walker Malformation- Progressive cystic enlargement of the 4th ventricle during fetal development, result in hydrocephalus and complete or partial agenesis of the cerebellar vermis (only 5-10% of congenital cases).
○ Type II Chiari Malformation- Also known as an Arnold-Chiari Malformation, this
is a structural defect in the cerebellum with a downward displacement the
cerebellar tissue through the foramen magnum.

Question 43

Communicating Hydrocephalus

Answer 43

● Communicating Hydrocephalus
results from the impaired
resorption of CSF
● In this case, there is no obstruction
blocking the flow of the CSF out of
the 4th ventricle
○ Instead, the rate of CSF production exceeds
the rate of CSF resorption, so an excessive
amount of CSF builds up

Question 44

Communicating Hydrocephalus pathophysiology

Answer 44

○ Impaired CSF resorption from the subarachnoid space usually occurs
due to dysfunction of the arachnoid granulations along the superior sagittal sinus
■ Congenital absence of the arachnoid villi is the fetal developmental explanation.
■ Acquired dysfunction can result from meningeal inflammation, usually secondary to either infection or subarachnoid blood

Question 45

Hydrocephalus S/S

Answer 45

○ Neurological findings depend on whether ICP has increased.
○ In infants, symptoms of increased ICP include high-pitched crying, irritability,
vomiting, lethargy, difficulty feeding, strabismus, and bulging fontanelles
■ Sunset eyes- eyes that appear to gaze downward
“Hydrocephalus,” Merck Manual Professional.
○ Older children may complain of headaches and/or decreased vision
○ In adults, symptoms of increased ICP include headaches, nausea, vomiting,
altered mental status, and vision impairment.
■ Papilledema can occur and is usually a late sign of increased ICP, and its
initial absence does not exclude hydrocephalus.
Hydrocephalus

Question 46

Hydrocephalus diagnosis

Answer 46

○ Congenital Hydrocephalus is often diagnosed
on routine prenatal ultrasound.
○ After birth, hydrocephalus may be suspected if
exam reveals an increased/increasing head
circumference, bulging fontanelles, or widely
separated cranial sutures.
■ In this case, Cranial Ultrasound is the
diagnostic study of choice

Question 47

Hydrocephalus diagnosis

Answer 47

○ If the diagnosis is suspected in older infants, children, or adults, CT Head and/or
MRI Brain are the preferred diagnostic studies.

Question 48

Hydrocephalus Treatment

Answer 48

○ Neurosurgery consult- Treatment depends on the etiology, severity, and whether the condition is progressive (ventricle size increasing).
○ Mild, non-progressive cases are often observed with serial imaging and head circumference measurements.
○ Progressive or severe hydrocephalus usually requires surgical treatment with a ventricular shunt.
■ Ventriculoperitoneal (VP) Shunt connects the right lateral ventricle to the peritoneal cavity of the abdomen via a plastic tube with a
one-way, pressure-relief valve.
○ Another potential option for Obstructive Hydrocephalus only that is becoming
increasing utilized in the US is a Third Ventriculostomy

Question 49

Normal Pressure Hydrocephalus

Answer 49

● Normal Pressure Hydrocephalus (NPH) is technically a form of
Communicating Hydrocephalus that does not result in overtly increased ICP.
● This does not present in infants and children, and generally develops
gradually sometime after 40 years of age (usually over 60 years of age)

Question 50

Normal Pressure Hydrocephalus etiology

Answer 50

○ Idiopathic (Primary) NPH: No clear underlying cause can be identified.
○ Secondary NPH: Underlying causes include trauma, infection, or hemorrhage
(often times occurring years after the eliciting event)

Question 51

Normal Pressure Hydrocephalus pathophysiology

Answer 51

○ Believed to result from a defect in CSF resorption in arachnoid granulations, just
to a lesser degree than other cases of Communicating Hydrocephalus

Question 52

Normal Pressure Hydrocephalus S/S

Answer 52

○ Patients with NPH exhibit a classic triad of signs and symptoms called
Hakim’s Triad (also known as Adams Triad):
■ Gait disturbance - magnetic gait, “feet are stuck to the floor.”
■ Cognitive impairment/Dementia
■ Urinary incontinence

Question 53

Normal Pressure Hydrocephalus diagnosis

Answer 53

○ After thorough evaluation of a patient presenting with these symptoms,
if NPH is considered a real possibility, brain imaging should be obtained.
■ In NPH, MRI (preferred over CT) may show ventricular enlargement
disproportionate to cortical atrophy.
○ Lumbar puncture should then be
performed to assess for increased ICP
■ In patients with NPH, CSF opening pressure should be normal,
although may be very slightly elevated in some

Question 54

Normal Pressure Hydrocephalus treatment

Answer 54

○ All patients with suspected or possible NPH should be referred to a
Neurologist for the LP and diagnostic trial.
○ If the patient responds well to the removal of CSF, they are generally
treated with a VP Shunt if they have acceptable surgical risk
○ Patients with NPH who are not felt to be good surgical candidates can
sometimes be treated successfully with serial LPs in a neurology clinic.

Question 55

Idiopathic Intracranial Hypertension

Answer 55

● Also known as Benign Intracranial Hypertension or Pseudotumor Cerebri,
Idiopathic Intracranial Hypertension (IIH) is NOT a type of Hydrocephalus.
● Typically occurs in females of childbearing age (often starts in early 20s)

Question 56

Idiopathic Intracranial Hypertension etiology

Answer 56

○ As the name implies, the cause is unknown.
○ Increased ICP occurs without a mass-occupying lesion or hydrocephalus, but
probably due to obstruction of cerebral venous drainage.
○ For reasons we don’t understand, IIH can
sometimes develop in children after a long
course of corticosteroids are stopped, or after
growth hormone is utilized.
○ Again for reasons we don’t understand, IIH
can also develop after patients take
Tetracyclines or large amounts of Vitamin A.

Question 57

Idiopathic Intracranial Hypertension S/S

Answer 57

○ Almost all patients (84%) have daily or near daily generalized
headaches of fluctuating intensity, often with nausea.
○ Transient visual obscuration occurs in about 68%
○ About 52% experience pulse synchronous tinnitus.
○ Subjective vision loss happens in about 32%, often beginning
peripherally and can be permanent (even if ICP is reduced).
○ Horizontal diplopia (due to 6th CN palsy) happens in about 18%

Question 58

Idiopathic Intracranial Hypertension diagnosis

Answer 58

○ If IIH is suspected, be sure to check visual fields and optic fundi, even if
the patient does not report visual symptoms.
○ MRI of the brain with and without contrast should be obtained.
■ Important to rule out an intracranial mass.
■ MRI is normal in IIH.
○ Ideally, MR Venogram will be performed at the same time, which will
rule out dural sinus thrombosis or stenosis.
○ Only after MRI reveals no contraindications, LP should be performed.
■ Elevated opening pressure is found in IIH (often > 250 cm H2O).
■ CSF studies should be otherwise normal.

Question 59

Idiopathic Intracranial Hypertension treatment

Answer 59

○ the patient should be referred to a Neurologist for evaluation, diagnosis (including LP), and treatment.
○ Once diagnosed, treatment is aimed at 1) reducing ICP, 2) preserving vision, and 3) relieving symptoms.
■ Acetazolamide (Diamox) is the first-line therapy.
■ Furosemide (Lasix) and Topiramate (Topamax) have been used as second-line agents.
○ NSAIDs are the preferred medication for headache relief PRN.
○ Patients with obesity are encouraged to lose weight
○ During active treatment, serial detailed eye exams should occur to monitor vision

Question 60

Idiopathic Intracranial Hypertension