of ocular or topical medicines.

Ironically, medicines for psychiatric and

neurologic disorders - anticholinergics, AEDs, antiparkinson agents,
opioids, and serotonin agents- readily cross the blood-brain barrier and
produce a delirium. In a surprising and paradoxical example,
intramuscular injections of olanzapine administered for schizophrenia
may produce confusion, agitation, anxiety, sedation, and more severely
depressed levels of consciousness rather than calming the patient.
Researchers have labeled this reaction the post-injection
delirium/sedation syndrome and attribute it to the medicine seeping into
the vasculature.
Another consideration is medicine withdrawal. Unlike the depressed
sensorium typically associated with delirium, withdrawal from
benzodiazepines, opioids, or nicotine may cause agitated delirium. In
addition, withdrawal from alcohol, barbiturates, and benzodiazepines but not nicotine - routinely causes seizures.

General Treatments
Even before arriving at an exact diagnosis or instituting Specific
treatment, physicians must ascertain that the patient has adequate
cerebral oxygen, blood glucose, fluid and electrolytes, nutrition, and
other necessities. Physician must control pain with narcotics if indicated,
but otherwise reduce or eliminate psychoactive drugs. Other preliminary
measures consist of providing orientation clues, such as illumination,
clocks, and calendars.
Antipsychotics can reduce dangerous and exhausting Activity,
hallucinations, and disordered thinking. Physician should hesitate before
prescribing antipsychotics or benzodiazepines to avoid respiratory
depression. Sometimes physicians can calm a dangerously disruptive
patient by restoring a missing substance or providing a reasonable
facsimile, such as methadone, a nicotine patch, or Even, in emergency,
an alcoholic beverage.

Hepatic Encephalopathy
A particularly interesting and frequently occurring variety of delirium is
hepatic encephalopathy. With hepatic insufficiency, mental function
and consciousness steadily decline. Mild confusion with either lethargy
or, less frequently, agitation may precede coma and overtly abnormal
liver function tests. In classic cases, the neurologic examination
demonstrates asterixis and the EEG shows triphasic waves.
Neurologists traditionally attribute hepatic encephalopathy to an
elevated serum concentration of ammonia (NH3). This mechanism
occurs in the common scenario of gastrointestinal bleeding or highprotein meals precipitating hepatic encephalopathy in patients with
cirrhosis. In these situations cirrhosis-induced portal hypertension
shunts NH3 released from protein in blood or food directly into the
systemic circulation. Because NH3 is a Small and nonionic (uncharged)
molecule, it readily penetrates the blood-brain barrier. As a treatment of
hepatic encephalopathy, physicians often attempt to convert ammonia
(NH3) to ammonium (NH4), which is ionic and unable to penetrate the
blood-brain barrier.
An alternative explanation for hepatic encephalopathy is
that
production of false neurotransmitters binds to benzodiazepine-gammaaminobutyric acid (GABA) receptors and increases GABA activity.
Thus, giving flumazenil, a benzodiazepine antagonist that interferes with
benzodiazepine-GABA receptors and carries some risk of precipitating
seizures, temporarily reduces hepatic encephalopathy symptoms.
PRECAUTIONS IN DIAGNOSING ALZHEIMER DISEASE
Even though this and other chapters have presented numerous causes of
dementia and delirium, Alzheimer disease occupies the default position
in the diagnosis of dementia. Physicians should maintain vigilance and
mind the red Flags that warn against its diagnosis (Box 7-5).

Although they certainly do not preclude a diagnosis of Alzheimer

disease, these red flags will help prevent a misdiagnosis in cases of
toxic-metabolic encephalopathy, psychiatric disorders, dementia in
young adults (see Box 7-2), and neurodegenerative illnesses that strike at
more than the brains cognitive centers.
BOX 7-4

Commode Cited Frequent Causes of Delirium

Fluid or electrolyte imbalance, especially dehydration

Hepatic or uremic encephalopathy, i.e., organ failure
Major surgery
Medicadons
Narcotics and alcohol
Pneumonia, urinary tract, and other nonneurologic
infections
BOX 7-5 Red Flags for an Alzheimer Disease Diagnosis
Age younger than 65 years: see Box 7-2
Fluctuating level of consciousness: see toxic-metabolic
encephalopathy, Lewy bodies dementia
Behavior, emotional, or personality disturbances over-shadowing
cognitive impairment: see frontotemporal dementia and HIV dementia
Rapidly - 6-12-month - progressive development, see Creutzfeldt- Jakob
disease, vCJD, paraneoplastic limbic encephalitis (Chapter 19), HAD,
frontotemporal dementia,
Presence of physical abnormalities
Gait impairment: see vascular dementia, HIV dementia, NPH
Lateral signs, e.g., hemiparesis, spasticity (corticospinal tract signs): see
vascular dementia
Movement disorders: see Box 18-4
Myoclonus: see Creutzfeldt-Jakob disease, paraneoplastic encephalitis
Rigidity, Bradykinesia (Parkinsonism): see dementia with Lewy bodies
and Parkinson disease

HIV human immunodeficiency virus; vCjD, variant CrcutzfeldtJakob disease; HAD, HIV-associated dementia; NPH, normal-pressure
hydrocephalus
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Chapter 7
Question and Answer
1.Which of the following statements is true regarding individuals with
mild cognitive impairment (MCI)?
a. They have impairment of their social or occupational activities.
b. As with Alzheimer disease, cholinesterase inhibitors slow the
cognitive decline in MCI.
c. Approximately 10% progress from MCI to
dementia each year.
d. The risk factors associated With MCI progressing to dementia differ
from those for developing Alzheimer disease.
Answer: MCI is most often the first clinical sign of alzheimer disease.
Because MCI individuals maintain their social and occupational
activities, neurologists can not diagnose them as having dementia.
However, each year approximately 10% of MCI individuals progress
from that stage to the next, dementia. The risk factors associated with
MCI individuals progressing to dementia are similar to those for
individuals developing
Alzheimer disease. For example, MCI
individuals carrying the E4-E4 alleles and those with a family history of
alzheimer disease are likely do progress to dementia. Physicians should
have MCI patients undergo tests for correctable causes of dementia.
Cholinesterase inhibitors do not slow the cognitive decline or reduce the
rate of deterioration of MCI into dementia.
2.Advancing age leads to loss of neurons in the cerebral cortex and
many deep structures. Which of the following structures is not subject to
age-related neuron loss?
a. Locus ceruleus
.

b. Suprachiasmatic nucleus
c. Substantia nigra
d. Nucleus basalis of Meynert
e. Mamillary bodies
Answer: e. The maxillary bodies resist age-related changes. in contrast,
age-related changes in the other structures contribute to disturbances in
affect (locus cerulcus), sleep (locus cemleus and suprachiasmatic
nucleus), and locomotion (substanda nigra).
3.In a 70-year-old man who has normal cognitive and physical Function,
which sensation is most likely to be lost?
a. Joint position
b. Vibration
c. Pain
d. Temperature
Answer: b. In normal individual older than 65 years, vibration sensation
declines to a greater degree than other sensations. Although loss of
position sense is less pronounced dan vibration sense, that loss is more
troublesome because it leads to gait impairment and falls. In contrast,
pain and temperature sensations remain remain relatively well preserved.
Preservation of pain sensation is well known to physicians who care for
elderly patients describing painful feet from osteoarthritis, peripheral
vascular disease, and diabetic neuropathy.
4. The diagnosis of normal-pressure hydrocephalus (NPH) has received
much attention because instalation of a ventricular peritoneal shunt may
correct the dementia. Most cases are idiopathic. Which conditions
predispose a patient to NPH?
a. Hypothyroidism
b. Meningitis and subarachnoid hemorrhage
c. Cysticercosis

d. Tuberous sclerosis
Answer: b. Both meningitis and subarachnoid hemorrhage can cause
communicating hydrocephalus that sometimes leads to NPH.
Cysticercosis and tuberous sclerosis cause obstructive hydrocephalus.
Nevertheless, most cases of NPH are idiopathic.
5. True or false: A cerebral cortex biopsy is appropriate for the diagnosis
of Alzheimer disease.
Answer: False. Although a definitive diagnosis is desirable, a single
cerebral cortex biopsy cannot provide it because the histologic changes
are quantitative rather than qualitative. For example, normal aged brains
contain the characteristic plaques and tangles - although in lesser
concentrations and different distributions. Neurologists also do not
request a cerebral biopsy for the diagnosis of frontotemporal dementia,
dementia with Lewy bodies, or vascular cognitive impairment (VCI),
which the preliminary version of the Diagnostic and Statistical Manual
of Mental Disorders, 5th edition (DSM-5) calls Vascular.
Neurocognotive Disorder. All these diseases are incurable and the
procedure carries risks of hemorrhage and seizures.
A biopsy may have benefits that outweigh the risks in the diagnosis of
Creutzfeldt-Jakob disease, variant Creutzfeldt-]akob disease (vCJD),
other infections, and neoplasms.
6. With which histologic feature is Alzheimer disease dementia most
closely associated?
a. Accumulation of tau
b. lncreased concentration of plaques