Case Studies

Question 1

Case 21

Answer 1

A 23-year-old woman complains of daytime sleepiness and poor sleep at night. Sometimes she has an uncontrollable urge to sleep during the daytime. When she feels sleepy, she takes 5– 15-minute naps and feels somewhat refreshed upon awakening. These episodes occur a few times per week. She has also noticed that occasionally her body feels somewhat limp and her head drops. These episodes last only a few seconds and seem to be prompted by laughing, getting very angry, or excited. A few times she has noticed brief episodes of complete paralysis while lying in bed at night prior to falling sleep. Sometimes she has strange and occasionally frightening visual hallucinations before she drifts off to sleep at night. She usually wakes up a few times each night. Her most disabling symptom is the daytime sleepiness, which interferes with her ability to concentrate. These symptoms began several years ago. Family history is negative. She is not taking any medications or drugs. The general physical and neurologic exam is normal. MRI of the brain is normal.

Question 2

Diagnosis

Answer 2

This patient has narcolepsy.

Question 3

What is narcolepsy?

Answer 3

Narcolepsy is a condition which causes abnormal sleep patterns. It is almost always an acquired disease and symptoms typically begin in older childhood or young adulthood.

Question 4

Symptoms

Answer 4

The most common symptom is daytime sleepiness, which often leads to “sleep attacks.” Nighttime sleep is often of poor quality, so the total sleep time during a 24-hour period is often normal.

Question 5

What is the role of REM in narcolepsy?

Answer 5

Some of the most characteristic and notable symptoms arise secondary to the intrusion of REM (rapid eye movement) states into waking hours. REM is a stage of normal sleep in which there is paralysis of all the muscles except those controlling eye movements and respiration. Dreams often occur in REM sleep. This intrusion of REM into waking hours accounts for episodes of cataplexy, sleep paralysis, and hypnagogic hallucinations.

Question 6

Cataplexy

Answer 6

Cataplexy refers to brief episodes of loss of muscle tone, which is brought about by intense emotions such as laughing or anger. This can cause falls or, in cases where it is just partial, a head drop or jaw drop. It can cause extreme social embarrassment.

Question 7

Sleep paralysis

Answer 7

Sleep paralysis refers to brief episodes of complete paralysis, which can occur just before sleep onset or upon waking from sleep.

Question 8

Hypnagogic hallucinations

Answer 8

Hypnagogic hallucinations are hallucinations, commonly visual and sometimes frightening, which occur before the onset of sleep (hypnagogic) or upon waking from sleep (hypnopompic).

Question 9

Testing for narcolepsy

Answer 9

Narcolepsy can be confirmed by a multiple sleep latency test (MSLT). An abnormally short onset of sleep (within 5 minutes) and an abnormally quick onset of the REM stage of sleep confirm the diagnosis of narcolepsy. A regular sleep study should be performed to look for other causes of excessive daytime sleepiness, such as obstructive sleep apnea.

Question 10

Cause of narcolepsy

Answer 10

The cause of narcolepsy has recently been determined. The posterior hypothalamus contains neurons that contain orexin (hypocretin). These neurons project widely, including to the cerebral cortex and brainstem. Orexin mediates wakefulness and alertness, and it has been demonstrated that a lack of orexin in animals, or an alteration of the orexin receptors, leads to symptoms reminiscent of narcolepsy. It is thought that there is a selective absence of these orexincontaining neurons in the posterior hypothalamus in narcolepsy.

Question 11

Etiology of narcolepsy

Answer 11

The etiology of this condition is unclear.

Question 12

Treatment

Answer 12

The sleepiness and sleep attacks are treated with stimulants such as amphetamines or methylphenidate. A new medication for this, which has less abuse potential and side effects, is modafinil. Cataplexy can be treated with tricyclic antidepressants or similar medicines, which promote the effects of amines such as norepinephrine, dopamine, or serotonin. These medications inhibit REM sleep.

Question 13

Case 21

Answer 13

A 38-year-old woman complained to her primary care physician of two separate attacks during which she experienced fear and anxiety. These occurred suddenly without warning or precipitation by any circumstance. These episodes were brief, lasting a minute or so each. She noted increasing levels of anxiety and irritability even in between these attacks. Friends and family were concerned about her increasingly “odd” behavior and unprovoked outbursts of anger. There were brief episodes during which she became incoherent. There was concern about panic attacks or even a more severe psychiatric condition such as schizophrenia. The patient had another attack that was witnessed by a friend. There was a sudden feeling of fear and anxiety as in the prior attacks, accompanied by agitation and crude verbalizations. This quickly progressed to loss of responsiveness and convulsive activity that lasted for less than a minute. After this episode she had a neurologic evaluation and testing.

Question 14

Description of the attacks

Answer 14

This patient initially had symptoms of a psychiatric disturbance and seemed to display some elements of psychosis. However, she then had another episode that began like the previous attacks but then clearly became a seizure.

Question 15

How is the seizure relevant?

Answer 15

The knowledge that she had a seizure shifts the whole scheme of diagnostic possibilities. A seizure work-up was performed, including an electroencephalogram (EEG) and magnetic resonance imaging (MRI) of the brain.

Question 16

Test results

Answer 16

The EEG showed epileptiform activity coming from the left anterior temporal region. The MRI revealed an astrocytoma in the left anteromedial temporal lobe.

Question 17

Treatment

Answer 17

The patient underwent resection of the tumor. There were subsequently no more seizures and many, but not all, of her other psychological symptoms improved.

Question 18

Psychological symptoms

Answer 18

Psychological symptoms are very common in epilepsy. They often occur as an aura preceding the onset of more characteristic manifestations of seizure. However, the aura in this case is actually the beginning of the seizure.

Question 19

Common manifestations

Answer 19

Fear, anxiety, anger, disorientation, bizarre behavior, altered perception, a feeling of déjà vu, and agitation are some of the more common manifestations. Psychological or emotional symptoms are associated with temporal lobe seizures, especially involving the anteromedial temporal lobe, and sometimes frontal lobe seizures.

Question 20

Most epileptogenic regions of the brain

Answer 20

Epileptogenic = capable of causing an epileptic attack

The most epileptogenic regions of the brain are the temporal and frontal lobes, especially the limbic regions.

Question 21

Differential diagnosis

Answer 21

Epilepsy with emotional or psychological manifestations is occasionally confused with psychiatric disease.

Question 22

Symptoms between seizures

Answer 22

Patients with epilepsy, especially temporal lobe epilepsy, sometimes display bizarre behaviors or personality or have psychological disturbances even between the seizures. This can occur in patients with lesions, such as tumors, in specific regions of the brain or even in patients without such lesions.

Question 23

Significance of this phenomenon

Answer 23

This leads to the hypothesis that the temporal lobe, specifically the medial temporal lobe, may be structurally or physiologically abnormal even if no lesion is detected there.

Question 24

Further investigation of temporal lobe

Answer 24

Very fine resolution MRI imaging of the temporal lobes, using coronal images, often shows medial temporal sclerosis in those with chronic temporal lobe epilepsy. This shows up as subtle scarring and loss of volume of the parahippocampal gyri. There is a loss of neurons and gliosis in the hippocampus and to a variable degree in the surrounding structures.

Question 25

Case 23

Answer 25

A 45-year-old woman, who was previously in perfect health, had two seizures in the past week. Both occurred suddenly and each lasted less than a minute. The first seizure started as twitching of the right side of the face, which progressed to twitching of her right hand and then her right leg. She felt some perioral numbness as well. There was no loss of consciousness or other symptoms, and she was aware of what had occurred. This happened while in bed. The second seizure, as described by her husband, started with facial twitching but she rapidly lost consciousness and then had a generalized convulsion. She bit her tongue and had blood in her mouth. She also had urinary incontinence. She began responding a few minutes after the convulsion, but she was still confused and somewhat agitated for about 30 minutes after that. She had never had a seizure before. In between these spells she had been normal, and examination was normal.

Question 26

Testing procedures

Answer 26

The onset of seizures in a previously healthy individual without a history of seizure mandates careful evaluation. Brain imaging is required, preferably with MRI (a CT is done in the emergency room setting to look for a cerebral hemorrhage).

Question 27

Test results

Answer 27

MRI in the patient discussed revealed a meningioma over the midlateral aspect of the left hemisphere, in the vicinity of the primary motor cortical area.

Question 28

First seizure

Answer 28

The first seizure experienced by this patient was a focal motor, or simple partial, seizure. Normal consciousness was maintained and motor manifestations occured only on the contralateral side to where the brain focus of the seizure was. In this case, the seizure focus began in or around the facial part of the left primary motor cortex and spread progressively to involve the upper extremity and then the lower extremity part of the primary motor cortex (refer to the somatotopic representation of the face and upper and lower limbs on the motor homunculus; see Fig. 23.9). This is referred to as a Jacksonian march or Jacksonian seizure. It is rare to see the full march of clonic activity, but it is historically and conceptually important to know about it.

Question 29

Second seizure

Answer 29

. The second seizure almost certainly had its onset in the same spot as the first one, except that this one spread rapidly and became generalized, i.e., involving both hemispheres. This generalization results in loss of consciousness and often generalized convulsions (generalized tonic-clonic seizures). Tongue biting and/or urinary incontinence is also often associated with generalized tonic-clonic seizures.

Question 30

Seizure with altered consciousness, but not generalized

Answer 30

When there is alteration of consciousness with a seizure but it is not generalized, it is called complex partial.

Question 31

Significance of a seizure

Answer 31

Seizures are a cortical phenomenon. A seizure indicates an abnormality of the electrophysiology of the cortical neurons.

Question 32

Cortical neuron hyperexcitability

Answer 32

The cortical neurons become hyperexcitable and typically produce “positive” symptoms rather than symptoms indicating loss of function.
The full electrophysiology of seizure initiation and progression is beyond the scope of this discussion.

Question 33

Manifestations of seizures

Answer 33

The manifestations of seizures are widely varied, and depend on which part of the cerebral cortex is affected.

Question 34

Order of most to least “epileptogenic” regions

Answer 34

The most “epileptogenic” regions, in descending order, are the temporal lobes, frontal lobes, parietal lobes, and occipital lobes.

Question 35

Primary vs. secondary seizures

Answer 35

Seizures are either primary or secondary.

Question 36

Secondary seizure

Answer 36

A secondary etiology is more common with new-onset seizures in adults, and can be caused by strokes, tumors, vascular malformations, hemorrhage, and any other lesion causing cortical irritation. Subcortical lesions do not cause seizures.

Question 37

Primary seizure

Answer 37

Primary seizures are more common in children, who often “outgrow” them, and there is no identifiable lesion on brain imaging. There is often a hereditary component. However, seizures in children can certainly be secondary and new-onset seizures in adults can be primary (or at least show no identifiable lesion).

Question 38

Case 8

Answer 38

A 68-year-old woman presents to the emergency room with a sudden onset of right arm and leg weakness and altered speech. The right side of her face is noted by the family to be “droopy” and they say she is speaking “gibberish.” This began very suddenly about 3 hours before presenting to the ER. The symptoms have been about the same since the onset. The history cannot be obtained from the patient herself since her speech is not intelligible. The exam shows the patient to be alert and attentive. She can speak words but they are contextually inaccurate and she cannot form understandable sentences or even phrases. She cannot speak the names of simple objects that are presented to her, and she cannot follow direction appropriately. The right side of her face and her right arm are very weak, while the right leg is only mildly weak. The rest of the neurologic exam is unremarkable.

Question 39

Diagnosis

Answer 39

This patient has had a stroke. It is in the distribution of the middle cerebral artery (MCA) on the left.

Question 40

Middle cerebral artery strokes

Answer 40

The MCA is a common target for stroke; it is sometimes in the full distribution of the MCA, but more commonly only part of it is affected.

Question 41

Characteristic symptoms of a MCA stroke

Answer 41

Some symptoms that are characteristic of MCA territory strokes include hemiparesis and/or hemisensory loss (contralateral), aphasia (usually only if the left MCA is affected), and sometimes hemineglect (contralateral, especially with right MCA stroke).

Question 42

Patient symptoms

Answer 42

This patient exhibits aphasia and hemiparesis. Some information cannot be ascertained in aphasic patients since they cannot talk about their symptoms.

Question 43

Two common etiologies of strokes

Answer 43

The two common etiologies of strokes are embolism and cerebral thrombosis.

Question 44

Source of emboli

Answer 44

Emboli commonly arise from a cardiac source.

Question 45

Source of thrombus

Answer 45

A thrombus forms within the heart and a piece or pieces break off, travel downstream, and become lodged within one or more cerebral arteries. A thrombus can also form within a cerebral artery, or one of the arteries leading to the brain (e.g., carotid).

Question 46

Result of blockage by emboli or thrombus

Answer 46

The blockage can lead to a reduction of blood flow that, if severe enough and prolonged, leads to infarction.

Question 47

Testing

Answer 47

This patient had an urgent head CT (to rule out hemorrhage). Other testing would include carotid ultrasound or cerebral magnetic resonance angiography (MRA) to look at the appropriate arterial circulation, and echocardiogram.

Question 48

Initiation cardiac thrombus

Answer 48

Cardiac thrombus is often prompted by atrial fibrillation, so it would be important to monitor the cardiac rhythm.

Question 49

Treatment for stroke

Answer 49

Treatment for stroke includes intravenous tissue plasminogen activator (TPA) if it can be started within 3 hours of the stroke onset, intraarterial thrombolysis if given within 6 hours of onset, carotid endarterectomy if there is severe carotid stenosis from the thrombus (this will only help prevent future strokes), aspirin or similar medications, or heparin.