Nearly half of patients with narcolepsy report that their sleepiness and cataplexy substantially interfere with their daily lives, including school, jobs, marriages, or social lives [1,2]. The mainstays of therapy are brief daytime naps and pharmacologic therapy.
There are several nonpharmacologic interventions that may benefit the patient with narcolepsy:
●Avoiding certain drugs – Some drugs should be avoided by patients with narcolepsy. Drugs that can worsen daytime sleepiness include benzodiazepines, opiates, antipsychotics, and alcohol. Other medications such as theophylline or excessive caffeine can cause insomnia, which can worsen daytime sleepiness. In addition, prazosin and other alpha-1 antagonists can worsen cataplexy.
●Napping/sleep hygiene – Behavioral interventions are often helpful for optimal control of narcolepsy. One or two well-timed 20 minute naps will often improve sleepiness for one to three hours though some patients only benefit from long naps [4]. If it can be arranged, a brief nap at work or school is often helpful.
Sleep deprivation may worsen narcolepsy symptoms and therefore patients should be counseled to maintain a regular and adequate sleep schedule [5].
●Psychosocial support – Patients with narcolepsy face various psychosocial and work-related problems throughout their lives; as a result, they may have
difficulty meeting economic and social responsibilities [6]. They also have the additional burden of coping with misperceptions about the causes and the involuntary nature of their symptoms. Common misconceptions, even among medical caregivers, are that sleep attacks and cataplexy (emotionally triggered muscle paralysis resulting in partial or complete collapse) are manifestations of poor motivation, denial, or avoidance. Thus, patients often benefit from
participation in support groups that focus on coping skills and identification of community resources to assist with administrative and medical issues.
Many patients will benefit from these nonpharmacologic approaches, but most also require medications that reduce sleepiness and cataplexy.
Modafinil has become a first line pharmacologic therapy because it provides good control of sleepiness, is generally well tolerated, and illicit use is rare. A
non-amphetamine "wakefulness promoting agent," its mechanism of action is not well understood, but it may increase dopaminergic signaling.
40. 68 yo woman, 3 month hx of spinning sensation. Feeling room spinning when she tries to turn over in bed, resolves in 1 min. No vomiting, but queasy. Normal hearing. Normal ocular movements if sitting, but coarse rotatory nystagmus to one side if head is
hanging from examination table. Abnormality in which site?
C. Otolith
Patients with benign paroxysmal positional vertigo (BPPV) present with recurrent episodes of vertigo that last one minute or less. Episodes are provoked by specific types of head movements, such as looking up while standing or sitting, lying down or getting up from bed, and rolling over in bed. The vertigo may be associated with nausea and
vomiting.
Hearing loss or symptoms are typically absent [14]. Patients with BPPV typically have no other neurologic complaints.
With the patient sitting, the neck is extended and turned to one side. The patient is then placed supine rapidly, so that the head hangs over the edge of the bed. The patient is kept in this position until 30 seconds has passed if no nystagmus occurs. The patient is then returned to upright, observed for another 30 seconds for nystagmus, and the maneuver is repeated with the head turned to the other side. A video demonstrating this maneuver can be viewed at
http://www.neurology.org/content/70/22/2067/suppl/DC2.
Diagnostic criteria employing the Dix-Hallpike maneuver have been proposed for posterior canal BPPV (figure 1) [18]:
●Nystagmus and vertigo usually appear with a latency of a few seconds and last less than 30 seconds
●It has a typical trajectory, beating upward and torsionally, with the upper poles of the eyes beating toward the ground
●After it stops and the patient sits up, the nystagmus will recur but in the opposite direction
●The patient should then have the maneuver repeated to the same side; with each repetition, the intensity and duration of nystagmus will diminish
Benign paroxysmal positional vertigo (BPPV) is commonly attributed to canalithiasis, ie, calcium debris within the semicircular canal [3]. This debris likely represents loose otoconia (calcium carbonate crystals) within the utricular sac.
The semicircular canals normally detect angular head accelerations. Heavy debris in the canal causes inappropriate movement of the endolymph with linear accelerations, such as gravity, and causes the erroneous sensation of spinning when the head shifts with respect to gravity.
41. 24 yo woman, ER after 1-hour generalized tonic-clonic seizure lasted 5 min. Immigrated from Central America 6 months ago. No medications. Drowsy but cooperative. 98.8F, pulse 80/min, resp 18/min, BP 150/90. Toxycology (-). CT head multiple enhancing lesions. Dx?
D. Neurocysticercosis
Neurocysticercosis was observed more frequently in emergency departments of Los Angeles, Phoenix, and Albuquerque (5.7 percent), which had a higher proportion of immigrant Hispanic patients than the other hospitals. Travelers to endemic areas represent another source of cysticercosis, although such infection accounts for a minority of cases in the United States.
The clinical manifestations depend upon whether the cysts are localized to the brain parenchyma, the extraparenchymal tissues, or both. In general, parenchymal cysts are associated with seizures and headache, while extraparenchymal cysts are associated with symptoms of elevated intracranial pressure (eg, headache, nausea, and vomiting) and may be accompanied by altered mental status. Other less common manifestations include mass effect, altered vision, focal neurologic signs, altered mental status, and meningitis. Fever is not typically present. Neurologic examination usually does not demonstrate focal signs in the absence of mass effect or stroke. Parenchymal cystic or enhancing lesions are the most common form of neurocysticercosis (NCC) in hospital-based series and is present in >60 percent of these patients [3,12-15]. The onset of symptomatic NCC has been estimated to peak at three to five years after infection, but it can be delayed for >30 years [14,16,17]. Later onset may be due to calcified lesions.
Ultimately, the cystic lesions either resolve or form a calcified granuloma. When present, the calcifications are associated with recurrent seizures, although the
mechanism of seizures associated with calcified lesions is not completely clear. Seizures may result from inflammation, perhaps from intermittent antigen release [6,7].
Alternatively, changes in brain plasticity and scarring (eg, hippocampal sclerosis) may result in epileptogenic foci [8,9]. Studies have highlighted a potential role of matrix metalloproteinases in the pathogenesis of seizures in neurocysticercosis, especially in patients with calcified lesions [10].
42. 19 yo woman, ER for seizure at dormitory party on campus. Drinking more water than usual, then silent and staring. Shaking for 1 minute. Unresponsive, Restless and grinds her teeth. 103.3F, pulse 90/min, resp 24/min BP 150/95. Profuse diaphoresis and piloerection. Pupils 5mm bilat. PT 16s, Na 114, Urea nitrogen 40, Creat 2, ALT 90, CK 1200. Intoxication for which substance?
C. Ecstasy
MDMA is a commonly abused drug, particularly among young party-goers at electronic dance music venues, including dance clubs and large music festivals. Typical effects include feelings of euphoria, wakefulness, intimacy, sexual arousal, and disinhibition.
sympathomimetic amphetamine that causes release of endogenous catecholamines.
MDMA differs somewhat from traditional amphetamines in that it is structurally similar to serotonin. This difference likely accounts for an increased release of serotonin and inhibition of serotonin reuptake [4,10,11].
This results in a toxicity profile for MDMA that is different from that of traditional amphetamines. Although typical findings of amphetamine toxicity (hypertension, tachycardia, hyperthermia, CNS stimulation) are often seen in MDMA toxicity, serotonergic toxicity (serotonin syndrome, SIADH) may be seen as well.
MDMA (3,4-methylenedioxymethamphetamine) increases alertness, reduces fatigue, and leads to feelings of increased physical and mental powers, and euphoria. Users
typically begin to experience the desired effects of MDMA approximately one hour following oral administration [10]. Minor adverse reactions, such as agitation, nausea, bruxism (grinding teeth), ataxia, diaphoresis, blurry vision, tachycardia, and
hypertension, can also occur at typical MDMA doses. These effects are usually self-limited and resolve within hours [14]. More serious effects are uncommon and described below.
Vital signs — MDMA can cause hypertension, tachycardia, and hyperthermia.
Cardiovascular stimulation — Life-threatening increases in heart rate and blood pressure may occur. Cardiovascular toxicity can include hypertensive emergencies, myocardial infarction, aortic dissection, and dysrhythmia [15-21]. In addition, catastrophic central neurologic hemorrhage, including intracranial hemorrhage and posterior spinal artery aneurysm, has been reported [22,23].
Hyperthermia and related effects — Hyperthermia may result from drug effects on the central nervous system (CNS), prolonged physical exertion (eg, dancing all night at a
"rave"), and environmental conditions (eg, dancing in a densely populated, hot room).
Both the stimulant effect of amphetamines and serotonin syndrome may contribute to severe hyperthermia in these patients [19,24]. Hyperthermia can lead to disseminated intravascular coagulation and rhabdomyolysis. (See 'Hyperthermia' below.)
Manifestations of hyponatremia — MDMA use can lead to hyponatremia due to a marked increase in fluid intake and in some patients, persistent secretion of antidiuretic hormone that slows the rate of water excretion. The belief among some MDMA users that they can avoid hyperthermia by drinking large amounts of water is the reason for increased fluid intake in many cases. The mechanisms that lead to hyponatremia are described separately. (See "Causes of hyponatremia in adults", section on 'Ecstasy (MDMA) intoxication'.)
Marked and often acute reductions in serum sodium can lead to serious neurologic manifestations including confusion, seizures, cerebral edema, cerebral herniation, and death. The serum sodium in such patients is usually below 120 meq/L (120 mmol/L).
Young women appear to be at increased risk for both symptomatic hyponatremia and residual neurologic injury.
Neurologic — Stimulation of the CNS is common and can manifest as agitation, hyperactivity, anxiety, and even delirium [24]. Seizures and status epilepticus can occur. Psychomotor agitation may be associated with hyperthermia as well as rhabdomyolysis.
Hepatotoxicity — Hepatotoxicity caused by MDMA poisoning is well recognized. Even in the absence of severe hyperthermia or disseminated intravascular coagulation,
hepatitis, centrilobular necrosis, and hepatic fibrosis may result from MDMA abuse [25,26]. Clinical findings are similar to other forms of toxin-induced hepatic injury and may include jaundice, abdominal pain, and vomiting. Elevations of bilirubin, aspartate transaminase (AST), and alanine transaminase (ALT) may be present.
Serotonin syndrome findings — Serotonin syndrome is a potentially life-threatening condition characterized by the triad of autonomic dysfunction, abnormal neuromuscular activity, and altered mental status. MDMA use can cause serotonin syndrome,
presumably via stimulation of massive serotonin release. Individuals who use MDMA in
combination with selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), or other drugs that increase 5-HT1A receptor activity (such as meperidine, tryptophan, or lithium) are at greater risk of developing serotonin syndrome [27-30].
43. 37 yo man, Er with 10-day hx increasingly severe headaches. Unremitting pain for 18h.
Pain is severe in pounding. Pulse 70/min, resp 16/min, BP 142/90. Mild swelling, dusky reddish-purple skin color with venous distention over head and neck. Papilledema. No neurological local findings. Most likely cause of intracranial HTN?