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Malignant Hyperthermia vs. Neuroleptic Malignant Syndrome vs. Serotonin
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Malignant Hyperthermia vs. Neuroleptic Malignant Syndrome vs. Serotonin Haloperidol (Haldol)
Syndrome  
Picmonic
2 mins
Malignant-man and Hiker-thermometer vs. Neuron-leopard Malignant-man vs. Silver-tonic Savage
Picmonic
Cold Agglutinin
Autoimmune
Malignant hyperthermia, neuroleptic malignant syndrome, and serotonin syndrome are all conditions that may present in a similar way. For
Hemolytic Anemia (C-
instance, autonomic instability and muscle rigidity are common in the presentation of these conditions. However similar these conditions AIHA)
may seem, they also have fundamentally di erent causes, clinical features, and approaches to treatment that distinguish them apart from Picmonic
3 mins
each other.  

Wol -Parkinson-
White Syndrome
KEY FACTS  HIDE Picmonic
 3 mins

1 Autonomic Instability
 Succinylcholine
Unstable Atomic-automobile
Picmonic
 2 mins
All three diseases feature autonomic instability, which can include signs like fever, tachycardia, hypertension, and diaphoresis.

Butorphanol


2 Muscle Rigidity Picmonic
 1 min
Muscle-man of Stone

Nonselective Alpha-
All three diseases also present with muscle rigidity, although the extent varies by disease. For example, the rigidity in neuroleptic Blockers
malignant syndrome is often severe and “lead pipe”, while the rigidity in serotonin syndrome is less so. Picmonic
 2 mins

MALIGNANT HYPERTHERMIA Neuroleptic

Malignant Syndrome


3 Ryanodine Receptor 1 Mutation Picmonic
 2 mins
Rihanna Receptor (1) Wand Mutant

Selective Serotonin
Malignant hyperthermia patients have a genetic predisposition due to mutations in skeletal muscle ion channels. Ryanodine receptor Reuptake Inhibitor
1, coded by the RYR1 gene, is a commonly a ected calcium channel that controls calcium release from the sarcoplasmic reticulum. (SSRI) Overview
Mutations in this channel result in excessive calcium accumulation within muscle cells after exposure to anesthetics or succinylcholine. Picmonic
 2 mins

4 Inhaled Anesthetics
 Opioids
Picmonic
A-Nest of Inhaled Anesthesia
 2 mins

A common trigger for malignant hyperthermia is inhaled anesthetics given during surgery, such as halothane and iso urane.
Therefore, suspect malignant hyperthermia if a post-surgical patient develops the acute onset of autonomic symptoms and muscle
rigidity.

5 Succinylcholine

Sucker-in-cola

Succinylcholine is a depolarizing neuromuscular blocking agent often used during procedures to paralyze muscles and facilitate
intubation. In myocytes with mutated calcium channels, however, succinylcholine will trigger excess calcium release and lead to
malignant hyperthermia.

6 Dantrolene

Denture-lion

Dantrolene is the treatment for malignant hyperthermia. It directly inhibits the ryanodine receptor in myocytes, thereby preventing
calcium release from the sarcoplasmic reticulum of muscle cells.

NEUROLEPTIC MALIGNANT SYNDROME

7 Antidopaminergic Medications

Ant-Tie Doberman

Neuroleptic malignant syndrome occurs after prolonged exposure to antidopaminergic medications. This dopamine blockade can lead
to both nervous system and musculoskeletal dysfunction. Antipsychotics like haloperidol, uphenazine, clozapine, and risperidone are
common causes. Antiemetics that are dopamine antagonists can also cause it, like metoclopramide or promethazine.

8 Hypore exia

Hippo-re ex-hammer

Neuroleptic malignant syndrome (NMS) presents with extreme muscle rigidity and hypore exia. The decreased re exes are key in
di erentiating between NMS and serotonin syndrome since serotonin presents with increased re exes. Additionally, the muscle
rigidity in NMS is often extreme and “lead pipe”, whereas rigidity is less severe in serotonin syndrome.

9 Myoglobinuria

Mayo-globe-urinal

Because NMS is associated with such extreme muscle rigidity, muscle breakdown often occurs, releasing creatine kinase and
myoglobin into the bloodstream. Myoglobinuria occurs when the kidneys lter myoglobin into the urine and can lead to acute renal
failure. Labs will show increased creatine kinase.

10 Dantrolene

Denture-lion

Similar to its use in malignant hyperthermia, dantrolene can treat NMS by directly acting on skeletal calcium channels and preventing
release of calcium from the sarcoplasmic reticulum. Bromocriptine, a dopamine agonist, is another medication used to directly
counteract the e ects of antidopaminergics. Lastly, the causative medications should be discontinued.

SEROTONIN SYNDROME

11 Serotonergic Medications

Silver-tonic

Serotonin syndrome is caused by excess serotonin levels from serotonergic medications that increase the levels of the
neurotransmitter. There are many medications that can cause this, and combining them increases the risk. Implicated medications
include psychiatric meds like SSRIs (eg., sertraline, escitalopram), MAOIs (eg., selegiline, phenelzine), SNRIs, or tricyclic antidepressants
(TCAs). Other serotonergic medications include ondansetron, triptans, and linezolid.

Community Resources:
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12 Hyperre exia

Hiker-re ex-hammer

Serotonin syndrome patients will exhibit fast, brisk re exes, termed hyperre exia. This is in contrast to neuroleptic malignant
syndrome, which has hypore exia.

13 Clonus

Clown

Serotonin syndrome is characterized by neuromuscular hyperactivity, which di erentiates it from neuroleptic malignant syndrome
and malignant hyperthermia, which lack these features. Neuromuscular hyperactivity can include clonus (involuntary muscle twitches),
as well as ataxia and tremors.

14 Cyproheptadine

Zippo-head

Cyproheptadine is a direct antiserotonergic agent with antihistamine and anticholinergic properties as well. It will provide antagonism
at serotonin receptors, counteracting the e ects of the serotonergic medications that caused the syndrome.

EDUCATIONAL AUDIO TRANSCRIPT  HIDE

This Picmonic compares the diseases malignant hyperthermia, neuroleptic malignant syndrome and serotonin syndrome using this
kart racing scene between the malignant man with hiker-thermometer, the neuron-leopard malignant-man and the silver-tonic savage.
These conditions all present with autonomic instability, the unstable Atomic-automobile, with signs like fever, tachycardia, and
diaphoresis. They also all cause muscle rigidity, shown by the Muscle-man of Stone, though to varying degrees. The di erences are as
follows. Malignant hyperthermia is caused by a genetic mutation of ryanodine receptor 1, the Rihanna Receptor (1) Wand Mutant. This
codes for a calcium channel in muscle cells which then releases excess calcium after patients are exposed to inhaled anesthetics like
halothane, shown as the A-Nest of Inhaled Anesthesia, or the paralytic succinylcholine, the sucker-in-cola. Suspect this disease when a
patient undergoes a surgery where these drugs are used and then develops autonomic signs and muscle rigidity. Malignant hyperthermia
can be treated with dantrolene, the Denture-lion, which inhibits the ryanodine receptor. In contrast, neuroleptic malignant syndrome
(NMS) is caused by anti-dopaminergic medications, the Ant-Tie Doberman, including antipsychotics like haloperidol and clozapine, as
well as metoclopramide and other anti-emetics. It occurs over weeks, while the other diseases are more acute. The lack of dopamine
inhibits normal muscle movement and results in severe hypore exia, the hippo-re ex-hammer. Muscle rigidity is often more severe than
in other diseases, leading to lead-pipe rigidity and severe muscle breakdown. Myoglobinuria, the mayo-globe-urinal, can be seen. The
treatment for this is dantrolene, the denture-lion, which inhibits the hyperactive muscle cells. Lastly, serotonin syndrome is caused by
serotonergic medication, the Silver-tonic, including many antidepressants like SSRIs, as well as ondansetron, linezolid, and various other
medications. Uniquely, it presents with signs of neuromuscular hyperactivity like hyperre exia, the hiker-re ex-hammer. Clonus, the
clown, is also common, as well as tremor and ataxia. The treatment is cyproheptadine, the Zippo-head, which antagonizes serotonin
receptors. 

So in summary, malignant hyperthermia, neuroleptic malignant syndrome, and serotonin syndrome all present with autonomic instability
and muscle rigidity. Malignant hyperthermia is caused by a mutation of ryanodine receptor 1, resulting in sensitivity to inhaled anesthetics
and succinylcholine, which can be treated with dantrolene. Neuroleptic malignant syndrome is caused by anti-dopaminergic medications
and presents with hypore exia, myoglobinuria, and lead-pipe rigidity. It can be treated with dantrolene. Lastly, serotonin syndrome is
caused by serotonergic medication, presents with hyperre exia and clonus, and is treated with cyproheptadine.

STORY AUDIO TRANSCRIPT  HIDE

Malignant hyperthermia, neuroleptic malignant syndrome and serotonin syndrome are three conditions that often get mixed up.
Although they are very di erent conditions, they all result after taking some kind of treatment and present with similar symptoms. So, it’s
important to know the di erences. To master these conditions, think of them as racers, driving their own vehicles in a Mario Kart-type
race. Because malignant hyperthermia often results after surgery, the malignant-man and his hiker-thermometer are driving an
ambulance; the ames from the thermometer acting as a turbo boost. Neuroleptic malignant syndrome, the neuron-leopard malignant-
man, results as a reaction to antidopaminergic medications or ant-tie Doberman meds as we like to call them. So think of him as driving a
dog catcher truck. The silver-tonic savage, representing serotonin syndrome, drives a clown car as it presents with clonus. 

Why are they racing? Because all of these conditions present with autonomic instability, think of them passing an unstable atomic-
automobile that crashed in the race. It was driven by a muscle-man of stone as these conditions all share that they can cause muscle
rigidity. 

Malignant-man and his hiker thermometer take the lead in the race. He is listening to Rihanna singing on her 1 wand mic in a receptor
mic stand but he should be paying more attention to the road because he has a patient in the back of his ambulance laying in a nest of
inhaled anesthesia. I guess you can say he puts the competition to sleep. He and his surgeon friend toss suckers-in-cola to get the other
racers stuck in their tracks. If the suckers-in-cola don’t do the trick, there is one thing that can stop them and that is the denture-lion, who
uses his big faux teeth to bite the bumper of the ambulance. 

This opens up the track for the neuron-leopard malignant man to take the lead! This big kitty hates dogs! Dobermans in particular. That’s
why they drive an ant-tie Doberman dog catching truck. On the back, they have a hippo who barely reacts but musters the strength to
use his re ex hammer to hit the mayo-globe-urinal which is their weapon against the competition. Fellow racers slip and slide out of
control in the mayo and pee. However, the leopard is no match for the denture-lion either. Their race ends as the two big cats faceo and
the lion wins. 

This leaves the silver-tonic savage and he thinks he gots this race in the bag. So much so, he is already celebrating by drinking a whole
bottle of silver-tonic. His re ex hammer-wielding hiker buddy has heightened re exes which he used to knock out the competition.
The savage borrowed this car from a real clown, who takes out other racers by spewing silver-tonic from his comical ower lapel. But
even the silver-tonic savage meets his fate at the end of the road when he is met with the zippo-head who burns out any chances of
winning this race. 

I guess you can say when it comes to this race, it doesn’t pay to play dirty.

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