Diagnosis should be considered if any 2 of the tetrad are present
Mental status changes are typically seen first and are commonly demonstrated by agitated delirium, catatonia, stupor, coma
Rigidity: so called lead-pipe rigidity and cogwheel rigidity, other motor deficits tremor.
Fever: defining symptom Temp of more than 38 are present in 87 percent, with temps of 40 degrees and above seen in 40%
Dysautonomnia variable presentation as it is defined as either excessive sympathetic or parasympathetic activation leading to tachycardia and hypertension or hypotension and orthoastasis even diaphoresis and tachypnea
Typically implicated are the 1st gen agent: haldol, fluphenazine
2nd gen antipsychotics- clozapine, risperidone, olanzapine
Anti-emetics metoclopramide, promethazine
While Symptoms typically develop within 2 weeks of starting the offending agent they may develop as quickly as after 1 dose or after years of being on that medication (such as with our patient)
Diagnosis should be considered if any 2 of the tetrad are present
Mental status changes are typically seen first and are commonly demonstrated by agitated delirium, catatonia, stupor, coma
Rigidity: so called lead-pipe rigidity and cogwheel rigidity, other motor deficits tremor.
Fever: defining symptom Temp of more than 38 are present in 87 percent, with temps of 40 degrees and above seen in 40%
Dysautonomnia variable presentation as it is defined as either excessive sympathetic or parasympathetic activation leading to tachycardia and hypertension or hypotension and orthoastasis even diaphoresis and tachypnea
Typically implicated are the 1st gen agent: haldol, fluphenazine
2nd gen antipsychotics- clozapine, risperidone, olanzapine
Anti-emetics metoclopramide, promethazine
While Symptoms typically develop within 2 weeks of starting the offending agent they may develop as quickly as after 1 dose or after years of being on that medication (such as with our patient)
Diagnosis should be considered if any 2 of the tetrad are present
Mental status changes are typically seen first and are commonly demonstrated by agitated delirium, catatonia, stupor, coma
Rigidity: so called lead-pipe rigidity and cogwheel rigidity, other motor deficits tremor.
Fever: defining symptom Temp of more than 38 are present in 87 percent, with temps of 40 degrees and above seen in 40%
Dysautonomnia variable presentation as it is defined as either excessive sympathetic or parasympathetic activation leading to tachycardia and hypertension or hypotension and orthoastasis even diaphoresis and tachypnea
Typically implicated are the 1st gen agent: haldol, fluphenazine
2nd gen antipsychotics- clozapine, risperidone, olanzapine
Anti-emetics metoclopramide, promethazine
While Symptoms typically develop within 2 weeks of starting the offending agent they may develop as quickly as after 1 dose or after years of being on that medication (such as with our patient)
Diagnosis should be considered if any 2 of the tetrad are present
Mental status changes are typically seen first and are commonly demonstrated by agitated delirium, catatonia, stupor, coma
Rigidity: so called lead-pipe rigidity and cogwheel rigidity, other motor deficits tremor.
Fever: defining symptom Temp of more than 38 are present in 87 percent, with temps of 40 degrees and above seen in 40%
Dysautonomnia variable presentation as it is defined as either excessive sympathetic or parasympathetic activation leading to tachycardia and hypertension or hypotension and orthoastasis even diaphoresis and tachypnea
Typically implicated are the 1st gen agent: haldol, fluphenazine
2nd gen antipsychotics- clozapine, risperidone, olanzapine
Anti-emetics metoclopramide, promethazine
While Symptoms typically develop within 2 weeks of starting the offending agent they may develop as quickly as after 1 dose or after years of being on that medication (such as with our patient)
While Symptoms typically develop within 2 weeks of starting the offending agent they may develop as quickly as after 1 dose or after years of being on that medication (such as with our patient)
It is thought that D2- receptor blockade at the level of the hypothalamus leads to hyperthermia/hyperpyrexia and autonomic instability
Dopamine blackade at the level of the nigrostriatal pathway which is involved in motor planning leads rigidity, tremor
Additionally it is hypothesized that neuroleptic agents cause a direct release of Ca from the sarcoplasmic reticulum leading to rigidity
It is thought that D2- receptor blockade at the level of the hypothalamus leads to hyperthermia/hyperpyrexia and autonomic instability
Dopamine blackade at the level of the nigrostriatal pathway which is involved in motor planning leads rigidity, tremor
Additionally it is hypothesized that neuroleptic agents cause a direct release of Ca from the sarcoplasmic reticulum leading to rigidity
It is thought that D2- receptor blockade at the level of the hypothalamus leads to hyperthermia/hyperpyrexia and autonomic instability
Dopamine blackade at the level of the nigrostriatal pathway which is involved in motor planning leads rigidity, tremor
Additionally it is hypothesized that neuroleptic agents cause a direct release of Ca from the sarcoplasmic reticulum leading to rigidity
It is thought that D2- receptor blockade at the level of the hypothalamus leads to hyperthermia/hyperpyrexia and autonomic instability
Dopamine blackade at the level of the nigrostriatal pathway which is involved in motor planning leads rigidity, tremor
Additionally it is hypothesized that neuroleptic agents cause a direct release of Ca from the sarcoplasmic reticulum leading to rigidity
It is thought that D2- receptor blockade at the level of the hypothalamus leads to hyperthermia/hyperpyrexia and autonomic instability
Dopamine blackade at the level of the nigrostriatal pathway which is involved in motor planning leads rigidity, tremor
Additionally it is hypothesized that neuroleptic agents cause a direct release of Ca from the sarcoplasmic reticulum leading to rigidity
NMS should be on the differential for pt with Parkinsons disease presenting with fever/rigidity in the setting of medication changes even from one dopamine agonist to another, holding of meds peri-operatively or even a dose reduction
Dehydration may be a risk factor vs complication
Questionable genetic predisposition in those with variant dopamine receptor allele which has been associated with reduced density of dopamine receptor function and activity-- reduction in the function of the D2 dopamine receptor
Common Lab abnormalities
Elevation of CK correlates with severity of the disease
In addition, it is important to rule-out: heat stroke, Meningitis or encephalitis, Brain abscess, Sepsis, Rabies, Rhabdomyolysis
Thyrotoxicosis, Pheochromocytoma, Drug-inducedMalignant hyperthermia
, toxic encephalopathies, agitated delirium, status epilepticus, and more benign drug-induced extrapyramidal symptoms
Due it it’s rarity, however, systematic clinical trials in NMS are difficult to perform and so no evidence-based treatment approach exists.
Dantrolene MOA directly acts on skeletal muscles, relaxation--inhibiting calcium release from the sarcoplasmic reticulum
Bromocriptine MOA Dopamine-agonist
Amantidine dopaminergic and anticholingergic
Prognosis- most resolve after 2 weeks
Treatment is not based on clinical trials but rather case reports and clinical experience and involves supportive care and medical therapy
Dantrolene MOA directly acts on skeletal muscles, relaxation--inhibiting calcium release from the sarcoplasmic reticulum
Bromocriptine MOA Dopamine-agonist
Amantidine dopaminergic and anticholingergic
Prognosis- most resolve after 2 weeks
Case Report of NMS 2/2 anti-psychotic use. Initial video shows classic cogwheel rigidity and tremor. The second video demonstrates the effects of Dantrolene IV 10 min after it is given
Here at VM we use illness scripts as a model to compare and contrast two similar but distinct disease states
Serotonin-antoginst- Cyprohepatadine
Dopamine- agonist Bromocriptine, Amantidine
Exposure to dopamine antagonist, or dopamine agonist withdrawal, within past 72 hours
Hyperthermia ( >38.0°C x2)
Rigidity
Mental status alteration
Creatine kinase elevation (at least 4 times the upper limit of normal)
Sympathetic nervous system lability,
Hypermetabolism, defined as heart-rate increase (≥25 percent above baseline) AND respiratory-rate increase (≥50 percent above baseline)
Negative work-up for infectious, toxic, metabolic, or neurologic causes
