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NEUROLEPTIC MALIGNANT
SYNDROME
CONTENTS
 Case Vignette
 Introduction
 Diagnosis
 Pathophysiology
 Risk factors
 Causative drugs
 Laboratory findings
 Differential Diagnosis
 Management
 Prognosis
 Conclusion
Case Vignette
• A 45 year old woman
• History of BPAD and hypertension
• Hospitalized with depressed mood of one month’s duration.
• In prior episodes, she had received antidepressants, lithium
and ECT.
• On admission, she was excited with idiosyncratic behavior
with confused speech and thought.
• Two doses of haloperidol were administered.
• Her excitement subsided.
• She became grandiose, garrulous and paced
continuously.
• Lithium carbonate was prescribed and fluphenazine
hydrochloride (5 mg Q.D.S. daily) was added.
• Within 48 hours, she exhibited bilateral cogwheel
rigidity
• Improved with IM promethazine hydrochloride.
• The next day, she became tremulous, had persistent cogwheel
and her temperature rose to 100 F.
• Contemplating neurotoxicity, both lithium and fluphenazine
were discontinued.
• Her condition worsened and she became mute, tremulous and
rigid and diaphoretic.
• B.P. and heart rate increased, temperature rose to 103.5 F.
• Lungs clear
• Abdomen- soft, non- tender, nil bowel sounds
• No meningism or focal neurological deficit
• Pupils – normal, reactive
• No clonus
• Reflexes normal
• WBC count was 13,500/ cubic mm and CPK was 1486 IU/l.
All other investigations WNL (including CT Brain and EEG).
How will you manage this case?
• Neuroleptic Malignant Syndrome
• Syndrome malin des neuroleptiques
Introduction
• Rare but potentially life-threatening idiosyncratic
reaction
• First description (Delay et al. )- 1960 - Haloperidol
• Incidence – 0.02 to 3 %
• Males > females (3:2)
• Age - < 20 years and > 65 years
• A retrospective study conducted in India showed
an incidence of 0.14%.
• NMS usually occurs after exposure to an neuroleptic
drug.
• On an average, onset is 4-14 days after the start of
therapy
• 90% of cases occur within 10 days.
• NMS can occur years into therapy.
• Once the syndrome starts, it usually evolves over 24-
Diagnostic criteria (DSM 5) (all 3 major or 2 major
and 2 minor)
• Major criteria (all
required)
1. Exposure to dopamine
antagonist or dopamine
agonist withdrawal with
72hours
2. Muscle rigidity
3. Hyperthermia (>100.4
deg. F or > 38 deg. C,
measured orally on at
least two occasions)
• Minor (at least 2 required)
1. Diaphoresis
2. Dysphagia
3. Tremor
4. Incontinence
5. Altered levels of
consciousness
6. Mutism
7. Tachycardia
8. Elevated or labile B.P.
70 %
Altered
consciousness
Autonomic instability
Generalized rigidity
with tremors
Hyperthermia
NMS
 Altered mental state
• Perplexity
• Delirium
• Stupor
• Coma
 Rigidity
• Generalized and extreme
• Lead pipe rigidity
• Superimposed on tremors  cog- wheel
• Generalized tremors
• Dyskinesia, dysarthria and myoclonus
• Catatonic symptoms (mutism, posturing, waxy
flexibility, catalepsy)
 Autonomic instability
• Tachycardia (in 88 percent)
• Labile or high blood pressure (in 61 to 77
percent),
• Tachypnoea (in 73 percent)
• Dysrhythmias
• Incontinence
• Diaphoresis- profuse (“greasy” sweat)
 Hyperthermia
• 100 to 105 degrees F
• May not be evident with second generation
antipsychotics
• May be fluctuating
• “Atypical” NMS:
- DSM 5 criteria not met
- Milder form
- Only hyperthermia and/or rigidity
- Clozapine, Aripiprazole and paliperidone
Pathophysiology
• Secondary to decreased dopamine (DA) activity in
central nervous system (CNS):
• • Blockade of dopamine type 2 receptors (D2
receptors)
• • Decreased availability of DA itself.
• Direct effect on peripheral skeletal muscles may play
an additive role
• Hypothalamic D2 receptor blockade results in an
elevated temperature set point
• Impairment of heat-dissipating mechanisms (eg.
cutaneous vasodilatation, sweating)
• Nigrostriatal blockade results in muscular rigidity.
• Peripherally, antipsychotics lead to increased
calcium release from the sarcoplasmic
reticulum
• Increased contractility, which can contribute
to hyperthermia, rigidity, and muscle cell
breakdown.
• Removing tonic inhibition from the
• Animal model studies- orexin-A (an excitatory
neuropeptide) can cause thermogenesis in a
manner unrelated to muscle activity.
• Orexin-1 receptor plays a role in the effects of
psychotropics on dopamine pathways
• And probably the clinical effects of these
agents (therapeutic and side effects).
Risk factors
• Genetics
• Young Males
• Dehydration/ malnutrition
• Exposure to high ambient temperatures
• Agitation or excitement
• Catatonic features, past or present
• Tardive dyskinesia, akathisia, EPS
Risk factors (contd..)
• Past history of NMS
• Sudden dose escalation of antipsychotics
• High potency antipsychotic or two or more
antipsychotics
• High potency antipsychotic with an
antidepressant or mood stabilizer (lithium)
• IM antipsychotic or depot antipsychotic
• Recent alcohol abuse with liver dysfunction
Risk factors (contd..)
• Alcohol use
• Trauma
• Infections
• Thyrotoxicosis,
• Premenstrual/ Post partum phase
Early signs
• Rapidly developed extra-pyramidal signs of
tremors, rigidity, dyskinesia to low or modest
doses of an antipsychotic
• Mania with fever
• Within 24 hours of initial - Catatonia
antipsychotic administration - Sialorrhoea
- Autonomic
instability
Pharmacological agents
Withdrawal of:
• Levodopa (L-DOPA)
• Tolcapone/entacapone
• Dopamine agonists (e.g.
bromocriptine)
• Amantadine
• Clozapine
Intoxication with:
Introduction of:
• Neuroleptics:
Phenothiazines,
butyrophenones,
thioxanthenes
• “Atypical”
antipsychotics:
clozapine, olanzapine,
risperidone, quetiapine
Abnormal laboratory findings
• Very high CPK
- 1000 – 10000 IU/L
• Low serum iron (11- 32 µmol/L)
- sensitive marker
- 5.17 µmol/L
• High LDH
• Leukocytosis with a left shift (10,000 to
Abnormal laboratory findings
• Proteinuria
• Myoglobinuria
• Thrombocytosis
• Metabolic acidosis
• Liver transaminases
elevated
• Diffuse EEG slowing
• Dyselectrolemia
- Hypocalcaemia,
- Hypomagnesaemia
- Hyperkalemia
- Hyper/ hyponatremia
Differential Diagnosis
• Other neuroleptic induced reactions
- Dystonia
- Akathisia
- Dyskinesias
- Pseudoparkinsonism
• Malignant Catatonia
- prodrome of excitement and agitation with
hyperthermia prior to the onset of rigidity
- episodes of catatonia while a patient is not
• Central nervous system infections
• Status epilepticus
• Stroke
• Brain trauma
• Neoplasms
• Acute intermittent porphyria
• Tetanus
• Thyroid Storm
• Heat stroke
Management
• Mainly supportive!!!
• Prevent complications
• ICU care is quintessential
• Discontinue all antipsychotics
• Assessment of the airway, breathing, and
circulation (ABCs)
• Assess safety and restrain if needed (chemical
preferred)
• Thiamine, dextrose (or rapid glucose
determination), and/or naloxone, in case of
alcohol withdrawal, hypoglycemia, and opioid
overdose
• Take a detailed drug history
Conservative management
• Circulatory and ventilatory support as needed.
• Antipyretics
• Evaporative cooling
• Ice packs (axilla)
• Cooled intravenous (IV) fluids
• Cooling blankets
• Ice water gastric lavage
• Prophylactic intubation for patients with
excessive salivation, swallowing dysfunction,
• If B.P. is significantly elevated
- Nitroprusside (cutaneous vasodilatation)
- Clonidine
• Heparin or low molecular weight heparin for
prevention of deep venous thrombosis
• Consultations – eclectic team approach
- Neurologist
- Nephrologist
- Cardiologist
- Psychiatrist
• Aggressive fluid resuscitation and alkalization
of urine
• Sodium bicarbonate
- prevent acute renal failure and
- enhance excretion of muscle breakdown
products
Pharmacotherapy
• Benzodiazepines
- For mild NMS
- Lorazepam -1 to 2 mg IM or IV every four to
six hours
- Diazepam 5 to 10 mg IV every eight hours.
• Bromocriptine mesylate
- Dopamine agonist
- 2.5 mg orally two or three times a day, increased
by 2.5 mg per 24 hours to a total daily dose of 45
mg.
- Can worsen psychosis and hypotension.
- Precipitate vomiting - should be used carefully in
patients at risk of aspiration.
- Premature discontinuation results in rebound
symptoms
- Safe in pregnancy
• Dantrolene
- Direct acting skeletal muscle relaxant
- 1–2.5 mg/kg body weight administered
initially
- followed by 1 mg/kg every 6 hours if rapid
resolution of the fever and rigidity is observed
- Maximum dose- 10 mg/kg
- Taper or switch to oral dantrolene after the
first few days.
- Oral dantrolene doses - 50 to 200 mg/d
- Continue for 10 days followed by a slow taper
to minimize relapse
- Side effects may include impairment of
respiratory or hepatic function
- Only in cases of NMS with extreme
temperature elevations, rigidity, and true
hypermetabolism
• With depot neuroleptics, treatment should be
continued up to 2–3 weeks beyond clinical
recovery.
• Amantadine
- Dopamine agonist
- Initial dose is 100 mg orally or via gastric tube
- Titrate upward as needed to a maximum dose
of 200 mg every 12 hours
- Caution- worsening of psychosis
- Levodopa, combined with the
dopadecarboxylase inhibitor carbidopa-
• Serial follow-up of CK and myoglobulin levels.
• Do not suddenly withdraw treatment despite
recovery.
• High chances of recurrence
• With depot neuroleptics, treatment should be
continued up to 2–3 weeks beyond clinical
recovery.
• Electro-convulsive therapy (ECT)
- Can help with the alteration of temperature,
level of consciousness, and diaphoresis.
- Effective if symptoms are refractory to
supportive care and pharmacotherapy
- Idiopathic malignant catatonia due to an
underlying psychotic disorder
- persistent residual catatonia and parkinsonism
after resolution of NMS
• Six to 10 treatments with bilateral electrode
placement
- It may also be useful in treating the underlying
psychiatric disease in patients who are unable
to take neuroleptics.
- ECT with anesthesia has generally been safe
- No increased incidence of malignant
hyperthermia from succinylcholine
administration.
• Risks- cardiac arrest, ventricular fibrillation
What will happen if you don’t
intervene?
• Dehydration
• Electrolyte imbalances
• Acute renal failure
associated with
rhabdomyolysis
• Cardiac arrhythmias
including torsade de
pointes and cardiac
arrest
• Myocardial infarction
• Cardiomyopathy
• Respiratory failure from
chest wall rigidity,
aspiration pneumonia,
pulmonary embolism
• Deep vein thrombosis
(DVT)
• Thrombocytopenia
• Disseminated
intravascular
coagulation (DIC)
• Seizures from
Restarting of antipsychotics
• Likelihood of developing NMS again as high as
30%
• reports of previous episodes should be
checked for accuracy
• indications for antipsychotics should be clearly
documented
• alternative medications should be considered
• risk factors should be reduced
• At least 2 weeks should be allowed to elapse
after recovery from NMS before rechallenge.
• 6 weeks for depot injections
• Low doses of low-potency conventional
antipsychotics or atypical antipsychotics
should be titrated gradually after a test dose.
• Patients should be carefully monitored for
early signs of NMS.
• Documented written consent
Prognosis
• Resolve within 2 weeks (reported mean
recovery times are 7–11 days).
• Cases persisting for 6 months with residual
catatonia and motor signs are reported.
• Risk factors for a prolonged course are depot
antipsychotic use and concomitant structural
brain disease.
Prognosis
• Most patients recover without neurologic
sequelae
• Except where there is severe hypoxia or
grossly elevated temperatures for a long
duration.
• Reported mortality rates for NMS are 5–20%.
• Disease severity and the occurrence of
medical complications are the strongest
predictors of mortality.
Conclusion
• Neuroleptic malignant syndrome is rare but
life-threatening medical emergency
• A diagnosis of exclusion
• Following usage of neuroleptics and abrupt
withdrawal of some drugs.
• Tetrad: Altered mental state, Rigidity,
Hyperthermia and Autonomic dysfunction
• Due to blockade of D2 receptors
References
• Eelco FM Wijdicks.
https://www.uptodate.com/contents/neurole
ptic-malignant-syndrome- 2019
• Stanley NC, Cabrina EC. Drug- Induced
Extrapyramidal Syndromes. Psychiatric Clinics
of North America 2016;Vol 3, No 3: 399- 400
• Vivian Ngo, Alfredo G, David L, et al. Emergent
Treatment of Neuroleptic Malignant
Syndrome Induced by Antipsychotic
Monotherapy Using Dantrolene. Clin Pract
References (contd.)
• P. Adnet, P. Lestavel, R. Krivosic‐Horber.
Neuroleptic malignant syndrome. BJA: British
Journal of Anaesthesia, Volume 85, Issue 1, 1
July 2000, Pages 129–135
• Jeffrey RS, Paul EK, Stanley NC. Neuroleptic
Malignant Syndrome. Am J Psychiatry 164:6,
June 2007: 870- 876.
• Brian DB. Neuroleptic Malignant Syndrome: A
Review for Neurohospitalists. 2011 Jan; 1(1):
41–47
Thank You

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NMS.pptx

  • 2. CONTENTS  Case Vignette  Introduction  Diagnosis  Pathophysiology  Risk factors  Causative drugs  Laboratory findings  Differential Diagnosis  Management  Prognosis  Conclusion
  • 3. Case Vignette • A 45 year old woman • History of BPAD and hypertension • Hospitalized with depressed mood of one month’s duration. • In prior episodes, she had received antidepressants, lithium and ECT. • On admission, she was excited with idiosyncratic behavior with confused speech and thought.
  • 4. • Two doses of haloperidol were administered. • Her excitement subsided. • She became grandiose, garrulous and paced continuously. • Lithium carbonate was prescribed and fluphenazine hydrochloride (5 mg Q.D.S. daily) was added. • Within 48 hours, she exhibited bilateral cogwheel rigidity • Improved with IM promethazine hydrochloride.
  • 5. • The next day, she became tremulous, had persistent cogwheel and her temperature rose to 100 F. • Contemplating neurotoxicity, both lithium and fluphenazine were discontinued. • Her condition worsened and she became mute, tremulous and rigid and diaphoretic. • B.P. and heart rate increased, temperature rose to 103.5 F.
  • 6. • Lungs clear • Abdomen- soft, non- tender, nil bowel sounds • No meningism or focal neurological deficit • Pupils – normal, reactive • No clonus • Reflexes normal • WBC count was 13,500/ cubic mm and CPK was 1486 IU/l. All other investigations WNL (including CT Brain and EEG). How will you manage this case?
  • 7. • Neuroleptic Malignant Syndrome • Syndrome malin des neuroleptiques
  • 8. Introduction • Rare but potentially life-threatening idiosyncratic reaction • First description (Delay et al. )- 1960 - Haloperidol • Incidence – 0.02 to 3 % • Males > females (3:2) • Age - < 20 years and > 65 years • A retrospective study conducted in India showed an incidence of 0.14%.
  • 9. • NMS usually occurs after exposure to an neuroleptic drug. • On an average, onset is 4-14 days after the start of therapy • 90% of cases occur within 10 days. • NMS can occur years into therapy. • Once the syndrome starts, it usually evolves over 24-
  • 10. Diagnostic criteria (DSM 5) (all 3 major or 2 major and 2 minor) • Major criteria (all required) 1. Exposure to dopamine antagonist or dopamine agonist withdrawal with 72hours 2. Muscle rigidity 3. Hyperthermia (>100.4 deg. F or > 38 deg. C, measured orally on at least two occasions) • Minor (at least 2 required) 1. Diaphoresis 2. Dysphagia 3. Tremor 4. Incontinence 5. Altered levels of consciousness 6. Mutism 7. Tachycardia 8. Elevated or labile B.P.
  • 11. 70 % Altered consciousness Autonomic instability Generalized rigidity with tremors Hyperthermia NMS
  • 12.  Altered mental state • Perplexity • Delirium • Stupor • Coma
  • 13.  Rigidity • Generalized and extreme • Lead pipe rigidity • Superimposed on tremors  cog- wheel • Generalized tremors • Dyskinesia, dysarthria and myoclonus • Catatonic symptoms (mutism, posturing, waxy flexibility, catalepsy)
  • 14.  Autonomic instability • Tachycardia (in 88 percent) • Labile or high blood pressure (in 61 to 77 percent), • Tachypnoea (in 73 percent) • Dysrhythmias • Incontinence • Diaphoresis- profuse (“greasy” sweat)
  • 15.  Hyperthermia • 100 to 105 degrees F • May not be evident with second generation antipsychotics • May be fluctuating
  • 16.
  • 17. • “Atypical” NMS: - DSM 5 criteria not met - Milder form - Only hyperthermia and/or rigidity - Clozapine, Aripiprazole and paliperidone
  • 18. Pathophysiology • Secondary to decreased dopamine (DA) activity in central nervous system (CNS): • • Blockade of dopamine type 2 receptors (D2 receptors) • • Decreased availability of DA itself. • Direct effect on peripheral skeletal muscles may play an additive role
  • 19.
  • 20. • Hypothalamic D2 receptor blockade results in an elevated temperature set point • Impairment of heat-dissipating mechanisms (eg. cutaneous vasodilatation, sweating) • Nigrostriatal blockade results in muscular rigidity.
  • 21. • Peripherally, antipsychotics lead to increased calcium release from the sarcoplasmic reticulum • Increased contractility, which can contribute to hyperthermia, rigidity, and muscle cell breakdown. • Removing tonic inhibition from the
  • 22. • Animal model studies- orexin-A (an excitatory neuropeptide) can cause thermogenesis in a manner unrelated to muscle activity. • Orexin-1 receptor plays a role in the effects of psychotropics on dopamine pathways • And probably the clinical effects of these agents (therapeutic and side effects).
  • 23. Risk factors • Genetics • Young Males • Dehydration/ malnutrition • Exposure to high ambient temperatures • Agitation or excitement • Catatonic features, past or present • Tardive dyskinesia, akathisia, EPS
  • 24. Risk factors (contd..) • Past history of NMS • Sudden dose escalation of antipsychotics • High potency antipsychotic or two or more antipsychotics • High potency antipsychotic with an antidepressant or mood stabilizer (lithium) • IM antipsychotic or depot antipsychotic • Recent alcohol abuse with liver dysfunction
  • 25. Risk factors (contd..) • Alcohol use • Trauma • Infections • Thyrotoxicosis, • Premenstrual/ Post partum phase
  • 26. Early signs • Rapidly developed extra-pyramidal signs of tremors, rigidity, dyskinesia to low or modest doses of an antipsychotic • Mania with fever • Within 24 hours of initial - Catatonia antipsychotic administration - Sialorrhoea - Autonomic instability
  • 27. Pharmacological agents Withdrawal of: • Levodopa (L-DOPA) • Tolcapone/entacapone • Dopamine agonists (e.g. bromocriptine) • Amantadine • Clozapine Intoxication with: Introduction of: • Neuroleptics: Phenothiazines, butyrophenones, thioxanthenes • “Atypical” antipsychotics: clozapine, olanzapine, risperidone, quetiapine
  • 28.
  • 29. Abnormal laboratory findings • Very high CPK - 1000 – 10000 IU/L • Low serum iron (11- 32 µmol/L) - sensitive marker - 5.17 µmol/L • High LDH • Leukocytosis with a left shift (10,000 to
  • 30. Abnormal laboratory findings • Proteinuria • Myoglobinuria • Thrombocytosis • Metabolic acidosis • Liver transaminases elevated • Diffuse EEG slowing • Dyselectrolemia - Hypocalcaemia, - Hypomagnesaemia - Hyperkalemia - Hyper/ hyponatremia
  • 31.
  • 32. Differential Diagnosis • Other neuroleptic induced reactions - Dystonia - Akathisia - Dyskinesias - Pseudoparkinsonism • Malignant Catatonia - prodrome of excitement and agitation with hyperthermia prior to the onset of rigidity - episodes of catatonia while a patient is not
  • 33. • Central nervous system infections • Status epilepticus • Stroke • Brain trauma • Neoplasms • Acute intermittent porphyria • Tetanus • Thyroid Storm • Heat stroke
  • 34. Management • Mainly supportive!!! • Prevent complications • ICU care is quintessential • Discontinue all antipsychotics
  • 35. • Assessment of the airway, breathing, and circulation (ABCs) • Assess safety and restrain if needed (chemical preferred) • Thiamine, dextrose (or rapid glucose determination), and/or naloxone, in case of alcohol withdrawal, hypoglycemia, and opioid overdose • Take a detailed drug history
  • 37. • Circulatory and ventilatory support as needed. • Antipyretics • Evaporative cooling • Ice packs (axilla) • Cooled intravenous (IV) fluids • Cooling blankets • Ice water gastric lavage • Prophylactic intubation for patients with excessive salivation, swallowing dysfunction,
  • 38. • If B.P. is significantly elevated - Nitroprusside (cutaneous vasodilatation) - Clonidine • Heparin or low molecular weight heparin for prevention of deep venous thrombosis
  • 39. • Consultations – eclectic team approach - Neurologist - Nephrologist - Cardiologist - Psychiatrist
  • 40. • Aggressive fluid resuscitation and alkalization of urine • Sodium bicarbonate - prevent acute renal failure and - enhance excretion of muscle breakdown products
  • 42. • Benzodiazepines - For mild NMS - Lorazepam -1 to 2 mg IM or IV every four to six hours - Diazepam 5 to 10 mg IV every eight hours.
  • 43. • Bromocriptine mesylate - Dopamine agonist - 2.5 mg orally two or three times a day, increased by 2.5 mg per 24 hours to a total daily dose of 45 mg. - Can worsen psychosis and hypotension. - Precipitate vomiting - should be used carefully in patients at risk of aspiration. - Premature discontinuation results in rebound symptoms - Safe in pregnancy
  • 44. • Dantrolene - Direct acting skeletal muscle relaxant - 1–2.5 mg/kg body weight administered initially - followed by 1 mg/kg every 6 hours if rapid resolution of the fever and rigidity is observed - Maximum dose- 10 mg/kg - Taper or switch to oral dantrolene after the first few days. - Oral dantrolene doses - 50 to 200 mg/d
  • 45. - Continue for 10 days followed by a slow taper to minimize relapse - Side effects may include impairment of respiratory or hepatic function - Only in cases of NMS with extreme temperature elevations, rigidity, and true hypermetabolism • With depot neuroleptics, treatment should be continued up to 2–3 weeks beyond clinical recovery.
  • 46. • Amantadine - Dopamine agonist - Initial dose is 100 mg orally or via gastric tube - Titrate upward as needed to a maximum dose of 200 mg every 12 hours - Caution- worsening of psychosis - Levodopa, combined with the dopadecarboxylase inhibitor carbidopa-
  • 47. • Serial follow-up of CK and myoglobulin levels. • Do not suddenly withdraw treatment despite recovery. • High chances of recurrence • With depot neuroleptics, treatment should be continued up to 2–3 weeks beyond clinical recovery.
  • 48. • Electro-convulsive therapy (ECT) - Can help with the alteration of temperature, level of consciousness, and diaphoresis. - Effective if symptoms are refractory to supportive care and pharmacotherapy - Idiopathic malignant catatonia due to an underlying psychotic disorder - persistent residual catatonia and parkinsonism after resolution of NMS • Six to 10 treatments with bilateral electrode placement
  • 49. - It may also be useful in treating the underlying psychiatric disease in patients who are unable to take neuroleptics. - ECT with anesthesia has generally been safe - No increased incidence of malignant hyperthermia from succinylcholine administration. • Risks- cardiac arrest, ventricular fibrillation
  • 50. What will happen if you don’t intervene? • Dehydration • Electrolyte imbalances • Acute renal failure associated with rhabdomyolysis • Cardiac arrhythmias including torsade de pointes and cardiac arrest • Myocardial infarction • Cardiomyopathy • Respiratory failure from chest wall rigidity, aspiration pneumonia, pulmonary embolism • Deep vein thrombosis (DVT) • Thrombocytopenia • Disseminated intravascular coagulation (DIC) • Seizures from
  • 51. Restarting of antipsychotics • Likelihood of developing NMS again as high as 30% • reports of previous episodes should be checked for accuracy • indications for antipsychotics should be clearly documented • alternative medications should be considered • risk factors should be reduced
  • 52. • At least 2 weeks should be allowed to elapse after recovery from NMS before rechallenge. • 6 weeks for depot injections • Low doses of low-potency conventional antipsychotics or atypical antipsychotics should be titrated gradually after a test dose. • Patients should be carefully monitored for early signs of NMS. • Documented written consent
  • 53. Prognosis • Resolve within 2 weeks (reported mean recovery times are 7–11 days). • Cases persisting for 6 months with residual catatonia and motor signs are reported. • Risk factors for a prolonged course are depot antipsychotic use and concomitant structural brain disease.
  • 54. Prognosis • Most patients recover without neurologic sequelae • Except where there is severe hypoxia or grossly elevated temperatures for a long duration. • Reported mortality rates for NMS are 5–20%. • Disease severity and the occurrence of medical complications are the strongest predictors of mortality.
  • 55. Conclusion • Neuroleptic malignant syndrome is rare but life-threatening medical emergency • A diagnosis of exclusion • Following usage of neuroleptics and abrupt withdrawal of some drugs. • Tetrad: Altered mental state, Rigidity, Hyperthermia and Autonomic dysfunction • Due to blockade of D2 receptors
  • 56. References • Eelco FM Wijdicks. https://www.uptodate.com/contents/neurole ptic-malignant-syndrome- 2019 • Stanley NC, Cabrina EC. Drug- Induced Extrapyramidal Syndromes. Psychiatric Clinics of North America 2016;Vol 3, No 3: 399- 400 • Vivian Ngo, Alfredo G, David L, et al. Emergent Treatment of Neuroleptic Malignant Syndrome Induced by Antipsychotic Monotherapy Using Dantrolene. Clin Pract
  • 57. References (contd.) • P. Adnet, P. Lestavel, R. Krivosic‐Horber. Neuroleptic malignant syndrome. BJA: British Journal of Anaesthesia, Volume 85, Issue 1, 1 July 2000, Pages 129–135 • Jeffrey RS, Paul EK, Stanley NC. Neuroleptic Malignant Syndrome. Am J Psychiatry 164:6, June 2007: 870- 876. • Brian DB. Neuroleptic Malignant Syndrome: A Review for Neurohospitalists. 2011 Jan; 1(1): 41–47

Editor's Notes

  1. Lead-pipe- stable resistance through all ranges of movement Chorea, dystonia Clozapine- rigidity is seldom seen. Rather DIAPHORESIS!!
  2. Neuroleptic malignant syndrome can occur as a result of changes in pre- or postsynaptic DA signaling. There are two mechanisms: 1. Reduced DA signaling resulting from sudden withdrawal of dopaminergic agents 2. Introduction of agents that block DA signaling
  3. Serotonin syndrome- Hunter’s criteria and Sternbach’s criteria