Extrapyramidal symptoms & nms

1. 1
Extrapyramidal Symptoms
Extrapyramidal symptoms (EPS), also known as extrapyramidal side effects (EPSE), are drug-induced
movement disorders that include acute and tardive symptoms.
Causes
Extrapyramidal symptoms are most commonly caused by typical antipsychotic drugs that antagonize
dopamine D2 receptors. The most common typical antipsychotics associated with EPS are haloperidol and
fluphenazine.
Other anti-dopaminergic drugs, like the antiemetic metoclopramide, can also result in extrapyramidal side
effects. Short and long-term use of antidepressants such as selective serotonin reuptake inhibitors (SSRI),
serotonin-norepinephrine reuptake inhibitors (SNRI), and norepinephrine-dopamine reuptake inhibitors (NDRI)
have also resulted in EPS. Specifically, duloxetine, sertraline, escitalopram, fluoxetine, and bupropion have been
linked to the induction of EPS. Other causes of extrapyramidal symptoms can include brain damage and
meningitis.
Clinical features
 Acute dystonic reactions: muscular spasms of neck, jaw, back, extremities, eyes, throat, and tongue;
highest risk in young men
 Akathisia: A feeling of internal motor restlessness that can present as tension, nervousness, or anxiety
 Pseudoparkinsonism: drug-induced parkinsonism (rigidity, bradykinesia (slowness of movement), tremor,
masked facies (medical), shuffling gait, stooped posture, sialorrhoea, and seborrhoea; greater risk in the
elderly).
 Tardive dyskinesia: involuntary muscle movements in the lower face and distal extremities; this can be a
chronic condition associated with long-term use of antipsychotics.
Treatment
Anticholinergic drugs are used to control neuroleptic-induced EPS, although akathisia may require beta
blockers or even benzodiazepines. If the EPS are induced by an antipsychotic, EPS may be reduced by dose
titration or by switching to an atypical antipsychotic, such as aripiprazole, ziprasidone, quetiapine, olanzapine,
risperidone, or clozapine.
Commonly used medications for EPS are anticholinergic agents such as benztropine (Cogentin),
diphenhydramine (Benadryl), and trihexyphenidyl (Artane). Another common course of treatment includes
dopamine agonist agents such as pramipexole. These medications reverse the symptoms of extrapyramidal side
effects caused by antipsychotics or other drugs that either directly or indirectly inhibit dopaminergic
neurotransmission.
Neuroleptic malignant syndrome
Definition
NMS is an idiosyncratic, life-threatening complication of treatment with antipsychotic drugs that is
characterized by fever, severe muscle rigidity, and autonomic and mental status changes
 life-threatening neurological disorder .
 mortality rate is 10-20%
Occurrence
 On Neuroleptics
 On withdrawal of neuroleptics or dopaminergic agonists
 adverse reaction to neuroleptic or antipsychotic drugs.

2. 2
 haloperidol or chlorpromazine have the greatest risk.
Clinical features
Classical tetrad of clinical features
1. Fever >38 C (100.4 F)
2. Muscle rigidity
3. Altered mental status - Drowsiness, agitation, confusion, delirium, coma
4. Autonomic instability - Fluctuations in BP, tachypnoea, tachycardia, sialorrhoea, diaphoresis, flushing,
skin pallor, incontinence
In addition,
 Extrapyramidal motor signs – Tremour, chorea, akinesia, dystonic movements.
 Other symptoms – Dysphagia, dyspnoea, abnoramal reflexes, mutism, seizures.
Development and course
 Heterogeneous in onset, presentation, progression and outcome.
 Onset – from hours to days.
o 16% : within 24hrs.
o 66% : within 1 week.
o Virtually all cases : within 30 days.
 Alteration in mental status and other neurological signs typically precede systemic signs. (>80%)
 Self-limited in most cases.
 Mean recovery time : 7-10 days.
o 63% : within 1 week.
o Nearly all : within 30 days.
 Mortality results from :
o respiratory failure
o cardiovascular collapse
o myoglobinuric renal failure
o arrhythmias
Risk factors
 Age, sex, time of year – not correlated with the risk.
 Not specific to any neuropsychiatric diagnosis.
 Catatonia – risk of progressing to NMS with antipsychotics.
 Agitation
 Dehydration
 Restraint
Complications
potential complications of neuroleptic malignant syndrome includes the following:
 Renal failure
 Cardiac arrest
 Aspiration
 Respiratory failure
 Seizure
 Pulmonary embolism

3. 3
 Hepatic failure
 Uncontrolled psychoses
Diagnostic Criteria according to DSM 5
 Exposure to Dopamine antagonist or dopamine agonist withdrawal, within past 72 hours
 Hyperthermia ( >100.4 o F on at least two occasions, measured orally)
 Rigidity
 Reduced or fluctuating levels of consciousness
 CK elevation (at least 4 times upper limit of normal)
 Sympathetic nervous system lability- defined as any two of the following
o a. Blood Pressure elevation (systolic or diastolic >= 25 % above baseline)
o b. Blood pressure fluctuation (>=20 mm Hg diastolic change or >=25 mm Hg systolic change
within 24 hours)
o c. Diaphoresis
o d. Urinary incontinence
 Hyper metabolism, defined as heart rate increase (>= 25% above baseline) and respiratory rate increase
(>= 50 % above baseline)
Differential diagnosis
 Infectious - Meningitis or encephalitis
 Psychiatric or neurological - catatonia , Agitated delirium , extrapyramidal side effects
 Toxic or pharmacological
 Endocrine -Thyrotoxicosis
 Environmental - Heatstroke
Investigations look like….
 FBC – Leucocytosis (WBC 10000-40000)
 CK – elevated (> 1000 IU/L)
 Urine analysis – myoglobinuria indicate poor prognosis.
 ABG – Metabolic acidosis
 Serum iron – reduced ( ? An acute phase response)
 Serum catecholamine - elevated
 CSF – 95% normal.
 Brain imaging – usually normal.
 EEG – generalized slowing.(metabolic encephalopathy)
Management
Management of Hyperthermia
 Cold sponging, ice packs, ice water enema
 Antipyretics: It may take 2 to 3 days for the temperature to normalize
Management of Hypotension and Dehydration
 I V fluids
 Injection Mephentine 15 mg / Dopamine / Dobutamine / Noradrenaline
Management of Severe Rigidity
 muscle relaxant drugs

4. 4
 levodopa – used to treat Parkinson's disease. It can improve ability to move and can decrease tremor,
stiffness, slowed movement, and unsteadiness.
Management of Myoglobinuria leading to acute renal shutdown
 Vigorous hydration – plenty of IV fluids to flush the kidney
 Isotonic saline boluses of 20 ml / kg should be initially administered with repeat boluses depending on the
hydration status of the patient
 This should be followed by continuous hydration with IV fluids
 Maintain blood pressure to an optimum level
 Achievement of urine output goal of 2-3 ml /kg/hr is recommended
 Follow up with mannitol to induce diuresis supported by administration of IV fluids has been advocated
ECT in NMS
A review found that ECT was consistently effective even after failed pharmacotherapy and that clinical
response often occurred over the course of the first several treatments. Treatment response to ECT was not
predicted by age, sex, psychiatric diagnosis, or any particular features of NMS. A typical ECT regimen for acute
NMS would include six to 10 treatments with bilateral electrode placement.
Antipsychotic use after NMS
 Estimated risk of 30% of developing NMS again with re-introduction of antipsychotics.
 Precautions:
o At least 2 weeks should be allowed from recovery before rechallenge.
o Low potency conventional antipsychotics/ atypical antipsychotics.
o Start with a low dose and titrate gradually.
o Careful monitoring for early signs of NMS.
Chandni Narayan
22.4.2021