catatonia and neuroleptic malignant syndrome

DR SALMAN KAREEMJUNIOR RESIDENT

DEPARTMENT OF PSYCHIATRY

Catatonia and Neuroleptic Malignant Syndrome

Catatonia is a state of apparent unresponsiveness to external stimuli in a person who is apparently awake, manifested by stupor.

First described by Kahlbaum (1874).

Diagnostic Criteria

The ICD–10 diagnosis of catatonic schizophrenia (category F20.2) requires that the patient prominently exhibits at least one of the following catatonic features, for at least 2 weeks: stupor, excitement, posturing, negativism, rigidity, waxy flexibility and command automatism (automatic obedience).

If a patient with severe depression is in a stupor, a diagnosis of ‘severe depressive episode with psychotic symptoms’ (F32.3) is made, even if there are no delusions or hallucinations.

Similarly, a patient with manic stupor will be diagnosed as having ‘mania with psychotic symptoms’ (F30.2).

Catatonia due to physical causes is diagnosed as ‘organic catatonic disorder.

In DSM–IV a diagnosis of ‘schizophrenia, catatonic type’ (code 295.20) is made if the clinical picture is dominated by at least two of the following: motor immobility, excessive motor activity, extreme negativism, peculiarities of voluntary movements, and echolalia/echopraxia.

If a physical cause is identified the diagnosis is ‘catatonic disorder due to a medical condition’ (code 293.89).

Mechanism of Action

Deficits in fetal cortical developmentDevelopmental disordersDopaminergic blockade - catatonia is caused by a

sudden and massive blockade of dopamine. Antipsychotics may actually precipitate a worsening of the condition.

Glutamatergic dysfunction - hyperactivity of glutamate, the primary excitatory neurotransmitter, has also been suggested as an underlying neurochemical dysfunction.

Clozapine-withdrawal catatonia is postulated to be due to cholinergic and serotonergic rebound hyperactivity.

Psychiatric condition

Acute stress disorder Anorexia nervosa Autistic disorder Brief reactive psychosis with catatonia Conversion disorder Hysteria Major depression, single episode with catatonic features Mood disorders Neuroleptic malignant syndrome Posttraumatic stress disorder Schizophrenia Substance intoxication (3,4-

methylenedioxymethamphetamine [ie, "ecstasy"], alcohol, amphetamine, phencyclidine, substance withdrawal, hypnotic-sedative, lorazepam

Neurologic conditons

Administration of agents that block postsynaptic dopamine receptors

Administration of sibutramine.

Akinetic-rigid syndromeArachnoid cyst in right

parietal regionAstrocytomaAtrophy of left amygdalaAutistic disorderBasilar artery thrombosisBilateral hemorrhagic lesions

of temporal lobes

Cerebellar catalepsyCerebral hemorrhageCerebral infarctCerebrovascular

diseaseCortical venous

thrombosisCentral pontine

myelinolysisCortical basal

ganglionic degeneration

DystoniaEncephalitis

(herpes, Trypanosoma cruzi)

Encephalopathy (Borrelia burgdorferi, human immunodeficiency virus [HIV] infection, Wernicke encephalopathy)

Familial fatal insomnia Fibromuscular dysplasia with

dissection of basilar artery Frontal lobotomy Head injury Huntington disease Hydrocephalus Hypopituitarism secondary to

postpartum hemorrhage Idiopathic recurring stupor

Inherited neurometabolic disorders

Locked-in syndrome Meningitis, tuberculous Meningoencephalitis Multiple sclerosis Neurosyphilis Nonconvulsive status epilepticus Pervasive developmental

disorders Pallidoluysian atrophy Paraneoplastic encephalitis Parkinsonism Postencephalitic parkinsonism

Progressive multifocal leukoencephalopathy

Progressive supranuclear palsy

Schizencephaly Seizures (complex with

partial symptomatology) Stiff-man syndrome Stroke Stupor Subarachnoid hemorrhage Subdural hematoma

Substance intoxication (alcohol, disulfiram, organic fluorides, phencyclidine)

Subthalamic mesencephalic tumor

Surgical removal of cerebellar tumor

Tay-Sachs disease Temporal lobe epilepsy Tuberous sclerosis Tumors Vegetative state Wilson disease 

Clinical presentation

typically episodic, with periods of remissionpresence of a variety of behavioral and

motoric traits – almost 2 dozen. Mutism Negativism Echopraxia Echolalia Waxy flexibility Withdrawal

Excited state –  people with catatonia may injure themselves and

assault others.  autonomic instability manifested by hyperthermia,

tachycardia, and hypertension Exhaustion

Immobile state  Akinesia and stupor   patient may appear unresponsive to external stimuli.  unable to eat  may exhibit catalepsy, the persistent maintenance of

spontaneous or imposed postures.

Posturing The patient is able to maintain the same posture

for long periods. An extreme version of posturing is catalepsy.

Waxy flexibility (cerea flexibilitas) The examiner is able to position the patient in

what would be highly uncomfortable postures, which are maintained for a considerable period of time.

Negativistic Phenomena

Gegenhalten  Rigidity demonstrate increasing resistance to passive

movement of the limbsAutomatic obedience (Mitgehen)

 patient moving in the direction of a slight push from the examiner in spite of the command to remain still

Motor persistence The patient persists with a particular movement

that has lost its initial relevance.withdrawal from all usual activities and refusal to

eat.

Stereotypies - patient repetitively performs apparently meaningless activities. Common motor stereotypes include the following: Nose wrinkling Repetitive movements of the mouth and the jaw Repetitive eye movements Repetitive tapping of the foot, the finger, or the hand Repetitive abdomen patting, shoulder shrugging, or

body rockin

PreservationAmbitendency

The patient alternates between resistance to and cooperation with the examiner’s instructions; for example, when asked to shake hands, the patient repeatedly extends and withdraws the hand.

Echophenomena Echolalia - Echolalia refers to the repetition of the

examiner’s words. Echopraxia - The patient imitates the actions of

the interviewer.

comprehensive physical examinationspecific emphasis on neurological signs, and

a thorough mental state examination, with special emphasis on identifying catatonic signs

history of similar episodes of catatonia is important to elicit. Determine whether the precipitating events of the earlier episode are present in the current episode

 emergency physician must quickly consider the presence of neuroleptic malignant syndrome, encephalitis, nonconvulsive status epilepticus, and acute psychosis.

must identify comorbid disorders, including schizophrenia, mood disorders, psychological stressors, medical conditions.

Catatonia and the related condition, neuroleptic malignant syndrome, may follow the administration of neuroleptic medications

Work up

Complete blood counts (CBC)s, electrolytes, and chemical analyses of blood.

 Fibrin D-dimer greater than 500 ng/mL. serum creatine kinase level and WBC count and

perform liver function tests, to rule out neuroleptic malignant syndrome.

Serum ceruloplasmin. magnetic resonance imaging (MRI) or computed

tomography (CT) scanning is indicated to rule out treatable mass lesion.

EEG is indicated to rule out a seizure disorder.

Further investigations (depending on findings on physical examination)

ElectroencephalographyUrine cultureBlood cultureTest for syphilisTest for HIVHeavy-metal screenAuto-antibody screenLumbar puncture

Differential diagnoses of catatonia

SchizophreniaDepressionManiaOrganic disorders: e.g. infections, epilepsy,

metabolic disordersDrugs: prescribed or recreationalHysteria (psychogenic catatonia)Idiopathic

Treatment and management

Due to risk of serious complications of catatonia, admission to an intensive care unit is the treatment of choice for a patient with catatonia.

Benzodiazepines are the drugs of choice for catatonia.unresponsive or in-sufficiently responsive to

benzodiazepines need electroconvulsive therapy (ECT) - functional psychiatric disorders (including schizophrenia) or organic causes.

Antipsychotics are generally not recommended during a catatonic phase even if there is an underlying psychotic illness such as schizophrenia, as the risk of precipitating neuroleptic malignant syndrome is considerably increased.

carbamazepine is effective in both the acute and maintenance phases of catatonia.

Combination of lithium and an antipsychotic may be an option in treatment-resistant catatonic stupor

NMDA antagonists: amantadine and memantine

Dopamine agonists (e.g. bromocriptine) and skeletal muscle relaxants (e.g. dantrolene), especially if neuroleptic malignant syndrome is suspected

other treatment

refusal to eat requires parenteral nutrition.Vitamin K deficiency must be identified and

treated in people with catatonia.Autonomic instability requires intravenous

fluids and monitoring of vital signs.

Neurolpetic malignant syndrome

life-threatening neurological disorder . mortality rate is 10-20%adverse reaction to neuroleptic or

antipsychotic drugs. haloperidol or chlorpromazine have the

greatest risk.

Clinical presentation

HyperthermiaDiaphoresis , tachycardia , elevated or labile blood

pressureDysphagia , incontinenceTremorChanges in the level of consciousness , ranging

from confusion to comaMutismLeukocytosisLab evidence of muscle injuryLiver enzyme elevation

pathophysiology

Mechanism of actionDopamine receptor blockadeGenetically reduced function of dopamine

receptor D2.

Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in breakdown of muscle, muscle rigidity, and hyperthermia.

 sympatho-adrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) 

treatment options and implications

Aggressive use of supportive measures as well as specific interventions.

 discontinue all antipsychoticsPatients should receive circulatory and

ventilatory support as needed.Cooling blankets and antipyretics can be used

to control temperatureAggressive fluid resuscitation and alkalization

of urine can help prevent acute renal failure and enhance excretion of muscle breakdown products

Lab findings

Increased LDHIncreased CKIncreased ASTIncreased ALTIncreased alkaline

phosphataseHyperuricemiaHyperphosphatemi

aMyoglobinemia

LeukocytosisThrombocytosisProteinuriaDecreased serum

ironIncreased

cerebrospinal fluid (CSF) protein

HypocalcemiaMyoglobinuria

medications

 Dantrolene has been used when needed to reduce muscle rigidity

 dopamine pathway medications such as bromocriptine.

 Benzodiazepines may be used to control agitation.

AmantadineLevodopa/ carbidopaECT.

complications

 potential complications of neuroleptic malignant syndrome includes the following: Rhabdomyolysis Renal failure Cardiac arrest Infection Aspiration Respiratory failure Seizure Pulmonary embolism Hepatic failure Uncontrolled psychoses

Thank you