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Clinical conundrum of Neuroleptic malignant syndrome
Clinical conundrum of Neuroleptic malignant syndrome
Dr. A.V. SRINIVASANDr. A.V. SRINIVASAN
9/9/03Madras Medical College
9/9/03Madras Medical College
INTRODUCTIONINTRODUCTION
IN ANY FIELD,
FIND THE STRANGEST THING
AND EXPLORE IT
John Archibald Wheeler
IN ANY FIELD,
FIND THE STRANGEST THING
AND EXPLORE IT
John Archibald Wheeler
Clinical Knowledge – Trinity principles
Clinical Knowledge – Trinity principles
Observation
Recording
Thinking
Observation
Recording
Thinking
ThinkingThinking
Thinking requires a process of consideration,
rumination and deliberation, which constitutes clinical
thought.
The whole art of medicine depends on the stimuli that
enter the mind of the physician, the processes that go
on in the mind, and the material produced by that mind
as a result.
Sustain - clinical neurology
Thinking requires a process of consideration,
rumination and deliberation, which constitutes clinical
thought.
The whole art of medicine depends on the stimuli that
enter the mind of the physician, the processes that go
on in the mind, and the material produced by that mind
as a result.
Sustain - clinical neurology
REVIEW OF LITERATUREREVIEW OF LITERATURE
“THE WORLD IS NOT ONLY QUEERER THAN
WE IMAGINE; IT IS QUEERER THAN WE CAN
IMAGINE”
- J B S Haldane
“THE WORLD IS NOT ONLY QUEERER THAN
WE IMAGINE; IT IS QUEERER THAN WE CAN
IMAGINE”
- J B S Haldane
CLINICAL FEATURESCLINICAL FEATURES1968 - Delay – NMS was described with
Fever, Pallor, Movement Disorder & Signs in the Lungs
1985 - LEVENSON CRITERIA
MAJOR MINOR
FEVER TACHYCARDIA
RIGIDITY ABNORMAL BLOOD PRESSURE
ELEVATED CK TACHYPNOEA
ALT. LEVEL OF CONSCIOUSNESS
PROFUSE SWEATING
LEUKOCYTOSIS
3 MAJOR
2 MAJOR AND 4 MINOR
1968 - Delay – NMS was described with
Fever, Pallor, Movement Disorder & Signs in the Lungs
1985 - LEVENSON CRITERIA
MAJOR MINOR
FEVER TACHYCARDIA
RIGIDITY ABNORMAL BLOOD PRESSURE
ELEVATED CK TACHYPNOEA
ALT. LEVEL OF CONSCIOUSNESS
PROFUSE SWEATING
LEUKOCYTOSIS
3 MAJOR
2 MAJOR AND 4 MINOR
POPE et al (1986) modified by KECK 1989POPE et al (1986) modified by KECK 1989
1. Hyperthermia : > 380 C in absence of other Etiologies
2. At least two of the Extra Pyramidal signs
3. At least two of the Autonomic Dysfunction
4. Retrospective Diagnosis
If documentation of one of the above criteria is inadequate,
diagnosis of possible NMS is permissible if the remaining two are
met - plus one of the following:
a) Clouded consciousness; delirium, mutism, stupor or coma
b) Leukocytosis (WCC > 15 x 109/1)
c) Serum CK > 1000 U/1
1. Hyperthermia : > 380 C in absence of other Etiologies
2. At least two of the Extra Pyramidal signs
3. At least two of the Autonomic Dysfunction
4. Retrospective Diagnosis
If documentation of one of the above criteria is inadequate,
diagnosis of possible NMS is permissible if the remaining two are
met - plus one of the following:
a) Clouded consciousness; delirium, mutism, stupor or coma
b) Leukocytosis (WCC > 15 x 109/1)
c) Serum CK > 1000 U/1
INCIDENCEINCIDENCE POPE 1.4% (12 MONTHS)
(1986)
SHALIV 0.4% (13 YRS)
(1986)
KECK 0.9% (12 YRS
(1989)
PROSPECTIVE STUDY
0.2%; 0.7%; 0.9%
(6M) (12M) (18M)
POPE 1.4% (12 MONTHS)
(1986)
SHALIV 0.4% (13 YRS)
(1986)
KECK 0.9% (12 YRS
(1989)
PROSPECTIVE STUDY
0.2%; 0.7%; 0.9%
(6M) (12M) (18M)
G-ADDONIZO et al 1987G-ADDONIZO et al 1987
AGE 12-79 Yrs Mean 40 yrs
10-19 11
20-29 21
30-39 27
40-49 20
50-59 18
60-69 15
70-79 3
SEX 63% MEN 37% WOMEN
AGE 12-79 Yrs Mean 40 yrs
10-19 11
20-29 21
30-39 27
40-49 20
50-59 18
60-69 15
70-79 3
SEX 63% MEN 37% WOMEN
PRIMARY PSYCHIATRIC DISORDERPRIMARY PSYCHIATRIC DISORDER SCHIZOPHRENIA 38 44% BIPOLAR (MANIA) 22 26%
MAJOR DEPRESSION 9 10%
Other Include: Schizo Affective
Atypical Psychosis
Alcohol Abuse 20%
Bipolar Depression
Mental Retardation
Organic Mental Syndrome
Dementia
SCHIZOPHRENIA 38 44% BIPOLAR (MANIA) 22 26%
MAJOR DEPRESSION 9 10%
Other Include: Schizo Affective
Atypical Psychosis
Alcohol Abuse 20%
Bipolar Depression
Mental Retardation
Organic Mental Syndrome
Dementia
PATIENTS AT RISK OF NMSPATIENTS AT RISK OF NMS 2 : 1
Occasionally in Children
Agitated Patients in ICU; Aids, Multiple Injuries, Infection
Physical Exhaustion & Dehydration
Preceding Psychomotor Agitation
Organic Brain Syndrome / MR
PD ; Hyponatremia
2 : 1
Occasionally in Children
Agitated Patients in ICU; Aids, Multiple Injuries, Infection
Physical Exhaustion & Dehydration
Preceding Psychomotor Agitation
Organic Brain Syndrome / MR
PD ; Hyponatremia
DRUGSDRUGS HALOPERIDOL 61 57%
CHLORPROMAZINE 28 24%
FLUPHENAZINE DECONATE 17 10%
LEVOPROMETHAZINE 10 9%
• > 1 NEUROLEPTIC 31 29%
DEPOT NEUROLEPTIC 18 17%
• IM NEUROLEPTIC 28 26%
• IV NEUROLEPTIC 3 3%
HALOPERIDOL 61 57%
CHLORPROMAZINE 28 24%
FLUPHENAZINE DECONATE 17 10%
LEVOPROMETHAZINE 10 9%
• > 1 NEUROLEPTIC 31 29%
DEPOT NEUROLEPTIC 18 17%
• IM NEUROLEPTIC 28 26%
• IV NEUROLEPTIC 3 3%
PRESENTATIONSPRESENTATIONS
COMPLETE PICTURE - 72 hrs
LOW GRADE PYREXIA - May precede NMS
MILD INCREASE OF DIASTOLIC BP
45 minutes - 65 days (5 days)
10 days - 89% cases
14 months - chlorpromazine fixed dose
COMPLETE PICTURE - 72 hrs
LOW GRADE PYREXIA - May precede NMS
MILD INCREASE OF DIASTOLIC BP
45 minutes - 65 days (5 days)
10 days - 89% cases
14 months - chlorpromazine fixed dose
COMPLICATIONS AND CAUSE OF DEATHCOMPLICATIONS AND CAUSE OF DEATH
• PNEUMONIA - 15
• RENAL FAILURE - 9
• CARDIAC ARREST - 7
• SEIZURES - 4
• SEPSIS - 3
• PULMONARY EMBOLISM - 3
CAUSES OF DEATH• CARDIO PULMONARY ARREST - 7
• PNEUMONIA - 5
• PULMONARY EMBOLISM - 3
• SEPSIS - 2
• HEPATO RENAL FAILURE - 2
• PNEUMONIA - 15
• RENAL FAILURE - 9
• CARDIAC ARREST - 7
• SEIZURES - 4
• SEPSIS - 3
• PULMONARY EMBOLISM - 3
CAUSES OF DEATH• CARDIO PULMONARY ARREST - 7
• PNEUMONIA - 5
• PULMONARY EMBOLISM - 3
• SEPSIS - 2
• HEPATO RENAL FAILURE - 2
DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS
Malignant Hyperthermia
Lethal Catatonia
Neuroleptic Induced Catatonia
Neuroleptic Induced Anti-Cholinergic Syndrome
Neuroleptic Induced Heat Stroke
The Serotonin Syndrome
Malignant Hyperthermia
Lethal Catatonia
Neuroleptic Induced Catatonia
Neuroleptic Induced Anti-Cholinergic Syndrome
Neuroleptic Induced Heat Stroke
The Serotonin Syndrome
TREATMENTTREATMENT
SUPPORTIVE MEASURES
• Dantrolene and Dopamine Agonists
• Other Drugs Therapy
• ECT
RE-USE OF NEUROLEPTICS
• Early Challenge
• Long Term Challenge
SUPPORTIVE MEASURES
• Dantrolene and Dopamine Agonists
• Other Drugs Therapy
• ECT
RE-USE OF NEUROLEPTICS
• Early Challenge
• Long Term Challenge
PATHOGENESISPATHOGENESIS
Abnormality of skeletal muscle
Abnormality of dopamine within the CNS
Autopsy findings
Abnormality of skeletal muscle
Abnormality of dopamine within the CNS
Autopsy findings
NMS Develops Earlier and Takes Longer
Time to Resolve in Schizophrenic Patients
Compared to Affective disorders
Mortality is Higher in Schizophrenics
NMS Develops Earlier and Takes Longer
Time to Resolve in Schizophrenic Patients
Compared to Affective disorders
Mortality is Higher in Schizophrenics
SRINIVASAN et al (1990)SRINIVASAN et al (1990)
Clinical Knowledge
Observations – First Trinity Principle
Clinical Knowledge
Observations – First Trinity Principle
The understanding of Clinical Conundrum of
Neuroleptic Malignant Syndrome would become
clearer when Schizophrenia and Affective disorders
are studied separately.
The understanding of Clinical Conundrum of
Neuroleptic Malignant Syndrome would become
clearer when Schizophrenia and Affective disorders
are studied separately.
Clinical Knowledge
Second Trinity Principle
Clinical Knowledge
Second Trinity Principle
Aims and ObjectivesAims and Objectives1. To study the clinical conundrum of the following symptoms of the
Neuroleptic Malignant Syndrome in Schizophrenia and Affective
disorder separately
a. Fever b. Altered sensorium
c. Extra pyramidal symptoms
d. Autonomic symptoms
2. To study the evolution of this syndrome in Schizophrenia and
Affective disorder
3. To study the resolution of this syndrome in Schizophrenia and
Affective disorder
1. To study the clinical conundrum of the following symptoms of the
Neuroleptic Malignant Syndrome in Schizophrenia and Affective
disorder separately
a. Fever b. Altered sensorium
c. Extra pyramidal symptoms
d. Autonomic symptoms
2. To study the evolution of this syndrome in Schizophrenia and
Affective disorder
3. To study the resolution of this syndrome in Schizophrenia and
Affective disorder
Aims and ObjectivesAims and Objectives
4. To study the neuroleptic drug and the duration of
Neuroleptic Malignant Syndrome in Schizophrenia
and Affective disorder
5. To study the mode of administration of the drug
and the clinical conundrum in Schizophrenia and
Affective disorder
6. To study the mortality in Schizophrenia and
Affective disorder
4. To study the neuroleptic drug and the duration of
Neuroleptic Malignant Syndrome in Schizophrenia
and Affective disorder
5. To study the mode of administration of the drug
and the clinical conundrum in Schizophrenia and
Affective disorder
6. To study the mortality in Schizophrenia and
Affective disorder
Inclusion criteriaInclusion criteria
1. Only cases with
(a) fever
(b) altered sensorium
(c) extra pyramidal and
(d) autonomic symptoms which formed the
clinical tetrad for diagnosis of NMS are included
2. Progression of symptoms was analysed by the method
used by Velamoor
1. Only cases with
(a) fever
(b) altered sensorium
(c) extra pyramidal and
(d) autonomic symptoms which formed the
clinical tetrad for diagnosis of NMS are included
2. Progression of symptoms was analysed by the method
used by Velamoor
1. Absence of primary psychiatric diagnosis
2. Due to other drug induced, systemic or
neuropsychiatric illness
Exclusion criteriaExclusion criteria
MethodologyMethodology
1. Data Collection
2. Data Presentation
3. Data Analysis
4. Data interpretation
1. Data Collection
2. Data Presentation
3. Data Analysis
4. Data interpretation
Data CollectionData Collection
1. Computer coded case sheet
2. Excel spread sheet
1. Computer coded case sheet
2. Excel spread sheet
Data PresentationData Presentation
Graphs
Dendrograms
Graphs
Dendrograms
Data Analysis Data Analysis
Tabulation
Statistical test of hypothesis
Correlation analysis
Factor Analysis
Cluster Analysis
Discriminant Analysis
Tabulation
Statistical test of hypothesis
Correlation analysis
Factor Analysis
Cluster Analysis
Discriminant Analysis
Summary statistics of Schizophrenia, Affective disorder, and NMS patients
Summary statistics of Schizophrenia, Affective disorder, and NMS patients
Schizophrenia Affective
Disorder
Age 32 43
Duration of illness 5 yrs 3 yrs
Onset 9 hrs 17 hrs
Schizophrenia Affective
Disorder
Age 32 43
Duration of illness 5 yrs 3 yrs
Onset 9 hrs 17 hrs
Important Observations Important Observations
Analysis of Variance indicate :
Schizophrenia and Affective disorder patients
differ significantly.
Analysis of Variance indicate :
Schizophrenia and Affective disorder patients
differ significantly.
Important Observations Important Observations
1. Age
2. Onset
3. Evolution
4. Resolution
5. EPS
6. ANS
7. Fever
8. Altered sensorium
Pre NMS Drug Pre NMS Drug
11 14
36 43
15 16
60 68
77 85
17 15
15 20
Onset (in hrs)
Evolution (in hrs)
Resolution (in days)
Extra PyramidalSymptoms (in hours)
AutonomicSymptoms (in hours)
Fever (in hrs)
Altered Sensorium(in hrs)
C H
Pre-NMS Drug
1. Haloperidol was the commonest drug used in both
Schizophrenia and Affective disorder - Statistically
analysed
2. Other drugs - smaller number of patients - not analysed
3. T-test for equality of Means did not show any evidence
for association between the groups and medication
1. Haloperidol was the commonest drug used in both
Schizophrenia and Affective disorder - Statistically
analysed
2. Other drugs - smaller number of patients - not analysed
3. T-test for equality of Means did not show any evidence
for association between the groups and medication
Important Observations Important Observations
The chi-square statistic indicates the rejection
of the hypothesis that there is uniformity in
giving bromocriptine to both the groups
The chi-square statistic indicates the rejection
of the hypothesis that there is uniformity in
giving bromocriptine to both the groups
Important Observations Important Observations
Factor Analysis of Parameters responsible for NMS Factor Analysis of Parameters responsible for NMS
Component Matrix
.906
.885
.805
.769
Extra PyramidalSymptoms (in hours)
AutonomicSymptoms (in hours)
Altered Sensorium(in hrs)
Fever (in hrs)
1
Component
Factor analysis of parameters for Schizophrenia Factor analysis of parameters for Schizophrenia
Component Matrix
.913
.888
.779
.497
Extra PyramidalSymptoms (in hours)
AutonomicSymptoms (in hours)
Fever (in hrs)
Altered Sensorium(in hrs)
1
Component
Factor Analysis of Parameters of Affective Disorder. Factor Analysis of Parameters of Affective Disorder.
Rotated Component Matrix
.955 .154
.931 .251
.181 .906
.200 .898
AutonomicSymptoms (in hours)
Extra PyramidalSymptoms (in hours)
Altered Sensorium(in hrs)
Fever (in hrs)
1 2
Component
Structure of Parameters – According to their importance
Structure of Parameters – According to their importance
Structure of Parameters - Rankwise
.898
.700
.597
.287
AutonomicSymptoms (in hours)
Extra PyramidalSymptoms (in hours)
Altered Sensorium(in hrs)
Fever (in hrs)
1
Function
Dendrogram showing the relationship between the parameters of NMS
Dendrogram showing the relationship between the parameters of NMS
Rescaled distance cluster combineRescaled distance cluster combine
0 5 10 15 20 25Variable num
Ext. Pyr
Aut. sym
Evolution
Onset
Fever
Alt. sen.
Resolution
Dendrogram showing the relationship between parameters of Schizophrenia patients
Dendrogram showing the relationship between parameters of Schizophrenia patients
Rescaled distance cluster combineRescaled distance cluster combine
0 5 10 15 20 25Variable num
Ext. Pyr
Aut. sym
Fever
Onset
Alt. Sen.
Evolution
Resolution
Dendrogram showing the relationship of parameters affective disorders
Dendrogram showing the relationship of parameters affective disorders
Rescaled distance cluster combineRescaled distance cluster combine
0 5 10 15 20 25Variable num
Onset
Fever
Alt. Sen.
Ext. Pyr.
Aut. Sym.
Evolution
Resolution
The Classification Function coefficients and the Group Centroids
The Classification Function coefficients and the Group Centroids
Classification Function Coefficients
-2.55E-02 -3.48E-02
6.294E-02 .133
.165 7.480E-02
-2.30E-02 6.808E-02
-2.837 -7.686
Extra PyramidalSymptoms (in hours)
AutonomicSymptoms (in hours)
Fever (in hrs)
Altered Sensorium(in hrs)
(Constant)
Schizophrenia
AffectiveDisorder
Type of patients
Fisher's linear discriminant functions
Functions at Group Centroids
-1.296
.864
Type of patientsSchizophrenia
Affective Disorder
1
Function
Classification of Schizophrenia and Affective Disorder Patients
Classification of Schizophrenia and Affective Disorder Patients
Classification Resultsa
17 3 20
2 28 30
85.0 15.0 100.0
6.7 93.3 100.0
Type of patientsSchizophrenia
Affective Disorder
Schizophrenia
Affective Disorder
Count
%
Original
Schizophrenia
AffectiveDisorder
Predicted GroupMembership
Total
90.0% of original grouped cases correctly classified.a.
b. Misclassification rate in the case of schizophrenia as affective disorder is near 15% and affective disorder wrongly classified as Schizophrenia is only around 7 per cent
AVS-CUV CriterionAVS-CUV Criterion
Clinically Definite : Autonomic symptoms and Signs, Extra Pyramidal Symptoms, Altered Sensorium and Fever
Clinically Probable : Autonomic Symptoms and Signs, Extra Pyramidal Symptoms
Clinically Possible : Altered Sensorium with Autonomic Symptoms or Extra Pyramidal
Clinically Definite : Autonomic symptoms and Signs, Extra Pyramidal Symptoms, Altered Sensorium and Fever
Clinically Probable : Autonomic Symptoms and Signs, Extra Pyramidal Symptoms
Clinically Possible : Altered Sensorium with Autonomic Symptoms or Extra Pyramidal
Validation of HypothesisValidation of Hypothesis
NilUnlikely3 patients LikelyMortality
11 days15 days23 days30 daysResolution
52 hours72 hours27 hours24 hoursEvolution
107 hours96 hours50 hours48 hoursAutonomic symptoms
85 hours96 hours40 hours48 hoursExtra pyramidal symptoms
26 hours24 hours10 hours12 hoursAltered sensorium
ValidatedHypothesisValidatedHypothesis
Affective disorderSchizophrenia
DISCUSSION Distribution of cases by Age
DISCUSSION Distribution of cases by Age
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Below 30 11 10 5 10
30-39 21 18 12 24
40-49 27 23 12 24
50-59 20 17 9 18
60-69 18 16 6 12
70-79 15 13 3 6
Over 80 3 2 3 6
Total 115 100 50 10
DISCUSSION (Contd...)
Distribution of cases by diagnosisDISCUSSION (Contd...)
Distribution of cases by diagnosis
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Schizophrenia 38 55 20 40
Affective Disorder 31 45 30 60
Total 69 100 50 100
DISCUSSION (Contd...) Distribution of cases by Age
DISCUSSION (Contd...) Distribution of cases by Age
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Age (Years) G. Addonizio (1987) Srinivasan (2002)
No. of Cases % No. of cases %
Below 40 11 34 5 29
Above 40 21 66 12 71
Total 32 100 17 100
DISCUSSION (Contd...) Mean age of OnsetDISCUSSION (Contd...) Mean age of Onset
Age (Years) G. Addonizio (1987) Srinivasan (2002)Mean age No. of Mean age No. of in Yrs. Cases in Yrs. Cases
Age (Years) G. Addonizio (1987) Srinivasan (2002)Mean age No. of Mean age No. of in Yrs. Cases in Yrs. Cases
All 40 115 39 50
DISCUSSION (Contd...) NMS Evolution daysDISCUSSION (Contd...) NMS Evolution days
Study DaysStudy Days
Srinivasan (2002) 1.7
Shaliv (1986) 4.8
Addonizio (1987) 14.0
Caroff – Wt. Avg. 7.5
DISCUSSION (Contd...) NMS Evolution days by diagnosis
(Srinivasan – 2002)
DISCUSSION (Contd...) NMS Evolution days by diagnosis
(Srinivasan – 2002)
Study DaysStudy Days
Schizophrenia 1.1
Affective Disorder 2.2
All Cases 1.7
DISCUSSION (Contd...) Resolution time - DaysDISCUSSION (Contd...)
Resolution time - Days
Study DaysStudy Days
Srinivasan (2002) 15.9
Shaliv (1986) NA
Addonizio (1987) 13.0
Caroff – Wt. Avg. NA
DISCUSSION (Contd...) NMS Resolution days by diagnosis
(Srinivasan – 2002)
DISCUSSION (Contd...) NMS Resolution days by diagnosis
(Srinivasan – 2002)
Study DaysStudy Days
Schizophrenia 20.3
Affective Disorder 11
All Cases 15.9
DISCUSSION (Contd...)DISCUSSION (Contd...)
Grace : Dopamine Release
Phasic (Behavioural Stimuli)
Tonic (Regulated by Prefrontal
Cortical Afferents)
Grace : Dopamine Release
Phasic (Behavioural Stimuli)
Tonic (Regulated by Prefrontal
Cortical Afferents)
DISCUSSION (Contd...) DOPAMINE - HYPOTHESIS
DISCUSSION (Contd...) DOPAMINE - HYPOTHESIS
Schizophrenia
• Hyper dopaminergic – Positive Symptom
• Hypo dopaminergic – Negative Symptom
Affective Disorder
• Hyper - Mania
• Hypo - Depression
Schizophrenia
• Hyper dopaminergic – Positive Symptom
• Hypo dopaminergic – Negative Symptom
Affective Disorder
• Hyper - Mania
• Hypo - Depression
DISCUSSION (Contd...) PET/ SPECT STUDIES
DISCUSSION (Contd...) PET/ SPECT STUDIES
Chronic Schizophrenia / Major Depression
• Dorso Lateral Pre Frontal Cortex -
Hypometabolism Proven
NMS
• Longer time to Resolve
• Mortality is more
Functional dopamine Level plays a Crucial Role
Chronic Schizophrenia / Major Depression
• Dorso Lateral Pre Frontal Cortex -
Hypometabolism Proven
NMS
• Longer time to Resolve
• Mortality is more
Functional dopamine Level plays a Crucial Role
Answer to clinical Conundrum (Puzzling problem for experts)
of NMS
Answer to clinical Conundrum (Puzzling problem for experts)
of NMSTonic Phasic = Normal
Cortex Basal Ganglia
D1 Receptor D2 Receptor
NEUROLEPTICS BLOCK
NORMAL BLOCKED Duration of NMS IS
Less Resolves Faster
BLOCKEDBLOCKED Duration is Longer
& Mortality is more
Tonic Phasic = Normal
Cortex Basal Ganglia
D1 Receptor D2 Receptor
NEUROLEPTICS BLOCK
NORMAL BLOCKED Duration of NMS IS
Less Resolves Faster
BLOCKEDBLOCKED Duration is Longer
& Mortality is more
ConclusionConclusionSchizophrenia
Average age at Schizophrenia occurs is 32 years; and duration is
nearly five years
Onset occurs at nine hours; evolution is nearly
27 hours; and resolution is 23 days
Altered sensorium is seen at 10 hours and fever comes 12 hours after
a person gets NMS
Extra pyramidal symptoms appears after 40 hours and autonomic
symptoms are seen at 50 hours
Schizophrenia
Average age at Schizophrenia occurs is 32 years; and duration is
nearly five years
Onset occurs at nine hours; evolution is nearly
27 hours; and resolution is 23 days
Altered sensorium is seen at 10 hours and fever comes 12 hours after
a person gets NMS
Extra pyramidal symptoms appears after 40 hours and autonomic
symptoms are seen at 50 hours
Conclusion (Contd…)Conclusion (Contd…)
Altered sensorium heralds the onset of NMS in
Schizophrenia;
Fever, extra pyramidal, autonomic signogether with
altered sensorium form the evolution of the clinical
conundrum of NMS in Schizophrenia
The disappearance of altered sensorium, fever, extra
pyramidal and autonomic signs form the resolution
of the syndrome
Altered sensorium heralds the onset of NMS in
Schizophrenia;
Fever, extra pyramidal, autonomic signogether with
altered sensorium form the evolution of the clinical
conundrum of NMS in Schizophrenia
The disappearance of altered sensorium, fever, extra
pyramidal and autonomic signs form the resolution
of the syndrome
Conclusion (Contd…)Conclusion (Contd…)
Affective Disorder The average age at Affective disorder occurs is 43 years and the average
duration is nearly 3 years
Onset of NMS in Affective disorder occurs at 17 hours; evolution time is
nearly 52 hours; and the resolution occurs after 11 days on the average
Fever occurs first, 17 hours after a person gets affected by NMS in Affective
disorder; Altered sensorium is seen nine hours after the fever; extra
pyramidal symptoms occur nearly three and half days later; and autonomic
symptoms are found four and half days after the syndrome affect the
patients
Affective Disorder The average age at Affective disorder occurs is 43 years and the average
duration is nearly 3 years
Onset of NMS in Affective disorder occurs at 17 hours; evolution time is
nearly 52 hours; and the resolution occurs after 11 days on the average
Fever occurs first, 17 hours after a person gets affected by NMS in Affective
disorder; Altered sensorium is seen nine hours after the fever; extra
pyramidal symptoms occur nearly three and half days later; and autonomic
symptoms are found four and half days after the syndrome affect the
patients
Conclusion (Contd…)Conclusion (Contd…)
Fever heralds the onset and later results in altered sensorium;
Extra pyramidal and autonomic symptoms are responsible for
completion in the clinical conundrum;
All the four, viz., fever, altered syndrome, extra pyramidal, and
autonomic symptoms form the clinical tetrad for diagnosis of
NMS; and
The disappearance of Fever, altered sensorium, extra
pyramidal, and autonomic form the resolution of the syndrome
Fever heralds the onset and later results in altered sensorium;
Extra pyramidal and autonomic symptoms are responsible for
completion in the clinical conundrum;
All the four, viz., fever, altered syndrome, extra pyramidal, and
autonomic symptoms form the clinical tetrad for diagnosis of
NMS; and
The disappearance of Fever, altered sensorium, extra
pyramidal, and autonomic form the resolution of the syndrome
ObservationPractical Neurology
ObservationPractical Neurology
Jose Biller, MD
Professor and Chairman,
Department of Neurology
Indiana University Medical Center, Indianapolis
Recommended Readings
Dr. Srinivasan AV, et al. Neuroleptic malignant syndrome. J
Neurol Neurosurg Psychiat
53:514-516, 1990
Jose Biller, MD
Professor and Chairman,
Department of Neurology
Indiana University Medical Center, Indianapolis
Recommended Readings
Dr. Srinivasan AV, et al. Neuroleptic malignant syndrome. J
Neurol Neurosurg Psychiat
53:514-516, 1990
Prospective study of fifty
patients
Prospective study of fifty
patients
Clinical Knowledge
Recording - Second Trinity Principle
Clinical Knowledge
Recording - Second Trinity Principle
Proposed new dopamine hypothesisProposed new dopamine hypothesis
Tonic Phasic Normal
Cortex Basal GangliaPredominantly Predominantly D2D1 receptor Receptor
Neuroleptics Block
Normal Blocked Duration of NMSis less resolvesfaster
Blocked Blocked Duration is longer &mortality is more
Clinical KnowledgeThinking - Third Trinity Principle
Clinical KnowledgeThinking - Third Trinity Principle
This thesis is dedicated to
the memory of my
Professor C.D. MARSDEN
for his helpful
comments and encouragement
This thesis is dedicated to
the memory of my
Professor C.D. MARSDEN
for his helpful
comments and encouragement
My sincere
Gratitude
and
Thanks
My sincere
Gratitude
and
Thanks
Dedicated to my family for making everything worthwhile
Dedicated to my family for making everything worthwhile