SlideShare a Scribd company logo
1 of 71
Download to read offline
Clinical conundrum of neuroleptic malignant syndrome
Clinical conundrum of
Neuroleptic malignant syndrome
        Dr. A.V. SRINIVASAN



                9/9/03
         Madras Medical College
INTRODUCTION

     IN ANY FIELD,
FIND THE STRANGEST THING
     AND EXPLORE IT

            John Archibald Wheeler
Clinical Knowledge –
 Trinity principles
     Observation

     Recording

     Thinking
Thinking
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 LITERATURE
“THE WORLD IS NOT ONLY QUEERER
THAN WE IMAGINE; IT IS QUEERER THAN
         WE CAN IMAGINE”

                      - J B S Haldane
CLINICAL FEATURES
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 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
INCIDENCE
  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 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
PRIMARY 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
PATIENTS 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
DRUGS
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%
PRESENTATIONS
 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 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
DIFFERENTIAL DIAGNOSIS
Malignant Hyperthermia
Lethal Catatonia
Neuroleptic Induced Catatonia
Neuroleptic Induced Anti-Cholinergic Syndrome
Neuroleptic Induced Heat Stroke
The Serotonin Syndrome
TREATMENT
SUPPORTIVE MEASURES
•   Dantrolene and Dopamine Agonists
•   Other Drugs Therapy
•   ECT

RE-USE OF NEUROLEPTICS
•   Early Challenge
•   Long Term Challenge
PATHOGENESIS

Abnormality of skeletal muscle

Abnormality of dopamine within the CNS

Autopsy findings
Clinical Knowledge
    Observations – First Trinity Principle


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)
Clinical Knowledge
            Second Trinity Principle



The   understanding       of   Clinical   Conundrum   of
Neuroleptic Malignant Syndrome would become
clearer when Schizophrenia and Affective disorders
are studied separately.
Aims and Objectives
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 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
Inclusion 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
Exclusion criteria

1. Absence of primary psychiatric diagnosis

2. Due to other drug induced, systemic or
  neuropsychiatric illness
Methodology

1. Data Collection

2. Data Presentation

3. Data Analysis

4. Data interpretation
Data Collection
1. Computer coded case sheet

2. Excel spread sheet
Data Presentation

  Graphs

  Dendrograms
Data Analysis
Tabulation

Statistical test of hypothesis

Correlation analysis

Factor Analysis

Cluster Analysis

Discriminant Analysis
Summary statistics of Schizophrenia,
Affective disorder, and NMS patients
Important Observations

                      Schizophrenia   Affective
                                      Disorder

Age                        32            43

Duration of illness       5 yrs         3 yrs

Onset                     9 hrs        17 hrs
Important Observations
Analysis of Variance indicate :

Schizophrenia and Affective disorder patients
differ significantly.
1. Age                   5. EPS

2. Onset                 6. ANS

3. Evolution             7. Fever

4. Resolution            8. Altered sensorium
Pre NMS Drug

                       Pre-NMS Drug
                       C          H
Onset (in hrs)            11        14
Evolution (in hrs)        36        43
Resolution (in days)      15        16
Extra Pyramidal
                         60         68
Symptoms (in hours)
Autonomic
                         77         85
Symptoms (in hours)
Fever (in hrs)           17         15
Altered Sensorium
                         15         20
(in hrs)
Important Observations

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


The chi-square statistic indicates the

rejection of the hypothesis that there is

uniformity in giving bromocriptine to both

the groups
Factor Analysis of Parameters responsible for NMS

                Component Matrix

                               Component
                                  1
         Extra Pyramidal
                                     .906
         Symptoms (in hours)
         Autonomic
                                     .885
         Symptoms (in hours)
         Altered Sensorium
                                     .805
         (in hrs)
         Fever (in hrs)              .769
Factor analysis of parameters for Schizophrenia

             Component Matrix


                            Component
                               1
      Extra Pyramidal
                                  .913
      Symptoms (in hours)
      Autonomic
                                  .888
      Symptoms (in hours)
      Fever (in hrs)              .779
      Altered Sensorium
                                  .497
      (in hrs)
Factor Analysis of Parameters of Affective Disorder.

             Rotated Component Matrix

                                 Component
                             1               2
      Autonomic
                                 .955            .154
      Symptoms (in hours)
      Extra Pyramidal
                                 .931            .251
      Symptoms (in hours)
      Altered Sensorium
                                 .181            .906
      (in hrs)
      Fever (in hrs)             .200            .898
Structure of Parameters –
According to their importance
  Structure of Parameters - Rankwise

                        Function
                           1
  Autonomic
                             .898
  Symptoms (in hours)
  Extra Pyramidal
                             .700
  Symptoms (in hours)
  Altered Sensorium
                             .597
  (in hrs)
  Fever (in hrs)             .287
Dendrogram showing the relationship between
          the parameters of NMS
               Rescaled distance cluster combine
               0       5       10       15         20   25
Variable num


Ext. Pyr
Aut. sym
Evolution
Onset
Fever
Alt. sen.
Resolution
Dendrogram showing the relationship between
    parameters of Schizophrenia patients
               Rescaled distance cluster combine
               0       5       10       15         20   25
Variable num


Ext. Pyr
Aut. sym
Fever
Onset
Alt. Sen.
Evolution
Resolution
Dendrogram showing the relationship of
        parameters affective disorders
               Rescaled distance cluster combine
               0       5       10       15         20   25
Variable num


Onset
Fever
Alt. Sen.
Ext. Pyr.
Aut. Sym.
Evolution
Resolution
The Classification Function coefficients and
             the Group Centroids

     Classification Function Coefficients

                            Type of patients
                         Schizophr    Affective
                                                     Functions at Group Centroids
                           enia       Disorder
Extra Pyramidal
                          -2.55E-02      -3.48E-02                        Function
Symptoms (in hours)
Autonomic                                            Type of patients        1
                         6.294E-02            .133
Symptoms (in hours)                                  Schizophrenia          -1.296
Fever (in hrs)                 .165      7.480E-02   Affective Disorder        .864
Altered Sensorium
                          -2.30E-02      6.808E-02
(in hrs)
(Constant)                   -2.837         -7.686
Fisher's linear discriminant functions
Classification of Schizophrenia and
          Affective Disorder Patients

                          Classification Resultsa


                                           Predicted Group
                                             Membership
                                        Schizophr    Affective
                   Type of patients       enia       Disorder     Total
Original   Count   Schizophrenia               17             3       20
                   Affective Disorder           2            28       30
           %       Schizophrenia             85.0         15.0     100.0
                   Affective Disorder         6.7         93.3     100.0
  a. 90.0% of original grouped cases correctly classified.
   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 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
Validation of Hypothesis
                  Schizophrenia           Affective disorder
              Hypothesis   Validated    Hypothesis   Validated

Altered       12 hours     10 hours     24 hours     26 hours
sensorium

Extra         48 hours     40 hours     96 hours     85 hours
pyramidal
symptoms

Autonomic     48 hours     50 hours     96 hours     107 hours
symptoms

Evolution     24 hours     27 hours     72 hours     52 hours
Resolution    30 days      23 days      15 days      11 days
Mortality     Likely       3 patients   Unlikely     Nil
DISCUSSION
              Distribution of cases by Age
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 diagnosis


 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

 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 Onset

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 days

Study                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)
   Study                Days


   Schizophrenia        1.1

   Affective Disorder   2.2

   All Cases            1.7
DISCUSSION (Contd...)
   Resolution time - Days

  Study             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)

   Study               Days

 Schizophrenia        20.3

 Affective Disorder   11

 All Cases            15.9
DISCUSSION     (Contd...)




Grace   :    Dopamine Release

             Phasic (Behavioural Stimuli)
             Tonic    (Regulated by Prefrontal

                       Cortical Afferents)
DISCUSSION       (Contd...)

      DOPAMINE - HYPOTHESIS

Schizophrenia
  •   Hyper dopaminergic – Positive Symptom
  •   Hypo dopaminergic – Negative Symptom

Affective Disorder
  •   Hyper     -    Mania
  •   Hypo      -    Depression
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
Answer to clinical
Conundrum (Puzzling problem for experts)
               of NMS
  Tonic         Phasic          = Normal
  Cortex        Basal Ganglia
  D1 Receptor   D2 Receptor


                NEUROLEPTICS BLOCK
  NORMAL        BLOCKED               Duration of NMS IS
                                      Less Resolves Faster


  BLOCKED       BLOCKED               Duration is Longer
                                      & Mortality is more
Conclusion
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…)
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…)
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…)
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
Observation
            Practical 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
Clinical Knowledge
Recording - Second Trinity Principle



Prospective study of fifty
           patients
Clinical Knowledge
          Thinking - Third Trinity Principle
Tonic           Phasic             Normal

Cortex          Basal Ganglia
Predominantly   Predominantly D2
D1 receptor     Receptor
                   Neuroleptics Block
Normal          Blocked                 Duration of NMS
                is less resolves
                faster
Blocked         Blocked                 Duration is
                longer &
                mortality is more

            Proposed new dopamine hypothesis
This thesis is dedicated to
the memory of my

Professor C.D. MARSDEN

for his helpful
comments and
encouragement
My sincere
Gratitude
   and
 Thanks
Clinical conundrum of neuroleptic malignant syndrome
Clinical conundrum of neuroleptic malignant syndrome
Clinical conundrum of neuroleptic malignant syndrome
Dedicated to my family for
making everything worthwhile
Clinical conundrum of neuroleptic malignant syndrome

More Related Content

What's hot

Neuroleptic Malignant Syndrome
Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome
Neuroleptic Malignant SyndromeMelissa Davis
 
Emergencies Caused By Psychiatric Drugs
Emergencies Caused By Psychiatric DrugsEmergencies Caused By Psychiatric Drugs
Emergencies Caused By Psychiatric DrugsShah Parind
 
Neuroleptic malignant syndrome
Neuroleptic malignant syndromeNeuroleptic malignant syndrome
Neuroleptic malignant syndromeMarvin Bayog
 
SSRIs and Serotonin Syndrome
SSRIs and Serotonin SyndromeSSRIs and Serotonin Syndrome
SSRIs and Serotonin SyndromeTeresa Chahine
 
Serotonin syndrome 2
Serotonin syndrome  2Serotonin syndrome  2
Serotonin syndrome 2samirelansary
 
Management of Epilepsy, GTCS,
 Management of Epilepsy, GTCS, Management of Epilepsy, GTCS,
Management of Epilepsy, GTCS,ankitamishra1402
 
Adverse effects antipsychotics dr ali
Adverse effects antipsychotics dr aliAdverse effects antipsychotics dr ali
Adverse effects antipsychotics dr aliOSMAN ALI MD
 
Management of adverse effect of antipsychotics 1
Management of adverse effect of antipsychotics 1Management of adverse effect of antipsychotics 1
Management of adverse effect of antipsychotics 1sadaf89
 
Serotonin syndrome 2
Serotonin syndrome  2Serotonin syndrome  2
Serotonin syndrome 2samirelansary
 
Neuroleptic malignant syndrome and catatonic disorders
Neuroleptic malignant syndrome and catatonic disordersNeuroleptic malignant syndrome and catatonic disorders
Neuroleptic malignant syndrome and catatonic disordersMelaku Yetbarek,MD
 
Antidepressants toxictiy
Antidepressants toxictiyAntidepressants toxictiy
Antidepressants toxictiyAmira Badr
 
Management of antipsychotic overdose
Management of antipsychotic overdoseManagement of antipsychotic overdose
Management of antipsychotic overdosesunil kumar daha
 
Adverse Effects of Antiepileptic Drugs
Adverse Effects of Antiepileptic Drugs Adverse Effects of Antiepileptic Drugs
Adverse Effects of Antiepileptic Drugs Ade Wijaya
 
Pharmacotheparapy of epilepsy
Pharmacotheparapy of epilepsyPharmacotheparapy of epilepsy
Pharmacotheparapy of epilepsyshubhangi buchade
 
Drug Therapy of Epilepsy (Antiepileptic Drugs)
Drug Therapy of Epilepsy (Antiepileptic Drugs)Drug Therapy of Epilepsy (Antiepileptic Drugs)
Drug Therapy of Epilepsy (Antiepileptic Drugs)Sawsan Aboul-Fotouh
 
Extrapyramidal symptoms & nms
Extrapyramidal symptoms & nmsExtrapyramidal symptoms & nms
Extrapyramidal symptoms & nmsChandni Narayan
 

What's hot (20)

Neuroleptic Malignant Syndrome
Neuroleptic Malignant SyndromeNeuroleptic Malignant Syndrome
Neuroleptic Malignant Syndrome
 
Emergencies Caused By Psychiatric Drugs
Emergencies Caused By Psychiatric DrugsEmergencies Caused By Psychiatric Drugs
Emergencies Caused By Psychiatric Drugs
 
Neuroleptic malignant syndrome
Neuroleptic malignant syndromeNeuroleptic malignant syndrome
Neuroleptic malignant syndrome
 
SSRIs and Serotonin Syndrome
SSRIs and Serotonin SyndromeSSRIs and Serotonin Syndrome
SSRIs and Serotonin Syndrome
 
SSRI poisoning
SSRI poisoningSSRI poisoning
SSRI poisoning
 
Serotonin Syndrome
Serotonin SyndromeSerotonin Syndrome
Serotonin Syndrome
 
Serotonin syndrome 2
Serotonin syndrome  2Serotonin syndrome  2
Serotonin syndrome 2
 
Management of Epilepsy, GTCS,
 Management of Epilepsy, GTCS, Management of Epilepsy, GTCS,
Management of Epilepsy, GTCS,
 
SerSyndrome
SerSyndromeSerSyndrome
SerSyndrome
 
Adverse effects antipsychotics dr ali
Adverse effects antipsychotics dr aliAdverse effects antipsychotics dr ali
Adverse effects antipsychotics dr ali
 
Management of adverse effect of antipsychotics 1
Management of adverse effect of antipsychotics 1Management of adverse effect of antipsychotics 1
Management of adverse effect of antipsychotics 1
 
Serotonin syndrome 2
Serotonin syndrome  2Serotonin syndrome  2
Serotonin syndrome 2
 
Neuroleptic malignant syndrome and catatonic disorders
Neuroleptic malignant syndrome and catatonic disordersNeuroleptic malignant syndrome and catatonic disorders
Neuroleptic malignant syndrome and catatonic disorders
 
Antidepressants toxictiy
Antidepressants toxictiyAntidepressants toxictiy
Antidepressants toxictiy
 
Management of antipsychotic overdose
Management of antipsychotic overdoseManagement of antipsychotic overdose
Management of antipsychotic overdose
 
Adverse Effects of Antiepileptic Drugs
Adverse Effects of Antiepileptic Drugs Adverse Effects of Antiepileptic Drugs
Adverse Effects of Antiepileptic Drugs
 
Pharmacotheparapy of epilepsy
Pharmacotheparapy of epilepsyPharmacotheparapy of epilepsy
Pharmacotheparapy of epilepsy
 
Drug Therapy of Epilepsy (Antiepileptic Drugs)
Drug Therapy of Epilepsy (Antiepileptic Drugs)Drug Therapy of Epilepsy (Antiepileptic Drugs)
Drug Therapy of Epilepsy (Antiepileptic Drugs)
 
Antiepileptics
Antiepileptics Antiepileptics
Antiepileptics
 
Extrapyramidal symptoms & nms
Extrapyramidal symptoms & nmsExtrapyramidal symptoms & nms
Extrapyramidal symptoms & nms
 

Similar to Clinical conundrum of neuroleptic malignant syndrome

Giovanni Broggi
Giovanni BroggiGiovanni Broggi
Giovanni Broggiagrilinea
 
Acute Meningoencephalitis - Thesis presentation
Acute Meningoencephalitis - Thesis presentationAcute Meningoencephalitis - Thesis presentation
Acute Meningoencephalitis - Thesis presentationAnkit Raiyani
 
Epilepsy in Children.pptx
Epilepsy in Children.pptxEpilepsy in Children.pptx
Epilepsy in Children.pptxCSN Vittal
 
Neurobiology of depression
Neurobiology of depressionNeurobiology of depression
Neurobiology of depressionSalman Kareem
 
Schizophrenia part 2
Schizophrenia    part 2Schizophrenia    part 2
Schizophrenia part 2Lama K Banna
 
Diagnostic methods
Diagnostic methodsDiagnostic methods
Diagnostic methodsOla
 
Neuroinflammatory_disorders_MS_Alhareb.pptx
Neuroinflammatory_disorders_MS_Alhareb.pptxNeuroinflammatory_disorders_MS_Alhareb.pptx
Neuroinflammatory_disorders_MS_Alhareb.pptxAhmedalmahdi16
 
osmotic deyelination syndrome
osmotic deyelination syndromeosmotic deyelination syndrome
osmotic deyelination syndromeSachin Adukia
 
NEUROLEPTIC MALIGNANT SYNDROME copy.pptx
NEUROLEPTIC MALIGNANT SYNDROME copy.pptxNEUROLEPTIC MALIGNANT SYNDROME copy.pptx
NEUROLEPTIC MALIGNANT SYNDROME copy.pptxduaashah4
 
Parkinson’s disease psychosis
Parkinson’s disease psychosisParkinson’s disease psychosis
Parkinson’s disease psychosisYasir Hameed
 
Atypical forms of the osmotic demyelination syndrome
Atypical forms of the osmotic demyelination syndromeAtypical forms of the osmotic demyelination syndrome
Atypical forms of the osmotic demyelination syndromeErwin Chiquete, MD, PhD
 
Practical issues in MULTIPLE SCLEROSIS
Practical issues in MULTIPLE SCLEROSISPractical issues in MULTIPLE SCLEROSIS
Practical issues in MULTIPLE SCLEROSISAmr Hassan
 
Coccain and Sympathomimatic
Coccain and Sympathomimatic Coccain and Sympathomimatic
Coccain and Sympathomimatic EM OMSB
 
Tuberculosis of central Nervous System- CNSTB
Tuberculosis of central Nervous System- CNSTBTuberculosis of central Nervous System- CNSTB
Tuberculosis of central Nervous System- CNSTBYatinBhole
 
Alcohol Related Brain Damage.ppt
Alcohol Related Brain Damage.pptAlcohol Related Brain Damage.ppt
Alcohol Related Brain Damage.pptssuserf5fc05
 

Similar to Clinical conundrum of neuroleptic malignant syndrome (20)

epilepsy
epilepsyepilepsy
epilepsy
 
Giovanni Broggi
Giovanni BroggiGiovanni Broggi
Giovanni Broggi
 
Epilepsy
EpilepsyEpilepsy
Epilepsy
 
Acute Meningoencephalitis - Thesis presentation
Acute Meningoencephalitis - Thesis presentationAcute Meningoencephalitis - Thesis presentation
Acute Meningoencephalitis - Thesis presentation
 
Epilepsy in Children.pptx
Epilepsy in Children.pptxEpilepsy in Children.pptx
Epilepsy in Children.pptx
 
Neurobiology of depression
Neurobiology of depressionNeurobiology of depression
Neurobiology of depression
 
1st seizure ppt
1st seizure ppt1st seizure ppt
1st seizure ppt
 
Diagnosis of CIDP
Diagnosis of CIDPDiagnosis of CIDP
Diagnosis of CIDP
 
Schizophrenia part 2
Schizophrenia    part 2Schizophrenia    part 2
Schizophrenia part 2
 
Diagnostic methods
Diagnostic methodsDiagnostic methods
Diagnostic methods
 
A Case of CIDP
A Case of CIDPA Case of CIDP
A Case of CIDP
 
Neuroinflammatory_disorders_MS_Alhareb.pptx
Neuroinflammatory_disorders_MS_Alhareb.pptxNeuroinflammatory_disorders_MS_Alhareb.pptx
Neuroinflammatory_disorders_MS_Alhareb.pptx
 
osmotic deyelination syndrome
osmotic deyelination syndromeosmotic deyelination syndrome
osmotic deyelination syndrome
 
NEUROLEPTIC MALIGNANT SYNDROME copy.pptx
NEUROLEPTIC MALIGNANT SYNDROME copy.pptxNEUROLEPTIC MALIGNANT SYNDROME copy.pptx
NEUROLEPTIC MALIGNANT SYNDROME copy.pptx
 
Parkinson’s disease psychosis
Parkinson’s disease psychosisParkinson’s disease psychosis
Parkinson’s disease psychosis
 
Atypical forms of the osmotic demyelination syndrome
Atypical forms of the osmotic demyelination syndromeAtypical forms of the osmotic demyelination syndrome
Atypical forms of the osmotic demyelination syndrome
 
Practical issues in MULTIPLE SCLEROSIS
Practical issues in MULTIPLE SCLEROSISPractical issues in MULTIPLE SCLEROSIS
Practical issues in MULTIPLE SCLEROSIS
 
Coccain and Sympathomimatic
Coccain and Sympathomimatic Coccain and Sympathomimatic
Coccain and Sympathomimatic
 
Tuberculosis of central Nervous System- CNSTB
Tuberculosis of central Nervous System- CNSTBTuberculosis of central Nervous System- CNSTB
Tuberculosis of central Nervous System- CNSTB
 
Alcohol Related Brain Damage.ppt
Alcohol Related Brain Damage.pptAlcohol Related Brain Damage.ppt
Alcohol Related Brain Damage.ppt
 

More from webzforu

Why controversies are of continuous relevance
Why controversies are of continuous relevanceWhy controversies are of continuous relevance
Why controversies are of continuous relevancewebzforu
 
When to start, switch or add in alzheimers disease memantine
When to start, switch or add in alzheimers disease memantineWhen to start, switch or add in alzheimers disease memantine
When to start, switch or add in alzheimers disease memantinewebzforu
 
Vertigo 2008
Vertigo 2008Vertigo 2008
Vertigo 2008webzforu
 
Vertigo 2010
Vertigo 2010Vertigo 2010
Vertigo 2010webzforu
 
Vertigo2010
Vertigo2010Vertigo2010
Vertigo2010webzforu
 
Vertigo and dizziness
Vertigo and dizzinessVertigo and dizziness
Vertigo and dizzinesswebzforu
 
Usa confirance
Usa confiranceUsa confirance
Usa confirancewebzforu
 
Unconscious sensory perception in a case of hemineglect
Unconscious sensory perception in a case of hemineglectUnconscious sensory perception in a case of hemineglect
Unconscious sensory perception in a case of hemineglectwebzforu
 
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...webzforu
 
Ten step approach to movement disorders
Ten step approach to movement disordersTen step approach to movement disorders
Ten step approach to movement disorderswebzforu
 
Stroke prevention a reality in this millennium
Stroke prevention a reality in this millenniumStroke prevention a reality in this millennium
Stroke prevention a reality in this millenniumwebzforu
 
Stroke and neuroprotection
Stroke and neuroprotectionStroke and neuroprotection
Stroke and neuroprotectionwebzforu
 
Sensory modulation in neurological rehabilitation
Sensory modulation in neurological rehabilitationSensory modulation in neurological rehabilitation
Sensory modulation in neurological rehabilitationwebzforu
 
Recovering repressed visual memories and in parietal lobe syndrome using vest...
Recovering repressed visual memories and in parietal lobe syndrome using vest...Recovering repressed visual memories and in parietal lobe syndrome using vest...
Recovering repressed visual memories and in parietal lobe syndrome using vest...webzforu
 
Recent advances in the mangement of extra pyramidal basal ganglia disorders
Recent advances in the mangement of extra pyramidal basal ganglia disorders Recent advances in the mangement of extra pyramidal basal ganglia disorders
Recent advances in the mangement of extra pyramidal basal ganglia disorders webzforu
 
Ragas dental college facical pain non odontogenic causes
Ragas dental college facical pain non odontogenic causesRagas dental college facical pain non odontogenic causes
Ragas dental college facical pain non odontogenic causeswebzforu
 
Practical algorithm for surgical management of facial pain
Practical algorithm for surgical management of facial painPractical algorithm for surgical management of facial pain
Practical algorithm for surgical management of facial painwebzforu
 
Pathophysiology of migraine
Pathophysiology of migrainePathophysiology of migraine
Pathophysiology of migrainewebzforu
 
Quality of life in post stroke patients-role of nootorpil
Quality of life in post stroke patients-role of nootorpilQuality of life in post stroke patients-role of nootorpil
Quality of life in post stroke patients-role of nootorpilwebzforu
 
Practice pearls diagnosis and prophylaxis of migraine
Practice pearls diagnosis and prophylaxis of migrainePractice pearls diagnosis and prophylaxis of migraine
Practice pearls diagnosis and prophylaxis of migrainewebzforu
 

More from webzforu (20)

Why controversies are of continuous relevance
Why controversies are of continuous relevanceWhy controversies are of continuous relevance
Why controversies are of continuous relevance
 
When to start, switch or add in alzheimers disease memantine
When to start, switch or add in alzheimers disease memantineWhen to start, switch or add in alzheimers disease memantine
When to start, switch or add in alzheimers disease memantine
 
Vertigo 2008
Vertigo 2008Vertigo 2008
Vertigo 2008
 
Vertigo 2010
Vertigo 2010Vertigo 2010
Vertigo 2010
 
Vertigo2010
Vertigo2010Vertigo2010
Vertigo2010
 
Vertigo and dizziness
Vertigo and dizzinessVertigo and dizziness
Vertigo and dizziness
 
Usa confirance
Usa confiranceUsa confirance
Usa confirance
 
Unconscious sensory perception in a case of hemineglect
Unconscious sensory perception in a case of hemineglectUnconscious sensory perception in a case of hemineglect
Unconscious sensory perception in a case of hemineglect
 
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...
Three pronged approach to migraine epilepsy and neuropathic pain–role of oxca...
 
Ten step approach to movement disorders
Ten step approach to movement disordersTen step approach to movement disorders
Ten step approach to movement disorders
 
Stroke prevention a reality in this millennium
Stroke prevention a reality in this millenniumStroke prevention a reality in this millennium
Stroke prevention a reality in this millennium
 
Stroke and neuroprotection
Stroke and neuroprotectionStroke and neuroprotection
Stroke and neuroprotection
 
Sensory modulation in neurological rehabilitation
Sensory modulation in neurological rehabilitationSensory modulation in neurological rehabilitation
Sensory modulation in neurological rehabilitation
 
Recovering repressed visual memories and in parietal lobe syndrome using vest...
Recovering repressed visual memories and in parietal lobe syndrome using vest...Recovering repressed visual memories and in parietal lobe syndrome using vest...
Recovering repressed visual memories and in parietal lobe syndrome using vest...
 
Recent advances in the mangement of extra pyramidal basal ganglia disorders
Recent advances in the mangement of extra pyramidal basal ganglia disorders Recent advances in the mangement of extra pyramidal basal ganglia disorders
Recent advances in the mangement of extra pyramidal basal ganglia disorders
 
Ragas dental college facical pain non odontogenic causes
Ragas dental college facical pain non odontogenic causesRagas dental college facical pain non odontogenic causes
Ragas dental college facical pain non odontogenic causes
 
Practical algorithm for surgical management of facial pain
Practical algorithm for surgical management of facial painPractical algorithm for surgical management of facial pain
Practical algorithm for surgical management of facial pain
 
Pathophysiology of migraine
Pathophysiology of migrainePathophysiology of migraine
Pathophysiology of migraine
 
Quality of life in post stroke patients-role of nootorpil
Quality of life in post stroke patients-role of nootorpilQuality of life in post stroke patients-role of nootorpil
Quality of life in post stroke patients-role of nootorpil
 
Practice pearls diagnosis and prophylaxis of migraine
Practice pearls diagnosis and prophylaxis of migrainePractice pearls diagnosis and prophylaxis of migraine
Practice pearls diagnosis and prophylaxis of migraine
 

Recently uploaded

Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxkomalt2001
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectiondrhanifmohdali
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.whalesdesign
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaSujoy Dasgupta
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdfHongBiThi1
 
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio..."Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio...Sujoy Dasgupta
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Peter Embi
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .Mohamed Rizk Khodair
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu Medical University
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfMedicoseAcademics
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdfHongBiThi1
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisSujoy Dasgupta
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 

Recently uploaded (20)

Basic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptxBasic structure of hair and hair growth cycle.pptx
Basic structure of hair and hair growth cycle.pptx
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
AORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissectionAORTIC DISSECTION and management of aortic dissection
AORTIC DISSECTION and management of aortic dissection
 
MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.MedMatch: Your Health, Our Mission. Pitch deck.
MedMatch: Your Health, Our Mission. Pitch deck.
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy DasguptaMale Infertility Panel Discussion by Dr Sujoy Dasgupta
Male Infertility Panel Discussion by Dr Sujoy Dasgupta
 
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdfSGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA    .pdf
SGK NGẠT NƯỚC ĐHYHN RẤT LÀ HAY NHA .pdf
 
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
Immune labs basics part 1 acute phase reactants ESR, CRP Ahmed Yehia Ismaeel,...
 
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio..."Radical excision of DIE in subferile women with deep infiltrating endometrio...
"Radical excision of DIE in subferile women with deep infiltrating endometrio...
 
Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024Clinical Research Informatics Year-in-Review 2024
Clinical Research Informatics Year-in-Review 2024
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
Neurological history taking (2024) .
Neurological  history  taking  (2024)  .Neurological  history  taking  (2024)  .
Neurological history taking (2024) .
 
Mental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil ThirusanguMental health Team. Dr Senthil Thirusangu
Mental health Team. Dr Senthil Thirusangu
 
Red Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdfRed Blood Cells_anemia & polycythemia.pdf
Red Blood Cells_anemia & polycythemia.pdf
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdfSGK ĐIỆN GIẬT ĐHYHN        RẤT LÀ HAY TUYỆT VỜI.pdf
SGK ĐIỆN GIẬT ĐHYHN RẤT LÀ HAY TUYỆT VỜI.pdf
 
Adenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosisAdenomyosis or Fibroid- making right diagnosis
Adenomyosis or Fibroid- making right diagnosis
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 

Clinical conundrum of neuroleptic malignant syndrome

  • 2. Clinical conundrum of Neuroleptic malignant syndrome Dr. A.V. SRINIVASAN 9/9/03 Madras Medical College
  • 3. INTRODUCTION IN ANY FIELD, FIND THE STRANGEST THING AND EXPLORE IT John Archibald Wheeler
  • 4. Clinical Knowledge – Trinity principles Observation Recording Thinking
  • 5. Thinking 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
  • 6. REVIEW OF LITERATURE “THE WORLD IS NOT ONLY QUEERER THAN WE IMAGINE; IT IS QUEERER THAN WE CAN IMAGINE” - J B S Haldane
  • 7. CLINICAL FEATURES 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
  • 8. POPE 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
  • 9. INCIDENCE 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)
  • 10. G-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
  • 11. PRIMARY 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
  • 12. PATIENTS 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
  • 13. DRUGS 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%
  • 14. PRESENTATIONS 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
  • 15. COMPLICATIONS 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
  • 16. DIFFERENTIAL DIAGNOSIS Malignant Hyperthermia Lethal Catatonia Neuroleptic Induced Catatonia Neuroleptic Induced Anti-Cholinergic Syndrome Neuroleptic Induced Heat Stroke The Serotonin Syndrome
  • 17. TREATMENT SUPPORTIVE MEASURES • Dantrolene and Dopamine Agonists • Other Drugs Therapy • ECT RE-USE OF NEUROLEPTICS • Early Challenge • Long Term Challenge
  • 18. PATHOGENESIS Abnormality of skeletal muscle Abnormality of dopamine within the CNS Autopsy findings
  • 19. Clinical Knowledge Observations – First Trinity Principle 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)
  • 20. Clinical Knowledge Second Trinity Principle The understanding of Clinical Conundrum of Neuroleptic Malignant Syndrome would become clearer when Schizophrenia and Affective disorders are studied separately.
  • 21. Aims and Objectives 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
  • 22. Aims 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
  • 23. Inclusion 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
  • 24. Exclusion criteria 1. Absence of primary psychiatric diagnosis 2. Due to other drug induced, systemic or neuropsychiatric illness
  • 25. Methodology 1. Data Collection 2. Data Presentation 3. Data Analysis 4. Data interpretation
  • 26. Data Collection 1. Computer coded case sheet 2. Excel spread sheet
  • 27. Data Presentation Graphs Dendrograms
  • 28. Data Analysis Tabulation Statistical test of hypothesis Correlation analysis Factor Analysis Cluster Analysis Discriminant Analysis
  • 29. Summary statistics of Schizophrenia, Affective disorder, and NMS patients
  • 30. Important Observations Schizophrenia Affective Disorder Age 32 43 Duration of illness 5 yrs 3 yrs Onset 9 hrs 17 hrs
  • 31. Important Observations Analysis of Variance indicate : Schizophrenia and Affective disorder patients differ significantly. 1. Age 5. EPS 2. Onset 6. ANS 3. Evolution 7. Fever 4. Resolution 8. Altered sensorium
  • 32. Pre NMS Drug Pre-NMS Drug C H Onset (in hrs) 11 14 Evolution (in hrs) 36 43 Resolution (in days) 15 16 Extra Pyramidal 60 68 Symptoms (in hours) Autonomic 77 85 Symptoms (in hours) Fever (in hrs) 17 15 Altered Sensorium 15 20 (in hrs)
  • 33. Important Observations 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
  • 34. Important Observations The chi-square statistic indicates the rejection of the hypothesis that there is uniformity in giving bromocriptine to both the groups
  • 35. Factor Analysis of Parameters responsible for NMS Component Matrix Component 1 Extra Pyramidal .906 Symptoms (in hours) Autonomic .885 Symptoms (in hours) Altered Sensorium .805 (in hrs) Fever (in hrs) .769
  • 36. Factor analysis of parameters for Schizophrenia Component Matrix Component 1 Extra Pyramidal .913 Symptoms (in hours) Autonomic .888 Symptoms (in hours) Fever (in hrs) .779 Altered Sensorium .497 (in hrs)
  • 37. Factor Analysis of Parameters of Affective Disorder. Rotated Component Matrix Component 1 2 Autonomic .955 .154 Symptoms (in hours) Extra Pyramidal .931 .251 Symptoms (in hours) Altered Sensorium .181 .906 (in hrs) Fever (in hrs) .200 .898
  • 38. Structure of Parameters – According to their importance Structure of Parameters - Rankwise Function 1 Autonomic .898 Symptoms (in hours) Extra Pyramidal .700 Symptoms (in hours) Altered Sensorium .597 (in hrs) Fever (in hrs) .287
  • 39. Dendrogram showing the relationship between the parameters of NMS Rescaled distance cluster combine 0 5 10 15 20 25 Variable num Ext. Pyr Aut. sym Evolution Onset Fever Alt. sen. Resolution
  • 40. Dendrogram showing the relationship between parameters of Schizophrenia patients Rescaled distance cluster combine 0 5 10 15 20 25 Variable num Ext. Pyr Aut. sym Fever Onset Alt. Sen. Evolution Resolution
  • 41. Dendrogram showing the relationship of parameters affective disorders Rescaled distance cluster combine 0 5 10 15 20 25 Variable num Onset Fever Alt. Sen. Ext. Pyr. Aut. Sym. Evolution Resolution
  • 42. The Classification Function coefficients and the Group Centroids Classification Function Coefficients Type of patients Schizophr Affective Functions at Group Centroids enia Disorder Extra Pyramidal -2.55E-02 -3.48E-02 Function Symptoms (in hours) Autonomic Type of patients 1 6.294E-02 .133 Symptoms (in hours) Schizophrenia -1.296 Fever (in hrs) .165 7.480E-02 Affective Disorder .864 Altered Sensorium -2.30E-02 6.808E-02 (in hrs) (Constant) -2.837 -7.686 Fisher's linear discriminant functions
  • 43. Classification of Schizophrenia and Affective Disorder Patients Classification Resultsa Predicted Group Membership Schizophr Affective Type of patients enia Disorder Total Original Count Schizophrenia 17 3 20 Affective Disorder 2 28 30 % Schizophrenia 85.0 15.0 100.0 Affective Disorder 6.7 93.3 100.0 a. 90.0% of original grouped cases correctly classified. 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
  • 44. AVS-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
  • 45. Validation of Hypothesis Schizophrenia Affective disorder Hypothesis Validated Hypothesis Validated Altered 12 hours 10 hours 24 hours 26 hours sensorium Extra 48 hours 40 hours 96 hours 85 hours pyramidal symptoms Autonomic 48 hours 50 hours 96 hours 107 hours symptoms Evolution 24 hours 27 hours 72 hours 52 hours Resolution 30 days 23 days 15 days 11 days Mortality Likely 3 patients Unlikely Nil
  • 46. DISCUSSION Distribution of cases by Age 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
  • 47. DISCUSSION (Contd...) Distribution of cases by diagnosis 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
  • 48. DISCUSSION (Contd...) Distribution of cases by Age 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
  • 49. DISCUSSION (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 All 40 115 39 50
  • 50. DISCUSSION (Contd...) NMS Evolution days Study Days Srinivasan (2002) 1.7 Shaliv (1986) 4.8 Addonizio (1987) 14.0 Caroff – Wt. Avg. 7.5
  • 51. DISCUSSION (Contd...) NMS Evolution days by diagnosis (Srinivasan – 2002) Study Days Schizophrenia 1.1 Affective Disorder 2.2 All Cases 1.7
  • 52. DISCUSSION (Contd...) Resolution time - Days Study Days Srinivasan (2002) 15.9 Shaliv (1986) NA Addonizio (1987) 13.0 Caroff – Wt. Avg. NA
  • 53. DISCUSSION (Contd...) NMS Resolution days by diagnosis (Srinivasan – 2002) Study Days Schizophrenia 20.3 Affective Disorder 11 All Cases 15.9
  • 54. DISCUSSION (Contd...) Grace : Dopamine Release Phasic (Behavioural Stimuli) Tonic (Regulated by Prefrontal Cortical Afferents)
  • 55. DISCUSSION (Contd...) DOPAMINE - HYPOTHESIS Schizophrenia • Hyper dopaminergic – Positive Symptom • Hypo dopaminergic – Negative Symptom Affective Disorder • Hyper - Mania • Hypo - Depression
  • 56. 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
  • 57. Answer to clinical Conundrum (Puzzling problem for experts) of NMS Tonic Phasic = Normal Cortex Basal Ganglia D1 Receptor D2 Receptor NEUROLEPTICS BLOCK NORMAL BLOCKED Duration of NMS IS Less Resolves Faster BLOCKED BLOCKED Duration is Longer & Mortality is more
  • 58. Conclusion 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
  • 59. 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
  • 60. 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
  • 61. 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
  • 62. Observation Practical 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
  • 63. Clinical Knowledge Recording - Second Trinity Principle Prospective study of fifty patients
  • 64. Clinical Knowledge Thinking - Third Trinity Principle Tonic Phasic Normal Cortex Basal Ganglia Predominantly Predominantly D2 D1 receptor Receptor Neuroleptics Block Normal Blocked Duration of NMS is less resolves faster Blocked Blocked Duration is longer & mortality is more Proposed new dopamine hypothesis
  • 65. This thesis is dedicated to the memory of my Professor C.D. MARSDEN for his helpful comments and encouragement
  • 66. My sincere Gratitude and Thanks
  • 70. Dedicated to my family for making everything worthwhile