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Catatonic signs in neuroleptic malignant syndrome
Catatonic Signs in Neuroleptic Monika
Koch, Sanjay
Chandragiri,
Malignant
Syed Rizvi, Georgios
Petrides,
Syndrome and Andrew
Francis
The study assessed catatonic signs in neuroleptic malignant syndrome (NMS). Records of inpatients meeting both stringent research criteria and DSM-IV criteria (n = 11) or only DSM-IV criteria (n = 5) for NMS were identified. The records were systematically rated on a 234tem rating scale for the presence of catatonic signs. Scores for NMS severity were related to the number of catatonic signs. Fifteen patients met
both research criteria for catatonia and DSM-IV motor criteria for organic catatonia. The sevedky scores of NMS correlated with the number of catatonic signs (Spearman p = +.71, P < .005). We conclude that multiple catatonic signs are present in NMS and the sever.* of NMS predicts the number of catatonic signs. Copyright 0 2000 by W.B. Saunders Company
ATONIA and neuroleptic malignant syndrome (NMS) are reported to share clinical features,‘*’ biochemical findings3e4 and treatment response.5-8 Some authors place them in the same spectrum of illness. 1.9Treatment implications make this relationship important because electroconvulsive therapy (ECT) and perhaps benzodiazepinesLJO+iltreat both, while neuroleptics precipitate NMS and may induce or worsen catatonia.9*‘0 Most of these observations derive from reviews or small case series lacking concurrent assessments and systematic criteria for either catatonia or NMS. The present study tested for an association between NMS and catatonia in a retrospective series by systematically assessing both conditions with strictly defined diagnostic criteria, and determined if quantitative estimates of severity were correlated.
was made by the presence of 1 or more signs from the DSM-IV (secondary catatonia. 293.89). A list of catatonic signs in both of these diagnostic systems is provided in Table 1. Rigidity is a motor sign common to NMS and catatonia. It was excluded here for the diagnosis of catatonia because of the uncertainty in differentiating catatonic rigidity from neurolepticinduced or extrapyramidal rigidity in a retrospective study. The autonomic instability that is an obligatory sign of NMS and also an item on the BFCRS was excluded in grading the severity of catatonia. (These steps were taken to reduce unintended bias in favor of our hypothesis.)
C
METHOD NMS cases were sought by a retrospective manual review of psychiatric consultation records and by a computer-aided search for an unexplained serum creatine phosphokinase (CPK) elevation in the discharge summaries of medical and psychiatric inpatients. Neuroleptic exposure, autonomic disturbance, and mental status changes were found in 27 cases. Of these, 16 met DSM-IV criteria” for NMS. Eleven of these 16 also met the stringent research criteria of Caroff et al.‘) for NMS. Both diagnostic schemes require fever plus rigidity (primary features) and either 2 (DSM-IV) or 5 (Caroff et al.) secondary features such as elevated CPK, leukocytosis, tachycardia, etc. (Table 1). The Caroff criteria specify a fever of at least 38°C. while the DSM-IV does not define a specific temperature. All diagnostic signs of NMS were present in the same 24-hour period. The severity of NMS was estimated using a quantitative scale developed by Hynes and Vickar. iJ This 8-point instrument allots 0 to 2 points for the degree of disturbance in 4 domains of NMS: fever and/or autonomic signs, mental status change, rigidity, and elevated CPK. The records of these 16 patients were then reviewed for catatonic signs within 24 hours of NMS onset using the 23-item Bush-Francis Catatonia Rating Scale (BFCRS), a standardized instrument for the detection of catatonia.15 A research diagnosis of catatonia was made by the presence of at least 2 of the 14 screening items on the BFCRS. A clinical diagnosis of catatonia Comprehensive
Psychiatry,
Vol. 41, No. 1 (January/February),
RESULTS
The 16 patients meeting criteria for NMS had a fever (mean 5 SD) of 101.1” + 1.6”F (range, 99.1” to 104°F; 101.7’ + 1.4”F for the 11 patients meeting Caroff et al. criteria), a CPK level of 2,698 +2,856 (range, 162 to 11,280), and a peak heart rate of 126 + 27 (range, 88 to 196). On the HynesVickar scale, the mean score was 4.4 (range, 2 to 7). Scores for subjects meeting the stricter Caroff et al. criteria (median, 5; range, 2 to 7) were significantly higher than for those meeting only DSM-IV criteria (median, 3; range, 3 to 4; Mann-Whitney U = 8, P < .005). The frequency of NMS signs is shown in Table 1. Fifteen of these 16 patients met the BFCRS criteria and DSM-IV criteria A (motor signs) for secondary catatonia. These included 10 males and 5 females (aged 17 to 59 years) with various clinical psychiatric diagnoses: schizophrenia (n = 4), bipolar disorder (n = 4), mental retardation (n = 2), and other diagnoses (n = 5). They had a mean of
From the Department of Psychiatry and Behavioral Sciences, State University of New York at Stony Brook, Stony Brook; and Department of Psychiatry, Research Division, Hillside Hospital, Lang Island Jewish Medical Center. Glen Oaks, NE Address reprint requests to Andrew Francis, Ph.D., M.D., Department of Psychiatry, Health Sciences Center T-IO, SUNY Stony Brook, Stony Brook, NY I I794. Copyright 6 2000 by W B. Saunders Company 0010~440x/00/4101-0012$10.00/0
2000: pp 73-75
73
74
KOCH
Table
1. Clinical Signs of Catatonia in the Patient Sample
Catatonic Signs In = 15)’
Mutismt Excitementt Withdrawal
PWCWil With Sign
and NMS
NMS Signs (n = 161
Percent With Sign
73 67 47
RigidityS§ FeverSI Elevated CPK or myo-
Negativismt Mannerisms
47 40
globinuriaS5 LeukocytosisS§
Posturing Rigidiw
33 33
TachycardiaSI Change in mental
Immobility/stupor-t Staring
33 20
tus*§ Hypertension
Waxy flexibility Echophenomenat
20 13
tension*§ Diaphoresis
Stereotypyt Verbigeration
13 7
rheaS§ MutismS
’
Grimacing
7
93 a7 sta-
81 75
or hypo-
75 69
or sialor-
50 37 0 -
Incontinence*5 TremorSI Metabolic acidosis§ Tachypnea
100 100 93
or hypox-
ia§ll Dysphagia*II *Screening signs from the BFCRS. tDSM-IV criteria A [motor signs] for catatonia general
medical
condition
secondary
to a
[293.89].
SDSM-IV criteria for NMS 1333.921. §Caroff et al. criteria for NMS. IfNot recorded or insufficient data. gfligidity on the BFCRS excludes tremor
or cogwheeling.
4.4 screening catatonic signs on the BFCRS. and 6.1 signs on the full-scale BFCRS (of 22 items, after excluding the sign “autonomic disturbance”). There was no difference in the number of catatonic signs between the 2 NMS groups (Mann-Whitney U = 16.5, P = .2). The frequency of catatonic signs is shown in Table 1. There was a strong positive correlation between the Hynes-Vickar NMS severity score and the number of catatonic signs on the BFCRS (Spearman p + .71, df = 13, P < .005). Figure 1 shows the relationship between NMS severity and catatonic signs.
ET AL
catatonia, but did so more than 24 hours preceding the onset of NMS. Catatonia is a syndrome that spans medical, neurologic, and psychiatric disease. The symptoms and sequelae of catatonia range from mild to lethal. NMS shares both the clinical features of catatonia. such as rigidity, autonomic instability, stupor, etc., and its wide range of severity. A severe form of catatonia, also called lethal, pernicious, or malignant catatonia, is considered clinically inseparable from NMS,‘.Z.9 although this view has been challenged.16 With respect to laboratory findings, the elevated CPK typical of NMS is present in catatonia,3 while serum iron is reduced in both NMS and catatonia.“.” Electroencephalographic abnormalities have been reported in both conditions.‘J.18,r9 The present study demonstrates a strong correlation between the estimates of severity for NMS and catatonia, strengthening the case for a relationship between the 2 disorders and consistent with a view of NMS as a severe variant of catatonia. The neurochemical basis of catatonia or NMS remains unknown, but multiple neurotransmitter systems may be critical. Dopaminergic pathways are implicated by the observation that agents which antagonize or deplete dopamine are associated with the induction of both catatoniaY,‘0*19and NMS.9.1j The treatment response of catatonia has been related to the level of dopamine metabolites.‘O Neuroleptics that block dopamine can worsen catatonia and may precipitate NMS in catatonic pa-
SEVERITY OF NMS AND CATATONIA 27 hl 16.
.
Caroff
2
D
DSM-IV
NMS NMS
0
,
0
LL 12 !z t -im a-
,
DISCUSSION
The results show that with standardized methods using defined criteria, 15 of 16 patients with NMS met simultaneous clinical and research criteria for catatonia. These data support the hypothesized similarity of NMS and catatonia.‘.2.4.g The strong positive correlation between measures of severity for catatonia and NMS further strengthens the close relationship between these entities. Of note, the sixteenth patient with NMS did meet all criteria for
A
lxx’ 2
3 4 5 6 7 Hynes-Vickar NMS Score
8
9
Fig 1. Correlation between Hynes-Vickar NMS severity score and number of catatonic signs on the BFCRS (22-item version, excluding item for autonomic signs) for cases of NMS diagnosed according to DSM-IV criteria and Caroff et al. criteria.
CATATONIA
IN NEUROLEPTIC
SYNDROME
75
tients.’ Gamma-aminobutyric acid (GABA)-ergic systems have also been proposed in the pathophysiology of catatonia,2’ consistent with the robust responsiveness of this condition to benzodiazepines. ‘I Benzodiazepines have also been reported as a successful treatment for NMS in a few case reports5.6.8 and in a case series that used strict
criteria and quantified treatment outcome.7 In addition, NMS and catatonia both respond to ECT.’ Our findings support the hypothesis of clinical similarities between NMS and catatonia. This finding has implications for treatment in that trials of benzodiazepines as the initial agent in both catatonia and NMS may be warranted.
REFERENCES I. Fink M. Neuroleptic malignant syndrome and catatonia. One entity or two? Biol Psychiatry 1996;39: I-4. 2. Carroll BT, Taylor RE. The non dichotomy between lethal catatonia and neuroleptic malignant syndrome. J Clin Psychopharmacol 1997; 17:235-238. 3. Northoff G. Wenke J. PRug B. Increase of serum creatinine phosphokinase in catatonia: an investigation in 32 acute catatonic patients. Psycho1 Med 1996;26:547-553. 4. Carroll BT. Goforth HW. Serum iron in catatonia. Biol Psychiatry 1995;38:776-777. 5. Miyaoka H. Shishkura K. Otsubo T, Moramatsu D. Kamijima K. Diazepam-responsive neuroleptic malignant syndrome: a diagnostic subtype’? Am J Psychiatry 1997;153:882 (letter). 6. Lew TY, Tollefson G. Chlorpromazine-induced neuroleptic syndrome and its response to lorazepam. Biol Psychiatry 1983;18:1441-1446. 7. Francis A, Chandragiri SS, Rizvi S, Koch M, Petrides G. Lorazepam treatment of neuroleptic malignant syndrome. Submitted. 8. Kontaxakis VP, Christodoulou GN, Markidis MP. HavakiKontaxaki BJ. Treatment of a mild form of neuroleptic malignant syndrome with oral diazepam. Acta Psychiatr Stand 1988;78:396-398. 9. White DAC. Catatonia and the neuroleptic malignant syndrome-a single entity? Br J Psychiatry 1992:161:558-560. IO. Fricchione G. Catatonia: a new indication for benzodiazepines? Biol Psychiatry 1989;26:761-765. 11. Francis A, Divadeenam K, Petrides G. Advances in the diagnosis and treatment of catatonia. Convuls Ther 1997; 12:259261.
12. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. Ed. 4. Washington, DC: American Psychiatric Press, 1994. 13. Caroff SN, Mann SC, Lazarus syndrome: diagnostic issues. Psychiatr
A. Neuroleptic malignant Ann 1991;21:130-147.
14. Hynes AFM. Vickar EL. Case study: neuroleptic malignant syndrome without pyrexia. J Am Acad Child Adolesc Psychiatry 1996;35:959-961. 15. Bush G. Fink M. Petrides G, Dowling E Francis A. Catatonia. I. Rating scale and standardized examination. Acta Psychiatr Stand 1996;93: I29- 136. 16. Castillo differentiation nant syndrome.
E. Rubin RT, Holsboer-Traschler E. Clinical between lethal catatonia and neuroleptic maligAm J Psychiatry 1989;146:324-328.
17. Rosebush PI, Mazurek ME Serum iron and neuroleptic malignant syndrome. Lancet 1991;338: 149-151. 18. Carroll BT. Boutros in patients with catatonic 1995:26:60&l.
NN. Clinical electroencephalograms disorders. Clin Electroencephalogr
19. Lazarus A, Mann SC, Caroff SN (eds). The Neuroleptic Malignant Syndrome and Related Conditions. Washington, DC: American Psychiatric Press, 1989. 20. Northoff G, Demisch L, Wenke J, Pflug B. Plasma homovanillic acid concentrations in catatonia. Biol Psychiatry 1996;39:436-443. 2 I. Wetzel H, Heuser I. Benkert 0. Stupor and affective state: alleviation of the psychomotor disturbances by lorazepam and recurrence of symptoms after Ro 15-1788. J Nerv Ment Dis 1987;175:240-242.
Koch, Sanjay
Chandragiri,
Malignant
Syed Rizvi, Georgios
Petrides,
Syndrome and Andrew
Francis
The study assessed catatonic signs in neuroleptic malignant syndrome (NMS). Records of inpatients meeting both stringent research criteria and DSM-IV criteria (n = 11) or only DSM-IV criteria (n = 5) for NMS were identified. The records were systematically rated on a 234tem rating scale for the presence of catatonic signs. Scores for NMS severity were related to the number of catatonic signs. Fifteen patients met
both research criteria for catatonia and DSM-IV motor criteria for organic catatonia. The sevedky scores of NMS correlated with the number of catatonic signs (Spearman p = +.71, P < .005). We conclude that multiple catatonic signs are present in NMS and the sever.* of NMS predicts the number of catatonic signs. Copyright 0 2000 by W.B. Saunders Company
ATONIA and neuroleptic malignant syndrome (NMS) are reported to share clinical features,‘*’ biochemical findings3e4 and treatment response.5-8 Some authors place them in the same spectrum of illness. 1.9Treatment implications make this relationship important because electroconvulsive therapy (ECT) and perhaps benzodiazepinesLJO+iltreat both, while neuroleptics precipitate NMS and may induce or worsen catatonia.9*‘0 Most of these observations derive from reviews or small case series lacking concurrent assessments and systematic criteria for either catatonia or NMS. The present study tested for an association between NMS and catatonia in a retrospective series by systematically assessing both conditions with strictly defined diagnostic criteria, and determined if quantitative estimates of severity were correlated.
was made by the presence of 1 or more signs from the DSM-IV (secondary catatonia. 293.89). A list of catatonic signs in both of these diagnostic systems is provided in Table 1. Rigidity is a motor sign common to NMS and catatonia. It was excluded here for the diagnosis of catatonia because of the uncertainty in differentiating catatonic rigidity from neurolepticinduced or extrapyramidal rigidity in a retrospective study. The autonomic instability that is an obligatory sign of NMS and also an item on the BFCRS was excluded in grading the severity of catatonia. (These steps were taken to reduce unintended bias in favor of our hypothesis.)
C
METHOD NMS cases were sought by a retrospective manual review of psychiatric consultation records and by a computer-aided search for an unexplained serum creatine phosphokinase (CPK) elevation in the discharge summaries of medical and psychiatric inpatients. Neuroleptic exposure, autonomic disturbance, and mental status changes were found in 27 cases. Of these, 16 met DSM-IV criteria” for NMS. Eleven of these 16 also met the stringent research criteria of Caroff et al.‘) for NMS. Both diagnostic schemes require fever plus rigidity (primary features) and either 2 (DSM-IV) or 5 (Caroff et al.) secondary features such as elevated CPK, leukocytosis, tachycardia, etc. (Table 1). The Caroff criteria specify a fever of at least 38°C. while the DSM-IV does not define a specific temperature. All diagnostic signs of NMS were present in the same 24-hour period. The severity of NMS was estimated using a quantitative scale developed by Hynes and Vickar. iJ This 8-point instrument allots 0 to 2 points for the degree of disturbance in 4 domains of NMS: fever and/or autonomic signs, mental status change, rigidity, and elevated CPK. The records of these 16 patients were then reviewed for catatonic signs within 24 hours of NMS onset using the 23-item Bush-Francis Catatonia Rating Scale (BFCRS), a standardized instrument for the detection of catatonia.15 A research diagnosis of catatonia was made by the presence of at least 2 of the 14 screening items on the BFCRS. A clinical diagnosis of catatonia Comprehensive
Psychiatry,
Vol. 41, No. 1 (January/February),
RESULTS
The 16 patients meeting criteria for NMS had a fever (mean 5 SD) of 101.1” + 1.6”F (range, 99.1” to 104°F; 101.7’ + 1.4”F for the 11 patients meeting Caroff et al. criteria), a CPK level of 2,698 +2,856 (range, 162 to 11,280), and a peak heart rate of 126 + 27 (range, 88 to 196). On the HynesVickar scale, the mean score was 4.4 (range, 2 to 7). Scores for subjects meeting the stricter Caroff et al. criteria (median, 5; range, 2 to 7) were significantly higher than for those meeting only DSM-IV criteria (median, 3; range, 3 to 4; Mann-Whitney U = 8, P < .005). The frequency of NMS signs is shown in Table 1. Fifteen of these 16 patients met the BFCRS criteria and DSM-IV criteria A (motor signs) for secondary catatonia. These included 10 males and 5 females (aged 17 to 59 years) with various clinical psychiatric diagnoses: schizophrenia (n = 4), bipolar disorder (n = 4), mental retardation (n = 2), and other diagnoses (n = 5). They had a mean of
From the Department of Psychiatry and Behavioral Sciences, State University of New York at Stony Brook, Stony Brook; and Department of Psychiatry, Research Division, Hillside Hospital, Lang Island Jewish Medical Center. Glen Oaks, NE Address reprint requests to Andrew Francis, Ph.D., M.D., Department of Psychiatry, Health Sciences Center T-IO, SUNY Stony Brook, Stony Brook, NY I I794. Copyright 6 2000 by W B. Saunders Company 0010~440x/00/4101-0012$10.00/0
2000: pp 73-75
73
74
KOCH
Table
1. Clinical Signs of Catatonia in the Patient Sample
Catatonic Signs In = 15)’
Mutismt Excitementt Withdrawal
PWCWil With Sign
and NMS
NMS Signs (n = 161
Percent With Sign
73 67 47
RigidityS§ FeverSI Elevated CPK or myo-
Negativismt Mannerisms
47 40
globinuriaS5 LeukocytosisS§
Posturing Rigidiw
33 33
TachycardiaSI Change in mental
Immobility/stupor-t Staring
33 20
tus*§ Hypertension
Waxy flexibility Echophenomenat
20 13
tension*§ Diaphoresis
Stereotypyt Verbigeration
13 7
rheaS§ MutismS
’
Grimacing
7
93 a7 sta-
81 75
or hypo-
75 69
or sialor-
50 37 0 -
Incontinence*5 TremorSI Metabolic acidosis§ Tachypnea
100 100 93
or hypox-
ia§ll Dysphagia*II *Screening signs from the BFCRS. tDSM-IV criteria A [motor signs] for catatonia general
medical
condition
secondary
to a
[293.89].
SDSM-IV criteria for NMS 1333.921. §Caroff et al. criteria for NMS. IfNot recorded or insufficient data. gfligidity on the BFCRS excludes tremor
or cogwheeling.
4.4 screening catatonic signs on the BFCRS. and 6.1 signs on the full-scale BFCRS (of 22 items, after excluding the sign “autonomic disturbance”). There was no difference in the number of catatonic signs between the 2 NMS groups (Mann-Whitney U = 16.5, P = .2). The frequency of catatonic signs is shown in Table 1. There was a strong positive correlation between the Hynes-Vickar NMS severity score and the number of catatonic signs on the BFCRS (Spearman p + .71, df = 13, P < .005). Figure 1 shows the relationship between NMS severity and catatonic signs.
ET AL
catatonia, but did so more than 24 hours preceding the onset of NMS. Catatonia is a syndrome that spans medical, neurologic, and psychiatric disease. The symptoms and sequelae of catatonia range from mild to lethal. NMS shares both the clinical features of catatonia. such as rigidity, autonomic instability, stupor, etc., and its wide range of severity. A severe form of catatonia, also called lethal, pernicious, or malignant catatonia, is considered clinically inseparable from NMS,‘.Z.9 although this view has been challenged.16 With respect to laboratory findings, the elevated CPK typical of NMS is present in catatonia,3 while serum iron is reduced in both NMS and catatonia.“.” Electroencephalographic abnormalities have been reported in both conditions.‘J.18,r9 The present study demonstrates a strong correlation between the estimates of severity for NMS and catatonia, strengthening the case for a relationship between the 2 disorders and consistent with a view of NMS as a severe variant of catatonia. The neurochemical basis of catatonia or NMS remains unknown, but multiple neurotransmitter systems may be critical. Dopaminergic pathways are implicated by the observation that agents which antagonize or deplete dopamine are associated with the induction of both catatoniaY,‘0*19and NMS.9.1j The treatment response of catatonia has been related to the level of dopamine metabolites.‘O Neuroleptics that block dopamine can worsen catatonia and may precipitate NMS in catatonic pa-
SEVERITY OF NMS AND CATATONIA 27 hl 16.
.
Caroff
2
D
DSM-IV
NMS NMS
0
,
0
LL 12 !z t -im a-
,
DISCUSSION
The results show that with standardized methods using defined criteria, 15 of 16 patients with NMS met simultaneous clinical and research criteria for catatonia. These data support the hypothesized similarity of NMS and catatonia.‘.2.4.g The strong positive correlation between measures of severity for catatonia and NMS further strengthens the close relationship between these entities. Of note, the sixteenth patient with NMS did meet all criteria for
A
lxx’ 2
3 4 5 6 7 Hynes-Vickar NMS Score
8
9
Fig 1. Correlation between Hynes-Vickar NMS severity score and number of catatonic signs on the BFCRS (22-item version, excluding item for autonomic signs) for cases of NMS diagnosed according to DSM-IV criteria and Caroff et al. criteria.
CATATONIA
IN NEUROLEPTIC
SYNDROME
75
tients.’ Gamma-aminobutyric acid (GABA)-ergic systems have also been proposed in the pathophysiology of catatonia,2’ consistent with the robust responsiveness of this condition to benzodiazepines. ‘I Benzodiazepines have also been reported as a successful treatment for NMS in a few case reports5.6.8 and in a case series that used strict
criteria and quantified treatment outcome.7 In addition, NMS and catatonia both respond to ECT.’ Our findings support the hypothesis of clinical similarities between NMS and catatonia. This finding has implications for treatment in that trials of benzodiazepines as the initial agent in both catatonia and NMS may be warranted.
REFERENCES I. Fink M. Neuroleptic malignant syndrome and catatonia. One entity or two? Biol Psychiatry 1996;39: I-4. 2. Carroll BT, Taylor RE. The non dichotomy between lethal catatonia and neuroleptic malignant syndrome. J Clin Psychopharmacol 1997; 17:235-238. 3. Northoff G. Wenke J. PRug B. Increase of serum creatinine phosphokinase in catatonia: an investigation in 32 acute catatonic patients. Psycho1 Med 1996;26:547-553. 4. Carroll BT. Goforth HW. Serum iron in catatonia. Biol Psychiatry 1995;38:776-777. 5. Miyaoka H. Shishkura K. Otsubo T, Moramatsu D. Kamijima K. Diazepam-responsive neuroleptic malignant syndrome: a diagnostic subtype’? Am J Psychiatry 1997;153:882 (letter). 6. Lew TY, Tollefson G. Chlorpromazine-induced neuroleptic syndrome and its response to lorazepam. Biol Psychiatry 1983;18:1441-1446. 7. Francis A, Chandragiri SS, Rizvi S, Koch M, Petrides G. Lorazepam treatment of neuroleptic malignant syndrome. Submitted. 8. Kontaxakis VP, Christodoulou GN, Markidis MP. HavakiKontaxaki BJ. Treatment of a mild form of neuroleptic malignant syndrome with oral diazepam. Acta Psychiatr Stand 1988;78:396-398. 9. White DAC. Catatonia and the neuroleptic malignant syndrome-a single entity? Br J Psychiatry 1992:161:558-560. IO. Fricchione G. Catatonia: a new indication for benzodiazepines? Biol Psychiatry 1989;26:761-765. 11. Francis A, Divadeenam K, Petrides G. Advances in the diagnosis and treatment of catatonia. Convuls Ther 1997; 12:259261.
12. American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders. Ed. 4. Washington, DC: American Psychiatric Press, 1994. 13. Caroff SN, Mann SC, Lazarus syndrome: diagnostic issues. Psychiatr
A. Neuroleptic malignant Ann 1991;21:130-147.
14. Hynes AFM. Vickar EL. Case study: neuroleptic malignant syndrome without pyrexia. J Am Acad Child Adolesc Psychiatry 1996;35:959-961. 15. Bush G. Fink M. Petrides G, Dowling E Francis A. Catatonia. I. Rating scale and standardized examination. Acta Psychiatr Stand 1996;93: I29- 136. 16. Castillo differentiation nant syndrome.
E. Rubin RT, Holsboer-Traschler E. Clinical between lethal catatonia and neuroleptic maligAm J Psychiatry 1989;146:324-328.
17. Rosebush PI, Mazurek ME Serum iron and neuroleptic malignant syndrome. Lancet 1991;338: 149-151. 18. Carroll BT. Boutros in patients with catatonic 1995:26:60&l.
NN. Clinical electroencephalograms disorders. Clin Electroencephalogr
19. Lazarus A, Mann SC, Caroff SN (eds). The Neuroleptic Malignant Syndrome and Related Conditions. Washington, DC: American Psychiatric Press, 1989. 20. Northoff G, Demisch L, Wenke J, Pflug B. Plasma homovanillic acid concentrations in catatonia. Biol Psychiatry 1996;39:436-443. 2 I. Wetzel H, Heuser I. Benkert 0. Stupor and affective state: alleviation of the psychomotor disturbances by lorazepam and recurrence of symptoms after Ro 15-1788. J Nerv Ment Dis 1987;175:240-242.