Muscle enzymes and white blood count as risk factors for the neuroleptic malignant syndrome

P.3 Psychotic disorders and antipsychotics

IP.3.050 I Neuroleptic malignant syndrome and psychosis in two siblings with gangliosidosis type II

I. Manor,H. Hermesh,H. Munitz, A. Weizman. Geha Psychiatric Hospital, P.O. Box 102, RabinMedicalCenter, Petach Tiqva and Sackler Faculty ofMedicine, Tel Aviv University, Israel GM-ll gangliosidosis (Tay-Sachs) is an autosomal recessive disease, which affects mostly Ashkenazi Jews. It is a metabolic disease caused by the accumulation of GM-ll ganglioside due to the deficiency of the enzyme tl-hexosaminidase A (Hex A). There are 3 types of GM-ll accordingto the age of onset. includinga rare adult type [l). GM-ll affects the striated muscles and the peripheral and central nervous systems. Neurological and psychiatric symptoms are frequent in those patients, including psychosis and depression [1). The coexistence of psychosis and this genetic disease may raise the possibility of its association with specific chromosomalregions, which are suggested as candidate regions for future targetedDNA researchin schizophrenia [2). Neuroleptic malignant syndrome (NMS) is a potentially lethal side effect of neuroleptic drugs, manifested by severe muscle rigidity and elevated temperature. It is also associated with some of the following: diaphoresis, dysphagia, tremor, incontinence, changes in level of consciousness, mutism, tachycardia, elevated or labile blood pressure, leucocytosis, and elevated serum CPK levels. NMS is not frequent and its incidence is 0.3~105%. There are only a few reports concerning the appearance of NMS in families. Neurologic disorders of the CNS are among the risk factors of NMS, and there is one recent report about the appearence of NMS in a patient with GM-ll [3). We report two cases of Jewish siblings sufferingfrom adult type GM2 gangliosidosis. The diagnosis of GM2wasbased on deteriorating neurological, especially motoric, function; cerebellar degeneration shown in brain CT and deficient Hex. A activity in serum leukocytes and skin fibroblasts. Both patients experienced acute psychosis with marked catatonic features. On the beginning of neuroleptic oral treatment, in moderate to very low dosages (7.5 mg haloperidol in the sister and levomepromazine 2.5 mg in the brother) both developed NMS. Following the recoveryfrom NMS, both patients' psychoses,including the catatonic features, were resistant to neuroleptic drugs and were successfully treated with electroconvulsive therapy. In conclusion, patients suffering from GM2 gangliosidosis with psychotic features may be a high risk group, liable to develop NMS. In addition, catatonia seems to be a prominent feature of the psychosis in these patients. The appearance of NMS as well as catatonia in patients suffering from the same genetic defect, suggestsa possibleoverlapof the two syndromes. References

[1] Navon R., AIgov Z. and Frisch A.(l986) Hexosaminidase A deficiency in adults. AmJ Med Gen 24: 179-196 [2] Goodman A.B. (1994) Medical conditions in Ashkenazi schizophrenic pedigrees. SchizBull 20: 507-517 [3] Rosebush P.I., MacQueenG.M., Clarke J.T.R., et aI. (1995) Late-onset TaySachs diseasepresenting as catatonicschizophrenia: Diagnostic and treatment issues. J Clin Psychiatry 56: 347-348.

IP.3.051 I factors Muscle enzymes and white blood count as risk for the neuroleptic malignant syndrome H. Hermesh,I. Manor,M. Gianella, H. Munitz, A. Weizman. Geha Psychiatric Hospital. RabinMedical Center, Petach Tiqva, P.O. Box 102, and SacklerFaculty ofMedicine. Tel Aviv University, Israel Neuroleptic Malignant Syndrome(NMS)is a potentially fatal side effect of neuroleptics. The DSM-IV criteria require severe muscle rigidity and elevated body temperature associatedwith the use of neuroleptics [1). At least two of the following signs should also be found: leucocytosis and elevated CK level, diaphoresis, dysphagia, tremor, incontinence, altered level of consciousness, mutism,tachycardia and labile blood pressure. Thereis almostno way to predictthe occurrence of NMSin an individual patient. Suggestedrisk factorsfor NMS are: previous NMS,agitation, restraining, I.M. injection, rapid dosage increase, affective disorder, and high ambient temperature [2]. Elevated CK levels have frequently been associated with acute psychosis (50%). We examined the hypothesis that psychosis-associated high levels of CK and WBC are risk factors

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for the development of NMS. This hypothesis stems from combining two observations; CPKemiaand leucocytosis are features of NMS, and markedCKernia occurring during acute psychosis characterizes specific patients (Manoret al., 1996,submitted for publication). The study population consisted of psychotic inpatients, and was divided into two groups: NMS group (N = 16) and non-NMS (NNMS) group, that served as a control group (N = 32). Two NNMS patients were matchedto each NMS patient by age (± 5 yrs.), gender, and year of first NMS episode. NMS patients had suffered at least one NNMS psychotic episode, clearly separated from the NMS episode they had, with at least one CK measurement during the beginning of each. BPRS score was > 40. NNMSpatientshad at least two separateacute psychoses and one CK measurement during the beginning of each. A survey of charts of all patients was conducted. Individual maximal retrograde and anterograde CK levels were recorded during each psychosis. CK levels during NMS episodes were excluded. CK levels were transformed to naturallogarithms (Ln). The Ln(AvgCK)s of NMS and of the NNMS groups were 6.46 ± 0.91 (911 ± 747 lUlL), and 5.24 ± 0.90 (343 ± 620 IU) respectively. Individual average of maximal CK levels during different psychoses (AvgCK) were calculated. Four ANOVARMs (1 x 3) demostrated that CK levelsin the NMSgroup were significantly higher than in the control group [F(2xJ5) = 10.5, P < 0.0001], whilst there were no significant difference betweenlevels of Ln(LDH),Ln(SGOT) and Ln(WBC) in the two groups[F(2x15) = 1.4,NS.;F(2xJ5) = 1.8,N.S. andF(2xI5) =0.47, N.S. respectively). Significant positive correlations were found betweenall the four measures [Pearson'sCorrelations = 0.30-0.75, P < 0.060-0.001) in the NNMSgroup but not in the NMS group. In conclusion, CK levels during acute NNMS psychoses are significantlyhigherin NMSpatients than in NNMSpatients.Levelsof the other three laboratory variables were not significantly different. Hence, high serum CK level in psychotic patients seems to be a specific risk factor for NMS in future psychoses. Practically, inclusion of CK in the initial routine battery of laboratory examinations of acutely psychotic patients seemsjustified. References [1] APA. Diagnostic andStatistical Manualof MentalDisorders (1994),4th edition, pp. 739-742, APA, Washington DC. [2] Keck,P.E.,Pope,H.G., Cohen,B.M., et aI. (1989)Riskfactorsfor neuroleptic malignant syndrome. Arch Gen Psychiatry 46, 914-918.

IP.3.052I

First episode schizophrenia: Treatment and outcome

Mario Amore,Magnani Katia, SerenaD' Ambrosio, Jose Mesa Mesa. Institute ofPsychiatry "P. Ottonello", University of BolognaViale Pepoli 5-40123-Bologna, Italy The outcome at five years of 52 patients who were elegible for a study of first schizophrenic episodes was assessed in terms of occupation, of number of days spent as an in-patient from the time of first admission, in terms of durationand nature of the disturbance preceding first admission, severity of symptomathology, and was related to premorbid social functioning. Patientswere recruitedover a 24-monthsfrom our inpatientunit. Only patients admitted for first-episode schizophrenia, diagnosed according to DSM-ill-R criteria, entered the study and were followed for up to five years. Patients withevidence of organicpsychosis, dementia, substanceabuse or I.Q. less than 70 were excluded. Treatment was not controlled to evaluate relationships between treatment and outcome. Patient were assessed with BPRS, CGI, SANS, SAPS, Premorbid Adjustment Scale and SCID-P. Patients showed a wide range of overall severity of psychopathology on admission as measured on BPRS totale scale score (range: 20-80). A history of good premorbid adjustment was found in 33.5% of cases; 50% showed a pattern of cronically poor functioning from adolescence through onset of first psychotic symptoms; 16.5% had a patternof progressive decline in functioning from adolescence through onsetof the firstpsychotic symptoms. The genderwasa distinctive factor: in the first group female patients had a better premorbidadjustment than