Neuroleptic malignant syndrome in a child treated with an atypical antipsychotic.

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.

Biochemical alterations during medication withdrawal in Parkinson's disease with and without neuroleptic malignant-like syndrome.

The object was to assess alterations in CSF concentrations of monoamine metabolites during withdrawal of medication in patients with Parkinson's disease in relation to the presence or absence of episodes resembling neuroleptic malignant syndrome (NMS). This syndrome is a fatal condition developing after neuroleptic therapy, and a neuroleptic malignant-like syndrome (NMLS) may also occur after withdrawal of antiparkinsonian drugs in patients with Parkinson's disease. Previous biochemical assays showed that the CSF concentration of the dopamine metabolite homovanillic acid (HVA) is an independent prognostic factor for development of NMLS in patients with Parkinson's disease. In the present study, CSF concentrations of HVA, the noradrenaline (norepinephrine) metabolite 3-methoxy-4-hydroxyphenylethylene glycol, and the serotonin metabolite 5-hydroxyindole acetic acid were assayed using high performance liquid chromatography with electrochemical detection. The study population consisted of nine patients with Parkinson's disease with NMLS and 12 without NMLS, in whom metabolites were assayed during both withdrawal and remedicated periods. Concentrations of HVA in the CSF were significantly lower during the withdrawal period than the medicated period regardless of whether patients developed NMLS, and HVA concentrations were comparably increased after remedication in both groups. However, HVA concentrations were significantly lower in patients with NMLS than in those without NMLS during both withdrawal and medicated periods. Other metabolites showed no significant differences. The present data provide further biochemical evidence for extremely suppressed central dopaminergic activity during NMLS, which may indicate a narrow safety margin for medication withdrawal in patients with Parkinson's disease.

Does dantrolene influence central dopamine and serotonin metabolism in the neuroleptic malignant syndrome? A retrospective study.

Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the cerebrospinal fluid (CSF) were determined twice in nine cases of neuroleptic malignant syndrome (NMS) during the active phase. During the test period, three cases received no dantrolene and six cases received dantrolene prior to the second CSF examination. In the group not administered dantrolene, the levels of HVA and 5-HIAA were lower on the second examination compared to the first, suggesting that the levels of these substances decreased during the course of NMS. In the group receiving dantrolene, the levels of HVA and 5-HIAA increased after administration compared with the preadministration levels. In particular, a significant difference in the changes in HVA was demonstrated between the two groups. This suggests that dantrolene influences central dopaminergic metabolism in the active phase of NMS.

Neuroleptic malignant syndrome: a study of CSF monoamine metabolism.

In 8 cases of typical neuroleptic malignant syndrome (NMS), homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), noradrenaline (NA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in the cerebrospinal fluid (CSF) were assayed during both the active phase of NMS and after recovery. Compared with levels in normal control subjects the levels of HVA were significantly lower in patients with active NMS. This finding supports the central dopamine blockade theory of NMS pathophysiology. In addition, the levels of HVA were significantly decreased after recovery, suggesting that there may be a decreased dopamine metabolism in patients susceptible to NMS. The levels of 5-HIAA in patients with active NMS and after recovery were also significantly lower than those in normal control group, suggesting a relationship between the development of NMS and a disturbance of serotonin metabolism. The levels of NA in patients with active NMS were significantly higher than in normal subjects, and were within normal range after recovery. The levels of MHPG had a tendency to increase in patients with active NMS, compared with levels during recovery. These findings are a result of increased sympathetic nervous system activity in patients with active NMS; however, they are also observed in other disorders and may well reflect the physical stress caused by NMS.

[Clinical course and CSF monoamine metabolism in neuroleptic malignant syndrome--a study of nine typical cases and five mild cases].

In nine typical cases and five mild cases of neuroleptic malignant syndrome (NMS), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in the cerebrospinal fluid (CSF) were assayed both during the active phase of NMS and after recovery. Compared with levels in normal control subjects, the levels of HVA were significantly lower in the active phase of typical NMS. This finding supports the central dopamine blockade theory of NMS pathophysiology. In addition, the levels of HVA were significantly decreased after recovery from typical NMS. This suggests that there may be a decreased dopamine metabolism in patients susceptible to NMS. The levels of 5-HIAA in the active phase of typical NMS and after recovery were also significantly lower than those in normal control group, suggesting a relationship between the development of NMS and a disturbance of serotonin metabolism. In mild cases, the levels of HVA and 5-HIAA in the active phase of NMS and after recovery were not different from those in normal control subjects. This suggests that there may be a difference in dopamine and serotonin metabolism between typical cases and mild cases. In both cases, the levels of NA in patients with active NMS were significantly higher than in normal subjects, and were within a normal range after recovery. The levels of MHPG were significantly increased in the active phase of typical NMS and had a tendency to increase in the active phase of mild cases, compared with levels in normal control subjects. The levels of MHPG after recovery in both cases were not different from those in normal control subjects. These findings are a result of increased sympathetic activity in active NMS. However, these findings are also observed in other disorders and probably reflect the physical stress caused by NMS.