Reminder of important clinical lesson
CASE REPORT
Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary Rupal Dosi, Annirudh Ambaliya, Harshal Joshi, Rushad Patell Department of Medicine, Medical College Baroda, Vadodara, Gujarat, India Correspondence to Dr Rushad Patell, [email protected] Accepted 6 June 2014
SUMMARY Serotonin syndrome and neuroleptic malignant syndrome are two drug toxidromes that have often overlapping and confusing clinical pictures. We report a case of a young man who presented with alteration of mental status, autonomic instability and neuromuscular hyperexcitability following ingestion of multiple psychiatric and antiepileptic medications. The patient satisfied criteria for serotonin syndrome and neuroleptic malignant syndrome, and based on the characteristic clinical features, laboratory findings and clinical course it was concluded that the patient had both toxidromes. The patient was managed with cyproheptadine and supportive measures, and recovered over the course of 3 weeks. A brief review of literature highlighting the diagnostic clues as well as the importance of recognising and distinguishing the often missed and confounding diagnoses follows.
BACKGROUND
To cite: Dosi R, Ambaliya A, Joshi H, et al. BMJ Case Rep Published online: [ please include Day Month Year] doi:10.1136/ bcr-2014-204154
Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are relatively rare, life-threatening adverse reactions to psychotropic medications. SS is a result of excessive stimulation of serotoninergic receptors in the peripheral and central nervous system (CNS), as a consequence of a variety of proserotinergic agents.1 2 NMS is on the other hand an idiopathic drug reaction to antipsychotics.3 It is important to be aware of the fact that both these uncommon diagnoses can often be missed, in part due to the fact that a significant proportion of prescribing doctors are not familiar with SS.4 As there is no specific diagnostic test, a high index of suspicion and an active effort to rule out other possible diagnoses is essential. Although culprit agents are often very useful in differentiating the two syndromes, polypharmacy, as in the case described, can make this valueless. SS is predominately a hyperkinetic syndrome with characteristic lower limb hyper-reflexia as opposed to the marked rigidity and hyporeflexia in NMS; however, several other overlapping clinical features make the two entities difficult to differentiate. Laboratory features have been described as being valuable to distinguish the two similarly presenting toxidromes, but are overall non-specific. There is a considerable difference in the overall clinical course that can be useful in separating the two; however, this is often not possible to assess during the first consultation and needs periodic review and frequent clinical evaluations to determine. Owing to the possible calamitous outcomes, patients should be recognised early, monitored closely and if
Dosi R, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204154
necessary managed aggressively. The importance of differentiating the two is even further heightened by the fact that bromocriptine, recommended in NMS has been shown to worsen SS and should be avoided; moreover, some neuroleptics have been suggested as agents in SS but can potentially precipitate and worsen NMS. Early and careful consideration of both diagnoses in the acute and critical care setting is recommended and an algorithm to handle such scenarios has been suggested.5
CASE PRESENTATION A 19-year-old male patient presented with a 4-month history of steadily worsening hallucinations and delusions. For these symptoms he was initially treated by a psychiatrist and started on valproate, lithium, olanzapine, risperidone and clonazepam. On the second day of starting the medication he developed excessive perspiration, rigors, high-grade continuous fever, agitation and aggressive behaviour. Initially considering this as an aggravation of his psychiatric behaviour the psychiatrist continued with the medications, which were eventually stopped after 4 days. Over the next 4–5 days of continuing medications his condition deteriorated so that he was completely non-responsive, akinetic and had no oral intake. He continued to have high-grade continuous fever and also developed diarrhoea. The patient was transferred to a hospital with a working diagnosis of metabolic versus infectious encephalopathy. There was no history of headache, photophobia, neck stiffness, vomiting, diplopia, jaundice, reduced urine output, convulsions, abnormal movements or posturing. There was no history of illicit drug use. The patient had been treated for a psychiatric illness about 2 years before this presentation but he was not on any medications for more than 18 months. On transfer to our service the patient was lying immobile in bed and not responding to commands. He had a temperature of 105°F (not responding to acetaminophen), was tachycardic (pulse 112/min) and tachypnoeic (respiratory rate 28/min). His blood pressure was 130/82 mm Hg. Also carpopedal spam was noted (figure 1) although Chvostek’s sign was negative. On a more detailed neurological examination, Glasgow Coma Scale was 6/15 (M4V1E1). A limited cranial nerve examination in the comatose patient revealed no abnormality. Pupils were noted to be bilaterally equal, round in shape, dilated and sluggishly reacting to light. Hypertonia was obvious 1
Reminder of important clinical lesson as serum parathormone levels were within normal levels. Serum creatine kinase levels were elevated 15 000 U/L (24–95) and serum iron was decreased to 30 μg/dL (49–181). Blood cultures and cerebrospinal fluid (CSF) analysis were normal. MRI of the brain did not reveal any abnormalities. EEG showed mild diffuse slowing but no epileptic activity. Serum thyroid-stimulating hormone was normal, urine porphobilinogen was negative and serum ceruloplasmin was within normal limits. Serum lithium levels were within therapeutic range (1.4 mmol/L, 0.5–1.5). A urine toxicological screen was run to rule out drug abuse. An ultrasound examination of the abdomen was normal. However, a chest roentgenogram revealed a paracardiac shadow suggestive of consolidation on the right.
DIFFERENTIAL DIAGNOSIS Figure 1 Carpopedal spasm was noted, corresponding to the hypocalcaemia.
in all four limbs (lead pipe rigidity) and hyper-reflexia including bilateral sustained ankle clonus was elicited (video 1). No other catatonic features such as waxy flexibility, posturing, persistence or automatic obedience were noted. Planter reflexes were down going. Also of note were hyperkinetic bowel sounds on auscultation of the abdomen.
INVESTIGATIONS Laboratory investigations revealed haemoglobin of 11.1 g/dL (13–18) normocytic and normochromic indices, raised leucocyte count of 15 300/mm3 (4000–11 000/mm3), elevated erythrocyte sedimentation rate 32 mm at the end of first hour and C reactive protein 67 mg/dL (
CASE REPORT
Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary Rupal Dosi, Annirudh Ambaliya, Harshal Joshi, Rushad Patell Department of Medicine, Medical College Baroda, Vadodara, Gujarat, India Correspondence to Dr Rushad Patell, [email protected] Accepted 6 June 2014
SUMMARY Serotonin syndrome and neuroleptic malignant syndrome are two drug toxidromes that have often overlapping and confusing clinical pictures. We report a case of a young man who presented with alteration of mental status, autonomic instability and neuromuscular hyperexcitability following ingestion of multiple psychiatric and antiepileptic medications. The patient satisfied criteria for serotonin syndrome and neuroleptic malignant syndrome, and based on the characteristic clinical features, laboratory findings and clinical course it was concluded that the patient had both toxidromes. The patient was managed with cyproheptadine and supportive measures, and recovered over the course of 3 weeks. A brief review of literature highlighting the diagnostic clues as well as the importance of recognising and distinguishing the often missed and confounding diagnoses follows.
BACKGROUND
To cite: Dosi R, Ambaliya A, Joshi H, et al. BMJ Case Rep Published online: [ please include Day Month Year] doi:10.1136/ bcr-2014-204154
Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are relatively rare, life-threatening adverse reactions to psychotropic medications. SS is a result of excessive stimulation of serotoninergic receptors in the peripheral and central nervous system (CNS), as a consequence of a variety of proserotinergic agents.1 2 NMS is on the other hand an idiopathic drug reaction to antipsychotics.3 It is important to be aware of the fact that both these uncommon diagnoses can often be missed, in part due to the fact that a significant proportion of prescribing doctors are not familiar with SS.4 As there is no specific diagnostic test, a high index of suspicion and an active effort to rule out other possible diagnoses is essential. Although culprit agents are often very useful in differentiating the two syndromes, polypharmacy, as in the case described, can make this valueless. SS is predominately a hyperkinetic syndrome with characteristic lower limb hyper-reflexia as opposed to the marked rigidity and hyporeflexia in NMS; however, several other overlapping clinical features make the two entities difficult to differentiate. Laboratory features have been described as being valuable to distinguish the two similarly presenting toxidromes, but are overall non-specific. There is a considerable difference in the overall clinical course that can be useful in separating the two; however, this is often not possible to assess during the first consultation and needs periodic review and frequent clinical evaluations to determine. Owing to the possible calamitous outcomes, patients should be recognised early, monitored closely and if
Dosi R, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2014-204154
necessary managed aggressively. The importance of differentiating the two is even further heightened by the fact that bromocriptine, recommended in NMS has been shown to worsen SS and should be avoided; moreover, some neuroleptics have been suggested as agents in SS but can potentially precipitate and worsen NMS. Early and careful consideration of both diagnoses in the acute and critical care setting is recommended and an algorithm to handle such scenarios has been suggested.5
CASE PRESENTATION A 19-year-old male patient presented with a 4-month history of steadily worsening hallucinations and delusions. For these symptoms he was initially treated by a psychiatrist and started on valproate, lithium, olanzapine, risperidone and clonazepam. On the second day of starting the medication he developed excessive perspiration, rigors, high-grade continuous fever, agitation and aggressive behaviour. Initially considering this as an aggravation of his psychiatric behaviour the psychiatrist continued with the medications, which were eventually stopped after 4 days. Over the next 4–5 days of continuing medications his condition deteriorated so that he was completely non-responsive, akinetic and had no oral intake. He continued to have high-grade continuous fever and also developed diarrhoea. The patient was transferred to a hospital with a working diagnosis of metabolic versus infectious encephalopathy. There was no history of headache, photophobia, neck stiffness, vomiting, diplopia, jaundice, reduced urine output, convulsions, abnormal movements or posturing. There was no history of illicit drug use. The patient had been treated for a psychiatric illness about 2 years before this presentation but he was not on any medications for more than 18 months. On transfer to our service the patient was lying immobile in bed and not responding to commands. He had a temperature of 105°F (not responding to acetaminophen), was tachycardic (pulse 112/min) and tachypnoeic (respiratory rate 28/min). His blood pressure was 130/82 mm Hg. Also carpopedal spam was noted (figure 1) although Chvostek’s sign was negative. On a more detailed neurological examination, Glasgow Coma Scale was 6/15 (M4V1E1). A limited cranial nerve examination in the comatose patient revealed no abnormality. Pupils were noted to be bilaterally equal, round in shape, dilated and sluggishly reacting to light. Hypertonia was obvious 1
Reminder of important clinical lesson as serum parathormone levels were within normal levels. Serum creatine kinase levels were elevated 15 000 U/L (24–95) and serum iron was decreased to 30 μg/dL (49–181). Blood cultures and cerebrospinal fluid (CSF) analysis were normal. MRI of the brain did not reveal any abnormalities. EEG showed mild diffuse slowing but no epileptic activity. Serum thyroid-stimulating hormone was normal, urine porphobilinogen was negative and serum ceruloplasmin was within normal limits. Serum lithium levels were within therapeutic range (1.4 mmol/L, 0.5–1.5). A urine toxicological screen was run to rule out drug abuse. An ultrasound examination of the abdomen was normal. However, a chest roentgenogram revealed a paracardiac shadow suggestive of consolidation on the right.
DIFFERENTIAL DIAGNOSIS Figure 1 Carpopedal spasm was noted, corresponding to the hypocalcaemia.
in all four limbs (lead pipe rigidity) and hyper-reflexia including bilateral sustained ankle clonus was elicited (video 1). No other catatonic features such as waxy flexibility, posturing, persistence or automatic obedience were noted. Planter reflexes were down going. Also of note were hyperkinetic bowel sounds on auscultation of the abdomen.
INVESTIGATIONS Laboratory investigations revealed haemoglobin of 11.1 g/dL (13–18) normocytic and normochromic indices, raised leucocyte count of 15 300/mm3 (4000–11 000/mm3), elevated erythrocyte sedimentation rate 32 mm at the end of first hour and C reactive protein 67 mg/dL (
