Parkinsonism and Related Disorders 21 (2015) 1284e1285
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Parkinsonism Hyperpyrexia Syndrome following Deep Brain Stimulation Keywords: Parkinson Disease Parkinsonism Hyperpyrexia Syndrome Deep Brain Stimulation
Parkinsonism Hyperpyrexia Syndrome (PHS) is a potentially fatal complication resulting from rapid reduction or withdrawal of levodopa or dopamine agonists in patients with Parkinson Disease. Clinical features include acute onset worsening of rigidity, confusion and autonomic instability. The diagnosis is often delayed as signs are masked by underlying disease [1]. In patients undergoing Deep Brain Stimulation surgery, PHS is rarely seen as the dopaminergic medications are stopped or reduced before surgery to prevent drug induced dyskinesia during the procedure and to obtain an ‛Offstate which can clinically guide the surgeon during intraoperative stimulation. We hereby present case report of a patient developing PHS as a complication of DBS surgery. This case adds to the slowly growing list of PHS patients following Deep Brain Stimulation. Our patient underwent Deep Brain Stimulation surgery thirteen years after onset of Parkinson's disease. His medications prior to surgery were Levodopa (1.5 g/day along with carbidopa), Entacapone (800 mg), Ropinirole (6 mg) and Amantadine (300 mg). His ‘on’ period lasted for 1.5e2 h and was associated with generalized dyskinesia. Ropinirole, Amantadine and Entacapone were gradually tapered and stopped one day prior to surgery. He underwent DBS after overnight levodopa withdrawal (12-h). The total duration of surgery was 12 h. The leads were placed in bilateral subthalamic nuclei followed by Implantable Pulse Generator (IPG) under general anesthesia. Patient received levodopa/carbidopa (100/25 mg) during the surgery after lead placement on one side and levodopa was restarted after the surgery 12 h later. On the postoperative night he developed severe rigidity, tremors, high grade fever (103 F) with tachycardia and drowsiness. His investigations showed leukocytosis and CT Brain revealed mild pneumocephalus. He was managed with IV fluids, paracetamol, cold sponging, empirical antibiotics and levodopa doses were increased to 2 g/day. Dantrolene was unavailable. Patient continued to be drowsy and febrile on postoperative day 2; he was intubated. His Serum CPK level was elevated (34,433u) and rose to 74,000 and later 128,000 units in next two days; he had myoglobulinuria. On the 4th postoperative day he developed
http://dx.doi.org/10.1016/j.parkreldis.2015.08.004 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
acute renal failure. His level of sensorium improved, limb rigidity and tremors were reduced between day 4 and 8 and CPK reduced to 43,000. On 8th day while on antibiotics, he continued to have fever and the chest X ray showed consolidation. His blood cultures grew gram negative bacilli for which antibiotics were optimized. Despite treatment his renal parameters worsened and he required hemodialysis. The akinetic rigid state improved but his sensorium worsened due to sepsis. His DBS was never switched ‘on’ as the assessment and programming was not possible. He later developed septicemic shock and succumbed on the 16th postoperative day. PHS usually occurs between 18 h and 7 days following rapid reduction or withdrawal of dopaminergic medications [1]. Infection, dehydration, addition of neuroleptics, poor compliance and absorption of levodopa and spontaneous motor fluctuations are known precipitants. The pathogenesis of PHS is currently not known. It is believed to be due to acute suppression of dopaminergic activity in the hypothalamus, nigrostriatal system and in the mesocortical dopaminergic system [6]. The mortality is due to rhabdomyolysis, acute renal failure, sepsis, disseminated intravascular coagulation, deep vein thrombosis and pulmonary embolism. Management involves dopamine therapy, adequate hydration and management of complications [1]. Five patients with PHS following DBS reported in the literature including the present one are shown in Table 1. The common risk factor for PHS in patients undergoing DBS was withdrawal of levodopa in pre-operative period. All patients had PHS within first two days except one who developed after 24 days. The delayed PHS in this patient was attributed to presence of dyskinesia in postoperative period masking the PHS symptoms [5]. Subthalamic nucleus stimulation has confounding effects on development of PHS. It can mask the parkinsonian features like rigidity and tremor thereby delaying the diagnosis3. It can also accelerate the recovery in patients with PHS [2,4]. In conclusion, PHS is a rare but potentially fatal complication following DBS. The practice of levodopa reduction or withdrawal prior to surgery can predispose to PHS. This complication can be prevented by recommending DBS to PD patients at an earlier stage when they can tolerate ‘off’ period for a longer time. Levodopa administration immediately following lead placement while the patient is waiting for IPG placement is another option to prevent PHS. However this can lead to severe dyskinesia in the postoperative period.
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1284e1285
1285
Table 1 Pre and postoperative clinical characteristics of patients with Parkinsonism Hyperpyrexia Syndrome (PHS) following Deep Brain Stimulation surgery. Linazasoro et al. (2004) [3] Kim et al. (2010) [2] Marios et al. (2011) [4] Urasaki et al. (2013) [5] Present patient Mean Sex Age(yrs) Age at onset(yrs) Duration of Medication/Disease(yrs) LED(mg) Preop UPDRS III(OFF) H&Y stage Dyskinesias (%/day) Drug withdrawal time, hours Peak body temperature (Degree Celsius) Peak blood pressure(mm Hg) Pulse rate(beats/min) Peak CK level(u/L) Tremor Rigidity Post op day PHS developed DBS activation Result
F 58 39 18/19 2300 77 4 þ 12 39.8 190/120 Tachycardia Normal e e Second Yes Recovered
F 66 55 10/11 1900 55 4 þ(70) 12 39 170/90 128 786 þ þ First Yes Recovered
M 54 40 NA/14 725 NA NA NA 18 40 165/94 e 1500 þ þ First Yes Recovered
F M 75 49 61 36 14/14 13/13 415 1500 NA 46 NA 4 NA þ(100) Reduced while DBS-ON Reduced 41 39.4 200/90 140/80 e 140 3711 1,28,000 þ þ þ Twenty fourth First Yes No Expired(MI) Expired(Sepsis)
57.67 43.5 12.6/14.2 1890 59.3
CK e Creatine kinase, H&Y e Hoehn and Yahr stage, LED e Levodopa equivalent dose, NA e Not available, UPDRS III e Unified Parkinson's Disease Rating Scale III.
References
Kudlu Village, Hosur Main Road, Bangalore, 560068, India
[1] Edward J. Newman, Donald G. Grosset, Peter G.E. Kennedy, The Parkinsonismhyperpyrexia syndrome, Neurocrit. Care 10 (2009) 136e140. [2] J.H. Kim, T.H. Kwon, S.B. Koh, J.Y. Park, Parkinsonismehyperpyrexia syndrome after deep brain stimulation surgery: case report, Neurosurgery 66 (2010) E1029. [3] G. Linazasoro, N.V. Blercom, A. Castro, Maria Dolores Dapena. Subthalamic deep brain stimulation masking possible malignant syndrome in Parkinson disease, Neurology 63 (2004) 589e590. [4] Marios S. Themistocleous, Efstathios J. Boviatsis, Lampis C. Stavrinou, Pantelis Stathis, Damianos E. Sakas, Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report, J. Med. Case Rep. 5 (2011) 255. [5] E. Urasaki, T. Fukudome, M. Hirose, S. Nakane, H. Matsuo, Y. Yamakawa, Neuroleptic malignant syndrome (parkinsonismehyperpyrexia syndrome)after deep brain stimulation of the subthalamic nucleus, J. Clin. Neurosci. 20 (5) (2013) 740e741. [6] Yoshikuni Mizunoa, Hideki Takubob, Eiiji Mizutac, Sadako Kuno, Malignant syndrome in Parkinson's disease: concept and review of the literature, Parkinsonism Relat. Disord. 9 (2013) S3eS9.
Shyla T. Govindappa, Masoom M. Abbas Parkinson's and Ageing Research Foundation, No 58, C/12, Micro Lab Compound,
Guruprasad Hosurkar Columbia Asia Hospital, 26/4, Brigade Gateway, Beside Metro, Malleswaram West, Bangalore, 560055, India Ravi Gopal Varma M S Ramaiah Medical College, New B E L Road, M S Ramaiah Nagar, MSRIT Post, Bangalore, 560054, India Uday B. Muthane* Parkinson's and Ageing Research Foundation, No 58, C/12, Micro Lab Compound, Kudlu Village, Hosur Main Road, Bangalore, 560068, India * Corresponding author. E-mail addresses: [email protected], [email protected] (U.B. Muthane).
9 June 2015
Contents lists available at ScienceDirect
Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis
Letter to the Editor
Parkinsonism Hyperpyrexia Syndrome following Deep Brain Stimulation Keywords: Parkinson Disease Parkinsonism Hyperpyrexia Syndrome Deep Brain Stimulation
Parkinsonism Hyperpyrexia Syndrome (PHS) is a potentially fatal complication resulting from rapid reduction or withdrawal of levodopa or dopamine agonists in patients with Parkinson Disease. Clinical features include acute onset worsening of rigidity, confusion and autonomic instability. The diagnosis is often delayed as signs are masked by underlying disease [1]. In patients undergoing Deep Brain Stimulation surgery, PHS is rarely seen as the dopaminergic medications are stopped or reduced before surgery to prevent drug induced dyskinesia during the procedure and to obtain an ‛Offstate which can clinically guide the surgeon during intraoperative stimulation. We hereby present case report of a patient developing PHS as a complication of DBS surgery. This case adds to the slowly growing list of PHS patients following Deep Brain Stimulation. Our patient underwent Deep Brain Stimulation surgery thirteen years after onset of Parkinson's disease. His medications prior to surgery were Levodopa (1.5 g/day along with carbidopa), Entacapone (800 mg), Ropinirole (6 mg) and Amantadine (300 mg). His ‘on’ period lasted for 1.5e2 h and was associated with generalized dyskinesia. Ropinirole, Amantadine and Entacapone were gradually tapered and stopped one day prior to surgery. He underwent DBS after overnight levodopa withdrawal (12-h). The total duration of surgery was 12 h. The leads were placed in bilateral subthalamic nuclei followed by Implantable Pulse Generator (IPG) under general anesthesia. Patient received levodopa/carbidopa (100/25 mg) during the surgery after lead placement on one side and levodopa was restarted after the surgery 12 h later. On the postoperative night he developed severe rigidity, tremors, high grade fever (103 F) with tachycardia and drowsiness. His investigations showed leukocytosis and CT Brain revealed mild pneumocephalus. He was managed with IV fluids, paracetamol, cold sponging, empirical antibiotics and levodopa doses were increased to 2 g/day. Dantrolene was unavailable. Patient continued to be drowsy and febrile on postoperative day 2; he was intubated. His Serum CPK level was elevated (34,433u) and rose to 74,000 and later 128,000 units in next two days; he had myoglobulinuria. On the 4th postoperative day he developed
http://dx.doi.org/10.1016/j.parkreldis.2015.08.004 1353-8020/© 2015 Elsevier Ltd. All rights reserved.
acute renal failure. His level of sensorium improved, limb rigidity and tremors were reduced between day 4 and 8 and CPK reduced to 43,000. On 8th day while on antibiotics, he continued to have fever and the chest X ray showed consolidation. His blood cultures grew gram negative bacilli for which antibiotics were optimized. Despite treatment his renal parameters worsened and he required hemodialysis. The akinetic rigid state improved but his sensorium worsened due to sepsis. His DBS was never switched ‘on’ as the assessment and programming was not possible. He later developed septicemic shock and succumbed on the 16th postoperative day. PHS usually occurs between 18 h and 7 days following rapid reduction or withdrawal of dopaminergic medications [1]. Infection, dehydration, addition of neuroleptics, poor compliance and absorption of levodopa and spontaneous motor fluctuations are known precipitants. The pathogenesis of PHS is currently not known. It is believed to be due to acute suppression of dopaminergic activity in the hypothalamus, nigrostriatal system and in the mesocortical dopaminergic system [6]. The mortality is due to rhabdomyolysis, acute renal failure, sepsis, disseminated intravascular coagulation, deep vein thrombosis and pulmonary embolism. Management involves dopamine therapy, adequate hydration and management of complications [1]. Five patients with PHS following DBS reported in the literature including the present one are shown in Table 1. The common risk factor for PHS in patients undergoing DBS was withdrawal of levodopa in pre-operative period. All patients had PHS within first two days except one who developed after 24 days. The delayed PHS in this patient was attributed to presence of dyskinesia in postoperative period masking the PHS symptoms [5]. Subthalamic nucleus stimulation has confounding effects on development of PHS. It can mask the parkinsonian features like rigidity and tremor thereby delaying the diagnosis3. It can also accelerate the recovery in patients with PHS [2,4]. In conclusion, PHS is a rare but potentially fatal complication following DBS. The practice of levodopa reduction or withdrawal prior to surgery can predispose to PHS. This complication can be prevented by recommending DBS to PD patients at an earlier stage when they can tolerate ‘off’ period for a longer time. Levodopa administration immediately following lead placement while the patient is waiting for IPG placement is another option to prevent PHS. However this can lead to severe dyskinesia in the postoperative period.
Letter to the Editor / Parkinsonism and Related Disorders 21 (2015) 1284e1285
1285
Table 1 Pre and postoperative clinical characteristics of patients with Parkinsonism Hyperpyrexia Syndrome (PHS) following Deep Brain Stimulation surgery. Linazasoro et al. (2004) [3] Kim et al. (2010) [2] Marios et al. (2011) [4] Urasaki et al. (2013) [5] Present patient Mean Sex Age(yrs) Age at onset(yrs) Duration of Medication/Disease(yrs) LED(mg) Preop UPDRS III(OFF) H&Y stage Dyskinesias (%/day) Drug withdrawal time, hours Peak body temperature (Degree Celsius) Peak blood pressure(mm Hg) Pulse rate(beats/min) Peak CK level(u/L) Tremor Rigidity Post op day PHS developed DBS activation Result
F 58 39 18/19 2300 77 4 þ 12 39.8 190/120 Tachycardia Normal e e Second Yes Recovered
F 66 55 10/11 1900 55 4 þ(70) 12 39 170/90 128 786 þ þ First Yes Recovered
M 54 40 NA/14 725 NA NA NA 18 40 165/94 e 1500 þ þ First Yes Recovered
F M 75 49 61 36 14/14 13/13 415 1500 NA 46 NA 4 NA þ(100) Reduced while DBS-ON Reduced 41 39.4 200/90 140/80 e 140 3711 1,28,000 þ þ þ Twenty fourth First Yes No Expired(MI) Expired(Sepsis)
57.67 43.5 12.6/14.2 1890 59.3
CK e Creatine kinase, H&Y e Hoehn and Yahr stage, LED e Levodopa equivalent dose, NA e Not available, UPDRS III e Unified Parkinson's Disease Rating Scale III.
References
Kudlu Village, Hosur Main Road, Bangalore, 560068, India
[1] Edward J. Newman, Donald G. Grosset, Peter G.E. Kennedy, The Parkinsonismhyperpyrexia syndrome, Neurocrit. Care 10 (2009) 136e140. [2] J.H. Kim, T.H. Kwon, S.B. Koh, J.Y. Park, Parkinsonismehyperpyrexia syndrome after deep brain stimulation surgery: case report, Neurosurgery 66 (2010) E1029. [3] G. Linazasoro, N.V. Blercom, A. Castro, Maria Dolores Dapena. Subthalamic deep brain stimulation masking possible malignant syndrome in Parkinson disease, Neurology 63 (2004) 589e590. [4] Marios S. Themistocleous, Efstathios J. Boviatsis, Lampis C. Stavrinou, Pantelis Stathis, Damianos E. Sakas, Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report, J. Med. Case Rep. 5 (2011) 255. [5] E. Urasaki, T. Fukudome, M. Hirose, S. Nakane, H. Matsuo, Y. Yamakawa, Neuroleptic malignant syndrome (parkinsonismehyperpyrexia syndrome)after deep brain stimulation of the subthalamic nucleus, J. Clin. Neurosci. 20 (5) (2013) 740e741. [6] Yoshikuni Mizunoa, Hideki Takubob, Eiiji Mizutac, Sadako Kuno, Malignant syndrome in Parkinson's disease: concept and review of the literature, Parkinsonism Relat. Disord. 9 (2013) S3eS9.
Shyla T. Govindappa, Masoom M. Abbas Parkinson's and Ageing Research Foundation, No 58, C/12, Micro Lab Compound,
Guruprasad Hosurkar Columbia Asia Hospital, 26/4, Brigade Gateway, Beside Metro, Malleswaram West, Bangalore, 560055, India Ravi Gopal Varma M S Ramaiah Medical College, New B E L Road, M S Ramaiah Nagar, MSRIT Post, Bangalore, 560054, India Uday B. Muthane* Parkinson's and Ageing Research Foundation, No 58, C/12, Micro Lab Compound, Kudlu Village, Hosur Main Road, Bangalore, 560068, India * Corresponding author. E-mail addresses: [email protected], [email protected] (U.B. Muthane).
9 June 2015
