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CASE REPORT
Year : 2020  |  Volume : 4  |  Issue : 1  |  Page : 84-86

Schizophrenia with segawa syndrome: A therapeutic challenge


1 Department of Psychiatry, BJGMC and Sassoon General Hospital, Pune, Maharashtra, India
2 Department of Psychiatry, PCMC's Postgraduate Institute, Yashwantrao Chavan Memorial Hospital, Pune, Maharashtra, India

Date of Submission09-Jul-2019
Date of Decision09-Aug-2019
Date of Acceptance04-Sep-2019
Date of Web Publication30-May-2020

Correspondence Address:
Dr. Disha Devang Parikh
Department of Psychiatry, BJGMC and Sassoon General Hospital, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_41_19

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  Abstract 


Segawa syndrome is inherited dystonia characterized by gait disturbance and dystonia. The patients benefit from the treatment with levodopa. Although behavioral changes are known to be associated with this condition, there is limited literature on psychosis. Levodopa has been known to induce psychosis, while antipsychotics can exacerbate dystonia. Hence, a calculated approach is required for adequate management of both the conditions. This case report describes a 32-year-old male with dystonia for 20 years and psychotic symptoms for 16 years. He was on levodopa 250 mg BD for 5 years but was taking three times the prescribed dose for 3 years along with erratic antipsychotic treatment. He was successfully treated with levodopa 250 mg BD to control his dystonia symptoms and clozapine 200 mg for psychotic symptoms. Schizophrenia with Segawa syndrome is a rare presentation. The case was challenging owing to the complexity of presenting symptoms as well as the treatment.

Keywords: Clozapine, levodopa, schizophrenia, Segawa syndrome


How to cite this article:
Parikh DD, Panse SN. Schizophrenia with segawa syndrome: A therapeutic challenge. Ann Indian Psychiatry 2020;4:84-6

How to cite this URL:
Parikh DD, Panse SN. Schizophrenia with segawa syndrome: A therapeutic challenge. Ann Indian Psychiatry [serial online] 2020 [cited 2020 Oct 30];4:84-6. Available from: https://www.anip.co.in/text.asp?2020/4/1/84/285499




  Introduction Top


Segawa syndrome (dopa-responsive dystonia) is a rare condition characterized by childhood onset of limb dystonia that fluctuates diurnally and significantly improves with levodopa treatment.[1]

A recent review of the literature showed increased frequency of psychiatric symptoms in patients with Segawa syndrome. Patients with GCH1 gene mutation had more psychiatric comorbidities and sleep disturbances as compared to the general population.[2],[3] However, there is only one documented case of dopa-responsive dystonia and psychotic symptoms occurring together, treated with benztropine and risperidone.[4]

Here, we present a case report of schizophrenia with Segawa syndrome. The management of this patient was challenging, given that the medications used for these two conditions have a counteracting mechanism of actions, thus requiring a calculated approach to achieve the said balance.


  Case Report Top


A 32-year-old unmarried male was admitted for exacerbation of psychotic symptoms for 1 year. The patient had a history of painful dystonia in the neck and trunk for 20 years. He took symptomatic treatment from a local physician for initial 2–3 years. He also developed psychotic symptoms characterized by suspiciousness, hearing unreal voices, irritability, and unprovoked aggression for 16 years, for which he was prescribed different antipsychotics. After that, he had a continuous course of illness with alternate exacerbations of psychosis and dystonia due to poor drug adherence. He cited exacerbation of dystonia as a reason for poor drug adherence to antipsychotics. He consulted a neurologist 5 years ago and was diagnosed with primary dystonia. He was prescribed levodopa combination (levodopa 250 mg + carbidopa 25 mg BD) and was treated with 15 botulinum injections for the cervical dystonia over a period of 2 years. The dystonia symptoms got relieved significantly on taking levodopa. If levodopa was reduced, the patient reported rigidity in the neck and dysphoria. The patient himself took 2–3 times the prescribed dose of levodopa to relieve the symptoms for the past 3 years. He was also on aripiprazole 15 mg for psychosis for 2 years, which he took erratically.

On mental status examination, he had a delusion of persecution and second person auditory hallucinations. His affect was irritable. His social judgment was impaired and insight was lacking. He was diagnosed as paranoid schizophrenia with movement disorder and all his basic laboratory investigations were sent. He was started on T. Promethazine 25 mg to manage dystonia whereas T. Levodopa was withheld as he was taking exceeding amounts by himself.

A probable diagnosis of Segawa syndrome was made by the neurologist based on the history and clinical findings. Molecular testing was not done due to nonavailability. Levodopa combination (levodopa 250 mg + carbidopa 25 mg BD) was restarted as advised by the neurologist under strict supervision. The patient was then started on antipsychotic clozapine 12.5 mg, as it has the least propensity to cause dystonia (extrapyramidal symptoms). Clozapine was increased to 200 mg gradually over a period of 15 days. The severity of dystonia decreased, and psychosis improved significantly. Psychoeducation sessions were conducted regarding course and management of the comorbid disorders. He was discharged on day 28 and was well maintained on outpatient follow-ups.


  Discussion Top


Segawa syndrome is a rare autosomal dominant disorder with GCH1 gene mutation. GCH1 is an enzyme that mediates the biosynthesis of tetrahydrobiopterin, an essential cofactor in the production of dopamine.[1] Reduction in dopamine interferes with the brain's ability to produce smooth physical movement, resulting in dystonia and Parkinsonian symptoms.[1] The symptoms include gait disturbance, postural dystonia, or trunk and focal dystonias. There is a marked diurnal variation in the symptoms. The symptoms become noticeably worse in the evening than in the morning. The prognosis is good with early and adequate treatment. The patients usually show a dramatic and sustained improvement when treated with levodopa.[1] Botulinum toxin injection is given for focal dystonias.[5] However, levodopa can also contribute to psychotic exacerbation and associated with a dependence potential.

In some cases, mood or behavioral symptoms may occur. Recently, there has been research on the psychiatric symptoms of dopa-responsive dystonia. In a study of patients with GCH1 gene deficiency, it was found that they had increased frequency of major depressive disorders, anxiety disorder, obsessive-compulsive disorder, and sleep disturbances as compared to the general population.[2] Another study found that more than 50% of the cases with GCH1 mutation presented with psychiatric symptoms.[3]

The patient described here had both schizophrenia and Segawa syndrome. The psychotic symptoms could either be independent or secondary to the neurological disorder. Levodopa can also contribute to the psychosis, given that it has been known to cause behavioral changes in patients with Parkinson's disease.[6],[7],[8] Another phenomenon associated with chronic levodopa use is dopamine dysregulation syndrome (DDS). It is caused by dysfunction of the reward system. Individuals taking dopaminergic medications for an extended length of time can develop a dependence on the same. The patient takes increasing amount of medicine and is unwilling to decrease the dose. There is irritability, dysphoria, and anhedonia on reducing dose. The compulsive drug use is due to neuroadaptations in dopamine projections to the accumbens circuitry. They also tend to hoard levodopa.[9] These symptoms were seen in our patient, and thus, a balancing act was required to manage the dystonia and psychotic symptoms [Figure 1].
Figure 1: Dopamine imbalance is central to the three disorders as described

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Managing Segawa syndrome and comorbid psychosis is difficult because of the counteracting treatments for these two conditions. Levodopa given for the dystonia increases dopamine levels, which can worsen psychosis. On the other hand, antipsychotics are dopamine receptor blockers, worsening dystonia. In our case, we used levodopa combination to control his dystonia symptoms and clozapine 200 mg for treating psychotic symptoms. The rationale for choosing clozapine was that it has been shown to be effective at treating psychosis in patients with Parkinson's disease.[10]


  Conclusion Top


The comorbid conditions in our patient posed a therapeutic challenge. Additional factors such as dependence potential of medication also required attention. In this case, schizophrenia and Segawa syndrome with DDS were managed with a gradual titration of clozapine and levodopa.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wijemanne S, Jankovic J. Dopa-responsive dystonia – Clinical and genetic heterogeneity. Nat Rev Neurol 2015;11:414-24.  Back to cited text no. 1
    
2.
Van Hove JL, Steyaert J, Matthijs G, Legius E, Theys P, Wevers R, et al. Expanded motor and psychiatric phenotype in autosomal dominant Segawa syndrome due to GTP cyclohydrolase deficiency. J Neurol Neurosurg Psychiatry 2006;77:18-23.  Back to cited text no. 2
    
3.
Trender-Gerhard I, Sweeney MG, Schwingenschuh P, Mir P, Edwards MJ, Gerhard A, et al. Autosomal-dominant GTPCH1-deficient DRD: Clinical characteristics and long-term outcome of 34 patients. J Neurol Neurosurg Psychiatry 2009;80:839-45.  Back to cited text no. 3
    
4.
Wang M, Sison JI. Management of psychosis in a patient with probable Dopa-responsive dystonia. Case Rep Psychiatry 2018;2018:8040491.  Back to cited text no. 4
    
5.
Camargo CH, Cattai L, Teive HA. Pain relief in cervical dystonia with botulinum toxin treatment. Toxins (Basel) 2015;7:2321-35.  Back to cited text no. 5
    
6.
Klawans HL. Psychiatric side effects during the treatment of Parkinson's disease. In: Obeso JA, editor. Continuous dopaminergic stimulation in Parkinson's disease. J Neural Transm (Vienna) 1988;27:117-22.  Back to cited text no. 6
    
7.
Beaulieu-Boire I, Lang AE. Behavioral effects of levodopa. Mov Disord 2015;30:90-102.  Back to cited text no. 7
    
8.
Kehagia AA. Neuropsychiatric symptoms in Parkinson's disease: Beyond complications. Front Psychiatry 2016;7:110.  Back to cited text no. 8
    
9.
O'Sullivan SS, Evans AH, Lees AJ. Dopamine dysregulation syndrome: An overview of its epidemiology, mechanisms and management. CNS Drugs 2009;23:157-70.  Back to cited text no. 9
    
10.
Klein C, Gordon J, Pollak L, Rabey JM. Clozapine in Parkinson's disease psychosis: 5-year follow-up review. Clin Neuropharmacol 2003;26:8-11.  Back to cited text no. 10
    


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