Therapy‐refractory schizophrenia in a patient who previously suffered from Meige’s syndrome

Abstract The main symptoms of Meige's syndrome are involuntary eye blinking with muddled speech and uncontrollable contraction of the platysma muscle characterized by segmental, primarily oromandibular, dystonia (hyperkinesia). It can also develop after long‐term medication of first‐ and second‐generation antipsychotics. Here, we report the case of a Japanese female schizophrenic patient comorbid with Meige's syndrome and hyperthyroidism. We discuss the relationship between the three diseases, that is, schizophrenia, Meige's syndrome, and hyperthyroidism. Our intention is to consider the important role of the cerebral basal ganglia, where little attention has been given in regard to schizophrenia and Meige's syndrome. A part of this article was presented in a poster section at the joint congress of the 28th Annual Meeting of the Japanese Society of Clinical Neuropsychopharmacology and the 48th Annual Meeting of the Japanese Society of Neuropsychopharmacology held in 2018.

She took lessons in various arts such as flower arrangement and tea ceremony in the home. In year X-14 (33 years of age), she began to dislike her father and had a medical examination in our hospital.
In year X-1 (46 years of age), delusion of injury for a neighbor worsened, and in year X, she was admitted to our hospital. The case report was presented in 2011 2 .

| The first hospitalization
Following administration of QTP, CZP, and TSP, schizophrenic symptoms such as delusion of reference and that of injury as well as Meige's syndrome symptoms improved at the time, but the auditory hallucinations remained. In year X + 10 (56 years of age), she was released from the hospital to a public health care institution and had received regular outpatient treatment every 2 weeks in our hospital. The major antipsychotics were BNS, QTP, ANP, OLZ, HPD, and RIS with LZM and BPD as adjunctive drugs. After approximately 3.5 months, she attempted to automutilate her wrist and was admitted for the second time.

| The second hospitalization
She was treated mainly with ANP and HPD. During her hospitalization, she suffered from irregular bleeding from the genital organs and transferred to a gynecologic hospital. After uterus extirpation following diagnosis of uterocervical cancer, she was admitted for the third time to our hospital. During this hospitalization, her hyperthyroidism was diagnosed as Basedow's disease or Hashimoto's disease ( Figure 1). improved, but the auditory hallucination speaks in a low voice like a whisper and general fatigue persisted. Thyroid function recovered almost, but not completely, to normal after 7 months (Figure 1).

| D ISCUSS I ON
The disturbances in the motor circuit in the basal ganglia are associated with Parkinson's disease but often accompanied by psychiatric disorders such as depression and hallucination. On the other hand, the disturbances in the nonmotor circuits are also related to mental illness 5 . We discuss three points below. Because of the long history of her illness, dopamine supersensitivity psychosis (DSP) cannot be ruled out, but this possibility can be excluded on the diagnostic basis of DSP 9 .
2. Meige's syndrome symptoms were relieved by PAL as reported 3 and CZP but the auditory hallucinations, monologues, muttering, and nervous prostration had not comparably recovered ( Figure   1). She said that her monologues spontaneously came from her mouth repeating what she was hearing. It seemed to be echolalia. This is a symptom of an autopsychic depersonalization, that is, weakness of the self.
We used both PAL and CZP for the treatment of Meige's syndrome, so we cannot compare the mechanisms of the improvement by PAL alone (ie, compared to RIS) 3 . However, the following probable mechanisms of PAL may have contributed: a) its physicochemical property (ie, osmotic-controlled release oral delivery system), b) its hydroxyl group at position 9 on the tetrahydropyridopyrimidine ring may result in a differential potency of the availability of a second messenger (eg, cAMP, IP3, and Ca 2+ ) 10  3. Regarding the mechanisms of the auditory hallucinations, the selfmonitoring hypothesis 12 and retrogression toward the bicameral mind 13 have been proposed. Thought echo (her persistent monologue, see Figure 1) and bicameral mind resemble each other 13 .
Auditory hallucinations are an abnormal disposal of the information that comes from self-speech (inner speech). The origin of an abnormal disposal is laterality 14 and a bicameral mind 13 . The left brain belongs to oneself (self-brain), and the right brain belongs to another person (others-brain). In the future, laterality must be examined to distinguish self and nonself for detailed knowledge of auditory hallucinations.

ACK N OWLED G M ENT
We are grateful to Mr A. Tomita for assistance with the design of

CO N FLI C T O F I NTE R E S T
No potential COI to disclose.

DATA AVA I L A B I L I T Y S TAT E M E N T
All the data that are available are shown in the text and Figure 2.