The Use of tDCS in a Patient with MECP2 Gene Mutation Presenting with Recurrent Catatonia: A Case Report

Methyl-CpG-binding protein 2 (MECP2) gene mutations are usually associated with Rett syndrome in females but are increasingly recognized as being responsible for a range of cranial, neurocognitive, and behavioral abnormalities, including catatonia, in males as well. ¹

Catatonia is a complex behavioral syndrome with varying etiologies that can be potentially fatal. ² Treatment options include general supportive measures, removal/correction of the cause if possible or identifiable, benzodiazepines, and electroconvulsive therapy (ECT). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are now being used for catatonia. ³

The aim of this case report of an adolescent male who presented with recurrent catatonia associated with an MECP2 gene mutation is to discuss the feasibility of using tDCS for therapeutic benefit in this condition. Written informed consent was obtained.

Case Report

An uneducated, right-handed male aged 17 years presented to the Dept. of Psychiatry with complaints of mutism, decreased oral intake, and posturing for about two weeks. There were no associated headaches, fevers, seizures, or focal neurologic deficits. There was no history suggestive of affective or psychotic illness. The Bush Francis Catatonia Rating Scale (BFCRS) score at the presentation was 6. A diagnosis of catatonia as per the DSM-5 diagnostic system was made. There was a history of five similar episodes over the past three years, lasting 3–4 weeks. These had been managed elsewhere, and there was no history of having received ECT in the past.

The patient was the first in birth order out of two children and was conceived out of a non-consanguineous marriage without regular antenatal visits. He was born at home by full-term normal vaginal delivery and cried immediately after birth. There was a delay in all developmental milestones and impairments in activities of daily living. The patient had an episode of epileptic seizure (ES) at the age of 8 years, with no recurrence. There was a history of intellectual disability among the mother and her two brothers.

The patient was noted to have microcephaly and large ears. Investigations included routine blood work, genetic testing, autoimmune markers, contrast-enhanced magnetic resonance imaging, a urine screen, and an electroencephalogram. Results were unremarkable except that on next-generation sequencing, he was detected with X-linked Syndromic 13 MRXS13 due to a mutation in the MECP2 gene. Diagnoses of intellectual developmental disorder (IDD) associated with the MECP2 mutation and recurrent catatonia were made.

General supportive measures were instituted. Oral lorazepam 8mg/day in four divided doses was given for three days but stopped after that as there was little improvement.

We considered ECT unsafe for this patient at this stage, considering his age, intellectual disability, and organic brain condition. rTMS was considered, but this technique requires patient cooperation and precise cranial targeting, which was difficult. rTMS is also associated with the risk of provoking an ES. Hence, a tDCS trial was instituted after receiving written informed consent from the parents. The usual safety protocols of the department, based on literature, were followed. ⁴ The stimulation parameters were 2 milliamperes (mA) of intensity administered for 20 minutes once daily with an anode at F3 (as per the 10-20 system) and a cathode at FP2 (right supraorbital area). ³ The Soterix 1x1 device with 5x5 cm carbon rubber electrodes fitted into a saline-saturated sponge was used. The patient tolerated tDCS well, and no adverse effects were noticed.

He received one session every day, started showing improvement after the third session, and was significantly improved by the eight session. Mutism improved first, followed by posturing and then negativism. Based on the maintenance of improvement and existing literature, ten sessions were administered. ³ BFCRS score was 0 after the tenth session. The mental status examination suggested intellectual disability, which was confirmed on a subsequent psychometric evaluation, in which his IQ was 63. No other active psychopathology was detected. On follow-up at one month, the patient was maintaining the improvement.

The index patient presented with cranial abnormalities, mild-to-moderate intellectual disability, and recurrent catatonia in a setting of MECP2 mutation. Catatonia can be a treatment challenge if the usual treatments are not effective or unsafe. rTMS has been used for catatonia in the past but was technically challenging and associated with the risk of provoking an ES in the index patient. ⁵ tDCS makes use of larger electrodes, may be more forgiving of minor targeting errors than rTMS, and may be safer with regard to the risk of ES. Thus, we used a commonly employed protocol for tDCS in catatonia. ³ To our knowledge, tDCS has not been used for this indication before. tDCS has been used safely for cognitive training in children with Rett syndrome. ⁶

Hypoactive/stuporous subtypes of catatonia may be associated with decreased dorsolateral prefrontal cortex (DLPFC) activity. Anodal stimulation is considered excitatory and, when delivered at F3 (overlying the DLPFC), may correct the hypoactivity in this region. ³

tDCS may be a useful and safe treatment modality for recurrent catatonia in males with the MECP2 mutation.