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

We read with interest the article by Adarsh et al. about a 17-year-old boy who had been suffering from mutism, decreased oral intake, and posturing for two weeks and scored 6 on the Bush-Francis Catatonia Rating Scale (BFCRS), which is why he was diagnosed as catatonia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic system. ¹ Such episodes had already occurred five times in the last three years and lasted three to four weeks. ¹ His medical history also included developmental delay, impaired activities of daily living, microcephaly, dysmorphism (large ears), and epileptic seizures at the age of eight years. ¹ Next-generation sequencing revealed a mutation in the MECP2 gene, which is why the patient was diagnosed with intellectual developmental disorder with X-linked syndromic 13 (MRXS13). ¹ The patient benefited significantly from transcranial direct current stimulation (tDCS). ¹ The study is convincing, but several points need to be discussed.

The first point is that the specific mutation in the MEPC2 gene that was held responsible for the phenotype of the index patient has not been reported. In order to assess whether the specific variant discovered in the index patient was truly pathogenic, it is necessary to know the specific variant, whether it occurred in homozygous or heterozygous form, whether it was inherited or sporadic, and whether the variant segregated with the phenotype in other affected first-degree relatives.

The second point is that none of the first-degree relatives were tested for the mutation. ¹ Since the mother and two of her brothers had a family history of intellectual disability, it would have been mandatory to test at least these three patients for the presence of the MECP2 mutation, which is held responsible for the phenotype of the index patient.

The third point is that the patient’s cerebrospinal fluid was not examined (CSF) to rule out meningitis, encephalitis, or vasculitis. Since catatonia can be a manifestation of encephalitis or meningitis, ² it would have been imperative to examine the CSF of the index patient for lymphocytic or granulocytic pleocytosis, CSF cultures, and virus panels.

The fourth point is that the index patient was not tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since SARS-CoV-2 infections have been reported to be associated with catatonia, ³ and since the case apparently occurred during the pandemic, it would have been imperative to rule out SARS-CoV-2 infection as the cause of the catatonia.

The fifth point is that the efficacy of a treatment cannot be assessed on the basis of a single case, but an appropriate study design with a sufficient number of patients is required. Whether tDCS is truly beneficial in patients with hypoactive (stuporous) catatonia can only be assessed by appropriately designed multicenter studies with sufficiently powered and homogeneous cohorts.

The sixth point is that tDCS is not free from adverse side effects. Although they are usually mild and limited to itching, tingling, headache, burning, and discomfort, ⁴ some cases have been reported in which tDCS was complicated by seizures. ⁵

In conclusion, this interesting study has limitations that relativize the results and their interpretation. Removing these limitations could strengthen the conclusions and reinforce the message of the study. Before catatonia can be attributable to a MECP2 variant, its pathogenicity needs to be established. Whether tDCS is truly beneficial in stuporous catatonia needs to be investigated in appropriately designed studies.