Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a devastating genetic white matter disorder whose onset often is characterized by neuropsychiatric symptoms followed or accompanied by motor impairment. To date, no cure exists for ALSP and patients rely on symptomatic treatment. Repetitive transcranial magnetic stimulation (rTMS) has never been used in patients with psychiatric symptoms secondary to genetic leukoencephalopathies.

A 54-year-old patient diagnosed with ALSP presented personality changes (e.g. verbal aggression, impulsivity, temper tantrums, and increasing judgement difficulties at work) and new-onset mood fluctuations, anxiety, and sleep disturbances. Bilateral 10 Hz rTMS stimulation of the dorsolateral prefrontal cortex (DLPFC) was used for most of the treatment course and a total of 62 treatment sessions were administered.The patient was assessed pre-, during and post-treatment with standardized tests: the Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ9) and Montreal Cognitive Assessment (MoCA).

After one month of treatment, the patient self-reported amelioration in energy level, mood, sleep, and ability to regulate emotions. Standardized test results reflected the improvement. The patient took two breaks from rTMS treatment and both times we observed mild decrease in mood, increased irritability, and agitation. Interestingly, with resuming treatment, the symptoms improved, as demonstrated by tests scores. Despite that, commitment to treatment was challenging, leading to ceasing rTMS treatment after 24 weeks from onset.

Our report is the first to describe rTMS efficacy to treat psychiatric symptoms in a patient with genetic leukoencephalopathy. RTMS represents an interesting alternative to pharmacological treatment in patients with genetic leukoencephalopathies who are already heavily medicated, may be refractory to standard pharmacological treatment or present unusual side effects. Prospective studies on larger cohorts will confirm the usefulness of rTMS to treat neuropsychiatric symptoms in these patients.