We present a peculiar case report of a patient with depression and burning mouth syndrome (BMS). Of particular interest is the resolution of oral symptoms following cerebral electrical stimulation. We believe that several useful reflections for dermatology can be drawn from this case.
A 60-year-old woman was admitted to the psychiatric hospital for the development, over the preceding years, of depression and, simultaneously, BMS, the diagnosis of which was confirmed after dermatologic evaluation (Table 1). Her only relevant history was a severe depressive episode 40 years earlier, which had completely resolved with electroconvulsive therapy (ECT).
Diagnostic process and treatments performed in the patient.
| Diagnostic test | Description and results |
|---|---|
| Basic blood tests (including thyroid hormones, complete blood count, and coagulation) | Findings consistent with controlled diabetes, with no other significant abnormalities. |
| Biopsy (oral mucosa) | No significant abnormalities. |
| Neuropsychological evaluation | 2 evaluations were performed 1 year apart:1) Mild cognitive impairment: slowed processing speed; deficits in attention, working memory, cognitive interference, planning, cognitive flexibility; reduced verbal fluency; and difficulties in verbal and visuospatial recall. These alterations persisted independently of mood improvement.2) At 1-year follow-up: worsening cognitive status, with severe memory impairment, visuospatial perception and construction difficulties, and progression of previously identified deficits. |
| Brain MRI | At 2nd evaluation: global vascular damage and cortical atrophy, predominantly affecting the frontotemporal lobes, greater than expected for age. |
| EEG (19 electrodes, 10–20 system) before and after ECT | Slower alpha activity (baseline rhythm 8Hz), commonly observed in mild cognitive impairment18 (Fig. 1). Excess theta activity in the frontomedial region. |
| Treatment | Description |
|---|---|
| Psychiatric pharmacologic treatment (maintained from the beginning) | Olanzapine 5mg/12h; diazepam 5mg/8h (additional 5mg if severe anxiety); clomipramine 75mg at night; lormetazepam 1mg at night (additional 1mg in case of insomnia). |
| Usual optimal medical treatment | Low-fat diet; levothyroxine 75mcg/24h; atorvastatin 10mg/24h. |
| Psychological treatment | - Cognitive behavioral therapy (operant conditioning): reinforcement program of alternative behaviors, initially effective but lost efficacy as the condition progressed.- Structured activity schedule aimed at distraction from unpleasant sensations, supported by occupational therapy. |
| Response to ECT | - Objectives and program: ECT sessions every 2 days, up to a maximum of 6; expected outcome: reduction of affective symptoms.- Unexpected results: Aafter the 1st ECT session, complete disappearance of oral symptoms. Affective symptoms improved but persisted, requiring additional sessions. The patient confirmed total absence of oral pain or sensations. Distress, restlessness, and despair resolved immediately.- Course of improvement: Anhedonia, apathy, and anergia persisted initially but resolved with subsequent sessions. The patient was discharged with full remission of treatment-resistant major depression and BMS. |
| Course and progression | Description |
|---|---|
| Initial | - Each ECT session produced temporary improvement of oral symptoms until relapse. Maintenance sessions were required every 2 months.- Over time, the duration of ECT effects decreased, while cognitive impairment became more evident. |
| Current | ECT sessions are ongoing, and symptoms remain within a tolerable range for both the patient and her environment. |
The main source of distress was oral symptoms. Lack of pharmacologic response led to the reintroduction of ECT, which had previously produced a favorable outcome. Surprisingly, after the first session of bilateral prefrontal cerebral electrical stimulation, BMS symptoms—and associated complaints—disappeared, an effect not anticipated from treatment. It appeared that ECT had resolved both depressive and cutaneous syndromes; however, after a symptom-free period, the patient required additional sessions.
In parallel, from the beginning of follow-up, signs of cognitive decline were observed, becoming progressively more evident. Neuropsychological assessments were performed at the center (Fig. 1 and Table 1), all suggesting cognitive impairment.
After 3 years, the patient experienced marked worsening in cognitive function, mood, and BMS symptoms, which remained the most disabling subjective complaint. On one occasion, the patient attempted to alleviate oral symptoms by repeatedly striking her temple with a hammer, leading to a new hospitalization. Symptom recurrence and associated distress caused anxiety, akathisia, hopelessness, and helplessness, and occasionally further suicide attempts, although less frequently due to close monitoring. Currently, the condition has been classified as vascular degenerative dementia. Periodic ECT is maintained, reproducing the same phenomenon of resolution of oral and depressive symptoms.
BMS, or glossodynia, is an idiopathic condition with a predominance in women. Symptoms often worsen during stressful life events and are more common in individuals with atypical psychological traits and a predisposition to depression and anxiety.1,2 It has a significant impact on quality of life, with reported cases of suicide.3,4 It represents a challenge for dermatologists: it requires appropriate diagnostic evaluation1 and has a difficult therapeutic approach, similar to that of other neuropathic pain disorders but with highly variable responses.5 A strong physician–patient relationship, realistic expectations, and a stepwise, proportionate treatment strategy are essential.1
We describe an extreme case in which BMS and depression appeared concomitantly. The most striking feature was the disappearance of oral symptoms following ECT applied to the frontal brain regions. Frontal brain regions are crucial for regulatory function; in patients with self-injurious behaviors, electrical abnormalities are frequently observed in the medial frontal regions,6 consistent with our patient's neuropsychological findings and abnormalities described in other cases.3
The literature describes similar overlaps between affective and somatic complaints, often associated with altered personality patterns.7 Neuropathic and psychogenic components may coexist in BMS,8 with evidence of peripheral, central, and combined nervous system alterations in this syndrome (Table 2). These findings may collectively suggest early central nervous system alterations that could explain treatment resistance and symptom persistence.
Explanations regarding the peripheral, central, and integrated origin of burning mouth syndrome.
| Peripheral nervous system | Evidence of peripheral functional alterations in BMS:- Higher oral sensory thresholds for temperature, taste, touch, and pain.- Increased sensory thresholds also observed after transient deafferentation experiments (nerve blockade with capsaicin) in healthy subjects, analogous to BMS patient models, supporting this hypothesis.- Additionally, BMS has been associated with mild small-fiber sensory and autonomic neuropathy, often accompanied by central nervous system alterations. |
| Central nervous system | Evidence of central nervous system alterations in patients with BMS:- Reduced brain volume and perfusion, both cortical and subcortical, compared with controls.- Increased activation of the so-called “pain matrix.” Affective brain regions (e.g., amygdala and anterior cingulate cortex) show increased activation and altered functional connectivity between frontal regions (medial prefrontal cortex, anterior cingulate cortex, ventromedial prefrontal cortex) and the bilateral amygdala in response to painful stimuli.- Reduced perfusion in temporal regions (bilateral middle temporal gyrus and insula), reflecting impaired central and peripheral integration. Decreased perfusion and volume suggest neuronal loss, whereas reduced inhibition and impaired organization (likely related to increased neuronal excitability) indicate altered global pain processing. |
| Integration of both systems | Several hypotheses explain the interaction between central and peripheral mechanisms:1) Two patient subtypes based on nervous system response: burning sensation may be classified as “peripheral” (reduced burning after lingual lidocaine injection) or “central” (increased burning after saline injection).2) Central pain model: despite peripheral damage, central alterations appear to be key. BMS may be considered nociplastic pain, defined as pain arising from altered nociception without clear evidence of tissue damage or somatosensory system disease.3) BMS symptoms as signs of global central dysfunction: chronic depression may represent a comorbid expression of underlying brain dysfunction, explaining the strong association between BMS and depression.4) Peripheral alterations leading to central dysfunction: similar to other chronic pain disorders, persistent peripheral stimuli may induce maladaptive central changes. BMS shares similarities with fibromyalgia (although localized to the oral cavity). Emerging evidence supports central inhibitory deficits and progressive peripheral damage capable of altering central pathways. Chronic nociceptive input may induce neuronal apoptosis and reduced brain volume in regions involved in processing pain, temperature, touch, and taste. |
| Warning signs of cognitive impairment (to be assessed in BMS) | Cutaneous:- Increased intensity of orofacial sensations- Increased frequency of complaints- Greater number of affected life domainsPsychological/subjective:- Greater emotional impact of oral symptoms- Increased ruminative thoughts related to oral burning- Anhedonia, hopelessness, and anxiety- Increased social withdrawal and sedentary behavior- Dependent and passive interaction style- Feelings of vulnerability and fear of being alone without supportCognitive impairment:- Psychomotor slowing and gait difficulties- Increased difficulty with daily activities- Impaired performance in new or complex tasks- Frequent forgetfulnessOther signs:- Poor response to psychopharmacologic treatment- Central nervous system degeneration evidenced by EEG and brain MRI, predominantly in frontal regions- Onset or increase of self-injurious behavior |
In our case, ECT was selected due to comorbidity with risk of self-harm and suicide, as reported in other BMS cases.3 Only 1 previous case of BMS successfully treated with ECT has been reported in Japan.9 Recently, other forms of cerebral electrical stimulation (simpler than ECT) have been proposed to improve pain and burning sensations, with promising results.10 This therapeutic response strongly suggests a possible central origin of BMS.
BMS and depression may also represent early manifestations of impaired cerebral integrity, particularly in predisposed individuals. Therefore, we consider it important to assess cognitive deficits in patients with BMS, as this may facilitate early interventions that extend beyond symptomatic treatment of psychocutaneous signs.
FundingNone declared.
Conflicts of interestNone declared.
