Hyperacusis in vestibular migraine successfully treated with galcanezumab: A case report

Abstract

Background

Hyperacusis, a heightened sensitivity to sound, can severely impair quality of life and remains difficult to treat.

Case

We report a 44-year-old woman with vestibular migraine who experienced persistent dizziness, tinnitus, and hyperacusis. Initial treatment with amitriptyline and traditional Kampo medicine improved her dizziness but not her auditory symptoms. Subsequently, galcanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody, was administered monthly. Over six months, her Khalfa Hyperacusis Questionnaire score improved markedly from 21 to 3, and her headache impulse test-6 score decreased from 66 to 58.

Conclusion

This case demonstrates a potential role for CGRP-targeted therapy in treating migraine-associated hyperacusis and suggests a broader application in sensory modulation disorders. To our knowledge, this is the first report to describe the successful use of galcanezumab in hyperacusis, offering new insights into migraine-related auditory hypersensitivity.

Graphical abstract

This is a visual representation of the abstract.

Introduction

Hyperacusis, a heightened sensitivity to normal sound levels, is a distressing auditory condition that significantly impacts patients’ quality of life. Unlike typical hearing disorders, hyperacusis can occur independently of hearing loss and currently lacks established treatment protocols. Some studies suggest a potential relationship between hyperacusis and migraine-associated allodynia, wherein normally non-painful stimuli are perceived as painful due to reduced sensory thresholds.

Hyperacusis is considered an integral feature of migraine and is thought to result from hypersensitivity of nociceptive circuits, which propagate from peripheral to spinal neurons and higher brain centers. Hyperacusis and phonophobia are both sound intolerance symptoms often reported in migraine patients, but they differ in clinical characteristics: phonophobia typically occurs during headache episodes and is defined as sound-induced exacerbation of pain, whereas hyperacusis can persist outside of migraine attacks and involves abnormal loudness perception to everyday sounds. Differentiating the two can be difficult; however, in our case, the auditory discomfort was continuous and present during interictal periods, suggesting hyperacusis rather than phonophobia. We used the Khalfa Hyperacusis Questionnaire (KHQ) to quantify this symptom and distinguish it from migraine-related phonophobia. Calcitonin gene-related peptide (CGRP) antagonists, including galcanezumab, have emerged as effective preventive therapies for chronic migraine. It is reported that prophylactic therapy for migraine also improves hyperacusis in migraine patients. ¹ However, to date, there have been no reports on how CGRP-related antibody drugs affect auditory hypersensitivity symptoms. Here, we report a case of hyperacusis associated with vestibular migraine that improved dramatically with galcanezumab therapy, providing insight into its therapeutic potential for hyperacusis.

Case presentation

A 44-year-old woman presented in September X with complaints of persistent dizziness, bilateral tinnitus, and heightened auditory sensitivity. She described the dizziness as rotational, accompanied by a constant “ringing” in her bilateral ears. She had a medical history of Meniere's disease, ² previously diagnosed at another institution, and long-standing migraine characterized by headache impulse test-6 (HIT-6) ³ score of 66. Audiometric evaluation revealed bilateral low-frequency hearing loss. Additionally, video HIT and posturography were performed to evaluate semicircular canal function and postural stability, respectively, both of which showed normal findings.^4,5

Given her history of recurrent vertiginous episodes linked to headaches, she was diagnosed with vestibular migraine. ⁶ Preventive therapy, consisting of low-dose amitriptyline (5 mg daily) and the traditional Japanese Kampo medicine goreisan, was initiated. While the dizziness resolved and her migraine frequency decreased from 16 to 8 attacks per month, her hyperacusis symptoms persisted. The KHQ ⁷ score remained high at 21 points (Figure 1) in January. The patient reported that bilateral tinnitus and hyperacusis were persistent, whereas dizziness occurred intermittently. Regarding her history of Meniere's disease, we were unable to obtain detailed information, as the diagnosis had been made at a different institution and medical records were unavailable. The bilateral low-frequency hearing loss remained unchanged throughout the course of treatment.

Figure 1.

Time course of auditory (KHQ) and headache (HIT-6) symptoms. KHQ was assessed in January, April, and June, while HIT-6 was recorded in September (baseline) and June. Black circles (●) indicate the timing of HIT-6 assessments, whereas black triangles (▴) indicate the timing of KHQ assessments.

Therapeutic intervention

In January X + 1, galcanezumab was introduced to further reduce migraine frequency. Over a treatment period of six months, the patient reported substantial improvements in her auditory symptoms. Her KHQ score progressively decreased from 21 to 14 and finally to 3. Simultaneously, her HIT-6 scores improved from 66 to 58 in June. The patient experienced a marked reduction in both migraine attacks and the intensity of hyperacusis, significantly enhancing her daily life. Despite partial improvement in headache frequency, residual attacks remained moderately severe and disabling. Galcanezumab was introduced to further suppress headache activity and evaluate possible effects on sensory symptoms. Amitriptyline was continued during galcanezumab treatment. However, since auditory symptoms did not improve during the prior 4 months of amitriptyline monotherapy, the observed auditory improvement is likely attributable to galcanezumab.

Discussion

This case underscores the potential link between hyperacusis and migraine-related mechanisms. CGRP, a neuropeptide implicated in migraine pathophysiology, is expressed in the cochlea's Type II spiral ganglion neurons and lateral olivocochlear system, suggesting its involvement in auditory processing. Migraine-induced central sensitization may exacerbate hyperacusis, aligning with the hypothesis that hyperacusis is a variant of allodynia affecting the auditory pathways. ⁸

Hyperacusis is considered an integral feature of migraine and is thought to result from hypersensitivity of nociceptive circuits spreading from peripheral to spinal neurons and higher brain centers. ⁸ Hyperacusis and phonophobia may also be related to migraine, aiding in its diagnosis and management. Multi-modal migraine prophylaxis therapy^1,9 has been shown to effectively improve symptoms in patients with hyperacusis, further supporting the link between these conditions. Additionally, studies indicate that anxiety and depression, often comorbid with migraine, may exacerbate hyperacusis by heightening sensory sensitivity. In this case, there was no clinical evidence of comorbid anxiety or depression based on detailed patient interviews and clinician assessments. Therefore, we consider psychological influence unlikely in the observed improvement, although the general association between migraine and psychiatric comorbidities remains important in broader clinical practice. This highlights the importance of addressing psychological comorbidities in patients with complex sensory conditions.

Hyperacusis, characterized by an increased sensitivity to everyday sounds, is not specifically recognized as a “headache-free migraine phenotype.” However, it is acknowledged as a form of sensory hypersensitivity that can occur in individuals with migraine, even during interictal periods when headaches are absent. ¹⁰ This suggests that some cases of hyperacusis may fall within the migraine spectrum, manifesting independently of headache episodes. Amitriptyline and Goreisan had already reduced the patient's headache frequency by half, from 16 to 8 attacks per month. However, hyperacusis persisted until galcanezumab was introduced. We recognize that the HIT-6 score reduction was modest. Therefore, our case may not fully support the concept of a “headache-free migraine phenotype,” but highlights potential benefit in treating residual sensory symptoms with CGRP antagonists.

Additionally, studies indicate that anxiety and depression, which are often comorbid with migraine, may exacerbate hyperacusis by heightening sensory sensitivity. This highlights the importance of addressing psychological comorbidities in patients with complex sensory conditions to achieve comprehensive management. ⁹ In this case, there was no clinical evidence of comorbid anxiety or depression based on patient interviews and clinical observation, making psychological influence less likely in the therapeutic effect.

Furthermore, lifestyle factors such as sleep quality and physical exercise play a critical role in managing migraine and associated sensory symptoms. Improved sleep and regular exercise have been shown to modulate central sensitization, potentially reducing the severity of hyperacusis in affected patients. These findings ¹⁰ suggest a multifaceted approach to managing hyperacusis, incorporating pharmacological and non-pharmacological strategies. In our case, no apparent insomnia was found, and no pharmacotherapy was introduced at this point.

Our finding is consistent with broader studies showing the efficacy of CGRP antagonists in reducing migraine-associated sensory symptoms.^1,10 The dramatic improvement in hyperacusis raises the possibility of extending CGRP-targeted therapies to patients with hyperacusis unaccompanied by headache, potentially identifying a headache-free migraine phenotype. While galcanezumab was associated with a notable improvement in hyperacusis, we cannot exclude the possibility that this was coincidental and unrelated to migraine pathophysiology. It is also plausible that galcanezumab exerted a direct modulatory effect on auditory pathways independent of headache suppression. Given the partial improvement in headache severity but marked change in auditory symptoms, this case raises the question of whether galcanezumab may be effective in treating hyperacusis outside of classic headache phenotypes. Although this case does not fulfill all criteria for a headache-free migraine phenotype, the disproportionate improvement in hyperacusis compared to headache symptoms suggests that CGRP-targeted therapy may benefit sensory symptoms even in the relative absence of headache. We do not claim to advocate definitively for this phenotype but highlight the need for further studies. Additionally, further exploration of the interplay between migraine, hyperacusis, and psychological factors could yield valuable insights for personalized treatment approaches.

Conclusion

This case highlights the efficacy of galcanezumab in treating hyperacusis associated with migraine, a condition with limited therapeutic options. Further research is needed to explore its broader applicability and to elucidate the underlying mechanisms linking hyperacusis and migraine. Such insights could pave the way for targeted interventions in sensory modulation disorders.

Clinical implications

• This is the first reported case of hyperacusis associated with vestibular migraine successfully treated with galcanezumab, a CGRP monoclonal antibody.

• KHQ score improved dramatically from 21 to 3 over six months of therapy.

• Migraine-related sensory hypersensitivity, such as hyperacusis, may be mediated by CGRP pathways, supporting a shared pathophysiological mechanism.

• This case highlights the potential utility of CGRP-targeted therapy in treating not only headaches but also associated auditory symptoms.

• The findings suggest a new therapeutic avenue for migraine-spectrum sensory modulation disorders beyond headache relief.