Musical Hallucinations In Patients With Lyme Disease

Raphael B. Stricker, MD, Edward E. Winger, MD

Disclosures

South Med J. 2003;96(7) 

In This Article

Discussion

Musical hallucinations are four times more common in women than in men, with an average age of onset of 60 years.[1] In the largest review of 46 cases, three quarters of patients had no psychiatric illness and two thirds suffered from deafness.[1] Whereas a gradual onset of hallucinations is associated with deafness, a sudden onset suggests the presence of brain lesions.[1] The type of music is often patriotic or lyrical and may reflect early childhood experiences, as in the case of our patients. The music may be perceived as annoying, intrusive, or pleasing, depending on the psychodynamics of the individual.[1] Various composers, from Beethoven, Schumann, and Donizetti to Brian Wilson of the Beach Boys, have reportedly been affected by these hallucinations.[2,3,4]

There has been controversy over whether musical hallucinations are caused by otologic or cerebral disease.[2,3,8] These hallucinations have been associated with stroke, epilepsy, brain tumors, alcohol withdrawal, psychotropic medications, and Parkinson's disease,[1,2,3,4,5,6,7,8] and they have been linked to cortical and midbrain infections, including neurosyphilis.[1,2,3,4] Furthermore, musical hallucinations have been described with pontine lesions and brain abscesses in the absence of deafness.[6,7,8] A recent study attributed these hallucinations to lesions in the right temporal lobe, which contains the auditory association area for nonverbal (eg, musical) stimuli.[5] Thus, cerebral disease may be responsible for musical hallucinations in certain cases.

Our patients developed musical hallucinations after initiation of oral antibiotic therapy for neurologic Lyme disease ( Table 1 ). Each patient had evidence of active Lyme disease that persisted despite oral antibiotic treatment. Patient 1 had a positive test for B. burgdorferi in cerebrospinal fluid after receiving oral antibiotics, and Patient 2 had persistent memory problems that failed to respond to oral doxycycline but improved with IV ceftriaxone. Neither patient had any evidence of hearing impairment, seizure activity, renal dysfunction, or neuropsychiatric illness before the onset of Lyme disease symptoms, and both patients had cerebral lesions documented on MRI scans. In addition, SPECT scanning revealed that Patient 2 had lesions in the right temporal lobe, the area that has been associated with nonverbal (eg, musical) auditory processing.[5] Thus, there was evidence of persistent spirochetal infection at the time that musical hallucinations supervened in each case, and involvement of the right temporal lobe was documented in one case.

Each patient was on stable doses of medications that have not been associated with musical hallucinations. Although antibiotic therapy could have been responsible for these symptoms, antibiotics have not previously been identified as a cause of musical hallucinations.[1,2,3,4,5,6,7,8] Furthermore, Patient 1 had received the same antibiotics (clarithromycin and amoxicillin) in the past without any side effects, and her musical hallucinations responded to IV antibiotic therapy. Patient 2 developed musical hallucinations after the onset of a Parkinson-like syndrome associated with positive testing for Lyme disease. Of note, the Parkinsonian symptoms resolved with oral doxycycline, but the musical hallucinations did not. However, the musical hallucinations resolved with IV antibiotic therapy and recurred when this treatment was discontinued. Although a causal relationship between Lyme disease and musical hallucinations was not definitively established in our patients, neurologic involvement with the spirochete B. burgdorferi appeared to be the most likely cause of these hallucinations. Whether the hallucinations were caused by cortical or brainstem abnormalities remains undetermined, but involvement of the right temporal lobe in Patient 2 suggests that cortical dysfunction was responsible for these symptoms. Musical hallucinations have been noted in several patients with hearing loss and chronic Lyme disease (R.B. Stricker, personal observation), so this auditory symptom may be more common than previously reported.

Lyme disease has been called the new "great imitator" because the protean manifestations of this spirochete-mediated infection are reminiscent of syphilis in the preantibiotic era.[11] On the basis of animal and human studies of the disease, evidence of infection may persist for months to years despite appropriate antibiotic therapy.[12,13,14] Recently, it has been shown that B. burgdorferi can persist in migratory macrophages,[15,16] explaining penetration of the organism into brain tissue and accounting for resistance to antibiotic therapy in neurologic Lyme disease. With increasing recognition of the disease, novel neurologic and immunologic features have been identified.[17,18] For example, CD57 lymphocytes comprise a natural killer cell subset that is selectively decreased in untreated patients with chronic Lyme disease.[18] Patient 1 had been treated repeatedly with oral antibiotics over 7 years, and her CD57 lymphocyte level was initially normal (Fig. 1). However, this level increased with IV antibiotic therapy, suggesting that the "normal" range may vary according to the stage of disease in patients with B. burgdorferi infection.[18] Patient 2 had decreased CD57 lymphocytes before the onset of musical hallucinations (Fig. 1), and the level remained low despite oral and IV antibiotic therapy. The recurrence of auditory hallucinations and a persistently low CD57 level in this patient support the concept of chronic infection with B. burgdorferi and the need for prolonged antibiotic therapy for chronic Lyme disease.[18,19,20,21]

In a previous study, we showed that patients with predominant neurologic symptoms of Lyme disease had significantly lower CD57 lymphocyte levels than patients with predominant musculoskeletal symptoms of the disease.[18] In addition to being located on lymphoid cells, the CD57 antigen (also known as Leu-7 or HNK-l) has been found on various central and peripheral nerve cells.[22,23,24] This glycoprotein antigen appears to function as a cell adhesion molecule that promotes cell-cell contact and neurite outgrowth of motor neurons.[22] On the basis of a recent study, CD57 may also play a role in immunologic signaling by binding interleukin-6.[25] Consequently, a decrease in neuronal expression of this glycoprotein might contribute to neurologic dysfunction and persistent spirochetal infection in the central nervous system. The relationship between immunologic dysfunction and neuropathology in Lyme disease merits further study.

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