Intact Musical Appreciation and Performance in a Man ...

Psychosomatics 2018:]:]]]–]]]

& 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

Case Report “Moon River”: Intact Musical Appreciation and Performance in a Man With Semantic Variant Primary Progressive Aphasia Patrick A. Ho, M.D., Theodore A. Stern, M.D., James K. Rustad, M.D.

“We’re after the same rainbow’s end, waiting 'round the bend. My huckleberry friend, Moon River, and me.”—From the song “Moon River”; Henry Mancini and Johnny Mercer © 1960

Introduction Aphasia is a symptom of several neurological conditions (including strokes, migraines, malignancies, infections, immune-mediated diseases, and neurodegenerative processes).1 However, impairment in language and music (i.e., appreciation and production) may not align closely with aphasia syndromes. We present the case of an elderly man who presented with progressive language deficits and personality changes, but with intact appreciation and performance of music, and discuss the differential diagnosis, the evaluation, and the treatment approaches. Case Vignette (Part 1) Dr. A, a 72-year-old right handed man with a medical history notable for hyperlipidemia, hypertension, a remote history of mitral valve prolapse, and a 5-year history of frontotemporal dementia (FTD) with semantic variant primary progressive aphasia (PPA), was referred by his primary care physician for psychiatric consultation and management of aberrant behaviors. Dr. A had been a university professor for 40 years before receiving the diagnosis of FTD, manifest by worsening irritability and increasing amounts of time rehearsing lectures that he had been delivering for decades (to conceal his memory lapses from his Psychosomatics ]:], ] 2018

students) at the expense of time with his family. When he was no longer able to hide his memory problems from others (e.g., he could not remember the names of teaching assistants with whom he worked closely daily or the names of the places where he was going for a sabbatical), he chose to retire. Five years before the current evaluation, Dr. A began to manifest word-finding difficulties and challenges with comprehension. Subsequently, he was unable to speak in full and meaningful sentences; instead, he repeated several phrases regardless of whether the phrases were appropriate to that situation. His personality changes and difficulty with speech led to an evaluation by a neurologist at a memory clinic. His initial work-up was notable for a computed tomography (CT) scan of his head (without contrast) showing an area of parenchymal tissue loss involving the left anterior tip which extended posteriorly in a perisylvian distribution. It was read by the neuroradiologist as being suggestive of an old left anterior division middle cerebral artery infarct with loss of temporal lobe tissue. Dr. A could identify that his mother and maternal grandmother may have had

Received March 2, 2018; revised March 27, 2018; accepted March 29, 2018. the Department of Psychiatry (P.A.H., J.K.R.), Geisel School of Medicine at Dartmouth; Dartmouth-Hitchcock Adult Psychiatry Residency Program (P.A.H.), Lebanon, NH; Department of Mental Health and Behavioral Sciences (J.K.R.), White River Junction VA Medical Center, White River Junction, VT; and Department of Psychiatry (T.A.S.), Massachusetts General Hospital, Harvard Medical School Boston, Boston, MA. Send correspondence and reprint requests to James K. Rustad, M.D., Department of Mental Health and Behavioral Sciences, White River Junction VA Medical Center, White River Junction, VT e-mail: [email protected] & 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

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Case Report dementia. Laboratory testing relevant to a dementia evaluation was unremarkable (e.g., thyroid stimulating hormone, folate, and vitamin B12). Physical and neurological examinations yielded no pertinent positive findings. Dr. A scored 27 on the Mini-Mental State Exam (MMSE)2 and 11 on the Alzheimer’s Disease Assessment Scale (ADAS).3 Neuropsychological test findings revealed a lateralized pattern of deficit with difficulty in new verbal learning. Retention was adequate relative to learning, and delayed recall was average. Visuospatial recall was superior. Visual-spatial functions and general reasoning were adequate. It was noted that all of the neuropsychological test findings lateralized to the left hemisphere and a magnetic resonance imaging (MRI) study of the brain without contrast was ordered. The MRI showed age-appropriate parenchymal volume loss and a more focal area of volume loss in the left anterior temporal lobe. The neuroradiologist commented that there was no gliotic signal on fluid-attenuated inversion recovery, which made it slightly less likely that these findings were related to a prior infarct. The neurologist in the memory center concluded that the lesion in the left temporal lobe was more likely to be accentuated focal atrophy and then ordered a positron emission tomography (PET) scan of the brain to help refine the differential diagnosis. F-18-fluorodeoxyglucose, threedimensional time-of-flight PET imaging of the head with CT attenuation correction showed decreased F-18-fluorodeoxyglucose uptake in the left temporal lobe (particularly the anterior temporal horn) with additional areas of hypometabolism seen in the left medial frontal cortex and anterior cingulate gyrus. There was preservation of metabolic activity in the parietal lobes. These findings were most consistent with a diagnosis of FTD. The neurologist at the memory center diagnosed Dr. A with FTD with semantic variant PPA. Over the next few years his behaviors continued to deteriorate and he was often irritable and short-tempered. Three years before the current evaluation, he had a repeat MMSE score of 20 (compared to 27 at baseline), and an ADAS score of 26 (compared to 11 at baseline). Before his illness, Dr. A had been a talented pianist. Even as his impairments in memory and speech progressed, Dr. A retained the ability to play the piano well; he seemed to “communicate” through piano playing. His wife provided several examples of songs that the patient had been performing on piano for decades, including “Moon River” (popularized by 2


Andy Williams, and recently covered by contemporary artist Frank Ocean). On examination, Dr. A was unable to provide a reliable history, as he was unable to comprehend spoken language. He was loud, impulsive, intrusive with strangers, and agitated in the presence of his wife. He withdrew to affectionate touch from his wife. He could speak fluently but nonsensically. He pointed at the shoes that others were wearing, and then pointed at his own shoes yelling “14,” which was his shoe size. When recordings of his favorite songs from the 1960s, specifically familiar to the patient from playing them on the piano, were played by the examiners he laughed and clapped. For example, when “Moon River” was played, he smiled, laughed, and cheered. “Try to Remember” (from the musical comedy “The Fantasticks”) causes him to whistle along with the tune. When “Louie, Louie” (by The Kingsmen) was played, he tapped his feet to the beat. Of note is that Dr. A did not respond to less familiar or unfamiliar music. Discussion PPA is a neurodegenerative syndrome marked by a gradual and progressive worsening of speech and language that can become profound.4 In the initial stages, other cognitive domains (e.g., memory) are often relatively spared. PPA has been noted to have an earlier onset (typically before age 65 years) relative to other neurodegenerative syndromes.1 PPA can be subdivided into agrammatic, logopenic, and semantic variants.5 In the agrammatic variant, word comprehension is typically intact but there is a loss of fluency with grammatically incorrect sentences. With the logopenic variant, grammar, and word comprehension remain intact, but there are profound wordfinding difficulties with fluctuating fluency and poor repetition. Finally, the semantic variant involves impaired object naming and word comprehension while fluency, repetition, and grammar are preserved. PPA can be diagnosed when language difficulties are prominent and there is relative sparing of other cognitive domains.4 Assessment can be challenging, as verbal abilities and word comprehension are central to most assessment tools used to test other cognitive domains. Most afflicted individuals maintain independent instrumental activities of daily living (e.g., cleaning, cooking, shopping, or taking medications), unless those Psychosomatics ]:], ] 2018


Ho et al. skills rely on language abilities.4 PPA is characterized by an asymmetric pattern of atrophy, typically affecting the language-dominant (left) hemisphere. The nondominant hemisphere can remain unaffected for several years, which accounts for the relative sparing of other cognitive domains. Each variant of PPA has a distinct pattern of atrophy.6 For example, in the agrammatic variant the inferior frontal gyrus, also known as the Broca’s area, is most often atrophied. In the logopenic variant, the temporoparietal junction (i.e., Wernicke’s area) shows disproportionate atrophy. Finally, in the semantic variant, the anterior temporal lobe is most affected. The aphasia patterns identified by cerebrovascular accident-based classic aphasiology do not quite fit the patterns that emerge in PPA.6 To explain this phenomenon, Mesulam used the metaphor of a circuit board and noted that neurodegeneration can be said to induce a short circuit that is slowly propagated throughout the affected network, whereas cerebrovascular lesions can be said to pull the plug on the network constituents at the core lesion site.6 Pure impairment of language is unlikely to be present in most patients with PPA.7 Indeed, more rigorous testing may eventually reveal cognitive impairments in nonlanguage domains. With that said, affected patients do exhibit a disturbance in speech and language that is disproportionate to other cognitive deficits, and that predominant sign persists as the disease progresses. For the most part, PPA seems to be sporadic without any identifiable risk factors.4 Recently, a point mutation on chromosome 17 has been identified as a possible risk factor for PPA. There are no available community-based estimates of the frequency of PPA, however, a rough figure can be estimated by taking into account that the etiology often lies in the frontotemporal lobar degeneration (FTLD)-related clinical spectrum.8 The prevalence of FTLD has been estimated in the range of 2.7–15.0 per 100,000, whereas the incidence of FTLD has been estimated at 2.2–3.5 per 100,000 person-years.8 There are 2 initial clinical presentations observed in patients with FTD.9 The behavioral variant of FTD includes those who develop executive dysfunction, inappropriate social conduct, and progressive behavioral change, whereas PPA describes those who have speech difficulties and progressive language decline. Approximately, 20– 40% of FTLD cases have PPA, based upon data from autopsy series (from several institutions) examining all syndromes associated with FTLD pathology.8 Psychosomatics ]:], ] 2018

The differential diagnosis for a person who presents with language impairment is broad.3 A stroke, especially one involving the middle cerebral artery, should be ruled out immediately. Infectious processes (e.g., herpes simplex encephalitis and Creutzfeldt-Jakob disease) should be considered, although infectious etiologies of aphasia tend to progress more rapidly than does PPA. Immunological disorders, such as multiple sclerosis, should also be considered. The work-up for primary progressive aphasia includes use of clinical scales (e.g., the MMSE2, Montreal Cognitive Assessment10), and rating tools to assess other deficits of cognitive function.3 For patients in whom PPA is suspected, imaging studies (e. g., a MRI scan of the brain) are indicated.1 The MRI seeks to evaluate severe atrophy in the anterior temporal lobe (that would be more prominent on the language-dominant hemisphere). Finally, an F-18fluorodeoxyglucose PET scan can assess hypometabolism in the language-dominant hemisphere. Case Vignette (Part 2) Low-dose quetiapine (12.5 mg by mouth twice a day) was prescribed for Dr. A’s agitation and irritability by his primary care provider. However, there was reluctance on the part of his wife to start the medication over concerns of potential side effects. Atypical antipsychotics are commonly used for behavioral disturbances in dementia, however, no agent has been approved for this purpose.11 It was explained to the patient and his wife that older patients with dementiarelated behavioral problems are at an increased risk of death (compared to placebo), and also have an increased risk of cerebrovascular events. Given quetiapine’s potential (through actions at 5-HT1A receptors) to contribute to efficacy for cognitive and affective symptoms in some patients, especially at moderate to high doses, and its calming properties, Dr. A's wife agreed that the potential for benefits outweighed the risk. He responded well to this initial intervention (e.g., decreased agitation), and at follow-up visit the quetiapine was increased to 25 mg by mouth twice a day to even better effect (e.g., his playing piano improved and he spoke more clearly). He had minimal side effects, and he also became more able to focus on, and accurately complete, Sudoku puzzles. www.psychosomaticsjournal.org


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Case Report Conclusion Consistent with the clinical observations of the neurologist, Oliver Sacks, in Musicophilia: Speech and Song, we described the case of a man with severe aphasia who retained his ability to appreciate music, play piano, and whistle along with tunes.12 Sacks documented observations from as early as 1745 that indicated brain damage could produce amusias (e.g., disturbances of musical expression or appreciation), Although many individuals suffer from both an aphasia and an amusia, some can manifest aphasia without amusia (such as our patient, Dr. A). Indeed, it has been reported for over 100 years that patients with severe nonfluent aphasia (i.e., Broca’s aphasia) are better at singing lyrics than they are at speaking the same words.13 Music, like language, involves a close pairing between the perception and production of hierarchicallyorganized sequential information.14 The ability to create and enjoy music may be mediated by a frontal-parietal mirror neuron system which possesses the capability to simulate others' intentions and actions by recruiting one's own motor system. Pleasure derived from music may arise from interactions between subcortical systems responsible for reward and valuation and cortical loops that facilitate predictions that emerge from sound patterns.15 Interestingly, functional MRI studies have shown that familiarity appears to be a crucial factor in making listeners emotionally engaged with music.16 Relevant in this regard, functional MRI data revealed that broad emotion-related limbic and paralimbic regions and reward circuitry were significantly more active for familiar music relative to unfamiliar music. This underlying neurobiology may provide explanation for the emotional excitement and pleasure displayed by Dr. A while listening to “Moon River” relative to other less familiar songs. Recent research combined transcranial magnetic stimulation (over the left

dorsolateral prefrontal cortex to directly modulate frontal-striatal function bidirectionally) with measures of motivation and pleasure during music listening and showed that the monetary value assigned to music, perceived pleasure, and psychophysiological measures of emotional arousal are all significantly increased by the excitation of frontal-striatal pathways.17 Moreover, inhibition of these frontal-striatal pathways leads to decreases in all of the aforementioned variables. The neurodegenerative processes that underlie the development of PPA affect brain regions important for regulation of affect, behavior, and cognition. There is often a tendency to focus on deficits in language and comprehension in this disease, however, clinicians should also be alert to psychiatric/behavioral manifestations and prioritize access to treatment. In our patient (Dr. A), outpatient psychiatric consultation, facilitated by primary care, led to use of a low-dose atypical antipsychotic and provision of support. This integrated care decreased caregiver burnout and improved quality of life for Dr. A and his caregiver. PPA is not merely an interesting neurological phenomenon; it is a syndrome with debilitating neurocognitive and psychiatric manifestations that requires monitoring and attention. For caregivers, it is quite burdensome to attend to an individual who cannot communicate. Case management and social work can also offer assistance, and help facilitate referrals to community resources (such as respite, home health, and adult day programs). Potential conflicts of interest: Dr. Stern is an employee of the Academy of Psychosomatic Medicine and has received royalties from Elsevier and the Massachusetts General Hospital Psychiatry Academy. Drs Ho and Rustad report no conflicts of interest related to the subject of this article. Drs Stern, Ho, and Rustad report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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