Auris Nasus Larynx 40 (2013) 327–329

Dysphagia due to isoniazid therapy for tuberculosis in a patientwith Lewy body dementia

Masafumi Ohki a,*, Niro Tayama b

a Department of Otolaryngology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe-shi, Saitama 350-8550, Japanb Department of Otolaryngology, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan

A R T I C L E I N F O

Article history:

Received 12 December 2011

Accepted 21 February 2012

Available online 17 May 2012

Keywords:

Tuberculosis

Isoniazid

Levodopa

Dysphagia

Parkinsonism

A B S T R A C T

Dementia with Lewy bodies (DLB) potentially causes dysphagia; however, the features and underlying

mechanism causing dysphagia have still not been clarified. We are the first to report a case of dysphagia

resulting from isoniazid therapy for tuberculosis in a DLB patient. A 74-year-old woman with DLB

developed dysphagia during treatment for tuberculous pleurisy. Oral videoendoscopic and videofluoro-

graphic swallowing examinations showed oropharyngeal dysphagia. The increased administration of

levodopa successfully ameliorated dysphagia. Therefore, dysphagia was ascribed to diminished levodopa

efficacy due to interaction with isoniazid. Thus, DLB patients receiving anti-tuberculous therapy should

be closely examined for potential changes in swallowing and Parkinsonism.

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1. Introduction

Dementia with Lewy bodies (DLB) is the second most commonform of degenerative dementia after Alzheimer disease. It ischaracterized by fluctuating cognitive impairment, Parkinsonismand recurrent visual hallucinations [1]. Patients in DLB sometimescomplain of dysphagia as a potentially serious complication.However, dysphagia in DLB has not been reported in detail. Weherein report the first case of dysphagia during isoniazid therapyfor the comorbidity of tuberculosis in a DLB patient. We discuss theinteraction between isoniazid and levodopa given to alleviatedysphagia.

2. Case report

A 74-year-old woman presented with 13 year history of upperlimb tremor and one year history of recurrent visual hallucinationsand mild dementia. The upper limb tremor was not resting tremor,and bradykinesia, rigidity or postural instability which suggestsparkinsonism did not appear before advent of recurrent visualhallucinations and dementia. One year after she started to realizesome people, mice or falling rain in her room as visualhallucination recurrently, she also developed difficulty withwalking, anorexia and weight loss. She had normal strength butslight rigidity in all four limbs and the neck. Reflexes were

* Corresponding author. Tel.: +81 49 228 3685; fax: +81 49 225 6312.

E-mail address: m-ohki@umin.ac.jp (M. Ohki).

0385-8146/$ – see front matter � 2012 Elsevier Ireland Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.anl.2012.02.005

bilaterally brisk in her upper limbs and normal in her lower limbs.Plantar reflexes were extensor bilaterally. She had slight restingtremor in all of her limbs and bradykinesia. The Hoehn and Yahrscale was 4 [2]. Her mini-mental state examination score was 24[3]. Brain magnetic resonance imaging showed mild diffuseatrophy of the cortex. Brain-perfusion single photon emissioncomputed tomography (SPECT) showed a tendency for hypoperfu-sion involving the entire brain area, especially bilateral occipitalhypoperfusion and slight hypoperfusion of both parietal lobes, theleft temporal lobe, the left frontal lobe, left basal ganglia and leftthalamus. Diagnosis of DLB applies to those who meet criteria forDLB and develop parkinsonism at any time after the onset ofdementia or develop dementia no more than 1 year after the onsetof parkinsonism, according to the 1 year rule [1]. Apparentparkinsonism did not appear before advent of recurrent visualhallucinations and dementia. DLB was ultimately diagnosedbecause of recurrent visual hallucinations, subsequent distinctiveParkinsonism and supportive features on SPECT perfusion scanwith reduced occipital activity [1]. She then began taking levodopa450 mg, cabergoline 1 mg and pramipexole 0.375 mg daily for theDLB. She maintained a Hoehn and Yahr score of 3 such that she hadbeen able to live independently. One year later, she suffered fromtuberculous pleurisy. Therefore, anti-tuberculosis treatment withrifampicin 450 mg, ethambutol 500 mg and isoniazid 300 mg dailywas started. She then began to experience difficulty swallowingwhich progressively became worse. About 20 days later, she was ina state of severe dysphagia and could barely take her medications.Three days thereafter she was admitted to our hospital because ofastasia and aphagia. Rigidity of the neck and limbs was apparent.

Fig. 1. VE using a 3-ml crystal violet-pigment bolus and VF using 3 ml of iopamidol. VE showed the pigmented bolus to flow into the pharynx and toward the glottis before

laryngeal elevation (a) and pooling of the bolus in the piriform recess of the hypopharynx with aspiration into the trachea (b). VF showed the oral stage of swallowing (c) and

the pharyngeal stage (d–g) indicating delayed onset of laryngeal elevation and poor laryngeal elevation (d), aspiration during swallowing (e), poor pharyngeal contraction (f)

and bolus residue in the piriform recess of the hypopharynx (g). Upper esophageal sphincter opening was good (f).

M. Ohki, N. Tayama / Auris Nasus Larynx 40 (2013) 327–329328

The Hoehn and Yahr scale was 5. She presented hoarseness butneither abnormal respiratory sound nor difficult breathing. An oralvideoendoscopic (VE) swallowing examination revealed a 3-mlcrystal violet-pigmented bolus to flow into the pharynx andtoward the glottis before laryngeal elevation (Fig. 1 a) and thebolus pooled in the piriform recess of the hypopharynx and wasaspirated into the trachea (Fig. 1b). Laryngofiberscopy showedneither laryngeal nerve palsy nor laryngeal tremor, but incompleteglottal closure demonstrating non-closure glottis pattern of

Fig. 2. VE and VF findings after increased levodopa administration. VE using a 3-ml cr

piriform recess of the hypopharynx and no aspiration into the trachea (a). VF using 3 ml

indicating improved timing of laryngeal elevation (c), no aspiration during swallowing

sphincter (e) and no bolus residue in the piriform recess of the hypopharynx (f).

spindle shape. A videofluorographic (VF) swallowing examinationusing 3 ml of iopamidol (Fig. 1c–g) showed delayed initiation ofswallowing, delayed onset of laryngeal elevation with poorlaryngeal elevation (Fig. 1d), aspiration during swallowing(Fig. 1e), poor pharyngeal contraction (Fig. 1f) and bolus residuein the piriform recess of the hypopharynx (Fig. 1g). The number oftongue elevations and swallowing were increased to clear thebolus in her pharynx. Opening of the upper esophageal sphincterwas adequate (Fig. 1f). These findings indicated impairment in the

ystal violet-pigmented bolus showed good clearance without bolus pooling in the

of iopamidol showed the oral stage of swallowing (b) and the pharyngeal stage (c–f)

(d), improved pharyngeal contraction (e), good opening of the upper esophageal

M. Ohki, N. Tayama / Auris Nasus Larynx 40 (2013) 327–329 329

oropharyngeal phase of swallowing. After admission, one intra-muscular 50-mg injection of levodopa transiently improved hersymptoms. Therefore, levodopa and cabergoline doses wereincreased to 600 mg and 1.25 mg daily, respectively. Rigiditygradually decreased. Sixteen days after admission, she was able tostart oral ingestion of food because the dysphagia showed partialrelief. Hoarseness was also relieved and laryngofiberscopy showedcomplete glottal closure. VE showed good swallowing withoutbolus flowing into the pharynx preceding laryngeal elevation orbolus pooling in the piriform recess of the hypopharynx (Fig. 2a).VF also indicated improved swallowing (Fig. 2b–f). The pharyngealstage revealed well-matched timing of laryngeal elevation andbetter pharyngeal contraction (Fig. 2c–e). Aspiration and boluspooling in the piriform recess of the hypopharynx disappeared,indicating good bolus clearance (Fig. 2e and f). On the 20th hospitalday, her swallowing function had nearly normalized and shebecame ambulatory though slight postural instability and rigiditypersisted. The Hoehn and Yahr scale improved to 3. Since then shehad not presented swallowing difficulty for 40 days. Therefore, shewas discharged.

3. Discussion

Patients with DLB frequently have eating and swallowingproblems [4,5], as well as those with PD [5,6]. The prevalence ofdysphagia was 11–21% in DLB but 18.5–100% in PD patients [5].Dysphagia has been considered to be associated with extrapyra-midal signs, autonomic dysfunction, fluctuations in cognition andpsychiatric problems [1]. However, features and mechanism ofdysphagia in DLB have not been reported in detail. Pathognomonicfeatures of DLB are Lewy bodies (LB) in the brainstem and cortex inaddition to the nigral LB degeneration characteristic of Parkinsondisorders (PD). We speculated that it is common, in part because ofthe clinical and pathological relationships between DLB and PD.Deglutition impairments in each of the oral, pharyngeal andesophageal phase have been reported in PD. Oral phase dysfunc-tion is characterized by lingual festination, increased numbers oftongue elevations, difficulty with bolus formation due to impairedmastication, oral preparatory lingual movements and delay in theswallowing reflex [7,8]. This deglutition impairment results fromPD-related bradykinesia and rigidity linked to impaired basalganglia motor control [8]. Abnormalities in the pharyngeal phaseinclude impaired motility, delayed onset of laryngeal elevation,vallecular and pyriform sinus stasis, supraglottic and glotticaspiration, deficient epiglottic positioning and range of motion,and increased numbers of swallows to clear the pharynx of a bolus[9]. Abnormal basal ganglionic suprasegmental control of medul-lary motor function or degeneration of brainstem nuclei, e.g.,dorsovagal nuclei and nuclei of the medullary reticular activatingsystem, is speculated to be the cause of pharyngeal phaseimpairment [10]. Esophageal phase abnormalities are delayedtransport, stasis and bolus redirection [10]. These abnormalitiesare due to an open or delayed opening of the lower esophagealsphincter. Abnormal esophageal movements are suggested toreflect degeneration of brainstem nuclei, dorsovagal nuclei or theesophageal myenteric plexus [7,11]. Levodopa effectively relievesParkinsonism in DLB or PD patients [12]. Levodopa improvesdysphagia in some, but not all, patients with PD [12]. However,

levodopa may induce choreic dyskinesias as a side effect. Thesechoreic dyskinesias are reportedly ameliorated during treatmentwith isoniazid for tuberculous infection [13,14]. Therefore,isoniazid is presumed to interfere with levodopa [13,14]. Levodopais decarboxylated to dopamine by the enzyme dopa decarboxylaseafter it reaches the cerebrospinal fluid. Isoniazid is considered toinhibit this enzyme [14]. Isoniazid penetrates well into cerebro-spinal fluid across the blood–brain barrier, with a cerebrospinalfluid penetration rate of approximately 86% [15]. Isoniazidentering the cerebrospinal fluid decreases dopamine as a resultof inhibiting dopa decarboxylase. In our case, dysphagia andexacerbation of the Parkinsonism of DLB were presumably inducedby reduced efficacy of levodopa due to the isoniazid. Increasing thelevodopa dose improved dysphagia and Parkinsonism in this case.In treating a patient suffering from DLB complicated by tubercu-losis, evaluation of swallowing and Parkinsonism are necessary.Isoniazid and levodopa doses should be adjusted when deteriora-tion of swallowing and Parkinsonism occur. In such cases, wesuggest two main ways to overcome this problem; i.e. increase oflevodopa dose and modified anti-tuberculosis chemotherapywithout isoniazid.

Conflict of interest

None.

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