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Botulinum toxin treatment for essential palatal tremors presenting with nasal clicks instead of pulsatile tinnitus: a case report

Head & Face Medicine201612:33

DOI: 10.1186/s13005-016-0129-6

Received: 30 August 2016

Accepted: 1 November 2016

Published: 22 November 2016

Abstract

Background

In this study, we report a rare case of an adult patient with essential palatal tremors (EPT) presenting as nasal clicks, instead of otic clicks or objective pulsatile tinnitus in common EPT.

Case presentation

Nasal endoscopic examination and EMG recordings of the soft palate muscles were performed to confirm the source of the clicks. Initial treatment with lidocaine provided symptomatic relief for four hours. The patient was then treated with four simultaneous injections of 12.5 U of botulinum toxin in four different sites of the soft palate. Palatal tremors and clicks completely disappeared within three months of treatment.

Conclusions

To our knowledge, this is the first case of EPT that presented with nasal clicks. We recommend that otolaryngologists should expect this rare occurrence in the clinical setting, and handle patients presenting with such symptoms with care and compassion in order not to worsen their psychological status.

Keywords

Case report Palatal tremors Botulinum toxin Inferior olive Pulsatile tinnitus Electromyography

Background

Palatal tremor i.s a rare movement disorder characterized by continuous rhythmic jerks of the soft palate that are often perceived as tinnitus [1]. Palatal tremors are classified as symptomatic palatal tremors (SPTs) and essential palatal tremors (EPTs). SPTs mainly present with neurological deficits such as dysarthria, nystagmus and ataxia. Abnormalities in the function of the nucleus dentatus, nucleus ruber and/or inferior olivary complex are known to contribute to the pathophysiology of SPT [2, 3]. SPTs rarely present with ear clicks and palatal movements, while EPTs almost exclusively present with ear clicks and palatal movements. Excessive contraction of the tensor veli palatini (TVP) muscle, which is innervated by the trigeminal nerve, is thought to be the cause of EPTs. According to the diagnostic criteria proposed by Deuschl et a1. [3, 4], no intracranial pathology is associated with EPTs. Patients have normal cerebellar function and pendular nystagmus. Furthermore, throat muscle involvement is not expected. In the literature, several cases of EPT associated with psychogenic factors, as well as those of unknown etiology, have been reported [5, 6].

Regardless of etiology, EPTs usually present with objective tinnitus of otic origin or ear clicks. However, EPTs with nasal clicks have hitherto not been reported. Here, we report the case of an adult patient with EPT presenting as nasal clicks who was effectively treated with botulinum toxin injection.

Case presentation

Patient history

A previously healthy 51-year-old man presented at our hospital with a chief complaint of clicking sounds heard in the nose. He mentioned that the noise was audible to others and disappeared during sleep. He had excessive phlegm for two years and pharyngalgia for one week. His birth, growth and developmental history were all normal. He had no history of head trauma, chronic ear disease, or neurological disorder. None of his family members had a history of nasal clicks or tinnitus. The patient had been very uncomfortable due to the persistent sound.

Physical examination and preliminary diagnosis

An otolaryngologist performed physical examination of the nose, mouth and pharynx; and found that the audible “clicking” noise originated from the nose (Additional file 1: Video S1). No anomaly other than a fast rhythmic tremor of the soft palate was observed upon physical examination. Other muscles in the pharynx, mouth and eyes did not seem to be involved based on these examinations. Results of audiometry, tympanometry and neurologic examinations including cranial magnetic resonance imaging (MRI) and neurological physical examinations were all normal. Rhythmic palatal movements produced a high-pitched “clicking” sound with a frequency of approximately 100 clicks per minute (Additional file 1: Video S1, Additional file 2: Video S2 and Additional file 3: Video S3). The examiner could clearly hear the sound at a distance of 10 cm from the nasal tip. When the patient was asked to tilt his neck slightly backward, the noise was reduced (Additional file 4: Video S4).

Additional file 1: Video S1. “Clicking” noise and video recorded by cellphone. (MP4 1840 kb)

Additional file 2: Video S2. Oropharyngeal examination video recorded by endoscopy. (MP4 1700 kb)

Additional file 3: Video S3. Nasopharyngeal examination video recorded by endoscopy. (MP4 7560 kb)

Additional file 4: Video S4. Tremor ceased when tilted backward. (MP4 6310 kb)

Laboratory results including routine blood work, antinuclear antibody analysis, thyroid tests, and hepatic and renal functions tests were all normal (Table 1). Computed tomography (CT) scans of the brain and cervical region did not show any abnormalities. A nasal sinus CT scan revealed fungal maxillary sinusitis on the left side (Fig. 1), which was treated by functional endoscopic sinus surgery. No signs of olivary nucleus hypertrophy or occupying lesions of the skull base were visible on MRI scans (Fig. 2).
Table 1

Laboratory results including routine blood work, antinuclear antibody analysis, thyroid tests, and hepatic and renal functions

Test name

Abbreviations

Item name

Results

Ref

Unit

OD value

Hepatitis B virus

HBSAG

HbsAg

0.688 (Negative)

<1.000

COI

0.688

AHBS

Anti-HBs

2.00 (Negative)

 

IU/L

2.000

HBEAG

HbeAg

0.101 (Negative)

<1.000

COI

0.101

AHBE

Anti-Hbe

1.56 (Negative)

>1.000

COI

1.560

AHBC

Anti-HBc

1.89 (Negative)

>1.000

COI

1.890

HIV,HCV,TPHA

HIV

HIV antibodies (screen)

Negative

Negative

 

0

HCV

Anti-HCV

Negative

Negative

 

0

TPHA

Treponema pallidum specific antibody

Negative

Negative

 

0

Electrolytes, liver and kidney function

ALT

Glutamic-pyruvic transaminase

19

0 ~ 50

U/L

19.000

AST

Glutamic oxalacetic transaminase

18

15 ~ 45

U/L

18.000

AS/AL

AST/ALT

0.95

  

0.947

ALP

Alkaline phosphatase

95

45 ~ 125

U/L

95.000

GGT

Glutamyl transpeptidase

35

10 ~ 60

U/L

35.000

TP

Total protein

78.9

61.0 ~ 79.0

g/L

78.900

ALB

Albumin

44.9

34.0 ~ 48.0

g/L

44.900

GLO

Globulin

34.0

24.8 ~ 38.8

g/L

34.000

A/G

ALB/GLB

1.3

1.2 ~ 2.0

 

1.321

TBIL

Total bilirubin

10.4

6.8 ~ 34.2

μmol/L

10.400

DBIL

Direct bilirubin

1.5

1.7 ~ 8.6

μmol/L

1.500

IBIL

Indirect bilirubin

8.9

4.8 ~ 25.0

μmol/L

8.900

GLU-S

Fasting blood-glucose

5.53

3.90 ~ 6.10

mmol/L

5.530

BUN

Serum urea

3.82

2.90 ~ 8.20

mmol/L

3.820

CREA

Creatinine

91.2

50.0 ~ 133.0

μmol/L

91.200

BU/CR

Serum urea/Creatinine

0.042

0.03 ~ 0.15

 

0.042

UA

Uric acid

260

149 ~ 416

μmol/L

260.000

NA

Sodium

137.5

137.0 ~ 147.0

mmol/L

137.500

K

Kalium

4.33

3.50 ~ 5.30

mmol/L

4.330

CL

Chlorine

105.3

99.0 ~ 110.0

mmol/L

105.300

Routine stool test

YS

Color

Yellow

  

0

JD

Toughness

Soft

  

0

NY

Mucus

Negative

  

0

BXQ

White blood cells (stool)

Negative

 

/High power field

0

HXB

Red blood cells (stool)

Negative

 

/High power field

0

NC

Pyocyte

Not found

 

/Low power field

0

AMB

Amebic protozoa

Not found

Not found

 

0

JMJ

Saccharomycopsis

Not found

Not found

 

0

HCL

Ova of roundworm

Not found

Not found

 

0

NX

Purulent blood

Negative

Negative

 

0

CL

Ovum

Not found

Not found

 

0

JSC

Parasite

Not found

  

0

Urine routines

COLOR

Color

Faint yellow

  

2.000

TURB

Turbidity

Clear

  

0

WBC

Leukocyte count

0.54

 

/High power field

0.540

WBC1

Leukocyte count

3.00

 

/μl

3.002

RBC

Erythrocyte count

1.80

 

/High power field

1.800

RBC1

Erythrocyte count

10.01

 

/μl

10.008

TMGX

Hyaline cast

2.90

 

/Low power field

2.900

WFLGX

Granular casts

Negative

Negative

/Low power field

−2.900

CG

Cellular cast

Negative

Negative

/Low power field

−2.900

LZSP

Squamous epithelial cell

5.80

 

/Low power field

2.000

BLD

Urine occult blood

Weakly positive (±)

Negative

 

0

BIL

Urine bilirubin

Negative

Negative

 

0

URO

Urobilinogen

Negative

Negative

 

0

KET

Urine acetone bodies

Negative

Negative

 

0

PRO

Qualitative test of urinary protein

Weakly positive (±)

Negative

 

0

SG

Urine specific gravity

1.019

1.003 ~ 1.03

 

1.019

NIT

Nitrite

Negative

Negative

 

0

GLU

Urine sugar

Negative

Negative

 

0

PH

pH

7.0

4.6 ~ 8

 

7.000

LEU

Neutrophil esterase

Negative

Negative

 

0

Blood coagulation

PT

Prothrombin time

12.00

12.00 ~ 15.00

Second

12.000

PTS-CP

Normal controls (PT)

12.50

 

Second

12.500

INR

International normalized ratio

0.95

0.85 ~ 1.15

 

0.950

APTT

Activated partial thromboplastin time

32.10

30.00 ~ 45.00

Second

32.100

APTTS-

Normal controls (APTT)

35.00

 

Second

35.000

TT

Thrombin time

16.30

14.00 ~ 18.00

Second

16.300

FIB

Fibrinogen

2.95

2.00 ~ 4.00

g/L

2.950

BBBC

Sample preservation

The sample retained for three days

  

1.000

Blood routine

WBC

Leukocyte count

7.00

4 ~ 10

×10^9/L

7.000

NEUT%

Ratio of neutrophil

0.647

  

0.647

LYMPH%

Ratio of lymphocyte

0.286

  

0.286

MONO%

Ratio of monocytes

0.044

  

0.044

EO%

Ratio of eosinophils

0.013

  

0.013

BASO%

Ratio of basophils

0.006

  

0.006

IG%

Ratio of immature granulocytes

0.004

  

0.004

YC1

Annormal lymphocytes

Not found

  

0

YZXB5

Juvenile cells

Not found

  

0

NEUT#

Neutrophil count

4.529

 

×10^9/L

4.529

LYMPH#

Lymphocyte count

2.002

 

×10^9/L

2.002

MONO#

monocyte count

0.308

 

×10^9/L

0.308

EO#

eosinophil count

0.091

 

×10^9/L

0.091

BASO#

Basophil count

0.042

 

×10^9/L

0.042

IG#

immature granulocyte count

0.028

 

×10^9/L

0.028

HGB

Hemoglobin

148

120 ~ 160

g/L

148.000

RBC

Erythrocyte count

4.88

4 ~ 5.5

×10^12/L

4.880

HCT

Hematokrit

0.429

0.4 ~ 0.54

 

0.429

MCV

Mean corpuscular volume

87.90

80 ~ 100

fl

87.900

MCH

Mean corpuscular hemoglobin

30.30

27 ~ 34

pg

30.300

MCHC

Mean corpuscular-hemoglobin concentration

345

320 ~ 360

g/L

345.000

RDW-CV

Red cell distribution width-CV

13.0

11.6 ~ 14.6

%

13.000

RDW-SD

Red cell distribution width-SD

41.5

 

fl

41.500

PLT

platelets counts

334

100 ~ 300

×10^9/L

334.000

PCT

Thrombocytocrit

0.34

0.11 ~ 0.28

 

0.340

MPV

Mean platelet volume

10.30

6.5 ~ 11

fl

10.300

P-LCR

Platelet-large cell ratio

27.40

 

%

27.400

PDW

Platelet distribution width

12.30

9 ~ 17

%

12.300

ZDKL

Toxic granulation

Negative

  

0

YHH

Nucleated red blood cell count

0.0

 

/100WBC

0

YCC

Abnormal cell

Not found

  

0

BBBC

Sample preservation

The sample retained for three days

  

1.000

Blood type

ABO

ABO blood group system

AB

  

0

RH

RH(D) blood group

Positive

  

0

Thyroid function tests

TOTT3

Total T3

0.78

0.87 ~ 1.78

ng/ml

0.780

TOTT4

Total T4

7.01

6.10 - 12.20

μg/dl

7.010

FT3

Free T3

2.52

2.50 ~ 3.90

pg/ml

2.520

FRT4

Free T4

0.88

0.61 ~ 1.12

ng/dl

0.880

TSH

Thyroid stimulating hormone

1.06

0.34 ~ 5.60

μIU/ml

1.060

Bronchofiberscope

 

Mould

Not found

  

0

  

Smear results

Found no acid fast bacilli

  

0

Fig. 1

Coronal CT image of sinuses, indicating fungal rhinosinusitis of the left maxillary sinus

Fig. 2

Cranial MRI image of the horizontal position. No occupying lesions or abnormal signal of the inferior olive was observed

Nasal endoscopic examination and sinus surgery

We then performed a nasal endoscopic examination. Involuntary rhythmic movements of the nasopharyngeal lateral wall or muscles surrounding the eustachian tube were not observed (Additional file 2: Video S2 and Additional file 3: Video S3). However, the torus tubarius was found to be involved. We identified the source of the clicks on the basis of the adjacency of the sound to the nose and throat. Thus, the nasal cavity was confirmed as the source of the sound.

Endoscopic sinus surgery was performed to open the left maxillary sinus. The patient was placed in the supine position. After endotracheal intubation and routine disinfection, sterile drapes were placed and the operation commenced. An adrenaline cotton sheet was placed in the left nasal mucosa to absorb nasal secretions. The middle turbinate root, agger and uncinate process of the left side were locally anesthetized by injecting lidocaine-containing adrenaline. Under 0° endoscopy, the left uncinate process was lifted by a nasal probe, and the tail section of the uncinate process was separated. The upper and lower ends of the uncinate process adjacent to the lateral nasal wall were excised with a curved scissor. The separated uncinate process was removed with an ethmoidal sinus forcep. Thereafter, the bone at the tail end of the uncinate process was removed with a detacher and the anterior fontanelle was removed with a back biting rongeur. Thus, the natural orifice of the maxillary sinus was expanded. The maxillary sinus observed with 70° endoscopy revealed several brown bean-curd-residue-like lesions. A subsequent pathological examination confirmed that they were mould clumps. We cleaned the lesions, flushed the maxillary sinus cavity with saline via a curved suction tube, and ensured that the sinus mucosa was smooth and without any residual lesions. The left nasal cavity was filled with one expansion sponge, and the operation was completed.

However, the “clicking” noise did not stop. In a follow-up exam three months after surgery, we confirmed that the ostium of the left maxillary sinus had significantly opened up, and the sinus was clean.

Electromyography

To determine the etiology of the nasal click, we recorded the activities of the soft palatal muscles including the TVP, palatopharyngeus, palatoglossus, levator veli palatini (LVP), and uvularis muscles by direct electromyography (EMG, Fig. 3). All the above-mentioned muscles except the TVP revealed abnormal waveforms. This was a highly unusual finding. The TPV is usually the main muscle associated with EPT. However, our EMG results revealed that all other muscles except the TVP were causing these contractions.
Fig. 3

EMG recordings of palatal tremor activities are shown

Treatment

The nasal clicks significantly affected the patient’s social life. The patient did not receive any other treatment from other hospitals before he arrived at our hospital. To explore whether blocking nerve impulse conduction can weaken or eliminate the tremors, we first injected 0.5 mL of 2% lidocaine into the palatal muscles including the palatopharyngeus, palatoglossus, LVP and uvularis muscles. Palatal tremors disappeared, but returned within four hours given that the effective time of lidocaine anesthesia is approximately 1.5 h. When the patient visited our hospital a week later, we modified the treatment strategy. Botulinum toxin was injected into four different regions (dose, 12.5 U/site) of the soft palatine (Fig. 4). The patient tolerated the injections well on the first day. On the second day, the patient experienced dragging pain, and his tongue twisted involuntarily when he had to open his mouth wide. Two weeks later, the pain subsided, and his lisp disappeared. The patient did not complain of excessive phlegm thereafter. No other side effects such as choking after drinking or difficulty in swallowing were reported. Three months after receiving botulinum toxin injections, the palatal tremors disappeared; and the patient felt well. However, eight months after the botulinum toxin injections, the palatal tremors recurred; but the frequency of the tremors and number of attacks were reduced. Rapid contractions of the velar muscles sometimes occurred when he was nervous or tired, or had consumed alcohol; but he could control them voluntarily (Additional file 5: Video S5). An EMG test at this point showed complete relief of the LVP and uvularis muscles besides palatoglossus and palatopharyngeus.
Fig. 4

Sites of botulinum toxin injections

Additional file 5: Video S5. Endoscopic record 8 months after injection. (MP4 22200 kb)

Discussion

Auditory clicks arising from the rhythmic contraction of any of the muscles in the ear and throat [1, 2] are regarded as a primary symptom of EPT. The case of our patient was unique, because the clicks were nasal in origin.

The tremors would stop when the patient was asleep. The palatal tremor cycle could not be restored by inhibition of the trigeminal nerve using lidocaine. Neurological examination results and brain MRI scans were normal. MRI scans have shown increased signal intensity on T2 weighted images in SPT patients with injury to the dentate-olivary complex, indicating hypertrophy of the olivary nucleus [7, 8]. MRI scans of our patient revealed no evidence of structural abnormalities. Thus, SPT was excluded as a cause. To our knowledge, this is the first case of EPT associated with nasal clicks instead of otic clicks.

Otic clicks are caused by abnormal contractions of both the TVP and LVP muscles. However, objective otic clicks due to LVP contractions have not been reported since 1996 [9]. In our patient, otic clicks were completely absent (Additional file 1: Video S1). Therefore, we suspected that some muscles of the soft palate other than the TVP such as the palatopharyngeus, palatoglossus, uvularis, and/or LVP muscles contributed to the nasal clicks. EMG results confirmed that all the above muscles were involved, except the TVP.

EPT clicks are affected by mouth opening, speaking [9], head position [10] and relaxation [11]. In our patient, tilting the head backwards and speaking could completely suppress the tremors.

No specific treatment has been reported for EPT. In 1997, Cakmur et al. [12] reported that a 16-year old girl, who had been diagnosed with EPT at the age of six, was successfully treated with flunarizine, which is a selective calcium entry blocker with antihistaminic, antiserotoninergic and antidopaminergic activity [13]. However, the tremor was found to recur after flunarizine was discontinued.

Campistol-Plana et al. [14] suggested that TPV and tubal pharynx muscles are controlled by the glossopharyngeal nerve and pharyngeal plexus. Their treatment of four pediatric patients with 2% lidocaine resulted in the gradual disappearance of palatal tremors.

Nasr and Brown reported that a 37-year-old man with a history of alcohol abuse, palatal tremors and ear clicks, and who had been hospitalized for excessive alcohol intake, has shown gradual improvement of ear clicks and frequency of tremors after being treated with lamotrigine, which is a sodium channel blocking antiepileptic drug [15]. However, the long-term success of this drug could not be determined, because the patient discontinued its use after being discharged from the hospital.

Botulinum toxin is a neurotoxin that blocks neuromuscular transmission by inhibiting the acetylcholine receptor. Since the establishment of botulinum toxin as a safe and tolerable treatment for various therapeutic indications [16] including migraine [17], cerebral palsy [18], and cervical and maxillofacial conditions [19], it has been sporadically tested for treating EPTs.

In some cases, botulinum toxin was directly injected into the soft palate to ameliorate symptoms [20, 21]. Its efficacy in EPT stems from the fact that it binds to cholinergic nerve endings and causes muscular paralysis, thereby reducing muscular contractions. Its long-term use has not been found to cause permanent muscular degeneration [22, 23].

Recently, Tobias et al. [24] reported that long-term botulinum toxin injections could relieve objective tinnitus in a 78-year-old woman with minimal side effects. However, the toxin yielded temporary effects and had to be administered every 5–6 months to prevent recurrence of symptoms that could affect the daily activities of the patient.

Anis and Pollak reported that a 36-year-old woman with EPT, who had failed to respond to conservative treatment with anxiolytics, was successfully treated with 2–3 injections of botulinum toxin [25]. Symptomatic relief was obtained within two days of injection.

Even though the source of the clicks in our patient was different from that reported in previous cases, we applied symptom-guided injections of botulinum toxin in our patient. Unlike the temporary relief provided by lidocaine injections, four simultaneous injections of botulinum toxin were found to diminish the tremors in our patient. Although our patient tolerated the treatment well, alleviation of symptoms required at least two weeks. Variability in time and dosage required for symptomatic relief in our patient and in patients reported in previous studies suggests that individualized titration of dose and frequency by close monitoring of symptoms may be critical in achieving long-term benefits, as suggested by Anis and Pollak [25].

Although the etiology of EPT remains unclear, some patients were found to have minor ailments [26] or symptoms such as otitis media, fever, or tonsillitis before the occurrence of EPTs. Our patient had excessive phlegm for two years and pharyngalgia for one week. We believe that these symptoms could be related to the etiology of EPT, because they were spontaneously relieved within 15 days after botulinum toxin treatment. Additional studies will be required to determine the pathogenesis of EPT with nasal clicks, as well as the occurrence of phlegm and pharyngalgia.

Conclusions

Tinnitus is the most common symptom of EPT. In this study, we report the first case of a patient with EPT who presented with nasal clicks, instead of objective pulsatile tinnitus. Similar to previous reports, botulinum toxin injections were found to alleviate symptoms and improve the quality of life of the patient for up to three months. Although the detailed pathophysiology and etiology of EPT that presented with nasal clicks remains unclear, we recommend that otolaryngologists should expect this rare occurrence in the clinical setting. Patients with this rare disorder usually have a poor social life. Therefore, clinicians should exercise care, patience and attention when handling such cases in order not to worsen the psychological status of the patient.

Abbreviations

CT: 

Computed tomography

EMG: 

Electromyography

EPT: 

Essential palatal tremor

LVP: 

Levator veli palatini

MRI: 

Magnetic resonance imaging

SPT: 

Symptomatic palatal tremor

TVP: 

Tensor veli palatini

Declarations

Acknowledgements

Not applicable.

Funding

Not applicable.

Availability of data and materials

The data and materials supporting the conclusions of this article are included within the article and its additional files.

Authors’ contributions

LN conceived of the study, participated in its design and coordination and helped to draft the manuscript. YY drafted the article and revising it critically for important intellectual content. SL participated in the EMG data. BL participated in the endoscopic data. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

The participant in this report signed the consent for publication of his personal data in any form (including individual details, images or videos) in this article.

Ethics approval and consent to participate

The participant in this report signed informed consent, participated voluntarily, and had the right to withdraw at any stage. Ethical approval was obtained from The Second Hospital of Wenzhou Medical University Research Ethics Committee. The ethics reference number is L-2016-17.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
ENT Department, The Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University

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