Abstract
Background
Swallowing deficits and freezing phenomena represent severe parkinsonian features. Freezing as a symptom occurring during swallowing has not been reported on yet.
Methods
We report on 3 patients with probable PSP‐parkinsonism (PSP‐P) who manifested freezing of swallowing (FOS).
Results
All 3 patients experienced severe weight loss in recent months. At examination, 1 patient had freezing of gait. Video fluoroscopy showed nonfunctional trembling movements of the tongue and palate during chewing and volitional swallowing, with a 6‐ to 8‐Hz frequency that is typical for freezing episodes during walking and finger tapping. These freezing episodes were accompanied by impaired oral bolus transportation. The pharyngeal phase was not relevantly affected.
Conclusions
FOS represents a novel disease feature of PSP‐P. The feature may have fundamental, but potentially treatable, consequences for patients' health and quality of life and may be considered in patients with degenerative parkinsonism who experience severe and unexplained weight loss.
Keywords: dysphagia, freezing, motor block, parkinsonism, swallowing
Freezing is a sudden, paroxysmal breakdown of movement. Freezing occurs regularly in advanced Parkinson's disease (PD) and in atypical parkinsonian disorders, such as PSP.1 The phenotype recognized best is freezing of gait (FOG), 2, 3, 4 although highly similar episodic phenomena can also occur during other movements, such as writing, finger tapping, or speaking.5, 6 Here, we describe a new phenotype in 3 patients (Table 1) who showed clear freezing episodes of the tongue and palate during chewing and volitional swallowing (Video S1).
Table 1.
Demographic and clinical data of the 3 PSP patients with FOS
| Patient 1 | Patient 2 | Patient 3 | |
|---|---|---|---|
| Sex | Female | Male | Female |
| Age at investigation | 70 | 50 | 71 |
| Disease duration | 6 years | 3 years | 4 years |
| H & Y stage | 4 | 2 | 3 |
| UPDRS‐III score | 93 | 16 | 46 |
| MMSE score | 25 | 26 | 22 |
| Medication |
l‐dopa 850 mg Amantadine 300 mg |
l‐dopa 1,000 mg Amantadine 400 mg |
l‐dopa 650 mg Amantadine 400 mg |
| FOS | Yes | Yes | Yes |
| FOG | Reported to occur at home | No | Yes |
MMSE, Mini–Mental State Examination; UPDRS‐III, motor part of the UPDRS.
Patient 1
A 64‐year‐old right‐handed Caucasian woman experienced slight gait disturbances and right‐sided fine motor deficits in 2008. She was initially diagnosed with PD in 2009 and responded well to even low doses of dopaminergic treatment. Three years after disease onset, she developed FOG, postural instability, falls, and supranuclear gaze palsy, whereas the most affected side changed from the right to the left. She was now diagnosed with PSP‐parkinsonism (PSP‐P). Subsequently, progressive speech difficulties occurred, which increasingly hampered verbal communication. During 2013, she experienced severe sialorrhea and swallowing problems, which she described as “having problems with transporting food in the right direction of the mouth, and problems with swallowing speed.” She massively lost weight during 2014, including 6 kg during the last 3 months before referral to the ward in September 2014. Upon admission, body mass index (BMI) was 14.6 kg/m2. Neurological examination revealed sialorrhea and hypomimia, up‐ and downward supranuclear gaze palsy, postural instability, severely hastened speech and repetition of syllables, axial and distal bradykinesia, rigidity, and resting tremor, all without lateralization. Gait was irregular, but without FOG (this did occasionally occur at home). The applause sign was positive. Cerebral MRI showed mild global atrophy. Chewing was slow and initiation of volitional swallowing was severely delayed. During swallowing, no clinical signs of aspiration occurred. Video fluoroscopy (16 and 32 frames per second) repetitively revealed severe and irregular 6‐ to 8‐Hz trembling of the tongue base and soft palate, as determined with slow motion view (not shown). Levodopa doses up to 850 mg and external cueing exercises did not influence this swallowing problem, and subsequent withdrawal of l‐dopa gave no clinical worsening.
Patient 2
A right‐handed Caucasian man developed bradykinesia and rigidity in 2011 when he was 47 years old. He responded well to high l‐dopa doses and to dopamine agonist therapy, without response fluctuations. He never manifested FOG. Relatives reported mild cognitive decline and aggressive behavior during the last months. He was referred to the ward in May 2014 because of 8‐kg weight loss during the previous 6 months. He personally experienced sialorrhea and “problems with tongue movement,” but no swallowing problems. Upon admission, BMI was 18.2 kg/m2. The patient experienced sialorrhea as his most troublesome symptom, but also reported chewing problems. Neurological examination—performed on his usual dopaminergic medication—revealed severe sialorrhea and hypomimia, problems with repeating the first syllables of words, hastened speech and speech pauses, axial hypokinesia, bradykinesia, and cogwheel rigidity in the arms. These signs were lateralized slightly to the right side. There were no involuntary movements, tremor, or vertical gaze palsy. Arm swing was reduced bilaterally, but gait and balance were otherwise normal (including tests for FOG). He had a positive applause sign, suggesting frontosubcortical dysfunction. Cerebral MRI was nondirectional. Taken together, we considered PSP‐P to be the most likely diagnosis. We examined his swallowing function in more detail. Chewing was difficult to initiate and execute, and initiation of volitional swallowing was severely delayed and regularly impossible. No clinical signs of aspiration during swallowing (e.g., coughing, throat clearing, or a change in voice quality) were observed. Video fluoroscopy revealed impaired oral bolus transportation with bradykinetic pumping movements of the tongue, and with trembling, irregular 6‐ to 8‐Hz movements of the tongue base and soft palate that suggested freezing.7 In the pharyngeal phase, slight abnormalities with ineffectual clearing of the vallecular and pyriform sinuses were observed with little bolus retention. l‐dopa doses up to 1,000 mg and cessation of dopaminergic therapy, as well as external cueing strategies, did not influence these swallowing problems, whereas 200 mg of intravenous amantadine slightly improved dysarthria and dysphagia.
Patient 3
A 67‐year‐old right‐handed Caucasian woman experienced left‐sided rigidity, resting tremor, and fine motor deficits in 2010. She was initially diagnosed with PD in 2011. Three years after disease onset, tremor disappeared and gait difficulties and FOG occurred. She simultaneously developed progressive and daily‐relevant speech difficulties. She also experienced sialorrhea and swallowing problems, which she described as “transport problems of fluids and food by the tongue.” In April 2014, she was referred to the ward because of 10‐kg weight loss during the previous 6 months. Upon admission, her BMI was 15.6 kg/m2. Neurological examination revealed mild sialorrhea and hypomimia, severely hastened speech and speech pauses, and slightly lateralized bradykinesia and rigidity. Severe FOG episodes occurred during turning and step initiation with 7‐ to 8‐Hz trembling of the legs (assessed with a wearable sensor at the knee, not shown). Neuropsychological examination showed deficits in executive functioning and orientation. Cerebral MRI was normal. Chewing was not obviously affected, but initiation of volitional swallowing was delayed. During swallowing, no clinical signs of aspiration occurred. Video fluoroscopy revealed impaired oral bolus transportation with insufficient tongue pumping movements and repetitive trembling, high‐frequency movements (5—8 Hz) of the tongue base and soft palate. In the pharyngeal phase, neither aspiration nor retentions were observed. l‐dopa doses up to 650 mg and cessation of dopaminergic therapy did not show any influence on these swallowing problems, whereas methylphenidate 30 mg/day (given to alleviate FOG8) slightly improved gait and dysarthria, but without significant effect on swallowing. External cueing strategies (tactile cueing of the cheeks and verbal rhythmic cueing with counting) did not improve the freezing of swallowing (FOS).
Discussion
This is the first report of FOS, which we present as associated with marked weight loss and dysphagia in patients presenting with PSP‐P. Our motivation for classifying the episodic movement of the soft palate and base of the tongue as freezing was based on the video fluoroscopy findings, which, in all 3 patients, showed trembling movements during chewing and volitional swallowing, with a frequency that is typical for freezing episodes in other body parts (e.g., walking2, 3, 4 and finger tapping5, 6). Similar to FOG—where motor blocks impede effective stepping movements—these freezing episodes during chewing and swallowing interfered with the normal process of deglutition. We cannot exclude with absolute certainty that the trembling does not represent, for example, tremor, oromandibular/pharyngeal apraxia, and myorhythmia9; however, we argue that irregularity and high frequency of the movement, presence of parkinsonian signs for up to 6 years and presence of only mild cognitive dysfunction, as well as absence of tremor, dystonia, and changes of consciousness at physical examination make these differential diagnoses improbable.
The phenotype of FOS was consistent across subjects and may therefore be indicative for clinical diagnosis: All 3 patients presented with cachexia, axial parkinsonism, sialorrhea, and hypophonic dysarthria with speech pauses and hastened speech. Moreover, video fluoroscopy revealed that FOS was accompanied by bradykinetic movements of the tongue. Only 1 patient had FOG during examination, so FOS can—comparably to freezing of the upper limbs—occur without FOG. Currently, we see video fluoroscopy as the diagnostic method of choice.
Previous observations confirm that dysphagia and severe weight loss are common in PSP.10, 11, 12 For example, in a study including 27 PSP patients, barium swallow and ultrasound showed that 70% had a delayed initiation of the swallowing reflex and 63% an impaired tongue motility.11 Another study examined 10 PSP patients using video fluoroscopy; all patients showed delayed or uncoordinated bolus transfer of the tongue.12 In another report, a PSP patient with severe weight loss exhibited pathological features typical of PSP.10 Note that these studies were performed in a time when freezing was not well recognized, so FOS may have been overlooked.
We do not know whether FOS is restricted to PSP‐P. Given that such patients resemble more advanced stages of PD (where dysphagia, dysarthria, and weight loss are common13), we recommend that FOS should also be considered in patients with parkinsonism in general who present with severe weight loss. Future studies should investigate the frequency of FOS in age‐related diseases with swallowing dysfunction and test whether FOS itself (and not [only] tongue and soft palate bradykinesia and other optional causes) contributes relevantly to dysphagia and weight loss.
Treatment of FOS appears difficult. Adequate doses of l‐dopa, methylphenidate, or amantadine had at best very limited success. External cueing—shown previously to be effective for FOG3, 14—was neither effective. The emphasis of FOS treatment strategies should be on existing management strategies for FOG,3, 15 which have to be explored in more detail regarding their usefulness in the swallowing deficit described here.
Author Roles
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
W.M.: 1A, 2B, 2A, 2B
T.W.R.: 1B, 1C, 2B
M.A.H.: 1B, 1C, 2B
B.B.: 1B, 1C, 2B
M.S.: 1C, 2B
A.B.: 1C, 2B
D.B.: 1C, 2B
E.S.: 1C, 2B
N.R.: 1C, 2B
D.D.: 1A, 2B
B.R.B.: 1A, 2B
Disclosures
Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.
Financial Disclosures for previous 12 months: W.M. receives funding from the European Union, from the Michael J Fox Foundation (MJFF), the Neuroalliance, and Janssen. He received funding from the Robert Bosch foundation and speaker honoraria from GlaxoSmithKline (GSK), Rölke Pharma, Licher, and UCB. T.W.R. received a travel grant from IPSEN (2014). M.A.H. received a travel grant from AbbVie (2015). M.S. receives funding from the Robert Bosch Foundation and the Volkswagenstiftung. He received speaker's honoraria from Actelion Pharmaceuticals (2012–2014). D.B. is a member of the advisory boards of Novartis, UCB Pharma GmbH, and Lundbeck. She received honoraria from UCB Pharma GmbH, TEVA, and Lundbeck and has been funded by grants from the MJFF, BmBF, dPV (German Parkinson's disease association), Center of Integrative Neurosciences, Internationale Parkinson Fonds, Janssen Pharmaceutica, Boehringer Ingelheim Pharma GmbH, TEVA Pharma GmbH, and UCB Pharma GmbH. D.D. served on the scientific advisory board for Novartis, Orkyn, and Aguettant and has received PHRC grants from the French Ministry of Health and research funding from France Parkinson and the ARSLA charity. He has received various honoraria from pharmaceutical companies for consultancy and lectures on Parkinson's disease at symposia. B.R.B. receives funding from the National Parkinson Foundation, the Nederlands organization for scientific research, International Parkinsonfonds, and the MJFF. He received honoraria from Danere, GSK, and UCB. B.B. received funding from the Deutsche Forschungsgemeinschaft (2011) and Wilhelm‐Schuler‐Stiftung (2011). He received travel grants from Bayer Vital (2010–2014).
Supporting information
A video accompanying this article is available in the supporting information here.
Video S1. Patient 1: A 70‐year‐old woman with PSP‐P shows severely hastened speech and repetition of syllables. Volitional swallowing of water is almost impossible even with a drinking straw. Video fluoroscopy reveals severe and irregular high‐frequency trembling of the tongue base and soft palate. Patient 2: A 50‐year‐old PSP‐P patient has severe difficulties initiating chewing. Volitional swallowing is impossible. Video fluoroscopy shows impaired oral bolus transportation with irregular high‐frequent movements of the tongue base and soft palate. Patient 3: A 71‐year‐old PSP‐P patient presents with delayed volitional swallowing. Severe FOG occurs during turning and step initiation. Video fluoroscopy reveals short high‐frequency movements of the tongue base and soft palate.
Walter Maetzler, Tim W. Rattay, and Markus A. Hobert contributed equally to this work.
Relevant disclosures and conflicts of interest are listed at the end of this article.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
A video accompanying this article is available in the supporting information here.
Video S1. Patient 1: A 70‐year‐old woman with PSP‐P shows severely hastened speech and repetition of syllables. Volitional swallowing of water is almost impossible even with a drinking straw. Video fluoroscopy reveals severe and irregular high‐frequency trembling of the tongue base and soft palate. Patient 2: A 50‐year‐old PSP‐P patient has severe difficulties initiating chewing. Volitional swallowing is impossible. Video fluoroscopy shows impaired oral bolus transportation with irregular high‐frequent movements of the tongue base and soft palate. Patient 3: A 71‐year‐old PSP‐P patient presents with delayed volitional swallowing. Severe FOG occurs during turning and step initiation. Video fluoroscopy reveals short high‐frequency movements of the tongue base and soft palate.