fiber optic endoscopic evaluation of swallowing ( fees ) revealed severe oropharyngeal dysphagia with poor oral bolus control , premature spillage leading to predeglutitive aspiration , a severely delayed swallowing reflex , and residues in the epiglottic valleculae and in the piriform sinus , with solid and half - solid consistencies tested , leading to postdeglutitive penetration and aspiration ( figure , c ) .
( a ) t1 gadolinium - enhanced axial mri shows no evidence of underlying brainstem or cranial nerve pathology .
( b ) no intrathecal immunoglobulin synthesis was observed in csf analysis using the reiber scheme .
( c ) fiber optic endoscopic evaluation of swallowing reveals postdeglutitive residue in the valleculae epiglotticae ( 3 ) , on top of the epiglottis ( 2 ) , and in the piriform sinuses ( 1 ) .
videofluoroscopic swallowing study showed poor oral bolus control and , as subsequently confirmed by high - resolution manometry , inadequate opening of the upper esophageal sphincter and ineffective esophageal peristalsis due to disharmonic and partially retrograde contractions .
cerebral mri ( figure , a ) including contrast - enhanced high - resolution imaging of brainstem and cranial nerves was unremarkable .
emg including repetitive nerve stimulation was normal without indication of a myasthenic reaction or myopathy .
serum acetylcholine receptor antibodies , muscle - specific tyrosine kinase antibodies , and titin antibodies were negative ( euroimmun ; lbeck , germany ) . screening for antiganglioside antibodies was negative .
ct examination of the chest and abdomen with contrast agent showed no evidence of malignancy .
screening for systemic autoimmune diseases and hematologic malignancy was negative . except for a probably irrelevant decrease in the serum / csf glucose quotient ( 0.4 , reference value 0.60.9 ) ,
no intrathecal immunoglobulin ( ig ) synthesis ( figure , b ) or isolated oligoclonal igg bands were observed and accordingly no antibody - producing plasma cells were found in the csf as revealed by flow cytometry .
autoantibody screening was positive for iglon5 igg ( + + + , 1:1,000 ) serum levels but no other known neural autoantibody .
csf was not analyzed for the presence of neural autoantibodies . however , as measured by the total igg ratio between csf and serum ( 0.003 ) , relevant csf titers of iglon5 igg can be expected even by passive diffusion .
sixteen days after admission , right - sided ptosis and peripheral facial palsy occurred , followed by respiratory deterioration necessitating orotracheal intubation and subsequent tracheotomy .
subsequent fees revealed bilateral vocal cord palsy with complete glottis closure . ambulatory polysomnography ( psg )
( somnoscreen ; somnomedics gmbh , randersacker , germany ) without videography and audiography was conducted in the intensive care unit ( icu ) .
it was applied according to american academy of sleep medicine ( aasm ) standard criteria ( aasm scoring manual 2.0 ) including eeg ( f4 , c4 , c3 , o2 , m1 , and m2 electrodes ) , electro - oculography , emg ( mental , both anterior tibialis muscles ) , cardiorespiratory recording ( single - channel ecg , thoracic and abdominal respiratory movements [ piezo ] , transcutaneous oxygen saturation ) , and body position .
sleep stages and associated events were scored according to suggested definition by sabater et al . at the time of psg ,
undifferentiated non - rem ( nrem ) sleep with frequent movement artifacts occurred during the first and second third of the night associated with recurring arousals with and without association with partly highly frequent periodic limb movements ( 92.2/h ) .
normal slow wave sleep , predominantly occurring in the last third of the night , was associated with frequent spindles .
rem sleep was reduced ( 1.5% ) and showed bursts of muscle activity in mentalis and tibial anterior muscles , compatible with rem sleep without atonia .
respiratory parameters were normal ( apnea hypopnea index 0.9/h , oxygen desaturation index 0.2/h , mean oxygen saturation 98% , minimal oxygen saturation 91% , breathing frequency 17/min ) . due to the absence of video recordings , rem sleep behavior disorder or purposeful behaviors were not assessable but recurrent motoric artifacts especially during undifferentiated nrem might be suspicious for possible behavior during rem and nrem sleep . due to the detection of iglon5 igg ,
an immune - mediated neuropathy of the cranial nerves or brainstem pathology was suspected and a total of 5 cycles of plasmapheresis ( treatment of 1.5 plasma volumes every other day ) combined with iv methylprednisolone pulse therapy ( 1 g / d for 5 consecutive days ) was initiated .
this treatment led to mild improvement of vocal cord paresis and marked remission of ptosis and facial nerve palsy .
after the patient was weaned from the respirator , fees revealed that although vocal cord paresis showed further improvement , severe pharyngeal dysphagia persisted .
the patient was transferred to a rehabilitation unit with a tracheal cannula in place without any oral intake .
nutrition was given via percutaneous endoscopic gastrostomy tube . at a follow - up visit 6 weeks later , dysphonia had substantially improved .
speaking was loud and clear when the cuff was deflated and the cannula was manually closed .
fees revealed that vocal cord paralysis had resolved and the patient was able to swallow her saliva without any problems .
when given small amounts of liquids , the swallowing reflex was triggered ; however , the whiteout was shortened and weak , corresponding to a reduced laryngeal elevation and weak pharyngeal contraction .
swallowing training started with small amounts of pudding textures , while nutrition was supplied by tube feeding .
no relapses of ptosis , facial nerve palsy , or other focal neurologic deficit were observed .
we present a case of a 77-year - old woman with slowly progressive neurogenic dysphagia as initial sign of anti - iglon5 syndrome . during the hospital
stay , multiple cranial nerves , either peripheral or central portions , were affected , leading to ptosis and facial nerve palsy on the right side .
instrumental dysphagia assessment revealed a complex pathophysiology involving the oral , pharyngeal , and esophageal phase of swallowing .
the first case series of 8 patients with anti - iglon5 syndrome was published in 2014 .
since then , 4 additional cases have been published ( table ) , all of which developed sleep abnormalities initially or during the course of the disease .
none of the patients presented initially with bulbar symptoms , whereas 10 of 12 patients developed neurogenic dysphagia during the course of the disease .
a patient with cranial nerve pathology evidenced by a bilateral ptosis was first reported in 2015 .
an overview of the clinical characteristics is provided in the table including published cases of anti - iglon5 syndrome until the present day .
clinical features , treatment , and outcome in contrast to all other published cases , the patient presented here did not show any of the previously reported symptoms , such as gait instability or chorea .
psg conducted in the icu revealed reduced sleep efficiency and the abnormal sleep architecture in nrem and rem sleep typically described in the anti - iglon5 syndrome .
video recording was not available to assess abnormal behaviors during nrem or rem sleep . with regards to treatment options ,
iv immunoglobulins were applied in 4/13 patients , iv steroids in 9/13 patients , and rituximab in 3/13 patients .
presented here , antibody depletion via plasmapheresis combined with immunosuppressive glucocorticoid therapy led to complete remission of ptosis , vocal cord paresis , and facial palsy , as well as partial remission of neurogenic dysphagia , making removal of the tracheal cannula possible during a follow - up visit . taken together , the exact role of iglon5 igg in the pathogenesis of the clinical presentations remains unclear .
iglon5 is a neuronal cell adhesion molecule predominantly expressed in the adult and developing cns but expression by peripheral nerve or skeletal or smooth muscle has not been reported so far .
the patients described so far have a broad variety of neurologic deficits as well as a heterogeneous disease course . treatment with immunosuppressants did not lead to sustained improvement in the majority of the published cases .
a suboptimal psg , lack of confirmatory antibody testing , and the absence of hla studies are limitations of this study .
the patient may have died before the syndrome had developed fully . in the patient described , the course of the disease and , in particular , the complete remission of most of the symptoms following antibody - depleting treatment may support the hypothesis of antibody - mediated effects as part of the underlying pathophysiology .
anti - iglon5 syndrome constitutes another rare differential diagnosis in patients presenting with isolated slowly progressive neurogenic dysphagia .
dr . schrder : study concept and design , acquisition of data , analysis and interpretation .
dr . melzer : analysis and interpretation , acquisition of data , critical revision of the manuscript for important intellectual content .
muhle : acquisition of data , critical revision of the manuscript for important intellectual content .
warnecke : analysis and interpretation , critical revision of the manuscript for important intellectual content .
dziewas : study concept and design , analysis and interpretation , critical revision of the manuscript for important intellectual content , study supervision .
n. melzer received travel funding and/or speaker honoraria from biogen idec , glaxosmithkline , teva , and fresenius medical care ; spends 5% of his time performing immunoadsorption ; and received research support from fresenius medical care and diamed . t. ruck received travel funding and/or speaker honoraria from genzyme , novartis , biogen , and teva ; and received research support from genzyme and novartis .
a. heidbreder received travel funding and/or speaker honoraria from air liquide , vital air , heinen+loewenstein , and ucb .
i. kleffner received travel funding and/or speaker honoraria from csl behring and received research support from imf .
t. warnecke received speaker honoraria from abbvie , teva , bayer , zamboon , and ucb ; and consulted for abbvie and ucb .
r. dziewas served on the scientific advisory board for boehringer ingelheim , pfizer , bms , bayer healthcare , daiichi sankyo , nestle health science , nutricia , fresenius , and infectopharm ; received travel funding and/or speaker honoraria from boehringer ingelheim , pfizer , bms , bayer healthcare , daiichi sankyo , nestle health science , nutricia , fresenius , and infectopharm ; and received research support from the german research foundation .
 objective : to report on dysphagia as initial sign in a case of anti - iglon5 syndrome and provide an overview of the current literature.methods:the diagnostic workup included cerebral mri , fiber optic endoscopic evaluation of swallowing ( fees ) with the fees tensilon test , a videofluoroscopic swallowing study , evoked potentials and peripheral nerve conduction studies , polysomnography , lumbar puncture , and screening for neural autoantibodies . 
 a systematic review of all published cases of iglon5 syndrome is provided.results:we report a case of anti - iglon5 syndrome presenting with slowly progressive neurogenic dysphagia . 
 fees revealed severe neurogenic dysphagia and bilateral palsy of the vocal cords . 
 autoantibody screening was positive for iglon5 igg ( + + + , 1:1,000 ) serum levels but no other known neural autoantibody . 
 polysomnography was highly suggestive of non - rem parasomnia . 
 symptoms were partially responsive to immunotherapy.conclusions:slowly progressive neurogenic dysphagia may occur as initial sign of anti - iglon5 syndrome highlighting another clinical presentation of this rare disease . 
Investigations.
DISCUSSION
AUTHOR CONTRIBUTIONS
STUDY FUNDING
DISCLOSURE