Progressive Ataxia and Palatal Tremor Is Not Associated with IgLON5 Antibodies: Results From Two Cases.

Progressive ataxia and palatal tremor (PAPT) and anti-IgLON5 disease share possible clinical presentations. Furthermore, both have been associated to a tauopathy mainly affecting the brainstem. Nonetheless, anti-IgLON5 antibodies have never been tested in PAPT. We report on two PAPT cases without evidence of anti-IgLON5 antibodies in both CSF and serum. Despite common clinical and pathological characteristics, PAPT and IgLON5 disease are two distinct entities.

Post-stroke palatal tremor as a clinical predictor of dysphagia and its neuroanatomical correlates in patients with midbrain and pontine lesions.

The precise associations between dysphagia and palatal tremor (PT) remain unknown. We aimed to identify the association between PT and dysphagia among patients with midbrain/pontine stroke, compare the characteristics of dysphagia between patients with PT (PT + dysphagia) and without PT (PT- dysphagia), and verify neuroanatomical predictors of PT + dysphagia in this patient population. This retrospective observational study enrolled 40 patients (34 males, 6 females; mean age: 95% confidence interval [CI], 56.6 ± 14.6 years) with first-ever midbrain or pontine stroke exhibiting brain stem lesions admitted to the stroke unit of a single rehabilitation hospital between January 2010 and April 2020. Main outcome measures included dysphagia and aspiration rates and videofluoroscopic swallowing study findings. Lesion localization was stratified according to established vascular territories. Associations between PT and dysphagia and lesion location according to PT and dysphagia were analyzed. Dysphagia and aspiration rates were greater among patients with PT than among those without PT (95% CI, p = 0.030 and p = 0.017, respectively). The proportion of patients exhibiting oral stage impairment (95% CI, p = 0.007) was greater in the PT + dysphagia group than in the PT- dysphagia group. The posterolateral portion of the midbrain and pons (95% CI, p = 0.001 and p < 0.001, respectively) were the lesions more often involved in the PT + dysphagia group. Patients with PT following midbrain/pontine stroke more frequently present with dysphagia than those without PT. Thus, they should be carefully examined for PT and delayed dysphagia, including oral stage impairment, if initial brain images show posterolateral midbrain and pons lesions.

[Hypertrophic olivary degeneration : Cause of new neurological symptoms after stroke]. / Hypertrophe Degeneration der Olive : Ursache neuerlicher neurologischer Symptome nach Schlaganfall.

BACKGROUND: Hypertrophic olivary degeneration (HOD) occurs as a result of a lesion in the anatomical functional loop of the Guillain-Mollaret triangle. Frequent causes are intracerebral hemorrhage and brain infarction. After a latent period of weeks to months after the index event a hyperintensity can initially be observed in magnetic resonance imaging T2/FLAIR-weighting and finally an enlargement of the affected olive. Characteristic symptoms are a rhythmic palatal tremor, a primarily vertical pendular nystagmus as well as Holmes' tremor of the upper limbs. AIM OF THE STUDY: The goal of this study was to illustrate the course of the disease and its clinical presentation in order to provide an improved understanding of the pathophysiology of HOD after stroke. MATERIAL AND METHODS: The neuroradiological database of the Goethe University Hospital was screened for HOD and related keywords (in German). Between 2010 and 2017 a total of 27 cases of HOD were identified, of which 12 patients had suffered a stroke in their medical history. RESULTS: The mean age of the 12 patients was 51.4 years (±13.6 years) and one third of the patients were women. Of the patients eight had an intracerebral hemorrhage, three an ischemic stroke and one had a subarachnoid hemorrhage as the causative event. The lesions were located in the pons (n = 7), cerebellum (n = 4) and pontomesencephalon (n = 1). The median latent period from the causative index event to radiological diagnosis was 24 months (min. 4 months, max. 115 months). The leading symptoms of HOD were palatal tremor (55%), Holmes' tremor (18%), pendular nystagmus (18%) and dysarthria (73%). A logopedic examination with flexible endoscopic evaluation of swallowing (FEES) could determine a palatal tremor in five out of nine cases. The diagnosis of HOD was named in the medical report in only 50% of the cases. CONCLUSION: Analysis of the dataset provided confirmation of the results in the literature that lesions within the Guillain-Mollaret triangle more often lead to HOD. Patients with corresponding symptoms should be closely observed over time with respect to the occurrence of corresponding clinical and imaging leading symptoms. Even though the named clinical symptoms are characteristic for HOD, in many cases the diagnosis is hampered and delayed by imprecise examination and misinterpretation of the symptoms. A logopedic examination using FEES in this collective often provided indicative information. Currently, no reliable data are available on the incidence of HOD after brainstem lesions or on potential preventive and treatment options. Future epidemiological and translational studies could perspectively enable valuable insights to be gained.

Palatal Tremor Revisited: Disorder with Nosological Diversity and Etiological Heterogeneity.

This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature. We highlight salient magnetic resonance imaging features, electrophysiological observations, and diverse etiologies in a large cohort of palatal tremor.

Tremor syndromes: A review.

Among the involuntary movement disorders, tremor is a common phenomenology seen in clinical practice. The important factors that need to be determined while assessing a patient with tremor include the phenomenology of tremor, presence or absence of other neurologic signs, and the effect of medications or alcohol. Tremor can broadly be classified based on the circumstances under which it occurs, i.e., rest or action. The basal ganglia-cerebello-thalamic and dentate-olivary circuits are involved in the generation of tremor. Experimental data have suggested the olivocerebellar system as the site of the central oscillator in essential tremor. Generation of tremor in Parkinson's disease results from loss of dopaminergic neurons of the retrorubral area causing dysfunction of the globus pallidus, which finally leads to abnormal firing pattern of the ventrolateral posterior neurons of the thalamus. Involvement of the cerebello-thalamic pathways leads to orthostatic tremor. Palatal tremor is thought to be generated by the cells of the inferior olive. Holmes tremor usually results from the disruption of the dentate-rubro-thalamic circuit and also the nigro-striatal circuit. Multiple drugs can cause tremors. Demyelinating neuropathies are associated with tremors. Involvement of the deep cerebellar nuclei, cerebellar outflow tracts and the cerebrocerebellar loops has been postulated in the cerebellar tremor production. Electrophysiological methods are valuable in characterizing tremors. In addition to the pharmacological therapy including botulinum toxin therapy, surgical therapies in form of DBS or lesional surgeries are beneficial in reducing the symptoms.

[Rare tremor syndromes]. / Seltene Tremorsyndrome.

BACKGROUND: There is a group of uncommon sporadic tremor syndromes, which are only partially taken into account in the current classification of tremor. Their knowledge is of diagnostic and therapeutic relevance and they should be considered in the differential diagnosis of frequent tremor syndromes. OBJECTIVE: Differential diagnostics and treatment of uncommon tremor syndromes. METHOD: Literature search (PubMed, Google Scholar). RESULTS: Holmes tremor, myorhythmia, palatal tremor, limb-shaking transient ischemic attack (TIA), tardive tremor, neuropathic tremor, tremor induced by peripheral trauma and orthostatic tremor syndrome are described. CONCLUSION: Uncommon sporadic tremor syndromes are mainly symptomatic with various underlying neurological or systemic pathologies. Their recognition accelerates the diagnostic process and has therapeutic relevance.

Progressive ataxia and palatal tremor: Two autopsy cases of a novel tauopathy.

BACKGROUND: Sporadic progressive ataxia and palatal tremor is a rare syndrome characterized by mid- to late-adult-onset symptomatic palatal tremor and slowly progressive cerebellar ataxia. To date, there has been only one autopsy report, which described a novel 4-repeat tauopathy with hypertrophic olivary degeneration and tau-positive inclusions in olivary neurons and dystrophic neuritic processes termed glomeruloid bodies. We report on 2 additional autopsy cases. METHODS: Sections from selected paraffin-embedded brain regions were stained with hematoxylin and eosin/Luxol fast blue and processed for phosphorylated tau, 3-repeat tau, 4-repeat tau, neurofilament, glial fibrillary acid protein, phosphorylated α-synuclein, phosphorylated TAR DNA-binding protein 43, beta-amyloid, and p62 immunohistochemistry. RESULTS: Two male patients were aged 74 and 64 years at onset. Both had clinical findings consistent with progressive ataxia and palatal tremor and T2 hyperintensity in the bilateral olives on MRI. Pathological findings included bilateral hypertrophic olivary degeneration accompanied by glomeruloid bodies, 3-repeat and 4-repeat tau-positive neuronal inclusions in the olive, and additional tauopathy in the midbrain, pons, and thalamus. Cerebellar cortical degeneration was extensive, but involvement of the dentate was minimal. P62-positive, but tau- and TAR DNA-binding protein 43-negative, inclusions in the cerebellum of 1 case was also a feature. CONCLUSIONS: Whereas our findings are largely in keeping with the previously published case report, we found a more extensive and mixed 3/4-repeat tauopathy and additional cerebellar p62 pathology, highlighting our incomplete understanding of the pathogenesis of this disease. © 2017 International Parkinson and Movement Disorder Society.

Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease).

Progressive ataxia and palatal tremor (PAPT) with hypertrophic olivary degeneration (HOD): A case report.

Palatal tremor has been subdivided into essential (EPT) and symptomatic palatal tremor (SPT). Progressive ataxia and palatal tremor syndrome (PAPT) is a subgroup of symptomatic palatal tremor (SPT). It can be divided into familial and sporadic forms. Sporadic PAPT is characterized by progressive cerebellar degeneration. The cause of sporadic PAPT remains uncertain. MRI examination found an enlarged appearance of the olivary nuclei with increased signal intensity on T2 and FLAIR images. Here we report a case of a mid-adult-onset man which presents a worsening cerebellar progressive ataxia with palatal tremor, in whom imaging reveals abnormalities of the olivary nuclei with tardive cerebellar atrophy which has been diagnosed as a sporadic PAPT.

External Laryngeal Tremor in Adult-Onset Alexander Disease: A Case Report.

Introduction: Alexander disease is caused by mutations in GFAP, the glial fibrillary acidic protein gene. External laryngeal tremor has not been reported in adult-onset Alexander disease (AOAxD). The aims of this work were to report one such case and to review the literature on palatopharyngeal tremor and AOAxD. Case Presentation: A 43-year-old man experienced involuntary movements at the front of his neck. Continuous, rhythmic vertical movements of the laryngeal skeleton, soft palate and tongue, and lower limb dysmetria were observed. The pathogenic GFAP variant c.994G>A; p.(Glu332Lys) was found. MRI demonstrated spinal cord and medulla oblongata atrophy and hyperintensities at the cerebellum and cerebral white matter. Conclusion: External laryngeal, palatopharyngeal tremor and cerebellar ataxia constituted a mild phenotype, as expected from this variant, herein reported in isolation for the third time. Imaging was consistent with AOAxD, including the so-called tadpole sign. Additional studies are necessary to define this infrequent disease.

[An autopsied patient with palatal tremor and fatal bilateral vocal cord abduction paralysis associated with bilateral cerebellar dentate nucleus infarction].

A 74-year-old male patient developed multiple infarcts of the brainstem and cerebellum, followed 14 months later by palatal tremor and bilateral vocal cord abduction paralysis, resulting in death due to type 2 respiratory failure. Pathologic analysis revealed old infarcts extending from the bilateral cerebellar cortices to the dentate nucleus, being more extensive on the right side, accompanied by Wallerian degeneration involving the left red nucleus, right central tegmentum tract, and inferior cerebellar peduncle, followed by pseudohypertrophy of the bilateral inferior olivary nuclei. These lesions, involving the Guillain-Mollaret triangle, may have been responsible for the palatal tremor. On the other hand, there were no evident causative lesions for the vocal cord abduction, including any in the nucleus ambiguus or posterior cricoarytenoid muscles. In this case it is possible that the dysfunction responsible for the palatal tremor may have affected the pathway from the central tegmentum tract, which is part of the Guillain-Mollaret triangle, to the vagus nerve arising from the nucleus ambiguus, which plays a role in vocal cord abduction, thus affecting the vocal cords and resulting in abduction paralysis.

Laryngeal, Pharyngeal and Respiratory Involvement in Palatal Tremor.

OBJECTIVE: To present cases of atypical palatal tremor (PT) and showcase the variable phenomenology of this condition. STUDY DESIGN: Retrospective case series. RESULTS: PT, or palatal myoclonus, is a movement disorder characterized by brief, involuntary rhythmic muscular contractions of the soft palate. Variants of PT have been described and include synchronous tremors in other branchial arch derivatives including the larynx, pharynx, neck, face, jaw, ocular and also respiratory and trunk muscles. We present 3 cases, including clinical videos, of atypical PT with extra-palatal manifestations, in addition to a brief discussion of the pathophysiology and management of this condition. CONCLUSION: Variations of PT are of interest to the practicing otolaryngologist as the clinical spectrum of this condition is wide and can present with laryngeal, pharyngeal, respiratory and other head and neck manifestations.

A 6-month trial of memantine for nystagmus and associated phenomena in oculopalatal tremor.

Introduction: Oculopalatal tremor (OPT) is a late manifestation of a Guillain-Mollaret triangle lesion. Memantine has been shown to improve nystagmus in OPT, but its long-term efficacy and putative distinct effects on each plane of nystagmus and on associated phenomena (e.g., gravity perception) are largely unknown. Methods: We conducted a 6-month open-label study to evaluate the effect of memantine in OPT patients. Baseline (visit 1), 2 (visit 2), and 6 months (visit 3) assessments included video-oculography, best corrected visual acuity (BCVA), visual function questionnaire (VFQ25), palatal tremor frequency, and subjective visual vertical (SVV). Memantine was titrated to 20 mg per day and stopped after 6 months. Results: We included six patients (5 females; mean age 68.5+/-9.7). At visit 2, nystagmus improved >50% only along the horizontal plane in two patients, while worsening >50% along the vertical and horizontal planes in 4 and 1 patients, respectively. At visit 3, previous improvement of nystagmus along the horizontal plane in two patients was not sustained, and it further worsened >50% along the vertical plane in 4. The mean vertical velocity and amplitude of nystagmus in the left eye significantly worsened from visit 2 to visit 3 (p = 0.028). Throughout the study, nystagmus frequency remained unchanged (p = 0.074), BCVA improved in both eyes (p = 0.047, p = 0.017), SVV progression was unpredictable (p = 0.513), and the mean VFQ-25 score (p = 0.223) and mean palatal frequency remained unchanged. Conclusion: The long-term use of memantine 20 mg per day in OPT produced a modest and only transient improvement in nystagmus, predominantly along the horizontal plane. Visual acuity improved, albeit without relevant changes in vision-related quality of life.

[A case of the palatal tremor that disappeared during swallowing, thought to be caused by microbleeds of bilateral dentate nucleus].

A 72-year-old female presented with slowly progressive dysphonia, which was a syllable-separated utterance, for three years. She had the rhythmic continues contraction of palatal and uvula muscles during speech with a frequency of about 2 Hz. The videoendoscopy showed that the rhythmic contraction, which synchronized in the nasopharynx and the larynx, did not disappear during vocalization. The swallowing videofluorography showed that the rhythmic contraction disappeared transiently during the swallowing reflex, and there was no aspiration. The MRI revealed olivary pseudohypertrophy and multiple microbleedings including the bilateral dentate nucleus. The degeneration of olivary nucleus secondary to the bilateral asymptomatic dentate nucleus microbleedings within the dentato-rubro-olivary pathway was thought to be a cause of palatal tremor. This is a first report that a dynamic relation between vocalization and swallowing in palatal tremor.

Objective tinnitus secondary to palatal tremor: Two case reports and brief literature review.

Objective tinnitus is defined as a type of tinnitus perceived by both the patient and external observer. This paper presents two cases of objective tinnitus related to palatal tremor, along with a literature review. Palatal tremor is a condition characterized by soft palate involuntary contractions. Two types of palatal tremor have been described: symptomatic palatal tremor and essential palatal tremor, with different clinical manifestations. Diagnostic workup is based on medical history and physical examination, including direct oropharynx exploration and cavum visualization through nasopharyngoscopy. Brain MRI is mandatory in all cases. If a secondary origin is suspected, additional lab tests should be performed based on clinical suspicion. First-line treatment is botulinum toxin injection into the levator veli palatini and tensor veli palatini muscles, with velopharyngeal insufficiency being its main adverse effect. Other medications have not been shown to be effective.

Botulinum Toxin Therapy for Oromandibular Dystonia and Other Movement Disorders in the Stomatognathic System.

Various movement disorders, such as oromandibular dystonia, oral dyskinesia, bruxism, functional (psychogenic) movement disorder, and tremors, exist in the stomatognathic system. Most patients experiencing involuntary movements due to these disorders visit dentists or oral surgeons, who may be the first healthcare providers. However, differential diagnoses require neurological and dental knowledge. This study aimed to review scientific advances in botulinum toxin therapy for these conditions. The results indicated that botulinum toxin injection is effective and safe, with few side effects in most cases when properly administered by an experienced clinician. The diagnosis and treatment of movement disorders in the stomatognathic system require both neurological and dental or oral surgical knowledge and skills, and well-designed multicenter trials with a multidisciplinary team approach must be necessary to ensure accurate diagnosis and proper treatment.