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

Abstract

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.

Introduction

There are 2 types of palatal tremor: Essential (EPT) and symptomatic (SPT). Syndrome of progressive ataxia with palatal tremor (PAPT) has been rarely described in literature, it includes an heterogenous group of diseases and can be sporadic or familial. PAPT refers to a progressive neurodegenerative disorder which is characterized by palatal tremor, cerebellar ataxia, and bulbar features on imaging.

Case report

A 57-year-old man was referred to our institution with a 1-year history of synchronous rhythmical movement of the palate, dysarthria, difficulty with coordination when reaching for items, and progressive difficulty in walking. There was no pertinent past medical history or family history. On clinical examination, the patient exhibited a widening of the sustentation polygon, lacked the ability to heel-toe walk, and walked with a wide-based gait. He presented with explosive dysarthria with finger-nose dysmetria. Apart from gaze-evoked and rebound nystagmus, The rest of the clinical examination revealed no abnormalities. Investigations revealed normal routine blood analysis, including: Thyroid-stimulating hormone (TSH), vitamin B12, antinuclear antibodies, lactate, and phytanic acid. Tests for a paraneoplastic cause of ataxia were negative. Audiological tests was normal. EMG and nerve conduction studies showed no abnormalities. Initial CT and evoked potentials were normal. Brain MRI revealed enlarged inferior olives that exhibited a high signal on T2- weighted and FLAIR images without cerebellar atrophy or supratentorial signal abnormalities (Fig. 1). The cerebellar ataxia worsened over time, a second MRI was performed 4 years later revealed the disappearance of olivary nuclei abnormalities (Fig. 2A). However, the patient had developed cerebellar atrophy (Fig. 1B and C). Genetic tests for polymerase gamma (POLG) mutation and spinocerebellar ataxia type 20 were negative. The clinical presentation, neuroimaging, investigations, and disease progression were consistent with a diagnosis of idiopathic progressive ataxia and palatal tremor (PAPT).

Fig. 1.

Sequential brain MRI scans: (A) Coronal T2-weighted section and (B) Axial FLAIR section: Bilateral and symmetric inferior olivary hypertrophy with increased signal intensity (red arrows). There are no sustentorial signal anomalies or cerebellar features.

Fig. 2.

Brain MRI performed 4 years later: (A) Axial T2-weighted section : Disappearance of olivary nuclei abnormalities,(B) coronal T2-weighted section and (C) Sagittal FLAIR section: Cerebellar atrophy.

Discussion

Palatal tremor (PT), or palatal myoclonus has been described as rhythmic movement of the anterior or posterior soft palate [1], often reported by the patient as an involuntary spasm in the throat, sometimes persists during sleep, and can affect speech and swallowing. PT is frequently associated with synchronous eye oscillations [2], oculopalatal tremor (OPT) refers to the synchronous combination of PT and pendular nystagmus. It can also be associated with synchronous movements of the larynx, pharynx, diaphragm, and facial muscles [2]. Palatal tremor (PT) has been categorized into essential (EPT) and symptomatic (SPT) forms [2].

The syndrome of progressive ataxia and palatal tremor (PAPT) is a rare, slowly progressive neurodegenerative disorder with palatal tremor, cerebellar ataxia, and bulbar features [3]. PAPT typically manifests in mid- to late-adult-onset [4], and is considered as a subtype of symptomatic palatal tremor (SPT). SPT is associated with lesions of the brainstem or cerebellar lesions within the dentato-rubro-olivary pathway [DROP] or Guillain-Mollaret triangle [4].

In contrast to other forms of SPT, in PAPT, ataxia progresses and is not usually the result of a monophasic illness[4].

Palatal tremor (PT) has been described in conjunction with the observation of hypertrophic olivary degeneration (HOD) [5].

Unilateral or bilateral hypertrophic olivary degeneration (HOD) in the medulla oblongata was first anatomically described in late nineteenth century [6].

Regarding neuropathology, the central tegmental tract, which connects the red nucleus and deep cerebellar nuclei projections to the inferior olives, is the site of origin of the injury in the majority of instances of oculopalatal tremor [3]. Olivary hypertrophy occurs as secondary phenomenon from deafferentation. However, in PAPT, the exact location of the lesion in uncertain [3]. There is mostly an isolated hypertrophic inferior olivary degeneration wich is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination [2], without a causative structural lesion identified on brainstem or cerebellar parenchyma. Some studies consider PAPT syndrome to be a tauopathy with abnormal accumulation of tau protein in the olivary nucleus [4]. PAPT can be divided into familial and sporadic forms [4] . In sporadic PAPT, the most prominent feature is progressive cerebellar degeneration, presenting as a poorly understood neurodegenerative disorder with onset in mid to late adulthood [4]. The etiology of sporadic PAPT remains elusive, and no single theory unifies its causes. However, some cases might be linked to polymerase gamma (POLG) mutations [7,8]. Familial PAPT is more complex than sporadic PAPT and may result from various etiologies including Alexander's disease, polymerase gamma mutations, spinocerebellar ataxia type 20, and GM2 gangliosidosis [4]. Familial PAPT differs from sporadic PAPT in having marked atrophy of cervical cord and brainstem with corticospinal signs, although the hypertrophic olivary appearance on MRI may be absent [1].

Clinical symptoms combines a palatal tremor with a cerebellar syndrome: Gait and limb ataxia, dysarthria, nystagmus and somtimes additional symptoms that are not necessarily related to cerebellar or brainstem disorder, such as autonomic involvement [4]. The cerebellar ataxia may precede or follow the occurrence of PT [9].

Radiological features on MRI are typicals. There is an hypertrophy and increased signal intensity within the olivary nucleus seen on in T2 /FLAIR or proton density-weighted, sometimes with cerebellar degeneration at a later stage. Hypertrophic olivary degeneration (HOD) on MRI is mostly bilateral in case of PAPT [2]. However, It may also be absent in some cases of familial PAPT [9,10]. These abnormal signals be seen within 6 months. Hypertrophy and high signal intensity persist for 3 ± 4 years, although the latter may return to normal over years [1].There is not a brainstem or cerebellar focal lesion, but there is a cerebellar atrophy progressing over years. Symptomatic PT or OPT becomes intensifies over the years, and once established, persists for life, although there are rare cases where PT or OPT has reportedly disappeared completely after many years [2].

In the context of our presented case of palatal tremor (PT) or palatal myoclonus, it is crucial to underscore the distinctive features that set it apart within the spectrum of this neurological condition. Our patient's presentation aligns with the syndrome of progressive ataxia and palatal tremor (PAPT), a rare and slowly progressive neurodegenerative disorder characterized by the triad of palatal tremor, cerebellar ataxia, and bulbar features. Notably, the radiological findings revealed typical hypertrophic olivary degeneration (HOD) on MRI, showcasing bilateral involvement, which is consistent with the majority of PAPT cases. However, what distinguishes our case is the absence of a causative structural lesion identified on brainstem or cerebellar parenchyma. This unique aspect challenges the conventional understanding of PAPT pathophysiology, as our patient exhibited isolated hypertrophic inferior olivary degeneration without associated structural abnormalities. Emphasizing these distinct radiological features not only contributes to the current understanding of PAPT but also alters the diagnostic approach, highlighting the need for careful consideration of atypical presentations in the assessment of this rare neurological syndrome.

The differential diagnosis is essentially made with diseases that can cause palatal myoclonus with or without cerebellar ataxia. Palatal myoclonus can be also caused by acute lesions such as brainstem or cerebellar hemorrhage, infarction, or trauma [5]. In this case, the clinical context and imaging can eliminate these diagnoses.

HOD should not be confused with other bulbar lesions such as demyelination, tumor or infection, which also presents a high signal intensity on proton density and T2- weighted images, with possible enhancement after injection of Gadolinium. It may mimics the finding of HOD, whereas HOD never enhances.

Finally, the hypertrophic olivary degeneration occurring in the context of PAPT syndrome cannot be confused with that which is secondary to a lesion of the Guillain-Mollaret triangle. In the latter case, it is always accompanied by a causal structural lesion, whereas in the PAPT syndrome, it occurs in isolation.

The prognosis of PAPT is similar to that of any neurodegenerative disease, characterized by progressive worsening over time at varying rates.

There is no known effective treatment for the progressive ataxia, which is the most disabling symptoms of PAPT [1]. Treatment is generally symptomatic. Therapeutic trials suggest gabapentin or memantine as valuable drugs to treat eye oscillations in OPT [2].

Conclusion

Progressive ataxia and palatal tremor PAPT represents a heterogeneous group of disorders. It may be sporadic or familial. Sporadic PAPT is a subgroup of SPT, in which the cerebellar syndrome progresses gradually and is not the result of a monophasic illness. The underlying mechanisms of palatal oscillations remain uncertain. Hypertrophic olivary degeneration is often identified on MRI, Cerebellar atrophy, while present, tends to occur at a later stage of the disease progression. Therapeutic trials have not yet found an effective therapy.

Patient consent

Written informed consent for publication was obtained from patient.