Hypertrophic Olivary Degeneration Research Articles

Successfull treatment of paroxysmal painful tonic spasms with carbamazepine in a patient with hypertrophic olivary degenaration

Hypertrophic olivary degeneration (HOD) is a rare phenomenon that can occur after different insults to the so-called Guillain-Mollaret triangle. Clinically, HOD presents as palatal tremor, dentatorubral tremor and/or ocular myoclonus.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk.Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered.Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures.Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.

Iron deposits in the red nucleus at long-term follow-up after hypertrophic olivary degeneration.

Hypertrophic olivary degeneration (HOD) is an uncommon trans-synaptic degenerating disease characterized by hypertrophy of the inferior olivary nucleus (ION). The disease typically results from interruptions of connections in the dentato-rubro-olivary pathway (DROP) or Guillain-Mollaret triangle (GMT), which encompasses the ipsilateral red nucleus (RN), ipsilateral ION, and contralateral dentate nucleus (DN). Before the advent of magnetic resonance imaging (MRI), HOD was only detectable by autopsy; however, MRI now makes it possible to diagnose HOD in vivo. Most reports about HOD are based on conventional MRI, with only one report using susceptibility-weighted imaging (SWI) (1), and no reports on combined application of SWI and diffusion tensor imaging (DTI). This report presents a case of unilateral HOD in a 66-year-old male 4 years post-cerebellar hemorrhage, who was examined with both SWI and DTI.

Primary intracranial germ cell tumour originating from right brachium Pontis with hypertrophic Olivary degeneration: a case report

BackgroundPrimary right brachium pontis germinoma with hypertrophic olivary degeneration (HOD) is extremely rare. A preoperative diagnosis is challenging due to the absence of characterized clinical and neuroimaging features, and biopsy should be considered.Case presentationA 20-year-old male patient presented with a case of primary intracranial germinoma originating from right brachium pontis with HOD manifesting as ocular myoclonus, nystagmus in both eyes, ataxic gait and incoordination of the limbs. Magnetic resonance imaging (MRI) revealed an irregular patchy lesion with hyperintensity on T2-weighted images (T2WI) and T2 fluid-attenuated inversion recovery (FLAIR) without enhancement by gadolinium (Gd). Furthermore, a focal hyperintense nodule on T2WI in the left inferior olive nucleus (ION) of the medulla oblongata was considered hypertrophic olivary degeneration (HOD) based on the patient’s symptoms and neuroimaging findings. Due to suspected demyelinating disease and low-grade glioma (LGG), a biopsy was planned. The pathological diagnosis was germinoma. Subsequently, he received chemoradiation therapy, resulting in the improvement of neurological deficits and the disappearance of the lesion on MRI.ConclusionA case of “Primary right brachium pontis germinoma with HOD” is reported for the first time. A preoperative diagnosis is challenging due to the fact of absence of clinical signs and symptoms and neuroimaging characteristics. However, patients can have favourable prognoses with appropriate evaluation and treatment.

Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor

De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.

Peribuccal and pharyngeal myorhythmia as a presenting symptom of hypertrophic olivary degeneration: Expert commentary

In this issue of the journal, Assenza et al. described an interesting case of unilateral perioral and pharyngeal myorhythmia associated with inferior olivary hypertrophy [1]. As part of the investigative workup, the authors used surface electromyography (EMG) to characterize the abnormal movements.

Peribuccal and pharyngeal myorhythmia as a presenting symptom of hypertrophic olivary degeneration

A 58-year-old woman underwent to a successful surgical treatment of a left cerebellar paravermian cavernous malformation. Seven months later she progressively developed involuntary contractions of the left peribuccal region. Neurological examination revealed repetitive, rhythmic, slow frequency jerks of the left corner of the mouth (Video, segment-1). She did not report swallowing difficulties, saliva pooling or ear clicks. However, a careful examination of the oral cavity revealed the presence of synchronous contractions of left pharyngeal muscles (Video, segment-2). The involuntary movements occurred at rest and were suppressed neither by voluntary activity nor by distractions manoeuvres with motor tasks, disappearing during sleep. No palatal or ocular movement abnormalities were observed. Surface electromyography recorded to the left orbicularis oris at rest showed repetitive synchronous 3-Hz rhythmic bursts with a mean duration of 130 msec (Fig. 1D and E), without any electroencephalographic correlation. 3T-brain MRI revealed FLAIR hyperintensity and hypertrophy of right inferior olivary nucleus (ION) consistent with hypertrophic olivary degeneration (HOD), associated with T2-hyperintensity and thinning of left superior cerebellar peduncle (Fig. 1A and B). DTI-based fiber direction failed in demonstrating the normal appearance of decussation of superior cerebellar peduncles, probably as a result of axonal degeneration processes of dentatorubral tract (Fig. 1, C). A diagnosis of isolated peribuccal and pharyngeal myorhythmia due to HOD was made. Clonazepam and pregabalin did not entail any benefit. Botulinum toxin type A injections was started and repeated every three months with 8 Xeomin® units injected into the left orbicularis oris and depressor anguli oris muscles, leading to persistent reduction of involuntary peribuccal contractions. To date, 24 months after surgery patient's conditions are stable with no palatal involvement.

A Paravermal Trans-Cerebellar Approach to the Posterior Fossa Tumor Causes Hypertrophic Olivary Degeneration by Dentate Nucleus Injury.

Simple SummaryPosterior fossa tumor surgery is challenging due to the proximity and exposure of cerebellar structures. A favorable operative approach is unknown. Following lesions to the dentato–rubro–olivary-pathway, a neurodegenerative disease called hypertrophic olivary degeneration (HOD) can occur. This study for the first time demonstrates that paravermal trans-cerebellar approaches are associated with a significantly higher likelihood of HOD on MRI when compared to other approaches. This finding can well be attributed to dentate nucleus (DN) injury. Furthermore, cerebellar mutism syndrome (CMS) was discussed in the literature to be correlated with HOD due to a functional overlap of pathways involved. We found no such correlation in this study, but HOD was shown to be a reliable indicator for surgical disruption of efferent cerebellar pathways involving the DN. Henceforth, neurosurgeons should consider more midline or lateral approaches in posterior fossa surgery to spare the DN whenever feasible, and focus on cerebellar functional anatomy in their preoperative planning.Background: In brain tumor surgery, injury to cerebellar connectivity pathways can induce a neurodegenerative disease called hypertrophic olivary degeneration (HOD), along with a disabling clinical syndrome. In children, cerebellar mutism syndrome (CMS) is another consequence of damage to cerebello–thalamo–cortical networks. The goal of this study was to compare paravermal trans-cerebellar to other more midline or lateral operative approaches in their risk of causing HOD on MR-imaging and CMS. Methods: We scanned our neurosurgical database for patients with surgical removal of pilocytic astrocytoma, ependymoma and medulloblastoma in the posterior fossa. Fifty patients with a mean age of 22.7 (±16.9) years were identified and analyzed. Results: HOD occurred in n = 10/50 (20%) patients within four months (median), always associated with contralateral dentate nucleus (DN)-lesions (p < 0.001). Patients with paravermal trans-cerebellar approach significantly more often developed HOD (7/11; 63.6%) when compared to other approaches (3/39; 7.7%; p < 0.001). Injury to the DN occurred more frequently after a paravermal approach (8/11 vs. 13/39 patients; p < 0.05). CMS was described for n = 12/50 patients (24%). Data indicated no correlation of radiological HOD and CMS development. Conclusions: A paravermal trans-cerebellar approach more likely causes HOD due to DN-injury when compared to more midline or lateral approaches. HOD is a radiological indicator for surgical disruption of cerebellar pathways involving the DN. Neurosurgeons should consider trajectories and approaches in the planning of posterior fossa surgery that spare the DN, whenever feasible.

Bilateral Hypertrophic Olivary Degeneration Following Brainstem Insult: A Retrospective Review and Examination of Causative Pathology

Hypertrophic olivary degeneration is a rare condition caused by a lesion in the Guillain-Mollaret triangle which leads to trans-synaptic degeneration resulting in the degenerative hypertrophy of the inferior olivary nucleus. This condition presents clinically with palatal tremor but can also produce ocular myoclonus or cerebellar signs. While any lesion that occurs within the Guillian-Mollaret triangle and results in the deafferentation of the inferior olive can lead to hypertrophic olivary degeneration, the most common etiologies include ischemic and hemorrhagic stroke, vascular malformation, neoplasm, and iatrogenic injury related to surgery. We report a series of 7 patients who presented with this condition bilaterally on MRI imaging, including 1 case which represents the first report of toxoplasmosis leading to the development of bilateral hypertrophic olivary degeneration and only the third reported case, unilateral or bilateral, related to an infectious etiology.

Hypertrophic olivary degeneration concomitant with bilateral middle cerebellar peduncles Wallerian degeneration following unilateral pontine infarction

BackgroundWallerian degeneration (WD) can occur in different projecting systems, such as corticospinal tract, dentate-rubro-olivary pathway, and corticopontocerebellar tract. However, the co-occurrence of hypertrophic olivary degeneration (HOD) and middle cerebellar peduncles (MCPs) degeneration secondary to unilateral pontine infarction in a single patient is extremely rare.Case presentationA 71-year-old man presented with acute onset of dizzness, slurred speech, and right-sided weakness. On the next day, his previous neurologic deficits deteriorated. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke of the left pons. After treatment with thrombolysis, antiplatelets, and rehabilitation training, his speaking and motor function improved moderately. At the 3-month follow-up, the MRI showed hyperintensity in the left medulla oblongata and bilateral MCPs on T2-weighted and FLAIR images, suggesting HOD as well as MCPs degeneration.ConclusionsIt is of great importance for us to know the anatomic knowledge of dentate-rubro-olivary and corticopontocerebellar pathways.

Bilateral hypertrophic olivary degeneration in genetic neurological disorders

Hypertrophic olivary degeneration (HOD) is a rare variant of transsynaptic degeneration in the inferior olivary nuclei due to a lesion within the dentato-rubro- olivary pathway, also known as the Guillain–Mollaret triangle. Bilateral HOD can be identified on MRI in patients with not only acquired but also genetic neurological disorders. The article describes patients with both common and rare genetic causes of the bilateral HOD. The pathophysiology of HOD is also briefly reviewed.

Palato-pharyngo-laryngeal myoclonus with recurrent retrograde feeding tube migration after cerebellar hemorrhagic stroke: a case report and review of hypertrophic olivary degeneration

BackgroundPalato-pharyngo-laryngeal myoclonus, a variant of palatal myoclonus, is characterized by involuntary rhythmic movements of palatal, pharyngeal, and laryngeal muscles. Symptomatic palatal myoclonus is classically associated with hypertrophic olivary degeneration on MRI imaging due to a lesion in the triangle of Guillain-Mollaret.Case presentationWe report a case of palato-pharyngo-laryngeal myoclonus in a patient post-cerebellar hemorrhagic stroke who presented with recurrent retrograde migration of his gastrojejunostomy feeding tubes. Treatment with either divalproex sodium or gabapentin resulted in a significant decrease in his gastrointestinal symptoms and no further episodes of gastrojejunostomy tube migration.ConclusionsThis case study indicates that the movement disorder associated with hypertrophic olivary degeneration may involve the gastrointestinal system. Anticonvulsants, such as gabapentin and divalproex sodium, may reduce the severity of gastrointestinal symptoms in cases associated with hypertrophic olivary degeneration. The anatomy of the Guillain-Mollaret triangle and the pathophysiology of hypertrophic olivary degeneration are reviewed.

Hypertrophic Olivary Degeneration Secondary to Head Trauma

Hypertrophic Olivary Degeneration Secondary to Head Trauma

Transaxonal degenerations of cerebellar connections: the value of anatomical knowledge.

The learning objectives of this review include recognition of the imaging characteristics of transaxonal degenerations involving cerebellar connections, the identification of potential encephalic lesions that can lead to these degenerations and correlation of the clinical manifestations with imaging findings that reflect this involvement. In this report, we review the neuroanatomical knowledge that provides a basis for identifying potential lesions that can result in these degenerations involving cerebellar structures. Hypertrophic olivary degeneration results from an injury that interrupts any of the components of the Guillain-Mollaret triangle. In this work, we describe cases of lesions in the dentate nucleus and central tegmental tract. The crossed cerebellar diaschisis presents specific imaging findings and clinical correlations associated with its acute and chronic phases. The Wallerian degeneration of the middle cerebellar peduncle is illustrated by fiber injury of the pontine cerebellar tracts. A T2-hyperintensity in the dentate nucleus due to a thalamic acute lesion (in ventral lateral nuclei) is also described. Each condition described here is documented by MRI images and is accompanied by teaching points and an anatomical review of the pathways involved. Neurologists and radiologists need to become familiar with the diagnosis of these conditions since their presentations are peculiar and often subtle, and can easily be misdiagnosed as ischemic events, degenerative disease, demyelinating disease or even tumors.

Oculopalatal tremor following sequential medullary infarcts that did not cause hypertrophic olivary degeneration

BackgroundThe syndrome of oculopalatal tremor is a known consequence of lesions in the dentate-olivary pathway. Hypertrophic degeneration of the inferior olive is a recognized pathological correlate of these lesions and hypothesized to cause tremorogenic olivary hypersynchrony. However, oculopalatal tremor also occurs in Alexander disease, which produces severe inferior olive degeneration without intervening hypertrophy.MethodsSerial clinical, imaging, video-oculography and kinematic tremor recording of a patient with oculopalatal and limb tremor.Case studyWe report an unusual presentation of oculopalatal tremor and right upper extremity myorhythmia following sequential right dorsolateral and left anteromedial medullary infarcts directly involving both inferior olives. As in adult Alexander disease, our patient did not have hypertrophic olivary degeneration during 10 years of follow-up.ConclusionContemporary theories have emphasized the role of cerebellar maladaptation in “shaping” oscillations generated elsewhere, the inferior olive in particular. Our patient and published Alexander disease cases illustrate that oculopalatal tremor can occur in the absence of hypertrophic olivary degeneration. Therefore, cerebellar maladaptation to any form of olivary damage may be the critical pathophysiology in producing oculopalatal tremor.

A Syndrome of Progressive Ataxia and Palatal Tremor (PAPT) in a Patient with Hypertrophic Olivary Degeneration.

A Syndrome of Progressive Ataxia and Palatal Tremor (PAPT) in a Patient with Hypertrophic Olivary Degeneration.

A meta-analysis of case studies and clinical characteristics of hypertrophic olivary degeneration secondary to brainstem infarction.

Transsynaptic degeneration in the cerebellum and brainstem may give rise to a rare neurological condition with various clinical manifestations, namely hypertrophic olivary degeneration. The classical manifestations of hypertrophic olivary degeneration comprise myoclonus, palatal tremor, ataxia, and ocular symptoms. Any lesions interrupting the dentate-rubro-olivary pathway, referred to as the anatomic Guillain-Mollaret triangle, contribute to the broad aetiologies of hypertrophic olivary degeneration. The clinical diagnosis depends primarily on the associated symptoms and the characteristic magnetic resonance imaging findings. Concerning treatment and prognosis, there are no widely accepted guidelines. Here, we identified 11 cases of hypertrophic olivary degeneration secondary to brainstem infarction from 1964 to the present. Combined with two of our cases, the clinical and imaging findings of 13 patients with hypertrophic olivary degeneration secondary to brainstem infarction were studied. A meta-analysis of case studies gives the correlation coefficient between infraction location and time to develop hypertrophic olivary degeneration as 0.217 (P = 0.393, P > 0.05). At the significance level of P < 0.05, there was no significant correlation between information location and time to develop hyperophic olivary degeneration. The χ2 between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration was 8.750 (P = 0.364, P > 0.05). At the significance level of P < 0.05, there was no significant correlation between infraction location and magnetic resonance imaging findings of hypertrophic olivary degeneration. Conclusion based on the analysis of available data suggests that when newly developed or progressive worsening motor symptoms are presented in patients with previous brainstem infarction, a diagnosis of hypertrophic olivary degeneration should be investigated.

Delayed Occurrence of Hypertrophic Olivary Degeneration after Therapy of Posterior Fossa Tumors: A Single Institution Retrospective Analysis.

(1) Background: A lesion within the dentato-rubro-olivary pathway (DROP) in the posterior fossa can cause secondary neurodegeneration of the inferior olivary nucleus: so-called hypertrophic olivary degeneration (HOD). The clinical syndrome of HOD occurs slowly over months and may be overlooked in progressive neuro-oncological diseases. Posterior fossa tumors are often located near these strategic structures. The goal of this study was to analyze the systematics of HOD occurrence in neuro-oncological patients. (2) Methods: The neuroradiological database of the university healthcare center was scanned for HOD-related terms from 2010 to 2019. After excluding patients with other causes of HOD, 12 datasets from neuro-oncological patients were analyzed under predetermined criteria. (3) Results: Patients received multimodal tumor treatments including neurosurgery, radiotherapy, and chemotherapy. HOD occurred both unilaterally (left n = 4; right n = 5) and bilaterally (n = 3). Though the mass effect of posterior fossa tumors had already affected strategic structures of the DROP, none of the patients showed signs of HOD on MRI until therapeutic measures including neurosurgery affecting the DROP were applied. HOD was visible on MRI within a median of 6 months after the neurosurgical intervention. In 67%, the presumed underlying surgical lesion in the DROP lay in the contralateral dentate nucleus. (4) Conclusion: In a selected cohort of neuro-oncological patients, therapeutic lesions within the DROP were associated with HOD occurrence.

Microsurgical Management of Midbrain Cavernous Malformations: Predictors of Outcome and Lesion Classification in 72 Patients.

Due to the complex segmental organization of the brainstem, it is preferable to study midbrain cavernous malformations (MCMs) separately from pontine and medullary lesions. To evaluate clinical results after microsurgical removal of MCMs, assess predictors for outcome and introduce a topographical classification of MCMs. A retrospective study was conducted on consecutive patients who underwent MCM resection. Clinical parameters before and after surgery, morphological CM features, surgical approaches and outcomes were analyzed. MCMs were classified according to their exact location within the midbrain and their axial and sagittal extension. The authors reviewed 72 patients (35 male). Lesions varied in size between 4 and 55 mm. The vast majority of patients benefited from surgery. The mean modified Rankin Scale (mRS) decreased significantly from 1.6 at admission to 1.3 at discharge and to 0.7 at follow-up (6-247 mo postoperatively). Five patients (6.9%) suffered from delayed hypertrophic olivary degeneration as visualized on magnetic resonance imaging. One male suffered from early postoperative re-bleeding that required surgical hematoma evacuation. There were no severe long tract impairment or other disabling complications, no delayed re-bleedings, and no surgical mortality. We present a new topographic classification of MCMs that may be useful for predicting the occurrence of postoperative eye movement disorders. Other predictors of persistent oculomotor disturbances are time interval between onset of symptoms and surgery, and patient's age over 40yr. Early surgery is recommendable in patients with oculomotor disturbances. MCM size over 18 mm, patient age over 40yr, and poor mRS at admission are important predictors for the long-term outcome.

Ocular Motor and Vestibular Disorders in Brainstem Disease.

The brainstem contains ocular motor and vestibular structures that, when damaged, produce specific eye movement disorders. In this review, we will discuss three brainstem syndromes with characteristic ocular motor and vestibular findings that can be highly localizing. First, we will discuss the lateral medullary (Wallenberg) syndrome, focusing on ocular lateropulsion, saccadic dysmetria, and the ocular tilt reaction. Second, we will review the medial longitudinal fasciculus syndrome including the ocular tilt reaction, nystagmus, and the vestibular-ocular reflex. Lastly, we will discuss hypertrophic olivary degeneration and oculopalatal tremor, which may develop weeks to months after a brainstem or cerebellar lesion. In these syndromes, the clinical ocular motor and vestibular examination is instrumental in localizing the lesion.