Bilateral Hypertrophic Olivary Degeneration Research Articles

Vestibular Rehabilitation of Patient with Hypertrophic Olivary Degeneration: A Case Report.

Background Hypertrophic olivary degeneration (HOD) is a rare disorder that typically develops in the weeks to months following a structural brainstem or cerebellar lesion in the Guillain-Mollaret triangle (GMT). Clinically, patients with HOD present with palatal myoclonus and nystagmus, which are difficult to treat and rarely resolve. Purpose The purpose of this case is to present the results of vestibular and balance assessments of a patient with bilateral HOD before and after vestibular rehabilitation. Methods This case report describes a 43-year-old trucker who presented with dizziness, blurred vision, and balance problems for more than 10 months, accompanied by new-onset tremors and ataxia for more than 6 months. The patient's characteristic clinical manifestations were palatal myoclonus and nystagmus. Magnetic resonance imaging (MRI) revealed bilateral HOD after an acute pontine hemorrhage. Comprehensive vestibular and balance assessments were performed. Results Vestibular and balance assessments demonstrated nystagmus, impaired vestibulo-ocular reflex (VOR), optokinetic reflex (OKR), and balance function. Following 4 months of vestibular rehabilitation, the patient's eye symptoms and balance function were improved. Conclusions The case presented here highlights the rare clinical manifestations of HOD after pontine hemorrhage. Vestibular rehabilitation training may be beneficial for the recovery of patients with HOD.

Clinical and Imaging Profile of Patients with Cerebrotendinous Xanthomatosis - a Video Case Series from India.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by bi-allelic pathogenic variants in CYP27A1 gene that results in the deposition of cholestanol in the eyes, tendons, soft tissues and nervous system leading to cataracts, xanthomas, and various neuropsychiatric manifestations. The aim of our study is to describe the clinical, radiological and genetic profile of patients with CTX. This is a retrospective chart review of patients with CTX diagnosed based on classical clinical and radiological findings. The available clinical details, and investigations, including imaging, electrophysiological, pathological and genetic data, were documented. Five patients (4 males) were recruited in the study. The median age at presentation was 32 years (range: 21-66 years). Walking difficulty was the most common symptom at presentation. All patients had cataracts, tendon xanthomas, eye movement abnormalities, dysarthria, pyramidal signs, ataxia and gait abnormality. Dystonia was noted in three patients. Palatal tremor and parkinsonism were noted in one patient each. In MRI brain, dentate, and corticospinal tract involvement were the most frequent imaging findings. Bilateral hypertrophic olivary degeneration was noted in one patient and hot cross bun sign in two. Three patients underwent genetic testing and all had pathogenic variants confirming the diagnosis. CTX is a rare treatable disorder. Apart from the usual neurological presentation with spastic-ataxia, it can present at a later age with parkinsonism. Typical patterns of imaging findings are helpful in early diagnosis which aids in the treatment to prevent the neurological sequelae of the disease.

Palatal Tremor and Central Sleep Apnea Accompanied by Bilateral Hypertrophic Olivary Degeneration after Brainstem Hemorrhage

Palatal Tremor and Central Sleep Apnea Accompanied by Bilateral Hypertrophic Olivary Degeneration after Brainstem Hemorrhage

Progressive Ataxia with Palatal Tremor: A Case Series (P9-11.006)

<h3>Objective:</h3> This case series adds to the limited literature about progressive ataxia with palatal tremor (PAPT) by describing clinical findings and the approach to diagnostic testing in six cases of PAPT. <h3>Background:</h3> PAPT is a rare clinical syndrome characterized by symptomatic palatal tremor and progressive cerebellar ataxia. Imaging typically shows bilateral hypertrophic olivary degeneration (HOD). Though published work based on autopsy cases suggests a novel tauopathy as a possible etiology of sporadic PAPT, the syndrome can arise from a variety of vascular, traumatic, autoimmune, or genetic causes. Despite its many possible underlying etiologies, the published literature provides little guidance on a systematic approach to diagnostic testing. <h3>Design/Methods:</h3> We retrospectively reviewed the charts of patients evaluated at the Ataxia Center at Massachusetts General Hospital between 2010–with clinical findings consistent with PAPT. Data were collected about disease presentation, disease progression, imaging findings and diagnostic testing. <h3>Results:</h3> Six patients with PAPT were identified. Average age of symptom onset was 61, range 54–65. Presenting symptoms were gait imbalance in three, and dysarthria, dysphagia, and throat tremor, respectively, in the rest. All developed palatal tremor (patient 6 with ear clicks), appendicular ataxia, and ataxic eye movements throughout their course. All patients had evidence of bilateral HOD on brain MRI. PAPT was attributed to cavernous malformations in patient 2 and multicompartmental hemorrhage in patient 4. The causes in the remainder are unknown. Diagnostic testing varied. Four patients (inclusive of patients 2 and 4) underwent whole exome sequencing, two underwent cerebrospinal fluid analysis (both non-inflammatory), four had celiac testing, and one was tested broadly for neuronal autoantibodies. <h3>Conclusions:</h3> PAPT is a clinical syndrome with a variety of etiologies. As in our study, literature suggests that diagnostic evaluation often varies. Systematic evaluation is important to find underlying causes and aid future research to better identify and study patients with idiopathic PAPT. <b>Disclosure:</b> Dr. Wruble has nothing to disclose. Dr. Gupta has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Biogen. The institution of Dr. Gupta has received research support from Biogen. Dr. Schmahmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medavante. Dr. Schmahmann has stock in Cadent. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. The institution of Dr. Balaban has received research support from Biogen.

Teaching Neuro Images : Hypertrophic olivary degeneration in a young man with POLG gene mutation

A 30-year-old man with sensorineural hearing loss presented with subacute somnolence, slurred speech, and unsteady gait following treatment with peginterferon α-2b and ribavirin for chronic hepatitis C virus. Examination revealed scanning speech, horizontal nystagmus, gait ataxia, and symmetric hyporeflexia with distal sensory loss. There was no palatal myoclonus. Metabolic and serologic workup and blood lactate were unrevealing. Brain MRI demonstrated bilateral hypertrophic olivary degeneration (HOD, figure). Whole exome sequencing identified a homozygous pathogenic p.W748S POLG mutation.1 Differential diagnosis of bilateral HOD includes mutations in the nuclear genes crucial to mitochondrial function, POLG and SURF1 .2

A syndrome of progressive ataxia and palatal tremor in a patient with mild bilateral idiopathic hypertrophic olivary degeneration

A syndrome of progressive ataxia and palatal tremor in a patient with mild bilateral idiopathic hypertrophic olivary degeneration

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.

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.

Abstract TP163: Hypertrophic Olive Degeneration Causing Novel Neurological Symptoms After Stroke: A Case Series

Background: Ischemic and hemorrhagic strokes in the brainstem and cerebellum can affect the dentate-rubro-olivary -pathway. Lesions in this functional loop (called triangle of Guillain and Mollaret ) may result in hypertrophic olivary degeneration (HOD). Characteristic symptoms include rhythmic palatal tremor, primarily vertical pendular nystagmus, and Holmes-tremor of the upper limbs. This case series explores the course of the disease and its clinical presentation, in order to provide an improved understanding of HOD after stroke. Materials and methods: The neuro-radiological database of our university hospital was scanned for the term hypertrophic olivary degeneration and related keywords (in German) . Between 2010 and 2017, a total of 27 HOD cases were identified, of which 12 patients had suffered a stroke in their medical history. Results: Mean age of the 12 patients was 51.4 (+/-13.6) years. Eight patients had intracerebral hemorrhage, 3 ischemic stroke and one subarachnoid hemorrhage as causative event. Lesions were located pontine (n=7), cerebellar (n=4), and ponto-mesencephalic (n=1). Leading symptoms were palatal tremor (55%), Holmes tremor (18%), pendular nystagmus (18%), and dysarthria (73%). Based on clinical findings and brain imaging we designed a model allowing to predicting the side of HOD according to lesion location (Figure). By this we were able to identify and illustrate lesion sites able to induce bilateral HOD. Conclusions: Strategic lesions within the Guillain-Mollaret-Triangle in the posterior fossa may lead to unilateral or bilateral HOD. Even though the clinical syndrome of HOD is characteristic, diagnosis is often prolonged due to imprecise examination and misinterpretation of the findings. Future studies are desirable defining the incidence of HOD and evaluating therapeutic options.

Hypertrophic Olivary Degeneration: Neurosurgical Perspective and Literature Review.

Hypertrophic olivary degeneration (HOD) occurs because of posterior fossa or brainstem lesions that disrupt the dentato-rubro-olivary tract, well known as the Guillain-Mollaret triangle. Clinical and radiologic hallmarks of this condition are palatal myoclonus and T2 hyperintensity of the inferior olivary complex on magnetic resonance imaging (MRI), respectively. Because symptomatic HOD can complicate the recovery of patients with posterior fossa or brainstem lesions, the purpose of this study is to evaluate clinical and imaging findings of patients with HOD. Sixteen patients (8 female and 8 male) with a mean age of 40.7 years, (range, 5-83 years) years were included in this study based on clinical symptoms and MRI findings. We reviewed the clinical and imaging findings in 16 cases of HOD at our institution. Seven patients (43.7%) had posterior fossa tumors, 6 patients (37.5%) had cavernoma, 2 patients (12.5%) sustained traumatic brain injury, and only 1 patient (6.2%) had cerebellar infarction. Posterior fossa surgery was performed in 13 (81.2%) of these patients. HOD was detected a mean of 7.2 months (range, 0.5-18 months) after surgery or primary neurologic insult. Unilateral HOD was observed in 10 patients (62.5%), while bilateral HOD was observed in only 6 patients (37.5%). Seven patients (43.7%) were asymptomatic for HOD, whereas 5 patients (31.2%) had symptoms attributable to HOD. Two patients died because of primary tumors, although mean follow-up after detection of HOD on MRI was 52.2 months (range, 1-120 months) in the remaining 14 patients. In these cases, no change in clinical symptoms or imaging findings was detected during follow-up. In this series, posterior fossa tumors and cavernomas were the most common causes of HOD. Although most of the patients with HOD remained asymptomatic, HOD complicated the course of recovery in almost one quarter of the patients included in this study. Neurosurgeons should be aware of HOD, which has characteristic clinical and imaging findings. In addition, HOD can complicate the recovery of patients with disruption to the dentato-rubro-olivary tract.

Bilateral hypertrophic olivary degeneration: case report of an exceedingly rare condition developed after pontine infarct (P1.292)

Bilateral hypertrophic olivary degeneration: case report of an exceedingly rare condition developed after pontine infarct (P1.292)

Post-operative pediatric cerebellar mutism syndrome and its association with hypertrophic olivary degeneration.

The dentato-thalamo-cortical (DTC) pathway is recognized as the anatomical substrate for postoperative pediatric cerebellar mutism (POPCMS), a well-recognized complication affecting up to 31% of children undergoing posterior fossa brain tumour resection. The proximal structures of the DTC pathway also form a segment of the Guillain and Mollaret triangle, a neural network which when disrupted causes hypertrophic olivary degeneration (HOD) of the inferior olivary nucleus (ION). We hypothesize that there is an association between the occurrence of POPCMS and HOD and aim to evaluate this on MR imaging using qualitative and quantitative analysis of the ION in children with and without POPCMS. In this retrospective study we qualitatively analysed the follow up MR imaging in 48 children who underwent posterior fossa tumour resection for presence of HOD. Quantitative analysis of the ION was possible in 28 children and was performed using semi-automated segmentation followed by feature extraction and feature selection techniques and relevance of the features to POPCMS were evaluated. The diagnosis of POPCMS was made independently based on clinical and nursing assessment notes. There was significant association between POPCMS and bilateral HOD (P=0.002) but not unilateral HOD. Quantitative analysis showed that hyperintensity in the left ION was the most relevant feature in children with POPCMS. Bilateral HOD can serve as a reliable radiological indicator in establishing the diagnosis of POPCMS particularly in equivocal cases. The strong association of signal change due to HOD in the left ION suggests that injury to the right proximal efferent cerebellar pathway plays an important role in the causation of POPCMS.

Bilateral Hypertrophic Olivary Degeneration and Holmes Tremor without Palatal Tremor: An Unusual Association.

BackgroundLesions in the Guillain–Mollaret triangle or dentate-rubro-olivary pathway may lead to hypertrophic olivary degeneration (HOD), a secondary trans-synaptic degeneration of the inferior olivary nucleus. HOD is usually associated with palatal tremor and rarely with Holmes tremor. Bilateral HOD is a very unusual condition and very few cases are reported.Case ReportWe report here two cases of bilateral HOD after two different vascular lesions located at the decussation of superior cerebellar peduncles, thus impairing both central tegmental tracts and interrupting bilaterally the dentate-rubral-olivary pathway. Interestingly, both developed bilateral Holmes tremor but not palatal tremor.DiscussionLesions in some of the components in the Guillain–Mollaret triangle may develop Holmes tremor with HOD and without palatal tremor. Magnetic resonance imaging is an invaluable tool in these cases. Better understanding of the pathways in this loop is needed.

Hypertrophic olivary degeneration: A clinico-radiologic study

IntroductionThe frequency and causes of hypertrophic olivary degeneration (HOD) are unknown. We compared the clinical and radiological characteristics of unilateral HOD and bilateral HOD. MethodsWe performed a search of a radiologic report database for patients who were radiologically diagnosed as having HOD. This database includes the patients examined at the Mayo Clinic in Florida and Arizona. We used the search terms “hypertrophic olivary degeneration”, “HOD”, and “olivary” in the reports recorded from 1995 to 2015. Pertinent medical records and magnetic resonance imaging (MRI) scans of the brain for those with HOD were reviewed retrospectively. ResultsWe identified 142 MRI studies on 95 cases who had radiologically proven HOD, 39 cases had unilateral HOD and 56 with bilateral HOD. In symptomatic cases, the most common symptom was ataxia. Palatal tremor was observed in almost half of all HOD cases. While cerebrovascular diseases were the most frequent etiology in both types of HOD (n = 24, 62% in unilateral; n = 17, 30% in bilateral), more than half of bilateral HOD cases had an unknown etiology (52%, n = 29), whereas only 13% (n = 5) of the unilateral cases had an unknown etiology (χ2 test, P < 0.001). The lesions of unilateral HOD had a tendency to improve radiologically over time, whereas those associated with bilateral HOD were likely to worsen (χ2 test, P < 0.05). ConclusionsOur study showed that bilateral HOD is more common than unilateral HOD. Half of bilateral HOD cases had no obvious cause and some worsened over time. This may implicate a possible primary neurodegenerative process.

Hypertrophic Olivary Degeneration After Pontine Hemorrhage: A Case Report

Introduction: Hypertrophic olivary degeneration (HOD) is a rarely neurologic disease, occurring after damage to the dentato-rubro-olivary pathway. Case presentation: A 50-year-old hypertensive man suffered pontine hemorrhage resulting in numerous neurological deficits. Neurologic examination 4 months after the hemorrhage showed mild to moderate improvement. 8 months after the hemorrhage, the patient developed truncal and limb tremors, unsteady gait and dysarthria. Magnetic resonance showed increasing bilateral hypertrophic olivary degeneration. Administration of clonazepam and levodopa were ineffective for symptom relief. Conclusion: This case was presented in order to describe the clinical manifestations of HOD and to recognize the possibility of hypertrophic olivary degeneration after the pontomesencephalic stroke.

A clinicoradiologic study of hypertrophic olivary degeneration

Objectives: To study the frequency and causation of hypertrophic olivary degeneration (HOD) reported in a radiologic database of the Mayo Clinic Florida and Arizona. HOD usually occurs following lesions involving the dento-rubro-olivary pathway. There are two types of HOD, unilateral and bilateral. Current literature suggests bilateral HOD is less frequent. The epidemiology and etiology of HOD are unknown, particularly bilateral HOD.

Postoperative posterior fossa syndrome: unraveling the etiology and underlying pathophysiology by using magnetic resonance imaging

Posterior fossa syndrome (PFS) is a severe, postoperative complication occurring in about 25 % of pediatric patients undergoing surgery for midline tumors in the posterior fossa. In recent years, MRI-based research elucidated the cause of PFS and shed new light on its putative pathophysiology. This review highlights the major advances arising from research of this topic. Postsurgical damage patterns in patients after posterior fossa surgery show that PFS results from bilateral surgical damage to the proximal efferent cerebellar pathways (pECPs). Surgical pECP disruption has other MRI-detectable effects that are more remote. Patients with PFS tend to develop global supratentorial cortical hypoperfusion, likely representing reversed, cerebello-cerebral diaschisis. Because this hypoperfusion is most prominent in frontal regions, cerebellar mutism may indicate a dominantly frontal lobe dysfunction, hence a peculiar form of speech apraxia. Injury to the pECP also leads to contralateral inferior olivary nucleus degeneration. When bilateral hypertrophic olivary degeneration (HOD) is observed after posterior fossa surgery, affected patients have clinical PFS. Therefore, it is suggested that bilateral HOD may be a sensitive and, in appropriate clinical settings, reliable a posteriori surrogate imaging indicator of bilateral disruption of the pECPs and consequently of PFS. Having such a "validation tool" presents new opportunities to develop better definitions for the phenotypes within the clinical spectrum of PFS. Anatomical and functional MRI techniques are suitable and valuable tools with which to detect structural changes and pathophysiological processes in the development and evolution of PFS and may be key, integral components of future clinical research endeavors.

MRI Findings in Nonlesional Hypertrophic Olivary Degeneration.

Investigate the relative frequency of nonlesional versus lesional hypertrophic olivary degeneration (HOD) and potential explanations for nonlesional HOD. Our radiology report database was queried for "HOD" in all head MRI reports between 7/1/2002 and 7/1/2013 and identified 138 patients. Specific absence of HOD or cases with lesions within the dento-rubro-olivary pathway (DROP) or extending into the inferior olivary nuclei (ION) were excluded (22 in total). For included patients, 19 locations with the anatomic potential to connect to the ION or DROP were reviewed and grouped into embryological categories, along with the use of the drug metronidazole. A total of 51 of 116 (44%) HOD patients did not have a causative lesion in the DROP. The 27/51 (53%) of these patients had progressive ataxia with palatal tremor (PAPT). The 28/51 (55%) patients had one or more lesions outside of the DROP and one of these 28 patients used metronidazole. The remaining 23/51 (45%; 19% of total HOD cohort) patients had no additional lesions in the brain and 6 of these 23 patients did not have a clinical diagnosis of PAPT. Forty-four percent of patients with HOD did not demonstrate an MRI-identifiable lesion in the DROP, and 45% of those patients did not have identifiable brain lesions outside of the DROP. Thus, nearly a fifth of HOD cases may be truly idiopathic. A majority of patients without a DROP lesion had bilateral HOD and two-thirds were male.

Frequency of Bilateral Hypertrophic Olivary Degeneration in a Large Retrospective Cohort

Hypertrophic olivary degeneration (HOD) is an uncommon type of transneuronal degeneration. Case reports and case series described in the literature provide a foundation of our current knowledge of HOD. These reports have described HOD most frequently to be unilateral and occurring in association with lesions in the dentato-rubro-olivary pathway. Our purpose was to evaluate the rate of bilateral versus unilateral HOD in a large case series. A retrospective review was performed to identify patients in which the phrase "hypertrophic olivary degeneration" occurred in the radiology report. A diagnosis of HOD was confirmed on imaging if there was focal hyperintensity on T2-weighted images confined to either or both inferior olivary nuclei. A total of 102 patients had findings consistent with HOD. Of these, 76% had findings bilaterally. In 44%, a lesion could not be identified to explain HOD. Bilateral HOD was common in both lesional and nonlesional group, though more common in the nonlesional group. This study demonstrates that HOD is frequently bilateral. In slightly over 50% of patients with HOD, a lesion can be identified. In just under 50% patients with HOD, a lesion could not be identified and in these cases HOD was present bilaterally in the majority.

Bilateral hypertrophic olivary nucleus degeneration on magnetic resonance imaging in children with Leigh and Leigh-like syndrome

Bilateral hypertrophic olivary degeneration on brain MRI has been reported in a few metabolic, genetic and neurodegenerative disorders, including mitochondrial disorders. In this report, we sought to analyse whether bilateral symmetrical inferior olivary nucleus hypertrophy is specifically associated with mitochondrial disorders in children. This retrospective study included 125 children (mean age, 7.6 ± 5 years; male:female, 2.6:1) diagnosed with various metabolic and genetic disorders during 2005-2012. The routine MRI sequences (T1 weighted, T2 weighted and fluid-attenuated inversion-recovery sequences) were analysed for the presence of bilateral symmetrical olivary hypertrophy and central tegmental tract or dentate nuclei signal changes. The other imaging findings and the final diagnoses were noted. The cohort included patients with Leigh and Leigh-like syndrome (n = 25), other mitochondrial diseases (n = 25), Wilson disease (n = 40), Type 1 glutaric aciduria (n = 14), maple syrup urine disease (n = 13), giant axonal neuropathy (n = 5) and L-2 hydroxy glutaric aciduria (n = 3). Bilateral inferior olivary nucleus hypertrophy was noted in 10 patients, all of whom belonged to the Leigh and Leigh-like syndrome group. Bilateral hypertrophic olivary degeneration on MRI is relatively often, but not routinely, seen in children with Leigh and Leigh-like syndrome. Early detection of this finding by radiologists and physicians may facilitate targeted metabolic testing in these children. This article highlights the occurrence of bilateral hypertrophic olivary nucleus degeneration on MRI in children with Leigh and Leigh-like syndrome, compared with other metabolic disorders.