Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Diaphragmatic myoclonus post cerebellar hemorrhage: a case report.

BACKGROUND: Diaphragmatic myoclonus is a rare motor disorder that affects muscle tone. It is characterized by involuntary movements of the abdominal wall and rhythmic, repetitive contractions of the accessory or respiratory muscles, all of which are innervated by the cervical nerve roots. CASE DESCRIPTION: We reviewed the case of a 57-year-old male patient who underwent surgery for a left cerebellar hemorrhage. He exhibited persistent myoclonus in the palate, jaw, and thoracoabdominal region. Following treatment, there was a significant reduction in flutter amplitude in these areas. CONCLUSION: The clinical rarity and variability of presentations often make diagnosis challenging and delayed. It is believed that this condition stems from abnormal excitation within the central nervous system or neural pathways that involve the phrenic nerve. Another potential mechanism is the direct irritation of the diaphragm. Ultrasound, chest fluoroscopy, and electromyography (EMG) can support the diagnosis. Various pharmacological and surgical treatments have been tried, yet specific treatment guidelines are still lacking.

Palatal myoclonus and hypertrophic olivary degeneration following wernekinck commissure syndrome: a case report.

BACKGROUND: Hypertrophic olivary degeneration (HOD), a rare form of transsynaptic degeneration, is secondary to dentato-rubro-olivary pathway injuries in some cases. We describe a unique case of an HOD patient who presented with palatal myoclonus secondary to Wernekinck commissure syndrome caused by a rare bilateral "heart-shaped" infarct lesion in the midbrain. CASE PRESENTATION: A 49-year-old man presented with progressive gait instability in the past 7 months. The patient had a history of posterior circulation ischemic stroke presenting with diplopia, slurred speech, and difficulty in swallowing and walking 3 years prior to admission. The symptoms improved after treatment. The feeling of imbalance appeared and was aggravated gradually in the past 7 months. Neurological examination demonstrated dysarthria, horizontal nystagmus, bilateral cerebellar ataxia, and 2-3 Hz rhythmic contractions of the soft palate and upper larynx. Magnetic resonance imaging (MRI) of the brain performed 3 years prior to this admission showed an acute midline lesion in the midbrain exhibiting a remarkable "heart appearance" on diffusion weighted imaging. MRI after this admission revealed T2 and FLAIR hyperintensity with hypertrophy of the bilateral inferior olivary nucleus. We considered a diagnosis of HOD resulting from a midbrain heart-shaped infarction, which caused Wernekinck commissure syndrome 3 years prior to admission and later HOD. Adamantanamine and B vitamins were administered for neurotrophic treatment. Rehabilitation training was also performed. One year later, the symptoms of this patient were neither improved nor aggravated. CONCLUSION: This case report suggests that patients with a history of midbrain injury, especially Wernekinck commissure injury, should be alert to the possibility of delayed bilateral HOD when new symptoms occur or original symptoms are aggravated.

The Guillain-Mollaret triangle: a key player in motor coordination and control with implications for neurological disorders.

The dentato-rubro-olivary pathway, also known as the Guillain-Mollaret triangle (GMT) or myoclonic triangle, consists of the dentate nucleus, the red nucleus, and the inferior olivary nucleus (ION). GMT is important for motor coordination and control, and abnormalities in this network can lead to various neurological disorders. The present study followed a systematic approach in conducting a review on GMT studies. The inclusion criteria were limited to human subjects with primary objectives of characterizing and evaluating GMT syndromes, and the methodology used was not a determining factor for eligibility. The search strategy used MeSH terms and keywords relevant to the study's objective in various databases until August 2022. A total of 76 studies were included in the review after assessing 527 articles for eligibility based on the final inclusion criteria. Most of the studies evaluated the GMT in human subjects, with the majority utilizing magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), or combination of them. The review found that Hypertrophic olivary degeneration (HOD), a common consequence of GMT damage, has diverse underlying causes, including stroke, brainstem cavernous malformations, and structural impairments. Palatal tremor, ocular myoclonus, ataxia, nystagmus, and vertigo were frequently reported symptoms associated with HOD. This systematic review provides comprehensive insights into the association between GMT and various neurological syndromes, shedding light on the diagnostic, etiological, and prognostic aspects of GMT dysfunction. Understanding the role of the GMT and its implications in movement disorders could pave the way for improved treatment options and better management of neurological conditions related to this critical brainstem pathway.

Holmes tremor: an updated review.

Holmes tremor is a rare movement disorder with rest, intention and postural components, characterized by high amplitude and low frequency. It occurs mainly as a result of impairment of dopaminergic nigrostriatal system and cerebellothalamocortical or dentato-rubro-olivary pathways. The aetiologies of this tremor vary widely, including cerebrovascular events, tumours, demyelination and infections. Diagnosis is based on clinical examination, neurophysiological and neuroimaging studies. Magnetic resonance imaging (MRI) scan of the brain is the gold standard method for revealing the location and potential cause of the lesion, whereas dopamine transporter single photon emission with the use of 123I-FP CIT is useful in assessing the functional integrity of the nigrostriatal pathway. Although various treatment options are available, including pharmacological agents, deep brain stimulation and regional surgical techniques, its treatment remains challenging. Our deeper understanding of the disruption of associated neural brain circuits combined with recent genetic and molecular evidence will drastically improve its clinical evaluation and management.

Structural damage burden and hypertrophic olivary degeneration in pediatric postoperative cerebellar mutism syndrome.

Cerebellar mutism syndrome (CMS) occurs in one out of four children after posterior fossa tumor surgery, with open questions regarding risk factors, pathophysiology, and prevention strategies. Because of similarities between several cerebellar syndromes, a common pathophysiology with damage to the dentato-thalamo-cortical and dentato-rubro-olivary pathways has been proposed. Hypertrophic olivary degeneration (HOD) is an imaging correlate of cerebellar injury observed for instance in stroke patients. Aim of this study was to investigate whether the occurrence and severity of CMS correlates with the extent of damage to the relevant anatomical structures and whether HOD is a time-dependent postoperative neuroimaging correlate of CMS. We performed a retrospective single center study of CMS patients compared with matched non-CMS controls. CMS occurred in 10 children (13% of the overall cohort) with a median age of 8 years. Dentate nucleus (DN) injury significantly correlated with CMS, and superior cerebellar peduncle (SCP) injury was associated by tendency. HOD was observed as a dynamic neuroimaging phenomenon in the postoperative course and its presence significantly correlated with CMS and DN injury. Children who later developed HOD had an earlier onset and tended to have longer persistence of CMS. These findings can guide surgical measures to protect the DN and SCP during posterior fossa tumor resections and to avoid a high damage burden (i.e., bilateral damage). Development of intraoperative neuromonitoring of the cerebellar efferent pathways as well as improved preoperative risk stratification could help to establish a patient-specific strategy with optimal balance between degree of resection and functional integrity.

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

BACKGROUND: Primary 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 PRESENTATION: A 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. CONCLUSION: A 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.

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

BACKGROUND: Wallerian 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 PRESENTATION: A 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. CONCLUSIONS: It is of great importance for us to know the anatomic knowledge of dentate-rubro-olivary and corticopontocerebellar pathways.

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

BACKGROUND: Palato-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 PRESENTATION: We 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. CONCLUSIONS: This 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.

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.

Transient Palatal Tremor and Action Induced Foot and Leg Dystonia due to Hypertrophic Olivary Degeneration: a Case Report.

Hypertrophic olivary degeneration (HOD) is a rare phenomenon that occurs after various insults to the Guillain-mollaret triangle (GMT). HOD is unique because the degeneration of inferior olivary nucleus becomes hypertrophic rather than atrophic. In this study, a 31-year-old woman developed HOD after pontine cavernoma surgery had been performed. The clinical manifestation was involuntary intorsion of right lower extremity during walking, which has not been reported in the literature. The woman also presented with palatal tremor, the most classic symptom of HOD. HOD's imaging trait include olive hypertrophy with increased T2 signal intensity on MRI, which are corresponding to the pathological findings. HOD is a self-limiting disease and excessive treatments are unnecessary.

[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.

Hypertrophic olivary degeneration in a 16-year-old girl after subtotal surgery of a brainstem pilocytic astrocytoma - a case report.

PURPOSE: Hypertrophic olivary degeneration (HOD) is a unique neurological condition caused by interruption of the dentato-rubro-olivary pathway, also known as the triangle of Guillain and Mollaret. Magnetic resonance (MR) imaging is the best modality to diagnose both the degeneration of the inferior olivary nucleus and the underlying cause. CASE REPORT: We describe a case of a unilateral HOD in a 16-year-old girl several months after a subtotal excision of a brainstem pilocytic astrocytoma. Taking into account the patient's history, tumour recurrence must have been considered, but the typical location and MR morphology, as well as the time of occurrence after brainstem surgery, contributed to the diagnosis of HOD. The causative factor was the interruption of the central tegmental tract, which forms one arm of the Guillain and Mollaret triangle. Additionally, this is an interesting case of a child, who stayed in a coma for several months following brainstem surgery, but finally was discharged home with only minor neurological defects and returned to normal life. CONCLUSIONS: Hypertrophic olivary degeneration is an infrequent neurological condition, especially in the paediatric population. Nevertheless, it should be considered when interpreting late postoperative scans of children with a history of a brain tumour.

Hypertrophic olivary degeneration in children after posterior fossa surgery. An underdiagnosed condition.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare transsynaptic form of degeneration occurring after injury to the dentato-rubro-olivary pathway ("Guillain-Mollaret triangle"). The majority of studies have described HOD resulting from posterior fossa (PF) hemorrhage or infarction. HOD in patients undergoing PF surgery has not been well characterized. These lesions are rare and symptomatic children with HOD are even more uncommon. The purpose of this study was to evaluate HOD that develops after PF operations in children. MATERIALS AND METHODS: A literature review was carried out describing 37 pediatric cases of HOD in 13 articles. In addition, two new cases of our own experience were included. CONCLUSIONS: HOD is a rare complication related after PF tumors surgery and symptoms may be misdiagnosed with pediatric cerebellar mutism syndrome. Children with HOD usually do not develop palatal tremor but ataxia is common.

Eight-and-a-half syndrome caused by a pontine haemorrhage: a case report and review of the literature.

BACKGROUND: Eight-and-a-half syndrome is caused by a lesion in the dorsal tegmentum of the caudal pons involving parapontine reticular formation and median longitudinal fasciculus, as well as the nucleus and/or the fasciculus of the facial nerve. It is characterized by one-and-a-half syndrome and an ipsilateral cranial nerve VII palsy. Also, many variants of eight-and-a-half syndrome have been described, including nine syndrome, thirteen-and-a-half syndrome and fifteen-and-a-half syndrome. METHODS: We describe a case of a 49-year-old man who presented with eight-and-a-half syndrome combined with contralateral hemiparesis. We reviewed the literature describing the related spectrum of eight-and-a-half syndrome associated with various etiologies. RESULTS: Brain computed tomography scan revealed a hyperdensity located in the left paramedian aspect of the dorsal pons. T2-weighted magnetic resonance imaging at the 11-month follow-up showed hyperintensity and enlargement of the inferior olivary nuclei, which were compatible with a diagnosis of hypertrophic olivary degeneration. In light of our observations and cases reported in the literature, we categorize the spectrum of eight-and-a-half syndrome into three types, namely classic eight-and-a-half syndrome, eight-and-a-half syndrome variants and eight-and-a-half plus syndrome. Besides, the clinical feature and outcome of the three types are discussed in this article. CONCLUSIONS: Recognition of the spectrum of eight-and-a-half syndrome allows precise anatomic localization of the lesion to pontine tegmentum region.

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.

The dentato-rubro-olivary pathway revisited: New MR imaging observations regarding hypertrophic olivary degeneration.

Hypertrophic olivary degeneration (HOD) following a lesion of the dentato-rubro-olivary pathway (DROP) is a well-known imaging finding and has extensively been described in the recent literature. We reviewed our patients with HOD as a result of a lesion of the DROP in order to analyze the disruption of the DROP and the resulting HOD in comparison with the literature. We observed unusual imaging findings in four patients. In two patients it concerned new observations related to the timing and imaging appearances of HOD. HOD became only visible 6 years after a lesion in the red nucleus in one patient and a cystic degeneration of the olivary nucleus was seen 3 years after the HOD in a second patient. In two patients we found HOD that could only be explained by the existence of an afferent feedback loop between the dentate nucleus and the inferior olivary nucleus and by the knowledge that these fibers run through the ipsilateral olivary nucleus before ending in the contralateral olivary nucleus. In one of these patients the lesion was located in the inferior cerebellar peduncle. In the other patient the lesion was located on the midline in the medulla oblongata. The imaging findings in these patients reveal new observations in the stages of imaging appearances in HOD and shed light on the forgotten dentato-olivary afferent feedback loop of the DROP. Clin. Anat. 30:543-549, 2017. © 2017 Wiley Periodicals, Inc.

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).