[A case of Holmes tremor in which 123I-IMP SPECT and MRI findings suggest damage to the cerebellothalamic tract and the dentato-rubro-olivary pathway].

A 75-year-old woman was referred to our department in October 2022 with ataxia and involuntary movements of the right upper and lower limbs. She had experienced a left pontine hemorrhage in March 2021, which was managed conservatively. However, she had residual right-sided hemiplegia. In addition, she had cerebellar ataxia and a 2 |Hz resting tremor of the right upper and lower limbs, which was enhanced while maintaining posture and contemplation. Based on her history, and the findings of MRI and nuclear medicine imaging, we diagnosed the patient with Holmes tremor due to pontine hemorrhage. Holmes tremor is a rare movement disorder secondary to brainstem and thalamic lesions, characterized by a unilateral low-frequency tremor. In this case, 123I-IMP SPECT and MRI shows damage to the cerebellothalamic tract and dentaro-rubro-olivary pathway.

Cerebellar cognitive affective syndrome with psychotic features in a patient with hypertrophic olivary degeneration.

Objective: Hypertrophic Olivary Degeneration is a rare condition causing transneuronal degeneration of the inferior olivary nucleus. Symptoms manifest as progressively worsening palatal tremor, ataxia, and eye movement disturbances that plateau after several months. Though rarely documented in the literature of this specific condition, disconnection of the inferior olivary nucleus from the cerebellum, and cerebellar atrophy represent a pathway to developing subsequent cerebellar cognitive affective syndrome. The presented case documents the neuropsychological sequelae of a 39-year-old female with a history of hypertrophic olivary degeneration and symptoms of palatal tremor, opsoclonus myoclonus, ataxia, and delusions. Method: Review of the patient's medical records, interviews with the patient and her father, and a neuropsychological assessment battery were used to collect data. Review of currently published literature lent to case conceptualization. Results: Neuropsychological testing revealed deficits in executive functioning, attention, and language. An anomalous, fixed persecutory delusion was revealed. Conclusion: Hypertrophic olivary degeneration creates disconnection syndromes between the inferior olivary nucleus, red nucleus, and cerebellum. Late stages of the disorder cause atrophy of the inferior olivary nucleus and adjacent structures. While the motor sequela is well documented, the neuropsychological and psychiatric impact is infrequently discussed in existing literature. We present the first case to detail the neuropsychological sequelae of hypertrophic olivary degeneration and propose a mechanism for the development of cognitive impairment and psychotic features within this condition.

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.

Long-standing myoclonic hand tremor as an isolated symptom of hypertrophic olivary degeneration.

Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions of the dentato-rubro-olivary pathway, usually bilateral. We presented a case of a 64-year old male with HOD caused by a unilateral, posterior pontine cavernoma. The patient has not developed the typical palate myoclonus until recently. Isolated hand myoclonus with coexisting asterixis was present for years. This case shows unique HOD symptomatology and emphasizes the important role of MRI in the differential diagnosis of monomelic myoclonus.

V180I genetic Creutzfeldt-Jakob disease: Severe degeneration of the inferior olivary nucleus in an autopsied patient with identification of the M2T prion strain.

Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81-year-old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic-type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD-MM2T but preserved in other patients with V180I gCJD and sCJD-MM1 (this patient, 2.3 ± 0.53/mm2 ; a patient with sCJD-MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD-MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here.

Hypertrophic olivary degeneration associated with bilateral vocal cord adductor dystonia.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition caused by lesions within the dentato-rubro-olivary pathway, resulting in ocular nystagmus and palatal myoclonus (oculopalatal tremor) but not usually dystonia. Dystonia is an uncommon association, and we present the first reported association of hypertrophic olivary degeneration with bilateral vocal cord dystonia. CASE PRESENTATION: A 33 year old male presented initially with acute hydrocephalus on the background of previous ventriculoperitoneal (VP) shunting for previously treated medulloblastoma. After revision of the VP shunt, the patient developed progressive hiccups and stridor leading to respiratory failure requiring intubation. Ocular pendular nystagmus and palatal myoclonus at 3 Hz was observed. Flexible nasendoscopy (FNE) demonstrated bilateral tonic adduction of the vocal folds with 3 Hz coarse supraglottic, pharyngeal and palatal rhythmic myoclonus. MRI imaging demonstrated T2 hyperintensity within the bilateral inferior olivary nuclei consistent with stage 3 radiological HOD. CONCLUSIONS: Dystonia is a rarely reported phenomenon in HOD but is not unexpected with the inferior olivary nucleus implicated in dystonic disorders. We report the association of HOD with bilateral vocal cord adductor dystonia, a potentially life threatening condition.

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.

A case report of hypertrophic olivine degeneration complicated with OSAHS exacerbation: Case report and retrospective analysis.

RATIONALE: Hypertrophic subolivine degeneration (HOD) was destroyed by Guillain-Mollaret triangle (GMT) due to various injuries, resulting in anterograde cavity-like degeneration of the lower olive nucleus. In addition, the brain stem is related to the muscle coordination of the upper respiratory tract. Obstructive sleep apnea hypopnea syndrome may affect the respiratory center due to the injury of the brain stem. Brain stem hemorrhage damage GMT, resulting in transsynaptic neuronal degeneration. Clinical manifestations can be complex, and enhanced magnetic resonance imaging can be helpful in distinguishing them. PATIENT CONCERNS: HOD is a self-limiting disease with no effective treatment and a long course of disease. Most patients can improve their symptoms after symptomatic treatment, and some patients can relieve their symptoms by themselves after 3 to 4 years. DIAGNOSIS INTERVENTIONS: The limbs wobble involuntarily. His clinical symptoms and signs are consistent with HOD. Imaging with a clear primary lesion confirmed HOD. After treatment with antiepileptic drugs, the patient's symptoms were relieved. Moreover, the patient had snoring and apnea, and respiratory sleep monitoring showed moderate obstructive sleep apnea hypopnea syndrome, which was treated with noninvasive ventilator. OUTCOMES: After treatment with antiepileptic drugs and noninvasive ventilator, the patient's symptoms were significantly relieved. LESSONS: HOD is a rare clinical disorder. Therefore, for similar patients, more attention should be paid to early diagnosis and treatment to avoid missed diagnosis, misdiagnosis and unnecessary intervention measures. The diagnosis can be confirmed by primary disease, clinical symptoms, and imaging based on GMT.

Is essential tremor a disorder of GABA dysfunction? No.

Although essential tremor is common, its underlying pathophysiology remains uncertain, and several hypotheses seek to explain the tremor mechanism. The GABA hypothesis states that disinhibition of deep cerebellar neurons due to reduced GABAergic input from Purkinje cells results in increased pacemaker activity, leading to rhythmic output to the thalamo-cortical circuit and resulting in tremor. However, some neuroimaging, spectroscopy, and pathology studies have not shown a clear or consistent GABA deficiency in essential tremor, and animal models have indicated that large reductions of Purkinje cell inhibition may improve tremor. Instead, tremor is increasingly attributable to dysfunction in oscillating networks, where altered (but not necessarily reduced) inhibitory signaling can result in tremor. Hypersynchrony of Purkinje cell activity may account for excessive oscillatory cerebellar output, with potential contributions along multiple sites of the olivocerebellar loop. Although older animal tremor models, such as harmaline tremor, have explored contributions from the inferior olivary body, increasing evidence has pointed to the role of aberrant climbing fiber synaptic organization in oscillatory cerebellar activity and tremor generation. New animal models such as hotfoot17j mice, which exhibit abnormal climbing fiber organization due to mutations in Grid2, have recapitulated many features of ET. Similar abnormal climbing fiber architecture and excessive cerebellar oscillations as measured by EEG have been found in humans with essential tremor. Further understanding of hypersynchrony and excessive oscillatory activity in ET phenotypes may lead to more targeted and effective treatment options.

Hypertrophic Olivary Degeneration Postoperatively Following Pilocytic Astrocytoma Resection.

A 25-year-old male presented with headaches 3 weeks after a car accident. His magnetic resonance imaging images showed a hemorrhagic vermis mass with fourth ventricle effacement. One month later, he underwent suboccipital craniotomy for removal of a pilocytic astrocytoma. A 3-month postoperative scan demonstrated a new area of medullary hyperintensity in the inferior olive, which was also present 7 months postoperatively consistent with hypertrophic olivary degeneration. This condition is caused by disruption to the dento-rubro-olivary pathway with magnetic resonance imaging enlargement of the inferior olivary nucleus and increased T2 signal. Hypertrophic olivary degeneration should be considered after cerebellar surgery and should not be mistaken for tumor recurrence.

Deep brain stimulation as a palliative treatment for myorhythmia: A case of failure.

BACKGROUND AND PURPOSE: Myorhythmia is a hyperkinetic movement disorder that derives from a disruption of the Guillain-Mollaret triangle, due to an identifiable structural lesion. It is often disabling and with disappointing control under medical treatment. METHODS: Herein, a case of myorhythmia secondary to a vascular insult in the brainstem is reported and an unsuccessful attempt to palliate it with functional neurosurgery. RESULTS: A 67-year-old man displayed a repetitive, rhythmic, slow 2-3 Hz movement, 6 months after suffering a pontomesencephalic hypertensive haematoma. The kinetic phenomenon affected the orbicular and low facial muscles, the neck, the thorax and the upper limbs. Furthermore, he exhibited tremor of the soft palate and pendular nystagmus. On T2-weighted magnetic resonance imaging, hypertrophic degeneration of the inferior olivary complex was seen. He was diagnosed with secondary myorhythmia and multiple pharmacological treatments were tested, but failed. Ultimately, deep brain stimulation with bilateral electrodes placed in the thalamic ventralis intermedius nucleus was offered. Unfortunately, no alleviation of the symptoms was achieved other than mild improvement in involuntary eye movements. CONCLUSIONS: This is the first case to report the use of deep brain stimulation for myorhythmia. Better understanding of the pathophysiology of this condition, and localization of the pacemaker, may allow identification of reliable neurosurgical therapeutic targets.

Bilateral Hypertrophic Olivary Degeneration as a Paraneoplastic Syndrome of a Poorly Differentiated Carcinoma of the Upper Gastrointestinal Tract: A Case Report and Literature Review.

INTRODUCTION: Hypertrophic olivary degeneration (HOD) is a unique form of trans-synaptic neuronal degeneration within the dentato-rubro-olivary pathway which is manifested by the enlargement and hyperintensities of the inferior olivary nucleus in the brain magnetic resonance imaging. CASE REPORT: We report a 53-year-old man admitted to our emergency department with a history of progressive ataxia and vertigo for 6 months before admission. Neurological examination revealed cerebellar dysfunction, and the brain magnetic resonance imaging showed bilateral HOD without an identifiable causative lesion within the brain or abnormal meningeal enhancement. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis, elevated protein, and negative cytology. Malignancy and paraneoplastic workup exhibited marked elevation of carbohydrate antigen 19-9 level and para-aortic lymphadenopathy. A histologic examination demonstrated the infiltration of lymph nodes by a malignant, poorly differentiated carcinomatous tumor that arises from the upper gastrointestinal tract. Considering the primary site of the tumor and HOD as a paraneoplastic effect of carcinoma, a FOLFIRINOX regimen, intravenous immunoglobulin, and pulse methylprednisolone were started. A follow-up imaging after 3 months depicted a significant resolution of HOD but the neurological status only mildly improved. The patient developed liver and adrenal metastasis over the following 6 months, culminating in his death. CONCLUSION: This study strengthens a relationship between HOD and malignancy as a paraneoplastic syndrome and provides a new incentive for further researches to confirm this association.

Quantitative evaluation of posture control in rats with inferior olive lesions.

Impairment of inferior olivary neurons (IONs) affects whole-body movements and results in abnormal gait and posture. Because IONs are activated by unpredicted motion rather than regular body movements, the postural dysfunction caused by ION lesions is expected to involve factors other than simple loss of feedback control. In this study, we measured the postural movements of rats with pharmacological ION lesions (IO rats) trained to stand on their hindlimbs. The coordination of body segments as well as the distribution and frequency characteristics of center of mass (COM) motion were analyzed. We determined that the lesion altered the peak properties of the power spectrum density of the COM, whereas changes in coordination and COM distribution were minor. To investigate how the observed properties reflected changes in the control system, we constructed a mathematical model of the standing rats and quantitatively identified the control system. We found an increase in linear proportional control and a decrease in differential and nonlinear control in IO rats compared with intact rats. The dystonia-like changes in body stiffness explain the nature of the linear proportional and differential control, and a disorder in the internal model is one possible cause of the decrease in nonlinear control.

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.

An autopsy case of corticobasal degeneration with inferior olivary hypertrophy.

We report autopsy results of a female patient who was confirmed pathologically as having corticobasal degeneration (CBD). This patient presented with progressive gait disturbance at the age of 66 years, and subsequently showed parkinsonism with a right-sided predominance and dementia. She was clinically diagnosed as having possible corticobasal syndrome without palatal myoclonus throughout the disease course. An autopsy at 72 years of age revealed that neuronal loss with gliosis was severe in the substantia nigra and the portion from hippocampal cornu ammonis (CA1) region to the parahippocampal gyrus, and mild-to-moderate in the basal ganglia, thalamus, red nucleus, dentate nucleus, and cerebral cortices, predominantly in the frontal lobe. Myelin pallor was observed in the pyramidal tract of the brainstem and central tegmental tract. Neurodegenerative or axonal degenerative findings were observed predominantly on the left side, except for the dentate nucleus, which was more affected on the right side. The inferior olivary nucleus exhibited hypertrophic degeneration predominantly on the left side. The topography of neurodegeneration was likely to correspond to the dentate nucleus and inferior olivary nucleus. Phosphorylated tau-immunoreactive pretangles, neurofibrillary tangles, coiled bodies, and threads were diffusely observed in the whole brain. The distribution of tau deposits was prominent in the deeper affected lesions of the dentate nucleus and inferior olivary nucleus. Inferior olivary hypertrophy is unusual in patients with CBD. It is highly possible that the neurodegeneration of the inferior olivary nucleus followed that of the dentate nucleus in our patient. Moreover, these results indicate not only the severity of neurodegenerative changes, but also that of tau deposition that could be related to the topography of the projections of the dentato-olivary pathway. Tau propagation and subsequent neurodegeneration along the fiber connections may have occurred. Our results support the possibility that progression of CBD lesions can be mediated by tau propagation.

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.

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.