Postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and hypertrophic olivary degeneration: A case report and literature review.

We presented a case of a 34-year-old male with postoperative brainstem cavernous malformations complicated with LGI1 encephalitis and secondary hypertrophic olivary degeneration (HOD). Due to recurrent dizziness and headache, the patient was diagnosed as brainstem cavernous malformations with recurrent hemorrhage and underwent resection. He subsequently developed unexplained abnormal mental behavior 1 month after the surgery, and diagnosed with LGI1 encephalitis. Six months later, cranial MRI showed HOD. This condition is rare in clinical practice,and a complex mechanism underlies the occurrence.

Monocular Torsional Oscillopsia in Dentato-olivary Disconnection.

Monocular torsional eye oscillations are a rare form of disconjugate nystagmus and the underlying pathophysiology is not well understood. Here, we present and discuss a case with disabling torsional oscillopsia in one eye only. The patient exhibited (i) spontaneous pendular torsional nystagmus of the left eye and (ii) rhythmic involuntary movements of the soft palate and uvula, consistent with the syndrome of oculopalatal tremor with monocular nystagmus. Brain MRI revealed an infarct of the left dentate nucleus in the cerebellum and, more caudally, a secondary hypertrophic degeneration of the right inferior olivary nucleus. To account for the presence of torsional nystagmus on the eye contralateral to the side of inferior olivary hypertrophy and ipsilateral to the lesioned dentate nucleus, we discuss the hypothesis of a (inferior olivary nucleus-mediated) malfunctioning adaptation of the anterior canal vestibulo-ocular reflex.

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.

Clinicopathological features of progressive supranuclear palsy with asymmetrical atrophy of the superior cerebellar peduncle.

Progressive supranuclear palsy (PSP) can be diagnosed despite the presence of asymmetrical parkinsonism depending on the clinical diagnostic criteria. Some studies have reported that atrophy of the superior cerebellar peduncle (SCP) is more frequent in PSP than in Parkinson's disease. There have also been reports of PSP cases with an asymmetrically atrophic SCP. Therefore, we analyzed 48 specimens from consecutive autopsy cases that were neuropathologically diagnosed as PSP to investigate the laterality of brain lesions, including the SCP. We measured the width of the SCP and evaluated the laterality of atrophy. We semi-quantitatively evaluated neuronal loss, atrophy/myelin pallor, and tau pathology in three steps. Asymmetrical atrophy of the SCP was present in seven (14.6%) of 48 cases. The atrophic side of the SCP corresponded to the dominant side of the tau pathology in the cerebellar dentate nucleus. It was opposite to the dominant side of the myelin pallor and tau pathology in the red nucleus and of the tau pathology in the central tegmental tract and inferior olivary nucleus, coinciding with the neurologically systematic anatomy of the Guillain-Mollaret triangle. Neurodegeneration of PSP can progress asymmetrically from one side to the initially intact side in PSP with an initial predominance of Richardson's syndrome, progressive gait freezing, ocular motor dysfunction, parkinsonism, or corticobasal syndrome. To our knowledge, no previous study has reported asymmetrical PSP neuropathology; this is the first study to report the presence of PSP cases with asymmetrical SCP atrophy and systematically asymmetrical degeneration of the Guillain-Mollaret triangle.

A 6-month trial of memantine for nystagmus and associated phenomena in oculopalatal tremor.

Introduction: Oculopalatal tremor (OPT) is a late manifestation of a Guillain-Mollaret triangle lesion. Memantine has been shown to improve nystagmus in OPT, but its long-term efficacy and putative distinct effects on each plane of nystagmus and on associated phenomena (e.g., gravity perception) are largely unknown. Methods: We conducted a 6-month open-label study to evaluate the effect of memantine in OPT patients. Baseline (visit 1), 2 (visit 2), and 6 months (visit 3) assessments included video-oculography, best corrected visual acuity (BCVA), visual function questionnaire (VFQ25), palatal tremor frequency, and subjective visual vertical (SVV). Memantine was titrated to 20 mg per day and stopped after 6 months. Results: We included six patients (5 females; mean age 68.5+/-9.7). At visit 2, nystagmus improved >50% only along the horizontal plane in two patients, while worsening >50% along the vertical and horizontal planes in 4 and 1 patients, respectively. At visit 3, previous improvement of nystagmus along the horizontal plane in two patients was not sustained, and it further worsened >50% along the vertical plane in 4. The mean vertical velocity and amplitude of nystagmus in the left eye significantly worsened from visit 2 to visit 3 (p = 0.028). Throughout the study, nystagmus frequency remained unchanged (p = 0.074), BCVA improved in both eyes (p = 0.047, p = 0.017), SVV progression was unpredictable (p = 0.513), and the mean VFQ-25 score (p = 0.223) and mean palatal frequency remained unchanged. Conclusion: The long-term use of memantine 20 mg per day in OPT produced a modest and only transient improvement in nystagmus, predominantly along the horizontal plane. Visual acuity improved, albeit without relevant changes in vision-related quality of life.

[A case of the palatal tremor that disappeared during swallowing, thought to be caused by microbleeds of bilateral dentate nucleus].

A 72-year-old female presented with slowly progressive dysphonia, which was a syllable-separated utterance, for three years. She had the rhythmic continues contraction of palatal and uvula muscles during speech with a frequency of about 2 Hz. The videoendoscopy showed that the rhythmic contraction, which synchronized in the nasopharynx and the larynx, did not disappear during vocalization. The swallowing videofluorography showed that the rhythmic contraction disappeared transiently during the swallowing reflex, and there was no aspiration. The MRI revealed olivary pseudohypertrophy and multiple microbleedings including the bilateral dentate nucleus. The degeneration of olivary nucleus secondary to the bilateral asymptomatic dentate nucleus microbleedings within the dentato-rubro-olivary pathway was thought to be a cause of palatal tremor. This is a first report that a dynamic relation between vocalization and swallowing in palatal tremor.

Hypertrophic olivary degeneration and palatal myoclonus from a Streptococcus intermedius infection of the brain: illustrative case.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition that can occur after disruption of the Guillain-Mollaret triangle. Clinically, HOD can present with palatal myoclonus with or without oculopalatal tremor, which sometimes results in symptomatic dysphagia and/or speech abnormalities. This condition is commonly associated with vascular lesions, with only three prior reported cases of HOD resulting from intracranial abscess. OBSERVATIONS: An otherwise healthy patient developed multiple intracranial abscesses. Biopsy showed gram-positive cocci; however, culture findings were negative. Polymerase chain reaction (PCR) identified Streptococcus intermedius. The patient demonstrated palatal myoclonus and vertical nystagmus, which resulted in persistent mild dysphagia and altered speech intonation. After appropriate antimicrobial therapy with resolution of the enhancing lesions, symptoms persisted. Follow-up imaging demonstrated progressive hypertrophy of the right olive with persistent disruption of the right-sided rubro-olivo fiber pathways. LESSONS: Although HOD classically occurs after vascular insult, it can also be seen as a postinfectious sequela. Despite eradication of the infection, palatal myoclonus and oculopalatal tremor may have a persistent impact on quality of life due to impaired speech and swallowing. This case emphasizes the utility of universal PCR in detecting fastidious organisms as well as diffusion tensor imaging for characterization of disrupted fiber pathways.

Imaging secondary neuronal degeneration.

OBJECTIVE: Distal nerve degeneration refers to the process of disintegration of a neuron or neuronal circuit as a consequence of distal damage. The end result of multiple etiologies, this finding is becoming common due to the increasing number of imaging tests done. This paper aims to define the different types of distal nerve damage, review the anatomy and function of the most commonly affected tracts, and illustrate distal nerve damage through diagrams and representative cases from routine practice. CONCLUSION: Knowing the distant response that can be expected according to the topography of a neuronal lesion is crucial to avoid diagnostic errors. Axonal degeneration and transsynaptic degeneration can be both antegrade and retrograde. Studies of cerebral metabolism, perfusion sequences, and diffusion sequences are showing increasingly earlier changes related to the same process; radiologists need to be aware of these changes.

Recognizing myorhythmia 4 months after stroke - A teaching video.

In this case study with video and neurophysiology, we describe a rare case of hemimyorhythmia occurring 4 months after a stroke with bilateral affection of the thalamus and right superior cerebellar peduncle (Guillain-Mollaret-triangle). This case and especially the video with the clinical and EMG presentation of a synchronous rhythmic pattern at 3,1 Hz makes an important educational contribution to the recognition of myorhythmia and discussed differential diagnoses.

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 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.

Oncologic causes of oculopalatal tremors: neurophysiology and treatment.

Oculopalatal tremor (OPT) is an acquired pathology characterized by continuous and rhythmical soft palatal movements combined with pendular nystagmus. Aside from vascular lesions, oncological masses affecting the dentatorubro-olivary pathway can impair brainstem and/or cerebellar pathways, manifesting as dyssynchronous movement. In this review, we delve into the neurophysiology of OPT along with oncological causes and treatment options based on the most recent clinical trial data. This literature review includes medication treatment data from clinical trials enrolling individuals with features of OPT, including acquired pendular nystagmus (APN). Trials were deemed eligible for inclusion in this review if one or more participants had symptoms determined by the trial authors to be caused by OPT. Trials investigating the treatment of APN secondary to a separate cause, such as multiple sclerosis, were excluded from this review. Several early treatments failed to demonstrate a benefit for patients with APN due to OPT. Trials of anticholinergic agents were largely ineffective and poorly tolerated. Botulinum toxin A demonstrated improvement in APN symptoms. Most recently, trials including memantine and gabapentin have demonstrated success with attenuation of APN. Surgical modalities such as DBS have yet to show improvement, though with only a single case report as evidence. Oculopalatal tremor is a unique manifestation of posterior fossa tumors disrupting the Guillain-Mollaret triangle. Symptom control through medication management has had limited success attributed to poor response and medication intolerance. Surgical modalities like DBS may have an emerging role in OPT treatment by targeting dyssynchronous activity in the dentatorubro-olivary pathway.

Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor.

Lesions in the Guillain-Mollaret (G-M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G-M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry.

Clinical and Imaging Profile of Patients with Palatal Tremor.

BACKGROUND: Palatal tremor (PT) is an uncommon movement disorder that may be classified into symptomatic (SPT) or essential (EPT). The etiology of SPT is varied, with involvement of the Guillain-Mollaret triangle (GMT) and inferior olivary hypertrophy. EPT is associated with ear clicks and normal imaging and may have a functional basis. OBJECTIVES: This study aims to explore the clinical and radiological features of a large cohort of patients with PT. METHODS: This is a retrospective chart review of patients with PT who were evaluated by the movement disorders subspeciality of the neurology department. Demographic, clinical, and imaging details of patients with PT were documented. RESULTS: A total of 22 patients with PT comprising 17 with SPT and 5 with EPT were included in this study. No patient was aware of the PT. Ear clicks were reported in 2 patients with SPT and in 3 patients with EPT. The most common etiology for SPT was vascular, followed by degenerative conditions. Patients with SPT had associated features such as tremor (70.6%), ataxia (64.7%), dystonia (52.9%), myoclonus (17.6%), and eye movement abnormalities (75%). Lesions involving the GMT were found in 82% of patients with SPT. Apart from PT, patients with EPT had no other motor symptoms, and imaging was normal. Of the patients with EPT, 2 had additional functional movement disorders. CONCLUSION: PT has significant etiological heterogeneity and can be easily missed because of the lack of awareness by patients. Involvement of the inferior olivary nucleus may not be necessarily observed. A functional etiology should be considered in cases of EPT.

Cough syncope and hyperventilation-induced convulsion in Chiari 1.5 malformation.

Chiari malformation type I (CM1) is defined as cerebellar tonsillar herniation below the level of the foramen magnum. Syncope, especially cough syncope, is a rare but important symptom of CM1 patients. Here, we report a CM1 patient, in combination with brainstem herniation (CM1.5), presenting with repetitive syncope who was successfully treated by decompressive surgery. A 43-year-old right-handed male, with 5-year history of repeated episodes of loss of consciousness in association with cough, was investigated. Neurological examination revealed slight muscle weakness, clumsiness, and sensory disturbance in the left upper limb. There was no sign of orthostatic hypotension or orthostatic intolerance. Cranial and spinal magnetic resonance imaging revealed a herniation of the cerebellar tonsils and a syringomyelia. Forced hyperventilation during electroencephalogram (EEG) induced brief generalized symmetric clonic convulsions with preserved consciousness, but no overt EEG seizure patterns or slow activities were found. Based on the diagnosis of CM1.5 with recurrent episodes of loss of consciousness, he underwent foramen magnum decompression. He has no recurrence of the episode after the surgery on 1 year follow-up. Decompressive surgery was an effective procedure for cough syncope and other symptoms of the current patient with CM1.5. Dissociation of cerebrospinal fluid pressure between the cranial and spinal compartments which leads further herniation of the cerebellar tonsils and subsequent compression on the cerebellum and the brainstem is considered to be the major mechanism of his cough syncope. Analysis of EEG can be useful not only to diagnose epileptic seizures but also to elucidate mechanisms of syncope and concurrent involuntary movements.

Temporal Evolution of Hypertrophic Olivary Degeneration in a Pediatric Patient: A Case Report and Review of Literature.

Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration seen after interruption of the dentato-rubro-olivary tract also known as the Guillain-Mollaret triangle (GMT). It is associated with hypertrophic changes of the inferior olive. Commonly reported in adults, this lesion presents with ataxia and oculopalatal myoclonus. Up to date, few cases have been published in the literature that refer to pediatric cases. This diagnosis is particularly important in the setting of brainstem tumor surgery as it should not be confused for tumor recurrence or metastasis, in turn avoiding unwarranted surgical intervention. We present the case of a 15-year-old male who underwent resection of a left superior cerebellar peduncle (SCP) pilocytic astrocytoma. On follow-up, magnetic resonance imaging (MRI) demonstrated evidence of mild residual tumor as well as progressive engorgement of the inferior olivary nucleus (ION). The patient was clinically asymptomatic and has since been observed expectantly without any issues. We were able to pinpoint the most probable location of injury in our patient's GMT. HOD remains a somewhat obscure entity. Its presentation may be early and not accompanied by significant neurologic findings, in contrast to what has been previously reported. Particularly in neoplastic cases, it may represent a diagnostic challenge and could be easily confused for tumor recurrence. A multidisciplinary approach for this entity, as with other pathologies, is of particular importance. Its proper recognition will result in the best outcomes for the patient.