Contralateral Dentate Nucleus Research Articles

Use of probabilistic tractography to provide reliable distinction of the motor and sensory thalamus for prospective targeting during asleep deep brain stimulation.

Accurate electrode placement is key to effective deep brain stimulation (DBS). The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for the treatment of essential tremor (ET). Retrospective tractography-based analysis of electrode placement has associated successful outcomes with modulation of motor input to VIM, but no study has yet evaluated the feasibility and efficacy of prospective presurgical tractography-based targeting alone. Therefore, the authors sought to demonstrate the safety and efficacy of probabilistic tractography-based VIM targeting in ET patients and to perform a systematic comparison of probabilistic and deterministic tractography. Fourteen patients with ET underwent preoperative diffusion imaging. Probabilistic tractography was applied for preoperative targeting, and deterministic tractography was performed as a comparison between methods. Tractography was performed using the motor and sensory areas as initiation seeds, the ipsilateral thalamus as an inclusion mask, and the contralateral dentate nucleus as a termination mask. Tract-density maps consisted of voxels with 10% or less of the maximum intensity and were superimposed onto anatomical images for presurgical planning. Target planning was based on probabilistic tract-density images and indirect target coordinates. Patients underwent robotic image-guided, image-verified implantation of directional DBS systems. Postoperative tremor scores with and without DBS were recorded. The center of gravity and Dice similarity coefficients were calculated and compared between tracking methods. Prospective probabilistic targeting of VIM was successful in all 14 patients. All patients experienced significant tremor reduction. Formal postoperative tremor scores were available for 9 patients, who demonstrated a mean 68.0% tremor reduction. Large differences between tracking methods were observed across patients. Probabilistic tractography-identified VIM fibers were more anterior, lateral, and superior than deterministic tractography-identified fibers, whereas probabilistic tractography-identified ventralis caudalis fibers were more posterior, lateral, and superior than deterministic tractography-identified fibers. Deterministic methods were unable to clearly distinguish between motor and sensory fibers in the majority of patients, but probabilistic methods produced distinct separation. Probabilistic tractography-based VIM targeting is safe and effective for the treatment of ET. Probabilistic tractography is more precise than deterministic tractography for the delineation of VIM and the ventralis caudalis nucleus of the thalamus. Deterministic algorithms tended to underestimate separation between motor and sensory fibers, which may have been due to its limitations with crossing fibers. Larger studies across multiple centers are necessary to further validate this method.

Palato-Pharyngo-Laryngeal Myoclonus with Facial Involvement After an Ischemic Stroke.

Palatal myoclonus, also described as palatal tremor, is characterized by rhythmic continuous 0.5 to 5 Hz movements of the soft palate and pharynx.1 There are two categories described: symptomatic palatal tremor, because of a brainstem or cerebellar lesion, and essential palatal tremor, with no associated structural lesion.2, 3 Palatal myoclonus can rarely be associated with synchronous myoclonus of other branchial arch muscles, the diaphragm, facial muscles, or even the extremities.2 One specific variant is termed palato-pharyngo-laryngeal myoclonus, which can result in dysphagia, dysphonia, and dysarthria.4 A 56-year-old woman awoke from sleep with new right-sided weakness and dizziness. Magnetic resonance imaging (MRI) of the brain showed restricted diffusion in the right superomedial cerebellum consistent with an acute infarct (Fig. 1). The etiology of stroke was atheroembolism from an aortic arch plaque atheroma, for which she was started on aspirin. The follow-up MRI of the brain 4 months later showed a new fluid-attenuated inversion recovery (FLAIR) signal abnormality in the left medulla involving the left inferior olivary nucleus, reflecting hypertrophic olivary degeneration related to the chronic cerebellar infarct in the proximity of the contralateral dentate nucleus (Fig. 2). Ten months after the stroke, the patient reported a subjective, rhythmic, non-suppressible “whooshing” sound in her right ear that did not correspond to her heart rate and persisted during sleep. A computed tomography (CT) angiogram of the head and neck ruled out any vascular abnormalities. Nasopharyngolaryngoscopy showed spasm of the hypopharyngeal musculature and larynx. The patient returned to clinic to report new involuntary twitching of the right lower face. On examination, she had ~2 Hz rhythmic myoclonus of the right lip, chin, and throat (Video 1) as well as the palate (Video 2). There was no evidence of facial weakness, ocular motility problems, dysarthria, or dysphagia. She was prescribed a trial of carbamazepine 200 mg twice daily for palatal tremor followed by baclofen 5 mg twice daily with mild relief. She declined to try clonazepam or botulinum toxin injections. Palato-pharyngo-laryngeal myoclonus is a rare condition that can be idiopathic or lesional. Symptoms of palatal tremor are usually delayed 6 to 9 months after the initial injury, but can be delayed up to 30 months.1 The etiology of palatal tremor is disruption of the dento-rubro-olivary pathway, known as the Guillain Mollaret triangle. A lesion in this pathway causes denervation of olivary neurons from inhibitory cerebellar inputs, leading to hypertrophy and sustained synchronized oscillations causing tremor.2, 3 We present a unique case of palato-pharyngo-laryngeal and facial myoclonus caused by an ischemic stroke of the cerebellum. The patient also had pulsatile tinnitus, which correlated with direct visualization of spasms of the palate, hypopharyngeal musculature, and larynx via nasopharyngolaryngoscopy. Pulsatile tinnitus is most common in essential palatal tremor because of contraction of the tensor veli palatini on the eustachian tube. Although symptomatic palatal tremor affects the levator veli palatini, it can also rarely cause subjective auditory phenomena, likely because of some fibers inserting on the eustachian tube.1, 5 The patient's mild improvement in symptoms with the combination of baclofen and carbamazepine suggest a potential therapeutic option that warrants further investigation. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique. C.L.N.: 1B, 1C, 3A S.Q.: 1B, 1C, 3A M.S.: 1A, 3B Per the University of Pennsylvania Institutional Review Board, “a single retrospective case report is a medical/educational activity and does not meet the Federal Policy for the Protection of Human Subjects definition of research which is a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Therefore, the activity does not require review by the IRB. Under HIPAA, a single case report is an activity to develop information to be shared for medical/educational purposes. Therefore, the use of protected health information to prepare a paper for publication of a single case report does not require IRB review for HIPAA purposes.” The patient provided verbal consent while at a clinic visit. The patient also provided signed/written consent which was mailed to the Neurology office. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. M.S. has received clinical trial support from AbbVie, Abbott, United States (US) World Meds, and Sanofi. C.L.N. and S.Q. have no other financial disclosures to report.

Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification.Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed.We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject variability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotactic targeting.

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

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

The Brain Connectome after Gamma Knife Radiosurgery of the Ventro-Intermediate Nucleus for Tremor: Marseille-Lausanne Radiobiology Study Protocol

Essential tremor (ET) is the most common movement disorder. Deep brain stimulation is the current gold standard for drug-resistant tremor, followed by radiofrequency lesioning. Stereotactic radiosurgery by Gamma Knife (GK) is considered as a minimally invasive alternative. The majority of procedures aim at the same target, thalamic ventro-intermediate nucleus (Vim). The primary aim is to assess the clinical response in relationship to neuroimaging changes, both at structural and functional level. All GK treatments are uniformly performed in our center using Guiot’s targeting and a radiation dose of 130 Gy. MR neuroimaging protocol includes structural imaging (T1-weighted and diffusion-weighted imaging [DWI]), resting-state functional MRI, and ¹⁸F-fluorodeoxyglucose-positron emission tomography. Neuroimaging changes are studied both at the level of the cerebello-thalamo-cortical tract (using the prior hypothesis based upon Vim’s circuitry: motor cortex, ipsilateral Vim, and contralateral cerebellar dentate nucleus) and also at global brain level (no prior hypothesis). This protocol aims at using modern neuroimaging techniques for studying Vim GK radiobiology for tremor, in relationship to clinical effects, particularly in ET patients. In perspective, using such an approach, patient selection could be based upon a specific brain connectome profile.

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

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

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

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

Hypertrophic olivary degeneration: A comprehensive review focusing on etiology

Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration characterized by hypertrophy of the inferior olivary nucleus situated in the olivary body, part of the medulla oblongata, representing a major source of input to the cerebellum. HOD typically results from focal lesions interrupting connections from the inferior olive within the dentato-rubro-olivary pathway (DROP), a region also known as the Guillain-Mollaret triangle (GMT) (red nucleus, inferior olivary nucleus, and contralateral dentate nucleus). Clinically, HOD presents classically as palatal tremor and can include dentatorubral tremor and/or ocular myoclonus. Oppenheim first described the enlargement of the ION in his post-mortem study. Since then, a limited number of cases have been reported in the literatures. Thus, we intended to describe the definition, pathophysiology, clinical features, radiological features, diagnosis, and current management of HOD. We provide a comprehensive review of HOD focusing on etiology. The present review may lead to a better understanding of HOD clinical characteristic with the goal of contributing to existing knowledge of this rare disease.

Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor.

PurposeTo evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methodsEight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.ResultsThe probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = −0.929, −0.75, −0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = −0.719, −0.976, −0.707, −0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).ConclusionOur data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Hierarchical Dynamic Causal Modeling of Resting-State fMRI Reveals Longitudinal Changes in Effective Connectivity in the Motor System after Thalamotomy for Essential Tremor.

Thalamotomy at the ventralis intermedius nucleus for essential tremor is known to cause changes in motor circuitry, but how a focal lesion leads to progressive changes in connectivity is not clear. To understand the mechanisms by which thalamotomy exerts enduring effects on motor circuitry, a quantitative analysis of directed or effective connectivity among motor-related areas is required. We characterized changes in effective connectivity of the motor system following thalamotomy using (spectral) dynamic causal modeling (spDCM) for resting-state fMRI. To differentiate long-lasting treatment effects from transient effects, and to identify symptom-related changes in effective connectivity, we subject longitudinal resting-state fMRI data to spDCM, acquired 1 day prior to, and 1 day, 7 days, and 3 months after thalamotomy using a non-cranium-opening MRI-guided focused ultrasound ablation technique. For the group-level (between subject) analysis of longitudinal (between-session) effects, we introduce a multilevel parametric empirical Bayes (PEB) analysis for spDCM. We found remarkably selective and consistent changes in effective connectivity from the ventrolateral nuclei and the supplementary motor area to the contralateral dentate nucleus after thalamotomy, which may be mediated via a polysynaptic thalamic–cortical–cerebellar motor loop. Crucially, changes in effective connectivity predicted changes in clinical motor-symptom scores after thalamotomy. This study speaks to the efficacy of thalamotomy in regulating the dentate nucleus in the context of treating essential tremor. Furthermore, it illustrates the utility of PEB for group-level analysis of dynamic causal modeling in quantifying longitudinal changes in effective connectivity; i.e., measuring long-term plasticity in human subjects non-invasively.

Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor.

Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome manifests as a synchronous tremor of the palate (PT) and/or eyes (OPT) that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This “symptomatic” condition requires a destructive lesion in the Guillain–Mollaret pathway, which spans from the contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic), brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not occur (or not reported), the main reported etiologies are Alexander disease, polymerase gamma mutation, and spinocerebellar ataxia type 20. Whether or not these are associated with specific degeneration of the dentato–olivary pathway remain to be determined. The most symptomatic consequence of OPT is eye oscillations. Therapeutic trials suggest gabapentin or memantine as valuable drugs to treat eye oscillations in OPT.

Imaging Features of Hypertrophic Olivary Degeneration.

Hypertrophic olivary degeneration (HOD) is a unique form of transneuronal degeneration caused by a disruption of the dentato-rubro-olivary pathway, also known as the triangle of Guillain-Mollaret. The triangle of Guillain-Mollaret is involved in fine voluntary motor control and consists of both the inferior olivary nucleus and the red nucleus on one side and the contralateral dentate nucleus. Clinically, patients classically present with symptomatic palatal myoclonus. Typical magnetic resonance imaging findings include T2-hyperintensity and enlargement of the inferior olivary nucleus evolving over time to atrophy with residual T2-hyperintensity. In this article, we provide a case-based illustration of the anatomy of the Guillain-Mollaret-triangle and the typical imaging findings of hypertrophic olivary degeneration.

The Guillain–Mollaret triangle in action

The Guillain–Mollaret triangle comprises the ipsilateral red nucleus in the midbrain, the inferior olive in the medulla and the contralateral dentate nucleus in the cerebellum: together, these form the dentato-rubro-olivary...

Hypertrophic Olivary Degeneration: A Neurosurgical Point of View

Hypertrophic olivary degeneration (HOD) is a rare form of transsynaptic degeneration characterized by hypertrophy of the inferior olivary nucleus situated in the olivary body, part of the medulla oblongata, representing a major source of input to the cerebellum. HOD typically results from focal lesions interrupting connections from the inferior olive within the dentato-rubro-olivary pathway, a region also known as the triangle of Guillain-Mollaret (TGM) (red nucleus, inferior olivary nucleus, and contralateral dentate nucleus). Clinically, HOD presents classically as palatal tremor and can include dentatorubral tremor and/or ocular myoclonus. The pathologic changes associated with HOD feature radiologic changes with the inferior olivary nucleus appearing larger and increasing its T2-weighted signal intensity on magnetic resonance images. HOD is commonly managed with pharmacotherapy but may require surgical intervention in extreme cases. HOD has been found to develop as a consequence of any injury that disrupts the TGM pathways (e.g., pontine cavernoma).These findings highlight the critical importance of a thorough knowledge of TGM anatomy to avoid secondary HOD. We present a patient who developed HOD secondary to resection of a tectal plate cavernous malformation and review the literature with an emphasis on the current knowledge of this disorder.

Hypertrophic Degeneration of the Inferior Olive Yields Erroneous Internal Estimates of Direction of Gravity (P02.255)

Objective: To investigate the role of the inferior olive (IO) for estimating direction of gravity. Background Central graviceptive pathways (CGP) connect the vestibular nuclei with cerebellar, brainstem and cortical areas. Acute lesions along the CGP lead to ocular torsion, skew deviation and subjective visual vertical (SVV) tilt. The IO is interconnected with the contralateral dentate nucleus and the ipsilateral red nucleus. Disruption of the central tegmental tract connecting the red nucleus with the IO may interfere with estimating direction of gravity. Design/Methods: We assessed the SVV in a 65yo man with a pontomesencephalic hemorrhage that included the medial vestibular nuclei, the right superior and lateral vestibular nucleus, the right interstitial nucleus of Cajal, the medial longitudinal fasciculus and central tegmental tract bilaterally. SVV was assessed at 16 days and 4 months after hemorrhage. Initially, he presented with gait ataxia, horizontal gaze palsy, impaired upgaze, and left-sided sensorimotor impairment. After four months he developed a vertical pendular nystagmus and increased gait ataxia. MR-imaging revealed a hypertrophic degeneration of the right IO. Results: Whereas SVV adjustments obtained at day 16 deviated 3.7° ipsilesional, large contralesional (-15.2°) deviations were found after four months. Conclusions: A shift from ipsilesional to contralesional SVV deviations in the presence of a hypertrophic degeneration of the IO was observed. We hypothesize that disrupted inhibitory GABA-ergic input from the red nucleus to the IO results in synchronized oscillations of IO neurons. These synchronized oscillations are signaled to the cerebellum, which results in a loss of inhibitory control that is normally provided through this pathway. This loss of inhibition could lead to hyperactivity of the dentate nucleus contralateral to the affected IO and consequently to a SVV tilt to the side of the overactive dentate nucleus. Such a mechanism would be in accordance to previous reports describing SVV tilts contralateral to an inhibited dentate nucleus. Supported by: Swiss National Science Foundation (3200B0-105434 and 32003B_130163/1), the Betty and David Koetser Foundation for Brain Research, Zurich, Switzerland, and the Center of Integrative Human Physiology, University of Zurich, Switzerland. Disclosure: Dr. Tarnutzer has nothing to disclose. Dr. Palla has nothing to disclose. Dr. Marti has nothing to disclose. Dr. Schuknecht has nothing to disclose. Dr. Straumann has nothing to disclose.

Vertical pendular nystagmus and hypertrophic inferior olivary nuclei degeneration: an “odd couple”

A 56-year-old man had a hypertensive pontine hemorrhage (Fig. 1a), which resulted in bilateral internuclear ophthalmoplegia, pseudobulbar palsy, and spastic ataxic tetraparesis. Three months after a stroke, while neurological deficits were recovering, the patient manifested progressively blurred vision and oscillopsia, corresponding to a vertical conjugate pendular nystagmus (PN) (video). Electronystagmography showed a 3-Hz frequency and 2–3 amplitude sinusoidal curve, with upand down-phases symmetric for direction and velocity, without null zones and torsional or gaze-evoked components. PN was not modified by eye covering, saccades, head thrust, 20 diopter prisms, optokinetic maneuvers, and sleep. Brain MRI (Fig. 1b, c) showed an hemosiderin-and ferritin-lined cleft confined to the dorsal pontine tegmentum and the central tegmental tract. MR-T2-WI images showed a symmetric enlargement of the inferior olivary nuclei with high signal intensity (Fig. 1c, d), which is the typical appearance of the hypertrophic inferior olivary nuclei degeneration (HIOND). PN did not improve with baclofene (up to 60 mg/day), pregabalin (up to 600 mg/day), memantine (up to 40 mg/ day), clonazepam (up to 3 mg/day), lamotrigine (50 mg/ day) worsened the condition. PN remained unchanged at 1 year of follow-up. The radiological hallmarks of the HIOND are the symmetric olivary enlargement with high T2 signal intensity (Fig. 1d), and the presence of distant lesions in specific locations: contralateral cerebellar dentate nucleus, contralateral superior cerebellar peduncle, ipsilateral dorsomedial red nucleus, and ipsilateral pontine tegmentum [1]. The HIOND, as demonstrated in pathological studies since the beginning of the 20th century [2], is a unique form of neuronal degeneration associated with enlargement, rather than atrophy. Olivary nuclei ‘‘hypertrophy’’ is due to the combination of astrocytosis, gemistocytes, and neuronal vacuolar cytoplasmic enlargement [2], due to abnormal soma-somatic gap junctions, hypertrophic thick neuritis, and demyelination [3]. As the association with specific remote lesions is constant, the HIOND is considered the effect (through transneuronal or transsynaptic degeneration) of the damage of the dentatorubral tract (connecting the dentate nucleus with the controlateral red nucleus) and the central tegmental tract (connecting the red nucleus to the ipsilateral inferior olive). The ensemble of these nuclei and tracts is known as the dentatorubral–olivary pathway or ‘‘Guillain-Mollaret triangle’’ (GMT). A recent study with diffusion tensor imaging (DTI) demonstrated signal changes in all anatomical components of the GMT in patients with HIOND at different stages [3], even when standard MRI is negative. In particular, PN has been related to the damage of the paramedian cerebellar tract projections to the pontine tegmentum and to the consequent denervation of the dorsal cap of the inferior olive. Tegmental pontine lesions, in the case of bilateral PN and Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6170-2) contains supplementary material, which is available to authorized users.

Hypertrophic Olivary Degeneration Following Pontine Cavernoma Hemorrhage

Introduction The triangular neuronal circuit between the red nucleus, the ipsilateral inferior olivary nucleus and the contralateral dentate nucleus as part of the extrapyramidal motor system was first described by Guillain & Mollaret in 1931 [1]. It consists of fibers running in the central tegmental tract from the red nucleus to the ipsilateral inferior olivary nucleus, from here to the contralateral dentate nucleus through the inferior cerebellar peduncle and from there via the dentatorubral tract running in the superior cerebellar peduncle back to the ipsilateral red nucleus (Figure 1). This neuronal circuit acts as an inhibitory system on cortical generated impulses by comparing them with their performance in the peripheral motor effector organs. Lesions including parts of the Guillain-Mollaret triangle may result in a rare, but characteristic hypertrophic degeneration of the inferior olivary nucleus [2].

An fMRI study of the motor system in patients with neuropsychiatric systemic lupus erythematosus

Functional cortical changes have been demonstrated in patients with several neurological conditions, including stroke, tumors and MS. The correlation found between the extent of fMRI activations and the extent and severity of brain structural damage suggests an adaptive role of these functional changes. In this study, we assess, using fMRI, the brain pattern of movement-associated cortical activations in neuropsychiatric systemic lupus erythematosus (NPSLE) patients and investigate whether the extent of cortical reorganization is associated with the extent of brain pathology, measured on dual-echo and diffusion tensor (DT) MR images. From 14 right-handed NPSLE patients and 14 matched controls, we obtained: (a) fMRI during the performance of repetitive flexion–extension of the last four fingers of the right hand; (b) dual-echo and (c) pulsed-gradient spin-echo echo-planar sequence to calculate DT MRI maps of the normal-appearing white (NAWM) and gray (NAGM) matter. Brain T2-visible abnormalities were detected in 11 NPSLE patients. Compared with controls, NPSLE patients had significantly higher NAWM fractional anisotropy histogram peak height ( P = 0.005), and more significant activations of the contralateral primary sensorimotor cortex, putamen and dentate nucleus. They also had more significant activations of several regions located in the frontal and parietal lobes as well as of MT/V5 and the middle occipital gyrus, bilaterally. Strong correlations (r values ranging from 0.79 to 0.87) were found between relative activations of sensorimotor areas and the extent and severity of brain damage. Movement-associated functional cortical changes do occur in patients with NPSLE and might contribute to the maintenance of their normal functional capacities.

Palatal myoclonus in a patient with a lateral thalamic infarction

Palatal myoclonus (PM) is characterized by rhythmic involuntary jerking movement of the soft palate and the pharyngopalatine arch, often involving the diaphragm and laryngeal muscles.1 The two distinct clinical entities, symptomatic PM and essential PM, arise from different pathophysiologic mechanisms.2 Symptomatic PM is usually associated with lesions located in the myoclonic triangle (the Guillain–Mollaret triangle). It consists of the red nucleus, inferior olive, contralateral cerebellar dentate nucleus, and the connecting pathways, namely the central tegmental tract, the inferior cerebellar peduncle, and superior cerebellar peduncle.3 Symptomatic PM may be isolated or more rarely associated with movements of the extremities such as tremor, choreoathetosis, and myoclonus.4,5 A 64-year-old man was referred for acute onset of motor impairment of the right arm. On admission neurologic examination revealed clumsiness of the right arm and right dysmetria on finger-to-nose test. On the fifth day the patient developed myoclonic movements …