Pontine Lesions Research Articles

DIPG-48. PRECISION GUIDED THERAPY PROVIDES CLINICAL BENEFIT IN H3K27-ALTERED DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND The utility of precision-guided therapeutic approaches to H3K27-altered diffused midline glioma (DMG) remains uncertain. The Australian Zero Childhood Cancer (ZERO) program combines molecular profiling (whole-genome sequencing (WGS), whole-transcriptome sequencing (RNAseq), and DNA methylation profiling), with in vitro high-throughput drug screening (HTS) and patient-derived xenograft (PDX) drug-efficacy testing in patients with high-risk cancer. METHODS We report on the cohort of patients enrolled with a DMG in the ZERO clinical trial between 2017 and 2023. RESULTS 68 patients were enrolled, predominantly at diagnosis (87%), with pontine lesions (66%) at a mean age of 8.7 years. 59 (87%) patients had WGS + RNAseq successfully performed. Most tumors harbored an H3F3A mutation (n=50), followed by HIST1H3B (n=11), HIST1H3C (n=2), HIST2H3C (n=1) and EZHIP overexpression (n=4). 37 samples were suitable for cell culture, with HTS successfully performed in 25 cases, and PDXs established in 7. Precision-guided therapy (PGT) was recommended by the ZERO multidisciplinary tumor board for 53 patients (78%), including 5 recommendations guided by HTS. PI3K/mTOR inhibitors and MEK inhibitors were the most recommended PGTs. 21 patients (31%), receiving 24 PGTs, were eligible for survival analysis. The clinical benefit rate (per RAPNO) was 52% for patients receiving PGT, with 5 patients exhibiting PR and 6 patients SD >6 months. Notably, the 5 PR included: a PR in a patient with BRAFV600E mutation to dabrafenib/trametinib, a near-CR in a patient with germline BRCA2 mutation to olaparib/durvalumab, a sustained PR in a patient with FGFR1 mutation to trametinib/bevacizumab and 2 patients with PIK3CA mutations who received PGT in the context of recent radiotherapy. Median overall survival of the PGT group was 21.2 months versus 11.8 months for the rest of the cohort (hazard ratio 0.67 [95%CI 0.39-1.1]). CONCLUSIONS These results, for the first time, highlight the potential clinical benefit of PGT in H3K27-altered DMG.

Expanding the reach of the trans-middle cerebellar peduncle approach: pontine cavernous malformations, tissue transgression beyond the safe entry zone, and the invisible triangle.

In the authors' microsurgical experience, the trans-middle cerebellar peduncle (MCP) approach to the lateral and central pons has been the most common approach to brainstem cavernous malformations (BSCMs). This approach through a well-tolerated safe entry zone (SEZ) allows a wide vertical or posterior trajectory, reaching pontine lesions extending into the midbrain, medulla, and pontine tegmentum. Better understanding of the relationships among lesion location, surgical trajectory, and long-term clinical outcomes could determine areas of safe passage. A single-surgeon cohort study of all primary trans-MCP BSCM resections was conducted from July 1, 2017, to June 30, 2021. Preoperative and postoperative MR images were independently reviewed by 3 investigators blinded to the intervention, using a standardized rubric to define BSCM regions of interest (ROIs) involved with a lesion or microsurgical tract. Statistical testing, including the chi-square test with the Bonferroni correction, logistic regression, and structural equation modeling, was performed to analyze relationships between ROIs and clinical outcomes. Thirty-one patients underwent primary trans-MCP BSCM resection during the study period. The median age was 50 years (IQR 24-49 years); 19 (61%) patients were female, and 12 (39%) were male. Seven (23%) patients had familial cavernous malformation syndromes. The median follow-up was 9 months (range 6-37 months). At the last follow-up, composite neurological outcomes were favorable: 22 (71%) patients had 0 (n = 12, 39%) or 1 (n = 10, 32%) major persistent deficit, 5 patients (16%) had 2 deficits, 2 (7%) had 3 deficits, and 1 patient each (3%) had 4 or 6 deficits. Unfavorable composite outcomes were significantly associated with lesions (OR 7.14, p = 0.04) or surgical tracts (OR 12.18, p < 0.001) extending from the superior cerebellar peduncle (SCP) into the contralateral medial midbrain. The ipsilateral dorsal pons was the most frequently implicated ROI involving a surgical tract and the development of new postoperative deficits. This region involved the rhomboid pontine territory and transgression of the pontine tegmentum (OR 7.53, p < 0.001). Structural equation modeling supported medial midbrain and pontine tegmentum transgression as the primary drivers of morbidity. Trans-MCP resection is a safe and effective treatment for BSCMs, including lesions with marked superior or inferior ipsilateral extension. Two trajectories are associated with increased neurological risk: first, a superomedial trajectory to lesions extending into the midbrain that transgresses the SCP, its decussation, or both; and second, a posteromedial trajectory to lesions extending into the pontine tegmentum. The corticospinal tract, SCP, and pontine tegmentum form an invisible triangle within the pontine white matter tolerant of transgression. When the surgeon works within this triangle, most deep pontine BSCMs, including large lesions, those with contralateral or posterior extension, and others extending into the midbrain and medulla, can be resected safely with the trans-MCP approach.

Medium-Term Effect of Pedunculopontine Nucleus Neurotoxic Lesion on Motor Function and Gene Expression of Protein Related to Dopaminergic Homeostasis in Rat

The hypothesis that early degeneration of the pedunculopontine nucleus (PPN) may be related to nigral degeneration has opened new avenues of basic research for this disease. It is not known how the motor function and nigrostriatal gene expression of TH, VMAT2 and DAT behave in an intermediate term (30 days) following the pontine lesion.

An isolated pontine infarct extending to the basal pontine surface has a higher abnormal ankle-brachial index

Patients with ischemic stroke and branch atheromatous disease (BAD) have worse neurological deficits and prognoses than those with small vessel occlusion (SVO). However, both disorders are forms of deep brain infarctions. This study aimed to investigate an MRI-based etiological classification for isolated pontine infarctions and assess differences in vascular risk factors and peripheral arterial disease among etiological subtypes. Consecutive data of patients admitted for acute ischemic stroke or transient ischemic attack between August 2016 and July 2019 were reviewed. Acute isolated pontine infarcts were classified into 3 groups: BAD, SVO, and large-artery atherosclerosis (LAA), according to basilar or vertebral artery steno-occlusion and the extent of the infarct lesion on the basal pontine surface as displayed on magnetic resonance imaging and angiography. Vascular risk factors, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity were analyzed in the 3 groups. Among 64 enrolled patients, BAD was the most common cause of isolated pontine infarct. The BAD group had a higher frequency of abnormal ABI and hypertension than the SVO group. The BAD group had abnormal ABI and hyperlipidemia more frequently than the LAA group. No significant difference was found in diabetes or brachial-ankle pulse wave velocity incidence between the BAD and SVO groups. ABI and vascular risk factors in the BAD group were more similar to those in the LAA group than to those in the SVD group. This finding suggests that pontine lesions extending to the basal pontine surface have an atherosclerotic mechanism in BAD, requiring potent antiplatelet therapy for the secondary prevention of ischemic stroke.

Radiofrequency thermocoagulation for the treatment of trigeminal neuralgia associated with a focal pontine lesion: illustrative case.

Trigeminal neuralgia (TN) associated with a focal pontine lesion is a rare but challenging condition. The origin of the lesion, which does not fulfill the diagnostic criteria for multiple sclerosis, remains disputable. Pain in such conditions is often refractory to treatment, including microvascular decompression. A 36-year-old female presented with a 3.5-year history of shooting pain in the right V2 distribution triggered by talking and chewing. She became less responsive to high-dose carbamazepine over time. Magnetic resonance imaging (MRI) revealed no neurovascular compression but an elongated lesion hyperintense on T2-weighted imaging and T2- fluid-attenuated inversion recovery and hypointense and nonenhancing on T1-magnetization prepared rapid gradient-echo imaging without restricted diffusion, hemorrhage, or supposed malformation along the right pontine trigeminal pathway (PTP). Two other similar lesions were found in the corpus callosum and left thalamus. All lesions were stable compared to MRI data obtained 2 years before. Cerebrospinal fluid contained no oligoclonal bands. Pain attacks ceased with right-sided gasserian radiofrequency thermocoagulation (RFTC), and at the 6-month follow-up, there was no recurrence. In patients with TN, preoperative neuroimaging should assess for brainstem lesions along the PTP. RFTC can be considered a treatment option in medication-refractory TN associated with a focal pontine lesion.

"Uncrossed Central Facial Paralysis" Caused by Pontine Infarction: A Case Report.

We report a patient with extraordinary pontine infarction-induced contralateral central facial palsy and weakened limb strength. This is a 66-year-old man with left arm movement difficulty for 10 days and worsening over the last 1 day. His left nasolabial fold flattening and left arm strength and sensory were decreased. He could not complete the finger-nose test well with his right hand. Magnetic resonance and magnetic resonance angiography tests confirmed his right pontine acute infarction but without large vessel stenosis or occlusion. "Uncrossed paralysis" patients may present with contralateral face and body weakness with pontine infarcts, if the infarct occurs above the level of the facial nucleus head, and may be simmilar with the higher level pontine lesions or cerebrum semisphere infarction, which need particular attention during clinical practice.

Approaches to the Middle Cerebellar Peduncle for Resection of Pontine Cavernomas.

The expanded retrosigmoid approach with splitting of the horizontal cerebellar fissure provides a more direct and shorter route for central and dorsolateral pontine lesions while minimizing retraction of tracts, nuclei, and cerebellum. 1-4. The middle cerebellar peduncle is partially covered by the petrosal surface of the cerebellum. The horizontal cerebellar fissure (petrosal fissure) divides the petrosal surface of the cerebellar hemisphere into superior and inferior parts. Splitting the petrosal fissure separates the superior and inferior petrosal surfaces and exposes the posterolateral middle cerebellar peduncle (posterior and lateral to the root entry zone of CN5). 1-4. Expanded retrosigmoid craniotomy is performed, including unroofing of the sigmoid sinus; petrosal fissure is split to expose the posterolateral middle cerebellar peduncle; entry point for resection of the cavernoma is identified; nims stimulator stimulator is used to confirm the absence of tracts and nuclei; myelotomy is performed; and cavernoma and its draining vein (but not the developmental venous anomaly) are removed using a combination of traction and countertraction against gliotic plane. Wide splitting of the horizontal cerebellar fissure minimizes retraction or resection of the cerebellum and offers the best angle of attack. Knowledge of brainstem anatomy and use of intraoperative navigation are critical to avoid complications. Far lateral through the middle cerebellar peduncle is a variant that can be used to resect pontine cavernomas if a caudocranial trajectory is preferred.The patient consented to the procedure and to the publication of her image.

Bickerstaff’s brainstem encephalitis: a rare case of neurologic complication in Ulcerative Colitis

Bickerstaff’s brainstem encephalitis is a rare autoimmune disorder that presents with ataxia, ophthalmoplegia, disturbance of consciousness and quadriplegia. A 45-year-old man with a history of ulcerative colitis (UC) taking mesalazine (5-aminosalicylic acid) visited the emergency room presenting with ataxia, ophthalmoplegia and a progressively worsening cognitive impairment. Cerebrospinal fluid analysis showed mild elevation in protein and white blood cell count and increased intracranial pressure. Anti-GQ1b autoantibodies were found positive in the patient’s serum and contrast-enhanced brain magnetic resonance imaging showed diffuse leptomeningeal enhancement and pontine lesions. Based on these findings and the patient’s clinical course and history, he was diagnosed with Bickerstaff’s brainstem encephalitis. Mesalazine was discontinued and high-dose steroid pulse therapy was started, followed by intravenous immunoglobulin, which resulted in gradual improvement of the neurologic symptoms. When an ulcerative colitis patient presents with progressive cognitive impairment, quadriplegia and disturbance of consciousness and gait, Bickerstaff brainstem encephalitis should be considered in the differential diagnosis and prompt immunotherapy may lead to favorable prognosis.

The Infratrigeminal Suprafloccular Approach to Intrapontine Lesions: An Anatomical Overview and Relevance for the Approach to Intrapontine Lesions.

Background and objectives Brainstem lesions have long been considered complex pathologies that may lead to permanent deficits or life-threatening complications, posing significant challenges for surgical removal. Among these lesions, intrapontine lesions are particularly challenging in the field of neurosurgery. However, with advancements in microsurgical anatomy knowledge and technology, these lesions have become more amenable to surgical treatment. In this study, the authors examine an infratrigeminal suprafloccular approach, which has been shown to be a safe surgical route, resulting in fewer postoperative complications, while evaluating the anatomical nuances of the approach and route. Methods Twenty cadaveric brainstem specimens were analyzed to assess the anatomy, focusing on the lateral aspect of the pons as a potential safe entry zone for intrapontine lesions. The authors consistently analyzed twenty brainstem specimens, carefully examining the pontine microsurgical anatomy. A triangular area of entrance was measured, with three sides or walls (X, Y, and Z) aiming to identify the safe zone that would spare the distinct pontine nuclei, ascending sensory pathways, corticospinal, corticonuclear, and corticopontine tracts of the brainstem. An illustrative case was adapted to the described safe entry zone for corroboration purposes. Results The authors measured three distinct lines on the lateral surface of the pons, named X, Y, and Z, forming a triangle in shape. Line X extended from the midpoint anteroposteriorly of the flocculus of the cerebellum to the apparent trigeminal exit in the lateral aspect of the pons. Line Y ran from the trigeminal exit in the pons to the apparent exit of the facial-vestibulocochlear complex in the far lateral aspect of the pontomedullary sulcus in the cerebellopontine fissure. Line Z represented the measurement from the vestibulocochlear complex to the midpoint anteroposteriorly of the flocculus of the cerebellum. The mean measurements were as follows: X = 14.41mm (range: 10mm to 20mm), Y = 13.1mm (range: 10mm to 21mm), and Z = 3mm (range: 2mm to 5mm). The mean surface area of the analyzed specimens within the triangle (formed by X, Y, and Z) was 20.1mm² (range: 10mm² to 40mm²). This area was identified as a safe zone for the entry of microsurgical approaches to intrapontine lesions, involving less retraction of the anterior pons and potentially sparing critical structures, such as the corticospinal tracts, pontine perforating arteries, tegmentum pontis, cranial nerve nuclei, substantia reticulata dorsally, and transverse pontine fibers. Microsurgical anatomical findings, combined with intraoperative monitoring in an illustrative case, consistently demonstrated that this entry area predicted less functional instability of the analyzed tracts and resulted in fewer postoperative complications. Conclusion Deep-seated pontine lesions present a complex range of pathologies with a high potential for devastating outcomes, particularly those involving hemorrhage. This study identifies and describes a presumed safe entry zone that allows for the creation of a surgical corridor for biopsy or microsurgical resection of these lesions, reducing morbidity in a previously considered impenetrable region.

Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia Secondary to Stroke: A Systematic Review and Clinical Case Presentation

Trigeminal neuralgia (TN) is a paroxysmal, unilateral, brief, shock-like pain in ≥1 divisions of the trigeminal nerve. It can result from multiple causes; however, TN secondary to stroke is very rare. We present the case of TN secondary to pontine infarction treated with incremental doses of neuropathic pain medication for >5 years before conservative management failed. He was then treated with stereotactic radiosurgery (SRS). Additionally, we conducted a systematic review using standard PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines for all the cases of TN with brainstem stroke from 1976 to2022. Our patient was an 82-year-old man. Magnetic resonance imaging demonstrated a pontine lesion consistent with stroke. The Barrow Neurological Institute (BNI) score at presentation was 5. He received a marginal dose of 60 Gy to the 80% isodose line in a single fraction to a volume of 0.05 cm3. The immediate post-treatment BNI score was 0 and remained at 0 for 3 months, when he experienced recurrence. The recurrence was treated with oxcarbazepine. His pain remained well controlled with a lower dose of oxcarbazepine, and he had no adverse effects at 1 year of follow-up with a BNI score of 3. The systemic review identified 21 case reports with a combined cohort of 25 patients with TN secondary to stroke. Only 3 patients were treated with SRS, 2 of whom reported symptom improvement at 6 months and 8 months of follow-up with no adverse events. Our case and literature review demonstrate durable and effective treatment with SRS, which can be considered a safe and effective treatment option for patients with stroke-associated TN.

Peritrigeminal Safe Entry Zone Access to Anterolateral Pons Using the Presigmoid Retrolabyrinthine Suprameatal Approach: A Cadaveric Morphometric Study.

Access to the anterolateral pontine lesions can be achieved through the peritrigeminal and supratrigeminal safe entry zones using Kawase, retrosigmoid, or translabyrinthine approaches. However, these approaches entail shallow extensive dissection, tangential access, and compromise vestibulocochlear function. We aimed to investigate infratentorial presigmoid retrolabyrinthine approach to access pontine lesions through the peritrigeminal zone. We performed 10 presigmoid retrolabyrinthine suprameatal approach dissections in 5 cadaveric heads. Anatomic-radiological characteristics and variations were evaluated. Six morphometric parameters were measured and analyzed to predict surgical accessibility. The pontine infratrigeminal area was accessible in all patients. The mean exposed area of the anterolateral pontine surface was 98.95 cm 2 (±38.11 cm 2 ). The mean length of the exposed trigeminal nerve was 7.9 cm (±2.9 cm). Preoperative anatomic-radiological parameters may allow to select patients with favorable anatomy that offers appropriate surgical accessibility to the anterior pontine cavernoma through a presigmoid retrolabyrinthine corridor. Anterolateral pontine lesions can be accessed through a minimally invasive infratentorial presigmoid retrolabyrinthine approach by targeting the infratrigeminal safe entry zone. Further clinical studies should be conducted to evaluate the viability of this technique for treating these complex pathologies in real clinical settings.

Unilateral Pendular Nystagmus in Multiple Sclerosis: A Case Series.

Acquired pendular nystagmus is most often seen in patients with demyelinating disease. Although it is often bilateral, rare cases may be monocular. There is paucity of data on the spectrum of clinical presentation, underlying mechanism, and response to treatment in patients with monocular pendular nystagmus. Retrospective case series of patients with monocular pendular nystagmus seen in 2 tertiary neuro-ophthalmology clinics between January 2019 and June 2022. All patients underwent a complete neuro-ophthalmological assessment and MRI. We describe 5 patients (3 women) aged 31-49 with monocular pendular nystagmus. All had a diagnosis of multiple sclerosis. Three patients had horizontal and 2 had vertical pendular nystagmus. The Snellen visual acuity in the eye with pendular nystagmus varied from 20/20 to 20/200. Two patients were asymptomatic and 3 suffered visually debilitating oscillopsia. Treatment response was available for 2 patients, both of which responded well to treatment with memantine. The pendular nystagmus was observed in the eye with worse visual acuity in 4 of 5 cases (80%). Three patients had bilateral pontine lesions, and 2 had unilateral pontine lesion ipsilateral to the side of nystagmus. Monocular pendular nystagmus in adults is seen most often in patients with multiple sclerosis. Asymmetry in brainstem lesions and afferent visual input may be the culprit. Treatment with memantine may result in significant improvement in symptomatic patients.

Demographic, Medical, and Clinical Characteristics of a Population-Based Sample of Patients With Long-lasting Locked-In Syndrome.

Patients with classic locked-in syndrome (LIS), typically caused by ventral pontine stroke, present with quadriplegia, mutism, intact consciousness, and communication skills limited to vertical gazing and/or blinking. Clinical presentations and definitions of LIS differ, especially regarding incomplete LIS. In our study, we explored the functional diversity of LIS, its outcomes, and the complexity of its course along with variations in the location of lesions and their potential significance for outcomes. A national cohort of patients with vascular LIS who remained in the LIS state for at least 6 weeks according to a functional definition of LIS was studied. Demographic, medical, and follow-up data, collected between 2012 and 2022, were obtained from the quality register of the Norwegian National Unit for Rehabilitation of Locked-In Syndrome. Outcomes in verbal communication, motor function, and dependency were evaluated according to criteria for being in or not in the LIS state. The modified Rankin scale and LIS motor recovery scale were applied. Descriptive analysis was performed. The relationship between lesion location and functional outcome was investigated. The sample included 51 patients (median age: 55.7 years, 36 male individuals), 43 of whom had follow-up data. Ischemic stroke was the most common etiology (n = 35). Twenty-three patients had emerged from the LIS state, mostly within 2 years after onset. All but 1 patient achieved some motor improvement, whereas only 3 achieved full motor recovery, and 88% had a persistently high level of dependence. The 3-year survival rate was 87%. Five patients had an isolated pontine lesion, whereas 80% showed various lesions outside the brain stem. Patients who emerged from the LIS state had a significantly lower prevalence of lesions outside the brain stem than patients who remained in the LIS state did. Investigating an unselected population-based sample of patients with vascular LIS offers important insights into the functional diversity of LIS. Although most patients remained severely disabled, even small improvements in function can substantially increase the potential for activity and participation. Additional lesions outside the brain stem seem to be common in long-lasting LIS and might be prognostic for remaining in the LIS state.

How I do it: intradural anterior petrosectomy.

The anterior transpetrosal approach (ATPA) is a cranial base approach for addressing upper petroclival or lateral pontine lesions. It is fundamentally an epidural procedure involving the drilling of the petrous apex. However, this approach has significant procedure-related morbidity, and the surgeon must perform a complete petrosectomy, as the intradural structures are not in view during the drilling. For selected cases, a rationale exists for choosing a tailor-made intradural anterior petrosectomy (IAP). This article describes the relevant surgical anatomy and the different surgical steps of the IAP. IAP represents a feasible alternative to the standard ATPA with the advantage of minimizing the extent of petrous bone removal to the individual need.

A case study of left visual neglect after right pontine lesion: pathophysiological evidence for the infratentorial involvement in human visual attention.

Hemispatial neglect, the inability to attend to the contralesional side of space, is the most common disturbance of visuospatial attention. Both hemispatial neglect and visuospatial attention are typically associated with extended cortical networks. Nevertheless, recent accounts challenge this so-called corticocentric view and postulate the participation of structures well beyond the telencephalic cortex, in particular advocating the role of the brainstem. However, to the best of our knowledge, hemispatial neglect after a brainstem lesion has not yet been described. We describe, for the first time in a human, the occurrence and remission of contralesional visual hemispatial neglect after a focal lesion in the right pons. Hemispatial neglect was assessed by means of video-oculography during free visual exploration, a very sensitive and established method, and its remission was followed up until 3 wk after stroke. Moreover, by means of a lesion-deficit approach complemented by imaging, we identify a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons. Our findings offer, for the first time in a human, causal, lesion-based support for recent seminal accounts postulating the role of infratentorial structures participating in the activity of cerebral cortical attentional networks mediating attentional processes.NEW & NOTEWORTHY Visuospatial attention and its most common disturbance, hemispatial neglect, are typically associated with extended cortical networks. However, recent accounts challenge this corticocentric view and advocate the role of infratentorial structures. We describe, for the first time in a human, the occurrence of contralesional visual hemispatial neglect after a focal lesion in the right pons. We provide causal, lesion-based evidence for a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons.

DIPG-like MYB-altered diffuse astrocytoma with durable response to intensive chemotherapy.

Pontine gliomas represent difficult to treat entity due to the location and heterogeneous biology varying from indolent low-grade gliomas to aggressive diffuse intrinsic pontine glioma (DIPG). Making the correct tumor diagnosis in the pontine location is thus critical. Here, we report a case study of a 14-month-old patient initially diagnosed as histone H3 wild-type DIPG. Due to the low age of the patient, the MRI appearance of DIPG, and anaplastic astrocytoma histology, intensive chemotherapy based on the HIT-SKK protocol with vinblastine maintenance chemotherapy was administered. Rapid clinical improvement and radiological regression of the tumor were observed with nearly complete remission with durable effect and excellent clinical condition more than 6.5years after diagnosis. Based on this unexpected therapeutic outcome, genome-wide DNA methylation array was employed and the sample was classified into the methylation class "Low-grade glioma, MYB(L1) altered." Additionally, RT-PCR revealed the presence of MYB::QKI fusion. Taken together, the histopathological classification, molecular-genetic and epigenetic features, clinical behavior, and pontine location have led us to reclassify the tumor as a pontine MYB-altered glioma. Our case demonstrates that more intensive chemotherapy can achieve long-term clinical effect in the treatment of MYB-altered pontine gliomas compared to previously used LGG-based regimens or radiotherapy. It also emphasizes the importance of a biopsy and a thorough molecular investigation of pontine lesions.

Dynamic changes of the direction and angle of radiographic ocular lateral deviation in patients with lateropulsion after stroke onset.

To examine if radiographic ocular lateral deviation (rOLD) could be provoked in stroke patients with mild-to-moderate lateropulsion according to vertical perception. In this single-center, retrospective study, acute stroke patients with mild-to-moderate lateropulsion assessed by the Scale for Contraversive Pushing were enrolled. Computed tomography or magnetic resonance imaging was performed on all patients on admission and then according to their conditions. The direction and angle of rOLD were compared among three groups according to the responsible lesion: lateral medullary (LM), pontine (P), and hemispheric (H). Sixty-six patients (male, 47; average age, 67years) were enrolled and divided into the LM (n = 37), P (n = 8), and H (n = 21) groups. All patients had body tilt. Patients in the LM group showed body tilt to the ipsilesional side during hospitalization, while those in the P and H groups tilted to the contralesional side. All patients had rOLD at the final assessment at an average of 13days after onset; patients in the P and H groups showed contralateral rOLD, while those in the LM group showed ipsilateral rOLD if they did not have cerebellar or pontine lesions. Significant decreases in the angle and changes in direction of rOLD according to lesion site were observed during hospitalization. Serial changes in rOLD findings after stroke onset are different according to the responsible lesion. The direction of rOLD in most patients is in accordance with vertical perception after the acute stage of stroke.

A Case of Monkeypox-associated Encephalomyelitis—Colorado, July–August, 2022 (P11-10.002)

<h3>Objective:</h3> Monkeypox virus (MPXV) disease was declared a public health emergency by the World Health Organization on July 23, 2022, making it imperative for neurologists to be aware of the potential neurologic implications of this outbreak. To aid in educating neurologists, we present a case of encephalomyelitis in the setting of confirmed MPXV infection. <h3>Background:</h3> MPXV is an orthopox virus in the Poxviridae family, which also includes variola virus (smallpox) and vaccina virus. Prior to May 2022, MPXV was largely confined to Central and Western Africa apart from occasional travel-related cases. However, rapid spread within primarily LGBTQ social networks has created an unexpected pandemic. Occasional reports of encephalitis have been reported in endemic regions with little detail. However, there have been a few reports worldwide of fatal encephalitis in presumed immunocompetent adults in the current pandemic as well as suspected secondary autoimmune encephalomyelitis as reported here. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A presumed immunocompetent, healthy, gay man in his 30s developed a febrile illness with a diffuse, itchy, vesiculopapular rash followed by progressive left upper and lower extremity weakness/numbness, urinary retention, headache, and intermittent priapism. CSF demonstrated a lymphocytic pleocytosis with elevated protein. Serum HIV antibody and nucleic acid tests were negative. Serum anti-MOG and AQP-4 antibody tests were negative. MRI brain showed multifocal T2/FLAIR subcortical, caudate, thalamic, splenium, and pontine lesions (some of which were partially enhancing). MRI spine showed a longitudinally-extensive, partially enhancing central cord T2 lesion from the cervical cord to conus. MPXV nucleic acid was confirmed from skin lesions but was not present in CSF. His symptoms gradually improved with oral tecovirimat and immunotherapy for suspected para-infectious autoimmune encephalomyelitis. <h3>Conclusions:</h3> MPXV can cause central nervous system disease, whether by direct viral invasion or a para-infectious autoimmune process. With prompt recognition and appropriate treatment, recovery can be achieved. <b>Disclosure:</b> Dr. Money has nothing to disclose. Dr. Hannan has nothing to disclose. Dr. Kleiner has nothing to disclose. Dr. Yuen has nothing to disclose. Mrs. Ferriman has nothing to disclose. Dr. Matthews has nothing to disclose. The institution of Dr. Beckham has received research support from Roche Diagnostics. The institution of Dr. Chauhan has received research support from NIH. The institution of an immediate family member of Dr. Chauhan has received research support from University of Colorado. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. The institution of Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Piquet has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Tyler has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Protagonist Therapeutics, Newark CA. Dr. Tyler has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Neurological Association/Wiley. Dr. Tyler has received intellectual property interests from a discovery or technology relating to health care. Dr. Tyler has received publishing royalties from a publication relating to health care. Dr. Tyler has a non-compensated relationship as a Director (ex officio) with American Neurological association that is relevant to AAN interests or activities. Dr. Tyler has a non-compensated relationship as a Director with International Society for Neurovirology that is relevant to AAN interests or activities. Dr. Pastula has nothing to disclose.

Cryoglobulinemia and Neuromyelitis optica: a case of progressive weakness and neurocognitive decline (P10-5.026)

<h3>Objective:</h3> Describe a case of a woman with mixed cryoglobulinemia who presented with progressive weakness and biopsy proven systemic vasculitis in the setting of Hepatitis C virus (HCV) negative serology. <h3>Background:</h3> The disease expression of mixed cryoglobulinemia vasculitis caused by HCV infection triggers the downstream B-cell arm of autoimmunity. <h3>Design/Methods:</h3> A 61 year old woman with a history of HCV infection, mixed cryoglobulinemia, mononeuritis multiplex secondary to nervous system vasculitis affecting peripheral nerves and hypertension presented with weakness that progressed to quadriparesis and neurocognitive decline over a period of eight months. <h3>Results:</h3> MRI examination of the brain showed bilateral ventral pontine lesions extending into the middle cerebellar peduncles, ventrolateral midbrain and cerebral peduncles as well as bilateral cortical frontal lobe lesions. Also present were intrinsic mixed intensity DWI/ADC lesions of undetermined etiology and extensive subcortical and periventricular white matter hyperintensities. CT angiography of her head and neck showed large vessel intracranial vasculopathy involving the bilateral MCA branches. Conventional angiogram, however, did not show any evidence of angiographic vasculitis. MRI spectroscopy was non-diagnostic. MRI of the neuroaxis showed a small focus of linear non-enhancing hyperintense lesion at the level of C3. EMG demonstrated severe generalized sensory-motor polyneuropathy with severe axonal loss. EEG showed mild to moderate diffuse slowing. CSF evaluation was negative, HCV viral load was undetectable, connective tissue markers (Anti-dsDNA, Anti-SCL70, Anti-CENTR, Anti-RNP, Anti-Smith, Anti-SSA/SSB, ANCA) were negative and the remaining serology was significant for elevated ESR, CRP, low C4 complements, positive anti-AQP4 antibodies titers (1:2560) and positive myelin basic protein. Brain biopsy showed perivascular lymphocytic inflammation, confirming vasculitis. Our patient completed courses of high dose steroids, IVIG and Rituximab with mild improvement in motor strength. <h3>Conclusions:</h3> Although an atypical feature of NMO, cryoglobulinemia with production of anti-AQP4 antibodies may, in part, contribute to development of a demyelinating process. <b>Disclosure:</b> Dr. Esechie has nothing to disclose. Dr. Harazeen has nothing to disclose. Dr. Rivera Vega has nothing to disclose. Dr. Thottempudi has nothing to disclose. Dr. Chhabra has stock in Pfizer. Dr. Chhabra has stock in Biogen. Dr. Chhabra has stock in Johnson and Johnson. Dr. Chhabra has stock in Medtronic. Dr. Shaltoni has nothing to disclose. Muhammad Zeeshan Memon, MD has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Wu has nothing to disclose.

Cavernous Malformations: What They Have Taught Us.

Cavernous Malformations: What They Have Taught Us.