Diencephalic syndrome-like presentation of brainstem tumor: a series case-based review.

PURPOSE: Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature. METHODS: A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis. RESULTS: In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9 months (median: 16 months; range: 1.5-72 months), whereas in our series of cases, the time was 32.5 months (median: 33 months; range: 7-57 months). CONCLUSION: Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause.

Glioblastoma multiforme with oculomotor nerve involvement: case report and literature review.

Gliomas involving the cranial nerves III-XIII are rare. Even rarer are glioblastomas multiforme (GBMs) with only 10 cases previously reported. Oculomotor nerve involvement was described in only 2 patients. The mechanisms proposed so far include an origin from the nerve itself or an extension within the nerve of a midbrain tumor. We report the case of a 69-year-old man who presented with an isolated left oculomotor nerve palsy. He was found to have a left temporal GBM extended to the frontal lobe. Diagnostics and intraoperative and pathological findings clearly demonstrated a massive infiltration of the cisternal portion of the left oculomotor nerve. We suppose this could be the first case of direct oculomotor nerve invasion by exophytic spread of a supratentorial GBM or by subarachnoid seeding from a temporal tumor. Less probably, it could be the first case of an oculomotor nerve GBM with a temporal lobe invasion.

Trigeminal trophic syndrome in a pediatric patient with diffuse intrinsic pontine glioma.

A 13-year-old girl with a history of diffuse intrinsic pontine glioma (DIPG) suffered from progressively worsening facial ulcerations secondary to paresthesia-induced self-excoriation. She was diagnosed with trigeminal trophic syndrome (TTS) induced by DIPG and struggled to heal her lesions in the background of this excoriation disorder. A multidisciplinary approach that included mood disorder management with sertraline and amitriptyline helped diminish paresthesia, improve her quality of life, and promote healing of the ulcers despite the progression of her DIPG. This case highlights the multifactorial complexity of TTS in pediatric patients and the need for successful management strategies.

Brainstem tumors may increase the impairment of behavioral emotional cognition in children.

PURPOSE: It remains unclear as to whether patients with brainstem tumor experience complex neuropsychiatric problems. In this cohort study, we specifically investigated behavioral, emotional and cognitive symptoms in pediatric patients with brainstem glioma and healthy individuals. METHODS: A total of 146 patients with pediatric brainstem tumors (aged 4-18 years old) and 46 age-matched healthy children were recruited to assess their behaviors and emotions examined by the Child Behavior Checklist. A variety of clinical factors were also analyzed. RESULTS: There were significant differences in most behavioral and emotional symptoms between pediatric patients and healthy subjects. Moreover, patients with pons tumors exhibited significantly higher scores than patients with medulla oblongata tumors (p = 0.012), particularly in concerning the syndrome categories of Withdrawn (p = 0.043), Anxious/depressed symptoms (p = 0.046), Thought Problems (p = 0.004), Attention deficits (p = 0.008), Externalizing problems (p = 0.013), and Aggressive behavior (p = 0.004). A tumor body located in the pontine (p = 0.01, OR = 4.5, 95% CI = 1.4-14.059) or DIPG in the midbrain (p = 0.002, OR = 3.818, 95% CI = 1.629-8.948) appears to act as a risk factor that is associated with more problems in patients with neuropsychiatric symptoms. CONCLUSIONS: Pediatric patients with brainstem tumors exhibit severe behavioral and emotional problems. Tumor invades the pontine and midbrain act a risk factor with more problems. It suggests that structural and functional abnormalities in the brainstem will cause prolonged behavioral problems and emotional-cognitive dysfunctions in young children.

3-Dimensional Exoscope for Far Lateral Approach to Pontomedullary Cavernous Malformation.

Brainstem cavernous malformations account for 15%-18% of all central nervous system cavernomas and are histologically characterized by thin-walled, low-pressure capillaries, classically without intervening brain tissue.1,2 Cavernomas may be sporadic, typically characterized by a single lesion, or inherited. The inherited form is most often autosomal dominant with incomplete penetrance and variable expression. Multiple cavernomas are associated with the familial form; although this is not always the case, genetic workup should be pursued.3,4 Clinical presentation typically includes focal neurologic deficit related to hemorrhage location, seizures, and rarely obstructive hydrocephalus.1,2 Indications for surgical management include severe or progressive neurologic dysfunction, lesion size ≥2 cm, recurring hemorrhages, and/or significant mass effect.5 Microsurgical resection of a cavernoma is associated with an overall 28% complication rate and perioperative neurologic morbidity upwards of 45% according to some series. Long-term surgical outcomes at 12 months are more reassuring: 84% reported their condition to have improved or remained the same, and the long-term morbidity rate is 14%.1,6 The location of the lesion dictates the approaches available-cavernomas in the pons or medulla are commonly approached via a retrosigmoid or retrolabyrinthine approach, while more ventral pathologies in this region necessitate a far lateral approach.1,5,7,8 In Videos 1 and 2, we describe our experience with an exoscope-assisted far lateral approach to a pontomedullary cavernoma in a 10-year-old male presenting with numerous cavernomas and confirmed gene mutation. We demonstrate the exoscope's unparalleled visualization of the anterolateral brainstem, with nominal condylar drilling. The patient and his parents consented to the procedure and publication.

Surgical Results of Brainstem Cavernous Malformation Haemorrhage.

AIM: To evaluate surgical treatment options, complications and neurological outcomes of patients with cavernous malformations (CMs) in the pons and medulla oblongata. MATERIAL AND METHODS: We retrospectively evaluated 25 brain stem CMs that we operated between 2009 and 2019. We operated all cases in the first month with suboccipital retrosigmoid and paramedian approach. The cases were evaluated concerning their demographic characteristics, lesion characteristics, radiological imaging results, surgical approach and neurological status. RESULTS: Overall, 15 patients had CMs in the pons and 10 in the medulla oblongata. The mean age of the patients was 33.48 years, and the cases included 15 male and 10 female patients. The average modified Rankin Score (mRS) score had a mean of 2.36 and median of 2 at the time of admission (Table I). The mean follow-up period was 4.64 years (1?10 years). In the last follow-up assessment, the average mRS score was mean = 1.84 and median = 1. In addition, 14 (56%) patients recovered, 7 (28%) did not show any changes, 3 (12%) got worse, and 1 (4%) died. In our case series, the admission complaints were cranial nerve paralysis (24%) in 6 cases, nausea and vomiting in 1 (4%) and hemiparesis in 17 (68%). CONCLUSION: Experience, correct surgical approach and good knowledge of neuroanatomy are important in brainstem CM haemorrhages. Imaging methods, neuronavigation and neuromonitoring use are essential for patients undergoing surgery. In the presence of all these factors, the prognosis of patients will be better.

Hypertrophic Olivary Degeneration and Holmes Tremor: Case Report and Review of the Literature.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is very rare type of degeneration that causes hypertrophy rather than atrophy. The classical presentation of HOD is palatal myoclonus. However, HOD may rarely present with Holmes tremor (HT). HT is unusual symptomatic tremor characterized by combination of rest and intention tremor. It has been reported in small case series, so far. CASE DESCRIPTION: In this study, a man aged 62 years with HOD and HT spreading to the upper and lower extremities after pontine-midbrain hemorrhage due to cavernoma was presented. CONCLUSIONS: Although pontine-midbrain hemorrhage may cause HT in the late period, HOD can be revealed on magnetic resonance imaging. Tract anatomy, especially the Guillain-Mollaret triangle, should be considered to explain the relationship between HT and HOD.

High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study.

BACKGROUND: No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients. OBJECTIVE: To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma. METHODS: We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol. RESULTS: We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas. CONCLUSION: We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations.

Infratentorial Supracerebellar Approach for Resection of Midbrain Cavernous Malformation: 3-Dimensional Operative Video.

Cavernous malformations (cavernomas) of the brain stem with recurrent hemorrhage may be amenable to microsurgical resection if they are present close to the surface. The risks of surgery need to be balanced with the natural history of the lesion and the accumulation of neurological deficits and risk to life with multiple hemorrhages. In this 3D operative video, we illustrate the technique for the resection of a dorsally located midbrain cavernous malformation. Informed consent was obtained for this procedure. The cavernoma is accessed with the use of a supracerebellar infratentorial approach. The infratentorial craniotomy and coagulation of the superior vermian veins is shown. A description is provided of the use of hemosiderin staining and the intercollicular relative "safe zone"1 as landmarks for the neurotomy. The technique of cavernoma dissection from the surrounding gliotic plane is shown and described. In this case, the patient required prolonged rehabilitation but fully recovered without residual deficit 1 yr following surgery.

(Doctor My child keeps falling over) unexpected MRI findings in children with history of frequent falls and dizziness: a case series.

Frequent falls and dizziness are common complaints in children. These symptoms can be caused by wide range of underlying pathologies including peripheral vestibular deficits, cardiac disease, central lesions, motor skills delay and psychogenic disorders. We report three paediatric cases who presented with complaints of repeated falls and imbalance. MRI scan revealed underlying brain lesions (frontal lobe arteriovenous malformation, exophytic brain stem glioma and cerebellomedullary angle arachnoid cyst with cerebellar tonsillar ectopia). By reporting these cases, we would like to emphasise the importance of a thorough assessment of children with similar symptoms by detailed clinical history, physical examination and maintaining low threshold for investigations, including radiological imaging. Taking in consideration, the wide range of differential diagnosis, the challenge of obtaining detailed history and difficulty of performing reliable physical examination in this age group. Management of underlying disorders can be medical, surgical or just observational.

Endoscopic Endonasal Approach for Urgent Decompression of Craniovertebral Junction in Syringobulbia.

BACKGROUND: Syringobulbia is an uncommon lesion that occurs in the central nervous system; it is often defined as a pathologic cavitation in the brainstem. The cases with partial blockage of the cerebrospinal fluid pathways at the level of the foramen magnum are more common and the most important group. The most common treatment of syringobulbia is craniovertebral decompression. CASE DESCRIPTION: This paper reports a case of a symptomatic syringobulbia in which an urgent endoscopic endonasal approach to the craniovertebral junction (CVJ) was done to limit bulbo-medullary compression and rapid neurologic deterioration. A 69-year-old man was admitted to the hospital because of acute onset of dysphonia, dysphagia, imbalance, and vomiting. Magnetic resonance imaging revealed a cystic lesion in the brainstem, suggestive of a syringobulbia in Klippel Feil syndrome with CVJ stenosis. CONCLUSIONS: This case report details the successful use of endoscopic endonasal anterior decompression to treat syringobulbia, and adds to the growing literature in support of the endonasal endoscopic approach as a safe and feasible means for decompressing the craniocervical junction, even in the setting of urgency. However, prudent patient selection, combined with sound clinical judgment, access to instrumentation, and intraoperative imaging cannot be overemphasized.

Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models.

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs.

Tenascin-C expression contributes to pediatric brainstem glioma tumor phenotype and represents a novel biomarker of disease.

Diffuse intrinsic pontine glioma (DIPG), an infiltrative, high grade glioma (HGG) affecting young children, has the highest mortality rate of all pediatric cancers. Despite treatment, average survival is less than twelve months, and five-year survival under 5%. We previously detected increased expression of Tenascin-C (TNC) protein in DIPG cerebrospinal fluid and tumor tissue relative to normal specimens. TNC is an extracellular matrix (ECM) glycoprotein that mediates cell-matrix interactions, guides migrating neurons during normal brain development and is thought to maintain the periventricular stem cell niche in the developing brain. Tumor TNC expression is reported in adult glioma and other cancers. However, the pattern and effects of TNC expression in DIPG has not been previously explored. Here, we characterize TNC expression in patient derived pediatric supratentorial HGG (n = 3) and DIPG (n = 6) cell lines, as well as pediatric glioma tumor (n = 50) and normal brain tissue specimens (n = 3). We found tumor specific TNC gene and protein overexpression that directly correlated with higher tumor grade (WHO III and IV, p = 0.05), H3K27 M mutation (p = 0.012), shorter progression free survival (p = 0.034), and poorer overall survival (0.041) in association with these factors. TNC knockdown via lentiviral shRNA transfection of HGG (n = 1) and DIPG (n = 3) cell lines resulted in decreased cell proliferation, migration, and invasion in vitro (p < 0.01), while TNC cDNA transfection resulted in increased cell migration, invasion and proliferation (p < 0.01) as well as altered cell morphology in H3K27 M mutant DIPG lines. Whole transcriptome sequencing analysis (RNA-Seq) on DIPG (n = 3) and HGG (n = 2) cell lines after TNC cDNA, shRNA, and empty vector control transfection revealed the effects of TNC expression level on global gene expression profiles. Together, our findings reveal TNC expression in DIPG in association with H3K27 M mutation and VEGF signaling, and suggest that TNC may contribute to DIPG tumor phenotype, and serve as a clinically detectable biomarker for DIPG.

Intracranial endodermal cyst presenting with nonobstructive hydrocephalus: A case report.

RATIONALE: Endodermal cysts are rare benign lesions in the central nervous system. Their common symptoms include headache and neck pain caused by mass effect or inflammatory reaction. We report the case of an elderly woman with intracranial endodermal cyst who presented with nonobstructive hydrocephalus. PATIENT CONCERNS: A 78-year-old woman presented with acute deterioration of consciousness caused by acute hydrocephalus. She subsequently underwent ventriculoperitoneal shunt placement. Eighteen months after this operation, she developed numbness of extremities and gait and progressive cognitive disturbances. DIAGNOSIS: Initially, the endodermal cyst could not be recognized, but it became clinically evident in the craniocervical junction after ventriculoperitoneal shunt placement. MRI revealed multiple cystic lesions in the pontomedullary cistern. Postoperative pathology confirmed the diagnosis of endodermal cyst. INTERVENTIONS: Subtotal resection of the cystic lesion was performed. Intra-operatively, multiple cysts containing a milky white fluid were noted and the medullary surface including the median and lateral apertures of the fourth ventricle were covered by thick, cloudy arachnoid membrane. OUTCOMES: Although the numbness of extremities improved after the surgery, she remained bedridden due to deterioration in cognitive function and generalized muscle weakness. The patient developed recurrence 2 months after the surgery; however, no additional surgery was performed owing to her poor general condition. LESSONS: Endodermal cysts rarely present with nonobstructive hydrocephalus caused by recurrent meningitis. In such cases, the lesions are often invisible on initial diagnostic imaging, and complete resection of the lesions is typically difficult because of strong adhesion between the cyst walls and contiguous vital structures.