New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus.

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

Safety and Efficacy of Biopsy in Patients with Diffuse Intrinsic Pontine Gliomas.

BACKGROUND: Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies. METHODS: This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques. RESULTS: A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality. CONCLUSIONS: Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy.

Surgery for longer duration supranuclear ophthalmoplegia secondary to brain stem cavernoma: A case report and literature review.

BACKGROUND: Previous reports revealed that patients with acquired paralytic strabismus caused by central nervous system diseases are primarily affected by the etiology and treatment of the condition. Strabismus correction for these acquired paralytic strabismus should be performed as soon as the primary disease has been stabilized for 6 months in order to archive a favorable surgical outcome. CASE: We followed an infrequent case of longer-lasting supranuclear ophthalmoplegia secondary to brain stem cavernoma. OBSERVATION: A 25-year-old Chinese Han female developed aberrant head posture and ipsilateral conjugate gaze palsies 8 years after the first brainstem hemorrhage caused by pontine cavernoma. The patient was diagnosed with supranuclear ophthalmic palsy and brain stem cavernoma after surgery. A resection-recession procedure along with a rectus muscle transposition was performed. The patient's abnormal head position disappeared, with a normal primary position. CONCLUSION: Resection-recession procedures combined with rectus muscle transposition works very well for longer duration large-angle strabismus caused by brain stem cavernoma.

[Brain Stem and Para-Brain Stem Lesions].

Surgeries for brainstem lesions and adjacent areas needs meticulous manipulation in the profoundly deep surgical field. Moreover, it is associated with a high risk of complications pertinent to resection. The opportunity for a surgeon to amass extensive surgical experience in these lesions is limited. Additionally, the reduced tissue mobility in the brainstem, compared to other lesions, makes selecting the optimal surgical approach critical. Preoperative simulation is pivotal in surmounting these challenges. However, the limitations of preoperative simulations should be recognized in accurately depicting diminutive vessels and cranial nerves around the brainstem. Incorporating intraoperative anatomical observations and data from intraoperative monitoring into a surgical strategy is imperative. Here, we present three cases in which we believe preoperative simulation was effective; a cavernous hemangioma of the brainstem, trochlear schwannoma, and diffuse midline glioma in the pons.

18 F-FDG Brain PET/MRI in Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids.

ABSTRACT: An 89-year-old man presented with progressive gait disturbance, diplopia, and ataxia. Initial brain MRI demonstrated T2/FLAIR hyperintense signal abnormality in the pons extending along the middle cerebellar peduncles into the cerebellum, with associated punctate, patchy, and linear enhancement on postcontrast imaging. Initially, this was attributed to brainstem encephalitis; however, sarcoidosis, histiocytosis, and paraneoplastic/autoimmune encephalitis remained on the differential. One month after initial MRI, 18 F-FDG brain PET/MRI was performed and showed marked pontine hypermetabolism corresponding to the signal abnormality and enhancement on structural imaging. Collectively, these findings are characteristic of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.

Keyhole Retrosigmoid Craniotomy for Lateral Pontine Cavernous Malformation.

With improvements in anesthesia, monitoring, and peroperative care, the surgical removal of intrinsic brainstem pathology has become a possibility.1 Although surgical removal of deep-seated lesions continues to have significant morbidity, at least temporarily, associated with it, removal of exophytic lesions can be accomplished with little disability for the patient. The key to a good outcome, when removing cerebral cavernous malformation, is preservation of adjacent neurovascular bundles, use of sharp dissection over blunt pulling, judicious use of cautery in and around the brainstem, and preservation of the developmental venous anomaly, when present. The authors present a case of a lateral pontine cerebral cavernous malformation that was exophytic at the lateral and peritrigeminal safe entry zones.2 Neuromonitoring was used an adjunct to ensure safety of the procedure. The lesion is accessed using a keyhole retrosigmoid craniotomy (Video 1). We do not routinely use lumbar drains for these procedures as careful arachnoid dissection can result in adequate cerebrospinal fluid release. The window of access to this area is between CN 5 and the CN 7/8 complex. The arachnoid over the nerves is preserved, but the layer between the nerves is exposed to gain access to the lateral pons. The lesion is sharply dissected from the lateral pons, taking care to save the developmental venous anomaly, from which this lesion arises.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

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

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: 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. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: 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. ESSENTIALS STEPS OF THE PROCEDURE: 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. PITFALLS/AVOIDANCE OF COMPLICATIONS: 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. VARIANTS AND INDICATIONS FOR THEIR USE: 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.

Safety and efficacy of the endoscopic transsphenoidal transclival approach performed using direct cortical stimulation for pontine cavernous malformations.

OBJECTIVE: Surgical treatment of brainstem cavernous malformations (CMs) is challenging. Surgery using the endoscopic transsphenoidal transclival approach (eTSTCA) is reported as a useful alternative for ventral brainstem CMs. However, CMs located in the ventral midline of the brainstem are rare, and only a small number of case reports on these CMs treated with the eTSTCA exist. The efficacy and safety of the eTSTCA have not yet been fully examined. METHODS: A retrospective analysis was performed for 5 consecutive patients who underwent surgery via the eTSTCA for treating ventral pontine CMs. RESULTS: The average maximum CM diameter was 26.0 mm (18-38 mm). All patients underwent MR-diffusion tensor imaging, which confirmed that the corticospinal tract (CST) deviated posteriorly or laterally to the CM. Direct brainstem cortical stimulation was performed to localize the CST before making the cortical incision. After the excision of the CM, the cavity was filled with artificial CSF to make an aqueous surgical field (wet-field technique) for observing the tumor cavity and confirming complete hemostasis and resection. Total removal was achieved in all patients. The preoperative modified Rankin Scale score was 3 in 3 patients and 4 in 2 patients, whereas it was 1 in 2 patients and 0 in 3 patients 3 months after surgery. Postoperative CSF leakage was observed in 1 patient, and transient abducens nerve palsy was observed in 1 patient. No other intra- or postoperative complications were observed. CONCLUSIONS: MR-diffusion tensor imaging and direct brainstem cortical stimulation were useful to ascertain the proximity of the CST to the CM. The endoscope provides a clear view even underwater, and it was safe and effective to observe the entire CM cavity and confirm complete hemostasis without additional retraction of the brainstem parenchyma, including the CST. The eTSTCA provides a direct access point to the lesion and may be a safer alternative treatment for patients whose CST deviates laterally or posteriorly to the CM.

Pontine tegmental cap dysplasia: the role of diffusion tensor imaging.

Pontine tegmental cap dysplasia (PTCD) is a rare hindbrain malformation syndrome. Recurrent aspiration pneumonia is a major cause of death during a first year of life. We report the case of month-old child with an inability to suck milk since birth and multiple convulsions. PTCD was identified using tractography and MRI. This case report describes the imaging findings, the role of diffusion tensor imaging in PTCD and its differentiating features from Joubert syndrome and related disorders (JSRDs). The constellation of imaging features in PTCD includes a midbrain appearance resembling a molar tooth, a flattened anterior pontine belly, hypoplastic middle cerebellar peduncles and dorsal pontine tegmental cap. 'Tegmental cap' is a transversely oriented abnormal bundle of fibres with absent superior cerebellar peduncle decussation. Accurate diagnosis with MRI and tractography and differentiating PTCD from JSRD would help the clinician for appropriate genetic counselling and prognosis.

Clinical outcomes of stereotactic biopsy on children with pontine diffuse midline glioma.

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data. RESULTS: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076). CONCLUSION: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment.

Recurrent haemorrhagic pontine cavernoma resection via a retrosigmoid microsurgical approach.

BACKGROUND: Brainstem cavernomas occasionally require surgical treatment. Appropriate patient selection and thorough understanding of the anatomy and technical nuances involved in microsurgical resection is a pre-requisite in undertaking these challenging cases. CASE DESCRIPTION: We present a video case of a patient with a recurrent haemorrhagic pontine cavernoma. A step-by-step commentary of surgical footage is provided along with clinical, anatomical and technical learning points pertinent to the safe surgical management of these lesions.

Long-term functional outcomes and complications of microsurgical resection of brainstem cavernous malformations: a systematic review and meta-analysis.

Brainstem cavernous malformations (CMs) encompass up to 20% of all intracranial CMs and are considered more aggressive than cerebral CMs because of their high annual bleeding rates. Microsurgical resection remains the primary treatment modality for CMs, but long-term functional outcomes and complications are heterogenous in the literature. The authors performed a systematic review on brainstem CMs in 4 databases: PubMed, EMBASE, Cochrane library, and Google Scholar. We included studies that reported on the long-term functional outcomes and complications of brainstem CMs microsurgical resection. A meta-analysis was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search yielded 4781 results, of which 19 studies met our inclusion criteria. Microsurgery was performed on 940 patients (mean age 35 years, 46.9% females). Most of the brainstem CMs were located in the pons (n = 475). The pooled proportions of improved, stable, and worsened functional outcomes after microsurgical resection of brainstem CMs were 56.7% (95% CI 48.4-64.6), 28.6% (95% CI 22.4-35.7), and 12.6% (95% CI 9.6-16.2), respectively. CMs located in the medulla were significantly (p = 0.003) associated with a higher proportion of improved outcome compared with those in the pons and midbrain. Complete resection was achieved in 93.3% (95% CI 89.8-95.7). The immediate postoperative complication rate was 37.2% (95% CI 29.3-45.9), with new-onset cranial nerve deficit being the most common complication. The permanent morbidity rate was 17.3% (95% CI 10.5-27.1), with a low mortality rate of 1% from the compiled study population during a mean follow-up of 58 months. Our analysis indicates that microsurgical resection of brainstem CMs can result in favorable long-term functional outcomes with transient complications in the majority of patients. Complete microsurgical resection of the CM is associated with a lower incidence of CM hemorrhage and the morbidity related to it.

Micro-Doppler for venous sinus localization in approaches to the cerebello-pontine angle.

BACKGROUND: Main anatomical landmarks of retrosigmoid craniotomy are transverse sinus (TS), sigmoid sinus (SS), and the confluence of both. Anatomical references and guidance based on preoperative imaging studies are less reliable in the posterior fossa than in the supratentorial region. Simple intraoperative real-time guidance methods are in demand to increase safety. METHODS: This manuscript describes the localization of TS, SS, and TS-SS junction by audio blood flow detection with a micro-Doppler system. CONCLUSION: This is an additional technique to increase safety during craniotomy and dura opening, widening the surgical corridor to secure margins without carrying risks nor increase surgical time.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

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