Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Pearls & Oy-sters: INO Plus From Downward Herniation-A Cautionary Tale Regarding Neuro-Ophthalmologic Signatures of Brainstem Compression.

Pupillary assessment is a quintessential part of the clinical examination in neuro-intensive care patients because it provides insight into the integrity of midbrain reflex arcs. Abnormal pupils, particularly anisocoria and later bilateral fixed mydriasis, are classically used to assess expansive intracranial processes because they are frequently considered early indicators of transtentorial midbrain compression due to elevated intracranial pressure. Complex ocular motor deficits mapping to the midbrain are rarely described in the setting of high transtentorial pressure. This is likely because ocular motor deficits typically occur in conjunction with decreased consciousness and corticospinal tract dysfunction reflecting advanced midbrain compromise. We present a case of left midbrain compression due to downward herniation in a patient with acute-on-chronic bilateral subdural hematoma. Ocular motor assessment demonstrated left internuclear ophthalmoplegia (INO) and an ocular tilt reaction, termed INO plus. However, pupillary, mental status, and sensorimotor examinations were unremarkable. Head magnetic resonance imaging revealed acute perforator ischemia in the left pontomesencephalic tegmentum, localizing to the ipsilateral medial longitudinal fasciculus and graviceptive oculocephalic circuits. Microvascular compromise secondary to mechanical pressure is discussed as a causative mechanism. We caution against overreliance on "telltale pupils" in suspected brainstem compression and recommend checking for other oculomotor signs.

Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness.

Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness in the human brain, but knowledge about the subcortical networks that sustain arousal in humans is incomplete. Here, we aimed to map the connectivity of a proposed subcortical arousal network that sustains wakefulness in the human brain, analogous to the cortical default mode network (DMN) that has been shown to contribute to awareness. We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) of three human brains, obtained at autopsy from neurologically normal individuals, with immunohistochemical staining of subcortical brain sections. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. Deterministic and probabilistic tractography analyses of the ex vivo diffusion MRI data revealed projection, association, and commissural pathways linking dAAN nodes with one another and with DMN nodes. Complementary analyses of in vivo 7-tesla resting-state functional MRI data from the Human Connectome Project identified the dopaminergic ventral tegmental area in the midbrain as a widely connected hub node at the nexus of the subcortical arousal and cortical awareness networks. Our network-based autopsy methods and connectivity data provide a putative neuroanatomic architecture for the integration of arousal and awareness in human consciousness.

Body representation after a stroke in the brainstem.

BACKGROUND: Lesion occurring in the brainstem may cause a postural tilt and balance disorders, which could be due to an inaccurate perception of the body orientation. The objective of this study was to determine the effects of a brainstem stroke on body representation in horizontal and frontal plane, and links with impaired posture and neuroanatomy. METHODS: Forty patients with stroke in left brainstem (L-BS) or right (R-BS) were compared with 15 matched control subjects (C). The subjective straight-ahead (SSA) was investigated using a method disentangling lateral deviation and tilt components of error. RESULTS: The L-BS patients had contralesional lateral deviation of SSA. In addition, they showed an ipsilesional tilt, more severe for the trunk than for the head. By contrast, in R-BS patients, the representation of the body midline was fairly accurate in both the horizontal and frontal planes and did not differ from that of control subjects. CONCLUSION: This work highlights an asymmetry of representation of body associated with left brainstem lesions extending to the right cerebral hemisphere. This deviation appears only after a left lesion, which may point to a vestibular dominance. These results open a new perspective of neuro-rehabilitation of postural disorders after a stroke, with the correction of the representation of body orientation.

Clinicoradiological features of probable chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described chronic inflammatory central nervous system disease. This case report describes a young female patient presenting with weakness in bilateral upper and lower limbs and tinnitus for 2 months. A neurological examination revealed signs of brainstem and cerebellar involvement. MRI brain showed characteristic features of CLIPPERS, with punctate and nodular enhancement in the pons and cerebellum. Differential diagnoses were systematically considered and excluded. The patient showed significant clinical and radiological improvement with steroid therapy. No clinical or radiological red flags occurred during the follow-up. This case underscores the critical role of integrating clinical and radiological findings to effectively diagnose and manage CLIPPERS. It emphasises the importance of ruling out alternative diagnoses through a thorough evaluation.

Uraemic brainstem encephalopathy mimicking ocular myasthenia: a case report.

BACKGROUND: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy. CASE PRESENTATION: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain. CONCLUSIONS: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia.

Altered functional connectivity of brainstem nuclei in new daily persistent headache: Evidence from resting-state functional magnetic resonance imaging.

OBJECTIVES: The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). METHODS: The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. RESULTS: Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus-central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area-parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). CONCLUSIONS: Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions.

Deep Learning-based Approach for Brainstem and Ventricular MR Planimetry: Application in Patients with Progressive Supranuclear Palsy.

Purpose To develop a fast and fully automated deep learning (DL)-based method for the MRI planimetric segmentation and measurement of the brainstem and ventricular structures most affected in patients with progressive supranuclear palsy (PSP). Materials and Methods In this retrospective study, T1-weighted MR images in healthy controls (n = 84) were used to train DL models for segmenting the midbrain, pons, middle cerebellar peduncle (MCP), superior cerebellar peduncle (SCP), third ventricle, and frontal horns (FHs). Internal, external, and clinical test datasets (n = 305) were used to assess segmentation model reliability. DL masks from test datasets were used to automatically extract midbrain and pons areas and the width of MCP, SCP, third ventricle, and FHs. Automated measurements were compared with those manually performed by an expert radiologist. Finally, these measures were combined to calculate the midbrain to pons area ratio, MR parkinsonism index (MRPI), and MRPI 2.0, which were used to differentiate patients with PSP (n = 71) from those with Parkinson disease (PD) (n = 129). Results Dice coefficients above 0.85 were found for all brain regions when comparing manual and DL-based segmentations. A strong correlation was observed between automated and manual measurements (Spearman ρ > 0.80, P < .001). DL-based measurements showed excellent performance in differentiating patients with PSP from those with PD, with an area under the receiver operating characteristic curve above 0.92. Conclusion The automated approach successfully segmented and measured the brainstem and ventricular structures. DL-based models may represent a useful approach to support the diagnosis of PSP and potentially other conditions associated with brainstem and ventricular alterations. Keywords: MR Imaging, Brain/Brain Stem, Segmentation, Quantification, Diagnosis, Convolutional Neural Network Supplemental material is available for this article. © RSNA, 2024 See also the commentary by Mohajer in this issue.

Brainstem toxicity after proton or photon therapy in children and young adults with localized intracranial ependymoma: A French retrospective study.

BACKGROUND AND PURPOSE: Ependymoma is the third most frequent childhood braintumor. Standard treatment is surgery followed by radiation therapy including proton therapy (PBT). Retrospective studies have reported higher rates of brainstem injury after PBT than after photon therapy (XRT). We report a national multicenter study of the incidence of brainstem injury after XRT versus PBT, and their correlations with dosimetric data. MATERIAL AND METHODS: We included all patients aged < 25 years who were treated with PBT or XRT for intracranial ependymoma at five French pediatric oncology reference centers between 2007 and 2020. We reviewed pre-irradiation MRI, follow-up MRIs over the 12 months post-treatment and clinical data. RESULTS: Of the 83 patients, 42 were treated with PBT, 37 with XRT, and 4 with both (median dose: 59.4 Gy, range: 53­60). No new or progressive symptomatic brainstem injury was found. Four patients presented asymptomatic radiographic changes (punctiform brainstem enhancement and FLAIR hypersignal), with median onset at 3.5 months (range: 3.0­9.4) after radiation therapy, and median offset at 7.6 months (range: 3.7­7.9). Two had been treated with PBT, one with XRT, and one with mixed XRT-PBT. Prescribed doses were 59.4, 55.8, 59.4 and 54 Gy. CONCLUSION: Asymptomatic radiographic changes occurred in 4.8% of patients with ependymoma in a large national series. There was no correlation with dose or technique. No symptomatic brainstem injury was identified.

Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. CONCLUSION: Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, especially the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.

Postoperative disappearance of leptomeningeal enhancement around the brainstem in glioblastoma.

PURPOSE: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. METHODS: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. RESULTS: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. CONCLUSIONS: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.

Role of autonomic, nociceptive, and limbic brainstem nuclei in core autism features.

Although multiple theories have speculated about the brainstem reticular formation's involvement in autistic behaviors, the in vivo imaging of brainstem nuclei needed to test these theories has proven technologically challenging. Using methods to improve brainstem imaging in children, this study set out to elucidate the role of the autonomic, nociceptive, and limbic brainstem nuclei in the autism features of 145 children (74 autistic children, 6.0-10.9 years). Participants completed an assessment of core autism features and diffusion- and T1-weighted imaging optimized to improve brainstem images. After data reduction via principal component analysis, correlational analyses examined associations among autism features and the microstructural properties of brainstem clusters. Independent replication was performed in 43 adolescents (24 autistic, 13.0-17.9 years). We found specific nuclei, most robustly the parvicellular reticular formation-alpha (PCRtA) and to a lesser degree the lateral parabrachial nucleus (LPB) and ventral tegmental parabrachial pigmented complex (VTA-PBP), to be associated with autism features. The PCRtA and some of the LPB associations were independently found in the replication sample, but the VTA-PBP associations were not. Consistent with theoretical perspectives, the findings suggest that individual differences in pontine reticular formation nuclei contribute to the prominence of autistic features. Specifically, the PCRtA, a nucleus involved in mastication, digestion, and cardio-respiration in animal models, was associated with social communication in children, while the LPB, a pain-network nucleus, was associated with repetitive behaviors. These findings highlight the contributions of key autonomic brainstem nuclei to the expression of core autism features.

Partially Reversible FLAIR Hyperintensity Along the Brainstem Surface in Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.

A 41-year-old woman presented with headache, fever, irritability, and confusion. She developed a coma after admission. MRI of the brain revealed periventricular and deep white matter lesions. Fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging hyperintensity along the brainstem surface was observed (Figure 1), considered a rare but characteristic finding in leptomeningeal carcinomatosis from lung cancer.1,2 However, serum tumor markers, CSF cytopathology, contrast-enhanced high-resolution chest CT, and whole-body PET were negative. Antiglial fibrillary acidic protein antibodies (cell-based assay) were positive in serum and CSF. After receiving intravenous methylprednisolone and immunoglobulin, the symptoms improved significantly. Repeated MRI of the brain showed partial resolution of the lesions (Figure 2). The lesions were possibly induced by immune-mediated intramyelinic edema.

Brainstem processing of cough sensory inputs in chronic cough hypersensitivity.

BACKGROUND: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI). METHODS: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation. FINDINGS: Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls. INTERPRETATION: Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs. FUNDING: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd.

Trans-radial artery microcatheter angiography-assisted juvenile ruptured brainstem arteriovenous malformation resection.

BACKGROUND: Due to their crucial functional location, surgical treatment of brainstem arteriovenous malformations (AVMs) has always been challenging. For unruptured AVMs, we can determine whether radiological therapy, interventional treatment, or surgical resection is feasible based on the AVM structure. However, for ruptured AVMs, microsurgical resection and interventional embolization are effective methods to prevent further rupture. In the microsurgical resection of AVMs, we usually use a hybrid operation to confirm the AVM structure and determine if the AVM is completely resected during the surgery. METHOD: We report a case of juvenile ruptured brainstem AVM resection. The right lateral position and left suboccipital retrosigmoid approach were used. We established an interventional approach via left radial artery and set a microcatheter in the feeding artery. Methylene blue injection via a microcatheter showed the AVM structure, and we totally resected the brainstem AVM under electrophysiological monitoring and navigation. Intraoperative angiography was performed to ensure complete resection without residual nidus. CONCLUSION: This case demonstrates that the trans-radial approach is convenient and safe for special positions in hybrid operations. Methylene blue injection via a microcatheter in the feeding artery provides clearer visualization of the AVM structure under the microscope.

Eagle jugular syndrome accompanied by de novo brainstem cavernous malformation: a case-based systematic review.

BACKGROUND: Eagle jugular syndrome (EJS), recently identified as a cause of cerebrovascular disease (CVD) due to venous obstruction by an elongated styloid process (SP), is reported here alongside a case of concurrent de novo cerebral cavernous malformation (CCM). This study aims to explore the potential causal relationship between EJS and de novo CCM through a comprehensive literature review. METHOD: Systematic literature reviews, spanning from 1995 to 2023, focused on EJS cases with definitive signs and symptoms and de novo CCM cases with detailed clinical characteristics. Data on the pathophysiology and clinical manifestations of EJS, as well as potential risk factors preceding de novo CCM, were collected to assess the relationship between the two conditions. RESULT: Among 14 patients from 11 articles on EJS, the most common presentation was increased intracranial hypertension (IIH), observed in 10 patients (71.4%), followed by dural sinus thrombosis in four patients (28.6%). In contrast, 30 patients from 28 articles were identified with de novo CCM, involving 37 lesions. In these cases, 13 patients developed CCM subsequent to developmental venous anomalies (43%), seven following dural arteriovenous fistula (dAVF) (23%), and two after sinus thrombosis (6%). In a specific case of de novo brainstem CCM, the development of an enlarged condylar emissary vein, indicative of venous congestion due to IJV compression by the elongated SP, was noted before the emergence of CCM. CONCLUSION: This study underscores that venous congestion, a primary result of symptomatic EJS, might lead to the development of de novo CCM. Thus, EJS could potentially be an indicator of CCM development. Further epidemiological and pathophysiological investigations focusing on venous circulation are necessary to clarify the causal relationship between EJS and CCM.

Coexistence of longitudinally extensive transverse myelitis and diffuse midline glioma in the brainstem in an adolescent boy with acute flaccid paralysis.

We present the case of a previously healthy 13-year-old boy who was admitted to the emergency department with acute flaccid paralysis. Magnetic resonance imaging revealed radiological evidence of longitudinally extensive transverse myelitis. Additionally, homogeneous T2 signal increase was observed in the pons and medulla oblongata, initially indicating brainstem encephalitis. Subsequent evaluations confirmed a coexistence of diffuse midline glioma (DMG) in the brain stem alongside acute transverse myelitis (ATM). Children with ATM generally have a more favorable prognosis than adults. However, despite the implementation of advanced treatment methods, the patient's quadriplegia did not improve and resulted in spinal cord sequela atrophy. DMG exhibits an aggressive growth pattern and lacks a known curative treatment. This case represents an exceedingly rare synchronous occurrence of aggressive conditions, underscoring the importance of raising awareness among physicians. Furthermore, we aim to discuss the radiologic differential diagnosis, as this is the first documented instance in the literature.