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Progress in Brain Research 2022Cavernous malformations are relatively common intracerebral malformations of which we only became properly aware after the introduction of MRI. They may be sporadic or...
Cavernous malformations are relatively common intracerebral malformations of which we only became properly aware after the introduction of MRI. They may be sporadic or familial. Familial CMs may be multiple and new lesions appear over time requiring intermittent MR control. Many sporadic CMs have no symptoms. The commonest location is in the supratentorial cerebral parenchyma presenting with epilepsy. The best treatment is microsurgery. A small proportion are in the brainstem and may rebleed and even be lethal. Treatment includes microsurgery and radiosurgery. Microsurgery cures the patient but has substantial problems with complications, deterioration and partial removal. Radiosurgery has taken time to demonstrate that it can over 2 years substantially reduce the risk of rebleeds without the risks of microsurgery. Both methods have a part to play in the treatment.
Topics: Brain Stem; Hemangioma, Cavernous, Central Nervous System; Humans; Intracranial Arteriovenous Malformations; Magnetic Resonance Imaging; Radiosurgery
PubMed: 35074077
DOI: 10.1016/bs.pbr.2021.10.029 -
Radiology Sep 2022A 64-year-old man presented with a 6-month history of lightheadedness, intermittent balance, and coordination difficulties. Two months before admission, symptoms became...
A 64-year-old man presented with a 6-month history of lightheadedness, intermittent balance, and coordination difficulties. Two months before admission, symptoms became more substantial and persistent, with a worsening sense of disequilibrium and unsteady gait. He reported difficulties pronouncing words and mild word-finding difficulties. His wife noted a change in his cognition and memory over the same time. His medical history included well-controlled chronic obstructive pulmonary disease (COPD) secondary to a long history of smoking with associated unintentional 30-lb (13.6-kg) weight loss over the previous 3 years, for which chest CT scanning was performed, revealing no abnormality. On clinical examination, the patient was alert and oriented but had slurred speech. A positive Romberg sign was noted, finger-to-nose and hand rapid alternating movement tests revealed impairment on the right side, and his gait was ataxic. The motor examination revealed normal muscle tone, bulk, and power in the upper and lower extremities. Sensory testing results were normal. Initial MRI of the brain at admission revealed abnormal findings in the left supratentorial brain (Figs 1-3). Of note, this patient's presentation predated the COVID-19 pandemic. Cerebrospinal fluid analysis revealed predominant pleocytosis (23 × 10/L; normal range, [0-5] × 10/L) (78% lymphocytes, 22% monocytes), elevated protein level (1.23 g/L; normal range, 0.19-0.64 g/L), oligoclonal bands (faint one or two), and a high immunoglobulin G index (0.130 g/L; normal reference, ≤0.059 g/L). Despite extensive initial work-up for inflammatory, infectious, autoimmune, or neoplastic causes, a definitive diagnosis was not reached. Thus, repeat MRI of the brain was performed 2 weeks after admission (Fig 4).
Topics: Brain; COVID-19; Humans; Lymphocytes; Magnetic Resonance Imaging; Male; Middle Aged; Pandemics
PubMed: 35994397
DOI: 10.1148/radiol.211953 -
Stroke Jun 2023Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the...
BACKGROUND
Major intracerebral hemorrhage (ICH) trials have largely been unable to demonstrate therapeutic benefit in improving functional outcomes. This may be partly due to the heterogeneity of ICH outcomes based on their location, where a small strategic ICH could be debilitating, thus confounding therapeutic effects. We aimed to determine the ideal hematoma volume cutoff for different ICH locations in predicting ICH outcomes.
METHODS
We retrospectively analyzed consecutive ICH patients enrolled in the University of Hong Kong prospective stroke registry from January 2011 to December 2018. Patients with premorbid modified Rankin Scale score >2 or who underwent neurosurgical intervention were excluded. ICH volume cutoff, sensitivity, and specificity in predicting respective 6-month neurological outcomes (good [modified Rankin Scale score 0-2], poor [modified Rankin Scale score 4-6], and mortality) for specific ICH locations were determined using receiver operating characteristic curves. Separate multivariate logistic regression models were also conducted for each location-specific volume cutoff to determine whether these cutoffs were independently associated with respective outcomes.
RESULTS
Among 533 ICHs, the volume cutoff for good outcome according to ICH location was 40.5 mL for lobar, 32.5 mL for putamen/external capsule, 5.5 mL for internal capsule/globus pallidus, 6.5 mL for thalamus, 17 mL for cerebellum, and 3 mL for brainstem. ICH smaller than the cutoff for all supratentorial sites had higher odds of good outcomes (all <0.05). Volumes exceeding 48 mL for lobar, 41 mL for putamen/external capsule, 6 mL for internal capsule/globus pallidus, 9.5 mL for thalamus, 22 mL for cerebellum, and 7.5 mL for brainstem were at greater risk of poor outcomes (all <0.05). Mortality risks were significantly higher for volumes that exceeded 89.5 mL for lobar, 42 mL for putamen/external capsule, and 21 mL for internal capsule/globus pallidus (all <0.001). All receiver operating characteristic models for location-specific cutoffs had good discriminant values (area under the curve >0.8), except in predicting good outcome for cerebellum.
CONCLUSIONS
ICH outcomes differed with location-specific hematoma size. Location-specific volume cutoff should be considered in patient selection for ICH trials.
Topics: Humans; Retrospective Studies; Cerebral Hemorrhage; Stroke; Globus Pallidus; Hematoma
PubMed: 37216445
DOI: 10.1161/STROKEAHA.122.041246 -
Journal of Clinical Oncology : Official... Mar 2023Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging....
PURPOSE
Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL.
PATIENTS AND METHODS
We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL.
RESULTS
Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, < .0001, log-rank test) and overall survival (OS, = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, = .0002; OS, = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value.
CONCLUSION
We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL.
UNLABELLED
[Media: see text].
Topics: Humans; Circulating Tumor DNA; Prognosis; Lymphoma, Non-Hodgkin; Supratentorial Neoplasms; Risk Assessment; Brain; Biomarkers, Tumor; Mutation
PubMed: 36542815
DOI: 10.1200/JCO.22.00826 -
Handbook of Clinical Neurology 2023Pain-sensitive structures in the head and neck, including the scalp, periosteum, meninges, and blood vessels, are innervated predominantly by the trigeminal and upper... (Review)
Review
Pain-sensitive structures in the head and neck, including the scalp, periosteum, meninges, and blood vessels, are innervated predominantly by the trigeminal and upper cervical nerves. The trigeminal nerve supplies most of the sensation to the head and face, with the ophthalmic division (V1) providing innervation to much of the supratentorial dura mater and vessels. This creates referral patterns for pain that may be misleading to clinicians and patients, as described by studies involving awake craniotomies and stimulation with electrical and mechanical stimuli. Most brain parenchyma and supratentorial vessels refer pain to the ipsilateral V1 territory, and less commonly the V2 or V3 region. The upper cervical nerves provide innervation to the posterior scalp, while the periauricular region and posterior fossa are territories with shared innervation. Afferent fibers that innervate the head and neck send nociceptive input to the trigeminocervical complex, which then projects to additional pain processing areas in the brainstem, thalamus, hypothalamus, and cortex. This chapter discusses the pain-sensitive structures in the head and neck, including pain referral patterns for many of these structures. It also provides an overview of peripheral and central nervous system structures responsible for transmitting and interpreting these nociceptive signals.
Topics: Humans; Headache; Pain; Brain; Dura Mater; Brain Stem
PubMed: 38043970
DOI: 10.1016/B978-0-12-823356-6.00001-9 -
Radiologie (Heidelberg, Germany) Aug 2023Pediatric brain tumors differ regarding location and histopathological features compared to those in adults. In children, 30% of pediatric brain tumors are... (Review)
Review
BACKGROUND
Pediatric brain tumors differ regarding location and histopathological features compared to those in adults. In children, 30% of pediatric brain tumors are supratentorial lesions. Low-grade astrocytomas, e.g. pilocystic astrocytoma or craniopharyngioma, are the most common tumors.
IMAGING MODALITIES
Magnetic resonance imaging (MRI) is the default imaging technique that is used to evaluate the findings. Ultrasound and cranial computed tomography (CCT) accompany the imaging, although CCT is mainly used in emergency situations.
TOPICS COVERED
The following article describes the most common pediatric supratentorial brain tumors with reference to imaging criteria as well as changes in the World Health Organization (WHO) classification.
Topics: Adult; Child; Humans; Brain Neoplasms; Brain; Supratentorial Neoplasms; Astrocytoma; Pituitary Neoplasms
PubMed: 37306748
DOI: 10.1007/s00117-023-01158-z -
Journal of Neurology Sep 2023Enhancing brain parenchymal disease, and especially tumefactive lesions, are an uncommon manifestation of neurosarcoidosis. Little is known about the clinical features...
BACKGROUND
Enhancing brain parenchymal disease, and especially tumefactive lesions, are an uncommon manifestation of neurosarcoidosis. Little is known about the clinical features of tumefactive lesions and their impact on management and outcomes, which this study aims to characterize.
METHODS
Patients with pathologically-confirmed sarcoidosis were retrospectively reviewed and included if brain lesions were: (1) intraparenchymal, (2) larger than 1 cm in diameter, and (3) associated with edema and/or mass effect.
RESULTS
Nine patients (9/214, 4.2%) were included. Median onset age was 37 years. Diagnosis was confirmed by brain parenchymal biopsies in 5 (55.6%). Median modified Rankin scale (mRS) score was 2 (range 1-4) at initial presentation. Common manifestations included headache (77.8%), cognitive dysfunction (66.7%), and seizures (44.4%). Sixteen lesions were present in 9 patients. The frontal lobe (31.3%) was most affected, followed by the subinsular region (12.5%), basal ganglia (12.5%%), cerebellum (12.5%), and pons (12.5%). MRI characteristics of the dominant lesions included spherical morphology (77.8%), perilesional edema (100.0%), mass effect (55.6%), well-demarcated borders (66.7%), and contrast enhancement (100.0%; 55.6% heterogeneous). Leptomeningitis was frequently present (77.8%). All required corticosteroid-sparing treatments, and most (55.6%) needed at least a third line of treatment (infliximab used in 44.4%). All patients relapsed (median 3 relapses, range 1-9). Median last mRS was 1.0 after median follow-up of 86 months, with significant residual deficits in 55.6%.
CONCLUSION
Tumefactive brain parenchymal lesions are uncommon, usually affect the supratentorial brain along with leptomeningitis, and are refractory to initial treatments with a high risk of relapse. Significant sequelae were encountered despite a favorable median last mRS.
Topics: Humans; Adult; Retrospective Studies; Brain; Central Nervous System Diseases; Sarcoidosis; Magnetic Resonance Imaging; Brain Diseases
PubMed: 37219604
DOI: 10.1007/s00415-023-11782-3 -
Acta Neuropathologica May 2023Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these...
Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.
Topics: Humans; Young Adult; Biomarkers, Tumor; Brain; Brain Neoplasms; Central Nervous System Neoplasms; Gene Fusion; Neoplasms, Neuroepithelial; Receptor Protein-Tyrosine Kinases; X-linked Nuclear Protein
PubMed: 36933012
DOI: 10.1007/s00401-023-02558-0 -
Pediatric Radiology Dec 2020Fetal MRI is the modality of choice to study supratentorial brain malformations. To accurately interpret the MRI, the radiologist needs to understand the normal sequence... (Review)
Review
Fetal MRI is the modality of choice to study supratentorial brain malformations. To accurately interpret the MRI, the radiologist needs to understand the normal sequence of events that occurs during prenatal brain development; this includes familiarity with the processes of hemispheric cleavage, formation of interhemispheric commissures, neuro-glial proliferation and migration, and cortical folding. Disruption of these processes results in malformations observed on fetal MRI including holoprosencephaly, callosal agenesis, heterotopic gray matter, lissencephaly and other malformations of cortical development (focal cortical dysplasia, polymicrogyria). The radiologist should also be familiar with findings that have high association with specific conditions affecting the central nervous system or other organ systems. This review summarizes and illustrates common patterns of supratentorial brain malformations and emphasizes aspects that are important to patient care.
Topics: Brain; Female; Fetus; Gray Matter; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malformations of Cortical Development; Nervous System Malformations; Pregnancy
PubMed: 33252760
DOI: 10.1007/s00247-020-04696-z