Cerebral Biopsy Research Articles

Diffuse meningeal melanocytosis – a silent culprit

Abstract Introduction/Objective Diffuse meningeal melanocytosis is a rare melanocytic proliferation that poses significant risk of severe hydrocephalus and mortality among children and young adults. Although the clonal melanocytes do not typically exhibit malignant morphological features, their capability for extensive invasion and malignant-like behavior necessitates tissue biopsy alongside immunohistochemical and molecular testing for definitive diagnosis. Methods/Case Report A 17-year-old male presented with progressive headaches, photophobia, and nausea, initially attributed to migraines. Neuro-opthalmological assessment revealed papilledema, leading to a diagnosis of idiopathic intracranial hypertension. Serial imaging showed fluctuating leptomeningeal enhancement and moderate communicating hydrocephalus without parenchymal lesions. Therapeutic lumbar punctures provided modest symptom improvement; increased opening pressure was observed. Evaluation of seven CSF specimens showed low glucose levels, increased cellularity consisting of bland appearing epithelioid cells of unknown etiology, and increased lymphocytes. Infectious causes were excluded. Due to the indeterminate CSF findings, discussion between the cytopathologist and neuro-opthamologist was crucial to facilitate tissue biopsy to exclude a neoplastic process. Subsequent shunt placement and cerebral cortex biopsy revealed neoplastic cells with sheet-like architecture coating the dura without overt brain invasion. The tumor cells had eosinophilic cytoplasm without pigment and enlarged nuclei with irregular contours, vesicular chromatin, and prominent nucleoli. No high-grade features were seen. Immunohistochemical stains were positive for MART1, HMB45, and PRAME, consistent with a melanocytic lesion. FISH melanoma panel was negative. The final diagnosis was diffuse meningeal melanocytic neoplasm, most consistent with meningeal melanocytosis. The patient received chemotherapy with improved symptoms and stable disease. Results (if a Case Study enter NA) NA Conclusion Diffuse meningeal melanocytosis is a challenging cytologic diagnosis as melanocytes can morphologically mimic lymphocytes and monocytes, and the low cellularity of CSF specimens often results in insufficient cell blocks for ancillary tests. The direct communication of the pathologist with the clinical team to correlate pathology, radiology, and clinical symptoms was essential to ensure the proper management of this patient.

Complete response in a lung adenocarcinoma with pleural metastases initially treated with gefitinib and switched to osimertinib after cerebral oligo-progression with unknown T790M mutation: a case report and review of literature

BackgroundFirst- and second-generation anti-epithelial growth factor receptor tyrosine kinase inhibitors have shown great efficacy in the treatment of advanced adenocarcinoma with epithelial growth factor receptor mutations, but this efficacy is limited by certain resistance mechanisms, in particular the T790M mutation, which must be screened before second-line treatment with osimertinib is indicated. The search for this mutation is sometimes difficult, especially in cases of intracranial relapse, through this case report we attempt to discuss the possibility of initiating treatment with osimertinib despite an unknown T790M mutation in such situation.Case reportWe present the case of a 70-year-old Moroccan male patient diagnosed with non-small cell lung carcinoma initially metastatic to the pleura with an epithelial growth factor receptor mutation who received gefitinib in first line with a complete response, he subsequently presented with cerebral oligo-progression with extra cranial stability. The patient was started on osimertinib with unknown T790M status, as it was impossible to perform a cerebral biopsy, the evolution was characterized by a partial response followed by stereotactic radiotherapy then a complete response for 2 years.ConclusionWe can discuss osimertinib as an option for patients with stage IV non-small cell lung cancer with brain oligo-progression on prior tyrosine kinase inhibitors and unknown T790M status, further studies are needed in this area.

A case of suspected gliomatosis cerebri: diagnostic and therapeutic challenges in a resource-poor setting.

We present a case of a 70-year-old male with gliomatosis cerebri (GC), who initially presented with behavioural changes and amnesia, which progressed to extrapyramidal and cortical dysfunction. Neuroimaging revealed possible extensive cerebral gliomatosis and brain biopsy showed reactive gliosis. Despite treatment with levodopa-carbidopa, the symptoms worsened, and he succumbed after 18 months. This case highlights the challenges in diagnosing and managing GC in a resource-poor setting.

Brainstorm: A case of granulomatous encephalitis

Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians’ unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly.

Intravenous immunoglobulin and rituximab in a treatment‐refractory COVID‐19‐associated central nervous system vasculitis: A case report and literature review

AbstractCentral nervous system (CNS) vasculitis is an uncommon inflammatory disease that affects the brain and spinal cord. It might present with headache, focal neurological deficits, seizures and encephalopathy. CNS vasculitis might be triggered by systemic vasculitides, connective tissue diseases, malignancies and infectious agents, including severe acute respiratory syndrome coronavirus 2. Diagnosis requires a combination of clinical presentation, serological and cerebral spinal fluid analysis, radiological findings (magnetic resonance imaging and conventional angiography), and brain biopsy. In the lack of randomized prospective studies, the treatment approach is based on retrospective cohort studies, anecdotal reports and therapeutic approaches derived from other vasculitides. In this report, we present a case of a 55‐year‐old man who presented with hemiparesthesia 39 days after coronavirus disease 2019 (COVID‐19) infection. During the disease course, the patient developed right‐sided hemiparesis and was referred to our center. Conventional angiogram suggested CNS vasculitis. After an extensive work‐up, systemic vasculitis was excluded. Despite having been treated with pulse steroid and cyclophosphamide, the patient experienced relapses. As we administered intravenous immunoglobulin and rituximab, remission was achieved both in clinical and radiological aspects. In this study, we present the first case of treatment‐refractory CNS vasculitis associated with COVID‐19, which was treated successfully with intravenous immunoglobulin and rituximab. Second, we report a review of COVID‐19‐related CNS vasculitis articles and applied treatment strategies published in English. To elucidate the mechanism of COVID‐19‐related CNS vasculitis, further research is needed.

Clinical and diagnostic observation of primary lymphoma of the central nervous system

Background. Lymphoma of the central nervous system (CNS), both primary and secondary, is a rare but very aggressive type of non-Hodgkin’s lymphoma. Primary CNS lymphoma (PCNSL) refers to cases confined to the CNS parenchyma, dura mater, leptomeninges, cranial nerves, and spinal cord or intraocular region. The prognosis of PCNSL has been very dismal with an overall survival of 1.5 months without treatment and a 5-year survival rate of 30%. Due to the introduction of high-dose methotrexatebased chemotherapy regimens, there has been substantial progress in treating patients with lymphomas of the CNS, leading to improved survival. Diagnosis and differential diagnosis of PCNSL can often cause complications because it may have similar clinical and radiological signs with some other tumors, primarily with high-grade gliomas and metastatic lesion of the CNS. Stereotactic biopsy remains the main diagnostic method.
 Purpose – to investigate the complexity of the diagnostic and therapeutic process in PCNSL on the example of a clinical case.
 Materials and methods. Clinical observation of patient K., 59 years old, who underwent examination and inpatient treatment at the Department of Radiation Pathology and Palliative Care of the State Organization «Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine» regarding multifocal lesions of the brain (volumetric formations of the white matter of the left hemisphere of the brain).
 Results and discussion. In this clinical case, the presence of multiple volumetric white matter formations of the left hemisphere of the brain in the frontal and temporal lobes of the brain with pronounced perifocal edema, mass effect and signal amplification from the described formations after the administration of a contrast agent in the patient in magnetic resonance imaging allowed us to assume metastatic lesion of the central nervous system. However, a comprehensive examination made it possible to exclude the presence of primary cancer, as well as an infectious lesion of the brain. The diagnosis of primary non-Hodgkin’s diffuse large B-cell lymphoma with damage to the central nervous system was established only after the neurosurgical removal of one of the neoplasms with the conduction of pathohistological and immunohistochemical studies.
 Conclusion. Multifocal brain injury often causes difficulties in diagnosis. Magnetic resonance imaging using T1, T2 and Flair imaging, although very important for the diagnosis of PCNSL, is not always specific. Timely cerebral biopsy with immunohistochemical examination remains the method of choice for verification of the pathological process, which is necessary for the correct treatment.

Síndrome meníngeo crónico. Afectación meníngea de etiología no infecciosa

Noninfectious chronic meningitis (NICM) is defined as meningeal inflammation unrelated to an infectious process that progresses with signs and symptoms which persist for more than four weeks. The most common clinical manifestation is headache in varying combinations with altered mental status, focal neurological signs, fever, nuchal rigidity, myelopathy, cranial neuropathies, or polyradiculopathies. The approach to NICM begins with a medical history, full physical examination, and additional tests (serological tests, brain imaging tests, lumbar puncture, and biopsy of skin lesions and lymph nodes). Cerebral and meningeal biopsy can be considered in cases that progress with progressive neurological decline and an inconclusive systemic or CSF study. Systemic diseases with meningeal involvement tend to progress with a combination of chronic or relapsing chronic meningitis and uveitis (uveo-meningeal syndromes). For the initial treatment, high doses of corticosteroids and, in refractory cases, immunosuppressants are required. Neoplastic meningitis presents with both solid tumors and with malignant cerebral and hematological neoplasms; its treatment depends on the type of neoplasm. The drugs most commonly associated with NICM are intravenous non-steroidal anti-inflammatory drugs, sulfamides, penicillins, and immunoglobulins. The prognosis is good, with improvement after withdrawal of the drug implicated.

Spontaneous intracerebral haemorrhage associated with early-onset cerebral amyloid angiopathy and Alzheimer’s disease neuropathological changes five decades after cadaveric dura mater graft

Cerebral amyloid angiopathy (CAA) is a small vessel disease, causing spontaneous intracerebral hemorrhage (ICH) in the elderly. It is strongly associated with Alzheimer disease (AD), as most CAA patients show deposition of Aβ—i.e. the basic component of parenchymal Alzheimer amyloid deposits—in the cerebral vessels. Iatrogenic early-onset CAA has been recently identified in patients with a history of traumatic brain injury or other cerebral as well as extra-cerebral lesions that led to neurosurgery or other medical procedures as intravascular embolization by cadaveric dura mater extracts many years before the first ICH event. In those patients, a transmission of Aβ seeds from neurosurgical instruments or from cadaveric dura mater exposure was suggested. We report a 51-year-old woman with unremarkable family history who presented abruptly with aphasia and right hemiparesis. A cerebral left lobar haemorrhagic stroke was documented by neuroimaging. Accurate anamnesis revealed a neurosurgical procedure with cadaveric dura mater graft at the age of 2 years for an arachnoid cyst. The neuropathological examination of the cerebral parietal biopsy showed severe amyloid angiopathy in many leptomeningeal and cortical vessels, as well as abundant parenchymal Aβ deposits, neurofibrillary tangles and neuropil threads. The mechanism involved in the human-to-human transmission of the Aβ proteinopathy remains to be clarified. In our patient the cadaver derived dura used for grafting is a very strong candidate as the source of the transmission. A systematic monitoring of individuals who have had neurosurgical procedures in early life, especially those involving cadaveric dural grafts, is required to determine the ratio of those affected by CAA many years later and unaffected. Moreover, our report confirms that in addition to vascular and parenchymal Aβ pathology, neurofibrillary changes indistinguishable from AD may develop in specific conditions with long latency period from the neurosurgical or embolization procedure.

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Frameless neuronavigation-assisted brain biopsy with electromagnetic tracking: how I do it?

In recent years, thanks to several technological innovations, stereotactic cerebral biopsies have evolved from frame-based to frameless neuronavigation-assisted techniques. The authors provide herein a detailed step-by-step description of the technique, shedding light on surgical tips and how to avoid complications. The practical application of the technique is demonstrated with a high-quality video. The neuronavigation-assisted brain biopsy with electromagnetic tracking is a "true frameless" procedure. It represents a simple, safe, and effective innovation for frameless biopsy of cerebral lesions. This technique is time efficient, offering a high degree of accuracy required for the establishment of a definitive diagnosis, enabling optimal further treatment, and thus improving patient outcome.

Characterisation of Severe Traumatic Brain Injury Severity from Fresh Cerebral Biopsy of Living Patients: An Immunohistochemical Study

Traumatic brain injury (TBI) is an extremely complex disease and current systems classifying TBI as mild, moderate, and severe often fail to capture this complexity. Neuroimaging cannot resolve the cellular and molecular changes due to lack of resolution, and post-mortem tissue examination may not adequately represent acute disease. Therefore, we examined the cellular and molecular sequelae of TBI in fresh brain samples and related these to clinical outcomes. Brain biopsies, obtained shortly after injury from 25 living adult patients suffering severe TBI, underwent immunohistochemical analysis. There were no adverse events. Immunostaining revealed various qualitative cellular and biomolecular changes relating to neuronal injury, dendritic injury, neurovascular injury, and neuroinflammation, which we classified into 4 subgroups for each injury type using the newly devised Yip, Hasan and Uff (YHU) grading system. Based on the Glasgow Outcome Scale-Extended, a total YHU grade of ≤8 or ≥11 had a favourable and unfavourable outcome, respectively. Biomolecular changes observed in fresh brain samples enabled classification of this heterogeneous patient population into various injury severity categories based on the cellular and molecular pathophysiology according to the YHU grading system, which correlated with outcome. This is the first study investigating the acute biomolecular response to TBI.

Central and Peripheral Nervous System Complications of Vasculitis Syndromes From Pathology to Bedside: Part 1-Central Nervous System.

Purpose of ReviewThe aim of this review is to provide a comprehensive update on the clinical assessment, diagnosis, complications, and treatment of primary central nervous system vasculitis (PCNSV).Recent FindingsThe developments in neuroimaging, molecular testing, and cerebral biopsy have enhanced clinical assessment and decision making, providing novel insights to prevent misdiagnosis increasing diagnostic certainty. Advances in imaging techniques visualizing the wall of intracranial vessels have improved the possibility to distinguish inflammatory from non-inflammatory vascular lesions. Large recent studies have revealed a more varied histopathological pictures and disclosed an association with amyloid angiopathy. Unfortunately, therapy remains largely empiric.SummaryPCNSV is a heterogeneous group of disorders encompassing different clinical subsets that may differ in terms of prognosis and therapy. Recent evidence has described a more benign course, with good response to therapy. New diagnostic techniques will play soon a pivotal role in the appropriate diagnosis and prompt management of PCNSV.

Rapid Diagnosis of Central Nervous System Scedosporiosis by Specific Quantitative Polymerase Chain Reaction Applied to Formalin-Fixed, Paraffin-Embedded Tissue.

Scedosporium (S.) apiospermum is a typical mold causing cerebral abscesses, often after near-drowning. Infections are associated with high morbidity and mortality due to diagnostic challenges including the need for prolonged incubation of cultures. In addition, histopathological differentiation from other filamentous fungi, including Aspergillus fumigatus, may not be possible, excluding early specific diagnosis and targeted therapy. Polymerase chain reaction (PCR) on tissue samples can rapidly identify fungi, leading to an earlier adequate treatment. Due to an extensive spectrum of causative fungi, broad-range PCRs with amplicon sequencing have been endorsed as the best DNA amplification strategy. We herein describe a case with brain abscesses due to S. apiospermum in a 66-year-old immunocompromised female patient. While broad-range PCR failed to identify a fungal pathogen from a cerebral biopsy demonstrating hyaline mold hyphae, specific quantitative PCR (qPCR) identified Scedosporium and ruled out Aspergillus, the most prevalent agent of central nervous system mold infection. A panel of specific qPCR assays, guided by the morphology of fungal elements in tissue or as a multiplex assay, may be a successful molecular approach to identify fungal agents of brain abscesses. This also applies in the presence of negative broad-range fungal PCR, therefore providing diagnostic and therapeutic potential for early specific management and improvement of patient clinical outcome.

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Diagnosis of Cerebral Aspergillosis.

Purpose: Cerebral aspergillosis (CA) is a rare but often fatal, difficult-to-diagnose, opportunistic infection. The utility of metagenomic next-generation sequencing (mNGS) for diagnosis of CA is unclear. We evaluated the usefulness of mNGS of the cerebrospinal fluid (CSF) for the diagnosis of CA.Methods: This prospective study involved seven consecutive patients with confirmed CA in whom CSF mNGS was performed. Serum (1→3)-β-D-glucan and galactomannan levels were determined, and histopathological examination and mNGS of the CSF were conducted. CSF specimens from three non-infected patients were used as positive controls.Results: mNGS of the CSF was positive in six of the seven confirmed CA cases (85.71% sensitivity). In the cryptococcal meningitis group (control), mNGS of the CSF was positive for Aspergillus in two patients (84.62% specificity). The positive likelihood ratio, negative likelihood ratio, and Youden’s index of mNGS for CA in the CSF were 5.565, 0.169, and 0.7, respectively. Among the six mNGS-positive cases, more than two Aspergillus species were found in four (4/6, 66.67%). In the positive controls, the addition of one A. fumigatus spore yielded a standardised species-specific read number (SDSSRN) of 25.45 by mNGS; the detection rate would be 0.98 if SDSSRN was 2.Conclusion: mNGS facilitates the diagnosis of CA and may reduce the need for cerebral biopsy in patients with suspected CA.Trial Registration Number: Chinese Clinical Trial Registry, ChiCTR1800020442.

Abstract 1122‐000216: Evacuation of Bilateral Intracerebral Hemorrhages Using a Novel Disposable Surgiscopic System: A Case Report

Introduction : Patients presenting with intracerebral hemorrhage (ICH) face higher rates of morbidity and mortality than other stroke patients. Currently, these patients are managed by surgical intervention and decompression or medical management, depending on categorization of the hemorrhage. Simultaneous, multifocal hemorrhages are a rare presentation of ICH that portend a worse prognosis. Here we report the treatment of bilateral simultaneous ICHs in a young patient with diagnostic cerebral angiography, biopsy, and bilateral minimally invasive surgiscopic ICH evacuation in a single procedure. Methods : The patient was a young female who presented to an outside hospital after two days of progressively worsening headaches and vomiting. Her medical history was significant for systemic lupus erythematosus (SLE), hypertension, chronic migraines, and opioid use disorder. In the emergency department, her mental status deteriorated, and she was intubated. Computed tomography (CT) scan was performed and showed a right parietal 43.3 cc ICH and a left parietal 38.7 cc ICH. MR angiogram and venogram showed no evidence of vascular malformations but were suggestive of potential cerebral venous sinus thrombosis. Upon arrival, the patient remained intubated but was able to open her eyes, follow commands, and respond to stimulation. The patient was brought to the angiosuite for diagnostic cerebral angiography which revealed diffuse intermittent arterial narrowing suggestive of vasculitis and patent venous sinuses. The patient was then positioned in the prone position and bilateral parietal 1.5 cm craniectomies were performed. Surgiscopic evacuation was performed sequentially using stereotactic navigation to access and evacuate each clot. A right parietal brain biopsy was performed at the minimally invasive cortical access point. Results : Active bleeding was encountered in both hematoma sites and was treated with a combination of irrigation and monopolar cautery transmitted through the Aurora Evacuator. After complete evacuation of the hematomas on both sides, an intraoperative conebeam CT was performed, demonstrating good right‐sided evacuation and resident left‐sided hematoma. Additional evacuation was performed on the left side and repeat conebeam CT demonstrated good bilateral evacuation. CT head on post operative day 1 showed 97.7% right‐sided evacuation and 81.5% left‐sided evacuation. The patient was treated with steroids for presumed vasculitis given the angiographic findings, which was later supported by the results of the brain biopsy. The patient made a good recovery and was discharged from the hospital alert and oriented, with CN II‐XII grossly intact, no focal deficits, and 5/5 strength in all extremities. Conclusions : Minimally invasive ICH evacuation can be performed in the angiosuite for ICH‐associated with vasculitis and even multifocal ICH when appropriate. Performing the procedure in the angiosuite permits completion of the diagnostic cerebral angiogram, brain biopsy, and hematoma evacuation at the same time, accelerating time to treatment for a patient with severe, symptomatic vasculitis.

Early-Onset Cerebral Amyloid Angiopathy and Alzheimer Disease Related to an APP Locus Triplication.

Background and ObjectiveTo report a triplication of the amyloid-β precursor protein (APP) locus along with relative messenger RNA (mRNA) expression in a family with autosomal dominant early-onset cerebral amyloid angiopathy (CAA) and Alzheimer disease (AD).MethodsFour copies of the APP gene were identified by quantitative multiplex PCR of short fluorescent fragments, fluorescent in situ hybridization (FISH), and array comparative genomic hybridization. APP mRNA levels were assessed using reverse-transcription–digital droplet PCR in the proband's whole blood and compared with 10 controls and 9 APP duplication carriers.ResultsBeginning at age 39 years, the proband developed severe episodic memory deficits with a CSF biomarker profile typical of AD and multiple lobar microbleeds in the posterior regions on brain MRI. His father had seizures and recurrent cerebral hemorrhage since the age of 37 years. His cerebral biopsy showed abundant perivascular amyloid deposits, leading to a diagnosis of CAA. In the proband, we identified 4 copies of a 506-kb region located on chromosome 21q21.3 and encompassing the whole APP gene without any other gene. FISH suggested that the genotype of the proband was 3 copies/1 copy corresponding to an APP locus triplication, which was consistent with the presence of 2 APP copies in the healthy mother and with the paternal medical history. Analysis of the APP mRNA level showed a 2-fold increase in the proband and a 1.8 fold increase in APP duplication carriers compared with controls.DiscussionIncreased copy number of APP is sufficient to cause AD and CAA, with likely earlier onset in case of triplication compared with duplication.

Good response to rituximab in chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids presenting as tumor‐like infratentorial lesion

AbstractBackgroundChronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) represents a T cell‐mediated inflammatory disorder typically characterized by multiple punctate gadolinium enhancement mainly involving the pontine region. Atypical onset with tumefactive infratentorial lesions has been rarely described, representing a significant diagnostic and therapeutic challenge.Case presentationWe describe a 58‐year‐old man who presented in November 2017 with left‐sided hemihypesthesia followed by gait imbalance and diplopia. The first magnetic resonance imaging scans showed an enhancing infratentorial tumefactive lesion empirically treated with intravenous steroids. Extensive laboratory work‐up for the most common causes of tumor‐like lesions was negative, whereas cerebral biopsy disclosed an accumulation of macrophages, perivascular T lymphocytes and rare B cells. Six months later a control magnetic resonance imaging showed multiple punctate hyperintensities in T2‐weighted images peppering the pons and upper cervical spinal cord, which were considered highly suggestive of CLIPPERS. After 3 months of oral prednisone, treatment with rituximab was initiated in April 2019, under which the patient's conditions fully stabilized.ConclusionsTumor‐like onset was found to be an extremely rare variant of CLIPPERS, which expands the spectrum of possible magnetic resonance imaging manifestation, which can be observed during the course of this disease. The efficacy of rituximab in the treatment of CLIPPERS syndrome supports the role of B cells as important regulators of T‐cell activity.

Primary Central Nervous System Vasculitis

Primary central nervous system (CNS) vasculitis is an uncommon disorder of unknown etiology that is restricted to the brain and spinal cord. Patients do not present with specific clinical features or a classical clinical course, and no blood or imaging investigations are available for diagnostic confirmation. Cerebral biopsy and angiography are the gold standards for diagnosis. No randomized clinical trials have described a therapeutic regimen effective for primary CNS vasculitis; therefore, treatment of primary CNS vasculitis is based on therapeutic strategies used for other types of vasculitis. Early diagnosis is important because corticosteroid-based treatment with or without concomitant cyclophosphamide administration can often prevent serious outcomes and may be followed by a favorable response. Several immunosuppressants such as mycophenolate mofetil, tumor necrosis factor-α blockers, and rituximab may be useful options for patients refractory to the aforementioned regimen. We describe some diagnostic and therapeutic approaches for the management of this condition, with a focus on the importance of obtaining tissue and angiographic evaluation (formal contrast-enhanced or magnetic resonance/computed tomography angiography).

Integrative analysis of physiological responses to high fat feeding with diffusion tensor images and neurochemical profiles of the mouse brain

BackgroundObesity proceeds with important physiological and microstructural alterations in the brain, but the precise relationships between the diet and feeding status, its physiological responses, and the observed neuroimaging repercussions, remain elusive. Here, we implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling.MethodsBrain DTI images were acquired from adult male C57BL6/J mice after 6 weeks of HFD, or standard diet (SD) administrations, both under the fed, and overnight fasted conditions. Metabolomic profiles of the cortex (Ctx), hippocampus (Hipc), and hypothalamus (Hyp) were determined by 1H high-resolution magic angle spinning (HRMAS) spectroscopy, in cerebral biopsies dissected after microwave fixation. Mean diffusivity (MD), fractional anisotropy (FA) maps, and HRMAS profiles were complemented with determinations of phenotypic alterations and plasma levels of appetite-related hormones, measured by indirect calorimetry and multiplex assays, respectively. We used Z-score and alternating least squares scaling (ALSCAL) analysis to investigate specific associations between diet and feeding status, physiological, and imaging parameters.ResultsHFD induced significant increases in body weight and the plasma levels of glucose and fatty acids in the fed and fasted conditions, as well as higher cerebral MD (Ctx, Hipc, Hyp), FA (Hipc), and mobile saturated fatty acids resonances (Ctx, Hipc, Hyp). Z-score and ASLCAL analysis identified the precise associations between physiological and imaging variables.ConclusionsThe present study reveals that diet and feeding conditions elicit prominent effects on specific imaging and spectroscopic parameters of the mouse brain that can be associated to the alterations in phenotypic and endocrine variables. Together, present results disclose a neuro-inflammatory response to HFD, characterized primarily by vasogenic edema and compensatory responses in osmolyte concentrations.

Frameless Stereotactic Biopsy with DTI-Based Tractography Integration: How to Adjust the Trajectory—A Case Series

Frameless stereotactic biopsy represents a minimally invasive procedure used for the histopathological diagnosis of brain tumors or to safely approach deep-seated lesions near eloquent areas not amenable for classical neurosurgical procedures. Traditionally, biopsy is performed relying on anatomical landmarks, but it can lead itself to intra- and postoperative complications, such as hemorrhage and fiber disruption. Diffusion tensor imaging (DTI) tractography represents a useful tool that can analyze the individual fiber tract conformation in cases of brain tumor and consequently identify the best biopsy trajectory, preserving white matter pathways. In our study, we present a novel technique that is based on the use of preoperative DTI for biopsy. Between January 2018 and January 2020, data about patients who underwent frameless biopsy using DTI tractography were retrospectively reviewed. The inclusion criterion was adult patients eligible for elective surgery for a single or multiple deep-seated lesions with contraindications to complete surgical resection. We included 12 patients (mean age of 67.9 [±9.6] years). A single cranial lesion was detected in 7 cases, and multiple lesions in 5 cases. The use of DTI enabled the identification of white matter pathways in all cases and adjustment of the biopsy trajectory based on anatomical landmarks in 7 cases. Postoperative hematoma was reported in 1 case, and histological diagnosis was obtained in 11 cases. According to our results, tractography is a useful tool that can enhance the safety of cerebral lesions biopsy sparing any fiber tract damages.