Abstract Primary central nervous system lymphoma (PCNSL) is a rare, aggressive subtype of non-Hodgkin lymphoma that arises within the central nervous system, often affecting immunocompromised individuals, particularly those with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Diagnostic and therapeutic challenges stem from its diverse clinical presentations, deep parenchymal involvement, and the protective effect of the blood–brain barrier, which limits chemotherapeutic penetration. While most cases are diffuse large B cell lymphomas, rare T cell variants highlight the critical role of tissue biopsy and immunohistochemistry in confirming diagnosis.We present five patients diagnosed with PCNSL who exhibited varied neurological symptoms, including headache, vomiting, behavioral changes, and focal deficits. Diagnostic workup included magnetic resonance imaging, positron emission tomography/computed tomography, cerebrospinal fluid (CSF) analysis, and stereotactic or open brain biopsy. Treatment was tailored based on immune status: immunocompetent patients received rituximab, methotrexate, procarbazine, and vincristine, while immunocompromised patients were treated with methotrexate, temozolomide, and rituximab. Radiotherapy was used selectively. One case involved surgical excision for a suspected meningioma, later confirmed as a rare T cell variant.Outcomes ranged from long-term remission to early mortality, particularly in HIV-positive patients with profound immunosuppression. This series emphasizes the importance of early treatment initiation, tailored therapy, and the consideration of rare pathological variants. Novel biomarkers, such as myeloid differentiation primary response 88 mutations and CSF cytokines such as interleukin-10 and chemokine CXCL13, show potential for improving diagnosis and prognosis but require further validation.

BackgroundDiagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy.Case presentations.The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3.ConclusionsTaken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.

Abstract INTRODUCTION GammaTile intracranial brachytherapy utilizing cesium-131 seeds has demonstrated encouraging safety and local control results in a single-arm precommercial study, and recently received Food and Drug Administration clearance. The authors report the first case of GammaTile intraoperative brachytherapy performed during an awake craniotomy. METHODS A 50-year-old man suffered a generalized tonic-clonic seizure while a vehicle passenger. MRI revealed a 2.8 cm left lateral frontal lesion nearing his Broca’s area. Open brain biopsy revealed IDH-wildtype MGMT unmethylated GBM. Unfortunately, despite several interventions (awake craniotomy, adjuvant chemoradiation with temozolomide, Avastin, tumor treating fields) he suffered tumor progression near the left parietal resection cavity. Due to the location of this tumor, re-resection was planned with awake craniotomy and language mapping. A preoperative planning session involving Radiation Oncology and Neurosurgery identified the area of the expected postoperative bed, and consequently five GammaTiles were ordered, each containing 4 cesium-131 3.5 U seeds. RESULTS During surgery, once the tumor was mapped, bipolar stimulation was performed while the patient spoke in complete sentences until going into speech arrest on the posterior edge of the gyrus, indicative of language cortex. Following this mapping, microsurgical maximal safe resection occurred, after which areas at risk for tumor residual/recurrence were determined in consultation with Radiation Oncology. Subsequently, Neurosurgery placed all five GammaTiles (20 cesium-131 seeds total) in customized forward fashion to optimally cover the dosimetric needs of these areas. Following GammaTile placement, closure was completed and radioactive surveys of the room remained within state statue. Postoperative dosimetry yielded excellent coverage, and speech function was maintained. CONCLUSIONS The first reported case of GammaTile intraoperative brachytherapy during awake craniotomy supports the safety and feasibility of this treatment strategy. This case indicates that for patients with tumors adjacent to eloquent cortex, awake craniotomy can allow for maximum safe resection and implantation of intraoperative brachytherapy.

Primary malignant melanoma of the meninges is an exceedingly rare neoplasm. Usually its symptoms include raised intracraneal pressure resulting from hydrocephalus seconday to tumoral obliteration of cisternal basal cisterns, but the passage of time from initial symptomalogy to diagnosis is frequently delayed. A 12-year-old male with primary letomeningeal melanoma is reported. At the beginning, he presented with vomiting, headache, complex seizures, fever four months before the admission in the hospital where progressive loss of consciouness after admission. Lumbar puncture reveled high protein level, normal glucose level and 50 leucocytes/mm3 with 86% polymorphic cells. Magnetic ressonance imaging of the brain was referred and in T1-weighted images revealed a diffuse enhancement of the leptomeninges on right frontal cortical. An open brain biopsy trough was performed, after exclusion of the infectious nervous system disease. Histological examination revealed massive infiltration of meninges with brown tumor cells. These cells stained positive for HMB-45, S-100 protein and vimentin. The patient received post operative radiation therapy, but died after three months of the diagnosis with septic shock and epileptical status

An 18-year-old woman gradually developed speech and gait disturbance for seven months. On admission, she presented with cerebellar ataxia and tetraparesis. Magnetic resonance images showed diffuse hyperintense lesions around the fourth ventricle in FLAIR, in addition to lesions of nodular diffusion restriction with enhancement. Heavily T2-weighted images revealed small cystic appearance within this lesion. We diagnosed her as classical medulloblastoma by open brain biopsy. We should consider medulloblastoma as a differential diagnosis of these characteristics around the fourth ventricle, even if magnetic resonance findings are atypical in point of no mass effect and heterogeneous enhancement.

BACKGROUNDThe WHO Disability Assessment Schedule (WHODAS) is a practical assessment instrument which measures level of functioning in the following six domains of life. Here we report a case of brain tumor who was evaluated with the 36-item full version of WHODAS 2.0 (self-administered mode), and discuss usefulness of the WHODAS.CASE PRESENTATIONA 69-year-old man was referred to our hospital with cognitive problems because of which he needed assistance for his ADLs at home. He was diagnosed as having primary central nervous system lymphoma (PCNSL) following open brain biopsy, and was transferred to our hospital for chemotherapy at 23 days after the biopsy. He showed no sign of motor or sensory impairments, but initial evaluation revealed that he had troubles in judgment in his ADLs mainly because of marked memory deficits. Motor, cognitive and total FIM score was 65/91, 22/35, and 87/126, respectively and MMSE score was 24/30. After 48 days of chemotherapy (3 courses of initial DeVIC and following R-MPV regimens), he was temporally discharged home before readmission for another chemotherapy. According to him and his family, he was then basically independent in ADLs at home. We implemented WHODAS 2.0 to demonstrate minute ADL problems of this patient at home so that we might focus on rehabilitation for specific problems at home. Sub-scores of the WHODAS were 15/30 for Cognition, 10/25 for Mobility, 4/20 for Self-care, 14/25 for Getting along, 12/20 for Life activities, and 27/40 for participation. In fact, he felt difficulty in the areas of “activity and participation”.DISCUSSIONThe WHODAS is useful to identify various problems in their daily livings even though patients were independent in ADLs. Patients with brain tumors often repeat hospitalization for medical treatment. We have to be alert to not only objective but subjective changes in ADLs at home.

An autopsy case of amyloid β-related angiitis with cognitive impairment, multiple infarcts and subcortical hemorrhage

Long-term utility and complication profile of open craniotomy for biopsy in patients with idiopathic encephalitis

Experiences at our institution show that flow cytometry analysis (FCA) has become routine clinical practice in the workup of patients with altered mental status, even if risk factors are low. To assess diagnostic accuracy of combined FCA and cytology in the diagnosis of central nervous system lymphoma in an unselected patient population with neurologic symptoms, including patients with no history of lymphoma or suspicious radiology. Between 2001 and 2011, cerebrospinal fluid was submitted from 373 patients for lymphoma screening by FCA. The medical records were reviewed for patient symptomatology, history of malignancy, brain imaging, FCA results, cytology results, brain biopsy, and clinical follow-up. A lymphoid malignancy was detected by FCA in 4% of cases. A positive diagnosis was more likely in patients with either a history of hematologic malignancy and/or a suspicious radiology result (P = .009). All patients with no history of lymphoma and no suspicious radiology (n = 102) had negative cytology, and none had a correspondingly positive FCA result. The positive and negative predictive values of combined cytology and FCA in the patients with history of lymphoma and/or abnormal imaging results were 92% and 89%, respectively, when compared with open brain tissue biopsy, and 89% and 86%, respectively, when compared with clinical follow-up. When low-risk patients were included, the positive predictive value remained at 92%, but the negative predictive value dropped to 52% with the open brain biopsy as the reference, and values did not change significantly for the group with clinical follow-up. Concurrent FCA and cytology are most useful in the appropriate clinical setting, and we propose a triage algorithm for how FCA on cerebrospinal fluid is best used.

A 47 year old female presented with sub–acute cognitive decline and personality change, without any significant focal neurology. An MRI scan showed extensive white matter signal change and oedema with...

Abstract BACKGROUND: Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking. OBJECTIVE: We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality. METHODS: A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested. RESULTS: Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P < .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01). CONCLUSION: Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

Acute myeloid leukemia (AML) is a hematologic malignancy that can present with central nervous system (CNS) symptoms. Neurological symptoms may result from the local accumulation of malignant cells in or near the brain (chloroma), infection, hemorrhage, or infarcts from leukostasis. Leukostasisis a syndrome that can include brain infarction due hyperviscosity of blood with vascular occlusion but CNS involvement is rarely encountered in adults. We report an unusual case of leukostasis in an adult who presented with multiple high attenuation intracranial masses on CT. While initially thought to represent chloromasthey proved to be hemorrhagic infarcts secondary toleukostasis on open brain biopsy. This condition is under-reported in the radiology literature and only rarely biopsy proven. We review in this paper the pathological, CT and MRI findings of leukostasis in order to increase awareness of this uncommon entity and facilitate diagnosis.

We present a case of a 53-year-old HIV negative man with a 2-month history of progressive recent memory disturbance, gait disturbance and urinary incontinence. On MRI, an infiltrative tumor in the brain and spinal cord was noted. Subsequent positron emission tomography studies along with bone marrow biopsy and serum protein electrophoresis showed no evidence of systemic disease. Open brain biopsy results revealed a small lymphocytic infiltrate with scattered plasma cells in a predominantly perivascular growth pattern. The morphology was consistent with involvement by a low-grade B-cell lymphoma. Immunohistochemical findings showed CD20+, CD10-, CD5-, TdT-, EBV-encoded RNA in situ- and IgM-. The above findings were consistent with involvement by a non-dural extranodal marginal zone B-cell lymphoma (MZBCL) primary to the brain and spinal cord. This is a case report of a CNS MZBCL of mucosa-associated lymphoid tissue type involving the brain and spinal cord parenchyma.

Balamuthia mandrillaris is a free-living ameba that causes amebic encephalitis. Herein, we report an autopsy case of Balamuthia encephalitis proven with polymerase chain reaction (PCR) and immunohistochemistry from paraffin-embedded brain biopsy specimens. A 68-year-old Japanese male presented at a hospital with progressive right hemiparesis approximately 3 months before his death. An open-brain biopsy specimen showed diffuse meningitis with massive coagulative necrosis. The perivascular spaces contained numerous lymphocytes, histiocytes and giant cells, although the etiology was not determined. The patient deteriorated into coma and died from cerebral herniation. Autopsy revealed abundant trophozoites and cysts in the subarachnoid and Virchow-Robin's spaces. Electron-micrographs of the amebic cysts showed a characteristic triple-walled envelope. The amebas were identified as Balamuthia mandrillaris based on immunohistochemical analysis from the autopsy and biopsy specimens. Primer sets designed to amplify approximately 200 bp bands of mitochondrial 16S rRNA gene of Balamuthia by PCR produced positive results from the biopsy specimens but negative results from the autopsy specimens. In summary, PCR to amplify shorter segments of DNA may be of diagnostic value in detecting suspected cases of balamuthiasis in formalin-fixed, paraffin-embedded specimens. Increased awareness and timely diagnosis of Balamuthia encephalitis might lead to earlier initiation of therapy and improved outcome.

Aims: The stereotactic brain biopsy is an essential diagnostic procedure in modern neurologic patient management. A side-cutting biopsy needle is one of the most widely used needle types. Recently we found a characteristic tissue artifact named “peripheral compressing artifact” in the brain tissues biopsied using a side-cutting needle of Leksell’s system. We investigate prevalence, possible cause and its clinical implication of this type of artifact. Materials and methods: We examined the biopsies from 80 patients (44 cases of gliomas, 13 lymphomas, 7 germ cell tumors, 2 other tumors, 1 metastatic carcinoma, 4 non-tumorous conditions such as demyelinating disease and 8 non-diagnostic) in the stereotactic biopsy group with a suspected brain tumor, who underwent a stereotactic brain biopsy using side-cutting needle of Leksell’s system. We also evaluated 16 cases of open brain biopsies without Leksell’s system as a control group. Results: The artifact is a semi-circular or band-like tissue compression in the periphery of the biopsied tissue. This artifact was found in 30 (37.5%) out of 80 cases and 57 (11.9%) out of 477 biopsied pieces. It might be produced during rotating of the inner cannula of the biopsy needle. Histologically, it might be misinterpreted as “hypercellular”, “spindle”, “well circumscribed”, or rarely as “pseudopalisading” especially in glioma. Conclusions: Awareness of this artifact would help making the appropriate pathological diagnosis for glioma.

Objective: Patients with acute to subacute neurologic decline undergo a battery of imaging and laboratory tests to determine a diagnosis and treatment plan. Often, after an extensive evaluation, a brain biopsy is recommended as yet another tool to assist in determining the diagnosis. The goal of this retrospective cohort analysis is to measure the sensitivity of open brain biopsy in this patient population, compare these results with the preoperative presumed diagnosis, and evaluate if the biopsy result significantly alters treatment. Methods: The authors reviewed the medical records of 135 consecutive patients who underwent open brain biopsies for acute to subacute progressive neurologic decline between January 1999 and September 2008 at a single institution. All patients with mass lesions, with HIV/AIDS, and who were younger than 20 years of age were excluded from the study. Fifty-one patients met these criteria and all preoperative tests, imaging, and treatment plans were examined and compared with postbiopsy interventions to determine the impact of the biopsy on patient outcome. Results: The sensitivity of open brain biopsy at our institution was 35%. The most common preoperative presumed diagnosis was vasculitis and the most common postoperative finding was Creutzfeldt-Jakob disease, followed by amyloid angiopathy. Postbiopsy hemorrhage was a complication in 4% of patients. Treatment plans changed as a direct result of the biopsy in 8% of patients, and in only 4% did the biopsy findings make a difference in disease course. Conclusion: In patients with progressive neurologic decline without a radiographic mass lesion or immunodeficiency, open brain biopsy often fails to provide a diagnosis and even more rarely does it significantly alter treatment.

A 54 year old lady presented with lethargy and 15 kg weight loss over the past year. CT scan of the head revealed left temporal lobe hypodensity with a discrete area of hemorrhage within the left mesial temporal lobe. Due to concerns about impending central herniation, lumbar puncture was not performed. MRI of the brain showed a large lesion of the left temporal lobe, extending to the left frontal lobe, and very patchy meningeal enhancement. There was a noncontiguous lesion of the right insula. A differential diagnosis of herpes simplex encephalitis (HSE) and multifocal infiltrative glioma was entertained. MR spectroscopy demonstrated an increased choline peak at the level of the medial left temporal lobe and MR perfusion demonstrated patchy areas of hyperperfusion within the left anterior temporal lobe, both suggestive of neoplastic disease. Following open brain biopsy, pathology revealed herpes simplex virus (HSV) positive nuclei in the cortex and subcortical white matter. As both herpes simplex encephalitis and low-grade glioma demontrate MRI findings of hypointensity on T1 images and hyperintensity on T2 images, the diagnosis of herpes encephalitis can be clouded by confounding factors, especially when cerebrospinal fluid (CSF) cannot be obtained.

Patients with acute to subacute neurologic decline undergo a battery of imaging and laboratory tests to determine a diagnosis and treatment plan. Often, after an extensive evaluation, a brain biopsy is recommended as yet another tool to assist in determining the diagnosis. The goal of this retrospective cohort analysis is to measure the sensitivity of open brain biopsy in this patient population, compare these results with the preoperative presumed diagnosis, and evaluate if the biopsy result significantly alters treatment. The authors reviewed the medical records of 135 consecutive patients who underwent open brain biopsies for acute to subacute progressive neurologic decline between January 1999 and September 2008 at a single institution. All patients with mass lesions, with HIV/AIDS, and who were younger than 20 years of age were excluded from the study. Fifty-one patients met these criteria and all preoperative tests, imaging, and treatment plans were examined and compared with postbiopsy interventions to determine the impact of the biopsy on patient outcome. The sensitivity of open brain biopsy at our institution was 35%. The most common preoperative presumed diagnosis was vasculitis and the most common postoperative finding was Creutzfeldt-Jakob disease, followed by amyloid angiopathy. Postbiopsy hemorrhage was a complication in 4% of patients. Treatment plans changed as a direct result of the biopsy in 8% of patients, and in only 4% did the biopsy findings make a difference in disease course. In patients with progressive neurologic decline without a radiographic mass lesion or immunodeficiency, open brain biopsy often fails to provide a diagnosis and even more rarely does it significantly alter treatment.

Infection with the saprophagous nematode Halicephalobus species is uncommon but has been reported in horses worldwide. Only 3 human cases have been previously described, all of which have been fatal. We report a fourth fatal case, which occurred in a 39-year-old woman who presented with meningeal signs, altered mental status, and a prodromal pruritic rash. Diagnostic evaluation included an open brain biopsy, which was diagnosed as granulomatous vasculitis. The patient subsequently died after a course of steroids and cyclophosphamide. At autopsy, a robust perivascular mixed inflammatory infiltration of the brain parenchyma, meninges, and ventricular system was present with larval forms and mature nematodes morphologically consistent with Halicephalobus deletrix . Although extremely rare, this organism needs to be considered in the differential diagnosis of human helminthic infection of the central nervous system.

Infection with the saprophagous nematode Halicephalobus species is uncommon but has been reported in horses worldwide. Only 3 human cases have been previously described, all of which have been fatal. We report a fourth fatal case, which occurred in a 39-year-old woman who presented with meningeal signs, altered mental status, and a prodromal pruritic rash. Diagnostic evaluation included an open brain biopsy, which was diagnosed as granulomatous vasculitis. The patient subsequently died after a course of steroids and cyclophosphamide. At autopsy, a robust perivascular mixed inflammatory infiltration of the brain parenchyma, meninges, and ventricular system was present with larval forms and mature nematodes morphologically consistent with Halicephalobus deletrix . Although extremely rare, this organism needs to be considered in the differential diagnosis of human helminthic infection of the central nervous system.