Isolated Central Nervous System Involvement Research Articles

Peripheral nervous system involvement accompanies central nervous system involvement in anti-glial fibrillary acidic protein (GFAP) antibody-related disease.

Glial fibrillary acidic protein (GFAP) is expressed by astrocytes in the central nervous system (CNS), but also by immature and regenerative Schwann cells in the peripheral nervous system (PNS). GFAP antibodies (GFAP-Abs) in cerebrospinal fluid (CSF) have been mainly described in patients with meningoencephalomyelitis. We aimed to study PNS symptoms in patients with CSF GFAP-Abs. We retrospectively included all patients tested positive for GFAP-Abs in the CSF by immunohistochemistry and confirmed by cell-based assay expressing human GFAPα since 2017, from two French reference centers. In a cohort of 103 CSF GFAP-Abs patients, 25 (24%) presented with PNS involvement. Among them, the median age at onset was 48years and 14/25 (56%) were female. Abnormal electroneuromyography was observed in 11/25 patients (44%), including eight isolated radiculopathies, one radiculopathy associated with polyneuropathy, one radiculopathy associated with sensory neuronopathy, and one demyelinating polyradiculoneuropathy. Cranial nerve involvement was observed in 18/25 patients (72%). All patients except one had an associated CNS involvement. The first manifestation of the disease concerned the PNS in three patients. First-line immunotherapy was administered to 18/24 patients (75%). The last follow-up modified Rankin Scale was ≤ 2 in 19/23 patients (83%). Patients with PNS involvement had significantly more bladder dysfunction than patients with isolated CNS involvement (68 vs 40.3%, p = 0.031). PNS involvement in GFAP-Abs autoimmunity is heterogeneous but not rare and is mostly represented by acute or subacute cranial nerve injury and/or lower limb radiculopathy. Rarely, PNS involvement can be the first manifestation revealing the disease.

Isolated CNS involvement in eosinophilic granulomatosis with polyangiitis treated with mepolizumab: A case report

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis disease involving small-sized vessels. The literature has reported involvement of the central nervous system (CNS) in 5% cases, and isolated CNS involvement is extremely rare. Due to its rarity and scarcity of clinical data, standardized treatment of isolated CNS involvement in EGPA is unclear. Mepolizumab, an anti-interleukin-5 monoclonal antibody, was previously introduced to treat EGPA with longer remission period, more patients showing remission, and reduction in prednisolone dose of those who already taking prednisolone compared to placebo. We describe a case of isolated CNS involvement in EGPA, confirmed by brain biopsy and treated with mepolizumab, which was refractory to conventional immunotherapy.

Central Nervous System Involvement in Epstein–Barr Virus-Related Post-Transplant Lymphoproliferative Disorders after Allogeneic Hematopoietic Stem Cell Transplantation

Central nervous system (CNS) involvement in Epstein–Barr virus-related post-transplant lymphoproliferative disorders (EBV-PTLDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poorly defined. We analyzed the incidence, clinical and pathological characteristics, and impact on outcomes of EBV-PTLDs with CNS involvement (CNS-PTLDs) in 1009 consecutive adult patients undergoing allo-HSCT at a single-center institution. Four hundred eighty-two patients received matched sibling donor (MSD) transplants, 388 umbilical cord blood transplants (UCBTs), 56 matched unrelated donor (MUD) transplants, and 83 haploidentical transplants. We detected 25 cases of biopsy-proven EBV-PTLDs. Of these, nine patients (36%) had CNS-PTLDs: six after UCBT (67%), one after MSD transplantation (11%), one after MUD transplantation (11%), and one after haploidentical transplantation (11%). The 5-year cumulative incidence risk of CNS-PTLDs was 0.9%. Median time from transplant to CNS-PTLDs was 187 days, and all patients had neurological symptoms at diagnosis. Six out of the nine cases (67%) occurred with systemic involvement, and three cases (33%) had isolated CNS involvement. The most frequent histological subtype was monomorphic EBV-PTLD, and laboratory characteristics were similar to EBV-PTLDs without CNS involvement. We observed statistical differences in the rate of positive EBV DNA detection in plasma between isolated CNS-PTLDs (detection in one out of three, 33%) and the rest of the EBV-PTLDs (100%) (P = .01). Treatment strategies included chemotherapy, radiotherapy, and T cell therapy. However, seven out of nine patients died due to progression of the CNS-PTLDs at a median time of 17 days (range, 8 to 163) from diagnosis. The 5-years overall survival in patients who developed CNS-PTLDs was 22% (95% confidence interval [CI], 7% to 75%) and 5-year treatment-related mortality was 78% (95% CI, 51% to 100%), with no statistically significant differences between CNS-PTLDs and the rest of the EBV-PTLDs. In conclusion, despite advances in EBV monitoring and treatment strategies, CNS-PTLDs remain an uncommon but serious complication after allo-HSCT, with very poor prognosis.

Primary Central Nervous System Lymphomatoid Granulomatosis: Systemic Review.

Lymphomatoid granulomatosis (LYG) is an infrequent lymphoproliferative disease that typically involves the lungs, but may also affect the central nervous system (CNS). Isolated CNS involvement is very rare, and its clinicopathological features have not been fully elucidated. Here, we systematically reviewed the English literature through PubMed to collect all relevant case reports and small case series with pathologically confirmed primary CNS-LYG. A total of 29 relevant articles with 40 cases were included in this systemic review. In cases where T cells and B cells were compared, T cells were predominant in 19 (79.2%), and B cells were predominant in 5 (20.8%). The overall infection rate of EBV was 48.1% (13/27), among which the infection rate was 40.9% (9/22) in immunocompetent patients and 80% (4/5) in immunodeficient (HIV-infected) patients. Among the patients who underwent pathological grading, 35.7% (5/14) were at grade I, 42.9% (6/14) were at grade II, and 21.4% were at grade III. In conclusion, primary CNS-LYG is closely related to EBV infection and some cases may be predominantly T-cell phenotype. Surgical resection may be effective for mass-like lesions, although there is still a lack of standard therapeutic regimen. Accurate grading of lesions is essential for treatment selection and prognosis evaluation.

Central nervous system candidiasis beyond neonates: Lessons from a nationwide study.

Candida is a yeast and is the most common cause of fungal infections worldwide. Candida central nervous system (CNS) infections are rare, severe, and poorly described. We report a retrospective study from January 2005 to December 2018 including patients aged≥28 days with proven or probable CNS candidiasis in France. Twenty-four patients were included (14 men, median age 51 years). Seventeen patients had CNS localization secondary to disseminated candidiasis from blood to CNS (10 with hematologic malignancies [HM], the seven other patients had infective endocarditis [IE]). Seven patients had isolated CNS involvement related to neurosurgery (n=2), CARD9 deficiency (n=2), intravenous drug use (n=1), diabetes mellitus (n=1), or no identified risk factor (n=1).During Candida CNS infections, brain lesions were meningitis abscesses or vascular complications. Cerebrospinal fluid (CSF) culture grew Candida spp. in 31% of cases. Forty-two percent of patients died from infection: 53% in case of disseminated infection (70% for HM) and 14% in case of localized infection.

Case study: mepolizumab prevents progression of eosinophilic granulomatosis with polyangiitis with involvement of the central nervous system which is refractory to conventional immunotherapy

Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis involving small-sized vessel. It manifests mainly as asthma or eosinophilia, but the literature reported involvement of the central nervous system (CNS) in 5%, while isolated CNS involvement is very rare. We describe a case of isolated CNS involvement of EGPA which was refractory to conventional immunotherapy and treated with mepolizumab, an anti-interluekin-5 monoclonal antibody. A previously healthy 51-year-old man was referred to the neurology department for memory decline persisting for a month. Magnetic resonance imaging (MRI) showed the multifocal lesion in the periventricular and frontal lobe. Analysis of cerebrospinal fluid revealed an elevated protein concentration and leukocytosis. Considering his age, clinical course, and laboratory findings, steroid and intravenous immunoglobulin was started for autoimmune encephalopathy. Two months after discharge, the patient experienced new symptom – gait disturbance. The follow-up MRI showed increased extent of the previous lesions and the new lesions. To confirm the diagnosis, brain biopsy was done, and the finding was consistent with EGPA. We decided to start mepolizumab as second-line treatment, and observe the stationary course and absence of further progression of the lesion in the follow-up MRI. Mepolizumab for EGPA patients was introduced to achieve protocol-defined remission and clinical benefit compared to the placebo group in the several studies. Our case signifies possibility of mepolizumab to halt further progression of the disease clinically and radiologically, for the patient with isolated CNS involvement of EGPA which is unresponsiveness to conventional immunotherapy.

Expression of CD56 is a risk factor for acute lymphocytic leukemia with central nervous system involvement in adults

ABSTRACTObjective: To gain further insights into the predisposing risk factors for central nervous system (CNS) involvement in patients with acute lymphocytic leukemia (ALL), the impact of CD56 expression in these patients was investigated.Methods: We reviewed the clinical features of CD56 expression in 588 consecutive ALL patients treated with systemic chemotherapy regimens between 2000 and 2014. The categorical data from CD56+ ALL patients were compared with those from CD56− ALL patients.Results: Among the 588 patients studied, 18.9% showed CD56 expression. The expression was significantly associated with CD33+, CD10−, CD15+, TdT−, and CD5+ immunophenotypes. After systemic chemotherapy, 8.8% patients showed CNS involvement, of which 3.2% exhibited combined recurrences and 5.6% exhibited isolated CNS involvement. The 5-year event-free survival was significantly lower for patients with CD56+ immunophenotype compared with patients with CD56− immunophenotype (22.5% vs. 32.7%, P = 0.04). Cumulative incidences of CNS involvement were significantly greater in the CD56+ cohort compared with the CD56− cohort (14.4% vs. 7.5%, P = 0.02). Multivariate analysis revealed CD56 expression to be statistically significant risk factors for CNS involvement.Conclusion: CD56 expression should be regarded as an independent risk factor for ALL with CNS involvement in adults.

Comprehensive Craniospinal Radiation for Controlling Central Nervous System Leukemia

To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.

Central nervous system involvement of hypereosinophilic syndrome: A report of 10 cases and a literature review

BackgroundThe central nervous system (CNS) may be affected in those cases of peripheral eosinophila without a secondary cause (hypereosinophilic syndrome, HES). The pathomechanism of CNS involvement in HES remained uncertain. MethodsWe included those with CNS symptoms and peripheral eosinophilia (>1500/μl) at the time of presentation. Those with identifiable causes of eosinophilia were excluded. In addition to data analysis of our cases, we reviewed the literature using the Medline database. ResultsTen patients were recruited. Half of them presented with altered mental status. None of the patients had significant risk factors such as endomyocardial disease (EMD). Their brain magnetic resonance imaging (MRI) showed multiple ischemic lesions in the border zone (BZ) and other cortical areas. In addition to our 10 cases we included 67 cases from a literature review. The total 77 cases were systemically analyzed. We found that the most common type of CNS involvement was cerebrovascular disease (CVD, 63.6%), multifocal lesions in BZ were the most common feature on MRI (45.5%), many patients presented with altered mental status (40.3%), and direct eosinophil infiltration into brain parenchyma was rare in pathologic studies and not found in the patients with CVD. Furthermore, although EMD was one of the major cardiac abnormalities (26.0%), cardiac workup more frequently showed non-EMD or normal findings. Cardiac abnormalities, altered mental status, and higher eosinophil counts were more common in those with poor outcomes, whereas an isolated CNS manifestation was more frequent in those with favorable outcomes. Finally, the presence of altered mental status was the most significant predictor of poor clinical outcomes, whereas isolated CNS involvement and corticosteroid treatment were significant predictors for favorable outcomes. ConclusionsMultiple lesions on MRI were suggestive of an embolic mechanism, but diagnostic workup failed to find significant risk factors such as EMD in the most cases. Impaired anticoagulation by eosinophilic cationic proteins could be an alternative mechanism. Direct invasion of eosinophils into the CNS was rare and those cases with isolated CNS manifestations showed a better prognosis. The preferential indirect involvement of CNS by eosinophils (“CNS-tropism”) may underlie the neurological manifestations of HES. Early administration of corticosteroid after ruling out secondary causes can be beneficial in HES with CNS manifestation.

Central Nervous System Involvement of Epstein Barr Virus Associated Lymphoproliferative Disorder in a Child with Acute Lymphoblastic Leukemia: Successful Treatment with Rituximab and Interferon-Alpha

Central nervous system (CNS) involvement of Epstein-Barr virus (EBV)-associated lymphoproliferative disease is a rare and serious complication in children with leukemia. Although rituximab therapy seems to be promising in these cases, persistent hypogammaglobulinemia may appear after treatment due to complete depletion of normal B lymphocytes in the peripheral blood. Here we report isolated CNS involvement of EBV-associated lymphoproliferative disorder in a 4-year-old boy with acute leukemia. The patient was treated with rituximab and interferon alpha; however, persistent hypogammaglobulinemia developed as a complication. Given the rarity of the complication in children receiving these agents, our experience with such a case may be helpful to others.Conflict of interest:None declared.

Secondary central nervous system (CNS) involvement in patients with diffuse large B-cell lymphoma: a therapeutic dilemma

Secondary central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) includes an isolated CNS relapse or CNS involvement with systemic disease progression. This rare but fatal clinical problem still remains a therapeutic dilemma in the management of DLBCL. However, there are limited data about its treatment outcome. In this study, we gathered 73 cases with secondary CNS involvement of DLBCL from 11 hospitals in Korea. The data were retrospectively compared according to the status of systemic disease (isolated vs. combined CNS involvement) and the use of high-dose methotrexate treatment (HD MTX). Twenty-nine patients showed isolated CNS involvement while 44 had combined CNS involvement with systemic relapse or progression. Thirty-three cases (45.2%) occurred within 6months from the initial diagnosis, and the majority of these were associated with systemic disease relapse or progression (n = 27). In isolated CNS involvement, HD MTX resulted in fewer treatment failures (3/11) than the other treatments such as other salvage chemotherapy and/or radiotherapy/intraventricular chemotherapy (14/15). However, neither HD MTX nor other treatments were effective at reducing the treatment failure rate in combined CNS involvement (8/10 and 23/30, respectively). Thus, isolated CNS involvement had a better survival than combined involvement (P = 0.008), but systemic disease progression was the main cause of death in combined as well as isolated CNS involvement. In conclusion, the prognosis of secondary CNS involvement was dismal even after intensive chemotherapy using HD MTX. Further research focusing on the development of an optimal treatment strategy is warranted.

Isolated central nervous system involvement in adult T‐cell lymphoma/leukaemia

Central nervous system (CNS) presentation of adult T-cell lymphoma/leukaemia is rare, and almost invariably associated with systemic disease. We report an unusual manifestation of adult T-cell lymphoma/leukaemia, with isolated CNS involvement and unusual imaging findings. We also describe objective response to antiviral therapy. To our knowledge, this is the first report of such presentation and response.

Posttransplant Lymphoproliferative Disorder: Significance of Central Nervous System Involvement

Background Few data exist regarding central nervous system (CNS) involvement in patients with posttransplant lymphoproliferative disorder (PTLD). The purpose of this study was to review the Israel Penn International Transplant Tumor Registry (IPITTR) experience with CNS involvement by PTLD. Methods Nine hundred ten PTLD cases from the United States were reported to the IPITTR and reviewed for CNS involvement. Results One hundred thirty-six transplant recipients with PTLD (15%) had CNS involvement. The highest incidence of CNS involvement occurred in pancreas (3 of 11; 27%) and kidney transplant recipients (76 of 429; 18%). Fifteen cases occurred in children and 121 cases in adults. For both children and adults, isolated CNS disease was associated with better survival when compared with multiple-site involvement (children: 29% vs 0%; adults: 12% vs 6%; P < .05). Three-year survival in PTLD patients with CNS involvement was 9.4% and without CNS involvement was 49.4% ( P < .01). Radiation therapy alone appeared to provide the best survival rates (25%). Conclusions CNS involvement in transplant recipients with PTLD carries an ominous prognosis; however, isolated CNS involvement has a better prognosis than CNS plus extracranial involvement. Radiation therapy alone provides the best results, but this may be a reflection of isolated CNS disease.

Vasculitis of the nervous system.

Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS."Primary angiitis of the CNS" is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.

Recurrent lymphomatoid granulomatosis and isolated CNS involvement

Lymphomatoid granulomatosis is a diseases affecting the pulmonary system which is not usually associated with involvement of the central nervous system (CNS). Isolated central nervous system involvment is rare. This case, of a 65-year-old male, was notable not only as a case of lymphomatoid granulomatosis with isolated central nervous system involvement, but also with the unusual occurrence of a temporal pattern of regression and recrudescence of individual lesions not related to therapeutic intervention.

Isolated CNS involvement in Ewing's sarcoma

Ewing's sarcoma, an uncommon malignant neoplasm of bone, represents about 10% of all the malignant primary bone tumors. The assumption that subclinical metastases are already present in patients with apparently localized tumor indicates the need for systemic therapy as an integral part of primary treatment. The usual sites of metastases are the lungs and skeletal system. Central nervous system (CNS) involvement is rare and is usually seen only in disseminated and fairly advanced disease. We report two patients in whom, after aggressive adjuvant chemotherapy, disease developed in the CNS without local recurrence. In one patient, meningeal involvement with malignant cells was identifiable in the cerebrospinal fluid; in the second patient, who presented with a space-occupying lesion, a diagnosis of arachnoid involvement was made histologically.

Actuarial risk of isolated cns involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolated CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving CNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to the CNS.