Primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (CNS) is an uncommon inflammatory disorder, with highly variable clinical presentation. It needs to be differentiated from several mimickers, such as CNS involvement in systemic vasculitides, connective tissue disorders, infectious disease, and leukodystrophy as well as neoplastic diseases. The diagnosis requires a combination of clinical and laboratory investigations, multimodal imaging, and histopathological examination, which should be available for confirmation. In the present paper, the histopathological features of primary angiitis of the CNS are described and highlighted to help pathologists avoid misdiagnosis of a treatable acquired disease.

Spectrum of MRI findings in central nervous system affection in Lyme neuroborreliosis.

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.

PET imaging of TREM1 identifies CNS-infiltrating myeloid cells in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that causes substantial morbidity and diminished quality of life. Evidence highlights the central role of myeloid lineage cells in the initiation and progression of MS. However, existing imaging strategies for detecting myeloid cells in the CNS cannot distinguish between beneficial and harmful immune responses. Thus, imaging strategies that specifically identify myeloid cells and their activation states are critical for MS disease staging and monitoring of therapeutic responses. We hypothesized that positron emission tomography (PET) imaging of triggering receptor expressed on myeloid cells 1 (TREM1) could be used to monitor deleterious innate immune responses and disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first validated TREM1 as a specific marker of proinflammatory, CNS-infiltrating, peripheral myeloid cells in mice with EAE. We show that the 64Cu-radiolabeled TREM1 antibody-based PET tracer monitored active disease with 14- to 17-fold higher sensitivity than translocator protein 18 kDa (TSPO)-PET imaging, the established approach for detecting neuroinflammation in vivo. We illustrate the therapeutic potential of attenuating TREM1 signaling both genetically and pharmacologically in the EAE mice and show that TREM1-PET imaging detected responses to an FDA-approved MS therapy with siponimod (BAF312) in these animals. Last, we observed TREM1+ cells in clinical brain biopsy samples from two treatment-naïve patients with MS but not in healthy control brain tissue. Thus, TREM1-PET imaging has potential for aiding in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.

Rara presentación de un linfoma espinal: informe de caso y diagnóstico mediante resonancia magnética / Rare presentation of a spinal lymphoma: case report and diagnosis by magnetic resonance imaging

El linfoma primario del sistema nervioso central es una forma de enfermedad extraganglionar originada en el cerebro, la leptomeninges, la médula espinal o los ojos. Los tumores espinales son neoplasias de baja prevalencia y pueden causar una morbimortalidad neurológica considerable. El linfoma aislado que surge dentro del conducto dural es la forma menos común de linfoma primario del sistema nervioso central: representa aproximadamente el 1% de los casos y se observa más a menudo en el contexto de diseminación secundaria que como el sitio primario de origen. Los síntomas son inespecíficos y dependen del nivel espinal involucrado. La presentación es insidiosa e incluye dorsalgia, debilidad y dificultad progresiva para la deambulación. La resonancia magnética es la modalidad de elección para búsqueda de lesiones dentro del conducto espinal/raquídeo, en pacientes que presentan síntomas neurológicos. El tratamiento quirúrgico no resulta útil, y el objetivo principal de la cirugía es conocer el diagnóstico histológico. (AU)

A primary central nervous system lymphoma is a form of extranodal disease originating in the brain, leptomeninges, spinal cord, or eyes. Spinal tumors are low-prevalence neoplasms and can cause considerable neurological morbidity and mortality. An isolated lymphoma emerging within the dural canal is the rarest form of primary central nervous system lymphoma: it accounts for approximately 1% of cases occurring more often in the context of secondary dissemination than as the primary site of origin. Symptoms are nonspecific and depend on the spinal level involved. The presentation is insidious and includes dorsalgia, weakness, and progressive difficulty in ambulatory function. MRI is the modality of choice to search for lesions within the spinal/rachial canal in patients presenting with neurological symptoms. Surgical treatment is not helpful, and the main objective of surgery is to know the histological diagnosis. (AU)

Neuro-Sjögren: A clinical-radiological paradox affecting the central nervous system.

Neurological manifestations can occur in up to 67% of patients with primary Sjögren's Syndrome, also known as Neuro-Sjogren's syndrome (NSS), and a 5% can present central nervous system involvement, with severe and possibly lethal consequences. We present the radiological follow-up of a patient with NSS who consulted for limb weakness and visual loss, and fourteen years later developed sicca symptoms. She was diagnosed with a saliva gland biopsy, and started treatment with steroids, cyclophosphamide, and then rituximab, achieving a favourable clinical response and stabilization of lesions. We discuss key aspects regarding the clinical presentation, diagnosis, imaging, and treatment of this elusive disease.

Update on pathology of central nervous system inflammatory demyelinating diseases.

Multiple sclerosis (MS) is by far the most common central nervous system inflammatory demyelinating disease (CNS-IDD). It is diagnosed according to detailed criteria based on clinical definitions, magnetic resonance imaging (MRI) and cerebrospinal fluid findings. However, in rare instances, atypical syndromes associated with CNS demyelination, such as unusual MRI findings or poor response to standard treatment, may eventually necessitate a CNS biopsy with neuropathological examination. Pathology remains the gold standard in the differentiation of atypical CNS-IDDs, the recognition of which is essential for establishing the correct prognosis and optimal therapy. However, one must bear in mind that between different CNS-IDDs there are still overlapping features, even in the pathology. In this review, we compare and highlight contrasts within a spectrum of CNS-IDDs from the neuropathological perspective. We characterise pathological hallmarks of active vs chronic multiple sclerosis. Also, we define differences in the pathology of MS, acute disseminated encephalomyelitis (ADEM), aquaporin 4-IgG positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOsd), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Detailed description of the particular CNS-IDD pathology is crucial on an individual patient level (when clinically justified in atypical cases) but also from a broader perspective i.e. to advance our understanding of the complex disease mechanisms. Recent immunobiological and pathological discoveries have led to the description of novel inflammatory CNS disorders that were previously classified as rare MS variants, such as NMOsd and MOGAD. Multiple sclerosis remains an umbrella diagnosis, as there is profound heterogeneity between patients. Advances in neuropathology research are likely to disentangle and define further CNS-IDDs that used to be categorised as multiple sclerosis.

An estimate of rate of deviation from NCCN guideline recommendations for central nervous system imaging in trials forming basis for drug approval in first line advanced non-small cell lung cancer (NSCLC).

IMPORTANCE: It is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols. OBJECTIVE: We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling). MAIN OUTCOMES AND MEASURES: Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging. RESULTS: A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations. CONCLUSIONS AND RELEVANCE: The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.

Imaging immune responses in neuroinflammatory diseases.

Innate and adaptive immune responses in the central nervous system (CNS) play critical roles in the pathogenesis of neurological diseases. In the first of a two-part special issue, leading researchers discuss how imaging modalities are used to monitor immune responses in several neurodegenerative diseases and glioblastoma and brain metastases. While comparative studies in humans between imaging and pathology are biased towards the end stage of disease, animal models can inform regarding how immune responses change with disease progression and as a result of treatment regimens. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are frequently used to image disease progression, and the articles indicate how one or more of these modalities have been applied to specific neuroimmune diseases. In addition, advanced microscopical imaging using two-dimensional photon microscopy and in vitro live cell imaging have also been applied to animal models. In this special issue (Parts 1 and 2), as well as the imaging modalities mentioned, several articles discuss biomarkers of disease and microscopical studies that have enabled characterization of immune responses. Future developments of imaging modalities should enable tracking of specific subsets of immune cells during disease allowing longitudinal monitoring of immune responses. These new approaches will be critical to more effectively monitor and thus target specific cell subsets for therapeutic interventions which may be applicable to a range of neurological diseases.

Mitochondrial Strokes: Diagnostic Challenges and Chameleons.

Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected in anyone with an acute/subacute onset of focal neurological symptoms at any age and are usually driven by seizures. Suggestive features of an underlying mitochondrial pathology include evolving MRI lesions, often originating within the posterior brain regions, the presence of multisystemic involvement, including diabetes, deafness, or cardiomyopathy, and a positive family history. The diagnosis of MELAS has important implications for those affected and their relatives, given it enables early initiation of appropriate treatment and genetic counselling. However, the diagnosis is frequently challenging, particularly during the acute phase of an event. We describe four cases of mitochondrial strokes to highlight the considerable overlap that exists with other neurological disorders, including viral and autoimmune encephalitis, ischemic stroke, and central nervous system (CNS) vasculitis, and discuss the clinical, laboratory, and imaging features that can help distinguish MELAS from these differential diagnoses.

Clinical characterization and outcomes of 85 patients with neurosarcoidosis.

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Encephalomyelitis associated with rheumatoid arthritis: a case report.

Encephalitis/encephalomyelitis in the course of rheumatoid arthritis (RA) remains a matter of debate. We present a case of a patient with encephalomyelitis associated with RA confirmed with post-mortem neuropathological examination. A 68-year-old woman with a long-standing, seropositive history of RA presented progressive disturbances of consciousness. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed an increase of signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images with corresponding restricted diffusion involving cerebral peduncles, pons, medulla oblongata, and cervical spinal cord and mild contrast-enhancement of the right cerebral peduncle. Extensive radiological and laboratory testing, including autoantibodies to paraneoplastic anti-neuronal and neuronal cell surface antigens, were all negative except for elevated rheumatoid factor. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with mononuclear cell predominance, mildly increased protein level, and negative viral PCRs, bacterial cultures, flow cytometry, and neuronal surface antibodies. Despite intensive treatment with corticosteroids, antibiotics, antiviral drugs, and intravenous immunoglobulin the patient died after 3 months of hospitalization. Post-mortem neuropathological examination revealed numerous, disseminated, heterochronous ischaemic lesions, rarely with haemorrhagic transformation, predominantly in the brainstem, and widespread, diffuse microglia and T-cell infiltrations with neuronal loss and astrogliosis, most severe in the frontal and temporal lobes. Mild, perivascular lymphocyte T infiltrations involved particularly small and medium-sized vessels and were associated with brainstem ischaemic lesions. The neuropathological picture confirmed diagnosis of encephalomyelitis, which together with the clinical course suggested association with RA. Concluding, encepha-lomyelitis due to RA remains a challenging, controversial entity that needs further research and the establishment of effective diagnostic and treatment guidelines.

A case of central nervous system lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates: a case report and literature review.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disease with angiocentric and angiodestructive infiltrates, and by definition, Epstein-Barr virus (EBV)-associated B-cell malignancy. It most frequently involves the lung, and in some cases, the lesions are confined to the central nervous system (isolated CNS-LYG). However, it remains a controversial disease in terms of pathophysiology, especially in those confined to the CNS. We report the case of a 37-year-old man with CNS lesion pathologically characterized by angiocentric, T-cell-rich lymphoid cell infiltrates that resembled CNS-LYG. The lesion was clinically aggressive with subacute onset and irregular ring-like enhancement on MRI. The resected specimen showed no cytological atypia, EBV-infected cells, or monoclonality for IgH and TCR gene rearrangements. Considering the possibility of latent malignancy, the patient was successfully treated with corticosteroid and chemoradiotherapy with high-dose methotrexate. The present case and the literature suggest that EBV-negative CNS lesions with angiocentric lymphoid infiltrates are probably heterogeneous in their pathogenesis, including those that could fit into the so-called CNS-LYG and those with T-cell predominance. The accumulation of similar cases is warranted for the classification and appropriate treatment of these lesions.

Differential imaging of atypical demyelinating lesions of the central nervous system.

The detection of atypical and sometimes aggressive or tumefactive demyelinating lesions of the central nervous system often poses difficulties in the differential diagnosis. The clinical presentation is generally aspecific, related to the location and similar to a number of different lesions, including neoplasms and other intracranial lesions with mass effect. CSF analysis may also be inconclusive, especially for lesions presenting as a single mass at onset. As a consequence, a brain biopsy is frequently performed for characterization. Advanced MRI imaging plays an important role in directing the diagnosis, reducing the rate of unnecessary biopsies and allowing a prompt start of therapy that is often crucial, especially in the case of infratentorial lesions. In this review, the main pattern of presentation of atypical inflammatory demyelinating diseases is discussed, with particular attention on the differential diagnosis and how to adequately define the correct etiology.

Neuronal intermediate filament IgGs in CSF: Autoimmune Axonopathy Biomarkers.

OBJECTIVES: To describe CSF-defined neuronal intermediate filament (NIF) autoimmunity. METHODS: NIF-IgG CSF-positive patients (41, 0.03% of 118599 tested, 1996-2019) were included (serum was neither sensitive nor specific). Criteria-based patient NIF-IgG staining of brain and myenteric NIFs was detected by indirect immunofluorescence assay (IFA); NIF-specificity was confirmed by cell-based assays (CBAs, alpha internexin, neurofilament light [NF-L]), heavy-[NF-H] chain). RESULTS: Sixty-one percent of 41 patients were men, median age, 61 years (range, 21-88). Syndromes were encephalopathy predominant (23), cerebellar ataxia predominant (11), or myeloradiculoneuropathies (7). MRI abnormalities (T2 hyperintensities of brain, spinal cord white matter tracts. and peripheral nerve axons) and neurophysiologic testing (EEG, EMG, evoked potentials) co-localized with clinical neurological phenotypes (multifocal in 29%). Thirty patients (73%) had ≥ 1 immunological perturbation: cancer (paraneoplastic), 22; systemic infection (parainfectious [including ehrlichosis, 3] or HIV), 7; checkpoint-inhibitor cancer immunotherapy, 4; other, 5. Cancers were as follows: neuroendocrine-lineage carcinomas, 12 (small cell, 6; Merkel cell, 5; pancreatic, 1 [11/12 had NF-L-IgG detected, versus 8/29 others, P = 0.0005]) and other, 11. Onset was predominantly subacute (92%) and accompanied by inflammatory CSF (75%), and immunotherapy response (77%). In contrast, CSF controls (15684 total) demonstrated NIF-IgG negativity (100% of test validation controls), and low frequencies of autoimmune diagnoses (20% of consecutively referred clinical specimens) and neuroendocrine-lineage carcinoma diagnosis (3.1% vs. 30% of NIF cases), P < 0.0001. Median NF-L protein concentration was higher in 8 NF-L-IgG-positive patients (median, 6718 ng/L) than 16 controls. INTERPRETATION: Neurological autoimmunity, defined by CSF-detected NIF-IgGs, represents a continuum of treatable axonopathies, sometimes paraneoplastic or parainfectious.

Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review.

Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other's neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol's damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.

Clinical and Radiological Characteristics of Children and Adults With First-Attack Myelin Oligodendrocyte Glycoprotein Antibody Disease and Analysis of Risk Factors for Predicting the Severity at Disease Onset in Central China.

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.

Pediatric CNS imaging and long-term effects of irradiation in pediatric oncology patients.

BACKGROUND: The aim of this study was to evaluate post-irradiation changes in the central nervous system (CNS) detected using magnetic resonance (MR) imaging. METHODS: Magnetic resonance images of 15 children with CNS tumors treated through whole-brain irradiation over 10 years were reviewed retrospectively. Variables such as age at the time of irradiation, total radiation dose, treatment length, and time interval between irradiation and MR changes, were evaluated. RESULTS: All patients included in the study had imaging abnormalities of the CNS. Eight patients (53%) developed CNS abnormalities within a short period of time - only a few months after irradiation (mean 4.8 months). Seven patients (47%) developed CNS abnormalities within a long time interval after treatment (mean 4.6 years). In almost all patients, a T2 increase in supra- and infratentorial white matter was observed. Follow-up examinations showed nine patients (60%) with cerebellar atrophy. CONCLUSIONS: In this sample of pediatric patients who underwent whole-brain irradiation, the time receiving irradiation was not related to the severity of the MR changes. A correlation between the age of the child or the length of the radiotherapy and the extent of the changes could not be confirmed. However, we observed a trend towards stronger brain parenchymal degeneration with cystic changes in the younger age group of children in our sample. Older children who received irradiation seem to be more susceptible to vascular dysplasia with cavernous hemangiomas and microbleeding.

Isolated blast crisis relapse in the central nervous system of a patient treating for a chronic myelogenous leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t (9;22) and the BCR-ABL fusion gene. The condition is relatively rare, accounting for 2.0% to 3.0% of childhood leukemia cases. CML has historically been a triphasic disease. Most patients are diagnosed in chronic phase. Without treatment, it inevitably progresses into a more aggressive accelerated phase and blast crisis. Some proportion of CML cases of blastic transformation develop an extramedullary disease that involves rarely central nervous system. This report describe an extremely rare case of 13-year-old girl with CML and extramedullary blast crisis in the central nervous system. Treatment options and monitoring of disease response are discussed.