Cerebrospinal Fluid Studies Research Articles

Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts

Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (Systemic Exertion Intolerance Disorder), is a disabling and often long-lasting disease that can drastically impair quality of life and physical/social functioning of the patients. Underlying pathological mechanisms are to a large extent unknown, but the presence of autoantibodies, cytokine pattern deviations and the presentation of cognitive and autonomic nervous system related symptoms provide evidence for ME being an immunological disorder with elements of autoimmunity. Increased levels of autoantibodies binding to adrenergic and muscarinic receptors in ME-patients have been reported. It is hypothesized that these autoantibodies have pathological significance and contribute to the ME-specific symptoms, however, these observations need to be validated.This study was designed to investigate potential differences in adrenergic and muscarinic receptor autoantibody levels in plasma and cerebrospinal fluid (CSF) samples between ME patients and gender and age-matched healthy controls, and to correlate the autoantibody levels to disease severity.We collected bodyfluids and health-related questionnaires from two Swedish ME cohorts, plasma and CSF from one of the cohorts (n ​= ​24), only plasma from the second cohort (n ​= ​24) together with plasma samples (n ​= ​24) and CSF (n ​= ​6) from healthy controls.All samples were analysed for IgG autoantibodies directed against Alpha- (α1, α2) and Beta- (β1-3) adrenergic receptors and Muscarinic (M) 1–5 acetylcholine receptors using an ELISA technique. The questionnaires were used as measures of disease severity.Significant increases in autoantibody levels in ME patients compared to controls were found for M3 and M4 -receptors in both cohorts and β1, β2, M3 and M4-receptors in one cohort. No significant correlations were found between autoantibody levels and disease severity. No significant levels of autoantibodies were detected in the CSF samples. These findings support previous findings that there exists a general pattern of increased antibody levels to adrenergic and muscarinic receptors within the ME patient group. However, the role of increased adrenergic and muscarinic receptor autoantibodies in the pathogenesis of ME is still uncertain and further research is needed to evaluate the clinical significance of these findings.

Pediatric Inflammatory and Autoimmune Neurologic Disorders at a Tertiary Medical Center.

To describe the spectrum of pediatric inflammatory neurologic diseases and compare the sensitivity of ancillary testing for these diagnoses. We analyzed clinical features and outcomes of 98 children with an immune-mediated central nervous system disorder. We compared sensitivities of each diagnostic modality. We identified the following diagnoses: acute cerebellar ataxia (n = 14; 14.3%), acute demyelinating encephalomyelitis (n = 13; 13.3%), multiple sclerosis (MS) (n = 18; 18.4%), anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis) (n = 15; 15.3%), encephalitis not otherwise specified (n = 12; 12.2%), and "Other" (n = 26; 26.5%). "Other" included acute transverse myelitis, neuromyelitis optica, central nervous system lupus, primary central nervous system vasculitis, Rasmussen encephalitis, opsoclonus myoclonus ataxia syndrome, and clinically isolated syndrome. The mean age of onset of all diagnoses was 7.9 ± 5.5 years. The diagnostic sensitivity of magnetic resonance imaging (MRI) for acute demyelinating encephalomyelitis and multiple sclerosis was 92.3% and 94.4%, respectively. Cerebrospinal fluid was sensitive for multiple sclerosis in 92.3%, where 75% of patients had cerebrospinal fluid oligoclonal bands. Electroencephalogram (EEG) coupled with cerebrospinal fluid studies was highly sensitive for anti-NMDAR encephalitis (100%). EEG was sensitive for acute demyelinating encephalomyelitis and encephalitis not otherwise specified (77.8% and 80%). No diagnostic studies were sensitive for acute cerebellar ataxia. Seventy-three percent of patients with multiple sclerosis had residual deficits. Thirty-six percent of anti-NMDAR encephalitis patients were nonverbal and wheel-chair bound. We found that MRI is useful for detecting multiple sclerosis and acute demyelinating encephalomyelitis, cerebrospinal fluid is helpful in diagnosing multiple sclerosis and anti-NMDAR encephalitis, and EEG is often abnormal in suspected anti-NMDAR encephalitis, acute demyelinating encephalomyelitis, and encephalitis not otherwise specified. Neurologic outcome at follow-up was unfavorable in patients with multiple sclerosis and anti-NMDAR encephalitis.

Immune reconstitution inflammatory syndrome in the central nervous system: Limitations for diagnosis in resource limited settings

IntroductionThe diagnosis of IRIS is based on evidence of clinical worsening and immune reconstitution in the setting of combined antiretroviral therapy (cART) initiation. While central nervous system IRIS (CNS IRIS) is thought to be prevalent in resource limited settings (RLS), its identification is constrained by limited data on pre-treatment HIV disease and diagnostic testing. A diagnosis can be improved with neuroimaging and cerebrospinal fluid (CSF) studies, which are not universally available in RLS. This study evaluated whether diagnoses of CNS IRIS could be achieved in a resource limited setting based on established criteria. MethodsA retrospective chart review of HIV+ individuals, on ARVs at the time of presentation in two cohort studies of suspected CNS opportunistic infection or tuberculous (TB) meningitis who were admitted to a tertiary care facility in Lusaka, Zambia. ResultsUsing currently validated criteria, none of the 254 participants evaluated could be diagnosed with CNS IRIS, as there was no information on post-treatment trajectory of HIV viral loads or CD4 counts. Only one participant had a definitive, non-IRIS infectious diagnosis based on comprehensive testing. Of the remaining 253 patients, 68 (27%) had an identified potential CNS pathogen, 92 (36%) had inflammatory CSF in the absence of a pathogen, and 94 (37%) had normal CSF despite presenting with CNS symptoms. ConclusionThe absence of HIV disease trajectory data, and lack of comprehensive diagnostic testing, compounded by a high prevalence of infectious pathogens, substantially limits the ability to diagnose CNS IRIS in RLS.

IVIG in childhood primary angiitis of the central nervous system: A case report

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy.A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years. Brain computed tomography scans revealed fine calcification in the right temporal and occipital lobes. Brain magnetic resonance imaging scans revealed white matter lesions, with gadolinium enhancement, which waxed, waned, and migrated for 1 year, without immunomodulatory therapies. A cerebrospinal fluid study showed pleocytosis (12 cells per µl). No clinical or serological findings suggested systemic inflammation or vasculitis. Brain angiography was unremarkable. Brain biopsy revealed thickened and hyalinized small vessels, with intramural infiltration of inflammatory cells, which confirmed the diagnosis of small-vessel PACNS. Because the patient developed surgical site infection following biopsy, the administration of monthly IVIG (2 g/kg) was prescribed, instead of immunosuppressive agents. After IVIG therapy, the patient remained stable, except for a single episode of mild radiological exacerbation at 16 months, which occurred when the IVIG interval was expanded. Oral prednisone was added and gradually tapered. At 50 months, his intellectual abilities and motor functions were normal, although he showed residual upper-left homonymous quadrantanopia and post-exercise headache. A temporary headache, associated with the immunoglobulin infusion, was resolved by slowing the infusion rate. PACNS should be treated aggressively to improve prognosis. However, when immunosuppressants are contraindicated, IVIG may be an alternative therapeutic option.

Plasma and Cerebrospinal Fluid Candidate Biomarkers of Neonatal Encephalopathy Severity and Neurodevelopmental Outcomes

To identify candidate biomarkers in both plasma and cerebrospinal fluid (CSF) that are associated with neonatal encephalopathy severity measured by encephalopathy grade, seizures, brain injury by magnetic resonance imaging (MRI), and neurodevelopmental outcomes at 15-30months. A retrospective cohort study of plasma (N=155, day of life 0-1) and CSF (n = 30, day of life 0-7) from neonates with neonatal encephalopathy and healthy neonatesborn at term (N=30, ≥36weeks of gestation) was conducted. We measured central nervous system necrosis (glial fibrillary acidic protein [GFAP], neurogranin [NRGN], tau), inflammatory (interleukin [IL]-6, IL-8, IL-10), and trophic (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor) proteins. Clinical outcomes were Sarnat scores of encephalopathy, seizures, MRI scores, and Bayley Scales of Infant and Toddler Development III at 15-30months. Plasma NRGN, tau, IL-6, IL-8, and IL-10 were greater, whereas BDNF and vascular endothelial growth factor were lower in patients with neonatal encephalopathy vs controls. In plasma, tau, GFAP, and NRGN were directly and BDNF inversely associated with encephalopathy grade. IL-6 was inversely related to seizures. Tau was directly related to MRI abnormalities. Tau was inversely associated with Bayley Scales of Infant and Toddler Development III cognitive and motor outcomes. In CSF, NRGN was inversely associated with cognitive, motor, and language measures. GFAP, IL-6, and IL-10 were inversely related to cognitive and motor outcomes. IL-8 was inversely related to motor outcomes. CSF candidate biomarkers showed no significant relationships with encephalopathy grade, seizures, or MRI abnormalities. Plasma candidate biomarkers predicted encephalopathy severity, seizures, MRI abnormalities, and neurodevelopmental outcomes at 15-30months.

Tuberculomas cerebrales simulando enfermedad metastásica

La tuberculosis es la principal causa de muerte debido a un agente infeccioso en el mundo, la afección del sistema nervioso central representa aproximadamente el 1% de todos los casos extrapulmonares. Provoca más de dos millones de muertes anuales y el 98% de estos casos ocurren en países en vías de desarrollo. Su presentación puede ser atípica, lo que conlleva al diagnóstico tardío y en ocasiones erróneo, principalmente en pacientes inmunocompetentes sin ningún otro factor de riesgo aparente, donde la demora diagnóstica es cuatro veces mayor que en inmunocomprometidos, el diagnostico lo constituye la alta sospecha clínica, apoyados por el estudio de líquido cefalorraquídeo y de imágenes, un tratamiento pronto y oportuno contribuye significativamente en el desenlace del paciente.
 A continuación, se presenta el caso de una paciente femenina de 42 años de edad inmunocompetente, quien tuvo una presentación insidiosa, lo cual demoró su diagnóstico.

Clinical features and diagnosis of tuberculous meningoencephalitis in patients infected with human immunodeficiency virus

The results of a prospective study of 66 patients aged 32,63,8 years infected with the human immunodeficiency virus who were treated in an anti-tuberculosis medical organization for tuberculosis meningoencephalitis are presented. Of these, 49 (74,2%) were newly diagnosed with tuberculosis, and 17 (25,8%) had relapses and chronic forms of tuberculosis. According to social characteristics, patients were distributed as follows: working - 9 (13,6%), non-working - 57 (86,4%), disabled people with tuberculosis - 4 (6,1%), persons who previously served their sentences in prison - 48 (72,7%). All the surveyed patients had bad habits: they continued to actively use psychoactive substances - 52 (78,8%) people, abused alcohol - 43 (65,2%), smoked - 60 (90,1%). In 97% of cases, tuberculosis of the meninges and Central nervous system was a complication of respiratory tuberculosis: tuberculosis of the intra-thoracic lymph nodes - 42,4%, disseminated pulmonary tuberculosis - 27,3%, infiltrative pulmonary tuberculosis - 22,7%, and caseous pneumonia- 7,6%. The most effective method for diagnosing the tuberculosis etiology of meningoencephalitis in patients infected with the human immunodeficiency virus is the study of cerebrospinal fluid using a polymerase chain reaction. Deoxyribonucleic acid of Mycobacterium tuberculosis was detected in 31 (47%) patients. The characteristics of the cerebrospinal fluid in the examined patients are presented as follows: a decrease in glucose in 45 (68,2%) patients, an increase in protein in 59 (89,4%), and cytosis at the upper limit of normal values in 10 (15,6%). High mortality rates (47,7%) in patients infected with the human immunodeficiency virus in combination with tuberculosis meningoencephalitis are associated with a high degree of immunosuppression.

Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid.

Molecular classification of medulloblastoma (MB) is well-established and reflects the cell origin and biological properties of tumor cells. However, limited data is available regarding the MB tumor microenvironment. Here, we present a mass spectrometry-based multi-omics pilot study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified characteristic tumor markers, including FSTL5, ART3, and FMOD, and revealed a strong prevalence of anti-inflammatory and tumor-promoting proteins characteristic for alternatively polarized myeloid cells in MB samples. The up-regulation of ADAMTS1, GAP43 and GPR37 indicated hypoxic conditions in the CSF of MB patients. This notion was independently supported by metabolomics, demonstrating the up-regulation of tryptophan, methionine, serine and lysine, which have all been described to be induced upon hypoxia in CSF. While cyclooxygenase products were hardly detectable, the epoxygenase product and beta-oxidation promoting lipid hormone 12,13-DiHOME was found to be strongly up-regulated. Taken together, the data suggest a vicious cycle driven by autophagy, the formation of 12,13-DiHOME and increased beta-oxidation, thus promoting a metabolic shift supporting the formation of drug resistance and stem cell properties of MB cells. In conclusion, the different omics-techniques clearly synergized and mutually supported a novel model for a specific pathomechanism.

Quantitative phenotype scan statistic (QPSS) reveals rare variant associations with Alzheimer\u2019s disease endophenotypes

BackgroundCurrent sequencing technologies have provided for a more comprehensive genome-wide assessment and have increased genotyping accuracy of rare variants. Scan statistic approaches have previously been adapted to genetic sequencing data. Unlike currently-employed association tests, scan-statistic-based approaches can both localize clusters of disease-related variants and, subsequently, examine the phenotype association within the resulting cluster. In this study, we present a novel Quantitative Phenotype Scan Statistic (QPSS) that extends an approach for dichotomous phenotypes to continuous outcomes in order to identify genomic regions where rare quantitative-phenotype-associated variants cluster.ResultsWe demonstrate the performance and practicality of QPSS with extensive simulations and an application to a whole-genome sequencing (WGS) study of cerebrospinal fluid (CSF) biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Using QPSS, we identify regions of rare variant enrichment associated with levels of AD-related proteins, CSF Aβ1–42 and p-tau181P.ConclusionsQPSS is implemented under the assumption that causal variants within a window have the same direction of effect. Typical self-contained tests employ a null hypothesis of no association between the target variant set and the phenotype. Therefore, an advantage of the proposed competitive test is that it is possible to refine a known region of interest to localize disease-associated clusters. The definition of clusters can be easily adapted based on variant function or annotation.

Anti-seizure therapy with a long-term, implanted intra-cerebroventricular delivery system for drug-resistant epilepsy: A first-in-man study

BackgroundA clinical feasibility study was undertaken at a single center of long-term intra-cerebroventricular drug delivery of the anti-seizure medication valproic acid, into the cerebrospinal fluid (CSF) in order to treat drug resistant focal seizures, using an implantable infusion system. The primary objective was to establish the dose range of VPA administered in this manner. Secondarily, safety, pharmacokinetics (PK) and a preliminary estimate of effectiveness were evaluated. MethodsIn this single arm study, five adult subjects, with 29–234 focal onset seizures per month from a seizure focus involving the mesial temporal lobe were implanted with the system (clinicaltrials.gov identifier NCT02899611). Oral valproic acid (VPA) had previously been ineffective in all subjects. Post-surgery, pharmacokinetic studies of CSF infused VPA were performed. Valproic acid doses were increased stepwise in a standardised protocol. FindingsThe procedure and implantation were well-tolerated by all subjects. Four subjects responded with > 50% seizure reduction at the highest tested dose of 160 mg/day. Two subjects experienced extended periods of complete seizure freedom. All five subjects reported significant quality of life improvement. No clinical dose limiting side effects were encountered and there was no evidence of local periventricular toxicity in three subjects who were evaluated with imaging (T2 MRI). Side effects included nausea and appetite loss but were not dose-limiting. Mean CSF valproic acid levels were 45 μg per ml (range 20–120 μg per ml), with corresponding serum levels of 4–14 μg per ml. Subjects have received therapy for up to 2.5 years in total . The efficacy analysis presented focuses on the period of time with the current pump with a mean 12.5 months, range 11.5–15 months. Pump failure requiring reimplantation was a significant initial issue in all subjects but resolved with use of pumps suitably compatible with long-term exposure to valproic acid. InterpretationThe study demonstrated that chronic intraventricular administration of valproic acid is safe and effective in subjects with medically refractory epilepsy over many months. The procedure for implanting the infusion system is safe and well-tolerated. High CSF levels are achieved with corresponding low serum levels and this therapy is shown to be effective despite unsuccessful earlier use of oral valproate preparations. Drug side effects were minimal. FundingThe study was funded by Cerebral Therapeutics Inc., Suite 137 12635 East Montview Blvd Aurora CO 80045.

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic.

In the last years, there has been a significant growth in the literature exploring the pathophysiology of vascular cognitive impairment (VCI). As an “umbrella term” encompassing any degree of vascular-related cognitive decline, VCI is deemed to be the most common cognitive disorder in the elderly, with a significant impact on social and healthcare expenses. Interestingly, some of the molecular, biochemical, and electrophysiological abnormalities detected in VCI seem to correlate with disease process and progression, eventually promoting an adaptive plasticity in some patients and a maladaptive, dysfunctional response in others. However, the exact relationships between vascular lesion, cognition, and neuroplasticity are not completely understood. Recent findings point out also the possibility to identify a panel of markers able to predict cognitive deterioration in the so-called “brain at risk” for vascular or mixed dementia. This will be of pivotal importance when designing trials of disease-modifying drugs or non-pharmacological approaches, including non-invasive neuromodulatory techniques. Taken together, these advances could make VCI a potentially preventable cause of both vascular and degenerative dementia in late life. This review provides a timely update on the recent serological, cerebrospinal fluid, histopathological, imaging, and neurophysiological studies on this “cutting-edge” topic, including the limitations, future perspectives and translational implications in the diagnosis and management of VCI patients.

Effective differentiation of mild cognitive impairment by functional brain graph analysis and computerized testing.

Community-dwelling African American elders are twice as likely to develop mild cognitive impairment (MCI) or Alzheimer’s disease and related dementias than older white Americans and therefore represent a significant at-risk group in need of early monitoring. More extensive imaging or cerebrospinal fluid studies represent significant barriers due to cost and burden. We combined functional connectivity and graph theoretical measures, derived from resting-state electroencephalography (EEG) recordings, with computerized cognitive testing to identify differences between persons with MCI and healthy controls based on a sample of community-dwelling African American elders. We found a significant decrease in functional connectivity and a less integrated graph topology in persons with MCI. A combination of functional connectivity, topological and cognition measurements is powerful for prediction of MCI and combined measures are clearly more effective for prediction than using a single approach. Specifically, by combining cognition features with functional connectivity and topological features the prediction improved compared with the classification using features from single cognitive or EEG domains, with an accuracy of 86.5%, compared with the accuracy of 77.5% of the best single approach. Community-dwelling African American elders find EEG and computerized testing acceptable and results are promising in terms of differentiating between healthy controls and persons with MCI living in the community.

Can CSF biomarkers predict future MS disease activity and severity?

Multiple sclerosis (MS) is a heterogeneous disease. With several disease modifying treatments of different mechanisms of action in use now and in development, it is important to identify reliable biomarkers to identify those higher risk MS patients in whom stronger but riskier treatments might be used, as well as to identify those for whom safer treatments of lower efficacy would be sufficient. Here we review cerebrospinal fluid (CSF) and blood biomarkers that show promise for differentiating people with MS who are at risk for severe disease and disability from those with more benign disease. We reviewed published literature for studies reporting biomarkers with predictive value in MS. Most studies of MS CSF found the presence of oligoclonal bands (both IgG and IgM), high IgG index and high levels of kappa light chains to each be associated with worse prognosis. Neurofilament light chain (NfL) and two markers of glial activation, glial fibrillary acidic protein (GFAP) and YKL-40, were higher in CSF of people with subsequent clinical progression or imaging evidence for neurodegeneration. Few reports have been made yet on the prognostic significance of blood NfL, but in one early report baseline, serum NfL (sNfL) predicted subsequent brain volume loss.

Different clinical and neuroimaging features of Japanese dementia siblings with a new N-terminal mutation (Val225Ala) of APP gene

Autosomal dominant amyloid precursor protein (APP) mutations in familial Alzheimer’s disease accelerate the amyloid beta (Aβ) pathology. Here we describe Japanese siblings with a new N-terminal mutation (a heterogeneous c.674T>C, p.Val225Ala) of the APP gene, developing a progressive dementia at 57 years and Aβ and tau pathologies in cerebrospinal fluid studies. However, the brother and sister showed different clinical and neuroimaging features, suggesting different Aβ pathologies for each sibling.

Study of cerebro-spinal fluid in HIV patients of southern Maharashtra population

Study of cerebro-spinal fluid in HIV patients of southern Maharashtra population

Rapidly Progressive Dementia as a Manifestation of Relapse in Mantle Cell Lymphoma: Experience in Diagnosis and Treatment

Rapidly progressive dementia is an entity that has a multiple and heterogeneous etiology. It is characterized by the alteration of two or more cognitive domains in a period of less than 1 to 2 years. The involvement of the central nervous system attributed to mantle cell lymphoma is rare with a poor prognosis in the short term and mainly debuts in the late stages of the disease as a relapse. A 61-year-old male with a history of mantle cell lymphoma who presents a relapse of the central nervous system, given by a clinical course compatible with a rapidly progressive dementia and which is confirmed by flow cytometry studies in cerebrospinal fluid, which show a 53 , 8% of mature lymphoid population: CD45, CD19, CD20, HLA-DR, BCL2. It presents an adequate response to management with a tyrosine kinase inhibitor (Ibrutinib), resolving clinical symptoms and imaging findings.

A 33-Year-Old Man with Progressive Diffuse and Focal Neuropsychiatric Signs without Localizing Correlates on Brain Imaging: A Systematic Approach to Diagnosis.

Introduction:Novel expensive diagnostic tests are rapidly emerging. However, the answer to the most complex clinical presentations is often inferred from a systematic approach to the differential diagnosis. This is especially the case in neuropsychiatric disorders that present with a mix of neurologic and psychiatric symptoms. This case report fills a gap in the literature by providing a systematic differential diagnosis of such neuropsychiatric presentations associated with non-focal brain imaging.Case Presentation:A 33-year-old African-American man presented with confusion, weakness, and tremors. He initially noted memory problems and over the following six months progressively became confused, developed speech difficulties and left sided weakness and tremors. On exam, he was predominantly abulic but with intermittent and extreme mood lability. He lacked insight and his attention was poor. He had mild facial weakness and spastic hemiparesis with action tremors on the left side. Magnetic Resonance Imaging of the brain demonstrated non-specific diffuse parenchymal volume loss. His serum and cerebrospinal fluid studies were positive for Rapid Plasma Reagin and Veneral Disease Research Laboratory tests, respectively, suggesting a diagnosis of paretic neurosyphilis.Conclusion:This is a case of a young man with neurosyphilis who presented with progressive subacute cognitive decline, associated with focal neurological signs but no focal lesions on brain imaging. Neurosyphilis is often misdiagnosed on medicine, psychiatry, and neurology inpatient units. In this report, we present an approach to conceptualize similar cases and provide a differential diagnosis that will help reach an accurate diagnosis more efficiently. Further, it raises awareness regarding neurosyphilis, a devastating but easily treatable condition.

Комплексное цитологическое и иммуноцитохимическое исследование ликвора в диагностике интракраниальных метастазов рака молочной железы

Introduction. Metastases of breast cancer are detected in 5 to 48% cases, depending on the biological tumor subtype, which is the second most common after lung cancer in men. Cytological liquor analysis is one of the “gold standards” for the metastatic brain lesion identification, and, among other modern approaches, it can increase the CNS metastasis detection. Breast cancer cell identification in cerebrospinal fluid is a poor prognostic factor. A cytological examination has a predictive significance for these patients: the absence of tumor cells in the cerebrospinal fluid can be considered the sign of the intrathecal therapy effectiveness. The accuracy of the cytological diagnosis directly depends on the detailed patient’s history. Immunocytochemical assays increase the sensitivity of the cytological diagnostics. The aim of the study was to evaluate the ca-pabilities of comprehensive cytological and immunocytochemical studies in the secondary cerebral lesions diagnosis in breast cancer patients. Materials and methods. We conducted 169 cytological studies in 55 breast cancer patients with brain metas-tases. Liquor samples were obtained using lumbar punctures. 36 patients underwent 44 immunocytochemical studies and 117 immunocytochemical reactions to clarify the cytological diagnosis. Results. The sensitivity of the cytological method was 69.8%. Immunocytochemistry increased the sensitiv-ity to 72.3%. In 29 patients, the tumor histogenesis was determined using an immunocytochemical assay. Conclusion. The liquor cytological analysis is frequently the only primary morphologic diagnostic method to detect breast cancer metastasis within the central nervous system. Immunocytochemical assay significantly expands the possibilities of cytological study, allowing health care specialists to detect single tumor cells in samples and determine the metastatic neoplasm histogenesis in most cases, which also increases sensitivity. Keywords: breast cancer, cytological and immunocytochemical study of cerebrospinal fluid

Intractable Headache in a Patient with Carcinoma Breast: Infiltrative or Infective - A Diagnostic Challenge

Chronic meningitis is the inflammation of meanings having varied clinical manifestations and diverse etiologies. Among them tuberculosis continues to be an important cause of chronic meningitis. To achieve the etiological diagnosis, examination of cerebrospinal fluid is mandatory. Carcinomatous meningitis, another rare cause of chronic meningitis is caused by infiltration of leptomeninges by malignant cells. Diagnostics old standard of carcinomatous meningitis is to demonstrate malignant cells in the cerebrospinaluid. In cerebrospinal fluid negative cases with high degree of suspicion, various biomarkers may assist to arrive at diagnosis. However examination of single sample, delayed processing and low volume cerebrospinal fluid analysis may give rise to false negative results. Were port a patient of breast carcinoma presenting with intractable headache misdiagnosed as tuberculosis meningitis. Definitive diagnosis of carcinomatous meningitis was established by repeated lumbar puncture and large volume of cerebrospinal fluid was sent for immediate processing. Our case emphasizes the importance of the above parameters of cerebrospinal fluid study to maximize the diagnostic accuracy and efficiency.

Criptococosis diseminada con compromiso esplénico y meníngeo en una paciente con sida

Se presenta el caso de una mujer de 37 años de edad, con diagnóstico reciente de infección por VIH, que consultó por cefalea, diarrea, vómito y fiebre de dos semanas de evolución. Se encontraba caquéctica con una gran esplenomegalia. El estudio del líquido cefalorraquídeo demostró una meningitis por Cryptococcus neoformans. Las imágenes diagnósticas evidenciaron una gran esplenomegalia con lesiones focales. La biopsia percutánea con aguja cortante N°18 de una de las lesiones focales confirmó la criptococosis esplénica. La paciente recibió tratamiento secuencial con anfotericina B y fluconazol con una evolución satisfactoria. Las lesiones esplénicas se resolvieron completamente y la paciente se encuentra actualmente asintomática y recibe profilaxis secundaria con fluconazol y terapia antirretroviral