Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central / Opsoclonus-myoclonus-ataxia syndrome associated with central nervous system HIV-1 escape phenomenon

INTRODUCCIÓN: El síndrome opsoclono-mioclono-ataxia (OMA) es un trastorno neurológico infrecuente caracterizado por movimientos oculares conjugados sacádicos involuntarios, mioclonías y ataxia. Existen pocos casos en la bibliografía de pacientes con virus de la inmunodeficiencia humana (VIH) y OMA. CASO CLÍNICO: Varón de 41 años y diagnóstico de infección por el VIH-1 desde 1997, que cursó con múltiples esquemas antirretrovirales debido a una pobre adhesión al tratamiento. En 2008 presentó una carga viral de 100.000 copias/mL y una cuenta linfocitaria CD4+ de 10 células/mm3. En 2013 sufrió un cuadro progresivo de 11 meses de evolución caracterizado por opsoclonía y ataxia. En ese momento, su carga viral era indetectable, y la cuenta de CD4+, de 606 células/mm3. Se descartaron infecciones oportunistas. El examen del líquido cefalorraquídeo demostró hiperproteinorraquia leve y una carga viral de 534 copias/mL. El examen del tropismo de correceptor en el líquido cefalorraquídeo demostró un uso selectivo de CCR5. La resonancia magnética cerebral objetivó atrofia hipocámpica e hiperintensidades en las secuencias ponderadas en T2. El paciente mostró una recuperación clínica franca y un aclaramiento de la carga viral en el líquido cefalorraquídeo tras el ajuste de antirretrovirales basado en la resistencia de genotipo y el análisis de tropismo. CONCLUSIONES: En pacientes con infección por el VIH y disfunción del sistema nervioso central sin infecciones oportunistas, debería llevarse a cabo una determinación de la carga viral en el plasma y el líquido cefalorraquídeo para descartar un potencial fenómeno de escape viral, así como exámenes de resistencia y tropismo para diseñar el tratamiento antirretroviral adecuado

INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurological disorder characterized by involuntary conjugate saccadic eye movements, myoclonus, and ataxia. Few reports exist on patients with HIV and OMA. CASE REPORT: A 41-year-old man diagnosed with HIV-1 infection in 1997 coursed with multiple anti-retroviral schemes as a consequence of poor adherence. In 2008 he presented an HIV-1 viral load of 100,000 copies/mL and a CD4+ T cell count of 10 cells/mm3. In 2013 our patient arrived with an 11-month history of progressive opsoclonus and ataxia. He had undetectable plasma HIV-1 RNA load and CD4+ of 606 cells/mm3. No opportunistic infections were found. Cerebrospinal fluid analysis showed mildly elevated protein concentration and HIV-1 viral load of 534 copies/mL. Cerebrospinal fluid co-receptor tropism test showed selective CCR5 usage. A brain magnetic resonance imaging showed hippocampal atrophy and T2-weighted hyperintensities. Our patient exhibited a dramatic recovery and cerebrospinal fluid HIV clearance after adjustment of anti-retroviral treatment based on genotyping resistance and tropism analyses. CONCLUSIONS: In patients with HIV presenting cengral nervous system dysfunction without opportunistic infections, cerebrospinal fluid and plasma HIV-1 viral load, resistance and tropism tests should be performed to assess a potential viral escape and to design the appropriate anti-retroviral therapy in an individual patient basis

Identification of risk factors for central nervous system metastasis in patients with breast cancer with neurologic symptoms.

BACKGROUND: The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm). METHODS: The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis. RESULTS: Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age <50 years at the time of BC diagnosis (odds ratio [OR], 2.5; 95% confidence interval [95% CI], 1.8-3.5 [P < .0001]), human epidermal growth factor receptor 2 (HER2)-positive status (HER2+) (OR, 3.6; 95% CI, 2.1-6.1 [P < .0001]), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9-5.3 [P < .001]), triple-negative subtype(OR, 2.4; 95% CI, 1.5-4 [P = .001]), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5-9.6 [P < .0001]) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3-15.1 months). CONCLUSIONS: CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro-oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple-negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non-CNS metastases.

Vertigo in patients with cancer: Red flag symptoms.

INTRODUCTION: Vertigo is a common condition occurring in the general population and is usually self-limited. Reports studying vertigo in patients with brain metastasis (BM), are scarce. Therefore, the aim of this study was to analyze if the presence of vertigo in cancer patients is associated with the presence of BM. METHODS: This study was conducted in a cancer referral center, where patients with confirmed systemic cancer sent for a neuro-oncologic consultation from May 2012 to March 2018 were included for review. RESULTS: Of 3220 patients, 723 were diagnosed with BM, and 204 had vertigo. Of these patients, 22.5% of those who had vertigo were diagnosed to have BM and 6% of those with BM had vertigo as an initial symptom (odds ratio [OR] 0.9; p = 0.9). An additional symptom was present in 104 patients with vertigo. Bivariate regression analysis disclosed a higher risk of having BM in patients with vertigo accompanied by headache (OR18.6; p < 0.0001), ataxia (OR12.1; p < 0.0001), seizures (OR10.9; p = 0.04), visual symptoms (OR10.4; p < 0.0001), speech impairment (OR6.3; p = 0.01), altered mental status (OR7.4; p < 0.0001), and focal weakness (OR7.4; p = 0.001), or focal sensitive complaint (OR6.9; p = 0.003). Vertigo with headache or ataxia remained statistically significant after multivariate analysis. CONCLUSION: In this cohort, a higher risk of having BM was associated with the presence of vertigo coexistent with headache, ataxia, seizures, visual symptoms, speech impairment, altered mental status, focal weakness, or focal sensitive complaint. On the basis of these results, these accompanying symptoms must be considered as red flags in patients with systemic cancer.

Clinical presentation, risk factors and outcome of central nervous system metastasis vs stroke in cancer patients.

BACKGROUND AND PURPOSE: Cancer and stroke are the second and third causes of death worldwide; brain metastases (BM) occur in one third of patients with cancer, any neurologic deficit in these population always prompts the clinician to discard metastases for their presence carries a bad outcome. Both might share clinical presentation and differences in their outcome are not entirely known. The aim was to compare risk factors, clinical presentation, and outcome of cancer patients with BM vs stroke. METHODS: A descriptive study with prospectively acquired data from a cancer referral center included patients seen at the neuro-oncologic unit from March 2011 to February 2018 with confirmed cancer who had BM or stroke. RESULTS: Six hundred and thirteen BM patients were compared with 268 with stroke and cancer. Demographic factors, cancer type, risk factors, clinical presentation, and outcome are presented. Median overall survival in months for those with any stroke was 15 (95%confidence interval [CI] 8.6-21.4)-5 (95%CI 0.12.4) for hemorrhagic stroke and 22 (95%CI 13.4-30.6) in the ischemic group-and for those with BM 12 (95%CI 10.4-13.6). Hemorrhagic stroke commonly found in stroke patients as well as focal motor weakness, aphasia, and altered mental status. BM was more common in breast and lung cancer with headache, visual complaint, and/or vertigo. CONCLUSION: Survival in cancer patients with BM is not that different than those with stroke, but clinical presentation and risk factors were found different.

Platelet count is associated with outcome in cancer patients with stroke.

INTRODUCTION: Cerebrovascular disease (CVD) and cancer are among the most common causes of mortality worldwide, preceded only by ischemic heart disease (IHD). Thrombocytopenia was shown to be associated with poor outcomes in IHD and CVD in the general population. This study aimed to assess the relationship of thrombocytopenia with poor outcomes in cancer patients with CVD. MATERIALS AND METHODS: Data on patients with concomitant CVD and cancer who were initially treated at a cancer referral center between January 2010 and December 2017 were included. Thrombocytopenia was defined as a platelet count < 150,000/mm3 during the first 24 h of CVD symptom onset. The IRB (CI/837/17) approved the review of clinical records. RESULTS: Among 268 cancer patients with CVD included in the study, 210 met the inclusion criteria. Median overall survival of the entire cohort was 7.2 months, which was significantly shorter in males (p = 0.029) and patients with hematologic tumors (p = 0.009), hemorrhagic CVD (p < 0.001), altered mental status (p < 0.001), and thrombocytopenia (p < 0.001). Multiple regression logistic analysis revealed that thrombocytopenia (risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.4) and altered mental status (RR 2.7, 95% CI 1.9-4.0) remained statistically significant risk factors for mortality. CONCLUSION: In cancer patients with CVD, thrombocytopenia at the time of CVD diagnosis and altered mental status during initial clinical evaluation were associated with higher mortality, which should be confirmed in future studies.

Diagnosis of brain metastases in breast cancer patients resulting from neurological symptoms.

OBJECTIVES: Breast cancer (BC) is the leading cause of morbidity and mortality. Neurological symptoms are highly feared because they are associated with central nervous system metastases (CNSm). So, we aimed to analyze the association of neurological symptoms with CNSm. PATIENTS & METHODS: Patients with BC referred for a neuro-oncological evaluation at a cancer referral center from June 2012 to December 2017 were included. Demographic, oncological history, comorbidities, clinical symptoms and signs, and their correlation with CNSm were prospectively acquired during consultation in a computerized database. Analyses included descriptive observations, bivariate, and logistic linear regression tests that compared associations. RESULTS: A total of 857 patients with BC were referred for assessment. The most frequently occurring symptoms included headache, focal motor weakness, focal-sensitive complaints, and visual complaints. Of the 1029 neuro-oncology diagnoses made, the most common were CNSm, primary headache, and chemotherapy-induced neuropathy. The risk factors associated with CNSm in patients with neurological symptoms were HER2+, younger age at cancer diagnosis, presence of extracranial metastases, and >1 neurological symptom (mainly headache: hazard ratio (HR), 2.1 [95% confidence interval (CI), 1.5-2.7]; visual complaints: HR, 2.3 (95%CI, 1.2-4.2); and ataxia: HR, 2.1 (95%CI,1.04-4.3). CONCLUSIONS: Clinical symptoms and cancer characteristics were correlated with the development of CNSm. Specific risk and protective factors were identified. Among BC patients with neurological symptoms, CNSm should always be considered, especially in patients with certain oncological and clinical features.