Rheumatoid meningitis: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Rheumatoid meningitis (RM) is a neurological complication of rheumatoid arthritis (RA). Current evidence is based on case reports and partial reviews. METHODS: This is a systematic review and meta-analysis following the PRISMA statement. The aim is to describe the characteristics of the disease, including clinical, imaging and laboratory findings, treatment, outcomes and prognosis reported in the literature. RESULTS: In all, 103 studies with 130 cases were included. RM affected adults with an average age of 62 years, with or without a previous RA diagnosis. RA activity and time with the disease were associated with a worse prognosis. Most common clinical manifestations were transient focal neurological signs (64.6%), systemic symptoms (51.3%), episodic headache (50.4%) and neuropsychiatric alterations (47.7%). Joint manifestations were present in only 27.4% of cases. Brain magnetic resonance imaging showed unilateral or bilateral involvement, predominantly frontoparietal. Both pachymeninges and leptomeninges were affected, the latter more frequently (82.88%). The laboratory findings included increased levels of rheumatoid factor (89.71%), anti-cyclic citrullinated peptide (89.47%), C-reactive protein (82.54%) and erythrocyte sedimentation rate (81.81%). Cerebrospinal fluid analysis showed an increase in the protein level (76.14%), with pleocytosis (85.19%) of mononuclear predominance (89.19%). Biopsy was performed in 72.52% of the patients. Corticosteroid pulse therapy was the main induction therapy. Disease relapse occurred in 31.17% of patients, whilst 54.54% had a full recovery. CONCLUSIONS: Rheumatoid meningitis must be considered in adult patients with or without RA diagnosis, high-dose corticosteroid induction therapy should be installed and maintenance therapy plays a key role. It is not recommended to use anti-TNF as an induction therapy. Nowadays, RM has a significantly better outcome. These findings may aid clinicians in timely RM diagnosis and treatment, thus improving its outcomes.

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.

Inclusion of the Symbol Digit Modalities Test in a revised assessment of 'no evidence of disease activity-4 (NEDA-4)' in Latin-American patients with multiple sclerosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), no evidence of disease activity-3 (NEDA-3) is defined as the absence of: (1) relapses; (2) disability progression; (3) MRI activity (new/enlarged T2 lesions and/or gadolinium-enhanced T1 lesions). NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized percentage brain volume change (a-PBVC) >-0.4%. In individual patients, brain volume assessment is confounded with normal aging, methodological limitations and fluid-shift related fluctuations in brain volume. Cognitive impairment has been proposed as another component that should be integrated into therapeutic algorithms for RRMS. We aim to determine the proportion of patients failing to meet NEDA-4 criteria and to appraise whether the Symbol Digit Modalities Test (SDMT) is capable of replacing a-PBVC as one of the components of NEDA-4. We hypothesize that NEDA-4 has the potential to capture the impact of DMT therapies in RRMS. METHODS: Forty-five patients were prospectively followed 1 and 2 years after their baseline assessment at the University of Chile Hospital. SIENA software was used to assess a-PBVC. RESULTS: At baseline, the patients had a mean age of 33.0 years (range 18-57), disease duration of 1.9 years (0.4-4), Expanded Disability Status Scale score of 1.3 (0-4), and 67% were female. The majority had RRMS (91% while 9% had clinically isolated syndrome (CIS)). Seventy-three percent were on the so-called first line DMTs such as interferons (53%), glatiramer acetate (13%), teriflunomide (9%), and 18% were on fingolimod. There was a serial decline in the proportion of NEDA: after 1 and 2 years of follow-up 60% and 47% met NEDA-3 status, and 38% and 27% met NEDA-4, respectively. At the last follow-up 21% remained on interferons, 47% were now on fingolimod, 4% on alemtuzumab and 2% on natalizumab. At year 1 and year 2, with the replacement of a-PBVC by SDMT, 53% and 40% of patients achieved a putative NEDA-4 status, respectively. CONCLUSION: Brain volumetric MRI has yet to be translated into clinical practice and SDMT may qualify as the fourth component of NEDA-4 definition. NEDA-4 has the potential to capture the impact of DMT therapies in RRMS earlier in the disease course of RRMS.

Self-reported urinary impairment identifies 'fast progressors' in terms of neuronal loss in multiple system atrophy.

INTRODUCTION: MSA is an adult-onset, sporadic, progressive parkinsonian syndrome characterised by the presence of akinesia, cerebellar dysfunction, autonomic failure and pyramidal signs. Annualized-whole-brain atrophy rate (a-WBAR) is an informative way to quantify disease progression. In this longitudinal work we investigate the correlations of a-WBAR with clinical scales for motor impairment, autonomic disability and cognitive decline in MSA and explore how atrophy progresses within the brain. METHOD: Fourty-one MSA patients were studied using Structural Imaging Evaluation with Normalization of Atrophy (SIENA). SIENA is an MRI-based algorithm that quantifies brain tissue volume. Clinical parameters were explored using the 18-item Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr Scale, the Frontal Assessment Battery and the Natural History and Neuroprotection in Parkinson Plus Syndromes scale (sub-items for orthostatic and urinary functions). RESULTS: The mean (±SD) age was 60.4 years ±â€¯7.7 and a-WBAR was 1.65% ±â€¯0.9. Demographics and clinical ratings at the time of the first scan were non-significantly associated with a-WBAR. The only exception was the baseline urinary score with a weak but significant association (R2 = 0.15, p = 0.04). Progression of grey matter atrophy was detected in the left superior temporal gyrus, right middle frontal gyrus, right frontopolar region and midbrain. CONCLUSION: Urinary impairment at baseline may help to identify 'fast progressors' in terms of neuronal loss, particularly in the frontal and temporal lobes. Thus, urinary impairment should be recognized as a key target for disease modifying therapeutic interventions in MSA.

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice.

Background: In relapsing-remitting multiple sclerosis, no evidence of disease activity-3 (NEDA-3) is defined as no relapses, no disability progression and no MRI activity. NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized brain volume loss (a-BVL) of ≤0.4%. Prospective real-world studies presenting data on NEDA-4 are scarce. Objective: To determine the proportion of patients failing to meet one or more NEDA-4 criteria and the contribution of each component to this failure. Methods: Forty-eight patients were followed for 12 months. Structural image evaluation, using normalization, of atrophy was used to assess a-BVL. Results: The patients had a mean age of 33.0 years (range 18-57), disease duration of 1.7 years (0.4-4) and Expanded Disability Status Scale score of 1.3 (0-4); 71% were women. All patients were on disease-modifying therapies. During follow-up, 21% of the patients had at least one relapse, 21% had disability progression, 8% had new T2 lesions, and 10% had gadolinium-enhanced lesions. Fifty-eight percent (28/48) achieved NEDA-3 status. a-BVL of >0.4% was observed in 52% (25/48). Only 29% (14/48) achieved NEDA-4 status. Conclusion: a-BVL is a good marker to detect subclinical disease activity. a-BVL is parameter to continue investigating for guiding clinical practice in relapsing-remitting multiple sclerosis.

Deep Brain Stimulation Surgery for Parkinson Disease Coexisting With Communicating Hydrocephalus: A Case Report.

We report a successful bilateral globus pallidus internus-deep brain stimulation (GPi-DBS) for a Parkinson disease (PD) patient with idiopathic normal pressure hydrocephalus (INPH) and an unusually long anterior commissure-posterior commissure (AC-PC) line. A 54-year-old man presented with a history of 3 months of severe shuffling gait, rigidity, slow movements of the left side limbs, and difficulty managing finances. A brain MRI revealed marked ventriculomegaly (Evans index = 0.42). The patient was diagnosed with INPH and a ventriculoperitoneal shunt was placed. Cognitive impairment improved, but walking disturbances, slowness, and rigidity persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. He was diagnosed with PD. After 7 years, the patient developed gait freezing and severe levodopa-induced dyskinesia. The patient underwent bilateral GPi-DBS. We used MRI/CT fusion techniques for anatomical indirect targeting. Indirect targeting is based on standardized stereotactic atlas and on a formula-derived method based on AC-PC landmarks. The AC-PC line was 40 mm (the usual length is between 19 and 32 mm). Intraoperative microelectrode recording was a non-expendable test, but multiple recordings were avoided to reduce the surgical risk of ventricular involvement. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 6 months after surgery. Deep brain stimulation surgery in PD with ventriculomegaly is a challenge. This procedure can result in a greater chance of breaching the ventricle, with risks of intraventricular hemorrhage and migration of cerebrospinal fluid into the brain parenchyma with target displacement. Furthermore, clinical judgment is paramount when recent onset of shuffling gait coexists with ventriculomegaly because the most common dilemma is differentiating between PD and INPH. For these reasons, neurologists and surgeons may refuse to operate on PD patients with ventriculomegaly. However, DBS should be considered for PD patients with motor complications when responsiveness to levodopa is demonstrated, even in the context of marked ventriculomegaly.

Encephalitis Associated to Metabotropic Glutamate Receptor 5 (mGluR5) Antibodies in Cerebrospinal Fluid.

A 68-years-old Hispanic man, complained of night sweats, low grade fewer, unexplained weight loss, and memory problems over 3 months. Abdominal tomography showed multiple intra-abdominal adenopathy and biopsy confirmed classic Hodgkin's lymphoma. He commenced treatment with chemotherapy. Three months later, he had acute onset of inattention, auditory hallucinations and alterations of anterograde memory. The patient developed psychomotor agitation, unresponsive to a combination of neuroleptics and benzodiazepines. Brain MRI showed a small established cerebellar infarction. Electroencephalogram was normal. Tests for toxic metabolic encephalopathy were negative. One oligoclonal IgG bands was found in the Cerebrospinal fluid (CSF), which was not observed in corresponding serum, but cell count and protein were normal. Extensive testing for infectious encephalitis was unremarkable. CSF testing for commercially available neural and non-neural autoantibodies was negative. The patient fulfilled the Gultekin diagnostic criteria for paraneoplastic limbic encephalitis and methylprednisolone IV 1g/d for 5 days was given. He recovered rapidly, with progressive improvement in memory and psychomotor agitation. After treatment commenced, results for antibodies to mGluR5 in CSF taken prior to treatment were returned as positive. mGluR5 is found on post-synaptic terminals of neurons and microglia and is expressed primarily in the hippocampus and amygdala. This case highlights the difficulties in diagnosing this type of encephalitis: the CSF did not show pleocytosis, the MRI showed only chronic change and the electroencephalogram was normal. The dramatic recovery after methylprednisolone help to better characterized the clinical spectrum of auto-immune encephalitis. Diagnosing anti mGlutR5 encephalitis may lead to potentially highly effective treatment option and may anticipate the diagnostic of a cancer. A high index of suspicion is needed to avoid missed diagnosis. In patients with unexplained encephalitis, testing for antibodies to mGluR5 in CSF and serum should be considered. When there is a reasonable index of suspicion of auto-immune encephalitis, treatment should not be delayed for the antibody results.

Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings.

Mutations in the ACTA2 gene lead to a multisystemic smooth muscle dysfunction syndrome that causes vascular disease, congenital mydriasis, and variable presentation of urinary and gastrointestinal problems. The heterozygous Arg179 mutation is associated with a distinctive cerebrovascular phenotype. We report the cases of two newborn siblings with heterozygous ACTA2 Arg179Cys substitution and provide neuroimaging exams that demonstrate the distinctive cerebrovascular phenotype, also associated with variable degree of hypoplasia of the vertebro-basilar circulation as well as hypoxic-ischemic lesions.

Paraganglioma del cuerpo carotideo: Revisión bibliográfica / Carotid body paraganglioma: Review of the literature

Introducción: Los paragangliomas son tumores neuroectodérmicos que suelen encontrarse adyacentes a estructuras ganglionares autonómicas. El paraganglioma carotídeo es un tumor parasimpático, habitualmente no secretor de hormonas y de bajo potencial maligno. Objetivo: Realizar una revisión de la literatura con conceptos actuales respecto al abordaje clínico y quirúrgico de esta patología. Diseño: Revisión narrativa de la literatura. Materiales y métodos: Se realizó una búsqueda en bases virtuales como Pubmed y Scielo utilizando los términos "paraganglioma" y "tumor del cuerpo carotídeo" con el fin de encontrar documentos actualizados sobre este tema. Resultados: De las fuentes bibliográficas halladas, se depuraron según impacto, población objeto y tiempo de publicación hasta obtener 48 documentos incluyendo artículos de revisión, reportes de caso y libros, de los cuales se sintetizó información sobre el abordaje del paraganglioma del cuerpo carotídeo. Conclusiones: Ante la presencia de una masa cervical lateral debe considerarse la posibilidad de un paraganglioma; la tomografía computada y la resonancia magnética permiten la aproximación diagnóstica y su clasificación inicial, mientras que la angiografía permite el uso de técnicas de embolización selectiva, cuyo uso en estos tumores es controvertido. La cirugía es el único tratamiento curativo y se considera el manejo de elección en la mayoría de los casos, mientras que la radioterapia se indica en aquellos casos de resecciones incompletas o cuando la cirugía está contraindicada.

Introduction: Paragangliomas are neuroectodermal tumors often found adjacent to autonomic ganglion structures. The carotid paraganglioma is a parasympathetic tumor, usually without hormone secretion function and low malignant potential. Objective: To review current concepts regarding the clinical and surgical management of this condition. Design: Narrative review of the literature. Materials and methods: A search was conducted throughout virtual bases such as Pubmed and Scielo using the terms "paraganglioma" and "carotid body tumor" in order to find updated documents on this topic. Results: From the bibliographical sources found, they were depurated by their impact, target population and publication time until 48 papers including review articles, case reports and books; from these literature, information on carotid body paraganglioma was synthesized. Conclusions: In the presence of a lateral neck mass, paraganglioma should be considered; computed tomography and magnetic resonance allows to do a diagnostic approaching and its initial classification, while angiography allows the use of selective embolization techniques, whose use on these tumors is controversial. Surgery is the only curative treatment and is considered the treatment of choice in most cases, while radiation therapy is indicated in cases of incomplete resection or when surgery is contraindicated.

Prevención primaria y secundaria de cardiopatía coronaria / Primary and secondary prevention of coronary cardiopathy

La prevención de enfermedad coronaria cada vez adquiere mayor relevancia por cuanto la enfermedad cardiovascular continúa siendo la principal causa de muerte en el mundo. Los factores de riesgo clásicos: tabaquismo, hipertensión arterial, hipercolesterolemia, diabetes, sedentarismo y obesidad además de la edad y de los factores genéticos, explican sobre el 90 por ciento de los infartos en el mundo, tanto en hombres como mujeres. Se desconoce aún el mecanismo por el cual la reducción de los factores de riesgo disminuye los eventos isquémicos coronarios y muchos de los mecanismos que aceleran o gatillan la ateroesclerosis, pese a nuestros mejores esfuerzos y a los avances en esta materia, la enfermedad coronaria aún existe. Contamos con fuerte evidencia que en prevención secundaria además de la reducción de los factores de riesgo, la terapia farmacológica con antiplaquetarios, betabloqueadores, inhibidores de enzima convertidora y estatinas, reducen el riesgo en forma significativa de presentar un segundo evento.

The prevention of coronary heart disease is becoming more relevant as cardiovascular disease remains the leading cause of death worldwide. Classic risk factors: current smoking, hypertension, hypercholesterolemia, diabetes, sedentary lifestyle and obesity in addition to age and genetic factors explain about 90 percent of acute myocardial infarction in the world, in both men and women. It is not known yet the mechanism by which the reduction of risk factors reduces ischemic coronary events and many of the mechanisms that initiate or accelerate atherosclerosis. Despite our best efforts and progress in this area, the disease still exists. We have strong evidence that secondary prevention in addition to reducing risk factors, with antiplatelet drug therapy, beta blockers, converting enzyme inhibitors and statins reduce significantly the risk of presenting a second ischemic event.