Utility of the Spanish version of the Everyday Cognition scale in the diagnosis of mild cognitive impairment and mild dementia in an older cohort from the Argentina-ADNI.

INTRODUCTION: The performance of activities of daily living in elderly patients with memory disorders is directly related to living independently and to autonomy. Documenting and assessing functional capacity through detailed scales is important for both diagnostic and treatment recommendations. The Everyday Cognition (ECog) scale is a relatively new informant-rated measure of cognitive and functional abilities. In the present study, the discriminant validity of the ECog scale was evaluated in cognitively intact controls (CN) and in patients with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) from the Argentina-ADNI cohort to establish diagnostic accuracy. In addition, we compared the sensitivity and specificity of ECog against Functional Assessment Questionnaire (FAQ) scale to discriminate among the three groups. METHODS: We evaluated 15 CN, 28 MCI, and 13 mild AD subjects. External, convergent and divergent validity and internal consistency were examined. RESULTS: The average total score on the ECog was significantly different across the three diagnostic syndromes (p < .05). The ECog was more sensitive than FAQ in discriminating between CN and MCI patients and between MCI and AD subjects. The ECog showed a strong correlation with FAQ, and moderate correlations with neuropsychological tests. Cronbach's alpha was .98. CONCLUSIONS: The ECog scale is an efficient instrument for the differentiation of individuals with mild dementia or MCI from normal older adults, with good accuracy and good correlation with other tests measuring daily and cognitive functions. Comparing against FAQ, ECog was more useful in assessing changes in functionality in MCI patients.

C9ORF72 G4C2-repeat expansion and frontotemporal dementia first reported case in Argentina.

We present a female patient aged 51 who developed behavioral disorders followed by cognitive impairment over 3 years. Neuropsychological, neuropsychiatric, and radiological features suggested a probable behavioral variant of frontotemporal dementia (bvFTD). A family history of amyotrophic lateral sclerosis and parkinsonism suggested the hexanucleotide repeat expansion G4C2 in C9ORF72 . We set up a two-step genotyping algorithm for the detection of the expansion using fragment-length analysis polymerase chain reaction (PCR) and repeat-primed PCR with fluorescent primers. We confirmed the presence of an expanded G4C2 allele in the patient. This represents the first documented case of bvFTD due to a C9ORF72 expansion in Argentina.

Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.

Alzheimer's disease (AD) is characterized by the accumulation of aggregated amyloid peptides in the brain parenchyma and within the walls of cerebral vessels. The hippocampus-a complex brain structure with a pivotal role in learning and memory-is implicated in this disease. However, there is limited data on vascular changes during AD pathological degeneration in this susceptible structure, which has distinctive vascular traits. Our aim was to evaluate vascular alterations in the hippocampus of AD patients and PDAPP-J20 mice-a model of AD-and to determine the impact of Aß40 and Aß42 on endothelial cell activation. We found a loss of physical astrocyte-endothelium interaction in the hippocampus of individuals with AD as compared to non-AD donors, along with reduced vascular density. Astrocyte-endothelial interactions and levels of the tight junction protein occludin were altered early in PDAPP-J20 mice, preceding any signs of morphological changes or disruption of the blood-brain barrier in these mice. At later stages, PDAPP-J20 mice exhibited decreased vascular density in the hippocampus and leakage of fluorescent tracers, indicating dysfunction of the vasculature and the BBB. In vitro studies showed that soluble Aß40 exposure in human brain microvascular endothelial cells (HBMEC) was sufficient to induce NFκB translocation to the nucleus, which may be linked with an observed reduction in occludin levels. The inhibition of the membrane receptor for advanced glycation end products (RAGE) prevented these changes in HBMEC. Additional results suggest that Aß42 indirectly affects the endothelium by inducing astrocytic factors. Furthermore, our results from human and mouse brain samples provide evidence for the crucial involvement of the hippocampal vasculature in Alzheimer's disease.

Downregulation of E-cadherin in pluripotent stem cells triggers partial EMT.

Epithelial to mesenchymal transition (EMT) is a critical cellular process that has been well characterized during embryonic development and cancer metastasis and it also is implicated in several physiological and pathological events including embryonic stem cell differentiation. During early stages of differentiation, human embryonic stem cells pass through EMT where deeper morphological, molecular and biochemical changes occur. Though initially considered as a decision between two states, EMT process is now regarded as a fluid transition where cells exist on a spectrum of intermediate states. In this work, using a CRISPR interference system in human embryonic stem cells, we describe a molecular characterization of the effects of downregulation of E-cadherin, one of the main initiation events of EMT, as a unique start signal. Our results suggest that the decrease and delocalization of E-cadherin causes an incomplete EMT where cells retain their undifferentiated state while expressing several characteristics of a mesenchymal-like phenotype. Namely, we found that E-cadherin downregulation induces SNAI1 and SNAI2 upregulation, promotes MALAT1 and LINC-ROR downregulation, modulates the expression of tight junction occludin 1 and gap junction connexin 43, increases human embryonic stem cells migratory capacity and delocalize ß-catenin. Altogether, we believe our results provide a useful tool to model the molecular events of an unstable intermediate state and further identify multiple layers of molecular changes that occur during partial EMT.

Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America. / Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica.

OBJECTIVE: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. METHODS: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aß1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. RESULTS: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. CONCLUSIONS: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice.

Brain MRI findings in children and adolescents with Fabry disease.

OBJECTIVE: To evaluate the presence of white matter and hemorrhagic lesions in brain MRI of children and adolescents with Fabry disease (FD). METHODS: Brain MRI studies in 44 consecutive children and teenagers (20 boys, mean age 14.6 years, range 7-21 years) were evaluated using classic sequences as well as, GRE-weighted images, for white matter lesions (WML) and chronic microbleed detection. All patients lacked history of stroke or TIA. Brain MRI findings in 46 consecutive children and adolescents without FD, referred for the evaluation of headaches (36 females, mean age 14.1 years, range 7-21 years) were evaluated as a control group. Additionally, we assessed the clinical manifestations of FD. RESULTS: Seven children (15.9%) with FD had brain MRI evidence of asymptomatic WML (5 girls, mean age 14.8 years, range: 13-20 years) compared with 3 children (6.5%) in the control group (p = 0.01). Brain abnormalities in patients with FD revealed WML, deep gray matter and infratentorial involvement. Three patients presented two lesions each. None of the children showed microbleeds. Regarding clinical manifestations, 90.9% of the patients had signs or symptoms of FD. CONCLUSION: We identified asymptomatic white matter brain lesions in 15.9% of children with FD without clinical history of stroke. FD is a treatable disorder that should be routinely included in the differential diagnosis of both symptomatic and asymptomatic brain lesions in children and adolescents. The detection of brain lesions may foster earlier treatment.

Protein stabilization by RSUME accounts for PTTG pituitary tumor abundance and oncogenicity.

Increased levels of the proto-oncogene pituitary tumor-transforming gene 1 (PTTG) have been repeatedly reported in several human solid tumors, especially in endocrine-related tumors such as pituitary adenomas. Securin PTTG has a critical role in pituitary tumorigenesis. However, the cause of upregulation has not been found yet, despite analyses made at the gene, promoter and mRNA level that show that no mutations, epigenetic modifications or other mechanisms that deregulate its expression may explain its overexpression and action as an oncogene. We describe that high PTTG protein levels are induced by the RWD-containing sumoylation enhancer (RWDD3 or RSUME), a protein originally identified in the same pituitary tumor cell line in which PTTG was also cloned. We demonstrate that PTTG and RSUME have a positive expression correlation in human pituitary adenomas. RSUME increases PTTG protein in pituitary tumor cell lines, prolongs the half-life of PTTG protein and regulates the PTTG induction by estradiol. As a consequence, RSUME enhances PTTG transcription factor and securin activities. PTTG hyperactivity on the cell cycle resulted in recurrent and unequal divisions without cytokinesis, and the consequential appearance of aneuploidies and multinucleated cells in the tumor. RSUME knockdown diminishes securin PTTG and reduces its tumorigenic potential in a xenograft mouse model. Taken together, our findings show that PTTG high protein steady state levels account for PTTG tumor abundance and demonstrate a critical role of RSUME in this process in pituitary tumor cells.

Surgical treatment of cerebellar hemangioblastomas.

BACKGROUND: Hemangioblastomas (HBL) are uncommon tumors of the central nervous system (CNS), corresponding to 1-2.5% of all intracranial tumors. They can present sporadically or in patients with von Hippel-Lindau (VHL) disease and are most often located in the cerebellum, brainstem, and spinal cord. VHL disease is a multiple neoplasia syndrome inherited in an autosomal dominant fashion and caused by a VHL suppressor gene deletion. We present our experience in the management of patients with cerebellar HBL. METHODS: Thirty consecutive patients with cerebellar HBL were included in this study. Hospital charts, radiological images, and operative records were reviewed. Modified Rankin scores were used to evaluate the clinical course. RESULTS: Thirty patients diagnosed with cerebellar HBL were operated. Complete total resection was achieved in 93% of the cases. Postoperatively, 83% of the patients showed good functional recovery. CONCLUSIONS: HBL of the cerebellum should be resected when symptomatic or when the tumor (or a tumor-associated cyst) shows signs of enlargement. Surgical intent should seek en bloc resection to minimize intraoperative bleeding. Patients with HBLs must be tested for VHL gene mutations, and in confirmed cases, relatives should be offered genetic counseling.

Detection of Helicobacter pylori in human carotid atherosclerotic plaques.

BACKGROUND AND PURPOSE: Several lines of evidence point toward a relationship between infection and atherosclerotic vascular disease. Thus, infection and inflammation often precede ischemic neurological events. Transient alterations in coagulation and direct arterial invasion by certain microorganisms have been reported. Helicobacter pylori infection is the major cause of peptic ulcer disease and appears to be a risk factor for ischemic cerebrovascular disease. However, in contrast to other chronic infectious agents, H pylori has not been consistently isolated from atherosclerotic lesions. METHODS: We investigated the presence of H pylori in 38 atherosclerotic plaques obtained at carotid endarterectomy by using morphological and immunohistochemical techniques and a highly sensitive polymerase chain reaction method. We performed immunohistochemical detection of intercellular adhesion molecule-1, a marker related to inflammatory cell response. We also examined 7 carotid arteries obtained at autopsy from subjects without carotid atherosclerosis. RESULTS: H pylori DNA was found in 20 of 38 atherosclerotic plaques. Ten of the H pylori DNA-positive plaques also showed morphological and immunohistochemical evidence of H pylori infection. None of 7 normal carotid arteries was positive for H pylori. Intercellular adhesion molecule-1 was expressed in 75% of H pylori-positive plaques and in 22% of H pylori-negative plaques. The presence of the microorganism was associated with male sex but was independent of age, vascular risk factor profile, and prior neurological symptoms. CONCLUSIONS: H pylori is present in a substantial number of carotid atherosclerotic lesions and is associated with features of inflammatory cell response. This study provides additional evidence of the relationship between H pylori infection and atherosclerotic disease.

Evidence for reflex activation of experiential complex partial seizures.

Reflex activation of seizures by thoughts or mental images is suggested by patients but has not been objectively demonstrated. The authors present a report of a man with experiential complex partial seizures reliably activated by thinking about his family home. During monitoring, such seizures were repeatedly induced in this way. Seizures were refractory to antiepileptic drugs, but ceased after left temporal resection. Pathologic examination showed cortical dysplasia.

Insomnia associated with thalamic involvement in E200K Creutzfeldt-Jakob disease.

BACKGROUND: Insomnia with predominant thalamic involvement and minor cortical and cerebellar pathologic changes is not characteristic of familial Creutzfeldt-Jakob disease (CJD) but is a hallmark of fatal familial insomnia. OBJECTIVE: To report a 53-year-old woman with intractable insomnia as her initial symptom of disease. METHODS: The authors characterized clinical, pathologic, and molecular features of the disease using EEG, polysomnography, neurohistology, Western blotting, protein sequencing, and prion protein (PrP) gene (PRNP) analysis. RESULTS: The patient developed dysgraphia, dysarthria, bulimia, myoclonus, memory loss, visual hallucinations, and opisthotonos, as well as pyramidal, extrapyramidal, and cerebellar signs. Polysomnographic studies showed an absence of stages 3 and 4, and REM. She died 8 months after onset. On neuropathologic examination, there was major thalamic involvement characterized by neuronal loss, spongiform changes, and prominent gliosis. The inferior olivary nuclei exhibited chromatolysis, neuronal loss, and gliosis. Spongiform changes were mild in the neocortex and not evident in the cerebellum. PrP immunopositivity was present in these areas as well as in the thalamus. PRNP analysis showed the haplotype E200K-129M. Western blot analysis showed the presence of proteinase K (PK)-resistant PrP (PrP(sc)) with the nonglycosylated isoform of approximately 21 kd, corresponding in size to that of type 1 PrP(sc). N-terminal protein sequencing demonstrated PK cleavage sites at glycine (G) 82 and G78, as previously reported in CJD with the E200K-129 M haplotype. CONCLUSIONS: Insomnia may be a prominent early symptom in cases of CJD linked to the E200K-129M haplotype in which the thalamus is severely affected.

Autosomal dominant neuromuscular disease with cylindrical spirals.

Cylindrical spirals (CS) have been reported in muscle biopsies from five individual cases, as well as in two belonging to one family where there was another affected member, clinically associated with cramps, pain, stiffness and/or weakness. Here we studied muscle biopsies of a 70-yr-old mother and her 52-yr-old son, the latter with an associated neuropathy, both with late clinical onset in whose family at least 10 other members, spanning five generations, were diversely affected by muscular weakness, gait disorders, motor impairment and/or scoliosis, featuring an autosomal dominant trait with variable expression. CS as the main pathological findings were observed by light microscopy mostly in type 2 fibres, consisting of subsarcolemmal or intermyofibrillar granular and/or rod-like clusters, bluish with haematoxylin, bright red with Gomori's modified trichrome, non- or lightly reactive with PAS, faintly coloured with NADH-TR, non-reactive with SDH or ATPase, strongly stained with non-specific esterase and myoadenylate deaminase. Ultrastructurally, CS appeared as concentrically wrapped lamellae 1-2 microns in diameter. On occasion CS merged into tubular vesicular structures strongly resembling tubular aggregates (TA). Dilation of terminal cisternae (TC) in their proximity supports an origin from the sarcoplasmic reticulum (SR). Variable gene expression possibly explains both the highly diverse clinical compromise and time of onset.

Duchenne muscular dystrophy and myotonic dystrophy in the same patient.

We report on the first patient identified with myotonic dystrophy and Duchenne muscular dystrophy (DMD). The family of the propositus had a strong history of myotonic dystrophy, and there was an intrafamilial pathological expansion of the responsible CTG repeat between the mildly affected mother (160 repeats; normal 27 repeats) and her more severely affected son (650 repeats), and his sister (650 repeats). The propositus was an isolated case of Duchenne muscular dystrophy with marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory post age 16. Myotonic dystrophy could interfere to some extent with the progression of Duchenne dystrophy. However, other interpretations are possible. Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry could be sufficient to ameliorate typical DMD clinical severity, or the patient may present a somatic mosaic. The pathophysiological interactions of these two unlinked disorders are discussed at the clinical and histopathological levels.

Childhood neuronal ceroid-lipofuscinoses in Argentina.

We report on 30 cases of neuronal ceroid lipofuscinoses (NCL), mainly diagnosed in 1985-1993 in Argentina, whose population is predominantly of European descent. Twenty-four cases were late infantile Jansky-Bielschowsky (LINCL) and 6 were juvenile Spielmeyer-Vogt (JNCL). Sex ratio was female:male, 20:10. Age range and mean at onset and at diagnosis for the LINCL cases were 1-6 years, mean 3.1, and 2-11 years, mean 5.5, and for the JNCL cases, 5-9 years, mean 7, and 9-18 years, mean 13, respectively. Cases were referred for biopsy after neurological examination, and most included complete electrophysiological [electroencephalography (EEG) with photic stimulation, electroretinography (ERG), and visual-evoked potential (VEP)], neuroimaging, and neurometabolic investigation. NCL was the first suspected clinical diagnosis, followed by mitochondrial encephalopathy in some cases of recent onset. Except for 1 case, clinical findings were homogeneous in LINCL, characterized by refractive epilepsy, mental regression and progressive deterioration, ataxia, myoclonia, and visual loss. Abnormal VEP, ERG, and EEG, with polyphasic high-voltage spikes when photic stimulation was performed at low frequency, were observed. Visual impairment and retinitis pigmentosa were early manifestations in 4/6 JNCL, followed by mental abnormalities, motor deterioration, and myoclonic jerks, while 2/4 followed an atypical course. In both variants inheritance was autosomal-recessive. Five out of 27 families had more than 1 affected member, 3 of whom were included in our series. Diagnosis was initially performed in conjunctival biopsy in 3 cases, skin in 5, muscle in 17, and brain in 5, though most cases had a concomitant biopsy from another tissue including nerve, and there was a single brain autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Dysembryoplastic neuroepithelial tumor: morphological, immunocytochemical, and deoxyribonucleic acid analyses in a pediatric series.

Overtreatment by radiotherapy and/or chemotherapy for central nervous system tumors in infancy and childhood may be deleterious, so the recognition of surgically curable clinicopathological entities is mandatory. The dysembryoplastic neuroepithelial tumor is a complex multinodular lesion consisting of glial nodules, associated with a specific glioneuronal element and/or with focal cortical dysplasia, and occurring in young patients presenting with intractable, mostly complex partial, seizures without neurological deterioration. We report on 14 patients; 9 were from a series of 600 pediatric patients with intracranial central nervous system tumors studied at a single institution from 1988 to 1993, and 5 were referred from other pediatric hospitals. Six tumors were frontal, six were temporal, one was parietal, and one was occipitoparietal. Computed tomographic scans disclosed hypodense lesions with cystic appearances in 4 patients and slight focal postcontrast enhancements in only 2 patients, whereas magnetic resonance imaging, available for 7 of 14 patients, showed hypointense lesions in T1-weighted images and hyperintense lesions in T2-weighted images. Deformities of the overlying cranium were also observed in five patients. The age range at the time of surgery (excluding a 20-year-old male patient who underwent surgery at the main pediatric hospital) was 2.6 to 13 years, with a mean of 6.68 years. The male to female patient ratio was 10:4, and the duration of symptoms was 0.2 to 6 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy.

Intractable seizures are the most common manifestation in severe cases of tuberous sclerosis. Multidrug resistance type 1 (MDR1) gene expression is directly linked to the resistance of tumor cells to chemotherapy as the major cause of treatment failure, but it has not been reported in tuberous sclerosis cells nor has the relationship between the MDR1 gene and antiepileptic drugs been described. A 4-month-old female is described with poorly controlled seizures secondary to tuberous sclerosis. The patient was treated with antiepileptic drugs, including phenytoin, phenobarbital, and lorazepam, without improvement of symptoms. Phenytoin blood levels were invariably subtherapeutic and ranged from 0.45 to 3.55 microg/mL, despite several consecutive intravenous loading doses. Surgical treatment with total resection of the brain lesions was performed as a last resort. Immunohistochemical analysis of the resected tissues revealed high levels of P-glycoprotein 170 expression, the product of the MDR1 gene. Both MDR1 gene expression and persistently low phenytoin levels likely share a common pathway liable to induce drug-resistant epilepsy.

Clues and pitfalls in stereotactic biopsy of the central nervous system.

We present a 6-year experience on 307 stereotactic biopsy specimens of the central nervous system using Leksell's and Talairach's systems independently and either Leksell or Sedan needles. Patients with deep cerebral lesions (basal ganglia, parasellar, pineal, or third ventricle), those located in highly functional areas or those poorly defined on imaging studies, as well as candidates for brachytherapy, were selected. Smear examination during surgery was a routine procedure followed by conventional histologic methods. Ages ranged from 8 months to 81 years (mean, 33.64 years). The series comprised 258 tumors, 28 nonneoplastic cases, and 21 nondiagnostic samples. Of the 258 tumors, 179 were supratentorial, 28 were infratentorial, 36 were of the pineal area, and 15 were from sellar and suprasellar regions. Results of the histologic examination showed the following: astrocytic tumors, 148 (57.36%); oligodendroglial, 25 (9.68%); ependymal, six (2.32%); primitive neuroectodermal tumors, 17, including 14 pineoblastomas (5.45%) and three medulloblastomas (1.16%), seven lymphomas (2.71%), seven meningiomas (2.71%), four schwannomas (1.55%), eight craniopharyngiomas (3.10%), 12 germinomas (4.65%), and 20 metastases (7.78%). Nontumoral cases included six arteriovenous malformations, six pyogenic lesions, seven infarcts, two hematomas, one multiple sclerosis plaque, one Fahr, one progressive multifocal leukoencephalopathy, one tuberculosis, one cysticercosis, and one Chagas' encephalitis. Awareness of the cerebellar granular layer in infratentorial targets as well as glial reaction around craniopharyngiomas is essential to avoid misdiagnosis. Difficulties were basically differential diagnosis between well-differentiated astrocytomas vs glial reaction, as well as poorly differentiated neoplasms vs metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Chronic hereditary ataxic polyneuropathy]. / Polineuropatia atáxica hereditaria crónica.

Sensory ataxic polyneuropathies are characterised by the presence of sensory ataxia due to damage to large myelinated sensory fibres, with total or relative preservation of muscle strength, pain and temperature sensation. Hereditary ataxic polyneuropathies are exceptional and very few families with this disorder have been reported so far. We here describe the neurological, electrophysiological and sural nerve biopsy data of four siblings with an ataxic chronic polyneuropathy, starting after age 50. They had an ataxic gait which worsened in darkness, horizontal nystagmus, hypo or areflexia, and severe impairment of limbs' propriocaption. Nerve conduction studies showed absent sensory nerve action potentials in all nerves tested. Somatosensory evoked potentials showed reduced amplitude and prolonged latencies. Sural nerve biopsy showed a severe loss of myelinated and unmyelinated fibres. Symptoms slowly progressed over the years. The recognition of this syndrome is important in the search for the etiology of chronic ataxic neuropathies.

Progressive multifocal leukoencephalopathy presenting as IRIS in an AIDS patient. A case report and literature review.

Progressive multifocal leukoencephalopathy causes an infection of the central nervous system by JC virus (JCV), a polyomavirus that destroys oligodendrocytes and their myelin processes. Here, we describe a patient with AIDS who developed a progressive multifocal leucoencephalopathy with the clinical and neuroimaging characteristics of the immune inflammatory reconstitution syndrome. Unlike other opportunistic infections, this disease can present when CD4 T cell counts are higher than those associated with AIDS and also when patients are receiving combined antiretroviral therapy. Clinical suspicion of this form of the disease is based on clinical examination that shows focal neurological deficits associated with magnetic resonance images findings. The histopathological examination of brain biopsy smears and the identification of JCV in cerebrospinal fluid or brain tissue are definitive for the diagnosis.

Adenomas no funcionantes: análisis retrospectivo de 202 pacientes / Non-functional adenomas: retrospective analysis of 202 patients

RESUMEN Los pacientes con adenomas hipofisarios constituyen una población heterogénea y requieren un enfoque individualizado. El objetivo de nuestro trabajo fue analizar nuestra población con adenomas hipofisarios no funcionantes (ACNF) y evaluar factores pronóstico de crecimiento (como el Ki-67) que ayuden en la toma de decisiones. Se realizó un análisis retrospectivo de 202 pacientes, incluyendo evaluación basal, enfoque terapéutico y evolución tumoral en 2 grupos: pacientes con conducta expectante (n = 69) y pacientes con cirugía (n = 133). La serie tuvo 55% de pacientes mujeres y la edad media al diagnóstico fue de 49 años. Los motivos de consulta más frecuentes fueron incidentaloma hipofisario y alteraciones visuales. Radiológicamente, 83% fueron macroadenomas, 77% invasivos y 55% mostraron compromiso visual. Entre los adenomas invasores, el 53% tenían disfunción hipofisaria, siendo el hipogonadismo el hallazgo más frecuente. El tratamiento inicial fue la cirugía en el 65,8% realizándose por vía transnasal en el 79% de los casos. Las complicaciones más frecuentes fueron diabetes insípida transitoria e hiponatremia, con mayor incidencia de diabetes insípida permanente en la cirugía transcraneal. La inmunohistoquímica mostró gonatropinomas en el 43,4% de los casos y fue negativa en el 37,7%. Doce adenomas tuvieron índice de proliferación Ki-67 ≥3%. Luego de la cirugía 56,8% de los pacientes mejoraron el campo visual, 22,6% recuperó alguna función endocrina y 18,8% agregó un nuevo déficit. En pacientes no operados, se observó crecimiento tumoral en 5,6% de los adenomas Hardy 1-2 y en el 21% de los Hardy 3-4. Entre los adenomas operados, aquellos sin resto tumoral postoperatorio no presentaron recurrencia. De los tumores con remanente postoperatorio (78,6%) no irradiados, el 41,5% mostró recrecimiento lesional al seguimiento. Este porcentaje se eleva a 66,6% en aquellos con Ki-67 ≥3% y disminuye a 12% en los que recibieron radioterapia.

ABSTRACT Patients with pituitary adenomas are a heterogeneous population and require an individualized approach. The aim of our study was to analyze our population of patients with nonfunctioning pituitary adenomas (NFA) and to evaluate prognostic growth factors (such as Ki-67) that help in decision making. A retrospective analysis of 202 patients, including baseline assessment, therapeutic approach and tumor evolution was performed in 2 groups: expectant management (n = 69) and surgery (n = 133). The mean age at diagnosis was 49 years, 55% women. The most frequent reasons for consultation were pituitary incidentaloma and visual impairment. Eighty three percent were macroadenomas, 77% invasive, and 55% with visual impairment. Among the invasive adenomas, 53% had pituitary dysfunction, with hypogonadism being the most frequent finding. The initial treatment was surgery in 65.8%, 79% of them through transnasal approach. The most frequent complications were transient diabetes insipidus and hyponatremia, with a higher incidence of permanent diabetes insipidus in transcranial surgery. The immunohistochemistry showed: 43.4% gonadotropinomas, 37.7% negative. Twelve adenomas had proliferation index Ki-67 ≥3%. After surgery, 56.8% improved the visual fields, 22.6% recovered some endocrine function and 18.8% added a new deficit. In non-operated patients, tumor growth was observed in 5.6% of the Hardy 1-2 adenomas and 21% of the Hardy 3-4 adenomas. Among the operated adenomas, those without postoperative tumor residue did not present recurrence. In tumors with non-irradiated postoperative remnant (78.6%), 41.5% increased. This percentage rises to 66.6% in those with Ki-67 ≥3%, and decreases to 12% in those who received radiotherapy.