Arnold-Chiari Malformation PDF

 Definition / general Chiari malformations, types I-IV, refer to a Arnold-Chiari Malformation spectrum of congenital hindbrain abnormalities affecting the structural relationships between...

 Definition / general Chiari malformations, types I-IV, refer to a Arnold-Chiari Malformation spectrum of congenital hindbrain abnormalities affecting the structural relationships between the brainstem, cerebellum, upper cervical cord and bony cranial base Scale of severity is rated I - IV with IV being the most severe Clinical features Chiari’s type I malformation is usually seen in older children and adults; type II is seen in infants and younger children Some patients are asymptomatic and the malformation does not interfere with activities of daily living Symptomatic patients often present with headaches, fatigue, muscle weakness, difficulty swallowing, vomiting, dizziness, nausea, tinnitus, impaired coordination, neck pain and speech problems Treatment Vitamin A and folic acid supplementation in pregnancy reduces the risk of its development In symptomatic cases, medications may ease certain symptoms such as pain Surgical shunting and decompression of the foramen magnum are the only treatments which reduce the impact of hydrocephalus and the progression of damage to the central nervous system Chiari type I malformation: elongation of one or both cerebellar tonsils, which protrude through the foramen magnum of the spinal canal and may become sclerotic; there may be associated syringomyelia or syringobulbia Chiari type II malformation: Most common cause of congenital hydrocephalus Cerebellar tonsils extend far down into the spinal canal, accompanied by an elongated fourth ventricle and brainstem There is a lumbar spina bifida with a meningomyelocele  Chiari type IIII malformation: further herniation of the cerebellum below the foramen magnum forming an encephalocele, in addition to spina bifida, syringomyelia and hydrocephalus Chiari type IV malformation: hypoplasia or aplasia of the cerebellum Dandy-Walker malformation Definition / general Dandy-Walker syndrome (DWS) is a congenital brain malformation involving the cerebellum The essential features are: enlargement of the posterior fossa, cystic dilatation of the fourth ventricle and agenesis of the vermis Clinical features The symptoms are related to hydrocephalus, cerebellar and cranial nerves dysfunction and to the presence of associated anomalies 80 - 90% present in the first year Prognostic factors The clinical course is very variable and depends on the severity of the associated central nervous system malformations, with neurologic development ranging from normal to severely intellectually disabled Treatment The goal of treatment is the control of the hydrocephalus and of the posterior fossa cyst Neural tube closure defects  Acute viral infections Herpes simplex encephalitis Definition / general Herpes simplex (HSV) encephalitis is a severe necrotizing viral infection preferentially involving the medial temporal and frontal lobes of the brain Pathophysiology Appears to arise independently of herpetic infections elsewhere in body (including herpes labialis Etiology Herpes simplex virus 1 (HSV1) causes > 90% of cases Herpes simplex virus 2 (HSV2) Clinical features Typically, follows a prodromal flu-like illness (including fever and headache) and manifests as superimposed behavioral changes, seizures, focal neurological signs and cognitive impairment Diagnosis CSF analysis typically demonstrates lymphocytosis (10 - 500x106/L, average 100x106/L) with or without red cells or xanthochromia, mildly elevated protein and normal or mildly decreased glucose Definite diagnosis is by PCR based detection of viral nucleic acid Immediate administration of intravenous acyclovir is recommended if the diagnosis is suspected Cytomegaloviral infections of the nervous system (CMV) Definition / general Cytomegalovirus (CMV) is the largest of the human herpes viruses and may cause a variety of clinical manifestations ranging from asymptomatic to fatal Severe, often fatal central (CNS) and peripheral nervous system infections are usually seen in patients with compromised immune systems or in maternal fetal infections in utero Epidemiology The vast majority of CMV CNS infections occur in patients with severe suppression of cell mediated immunity; infections are only rarely reported in apparently immunocompetent patients Prior to combined antiretroviral therapy, CMV nervous system infections usually occurred in AIDS patients; currently, they are seen as complications of organ transplantation, especially bone marrow and hematopoietic stem cell Cytomegalovirus is also the most common pathogen causing congenital fetal infection, resulting in severe neurological damage Diagnosis Radiology description Due to the absence of specific clinical symptomatology, diagnosis Cytomegaloviral encephalitis tends to localize to the usually requires polymerase chain reaction amplification of ependymal and subependymal regions cytomegaloviral genome from cerebrospinal fluid or other specimens Gross description Necrotizing and haemorragic encephalitis Microscopic (histologic) description Although immunohistochemical staining for Cytomegalovirus may be used as a confirmational assay, the distinctive nuclear and cytoplasmic cytopathic changes on routinely stained sections are diagnostic Toxoplasmosis Toxoplasma gondii is a prevalent obligate intracellular parasite Ability to form chronic and nonimmunogenic bradyzoite cysts, which typically form in the brain and muscle cells of infected mammals, including humans In the majority of immunocompetent individuals, primary or chronic (latent) infections are asymptomatic, however certain populations are at higher risk for severe disease, including congenitally infected fetuses, newborns and immunodeficient patients, particularly those with T-cell immunity deficiency, such as hematologic malignancies, bone marrow and solid organ transplant and acquired immune deficiency syndrome (AIDS). Cerebral toxoplasmosis is usually caused by reactivation of the latent cystic form of T. gondii in the central nervous system (CNS) and it as a major cause of morbidity and mortality among human immunodeficiency virus (HIV) infected patients, particularly in developing countries.  Rhinocerebral mucormycosis Mucormycosis is a rare life-threatening fungal infection occurring primarily in patients with diabetics or immunocompromised patients Networks of aseptate hyphae in straight angle, secondary to mucormycosis fungal infection. Alzheimer's disease Chronic neurodegenerative disease that usually starts slowly and gradually worsens over time. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. Causes ▪ Genetic ▪ Cholinergic hypothesis ▪ Amyloid hypothesis ▪ Tau hypothesis ▪ Other hypotheses: inflammatory, infections, air pollution….  This is a neurofibrillary "tangle" of Alzheimer's disease. The tangle appears as long pink filaments in the cytoplasm. They are composed of cytoskeletal intermediate filaments. The characteristic microscopic findings of Alzheimer disease include neuritic plaques ("senile plaques") which are extracellular deposits of the amyloid beta-protein (Aß). In the more numerous, smaller diffuse plaques this Aß alone is present as filamentous masses. However, the diagnostic neuritic plaques also have dystrophic dilated and tortuous neurites, microglia, and surrounding reactive astrocytes. These plaques are best seen with a silver stain, as seen here in a case with many plaques of varying size. Neurofibrillary “tangle” of Alzheimer disease are also seen best microscopically with a silver stain, as shown here. Though a distinctive morphologic finding, the presence of these tangles is not a diagnostic criterion for Alzheimer disease.  Dementia with Lewy bodies Dementia with Lewy bodies (DLB) is a type of dementia accompanied by changes in behavior, cognition, and movement. Dementia with Lewy bodies (DLB) is a progressive neurodegenerative dementia. Together with Parkinson's disease dementia, it is one of the Lewy body dementias, The exact cause is unknown, but involves widespread deposits of abnormal clumps of alpha-synuclein protein known as Lewy bodies in neurons. DLB is one of the three most common types of dementia, along with Alzheimer's, and vascular dementia Parkinson disease  Creutzfeldt-Jakob disease Prion disease results from the benign form of a prion protein changing to an insoluble protease resistant form → formation of plaques in brain Caused by prion protein that assumes an abnormal configuration, which promotes change to abnormal configuration of other proteins Is human equivalent of "mad cow disease", due to epidemic of bovine spongiform encephalopathy Symptoms: Behavioral change, cerebellar ataxia and dementia Amyloid plaques are found in approximately 10% of Spongiosis (vacuolation) and neuronal loss are prominent histopathologic cases of CJD. This light photomicrograph of brain features of CJD. This light photomicrograph of brain tissue in a case of tissue reveals the presence of typical amyloid vCJD shows extensive vacuolation in the cortex with associated neuronal plaques found in a case of vCJD. The plaques are loss variable in size and consist of a hyaline eosinophilic core with a peripheral margin of radiating fibrils surrounded by a pale halo  Choroid plexus cyst Definition / general Small cyst of choroid plexus containing CSF Radiology description On CT and MRI, usually show CSF density Microscopic (histologic) description Cyst wall lined by cuboidal to columnar epithelium Choroid plexus papilloma Definition / general Rare ( < 1% of intracranial neoplasms), slow growing tumor commonly in ventricular system and associated with hydrocephalus due to excess production of CSF or direct tumor obstruction of CSF flow 85% occur at age 10 years or less; often present at birth 10 - 30% become histologically malignant High survival unless becomes malignant (then 5 year survival is 26%) although histology does not predict behavior Gross description Larger than normal choroid plexus Lobulated encapsulated mass Microscopic (histologic) description Resembles normal choroid plexus with single layer of epithelial cells overlying a fibrovascular core Epithelial cells are more crowded and piled up than normal Mild atypia May have vascular stalk that provides mobility within ventricular system Glial tumors Definition / general Most common CNS tumor Includes astrocytoma, ependymoma, glioblastoma, oligodendroglioma and various subtypes / combinations Diagnosis of "glioma" may be used for frozen section but is not a final diagnosis Important to identify oligodendroglial component, due to effectiveness of chemotherapy for these gliomas Histological grading of diffuse astrocytic tumors According to the 2016 WHO classification, diffuse astrocytomas are graded using a three tiered system (II, III and IV); there are no grade I infiltrating astrocytomas WHO grading scheme is based on the presence or absence of four histological parameters: 1. Nuclear atypia: defined as nuclear pleomorphism and hyperchromasia 2. Mitoses Must be unequivocal Solitary mitosis in a large specimen does not justify the WHO grade III designation Ki67 proliferation index aids in the separation of grade II from grade III tumors 3. Microvascular proliferation: two forms are recognized Glomeruloid type, which is more common but prognostically less significant since it is also commonly encountered in low grade gliomas such as pilocytic astrocytoma Endothelial proliferation within the lumen of larger vessels, which is less common but is more closely associated with high grade gliomas 4. Necrosis: two types are recognized Coagulative necrosis Pseudopalisading necrosis WHO histological grading of diffuse WHO histological grading of localized astrocytic tumors astrocytic tumors WHO grade II tumors (diffuse astrocytoma): Pilocytic astrocytoma corresponds to WHO show only nuclear atypia grade I WHO grade III tumors (anaplastic Subependymal giant cell astrocytoma corresponds to WHO grade I astrocytoma): show nuclear atypia with focal or dispersed anaplasia, significant Pleomorphic xanthoastrocytoma corresponds to proliferative activity and mitoses WHO grade II and anaplastic pleomorphic xanthoastrocytoma corresponds to WHO grade WHO grade IV tumors (glioblastoma): show III nuclear atypia, mitoses, microvascular proliferation or necrosis Pilocytic astrocytoma - grade I Definition / general Pilocytic means "hair-like," due to long, bipolar processes Most common CNS neoplasm of childhood Better prognosis than diffuse types, particularly if resectable (such as cerebellar tumors) WHO grade I Epidemiology Most commonly arises during the first two decades of life (peak age 8 - 13 years) Sites Usually involves midline structures in posterior fossa including cerebellum Radiology description Pilocytic astrocytomas are well circumscribed and contrast enhancing, often cystic masses Some assume cyst mural nodule architecture Gross description Discrete and often cystic Microcystic or macrocystic; may have mural nodule Microscopic (histologic) description Bipolar neoplastic cells with elongated hair-like processes that are arranged in parallel bundles and resemble mats of hair Rosenthal fibers (tapered corkscrew shaped, brightly eosinophilic, hyaline masses), often associated with eosinophilic protein droplets (resembling foamy macrophages) Rarely malignant degeneration with hypercellularity, mitotic figures and necrosis Characterized by a biphasic pattern with varying proportions of piloid areas alternating with spongy areas Piloid areas are formed of compacted strongly GFAP+ bipolar cells (with hair-like bipolar processes) associated with Rosenthal fibers Spongy areas are loosely textured and formed of weakly GFAP+ multipolar cells (protoplasmic astrocytes) associated with microcysts and eosinophilic granular bodies (brightly eosinophilic PAS+ globular aggregates) Degenerative changes include hyalinized blood vessels, infarct-like necrosis, degenerative nuclear atypia, calcification, hemosiderin deposits and lymphocytic infiltrate  Pilocytic Astrocytoma (PA) characteristically exhibits biphasic Rosenthal fibers morphology featuring densely fibrillar, compact regions alternating with loosely-cohesive microcystic or myxoid areas Photomicrograph demonstrating GFAP-immunoreactivity in a pilocytic astrocytoma. Ependymoma Definition / general Slowly growing tumor of ependymal cells arising from walls of ventricles or spinal canal Exhibit glial (GFAP+) and epithelial (EMA+) differentiation Epidemiology 3 - 9% of primary CNS tumors More common in children Infratentorial ependymomas more common in children; cause hydrocephalus from obstruction if in posterior fossa Spinal tumours more common in adults (30 - 40 years); better able to excise completely and generally better prognosis at this site WHO grade II Radiology description Well circumscribed lesions with variable enhancement Gross description Soft tan masses Grows exophytically into fourth ventricle Microscopic (histologic) description Moderately cellular, composed of monomorphic cells with round / oval nuclei and salt and pepper chromatin No / rare mitoses are rare Key histological features are perivascular pseudorosettes and ependymal rosettes Ependymal rosettes and ependymal canals: Composed of columnar cells arranged around a central lumen Lumen may be round or oval, does not have a hypereosinophilic border True rosettes are diagnostic of ependymoma but not always present Perivascular (pseudo) rosettes: Ependymal cell processes directed towards vessel wall, processes become thinner as they extend around blood vessel with formation of perivascular anuclear zones of GFAP+ fibrillary processes More common than ependymal rosettes in ependymoma but also present in glioma Diffuse astrocytoma Definition / general Well differentiated diffusely infiltrating glioma with astrocytic features Epidemiology Most commonly affects young adults in their mid 30s Sites Occurs throughout the CNS but is preferentially located in the cerebral hemispheres especially the frontal lobes Clinical features Gradual onset of symptoms Seizures are a common symptom in cerebral hemispheric lesions Changes in behavior or personality, especially in frontal lobe tumors Uncommonly, site dependent neurological deficits Manifestations of increased intracranial pressure Grading WHO grade II WHO grade III (Anaplastic Astrocytoma) Radiology description Expanding intra-axial poorly defined mass of low signal Variable peritumoral edema and mass effect No contrast enhancement Enhancement indicates tumor progression to higher grades Gross description Ill defined neoplasm with blurring of gray white junction and expansion of the infiltrated brain areas Variable textures: firm, soft, gelatinous, granular Variable microcystic change imparting a spongy appearance Variable calcification with a gritty sensation Microscopic (histologic) description Infiltrative, diffuse growth pattern Moderately cellular Irregular cell distribution Nuclear atypia is typical, yet variable: enlarged elongated hyperchromatic irregular nuclei This glioma with cystic spaces is arising in the peripheral cerebral hemisphere. As No mitotic activity (a single mitosis in a sizable specimen is allowed) in most gliomas, it is difficult to tell where the margin is located. Gliomas in No necrosis or microvascular proliferation adults typically arise in the cerebral hemispheres, above the tentorium. Anaplastic Astrocytoma Oligodendroglioma Essential features Morphology typically resembles that of oligodendrocytes with rounded nuclei and artifactually clear surrounding cytoplasm on routinely processed specimens Histologic features often include a branching capillary pattern and microcalcifications Preferentially occurs in adult patients within the cerebral hemispheres Epidemiology Peak incidence age 35 - 44 years Sites Most commonly found in the cortex and white matter of the cerebral hemispheres Frontal lobe is the most common location (> 50% of cases) Grading Grade II of III (anaplastic) Radiology description CT scan typically shows a hypodense or isodense mass lesion that is well demarcated and located in the cerebral hemispheres - either the cortex or subcortical white matter Calcifications can be present Gross description Typically a soft, relatively well defined, greyish pink mass arising in the cortex or subcortical white matter Calcifications may lead to a gritty texture; in extreme cases dense calcifications can present as intratumoral stones Microscopic (histologic) description Diffusely infiltrating tumor with moderate cellularity Tumor cells are typically monomorphic with round nuclei, salt and pepper chromatin pattern and inconspicuous nucleoli Routinely processed formalin fixed, paraffin embedded material often shows artifactual retraction of the cytoplasm leading to the characteristic "fried egg" appearance of tumor cells Dense network of fine branching capillaries, classically referred to as a "chicken wire" pattern, is often seen Small punctate calcifications, particularly along blood vessels, may be present but this is not a specific finding Mitoses are allowed but should be infrequent "Chicken wire" vessels Glioblastoma multiforme Definition / general Malignant primary brain tumor with predominant astrocytic differentiation WHO grade IV "Multiforme" due to variegated gross appearance (firm white areas, yellow necrotic areas, hemorrhagic areas and cystic areas) as well as diverse histological features Sites Usually supratentorial; uncommon in cerebellum, rare in spinal cord Clinical features 12 - 15% of adult intracranial tumors, 50 - 60% of astrocytic neoplasms Either primary or secondary (develops slowly from grade II or III astrocytoma) May be under graded on small stereotactic biopsies due to regional heterogeneity Median survival is 1 year; 5 year survival < 5%; Radiology description Contrast enhancing (ring pattern is characteristic), large, surrounded by peritumoral edema, mass effect Gross description Large tumors are poorly delineated Usually solitary but may cross midline through corpus callosum, massa intermedia or anterior commissure to produce a "butterfly" lesion Often peritumoral edema Cut section is variegated (yellowish necrotic central area, grayish peripheral rim, recent and old hemorrhage, cysts due to liquefied necrotic tumor tissue) Usually intraparenchymal Astrocytomas can range from low grade to high grade. Seen here is the highest grade and the worst possible form of glioma--a glioblastoma (previously glioblastoma multiforme). They occur in adults. Glioblastomas are quite vascular with prominent areas of necrosis and hemorrhage. Note how this large mass has crossed the midline to the opposite hemisphere. Butterfly glioma Microscopic (histologic) description High grade astrocytoma (anaplastic, nuclear atypia, cellular pleomorphism, mitotic activity) Microvascular proliferation (formerly "endothelial proliferation") with thickened vascular walls due to endothelial cell hyperplasia (increase in nuclei in vessel wall) and hypertrophy; also formation of multiple lumina resembling glomerulus Usually hypercellular with mitotic figures (some atypical), multinucleated tumor cells, bizarre nuclei, karyorrhectic cells May have pseudopalisading necrosis (tumor cells around necrotic zones) pseudopalisading with necrosis Glioblastoma. Vascular endothelial proliferation. Astroblastoma Definition / general Rare ( < 3% of primary brain gliomas), compact glial neoplasm with perivascular pseudorosettes formed of GFAP+ cells arranged around central, often sclerotic, blood vessels Epidemiology Usually children and young adults, median age 11 years Radiology description Discrete supratentorial cerebral, often superficial, contrast enhancing mass Cystic change is common Gross description Well circumscribed, peripheral, cerebral hemispheric masses Firm, often cystic Microscopic (histologic) description Well circumscribed with discrete pushing borders, occasionally infiltrative in high grade lesions Perivascular pseudorosettes resembling ependymoma but with thick processes from cell body to adventitia of vessel Also vascular hyalinization Embryonal tumors Medulloblastoma Essential features Small round undifferentiated cells with mild to moderate nuclear pleomorphism High mitotic count Cerebellum and dorsal brain, fourth ventricle Epidemiology Medulloblastoma is the most common CNS embryonal tumor of childhood and second only to pilocytic astrocytocytoma of all intracranial neoplasms Sites Fourth ventricle or cerebellar parenchyma Clinical features Signs and symptoms of increased intracranial pressure (headache, nausea, vomiting) Grading WHO grade IV Radiology description Solid, intensely contrast enhancing masses on CT and MRI Microscopic (histologic) description Classic medulloblastoma: Small blue round cell tumor Syncytial arrangement of densely packed undifferentiated cells (embryonal cells) Mitosis with apoptotic bodies Homer Wright rosettes Homer-Wright Rosettes The irregular posterior fossa mass that is seen here near the midline of the cerebellum and extending into the fourth ventricle above the brainstem is a medulloblastoma. This is one of the "small round blue cell" tumors and it most often occurs in children.  Meningeal tumors Meningioma Definition / general Most common primary brain tumor (20 - 30% of brain tumors, 6 per 100K annually) Derive from arachnoid cap cells (associated with dura mater, choroid plexus) Grow along external surface of brain or within ventricular system Slow growing (may grow rapidly during pregnancy), symptoms vague or related to brain compression Usually adults Female predominance: 2/3 of cerebral meningiomas occur in women Usually solitary; multiple tumors (seen in 1 - 6%) are occasionally associated with neurofibromatosis 2 Three grades exist based on WHO criteria Most are WHO grade I (benign) ~6% are WHO grade II (increased likelihood of recurrence) Rarely are WHO grade III (malignant with metastatic potential) Radiology description Strong and homogenous enhancement on MRI with contrast Usually display a "dural tail" Gross description Rounded and well circumscribed Attached to dura Tumor separates readily from brain May grow en plaque (along dural surface) and cause reactive (hyperostotic) bone changes This circumscribed reddish-yellow firm neoplasm beneath the dura next to the falx is a meningioma. The superior parasagittal location is quite common. Note how this meningioma beneath the dura has compressed the underlying cerebral hemisphere. Rarely, meningiomas can be more aggressive and invade underlying cerebrum or overlying bone. Microscopic (histologic) description Arachnoid plane exists between meningioma and CNS parenchyma Lobulated architecture, often contain "meningothelial" whorls Syncytial cells with indistinct cell membranes Eosinophilic cytoplasm Round uniform nuclei, intranuclear pseudoinclusions common May contain psammoma bodies Rarely necrosis or extensive hemorrhage Metastatic tumors Definition / general Most common brain tumors in community hospitals are metastases Primary is usually known: melanoma or carcinoma (lung, breast, kidney and GU) Meningeal carcinomatosis:Represents 4-8% of metastatic brain tumors Diffuse spread of tumor in subarachnoid space Associated with carcinoma of lung and breast Poor prognosis Gross description Seen here is a metastasis from a lung carcinoma. Sharply demarcated lesion at gray-white matter Metastases most often appear at the border of the junction, surrounded by edema grey and white matter in the distribution of the middle cerebral artery, as in this case, because that is where the blood flow (vascular distribution) is most likely to take metastases. Multiple tumor masses suggest a metastatic, not primary, malignant neoplasm Lecturas recomendadas