ࡱ>  /1&'()*+,-.5@ 2bjbj22 3XXT\\\\| d4sss```````$,fR~hTA`qssA`d0,0,0,)`0,`0,0,,K// 4\c/77(d0dk/,hhh//h/sGN0, sssA`A`D&, DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherCushings DiseasePituitary Hypersecretion of ACTH (usually a microadenoma)! Cortisol Obesity, Moon Face, Buffalo Hump, Osteoporosis Hirsutism, ! Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle WeaknessMoon Face Buffalo Hump55-75% of endogenous cases, more common in women Diffuse Bilateral Adrenal Hyperplasia w/ thick yellow cortex Suppression by High Dose Dexamethasone Inferior Petrosal Sinus gradient of 3:1Cushings Syndrome (Ectopic ACTH or CRH)Nonpituitary Neoplasm Secretion (Small Carcinoma, Bronchial & Pancreatic Carcinoids, Thymoma, Pheochromocytoma, Gastrinoma)! Cortisol Obesity, Moon Face, Buffalo Hump, Osteoporosis Hirsutism, ! Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle WeaknessSmall Cell CarcinomaMost common in men Diffuse Bilateral Adrenal Hyperplasia w/out nodularity of Bronchial Carcinoids suppressed by ! dose dexamethasoneCushings Syndrome (Adrenal Hypersecretion)Adrenal Adenoma Adrenal Carcinoma Adrenal Nodular Hyperplasia! Cortisol Obesity, Moon Face, Buffalo Hump, Osteoporosis Hirsutism, ! Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle Weakness! CRH & ACTH! CRH & ACTH Atrophy of adjacent cortex & contralateral adrenal cortexCushings Syndrome (Exogenous Cortisol Excess)Exogenous Cortisol Excess! Cortisol Obesity, Moon Face, Buffalo Hump, Osteoporosis Hirsutism, ! Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle WeaknessPrednisoneMost common source is Prednisone ! Pituitary ACTH & Small Adrenal Glands with thin cortex Zona Glomerulosa not affectedPseudo-Cushings Syndrome (Temporary Cortisol Excess)Depression, Alcoholism, Obesity, Eating Disorder, Stress & Illness! Cortisol Obesity, Moon Face, Buffalo Hump, Osteoporosis Hirsutism, ! Infections, HT, Thin Skin, Easy Bruising, Red Stria & Muscle WeaknessPrimary Aldosteronism (! Renin  Conn s Syndrome)Aldosterone secreting Adenoma! Aldosterone HT, ! Serum K+, ! Extracellular fluid, Alkalosis Weakness, Paesthesias, Visual Disturbances Headaches, Tetany, Cardiac decompensation! Renin & ! AldosteroneSmall yellow encapsulated tumor found usually on left & in @& Low Plasma Renin Activity (PRA) Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test)Primary Aldosteronism (! Renin  Adrenal Hyperplasia)Idiopathic! Aldosterone HT, ! Serum K+, ! Extracellular fluid, Alkalosis Weakness, Paesthesias, Visual Disturbances Headaches, Tetany, Cardiac decompensation! Renin & ! AldosteroneBilateral idiopathic hyperplasia = less common than Conn s Treat w/ spironolactone & something for HT Low Plasma Renin Activity (PRA) Aldosterone > 10 ng/dL after IV Saline (Saline Suppression Test)Secondary Aldosteronism (! Renin)Renal Artery Stenosis Renin producing tunor Chronic edema! Aldosterone HT, ! Serum K+, ! Extracellular fluid, Alkalosis Weakness, Paesthesias, Visual Disturbances Headaches, Tetany, Cardiac decompensation! Renin & ! AldosteroneHigh Plasma Renin Activity (PRA)Hyporenemic HypoaldosteronismBlack Licorice Chewing Tobacco! Aldosterone HypertensionCongenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)21-Hydroxylase Deficiency (CYP21A2 Deficiency)! ACTH & DHEA ! virilization  Classic = ! Aldosterone & Cortisol; ! Renin  Classic w/out wasting = nl Ald & ! Cortisol  Non-classical = nl Aldosterone & CortisolMost common cause of CAH & of ambiguous genitalia Hallmark is increased 17-Hydroxyprogesterone Treatment = replace aldosterone & cortisolCongenital Adrenal Hyperplasia (11b-Hydroxylase Deficiency)11b-Hydroxylase Deficiency! ACTH & DHEA ! virilization ! Deoxycortisone ! Aldosterone, Renin & CortisolCongenital Adrenal Hyperplasia (17a-Hydroxylase Deficiency)17a-Hydroxylase Deficiency! Aldosterone & ACTH ! Cortisol & Sex Steroids Hypertension & HypokalemiaAdrenal Pathology Adrenal Pathology (contd.) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherCortical Hypofunction (Primary Acute Insufficiency)Immediate steroid need Rapid steroid withdrawal Mass Destruction (DIC,Hemorrhage)! ACTH1) Immediate need for steroids  glands unable to respond 2) Rapid Withdrawal of steroids 3) Massive destruction  hemorrhage, anticoagulants, DICWaterhouse-Friderichsen SyndromeBacteremic InfectionAdrenal Hemorrhage ! Cortical Hypofunction! ACTHMore common in childrenCortical Hypofunction (Primary Chronic Insufficiency) (Addison s Disease)Autoimmune (majority) TB, Histoplasmosis, Carcinoma AIDS, Amyloidosis, Sarcoidosis HemochromatosisDestruction of adrenal cortex only Fatigue, muscle weakness, weight loss, GI upset Hypoglycemia, Salt craving, Prerenal Azotemia Acidosis, Hypotension & Hyperpigmentation! ACTHThin cortex w/ lymph infiltrates unaffected medullaCortical Hypofunction (Primary Chronic Insufficiency) (Addisons Disease) Subtype IAutoimmune (majority) TB, Histoplasmosis, Carcinoma AIDS, Amyloidosis, Sarcoidosis Hemochromatosis1) Adrenal insufficiency same as above 2) Hypoparathyroidism & Candidiasis! ACTHThin cortex w/ lymph infiltrates  unaffected medullaCortical Hypofunction (Primary Chronic Insufficiency) (Addison s Disease) Subtype II Schmidt s SyndromeAutoimmune (majority) TB, Histoplasmosis, Carcinoma AIDS, Amyloidosis, Sarcoidosis Hemochromatosis1) Adrenal insufficiency  same as above 2) Autoimmune thyroid disease & Type I DM! ACTHThin cortex w/ lymph infiltrates  unaffected medullaCortical Hypofunction (Primary Chronic Insufficiency) (Failure of Cortisol Production)Congenital Adrenal Hyperplasia Enzyme Inhibitor (ex. = ketoconazole)! ACTHCortical Hypofunction (Chronic 2/3 Insufficiency)Carcinoma, Infection, Irradiation, Infarction Prolonged use of steroids!! ACTHFatigue, muscle weakness, weight loss, GI upset Hypoglycemia, Salt craving,No aldosterone or ACTH deficiency Features of panhypopituitarism Delayed response to prolonged ACTH stimulation testPheochromocytomaMEN Type II or IIIHT with or without paroxysmal attacks Headaches, sweating, fever, GI upset, anxiety Palpitations orthostatic HT, numbness Cardiac manifestationsAdrenomedullary Chromafin cellsMost are solitary & in medulla; pink colored; large = encapsulated Diagnosis = Normetanephrine & metanephrine in plasma Clonidine useful in exclusion; Paroxysms can be provoked Rule of 10s = 10% extrarenal, bilateral, malignant, familialMEN Syndrome Type I (Wermer Syndrome)Parathyroid hyperplasia Pituitary adenomas Pancreatic islet tumorsMEN Syndrome Type II (Sipple Syndrome)Pheochromocytoma Medullary Thyroid carcinoma Parathyroid hyperplasiaMEN IIA = Parathyroid Adenoma MEN IIB = Mucocutaneous ganglioneuromas & Marfanoid habitusMEN Syndrome Type IIIPheochromocytoma Medullary Thyroid carcinoma Mucosal neuromas/Marfanoid features Endocrine Pancreas Pathology DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherPrimary Diabetes Mellitus Type IGenetic (HLA-DR3 &4) Autoimmune Antibodies Environment (Viral Infection)Blindness (Lens, Retina, Optic Nerve) CV disease (MI, stroke, gangrene) Nephropathy & Infections (Mucomycosis) Peripheral Neuropathy, Polydipsia & PolyuriaHLA-DR3&4 Diabetic ketoacidosisMI is #1 cause of death; Diabetic ketoacidosis Glycosylated collagens !Advanced Glycosylation End Products Intracellular hyperglycemia!Sorbitol (lens & Schwann Cell)Primary Diabetes Mellitus Type IIGenetic (not HLA related) Obesity Insulin Deficiency Insulin Resistance (receptor & GLUT)Blindness (Lens, Retina, Optic Nerve) CV disease (MI, stroke, gangrene) Nephropathy & Infections (Mucomycosis) Peripheral Neuropathy, Polydipsia & PolyuriaHyperosmolar ComaMI is #1 cause of death; Hyperosmolar Coma Glycosylated collagens !Advanced Glycosylation End Products Intracellular hyperglycemia!Sorbitol (lens & Schwann Cell)Secondary Diabetes MellitusPancreatitis Pancreatic Cancer DrugsDestruction of islets after disease Thyroid Pathology DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherDiffuse Non-Toxic Goiter (Endemic)Dietary ! iodine goitrogens Hyperplastic enlargement of thyroid ! T3/T4 ! TSHInvolves whole gland More commonDiffuse Non-Toxic Goiter (Sporadic)Substance interfering with synthesis Hereditary enzyme defectHyperplastic enlargement of thyroid ! T3/T4 ! TSHYoung femalesTypically young femalesMultinodal GoiterHyperplastic enlargement of thyroid ! T3/T4 & ! TSH Recurrent hyperplasia & involution Irregular with Nodules & CystsNodules/Cysts IrregularHemorrhage, scarring & calcificationPlummer s SyndromeHyperfunctioning Goiter! T3/T4Toxic multinodal goiter No skin/eye changes of Grave s DiseaseGraves DiseaseAutoimmune (LATS/TSI & TGI) Genetic? (HLA-B8 & DR3)Thyrotoxicosis (with diffuse hyperplasia) Ophthalmopathy (Paralysis & exopthalmos) Dermopathy (Pretibial myxedema)Typically females Treatment: PTU, methimazole, radioiodine & surgery Eye Muscle Paralysis & Exopthalmos NOT seen in ThyrotoxicosisThyrotoxicosisHyperfunctioning Thyroid Leakage from Thyroid Ingestion of iodide or SynthroidCardiac: !HR,A-fib,Cardiomegaly, CHF Neuromuscular: Hyperreflexia,tremor,wasting Skin: Heat Intolerance, ! Sweat & Pigmentation ! Appetite, GI motility, Osteoporosis, EyesHeat Intolerance Lid Lag ! CholesterolLow TSH (suggestive) & High T4 (confirms) Hyperpigmentation over extensor surfaces Uncommon causes: Hydatiform mole, Struma ovarii, carcinomas Treatment: b Blockers, Propylthiuracil (PTU) , Iodide, AblationPrimary HypothyroidismInsufficient Parenchyma Hashimoto Thyroiditis (Autoimmune) Developmental, Radiation AblationAnemia, ! Cholesterol, ! Na+, Myxedema Cold Intolerance, Fatigue, Depression, Lethargy Weight !, Edema, Constipation, Cardiomyopathy Delayed reflexes (achilles) & Coma (If severe)! Cholesterol MyxedemaHigh TSH (suggestive) & Low Free T4 (confirms) Therapy = T4 replacement (TSH takes 6-8 weeks to normalize) Low TSH after Tx ! osteoporosis & arrythmiasSeondary HypothyroidismPituitary LesionTSH is unreliable; Use T4 to make diagnosis TRH stimulation Test = no responseTertiary HypothyroidismHypothalamic LesionTSH is unreliable; Use T4 to make diagnosis TRH stimulation Test = delayed response (60 min)Hypothyroidism - Other! Synthesis Idiopathic (block of TSH receptors Heriditary, Hashimoto Thyroiditis Lithium, Iodides, p-aminosalicylateUse increased dose of T4 during pregnancyCretinismInfant Hypothyroidism Early Childhood HypothyroidismMental Retardation Short Stature, Coarse Facial Features Umbilical Hernia Protruding TongueProtruding Tongue Umbilical HerniaFetal HypothyroidismThyroid Agenesis Iodine Deficiency Congenital Synthetic DefectDelayed Brain Development Deafness & Mutism Spasticity Severe Mental RetardationDeaf & Mute Thyroid Pathology (contd) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherChronic Autoimmune Thyroiditis (Hashimoto Thyroiditis)TPO Antibodies (99% sensitive) Deficiency of Suppressor T Cells Genetic? (HLA-DR3 &5) TSH antibodies blocking receptorDiffusely but painlessly enlarged Thyroid Lymph infiltrates & follicles Hurthle Cells (granular cytoplasm)Early transient Thyrotoxicosis Later HypothyroidismFemale Predominance Early transient Thyrotoxicosis, Later Hypothyroidism Risk for B Cell Lymphomas Other antibodies: Thyroglobulin, Thyroid Peroxidase, I transporterSubacute Thyroiditis (DeQuervains/Granulomatous)Viral (Mumps, Influenza, Coxsackie)Painful, diffusely enlarged Thyroid Giant Cells & Macrophages (like granuloma)PainfulSelf LimitedPalpation ThyroiditisVigorous Palpation Disuption of folliclesGiant Cells & Macrophages (like granuloma)Subacute Lymphocyte ThyroiditisIdiopathicPainless Goitrous EnlargementPost-PartumSelf Limited Often seen in post-partum womenRiedels ThyroiditisFibrosing Thyroiditis - Painless Hard glandCauses Laryngeal Nerve Paralysis (SOB & difficulty swallowing) Simulates malignancy May be associated with fibrosis elsewhereFollicular AdenomaBenign, solitary, encapsulated Doesnt take up iodineMajority of Thyroid neoplasms Not likely to cause thyrotoxicosis May make more T3 than T4Papillary CarcinomaRET gene mutation (MEN II) RAS gene mutation Radiation exposure (most common)Encapsulated or Infiltrating Complex branching papillae Optically Clear nuclei & Psammoma bodies Intranuclear inclusions, groovesRadiation Little Orphan Annie Nodal MetastasisMost common thyroid cancer  ! incidence in Gardner Syndrome Optically clear nuclei in  Little Orphan Annie Cells Metastisize to regional nodes; Usually indolent growth Treatment = Thyroidectomy & radioiodine therapy, Survival 98%Follicular CarcinomaRAS gene mutationVascular or Capsular InvasionInvasion Blood Metastasis2nd most common - Survival 92% Hematogenously spread to bone, lungs & brain Treatment lobectomy or thyroidectomy, radioiodine (if invasive)Hurthle Cell Neoplasm (Adenoma or Carcinoma)RAS gene mutationAbundent granular cytoplasmBehave the same as follicular cell carcinoma/adenomaMedullary CarcinomaRET gene mutation (MEN II) RAS gene mutationParafollicular C Cells (neuroendocrine) Nodule or multifocal Not encapsulated, round or spindle cells Amyloid( Calcitonin) tumor stromaAmyloid Stroma Calcitonin Not encapsulatedRare most sporadic, 20% as MEN II or familial May be paraneoplastic (CEA, somatostatin, serotonin & VIP) Metastasize in blood to lung, liver, bone & nodes Treatment = ThyroidectomyAnaplastic CarcinomasRAS gene mutation P53 gene mutationUndifferentiated neoplasms Large, locally invasive, rapidly growingElderly FatalPoor prognosis uniformly fatal Loss of I uptake & ! Thyroglobulin Survival less than 1 year from diagnosis Possibly derived from Papillary Carcinoma Leukemia & Lymphoma DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherAcute Lymphoblastic Leukemia (ALL)Trisomy 21, Bloom s, Fanconis Radiation Alkylating Agents, Benzene ViralRapid Onset, > 20% Blasts Bone Pain, CNS & Testes Involvement HSmegaly, Anemia & Thrombocytopenia T Type = lymphadenopathy & mediastinal massChildren TdT+, Scant agranular cytoplasmCells similar to lymphoblastic lymphoma Generally good prognosis (70%) = ! WBC, t12:21, < 9yo, diploidy Bad = WBC (>10K), T-Type, t9:22, 11q23, organomegaly 3 types: Pre B (85%), Pre T (15%), B  like Burkitts (2%)Acute Myeloid Leukemia (AML)Trisomy 21, Bloom s, Fanconi s Radiation Alkylating Agents, Benzene ViralRapid Onset, > 20% Blasts Anemia & Thrombocytopenia Monocytic = gum hyperplasia Promyelocytic (M3) = DIC, !WBCAuer rods CD13, CD15, CD33 Granular CytoplasmFair prognosis (40%), Usually adults Frequent infections & mucosal bleeding Good = t8:21, t15:17 (treat w/ RA) & Chrom 16 abnormalities Bad = t9:22, 11q23, origin from myelodysplasia or treatmentAcute Leukemia of Ambiguous LineageTrisomy 21, Blooms, Fanconis Radiation Alkylating Agents, Benzene ViralMyeloid & Lymphoid featuresPoor prognosisChronic Myeloid Leukemia (CML)Trisomy 21, Blooms, Fanconis Radiation Alkylating Agents, Benzene ViralGradual onset, Mature Cells 100% cellular Bone Marrow (no fat) Pluripotent Stem Cells!Granulocytes Splenomegaly = Draggin Sensation! LAP t9:22 or bcr-abl Pluripotent Stem CellsUsually adults, Philadelphia Chromosome (t 9:22) bcr-abl ! Tyrosine Kinase activity ( Treat with Gleevec) ! Leukocyte Alkaline Phosphatase (LAP) Poor Prognosis - Always goes to blast crisis (AML or ALL)Chronic Lymphocytic Leukemia (CLL)Trisomy 21, Bloom s, Fanconi s Alkylating Agents, Benzene ViralGradual onset, Mature Cells, Hepatosplenomegaly Clonal B Cell Disorder (small lymphocytes) ! Infections HypogammoglobulinemiaNot radiation CD5, CD20, CD23 Del 13q RichterSyndromeUsually adults (most common adult leukemia in west) Same as CLL; indolent, not affected by therapy Some have large cell transformation (Richter Syndrome) Bad = trisomy 12, CD38 & de1 11qHairy Cell Leukemia (HCL)Trisomy 21, Blooms, Fanconis Alkylating Agents, Benzene ViralGradual onset Bacterial & Mycobacterial Infections Beefy Red Splenomegaly, ! Reticulin in BM TRAP+ B CellsAdult Men Not radiation  Fried Egg appearance TRAP+Usually adult men (2% of leukemias) Fair prognosis (40%) Pancytopenia (70%), Neutropenia & Monocytopenia (90-100%) Good Treatment - 2-CDA, pentostatin & interferonMyelodysplastic SyndromeIdiopathic Therapy related (ex. Radiation)BM = Hypercellular, Periphery = Pancytopenia <20% blasts in BM, Megaloblastic appearance Anemia, Infection, HemorrhageRinged Sideroblasts Chromosome 5,7,8Many subtypes based on ringed sideroblasts & blast counts May progress to AML Very poor prognosis Chromosome 5,7,8 abnormalitiesPolycythemia VeraGrowth Factor Mutations! RBC, Platelets & Granulocytes Fibrotic Marrow, Hypertension, Pruritis, Gout DVT, MI, Stroke! erythropoietin ! Hematocrit Hypertension & Hemorrhage ! ViscosityEarly organomegaly due to congestion Late organomegaly due to extramedullary erythropoiesis Spent Phase = Fibrotic Marrow Fair to good prognosis (depends on treatment-phlebotomy)Chronic Idiopathic Myelofibrosis (Agnogenic Myeloid Metaplasia)Early progression to myelofibrosis (spent phase) Pancytopenia & Etramedullar hematopoiesis Excess collagen from fibroblasts Markedly enlarged spleen, GoutPDGF & TGF-b Dacrocytes ReticulinDacrocytes (teardrop cells) & enlarged platelets in periphery  Sensation of fullness Prognosis is difficult to predict Transformation ot AML (20%)Essential ThrombocythemiaIdiopathicMarked Thrombocytosis (>600,000) Large Platelets Thrombosis & HemorrhageLarge Platelets No myelofibrosisLeast common of myeloproliferative disorders Diagnosis by exclusion Good prognosis (>10 year survival)Hodgkins Disease (Lymphocyte Predominance)EBVPredominance of lymphocytes/hystiocytes Typically a cervical node Cd20 & CD45No Typical Reed Sternberg Cells Lymphohystocytic Cells B Cell Lymphoma CD20 & CD45Men more common Best Prognosis Can turn into Diffuse Large B Cell LymphomaHodgkins Disease (Lymphocyte Rich)EBVPredominance of lymphocytes/hystiocytes CD15 & CD30No Typical Reed Sternberg Cells Lymphohystocytic CellsMen more common Can turn into Diffuse Large B Cell LymphomaLeukemia & Lymphoma (Contd.) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherHodgkins Disease (Nodular Sclerosis)EBVCervical, Supraclavicular or mediastinal nodes Variable cell composition & necrosis CD15 & CD30Lacunar Reed Sternberg Cells Collagen Bands WomenMost common type; affects adolescent or young adult women Staging (usually I or II) determines treatment; Good prognosisHodgkins Disease (Mixed Cellularity)EBVVariable cell composition & focal necrosis Disordered fibrosis Eosinophils, Plasma & T Cells CD15 & CD30Classic Reed Sternberg Cells2nd most common type; men more common Staging determines treatment; Guarded prognosisHodgkins Disease (Lymphocyte Depletion)EBV1) Diffuse Fibrosis RS Cells embedded in fibrous stroma 2) Reticular RS Cells in sheets ! #s of Reed Sternberg CellsPoor Prognosis Many Reed Sternberg Cells Bone MarrowFairly common  usually in older patients Often Bone Marrow Involvement (Stage III or IV) Poor prognosis Usually not a true Hodgkin s Lymphoma?Small Lymphocytic LymphomaTrisomy 21, Bloom s, Fanconi s Alkylating Agents, Benzene ViralGradual onset, Mature Cells, Hepatosplenomegaly Clonal B Cell Disorder (small lymphocytes) ! Infections HypogammoglobulinemiaNot radiation CD5, CD20, CD23 Del 13q RichterSyndromeUsually adults (most common adult leukemia in west) Same as CLL; indolent, not affected by therapy Some have large cell transformation (Richter Syndrome) Bad = trisomy 12, CD38 & de1 11qFollicular LymphomaNodular Growth Pattern with 2 cell types 1) Centrocytes = cleaved nuclear contours 2) Centroblasts = clear chromatin & multinucleate Bone Marrow frequently involvedCD10,CD20,CD23 BCL-2, t14:18Fairly Common; indolent, not affected by therapy May transform to diffuse large B cell lymphomaMantle Cell LymphomaAtrophied germinal center Small cells with cleaved nuclear contourCD5 & CD20 BCL-1, t11:14Not indolent or treatableMarginal Zone B-Cell Lymphoma (MALT Type)H. Pylori Autoimmune (Sjogren, Hashimoto)Large B Cells, some plasma cellsCD20Common in GI Tract, Indolent, not dependent on treatmentDiffuse Large B-Cell LymphomaEBV HSV8Large cell size, diffuse growth patternT14:18, t8:14, t13:14 BCL2,C-Myc,BCL6Very Common, Very Aggressive Prognosis depends on treatment, BCL-6 = good prognosis Burkitts LymphomaEBVStarry Sky pictureStarry Sky picture CD10,CD19,CD20 C-MycOne of three bad types in kids Highest growth fraction of all tumors Most manifest as extra-nodal sites Responsive to treatment, but poor prognosisLymphoblastic Lymphoma (T/B)Mediastinal Mass like HodgkinsCD3, TdT+, TCL-1 (T Type)One of three bad types in kids Responsive to treatment, but poor prognosisAnaplastic Large T/Null Cell LymphomaCD3, CD30 ALK, EMA t2:5One of three bad types in kids Uncommon in adults, Common in children Presents in extra-nodal tissue Usually T, not B cellPeripheral T-Cell LymphomaEBVExtranodal NK/T Cell Lymphoma Nasal Type eats face offCD3Poor Prognosis; Common in Asia, uncommon in US Leukemia & Lymphoma (Contd. 2) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherMycosis fungoidesCerebriform nucleiCD4 Polyclonal IgIndolent Cutaneous disorder Extracutaneous spread (Leukemia = Sezary Syndrome)Multiple MyelomaRadiation, Chemicals, Asbestos Black Race HSV8?Painful Bone Destruction, ! Humoral Immunity Plasmacytosis with IL-6, Vertebral Fractures M Protein, Bence Jones proteins, Hypercalcemia Can spread to nodes, skin, etcM Protein Bence Jones Protein Hypercalcemia IL-6Most common 1 malignant tumor of bone Complications: Renal failure, Amyloidosis, AML (rarely) Fair prognosis (3 yr)1 AmyloidosisRadiation, Chemicals, Asbestos Black Race Multiple MyelomaPlasmocytosis with ! Light Chain Production Fibrils of b-pleated sheets that stain Congo Red Large tongue, Neuropathy, GI Arrythmias, CHFLarge TongueUsually immunoglobulin light chain2 AmyloidosisChronic Infection or InflammationFibrils of b-pleated sheets that stain Congo Red HSmegaly, ProteinuriaHSmegaly, ProteinuriaMonoclonal Gammopathy of Undetermined SignificanceAgingM Proteins without other symptomsMost common monoclonal gammopathy Diagnosis of exclusion, IgG < 3.5 May develop into multiple Myeloma Requires no treatment Pituitary Pathology DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherProlactinoma! Prolactin Amenorrhea, Galactorrhea, Infertility, Loss of LibidoMost common secretory adenoma of anterior lobe Effects less obvious in postmenopausal women Treated with bromocriptineHyperprolactinemiaInjury to pituitary stalk Compression Trauma to Hypothalamus, Infection Drugs (Phenylthiazines)! Prolactin ProlactinDue to decreased dopamine to the anterior lobe Non-prolactin secreting adenomas may compress stalkSomatotroph Adenoma! Growth Hormone ! ! Hepatic IGF-1 Some produce prolactin as well Acromegaly (adults) & Gigantism (children) DM, HT, CHF, arthritis, weakness, GI carcinomaIGF-1Second most common secretory adenoma of anterior lobe Treatment = transsphenoidal resection, bromocriptine & radiation Acromegaly = hands, feet, face skin & visceraCorticotroph Adenoma! ACTH! ! Cortisol (Cushing s Disease) Moon facies, central obesity, striae, bruising Osteoporosis, DM & HTACTH Microadenoma90% are microadenomas Treatment = transsphenoidal resectionGonadotroph AdenomaNo clinical syndromeSecrete hormones inefficiently and variablyThyrotroph AdenomaRarestSheehan s SyndromePregnancy & Lactotroph Hypertrophy Hypotension, DIC Sickle Cell Anemia, ! ICPHypopituitarismMost common cause of anterior lobe ischemic necrosisEmpty Sella SyndromeMaldevelopment of diaphragma sella Pituitary Apoplexy Sheehans Syndrome AblationDepends on number of residual cells Hypopituitarism No syndromeMaldevelopment = Arachnoid Herniation via enlarged openingDiabetes InsipidusInterruption of DA to Posterior Lobe Trauma Tumor InflammationLarge volume of dilute urine! ADHTreatment = Administer ADHSyndrome of Inappropriate ADH (SIADH)Ectopic ADH (Small Cell Carcinoma) Lung Disease (TB) Intracranial Lesions (! Inhibition) DrugsWater Retention, Hyponatremia GI Upset, Cerebral Edema! ADHTreatment = Water Restriction, Slow normalization of Na+ (Rapid Normalization can cause Central Pontine Myelinolysis)Hypothalamic TumorsHyperpituitarism, Hypopituitarism Diabetes InsipidusGlioma & Craniopharyngioma are most common CNS Pathology DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherConcussionBlunt non-penetrating injuryReversible Paralysis ImmediateReversible Traumatic Paralysis Ocurring Immediately After InjuryContusionStress on parenchymal vessels Coup CountercoupSeizures Cognitive & Personality Changes Headaches DizzinessIntact pia-glial membraneMost common sites: Frontal Pole, Temporal Pole, Medial orbital surface of the temporal lobe Pia-arachnoid not penetrated Occur at crests of gyriLacerationsPenetrating WoundsSubarachnoid bleeding Satellite petichial hemorrhages Edema in tissueMeningocerebral cicatrixTraumatic disruption of pia-arachnoid and brain surface Meningocerebral cicatrix (glial scar) = epileptogenic focusEpidural HemorrhageFracture Most = Arterial (Middle Meningeal) Rarely = Dural Sinus, Bridging VeinsImmediate Loss of Consciousness Lucid Interval Later Loss of ConsciousnessCollection of blood between dura and skull Lenticular shaped hematomaAcute Subdural HemorrhageSuperficial Cortical Bridging Veins Dural Sinus Laceration Depressed Fractures Bullet Wounds48 hours-days; appears as clotted blood Gradual Loss of Consiousness Hemiparesis ! Hemiplegia Evidence of Herniation (if > 60 cc)Clotted BloodMore Common than epidural hemorrhage Typically seen in infants, elderly & alcoholics Sheet of blood between dura & arachnoid; forms hyaline sacSubacute Subdural HemorrhageSuperficial Cortical Bridging Veins Dural Sinus Laceration Depressed Fractures Bullet WoundsClotted & Fluid Blood Gradual Loss of Consiousness Hemiparesis ! Hemiplegia Evidence of Herniation (if > 60 cc)Clotted & Fluid BloodMore Common than epidural hemorrhage Typically seen in infants, elderly & alcoholics Sheet of blood between dura & arachnoid; forms hyaline sacChronic Subdural HemorrhageSuperficial Cortical Bridging Veins Dural Sinus Laceration Depressed Fractures Bullet Wounds> 3 weeks & Liquefied Hematoma Gradual Loss of Consiousness Hemiparesis ! Hemiplegia Evidence of Herniation (if > 60 cc)Liquefied Hematoma Minor Precipitating EventMore Common than epidural hemorrhage Typically seen in infants, elderly & alcoholics Sheet of blood between dura & arachnoid; forms hyaline sac Slow Bleeding, No immediate symptoms, Minor precipitating eventSubarachnoid HemorrhageTrauma Superficial Cortical Veins Surface cortical lacerations Surface cortical contusionsStiff Neck, Alterations in Consciousness Vasospasm & HydrocephalusStiff NeckUsually multiple and smallIntracerebral HematomaRupture of Intrinsic Cerebral VesselsNot in contact with the cortical surface, usually solitary Frontal & Temporal Lobes are most common sitesCranial Nerve DamageCranial FracturesDamage usually occurs where nerves exit through foramina Most Common = CNI, CNII, CN V & CN VIPontomedullary AvulsionMarked Hyperextension of neckPoor prognosis, Immediately fatal if complete, die later if incompleteDiffuse Axonal Injury (1 Axotomy)Diffuse Shearing of axonsUnconscious from moment of impact No lucid interval Ca2+ influx & swelling Microtubule depolymerization, Calpain activationCalpainResults in disconnection of distal axonal segment Most common sites = Corpus Callosum & S. Cerebellar Peduncles CNS Pathology (Contd.) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherDiffuse Axonal Injury (2 Axotomy)Small axonal membrane tears that resealUnconscious from moment of impact No lucid interval Ca2+ activated proteases, repair fails Axoplasmic transport causes swellingAxoplasmic TransportResults in disconnection of distal axonal segment Most common sites = Corpus Callosum & S. Cerebellar PedunclesHypoxic Brain InjuryGreatest Damage = Hippocampus, Caudate, Putamen, Cortical Layers 3 & 5, Purkinje Cells of Cerebellum Diffuse or localized to watershed zoneBrain SwellingMechanical Damage Blood Vessel Impairment VasodilationWhite Matter Swelling Diffuse SwellingWhite matter swelling adjacent to contusion Diffuse Swelling of One or Both HemispheresMultiple Petechial HemorrhagesAcceleration/Deceleration?Frontal & Temporal Lobes (White Matter) Thalamus BrainstemUsually seen in patients who die soon after head injuryFat EmbolismFractures of Limbs or Limb Giurdles (Fat enters veins)3-4 d = white matter petichiae, capillary necrosis 4-7d = grey matter alterations, fat in capillaries 12d-3m = many infarcts in cortex & pons >3 m = atrophy of white matterUsually only seen in adults (children have less fat)Early Post Traumatic EpilepsyWithin first weekOccurs during first week More common in children than adults Associated with: Hematoma, Depressed Fracture, AmnesiaLate Post Traumatic EpilepsyBlunt Head InjuryAfter first weekMost common complication of blunt head injury Occurs later than one week ! Risk = Hematoma, Depressed Fracture, Early Epilepsy Multiple SclerosisT-Cell Autoimmune against Myelin Unknown Distance from equator, Environment GeneticDiagnosis = 2 lesions & 2 symptoms Visual Impairment, Weakness, Dysarthria Ataxia, Vertigo, Urinary Symptoms CSF = ! Mono s & IgG (OCB-not in serum)Young Women, CNS Plaques Variability Oligoclonal Bands (OCB)Commonest in young women; Affects CNS myelin, Variable course Acute Plaque: Sharp Border, Inflammation & Edema, Demyelination Inactive Plaque: Sharp Border, No Inflammation Edema or Myelin Shadow Plaque: Poor Border, Thin Myelin at PeripheryDevic Disease (Neuromyelitis Optica)Spinal Cord & CN II OnlySevere necrotic lesions in spinal cord and optic nerve only Rapidly progressiveAcute Multiple Sclerosis (Marburg Type)Fatal in 1-6 months Severe & Rapid with extensive involvement of brain & spinal cordCentral Pontine MyelinolysisRapid Correction of Hyponatremia Sever Electrolyte Imbalance Alcoholism, Liver Transplant Burns, Malnutrition Rapidly evolving quadriplegiaCNSSymmetric demyelination in the center of the base of the pons Can affect tegmentum occasionally Outcome is variable: Complete Recovery!FatalGuillian-Barre SyndromeAcute Influenza-like Illness CMV & Campylobacter jejuni Immunization Autoimmune?Inflammation/Demyelination of Nerves & roots Cranial & Spinal Motor Roots = Severe Ascending ParalysisPNS Ascending ParalysisTreatment: Supportive, Plasmapheresis, IV Immunoglobulin Outcome: Complete recovery is most common, rarely fatal Death due to respiratory paralysis CNS Pathology (Contd. 2) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherSpina Bifida OccultaFolate DeficiencyUsually assymptomatic Non-closed vertebral arches without cyst Stigmata: Hypertrichosis,Dimple,Lipoma,Nevus Sacral, Anorectal or UG DefectStigmata (Hypertrichosis)Variable cord anomalySpina Bifida CysticaFolate DeficiencyNon-closed vertebral arches with cyst Meningocele or MyelomeningoceleCystMeningocele: Meninges protrude through vertebral defect Myelomeningocele: Meninges & Spinal cord protrude through defect Most survive > 1 year, but frequently have progressive deterioration Disabilities are usual: paraplegia, incontinence, infection, learningArnold-Chiari Type IIMental Retardation1) Myelomeningocele 2) Elongation of Inferior Vermis & Brain Stem with displacement i into spinal canal 3) HydrocephalusAnnencephalyFolate DeficiencyAbsence of cerebrum & calvariumMost common congenital malformation of the brain Stillborn or die shortly after birthIntraventricular Hemorrhage (IVH)Preterm Birth Periventricular Germinal MatrixPreterm Periventricular Germinal MatrixMost common neonatal intracranial hemorrhage PV Germinal Matrix is fragile, fibrinolytic & persists until 34 weeks Variable: May be focal & asymptomatic, may spread into ventriclesPeriventricular Leukomalacia (PVL)Infarction of Periventricular White Matter (Centrum Semiovale)Initially non-specific Later: Spastic Motor Dysfunction Paraplegia/Quadraplegia develops in survivingPreterm Centrum SemiovaleCommon ischemic lesion of preterm infant Centrum Ovale = vulnerable boundry zone (Ventriculopetal & Ventriculofugal Arteries) Usually not without permanent sequelaeDiffuse AstrocytomaDiffusely infiltrate w/o clear margins Found in white matter of cerebrumDiffusely Infiltrative No Clear Margins Cerebrum20% of gliomas, Rarely Resectable, Progress towards anaplastic Graded on: Hypercellularity, endothelial changes & necrosis Poor PrognosisBrainstem Glioma (Atrocytoma Subgroup)Occur in Pons, infiltrate widely CN Palsies, Long Tract signs, Gait abnormalities Emesis & Cerebellar SignsChildren (2nd decade) PonsRange of grades includes glioblastoma Surgical removal not possiblePilocytic AstrocytomCircumscribed, low grade, histology = biphasic Cerebellum, Hypothalamus, Optic Chiasm/Nerve Rosenthal FibersCircumscribed Midline Rosenthal Fibers Von Recklinghausens (NF I)Young>Old Optic Nerve Gliomas associated with Von Recklinghausens (NF I)Cerebellar Pilocytic Astrocytoma60% cystic Endothelial proliferation & pleomorphismChildren (2nd decade)Most common astrocytoma of childhood Good PrognosisSubependymal Giant Cell TumorVascular Intraventricular Mass Cells = Large, mix between astrocyte & neuronIntraventricular Tuberous Sclerosis HemorrhageBenign but cause problems due to location & hemorrhagingGlioblastoma MultiformeSupratentorial Rapid growth, endothelial proliferation, necrosis Hemorrhagic Foci, Often zones of mixed tumor May Metastasize (CSF)Common Adults Always Recurs MetastasisMost common glioma, Usually in older adults Most invasive & aggressive, highly infiltrative Tumor always recurs with resection, poor prognosis Mix: Oligodendroglioma,Ependymoma,Astrocytoma,Neuroectederm CNS Pathology (Contd. 3) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherOligodendrogliomaCerebral White Matter, Focal Calcification Fried Egg Appearance, Highly vascularizedFocal Calcification LOH 1p, LOH 19q CDKN2AUnusual in children Good = both LOH 1p & 19q Bad = CDKN2AEpendymomaVentricular System (4th Ventricle is usual) Rosette & Pseudorosette Arrangement Vascularized, differentiated & demarcated May Metastasize4th Ventricle NF II Rosettes & Pseudorosettes MetastasisAll ages, but more often young>old & children = infratentorial Most common spinal intramedullary glioma, Associated w/ NF II Best to Worst: Spinal Cord, Cerebrum, Posterior FossaMyxopapillary EpendymomaMucinous Degeneration of StromaCauda Equina Fila Terminale Adults Mucinous Degeneration of StromaRare in Children, Usually benign Can be locally destructive, Metastatic & can recurSubependymomaUsually 4th Ventricle Extend of caudate or Septum into Lat Ventricle4th VentricleBenign, cured by excisionMedulloblastomaChildren = midline, young adults = lateral Grows in sheets or rosettes May Metastasize into CSFSheets or Rosettes CSF Metastasis Myc Amp & LOH 17p Retinal S, Rhodopsin, TrkC RYoung>Old, Accounts for 1/3 of posterior fossa neoplasms Invades leptomeninges & seeds CSF, Good prog except large cell Bad = < 3yo, Mets, Large Cell Variant, Myc Amp, LOH 17p Good = Retinal S Antigen, Rhodopsin & TrkC receptorMeningiomaGrows in sheets w/ poor cytoplasmic borders Whorls & Psammoma Bodies 4Fhj    # $ > T U   B 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mn()45JLa7()|}~·¬ʡʖʊʊh&h6{CJaJh6{h6{CJH*aJhubh6{CJaJh&hUCJaJhubh1TCJaJh&h1TCJaJh1TCJaJh6{CJaJhUhUCJH*aJhUhHhUCJaJhUCJaJhubhUCJaJ2()4@!$L$&`#$/If]^La$b$gdzkdh$$IflErp(8:  H L t 6`0:44 lae445a7u$p$&`#$/If]^pa$b$gdz$$&`#$/If]a$b$gdz$$&`#$/If]^a$b$gdz @!$L$&`#$/If]^La$b$gdzkdY$$IflErp(8:  H L t 6`0:44 lae4 )J}$p$&`#$/If]^pa$b$gd6{$$&`#$/If]^a$b$gdz}~@!$L$&`#$/If]^La$b$gdzkdJ$$IflErp(8:  H L t 6`0:44 lae4$p$&`#$/If]^pa$b$gd6{$$&`#$/If]^a$b$gd6{$$&`#$/If]^a$b$gdz 67Skld5d6d;dBreast>Melanoma>Kidney>GI TractParenchymal Metastasis (Metastatic Neoplasms to CNS)More common in Cerebrum than Cerebellum Lodge in grey matter at junction with white matterUsually Multiple Cerebrum Grey MatterMost Common = Lung>Breast>Melanoma>Kidney>GI TractTransient Ischemic Attack (TIA)Deficits occur & disappear completely; Important Predictor of Stroke (if greater than 30-60 minutes causes infarction) of patients have a diffusion weighted MRI abnormalityCerebral InfarctionCarotid,Vertebral, Basilar Atherosclerosis Age>60, Arteriorsclerosis (DM & HT) Inflammation, Compression, Spasm Polycythemia, Hypotension, ! O2Middle>Posterior>Anterior Cerebral Arteries Vasodilation & Immediate Metabolic Change Acidosis; Edema; ! Glu; Ca2+ Influx; Free Radical PMNs; c-fos, cjun & HSPsStuttering Onset, at night Older Patients & TIA Atherosclerosis c-fos, cjun & HSPsIschemic Necrosis; Most common of all CV Disease 1-2d: loss of definition of grey & white, edema; 2-10d: demarcation >10d: liquefaction & cyst formation Goal of focal ischemic stroke is to protect penumbraCerebral EmbolusHeart Arrhythmias & MI Aorta & Carotid Plaques Endocarditis Surgery & TraumaMiddle Cerebral Artery Lesions in cortex & corticomedullary junctionArrhythmias & MI Sudden Onset Multiple Regions Rapid Improvement (some)Fat emboli cause petichial hemorrhages in white matter of cerebrum Change of no flow/reflow hemorrhageCerebral HemorrhageHypertension AmyloidCharcot-Bouchard Aneurysms Disection of parenchyma, rupture into ventricles Hematoma ringed by petichiae Large amounts of hemosiderin after recoveryHypertension Waking Hours 50% Coma Some stiff neck/headachePutamen & Pons = Death;Thalamus & Cerebellum = Recoverable Older pts with amyloid can get lobar hemorrhage w/o hypertension High 30 day mortalitySubarachnoid HemorrhageHead Trauma Ruptured Aneurysms, Neoplasms Arteriovenous Malformations, Dyscrasias Extension of HemorrhageArterial Spasms & Cerebral Infarction HydrocephalusHead Trauma (Saccular Aneurysm) Sudden Onset during Day Headache & Stiff Neck in all Younger Patients; Seizures CNS Pathology (Contd. 5) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherLacunar InfarctionHypertensionFibrinoid necrosis Hyalinization of media & narrowing of lumen Grey Matter, Internal Capsule, Basis Pontis & Centra SemiovalesSmall (< 1 cm)Mycotic AneurismBacterial EmboliDistal to bifurcation of Circle of WillisCerebral EmbolusCause Subarachnoid & Intracerebral HemorrhageCharcot-Bouchard AneurysmsHypertensionFound on penetrating intraparenchymal arteries Cerebral Hemispheres, Cerebellum & BrainstemCerebral HemorrhageMicroaneurysmsSaccular AneurysmsCongenital Defect at Bifurcation Degeneration of IEL Atherosclerosis85% in anterior circulation Internal Carotid, Anterior Cerebral & Anterior Communicating Hemorrhage or CompressionSubarachnoid HemorrhageBerry Aneurysm Multiple in 20% of patientsFusiform AneurysmsVertenral, Basilar or Internal Carotid Segmentally Dilated CompressionDont RuptureCapillary TelangiectasisPons or Cerebral White Matter Focal Seizures Repeated Subarachnoid Hemorrhage Intracranial BruitsPons or Cerebral White MatterSmall Dilated Capillaries separated by neural tissueCavernous MalformationsFocal Seizures Repeated Subarachnoid Hemorrhage Intracranial BruitsDilated Sinusoidal Vessels without neural tissueArteriovenous MalformationFound along Middle Cerebral Artery Focal Seizures Repeated Subarachnoid Hemorrhage Intracranial BruitsMiddle Cerebral ArteryComposed of arteries & VeinsVenous MalformationFound over Subarachnoid Space over Cord Focal Seizures Repeated Subarachnoid Hemorrhage Intracranial BruitsSubarachnoid Space over CordLarge Numbers of Veins Venous Occlusive DiseaseInfection, Heart Disease, Post-op Trauma Carcinoma, Fever, Dyscrasias, Dehydration, Cachexia, Hypotension PuerperiumSuperior Sagital Sinus or Superior Cerebral Veins Hemorrhage into leptomeninges Hemorrhagic Infarction Hemorrhage in cortex (white matter)Sinus or VeinsBad = If thrombosis spreads into bridging veins (dont use TPA)Acute Pyogenic Meningitis (Bacterial)Neonates: Group B Strep & E. coli <2 y: S. pneumoniae (H. influenza?) >2 y: N. meningitides Elderly: S. pneumoniae & ListeriaFever, Headache, Photophobia, Nuchal Rigidity Change in mental status ! CSF Pressure, PMNs, Protein; ! Glucose Hydrocephaly, Infarct, Seizures, CN Palsies! Glucose (CSF) PMNs Medical EmergencyA leptomeningitis (leptomeninges & subarachnoid CSF) With Treatment: Complete resolution or with mild impairment Complications: Hydrocephaly, Infarct, Blindess, Deafness, Ocular Palsy, SeizuresAseptic Meningitis (Viral)Enterovirus (Echovirus, Coxsackie or Poliovirus)Effects more mild than Bacterial ! CSF Pressure, Lymphocytes, Protein LymphocytesUsually self-limiting, no long term effects CNS Pathology (Contd. 6) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherChronic Meningitis (Mycobacterial)Mycobacteria (TB)Less Fulminating than Bacterial ! CSF Pressure, Mono s or Mixed, Protein Basal Meninges Granulomatous Reaction (not pyogenic)!! Protein Mononuclear Cell Basal MeningesMeningoencephalitis (Meninges & Brain Parenchyma) Very hard to treat, high rate of complications CSF Protein may be very high with TBChronic Meningitis (Fungal)Candida Mucor (with Diabetic Ketoacidosis) Aspergillus Cryptococcal (with AIDS)Less Fulminating than Bacterial ! CSF Pressure, Mono s or Mixed, Protein Basal Meninges Granulomatous Reaction (not pyogenic)!! Protein Mononuclear Cell AIDS & Diabetes Basal MeningesMeningoencephalitis (Meninges & Brain Parenchyma) Very hard to treat, high rate of complications CSF Protein may be very high with TB Mucor & Aspergillus tend to invade blood vessels (hemorrhagic)Brain AbscessBacteria (Staph & Strep) Fungi (often immunodeficient) Protozoa (Toxoplasma - AIDS)Herniation due to mass effect Rupture into ventriclesPredisposed: Endocarditis; Heart Disease; Lung, Sinus & Tooth InfectionsViral Encephalitis (Arbovirus)Eastern Equine-Epidemic West Nile Epidemic Western EquineMononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion BodiesEastern Equine = most virulent, 20-40% mortalityViral Encephalitis (Herpes Simplex Type I)HSV-1Mononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion BodiesInferior Temporal & Frontal LobesHSV-1 = Most common cause of sporadic acute encephalitis Labial Herpes not a significant risk factor Treatment = Acyclovir Tropism for Temporal & Frontal Lobes except in neonates (pan)Viral Encephalitis (Herpes Simplex Type IIK)HSV-2Mononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion BodiesIn immunodeficient pts & neonates; In others = aseptic meningitis High Risk = Babies born to mothers with active genital herpes Neonates = generalized panencephalitis (no tropism) like aboveViral Encephalitis (Varicella Zoster Virus)VZVMononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion Bodies Inflammation of a sensory ganglionPosterior Ganglionitis LatencyExemplifies latencyViral Encephalitis (Rabies)RabiesMononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion Bodies HyperexcitabilityHyperexcitability PharyngospasmPeripheral Nervous System as route of entry (slowly spreads along peripheral nerves) Slight Touch: Pain,Violent Motor Response, Convulsions Swallowing: Pharyngospasm (fear of water)Viral Encephalitis (Cytomegalovirus)CMVMononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion BodiesPeriventricularMost common opportunistic virus infecting CNS in AIDS Succeptability in fetuses & immunodeficient Periventricular localizationProgressive Multifocal LeukoencephalopathyJC VirusMononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion Bodies Widespread loss of myelinOligodendrocytes Loss of myelinOnly immunodeficient individuals succeptable Tropism for oligodendrocytes Poor PrognosisViral Encephalitis (HIV)HIV-1Mononuclear Infiltrate, Microglial Nodules Neuronophagia, Viral Inclusion Bodies Dementia, Ataxia, Incontinence, Seizures Cerebral Atrophy, VentriculomegalyDoesnt Infect NeuronsInfected: Macrophages, Giant Cells Microglia (NOT neurons) Can lead to: Toxo, CMV, Cryptomeningitis, PML 2 most common focal lesions: Toxo Abscess & 1 Lymphoma Infection is rare in congenital AIDSNeurosyphilis (Tertiary Syphilis)Treponema pallidumAbsence of Deep Tendon Reflexes Charcot Joints Lightning PainsMeningovascular: Meningitis, Meningeal Arteritis Paretic: Invastion of parenchyma (dementia & motor instability) Tabes Dorsalis: Destruction of Dorsal Roots (Ataxia, Skin & Joint Lesions[Charcot Joints], Dysesthesia, No deep tendon reflexes) CNS Pathology (Contd. 7) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherNeuroborreliosis (Lyme Disease)Borrelia burgdorferiMeningitis Encephalopathy Facial-nerve paralysis PolyneuropathiesMajor arthropod born disease in US; Evolves through 3 stages Nervous System involved in Stage 2 (months) & 3 (years)Transmissible Spongiform EncephalopathyPrion (PrPSc) Sporadic Genetic InfectiousDementia, Ataxia, Insomnia, Paraplegia Paresthesias, Deviant Behavior No Inflammation; Vacuolization of Tissue (Dementia & Startle Myoclonus = CJD)PrPSc No InflammationMost Common is Sporadic = Creutzfield-Jakob Disease (CJD) Infection: Corneal Transplants, Electrodes, Dural Grafts & GH Course is relentlessly progressive, fatal in a yearAlzheimers DiseaseHead Trauma, Early Low Linguistic Skill Low Educational Achievement APO E-4 APP(21), PS1, PS2 & Chr 10 MutationsProgressive decline in memory & cognitive fxn Personality & Behavioral Changes Neurofibrillary Tangles (Tau) & Plaques (Ab) Loss of CAT & AcetylcholineesteraseAPP, PS1,PS2 Tau Tangles Ab Plaques of pts over 85 have AD Areas Affected: Basal Nucleus (Ach), Locus Ceruleus (NE) & Dorsal Tegmentum (5HT); Entorhinal Cortex & Hippocampus Treatment: Cholinesterase Inhibitors, NMDA Antagonists & Vit. 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of Posture, Equilibrium & Autonomic Funciton; Dementia Substantia Nigra & Locus Ceruleus DamagedSubstantia Nigra Locus Ceruleus Lewy Bodies Loss of melanin & DopamineMost Frequent Basal Ganglia Disorder 12 genetic mutations: PARK 1-10, NR4A2, Synphilin-1Dementia with Lewy BodiesDementia, Psychoitc Behavior, Parkinsonism Lewy Bodies, Senile Plaques, TanglesSecond Most Common Dementia of ElderlyHuntingtons DiseaseGenetic (AD) HD gene = Chr 4 p16.3 (36-121 CAGs)Choreoathetoid Movement & Dementia GABAergic medium spiny striated neurons Atrophy of Caudate & Putamen Ventricular Enlargement & Frontal Lobe Atrophy! GABA, Glu Decarboxylase, CATGenetic Test available for confirmation Patients have a high suicide rateFriedreichs AtaxiaGenetic (AR) Frataxin = 9q13-q21.1 (200-900 GAAs)Limb & Trunk Ataxia Loss of limb proprioception & deep tendon reflex Dysarthria & Extensor Plantar Response Kyphoscoliosis, Cardiomyopathy & DMSmall Spinal CordMost Common Inherited Ataxia Degeneration of posterior spinal cord Frataxin = unknown function, but disease due to loss of functionSpinocerebellar Ataxia Type IGenetic Triplet Repeats within geneSecond Most CommonDentato-rubro-pallido-luysian AtrophyGenetic Triplet Repeats within geneMachado-Joseph DiseaseGenetic Triplet Repeats within geneAmyotrophic Lateral SclerosisExcitotoxins, Viral Infection Immunological Abnormalities Trace Elements & Free Radicals Genetic (10%) Chr 21Upper & Lower Motor Neuron Degeneration Lower: Atrophy, Fasiculations, No reflexes Upper: Hyperreflexia, spasticity Demyelination & atrophy of anterior cordUpper & Lower Motor Neuron No inflammatory reactionMore common in men; rapid progression toward death Familial ALS = Superoxide Dismutase gene on Chr 21 Difficulty swallowing & chewing; Cell loss most intense in cervical No inflammatory reaction CNS Pathology (Contd. 8) DiseaseCause/Risk FactorsSymptomsBuzzwordsOtherProgressive Bulbar PalsyBrainstem Motor NucleiRapidly ProgressiveProgressive Spinal Muscular AtrophyAnterior Horn Cells & Nerve RootAnterior HornNo change in corticospinal tractPrimary Lateral SclerosisCorticospinal TractCorticospinal TractALS-Parkinsonism Dementia Complex of Guam23M@!$L$&`#$/If]^La$b$gdekd$$IflErp(8:  H L t 6`0:44 lae4MNyƑ$p$&`#$/If]^pa$b$gde$$&`#$/If]^a$b$gdeƑǑܑ@!$L$&`#$/If]^La$b$gdekd$$IflErp(8:  H L t 6`0:44 lae4ܑ`H֓ $p$&`#$/If]^pa$b$gde$$&`#$/If]^a$b$gde "@!$L$&`#$/If]^La$b$gdekdڷ$$IflErp(8:  H L t 6`0:44 lae4"/Th9z$p$&`#$/If]^pa$b$gde$$&`#$/If]^a$b$gde z{ѕҕӕ 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