AM Report 03/07/17: Neurocysticercosis

Cysticercosis 

-Caused by the larval stage of the pork tapeworm (Taenia Solium)
-Humans get cysticercosis by drinking/eating water/food contaminated by tapeworm eggs (eg: infected pork)
-See life cycle below

Cysticercosis_LifeCycle

Clinical syndromes

Neurocysticercosis
Parenchymal
Extra-Parenchymal (Intraventricular/sub-arachnoid/intraocular/spinal)
-Extraneural cysticercosis

Clinical presentation

Parenchymal cysts
Seizures/headache-Most common cause of adult onset seizures in many countries (70 % of patients)-esp. Latin America, India, Africa, and China
-Can be YEARS after infection. Most never cause symptoms and identified incidentally

Extraparenchymal cysts:
-Increased ICP- HYDROCEPHALUS, headache, nausea, vomiting, AMS
-Intraventricular cysts can cause obstructive hydrocephalus (nausea/vomiting/headache), subarachnoid cysts, spinal (<1%), ocular, extra-neural (subQ/intramuscular)

How do you make the diagnosis?

-Stool O&P usually negative as chronic infection
-Peripheral eosinophilia is NOT commonly seen
-If you have a patient from an endemic area with seizure and enhancing lesion on MRI-very likely to be Taenia Solium. 
-See criteria below as definitive diagnosis requires at least one absolute criterion or two major plus one minor and one epidemiologic criterion

diagnostic criteria
Reference: UpToDate

Note that identification of the Scolex (anterior end with hooks) in cystic lesion is pathognomonic. 
-Serology with EITB (enzyme linked immunoelectrotransfer blot)antibody to T.solium, 83-100 % sensitive, 100 % specific but lab dependent)-takes a while to come back
-A detailed eye exam should be done to rule out ocular cysticercosis 
-Brain biopsy rarely done as can be diagnosed by above 

Differential Diagnosis (not complete) but do not miss other infectious causes!
Toxoplasmosis
-Cryptococcus
-Brain abscess
-Nocardiosis
-Septic emboli
-TB/fungal
-Meningeal carcinomatosis
-Glioblastoma

Treatment 

Seizure control (controversial but esp. if multiple lesions, parenchymal involvement, or presenting with seizure)
-Treatment of increased ICP
Antiparasitic therapy (Albendazole + Praziquantel with better efficacy, always given with or after anti-inflammatory therapy (steroids) due to inflammation with dying cysts. Can RECUR after treatment so needs to be tailored to imaging and symptoms.
-Surgical management if ocular or spinal lesions

AM Report 02/28/17: Sphincter of Oddi dysfunction (SOD)

Sphincter of Oddi 

-Found at the confluence of the distal CBD and the pancreatic duct as they enter the duodenum
-Usually during fasting, the Sphincter of Oddi allows bile to be released into duodenum via contractions and working with the MMC (migratory motor complex)
-When this does NOT happen, you can get SOD

SOD
SOD is also known as:

-Biliary Spasm
-Biliary dyskinesia
-Papillary stenosis
-Post-cholecystectomy syndrome 

Two main diseases that SOD can cause

-Biliary pain
-Idiopathic recurrent acute pancreatitis

Epidemiology and Clinical manifestations

-Usually seen in middle aged women who have undergone cholecystectomy (not always)
-Presents as  biliary pain , usually RUQ/Epigastric, lasting 30 minutes-hours
-Labs show elevated AST/ALT/ALK that can normalize between attacks, CBD dilated > 8 mm with normal amylase/lipase
Rome IV Criteria (+ Biliary pain, no bile duct stones/structural abnormalities, elevated liver enzymes or dilated bile ducts but NOT both)

What is a normal CBD?

-95 % normal patients with CBD < 6 mm but increases with age (~upper limit corresponds to decade of life)
Can see CBD up to 10 mm post-cholecystectomy

How do you make the diagnosis?

It is a diagnosis of exclusion!! 

-Exclude IBS (do symptoms get better/worse with constipation/diarrhea)
-Start with LFT and pancreatic enzymes (rule out pancreatitis)
-Next check transabdominal ultrasound (rule out stone)
-Then MRCP vs. EUS/ERCP (is there a Structural issue?)
-Hepatobiliary scintigraphy
-Best way to diagnose it is via Sphincter of Oddi manometry for definite diagnosis. 

Treatment

-Medical treatment (not great)- smooth muscle relaxers, CCB, nitrates
-Surgical treatment: Endoscopic sphincterotomy, ultimately may need surgery for biliary and pancreatic sphincterotomy

 

AM report 02/23/17: Subarachnoid Hemorrhage

Clinical presentation of SAH

THUNDERCLAP headache (!)- 97 % present with sudden onset severe HA-worse headache of their life.
-Can be associated with LOC (if severe), nausea, vomiting, meningismus, CN deficits, seizures (10 %), and SUDDEN DEATH (10-15 %)
-30-50 % have a sentinel headache preceding SAH

Making the diagnosis

-Always start with non-contrast HEAD CT
-Picks up 92 % of SAH if <24 hours but sensitivity is highest in first 6-12 hours after SAH (~nearly 100 %!) but drops to about 60 % by 5d.
-If negative, proceed with LP ~12 hours later (may be falsely negative early)

sah
SAH on CT scan

What do you see on LP if SAH?

-Elevated opening pressure
-Significantly elevated RBC count with bloody tap that does not clear (although RBC count can go down) so not always helpful to distinguish from traumatic tap
Xanthochromia (pinkish-yellowish tint)-due to hemoglobin degradation products and means blood has  been in the CSF for at least 2 hours
Excellent sensitivity/specificity if done <12 hours from SAH but can also see Xanthochromia if high protein content, systemic bilirubin>15, and very traumatic tap (RBC>100k)

Xanthochromia

Etiologies of non-traumatic SAH
(not a complete list)

ANEURYSMS (Most Common)

Perimesencephalic
-Vascular malformations
-Arterial dissection
-Cerebral venous thromboses
-Cocaine abuse
-In setting of anticoagulation
-Reversible Cerebral Vasoconstriction Syndrome (RCVS)

Complications of SAH

51 % die from SAH so very high mortality

Rebleeding (highest in first 24 hours)
Hydrocephalus (early)-May need VP shunt
-Vasospasm (delayed cerebral ischemia)
-Increased ICP 
Seizures-May need AEDs
Cardiac Arrhythmias 

Treatment

-If aneurysm-treat with surgical clipping or endovascular coiling. 
-Prevent vasospasm with Nimodipine 60 mg PO q4h

 

AM Report 2/27/17: Hematology Board Review

Shistocytes indicate intravascular hemolysis

picture1

Disseminated Intravascular Coagulation (DIC):
Characteristics:
– Activation of coagulation
– Generation of thrombin
– Consumption of clotting factors
– Destruction of platelets

Lab findings:
-Elevated PT (due to consumption of factor VII ~ shortest half life)
– +/- Elevated PTT
– Low fibrinogen
– Elevated D-Dimer
– Low platelets
– MAHA (~50% of patients)
* Coagulation studies will be NORMAL in TTP – one way to differentiate from DIC.


Thrombotic Thrombocytopenia Purpura (TTP):

Due to a deficiency with ADAMTS13

Pentad (remember FAT RN) of TTP:
1) Fever
2) Anemia (microangiopathic hemolytic)
3) Thrombocytopenia
4) Renal disease
5) CNS disease (encephalopathy)

Other causes of MAHA (not a complete list):
– DIC
– HELLP
– Antiphospholipid syndrome
– Malignant hypertension
– Vasculitis
– Scleroderma renal crisis
– Many more…

Hereditary Hemochromatosis:

Triad:
Diabetes
Cirrhosis
Skin bronzing


Associated conditions:
– CPPD
– Arthropathy
– Hypogonadism
– Heart disease
– Destructive arthritis

Treatment:
Phlebotomy

*Caution patients about eating raw seafood or undercooked pork – increased incidence of Vibro vulnificus and Yersinia entercolitica in iron overload

von Willebrand Disease (vWD):
– MOST COMMON inherited bleeding disorder
– Symptoms similar to platelet disorders: nosebleeds, easy bruising, bleeding gums, and post-surgical bleeding; GYN bleeding is especially common.

Underlying problem:
– vWF protects factor VIII from degradation

Lab abnormalities:
– prolonged aPTT (see below) – due to degradated factor VIII
picture4

Treatment:
– DDAVP (desmopressin) – causes preformed stores of vWF and factor VIII to be released from endothelial cells

Hereditary Spherocytosis:
– Due to mutations causing deficiencies/dysfunction in erythrocyte membrane proteins – reducing surface-to-volume ratio
– Patient’s are at an increased risk of pigmented (bilirubin) gallstones

Lab abnormalities:
– Spherocytes on blood smear
– Varying degrees of anemia/reticulocytosis/bilirubin elevation
– ↑ MCHC reflecting membrane loss – CHARACTERISTIC
picture8
– see spherocytes on peripheral smear
– Osmotic fragility test can aid in the diagnosis when it is not clear (i.e. no family history)

Treatment options:
– Folate supplementation
– Splenomegaly (reduces hemolysis) ~ reserved for severe form; ensure vaccination against encapsulated organisms S. pneumoniae, H. influenza, N. meningitidis

Polycythemia vera (PV):
– PV is a disorder of myeloid/erythroid stem cell that causes erythropoietin-independent proliferation of erythrocytes
– Activating mutation of JAK2 (JAK2 V617F) is present in ~95% of PV

First step in making the diagnosis of PV:
– Exclude secondary causes of elevated Hct/red cell mass: chronic hypoxia and excess erythropoietin

Clues to the diagnosis of PV:
– Itching after a shower (aquagenic pruritus)
– Painful/red palms/soles (erythromelagia)
– Splenomegaly

Treatment:
– Phlebotomy (goal Hct <45%)
– +/- Myelosuppression (hydroxyurea)
– Aspirin

*Look out for a question that introduces acute leukemia in a patient with a history of PV

Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD):
– X-linked – therefore men are primarily affected
– G6PD is important for cells to counterbalance oxidative stress

Known triggers (not a full list):
– Medications: Sulfonamides, Nitrofurantonin, Anti-malarials, Rasburicase
– Naphthalene in mothballs
– Fava beans
– Infection

Peripheral smear:
Bite cells: membrane defect that appears as a semicircular “bite” has been taken out of an erythrocytes – caused by removal of denatured hemoglobin by macrophages in the spleen
Picture5.png
Heinz bodies: denatured oxidized hemoglobin visualized as intranuclear inclusions
picture6

picture7

Antiphospholipid Antibody Syndrome (APLS):
– Need ONE LAB criteria (confirmed 12 weeks apart) and ONE CLINICAL criteria

Lab Criteria:

– B2 Glycoprotein
– Anti-Cardiolipin antibody
– Lupus anticoagulant (measured as DRVVT that does not correct with mixing study)
*Positivity of all three lab tests is associated with the highest risk of thrombosis and pregnancy loss.

Clinical Criteria:
– Any thrombosis (venous or arterial)
– Fetal loss/miscarriage

Clinical Features of APLS:
– Prolonged PTT (50%)
– Livedo reticularis (20%)
– Cardiac valvular disease ~ MR
– DVT (32%)
– Stroke (13%)
– Hemolytic anemia (7%)

Paroxysmal Nocturnal Hemoglobinuria (PNH):
– PNH is an acquired disease – results in cells (RBCs, WBCs, platelets) lacking normally attached surface proteins
– CD55/CD59 are responsible for inactivating complement on RBC surface; lacking this protein, therefore, results in more complement-mediated lysis

Why does it occur at night?
– Complement-mediated lysis occurs more readily at lower pH levels and PCO2 levels rise at night – so patients report AM hematuria

Other associated conditions (besides hemolysis)
– Developing thrombosis (at unusual sites) – not fully explained; consider PNH in patients with both venous/arterial clots – Budd-Chiari syndrome may be a clue!

Treatment:
– Eculizumab – anti-CD5 monoclonal antibody that ceases hemolysis by inhibiting complement

Hairy Cell Leukemia (HCL):
Two clues to help make the diagnosis:
– Photo showing thread-like projections emanating from the cell surface (i.e. “hairy” appearing cells)
picture9
– Bone marrow biopsy resulting in a “dry tap” – occurs when marrow is difficult to extract due to firbrosis (seen in some cases of HCL)

Waldenström Macroglobulinemia:
– Key is to know that Waldenström’s overproduces the IgM paraprotein, but myeloma rarely does – it usually overproduces the IgG

Diagnosis:
– Clinical
– IgM monoclonal gammopathy
– Marrow biospy showing >10% lymphoplasmacytic cells
– Flow cytometry

Treatment:
– Plasmapheresis for hyper-viscosity
– Rituximab



 

AM Report 2/21/17: Chronic Myeloid Leukemia

Remember the breakdown and differentiation between AML, ALL, CML, CLL.  It starts with understanding the cell line formation:

cdr526538

Nice overview provided by Khan Academy: https://www.khanacademy.org/science/health-and-medicine/hematologic-system-diseases-2/leukemia/v/leukemia-classifications

Condition Epidemiology Clinical Signs/Symptoms CBC Morphology Translocations
Acute Lymphoblastic Leukemia (ALL) Childen (2-5 yo), male > female, association with Downs syndrome ↓ RBCs, ↓ PMNs, ↓ platelets, +HSM, bone pain, CNS manifestions, tumor lysis syndrome, mediastinal mass Anemia, thrombocytopenia, variable WBC (>25% lymphobasts) Condensed chromatin, scant cytoplasm, B cell – CD10+, Tdt+ t (12;21) kids – good prognosis; t(9;22) – poor prognosis
Chronic Lymphoblastic Leukemia (CLL) Adults Male >>> Female Asymptomatic or nonspecific, autoimmune hemolytic anemia Lymphocytosis >5000, low platelets, ↓ antibodies (hypogammaglobulinemia) Smudge cells, condensed chromatin, scant cytoplasm
Acute Myeloid Leukemia (AML) Adults > 60 yo (mean 67) Spontnaeous bleeding, petechiae, ecchymosis, DIC Anemia, thombocytopenia, >30% myeloblasts Auer rods, myeloblasts, monoblasts t (15;17) – APML – treat with ATRA
Chronic Myeloid Leukemia (CML) Ages 20-50; Rare in children Insidious onset, mild symptoms, splenomegaly Symptomatic WBC > 200k Hypercellular marrow t (9;22) – BCR-ABL – treat with TKI

970-174072 Smudge Cells (CLL)

auer-rod Auer Rods (AML)