Thanks to Katie for presenting the interesting case of a young man with history of disseminated TB with TB meningitis and hydrocephalus requiring VP shunts, admitted for acute LUE weakness, L homonymous hemianopsia, and memory impairment, found to have acute strokes in multiple vascular territories due to TB related CNS vasculitis!
Remember that arterial dissection is the most common cause of stroke in a young patient.
CNS vasculitis can be primary or secondary to a systemic illness. It typically presents with infarcts in multiple vascular territories. Treatment involves immunosuppression with high dose steroids + cytoxan/rituxan.
CNS vasculitis is the most common cause of severe neurologic deficit in patients with TB meningitis.
Vasculitis in CNS TB is the result of a hypersensitivity reaction to proteins released from the bacteria.
TB meningitis requires an extended course of anti-TB treatment, generally up to 1 year or more. Serial LPs are obtained to monitor adequate response to therapy.
Etiologies of stroke in a young adult
Coagulopathy (think of conditions that cause both arterial and venous thrombosis)
Leukostasis in setting of leukemia
Myeloproliferative disorders (PV, ET, CML)
Paroxysmal nocturnal hemoglobinuria
Dissection (most common cause of stroke in a young person)
Malformations (AVMs, aneurysms, moyamoya)
Cerebral venous sinus thrombosis
Large vessel: Takayasu, GCS
Small to medium: Kawasaki, PAN, ANCA-associated
Fungi (esp cocci)
Collagen vascular disease (i.e. lupus)
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)
Organic acid disorders
Cocaine and meth
Rheumatic valve disease
Mitral valve prolapse
Endocarditis with septic emboli
Three main manifestations:
TB meningitis (most common presentation in low incidence settings like the US)
Spinal tuberculous arachnoiditis
Spillage of tubercular protein into the subarachnoid space results in an intense hypersensitivity reaction and inflammation resulting in
Proliferative arachnoiditis (fibrous mass encasing cranial nerves and vessels adjacent to it)
Vasculitis with resultant aneurysm, thrombosis, and infarction
1% of all TB cases, 5% of all extrapulmonary TB cases
Meningitic phase: meningismus, headache, vomiting, lethargy, confusion, CNS signs, some motor deficits
Paralytic phase: stupor, coma, seizures, hemiparesis (death within 5-8 weeks)
Characteristic CSF findings of low glucose, elevated protein, lymphocytic pleocytosis
CSF AFB smear and culture: in general, a minimum of 3 serial LPs should be performed, as diagnostic yield increases f
Nucleic acid tests: Xpert MTB/RIF assay should be submitted in the setting of high clinical suspicion and negative AFB staining.
Intensive phase (2 months): four drugs RIPE. Ethambutol has poor CNS penetration so some use fluoroquinolones instead.
Continuation phase (7-10 months)
A review of 9 trials on 1337 patients found that use of steroids reduced death and disability by ~25%.
Benefit higher if started earlier in disease process.
Treat for 8 weeks, slow taper.
A retrospective study in Stroke 2018 on patients with TB meningitis found that those >40, with concurrent HTN, dysplipidemia, and DM were more likely to have this complication. Some small case series showing benefit in reducing future strokes with the use of Aspirin.
Bri presented a case of a gentleman with multiple medical comorbidities with a recent lap chole presenting with confusion. His labs were significant for anemia, thrombocytopenia, elevated indirect bilirubin, elevated LDH, and undetectable haptoglobin. A smear revealed numerous schistocytes concerning for MAHA. ADAMTS13 levels were found to be very low, and the presence of an ADAMTS13 inhibitor was detected as well. This presentation is consistent with thrombotic thrombocytopenic purpura (TTP)!
Common differential for microangiopathic hemolytic anemia (MAHA):
TTP/HUS, atypical HUS
Mechanical heart valves
Severe B12 deficiency
Rare, most often > 40 in adults, congenital ADAMTS13 deficiencies can be seen in kids (Upshaw-Schulman Syndrome, autosomal recessive)
2:1 female to male predominance
Non-immune mediated platelet and RBC destruction due to mechanical shearing of platelets and RBC when they pass through platelet/fibrin deposits on small vessel walls in absence of ADAMTS13 activity.
Further consumption of plts via formation of microthrombi in small arterioles/capillaries, brain/heart/kidneys are especially affected.
ADAMTS13 cleaves VWF, preventing large multimer formation on vessel walls
Thanks to Tim for presenting the interesting case of a middle-aged man with h/o inadequately treated syphilis who presented with neck stiffness worse in the mornings, back pain, and blurry vision, admitted for presumed neurosyphilis. Exam revealed inflammation of T2/T3 joints, L SI joint tenderness, and an inflamed R foot with dactylitis of the 3rd and 4th digits. Further history revealed a recent gonorrhea/chlamydia for which he was treated and HLA B27 positivity consistent with reactive arthritis! He was started on NSAIDs with significant improvement of symptoms.
Neurosyphilis is most commonly seen in HIV positive patients and can present at any time after infection.
Early neurosyphilis occurs within the first year after infection and involves the CNS, meninges, and vasculature
Neurosyphilis presents with posterior uveitis or pan-uveitis whereas reactive arthritis presents with anterior uveitis
Late neurosyphilis occurs >10 years after infection and involves the brain and spinal cord parenchyma
The four main spondyloarthropathies are ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and IBD-related arthritis.
The genital pathogen most commonly associated with reactive arthritis is chlamydia trachomatis.
Our doctor-in-training Jacqueline presented a middle man with infrequent medical care, with a history of heavy alcohol use, who presents with generalized swelling and anorexia. He was septic on presentation with a distended abdomen. Ascitic fluid anlysis was concerning for bacterial peritonitis, and blood cultures (4/4 bottles) were positive for acinetobacter with OXA resistance marker!
Spontaneous bacterial peritonitis
Important to distinguish between Spontaneous bacterial peritonitis (SBP) vs Secondary bacterial peritonitis (also SBP but for the sake of clarity, SBP from this point on will refer to spontaneous bacterial peritonitis)
Secondary: Bacterial peritonitis secondary to something else besides spontaneous, i.e. bowel perforation, surgery.
100% mortality without surgical intervention. Surgical risk is high but patient mortality is almost guaranteed without surgery!
If Spontaneous BP, mortality can approach 80% with abdominal surgery.
Diagnosis: history, fluid analysis
Cultures from peritoneal fluid usually polymicrobial (gut flora)
Tertiary bacterial peritonitis: Persistence of peritonitis or abscess following adequate treatment of primary or secondary peritonitis
Pts with cirrhotic ascites, suspect SBP in all these patients, and also pts with ascites suffering from a GIB.
Organisms: E.coli, Klebsiella, strep pneumo are most common, usually single organism
Less common: Acinetobacter, pseudomonas, proteus
If polymicrobial of anaerobes, suspect secondary bacterial peritonitis
Rarely fungal but they have been described, poor prognosis.
S/S of ascites
May have fever, malaise, encephalopathy, decompensated liver cirrhosis, peritoneal signs sometimes.
Frequently an instigator for hepatorenal syndrome in cirrhotic patients.
PMN > 250 cells/mL
Absence of secondary causes
Cefotaxime 2g Q8H
Ceftriaxone once daily is an alterative with some evidence trending toward improved survival and less ICU stay with 2g daily dosing vs 1g.
Cefepime 1-2g Q8H is an alternative as well esp for resistant pathogens.
Fluoroquinolones: Consider alternative if pt already on a quinolone for prophylaxis prior to developing SBP. Can use Cipro, Levo, or Moxi.
Beta lactam/Beta lactamase inhibitors i.e. Zosyn
Duration: At least 5 days
Albumin: Recommended, RCT published in NEJM in 1999 established the administration of albumin decreases the incidence of renal failure with albumin + antibiotics as well as decrease in mortality.
Patients in the study who were most likely to benefit from albumin had:
Bili > 4
Cr > 1
BUN > 30
1.5g albumin /kg on day 1, the 1.0g/kg on day 3. Dose limited to max of 100g
HRS (Hepatorenal syndrome): 1.0g/kg albumin days 1 & 2 and see if renal function improves (albumin challenge)
Renal failure can be seen in 30-40% of patients with SBP
Prognosis tends to be poor once HRS sets in
Type 1: Rapid progressive decline, 50% 1 month mortality
Type 2: More subacute/chronic, not associated with an inciting event, median survival 6 months
Cirrhotics presenting with GIB should get primary prophylaxis, total duration of therapy x 7 days
Ascitic protein < 1.0 g/dL can also be considered (RCT published in Journal of Hepatology in 2008)
Ascitic protein <1 and Childs Pugh > 9 or T.bili > 3 or renal dysfunction: can also consider long-term primary prophylaxis, based on an RCT from Gastroenterology in 2007, drug of study was norfloxacin.
Indicated after first episode of SBP, one year recurrence rate of 40-70%, mortality rate of 50-70%
Meds: Norfloxacin or cipro daily, Bactrim also an equivocal alternative
Certain strains can survive in a desiccated environment for weeks.
Most commonly in ventilator associated pneumonia and blood stream infection (1.5% – 2.4%)
Others: Central line, catheters, surgical site infection
Can be contamination, pts and health care workers can be colonized
Can also present as endocarditis or meningitis or ocular infection (contact lens)
Peritonitis secondary to acinetobacter usually more common in peritoneal dialysis patients.
Prior antibiotics, especially beta lactams, carbapenems, fluoroquinolones
Presence of catheters, ICU
PD (especially in setting of peritonitis secondary to actinobacteria)
Trauma, burn, immunosuppression
Increasingly resistant, both acquired and inherent
ESBL phenotype also emerging
1st line: cephalosporin (ceftaz, cefepime), beta-lactam/beta lactamase inhibitor, carbapenems are highly effective, ampicillin0sulbactam is also very effective.
Sometimes combination therapy is used i.e. with a fluoroquinolone or aminoglycoside due to concerns of emerging and acquired resistance but limited data on combo therapy vs emergences of resistance or whether clinical outcome is improved.
Other possible options: minocycline, tigecycline, polymyxins
2x more likely to die from a carbapenem resistant strain
Thanks to Austin for presenting the case of an elderly woman with h/o psychiatric disorder who presented with acute/subacute onset of AMS, severe hypothermia, sinus bradycardia, and hypotension with work up revealing hypothyroidism suspicious for myxedema coma!
Exam findings for hypothermiachange depending on severity of hypothermia (see below).
It is crucial to measure core body temperature for accuracy especially when you are rewarming the patient (esophageal is the best, rectal/bladder are ok prior to rewarming but can remain low in spite of increasing core body temp so do not rely on these metrics alone)
Think of etiologies of hypothermia broadly within the categories of increased loss or decreased heat generation.
The most common causes of hypothermia are sepsis, exposure, and hypoglycemia.
The hallmarks of myxedema coma are AMS, hypothermia, and a precipitating event (i.e. infection, exposure, meds, etc.)
Myxedema coma is a medical emergency with a high mortality rate. So consult endocrine early when you are suspecting it.
Always treat myxedema coma with levothyroxine AND steroids until you have ruled out a concurrent adrenal insufficiency.
↑ HR, ↑ RR, ↑ BP, hyperventilation
Body’s attempt to preserve heat. When peripheral vasoconstriction occurs to keep blood closer to vital organs, BP rises. Kidneys see this rise in BP and act to correct it by dumping fluid! (Oh kidneys…)
Humidified inspired air
Confusion, slurred speech
↓ HR, hypoventilation
Can also start to notice other cardiac manifestations such as prolonged QTc, QRS, osborn (J) waves, ST elevations/depressions.
↓ renal blood flow
Passive, external (see above) PLUS
Forced heated air
Warm water immersion
Warm humidified air (42°C)
Warm IV fluids (42°C)
Body cavity lavage (in trauma patients only)
Edema (due to poor renal blood flow) of extremities and lung
↓ HR, ↓ BP (due to drop in cardiac output), hypoventilation, ventricular arrhythmias
Cardiac manifestations more common as with moderate hypothermia
mechanism is poorly understood but thought to be due to paralysis of the nerves regular vascular muscle tone leading to vasodilation and sensation of a heat flush which results in the patient wanting to take their clothes off.
Any of the above (passive external, active external, active internal) and/or
Etiologies of hypothermia:
Items in red above are the most common causes of hypothermia.
Less reliable since labs have to be warmed prior to processing
ABG is often inaccurate
Coagulopathy may be masked
Hyperkalemia due to rewarming
Complications of rewarming:
Hypotension due to peripheral vasodilation
Ileus and urinary retention
Core temperature after-drop (a condition in which cold peripheral blood gets shunted to the core and results in further decline in temperature. You can avoid this by active internal rewarming like warmed IV fluids)
Yonglu presented a middle age man with no medical history presenting with syncope. In the preceding months, he has been having non-specific fatigue, decreased exercise tolerance, dizziness, and diaphoresis. He was found to be hypoglycemic after this syncopal episode, and in the hospital his labs were consistent with hyperinsulinism when he was in a hypoglycemic state. CT revealed diffuse liver masses concerning for HCC, as well as a lesion on his left iliac crest appearing to be an osteosarcoma. He was also found to have a pancreatic mass as well…
Three malignant processes? Octreotide scan revealed increased uptake at these regions, and biopsy of the liver revealed a diagnosis of a neuroendocrine tumor!
When we think about hypoglycemia, its pattern can actually give us a clue.
Fasting: Most common
Post-prandial: non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), post-bariatric surgery hyperinsulinemic hypoglycemia
Both: Insulin autoantibody, insulinoma
Rare, not enough data
Small cohort: median age 48 years, 77% men
MEN Type 1: Younger presentation, 20s
Pancreatic islet cell origin
Generally benign, single vs multiple
Rare to be malignant (10%)
Pattern: fasting hypoglycemia mainly but can be both
May have some sympathoadrenal sx i.e. palpitations, diaphoresis (seen in this patient), tremulousness
Likes to spread to liver, rarely can have bony mets (~13%)
Whipple’s Triad: Presence of all three demonstrates “true” hypoglycemia
Symptoms of hypoglycemia
Low plasma glucose at time of symptoms
Relief of symptoms when glucose is back to normal
Evidence of inappropriately high serum insulin during episode of hypoglycemia
72 hour fasting plasma glucose test: Supervised fast in order to bring on hypoglycemia in order to evaluate etiology. If pt has underlying hyperinsulinism, 95-99% of the time they will be hypoglycemia within 48 hours of fasting.
Blood test is drawn when pt has sx of hypoglycemia
Test: Glucose, insulin, proinsulin, and c-peptide level.
Normal: suppression of endogenous insulin
Abnormal: Inappropriately elevated insulin, pro-insulin, and c-peptide in setting of hypoglycemia.
Octreotide scan: Increased uptake seen in tumors of neuroendocrine etiology, more sensitive than US, CT, or MRI for detection of somatostatin receptor positive tumors
Evidence of hyperinsulinism
High insulin level
Chromogranin A: used to help diagnose carcinoid tumors (NET of the digestive tract and lungs). Nowadays carcinoid is generally used to refer to well differentiated NETs originating in the lungs. GI tract tumors are now termed NET.
Localized lesion: Surgical resection is curative
Octreotide: Inhibits growth hormone secretion, can switch to Q-monthly formulation
Diazoxide: Diminishes insulin secretion, side effects include hirsutism and edema
Radiation therapy: Data also limited in utility but can be consider if evidence of bony mets (which is also rare for NET)
Minority of NET, namely high-grade, well differentiated with Ki67 index > 20%, are rare and there is no consensus on how to treat these patients. These patients generally respond poorly to platinum/etoposide based regimens used to treat most NETs.
Other options: Temozolomide, Sunitinib (RTK inhibitor), Everolimus (mTOR inhibitor)
Helpful table for hypoglycemia work up.
Beta-hydroxybutyrate (BHB) is by product of alternate metabolism (more specifically ketone bodies) in a fasting state, so it can be elevated in setting of prolonged fasting (not just DKA).
Also thanks to Arathi for pointing out that insulin has a negative feedback on this process, hence in a hyperinsulinemic state (despite concurrent hypoglycemia), beta hydroxybutyrate would be very low!
Insulinomas can appear like hypoglycemia secondary to oral glycemic agents, but the key is the oral glycemic agent screen would be positive in the latter case!
IGF-omas can cause s/sx hypoglycemia due to similarity with insulin. Expect IGF2 levels to be elevated in such cases and elevated BHB.
Please refer to this helpful review article if you want to know more about NETs!
Also please refer to this paper for a case report on AFP-producing pancreatic NET (AFP elevated in this patient!)
Our doctor-in-training, Jacqueline, presented a case of a 46yo man with a complicated abdominal surgical history, as well as schizophrenia, who presents with acute onset vague abdominal pain. He could not provide any remarkable history (other than abd pain and losing a bag of coins), and his exam was otherwise benign except for mild diffused abdominal pain…
The mystery was resolved on a radiography.
Foreign Body Ingestion
Mostly in kids, peaks 1-2 years of age
Adults: Typically, accidental (95% of cases) usually related to fish, chicken bones, or toothpicks. More common in older adults, pts with mental illnesses, intoxicated, or inmates (drug trafficking, packers vs stuffers).
Most frequent cause of esophageal obstruction = food bolus on existing stricture
Chest pain/abdominal pain
Fever, shock (perforation)
Imaging, clinical history
Will depend on stability, the location, nature of the objects ingested, and progression.
Expectant management for most blunt objects, ~ 70-80% of objects will pass by day 4. Consider surgical/endoscopic intervention if failure to progress
Local necrosis secondary to pressure, electrical current, or caustic chemicals.
Ulceration can occur within 2-4 hours
Perforation can be seen as early as 4-8 hours
VERY IMPORTANT to distinguish between coin batteries (thicker, concentric circles) vs coins (thinner, confluent)!
Higher chance of complications if multiple magnets and/or metallic objects were ingested.
Can react with metal external of the body and cause injury
Localized bowel necrosis, obstruction
Prompt removal endoscopically if in esophagus or stomach.
Beyond stomach: Surgery if symptomatic or failure to progress
Single magnet: Expectant management, serial XR, monitor progress, don’t be around anything ferromagnetic
High risk of perforation/injury if in esophagus, medical emergency
Immediately endoscopic removal if in esophagus
Stomach/proximal duodenum: still consider urgent endoscopic removal, complication risk varies from as low as 10% to 40%
Beyond and failure to progress: Surgical intervention recommended.
Packers vs Stuffers
Packers: Carefully PACKING illicit substances into packages, lower chance of leakage (image adapted from Vectortoons.com)
Stuffers: Hastily STUFFING illicit substances to hide evidence from law enforcement (image adapted from Family Guy), higher chance of content leakage.
Packers: Whole-bowel irrigation safe and feasible
Opioid (CNS depression, hypoventilation, pinpoint pupils): IV Naloxone 0.05 in nonapneic patients, 0.2 – 1mg in apneic patients. Larger doses may be required if pt ingested a large amount of heroin.
Sympathomimetic (agitation, hypertension, hyperthermia): Symptomatic management, airway monitoring, temperature control. AVOID pure beta blockers. Can consider GI decontamination but consult Poison Control.
If suspecting ingestion of potentially toxic substance, don’t hesitate to call Poison Control!