Diagnostic Tests for SARS-CoV2

DETECTION OF VIRAL RNA (RT-PCR tests)

1. RT PCR targets the following genes
   1. env – envelope
   2. N – nucleocapsid
   3. S – spike
   4. RdRp – RNA-dependent RNA polymerase
   5. ORF1 genes
2. Cycle threshold
   1. number of replication cycles required to produced a fluorescent signal
   2. lower Ct values represent higher viral RNA loads
   3. Ct value <40 clinically reported as PCR positive
   4. Ct values in severely ill patients are lower than mild cases
3. (+) PCR result reflects only detection of the viral RNA, not necessarily indicate presence of viable virus
4. Sn/Sp
   1. RT-PCR positivity
      1. BAL specimen (93%)
      2. sputum (72%)
      3. nasal swab (63%)
      4. pharyngeal swab (32%)
   2. Specificity is 100%

DETECTION OF ANTIBODIES

1. most sensitive and earliest serological maker is TOTAL ANTIBODIES, which increase from 2nd week of symptom onset
2. IgM and IgG ELISA have been found (+) as early as Day 4 of symptom onset
   1. higher levels in second and third week
   2. IgG and IgM seroconversion occurred in all patients between third and fourth week
   3. IgM begins to decline and reach lower levels by week 5 and disappears by week 7
   4. IgG persists beyond 7 weeks
3. >95% specificity for diagnosis of COVID-19
4. Sn/Sp
   1. majority of Ab are produced against NC (most abundant protein of the virus), tests to detect Ab would be most sensitive
   2. receptor-binding domain of S (RBD-S) protein is the host attachment protein, would be more specific and expected to be neutralizing

References:

Sethuraman, N., Jeremiah, S., & Ryo, A. (2020). Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. doi: 10.1001/jama.2020.8259

Holmes, K. (2003). SARS-Associated Coronavirus. New England Journal Of Medicine, 348(20), 1948-1951. doi: 10.1056/nejmp030078

Neurogenic Stress Cardiomyopathy

Proposed Mechanism for HCP causing Takotsubo:

Sympathetic control of the heart is mediated by hypothalamic nuclei that abut the walls of the third ventricle.  Specifically, dysfunction of PVN and DMN has been linked to catecholamine-induced myocardial necrosis.  Hydrocephalus may disrupt these centers, although intracranial hypertension may not be necessary for this to occur.

 

*Paraventricular nucleus (PVN):   TRH release, CRH relesase, oxytocin release, vasopressin release, somatostatin release

**Dorsomedial nucleus (DMN): BP, HR, GI stimulation

 

Reference:

Gharaibeh, Kamel, Jackie Scott, and Nicholas A. Morris. “Neurogenic Stress Cardiomyopathy Precipitated By Acute Hydrocephalus After Aneurysmal Subarachnoid Hemorrhage.” Neurocritical Care (2017): n. pag. Web. 14 Aug. 2017.

“Hypothalamus.” En.wikipedia.org. N.p., 2017. Web. 14 Aug. 2017.

Upper Extremity Veins

Deep Veins:

1. paired ulnar, radial and interosseous veins in forearm

2. paired brachial veins of upper arm

3. axillary vein (continues as subclavian vein)

 

Superficial Veins:

 

1. cephalic vein
2. basilic vein

 

References

“Deep Veins Of The Upper Extremity.” Uptodate.com. Web. 27 July 2017.

“Primary (Spontaneous) Upper Extremity Deep Vein Thrombosis.” Uptodate.com. 27 July 2017.

Diabetes Insipidus

Production of arginine vasopressin – by magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus.  Transported to the neurohypophysis via hypothalamo-hypophyseal tract.  Injury to these structures leads to DI.

 

 

Triphasic response in DI:

1. First phase – DI caused by “stunning” of the magnocellular neurons, no AVP secretion.
2. Second phase – injured hypothalamic cells degenerate and release their stored AVP
3. Third phase – if majority of these neurons are destroyed, permanent phase of DI begins

 

 

 

Reference:

Schreckinger, Matthew, Nicholas Szerlip, and Sandeep Mittal. “Diabetes Insipidus Following Resection Of Pituitary Tumors”. Clinical Neurology and Neurosurgery 115.2 (2013): 121-126.

 

 

RANDOM NOTES ON Diabetes insipidus (DI)

Nephrogenic DI – renal insensitivity to vasopressin, acquired or genetic; lithium

Central DI – deficiency in production of ADH

• Related to extent of excision
• Usually transient phenomenon after surgery
• SIADH in second phase – follow serum Na on day 7
• Symptoms: polyuria, nocturia, polydipsia / thirst

 

Patients with DI, especially if drowsy and unable to maintain adequate fluid intake, can rapidly become dehydrated.

 

ALGORITHM:

Measure Is and Os hourly, sum every 6 hours

Foley catheter

Onset of dilute polyuria UOP >250cc/hr x2  hours

Check other reasons:

1. diuretics
2. large resuscitation
3. mannitol
4. hyperglycemic
5. salt wasting

Labs

1. USG <1.005
2. UOsm 50-200 (<serum)
3. Hypernatremia

? rountine serum Na – every 6 hours on day 1, then every 12h until stable, then daily x 1 week

Replace fluids

1. normal saline to replace previous hour output, switch to 0.45% saline if UO 4-6ml/kg/h, switch to D5W if >6 ml/kg/h
2. if awake, fluids ad libidum; may be able to maintain fluid balance by drinking to satiety, still DDAVP so patients can sleep comfortably at night

DDAVP (1-desamino-8-D-argnine vasopressin)

• DDAVP: activates V2R – water reabsorption in kidney; mobilizes water channel aquaporin to luminal membrane of DCT and CD
• Liquid form – given intranasal; oral tablet form; parenteral form

 

	Tablets	Spray	Solution for injection
Dose comparison	100 mcg	2.5 mcg	N/A
	200 mcg	5 mcg	Less than 0.5 mcg
	400 mcg	10 mcg	Less than 1 mcg

 

• Usual dose 1 ug q12h
• Empiric – give minimum dose required to control polyuria; goal to control nocturia, partial control of polyuria during the day
• Water retention à hyponatremia is a potential risk; patient education, serum NaHS

 

ENDOCRINE

Post-op complications: hematomas, epistaxis, HCP, CSF leaks, meningitis

Preop labs with hypopituitarism – stress doses of hormonal replacement; keep on physiological dose until outpatient assessment

Lab tests post-op for evidence of early endocrinological remission

Cushing – no steroids unless necessary; serum cortisol q6h until nadir; if <5 + symptoms, start glucocorticoid therapy and then transition to maintenance doses until outpatient reassessment

Normal cortisol function prior to surgery – no steroids; assess post-o with AM fasting cortisol on POD1 or POD2; new start steroid replacement if cortisol <10 until reassessed outpatient

Acromegaly – POD1 serum GH level predicts early remission; delayed IGF1 level 6 weeks after

Prolactinomas – POD 1 AM prolactin level normalizes with remission

 

Moyamoya Direct Bypass Surgery

Technique for Direct Bypass Surgery:

 

• Map out STA anterior to zygomatic arch for 8-9cm, using Doppler.

 

• Dissect STA and vascular cuff under microscope.

 

• Incise temporalis muscle in H-shaped fashion.
• Create 6x6cm craniotomy over frontotemporal region.

 

• Open dura wide over Sylvian fissure, under high magnification, identify M4 recipient artery.

 

 

• Cut distal STA at 45 degrees, place temporary clips on recipient artery.
• Make an elliptical arteriotomy over M4 branch.
• Perform end-to-side anastomosis using 10 to 0 interrupted suture under high magnification.
• Remove temporary clips from recipient and proximal STA once bypass completed.

 

• Place STA and vascularized cuff in close apposition to cortical surface to facilitate delayed collateralization

 

Reference:

Liu, Jonathan J., and Gary K. Steinberg. “Direct Versus Indirect Bypass For Moyamoya Disease”. Neurosurgery Clinics of North America 28.3 (2017): 361-374.

Framework for Classification of the Epilepsies

Reference:

Scheffer, Ingrid E. et al. “ILAE Classification Of The Epilepsies: Position Paper Of The ILAE Commission For Classification And Terminology”. Epilepsia (2017): n. pag. Web. 19 Mar. 2017.

Clotting Cascade and Anticoagulants

Clotting cascade and anticoagulants.

 

Reference:

Raval, Amish N. et al. “Management Of Patients On Non–Vitamin K Antagonist Oral Anticoagulants In The Acute Care And Periprocedural Setting: A Scientific Statement From The American Heart Association”. Circulation (2017): CIR.0000000000000477.

Classification of Hydrocephalus

 

The first level of classification of hydrocephalus should be based on the point where flow of CSF is restricted.  These potential sites of restriction would include:

• the foramen of Monro
• the aqueduct of Sylvius
• the basal cisterns
• the arachnoid granulations
• theoutflow of venous blood from dural venous sinuses

Hydrocephalus without a point of obstruction or increased resistance to flow would be communicating hydrocephalus.

After the point of obstruction has been determined, the classification should then include the etiology of the condition, chronicity and age of the person.

[ABOVE] Illustration derived from applying engineering principles to the study of ventricular volume regulation.  The CSF system is illustrated using a compartmental model, with each compartment having its own pressure and volume related to CSF flow.  Circuit Diagram of the CSF pathway as a hydraulic analog of an electrical circuit.

[BELOW] Six compartment model of the CSF pathways.

 

[BELOW] Artist rendering of the circuit diagram.

 

Based on their studies, there were no pressure differential anywhere within the system.  Pulse wave was transmitted undiminished and instantaneously to all transducers intracranialy.  This means that the brain is a viscoelastic substance, acting as a fluid chamber where changes in pressure are transmitted instantaneously and fully to all areas.

Exception to the rule:  If one of the lateral ventricles was drained to subatmospheric pressure, a pressure differential of 12mm Hg can be measured.  This is seen in “post-shunt ventricular asymmetry” – in children who are shunted, septum pellucidum is drawn toward shunted ventricle and rests on head of caudate nucleus leading to a functional and reversible obstruction of flow.

NPH – likely obstruction between spinal and cortical subarachnoid spaces, dense arachnoidal thickening around brainstem in posterior fossa, blockage results from either SAH or infection, frequently involves area around brainstem selectively, amenable to endoscopic III ventriculostomy

Increased pressure in dural venous sinus results in pseudotumor cerebri and not HCP.  Drainage of CSF into venous sinuses requires a gradient between ICP and sagital sinus pressure of 5-7mm Hg.  If pressure in sagittal sinus is elevated, ICP must elevated in order for CSF to be absorbed.  ICP slowly goes up until CSF can be absorbed (if skull volume is fixed).  In cases of large craniectomies, ICP is in communication with atmospheric pressure.  ICP cannot go above atmospheric pressure and patient develops hydrocephalus.

Study done in rabbits where SSS was occluded.  Rabbits whose skull was intact developed intracranial hypertension without ventriculomegaly.  Craniectomized rabbits developed hydrocephalus.

Table below shows the treatment options for each point of obstruction in the CSF pathway.

 

Reference

Rekate, Harold L. “A Consensus On The Classification Of Hydrocephalus: Its Utility In The Assessment Of Abnormalities Of Cerebrospinal Fluid Dynamics”. Child’s Nervous System 27.10 (2011): 1535-1541.

ICA Segments

Segmental classification of internal carotid artery:

Reference:

Lee, Thomas et al. “Management Of Carotid Artery Trauma”. Craniomaxillofacial Trauma and Reconstruction 07.03 (2014): 175-189.

Modified Raymond–Roy Classification

• Class I: complete obliteration
• Class II: residual neck
• Class IIIa: residual aneurysm with contrast within coil interstices
• Class IIIb: residual aneurysm with contrast along aneurysm wall

 

 

<click here to access MS ppt file>

 

 

References:

Hospital, Massachusetts. “Endovascular Procedures To Prevent Ruptured Brain Aneurysms”. Massachusetts General Hospital. N.p., 2016. Web. 11 Dec. 2016.

Mascitelli, Justin R et al. “An Update To The Raymond–Roy Occlusion Classification Of Intracranial Aneurysms Treated With Coil Embolization”. Journal of NeuroInterventional Surgery 7.7 (2014): 496-502.