Category Archives: Uncategorized

Cannabinoids

Important cannabinoids:

Mechanism of Action:

Modulation of the endocannabinoid system by phytocannabinoids.

Figure illustrates basic actions of endogenous cannabinoids anandamide (AN) and 2-arachidonylglycerol (2-AG) on the G protein-coupled cannabinoid receptors 1 and 2 (CB1 and CB2) in presynaptic neurons in both the central and peripheral nervous system.

Green-shaded compounds are common phytocannabinoids and other herbal inclusions in hemp oils that affect normal endocannabinoid through modulation of the CB receptors (eg, THC agonism of CB1 receptors) or by other routes s.a. inhibition of enzymatic breakdown of endocannabinoids or other receptor modulation.

BCP = Beta caryophyllene

GABA = gamma-aminobutyric acid

TRPV = transient receptor potential vanilloid

Figure below lists the current laws regarding CBD oils and medical marijuana in the US. For most up to date information, see website from National Conference of State Legislatures.

Federal government and DEA still consider CBD and hemp oils to be schedule I substances. DEA recently reduced Epidiolex (pure CBD drug recently FDA_approved) to schedule V classification.

Epidiolex is approved for:

  • Intractable epilepsy conditions
  • Dravet syndrome
  • Lennox-Gastaut syndrome

Reference:

VanDolah, H., Bauer, B. and Mauck, K. (2019). Clinicians’ Guide to Cannabidiol and Hemp Oils. Mayo Clinic Proceedings, 94(9), pp.1840-1851.

Advertisements

SPECT for Preoperative Evaluation Before Cardiac Surgery

SPECT is the most useful method for quantification of cerebral blood flow. Brain perfusion SPECT, with the use of acetazolamide, can detect hemodynamic compromise. With acetazolamide injection, perfusion is increased in areas where cerebral perfusion reserve is preserved, whereas areas with decreased cerebral perfusion reserve show no increase or decrease in perfusion because of intracerebral steal phenomenon.

Misery Perfusion

  • Impaired cerebral perfusion reserve
  • Excessive fall in BP and systemic hemodynamic disturbances lead to hemodynamic ischemic stroke
  • Reduced regional cerebral blood flow (<80% normal) and reduced regional cerebral reactivity (<10%)

Unacceptable depletion of cerebral perfusion reserve is defined as rCBF in ipsilateral MCA <=34 ml/100g/min with reserve cerebral blood response of <=1%. Patients with impaired perfusion should undergo prophylaxis STA to MCA anastomosis 1 month prior to cardiac surgery. If cerebral perfusion reserve is lower than safe limits, some preoperative prophylactic craniocervical intervention may be crucial, s.a. Carotid artery stenting, CEA and STA to MCA bypass.

Figure. Brain perfusion SPECT showing significant reductio in CBF at ready and reactivity to acetazolamide in L MCA territory.

Reference:

Tayama, E., Mori, R., Ueda, T., Imasaka, K., Tomita, Y. and Morita, S. (2019). Quantitative evaluation using single-photon emission computed tomography with acetazolamide is reliable for preoperative evaluation before cardiac surgery in severe carotid intracranial artery stenotic and/or occlusive disease: a case report. Journal of Cardiothoracic Surgery, 14(1).

Neurolymphomatosis

Neurolymphomatosis – malignant invasion of nerves, presents with severe asymmetric pain. Case below.

Patient with diffuse large B-cell lymphoma presents with 3 months of progressive pain and weakness. Exam shows asymmetric face, arm, leg weakness with absent reflexes. CSF normal twice including cytopathology and flow cytometry.

Next steps?

  • PET showed widespread avidity, including bilateral brachial and lumbosacral plexi
  • NCV / EMG showed reduced motor amplitudes but normal sensory responsive
  • Sciatic nerve biopsy confirmed neurolymphomatosis

PET Scan of patient:

  • Full body diffuse uptake (A)
  • R facial nerve (B)
  • sciatic and femoral nerves (C)
  • bilateral brachial and lumbosacral plexi (D)
  • C3/C4 roots (E)

TREATMENT:

  • Rituximab + ifosfamide, carboplatin, etoposide chemotherapy x 2 cycles
  • Autologous bone marrow transplant

TAKE HOME: CSF studies have low sensitivity, diagnosis often depends on PET and biopsy.

Reference:

DeBoer, S., Lesche, S., Rodriguez, F. and Ostrow, L. (2019). Teaching NeuroImages: Neurolymphomatosis. Neurology, 93(12), pp.e1229-e1230.

Patient Navigator to Reduce Readmissions (PArTNER) Study

Ongoing study utilizing community health worker and peer coaches to reduce readmission rate. Results of study pending, but the methodology is worth taking a look. Journal article listed in reference at the end of blog.

Black triangle = CHW-led interventions

White triangle = peer coach-led interventions

3 tables in the article provides a comprehensive task list for the discharge process.

Reference:

Prieto-Centurion, V., Basu, S., Bracken, N., Calhoun, E., Dickens, C., DiDomenico, R., Gallardo, R., Gordeuk, V., Gutierrez-Kapheim, M., Hsu, L., Illendula, S., Joo, M., Kazmi, U., Mutso, A., Pickard, A., Pittendrigh, B., Sullivan, J., Williams, M. and Krishnan, J. (2019). Design of the patient navigator to Reduce Readmissions (PArTNER) study: A pragmatic clinical effectiveness trial. Contemporary Clinical Trials Communications, 15, p.100420.

Posterior Reversble Encephalopathy Syndrome (PRES)

Symptoms:

  • Headache
  • Altered mental status
  • Seizures
  • Visual loss

Most common etiologies

  • Moderate to severe hypertension
  • Preeclampsia / eclampsia
  • Infection with sepsis / shock
  • Autoimmune diseases (SLE)
  • Multi drug chemotherapy regimen

Typical Imaging

  • Near symmetric hemispheric vasogenic edema affecting SCWM often extending to involve overlying cortex
  • DWI confirms vasogenic nature of edema, with absence of restricted diffusion

Patterns of edema distribution

  • Holohemispheric watershed pattern
  • Superior frontal sulcus pattern
  • Dominant parietal-occipital pattern
  • 98% exhibit some involvement of parieto-occipital regions

PATHOPHYSIOLOGY / THEORIES

Theory #1

  • Severe HTN exceeding natural autoregulatory limited of the brain results in injury to capillary bed, fluid egress, vasogenic edema
  • Supported by common occurrence of HTN in patients with PRES (50-70%)
  • demonstrated in animal studies and experimentally elevated BP
  • Reports of hyperperfusion in patients imaged with SPECT.
  • BUT: PRES can develop in patients with normal or only mildly increased BP
  • Studies demonstrating hypoperfusion in PRES
  • Lack of correlation with degree of edema and severity of HTN

Theory #2

  • Vasoconstriction develops due to autoregulatory compensation of severe HTN and leads to reduced brain perfusion, ischemia, development of vasogenic edema
  • If undreamed, leads to infarction, development of diffusion restriction
  • Supported by development of PRES in systemic conditions with endothelial injury and lack of sever eHTN (sepsis, bone marrow transplantation, systemic chemotherapy)
  • Catheter angio demonstrates vasculopathy in PRES (vasoconstriction and reduced perfusion)
  • Imaging studies with MR perfusion demonstrates hypoperfusion in PRES

Theory #3

  • Immune system activation resulting in cascade that induces endothelial dysfunction
  • Cytokines (TNF alpha, IL1) released due to systemic insult and induces expression of adhesion molecules which interact with circulating WBCs and trigger release of reactive oxygen species and proteas is leading to endothelial damage and fluid leak
  • Cytokines can also cause astrocytes to produce VEGF, increases BBB permeability, and activates vesicular-vacuoles organelle leading to extravasation
  • Circulating VEGF is increased in pre-eclampsia patients
  • Increased levels of LAM associated with preeclampsia, allogeneic BMT, solid organ transplantation, infection/sepsis/shock
  • Ergo, THN and vasoconstriction are consequences and not primary causative factors in PRES

Theory #4

  • AVP hypersecretion
  • Eclampsia / sepsis associated with AVP hypersecretion – theory states that this increase in AVP secretion or AVP receptor density results in activation of vasopressin V1a with associated cereb real vasoconstriction, endothelial dysfunction and cerebral ischemia resulting in cytotoxic edema, which may then lead to increased endothelial permeability and subsequent vasogenic edema
  • Possibility of pharmacology treatment of PRES targeting the AVP axis

Examples of Atypical MRIs for PRES

Reference:

Saad, A., Chaudhari, R. and Wintermark, M. (2019). Imaging of Atypical and Complicated Posterior Reversible Encephalopathy Syndrome. Frontiers in Neurology, 10.

When to call palliative care in neurosurgery?

Neurosurgeons are often at odds with the palliative care team with goals of care discussions in patients with brain tumors. Often, palliative care team consult is delayed, fearing that a discussion with the team will lead to earlier withdrawal of care. Neurointensivists are often caught in between, having to balance the need to engage patients and families in end of life discussions, and at the same time, understanding how such a conversation can disrupt previously established neurosurgical plans and derail the therapeutic relationship between the neurosurgeon and his/her patient.

This dilemma – to treat aggressively or to palliate symptoms – exists because of two realities: first, prognostication in neurooncology is imperfect, and second, surgical interventions are not completely harmless. If cancer prognostication were perfect, then decisions to withdraw care would be based solely on the values of the patient and family rather than on a gamble that a therapeutic option will be beneficial. Patient denial (“hoping against hope”, “waiting for a miracle”) will be minimized if physicians can provide accurate prognostic information to the family. If interventions were harmless, then the decision to treat when treatment is not curative or when the benefit of treatment is uncertain, would be easier to make. Unfortunately, that is not the current state of affairs, hence this discussion.

Based on the article I read on 10/08 (see previous blog), I thought it would be interesting to apply the same form of analysis to this issue. I made this table of 8 scenarios, which clarified for myself where I lie in deciding for aggressive treatment or palliation.

I have made the following assumptions:

  • the final decision is and should be made by the family and the patient who are fully informed of the prognosis as best available in the current medical literature and the risks and benefits of medical or surgical treatment
  • Physicians and health care providers can influence this decision-making process significantly, as well as clergy, friends and family
  • we want to save lives whenever possible, and prolong life (with good quality) whenever we cannot. We want to comfort always. We want to be truthful always.

In scenarios 1 and 2, and 7 and 8, where intervention is curative or harmful, the decision is straightforward. The right decision is to treat when intervention is curative and palliate when the intervention is harmful.

In scenarios 3 and 4, where intervention merely prolongs life (with good QOL), and scenarios 5 and 6, where intervention may have no benefit or merely prolongs life without preserving a good QOL, the decision is less clear. To improve decision-making in these scenarios, we should think about the following:

  • What is significant prolonging of life? Significant in research studies depends on the p value, which may not align with what the family or patient believes is significant.
  • How much disruption of life from the medical intervention is the patient / family willing to endure?
  • How certain are we that the intervention has no benefit, or merely prolongs life? Are there outliers? Are there subgroups that respond better, and is the patient possibly in that subgroup?

No matter how frequently I’ve had these discussions with different families in the neurocritical care unit, I have still yet to reach a level of comfort that I’m doing things the right way. The discussion is never easy, but with the stakes involved, I believe the discussion should never be an easy one. If it were, then maybe some degree of thoughtfulness on the case may be lacking.

Physician Liability When Using Artificial Intelligence

Table represents potential outcomes when a doctor uses artificial intelligence in the care of a patient. Physician asks a clinical question to which the AI makes 1 of 2 recommendations – the AI could be correct or incorrect, and the physician can follow or reject the recommendation.

Eight possible scenarios can result, and each scenario is treated differently under US law.

  • First, if there is no injury, there will be no liability (green boxes – scenarios 1, 4, 5, 8).
  • Second, the law typically privileges the standard of care, regardless of its effectiveness in a particular case, regardless of the outcome (Scenarios 1, 3, 6, and 8).
  • A physician faces liability only when he/she does not follow the standard of care, and an injury results (Scenario 2 and 7).

AI, from a liability perspective, is then used as a confirmatory tool to support existing decision-making processes, and not as a way to improve care (Scenario 6).

Interesting analysis.

Reference:

Price, W., Gerke, S. and Cohen, I. (2019). Potential Liability for Physicians Using Artificial Intelligence. JAMA.