Encephalopathy Work-up

Screening tests

  • Serum glucose, electrolytes, calcium/phosphorus, uric acid, lactate and pyruvate, liver, renal and thyroid function tests, blood gasses
  • Prolactin levels (10 to 20 min after suspected seizure, diagnosis seizure vs. psychogenic nonepileptic seizure)
  • Serum CK
  • ANA, ENA, ANCA, RF, complement, ACE, anti-thyroglobulin and anti-thyroperoxidase antibodies (Hashimoto disease), autoantibody panel (thyroid antimicrosomal, antiparietal),  immunoglobulins
  • Serum ceruloplasmin and copper, 24h urinary copper, slit lamp, liver biopsy (WD)
  • CBC, ESR, CRP, plasma fibrinogen
  • Coagulation profile (protein C and S, ATIII, Factor Leiden V, APLS, anticardiolipin)
  • Serum vitamin B12 and folic acid
  • RPR, TPHA
  • Serum cortisol, PTH and osmolality.
  • Serology: HIV, HSV, adenovirus, CMV, Coxsackie, polio, echovirus, hepatitis (A,B,C), parvovirus B19, mycoplasma, toxoplasma, VDRL, cysticercosis
  • Blood and urine organic acids and carnitine
  • Chest X-ray
  • PPD
  • Echocardiogram
  • EEG (non-convulsive status epilepticus), VEP, EMG/NCVs
  • Brain MRI, MRA
  • Conventional angiogram (CNS vasculitis)
  • serum ammonium

CSF

  • Besides routine analysis (chemistry, cell count, smear and stainings): lactate and pyruvate (mitochondrial disease), oligoclonal bands, IgG index, VDRL, viral (measles titer), fungal, PCR (T. Whippleii, JC virus, HSV, CMV, VZV), Ziehl staining, repeated cytology,
  • anti-thyroglobulin and anti-thyroperoxidase antibodies (Hashimoto disease).

Specific investigations

Blood/serum

  • 14-3-3 protein (CJD) (stable at room temperature and can be sent by regular mail)
  • Aminolevulinic acid, porphobilinogen, uroporphyrins, coproporphyrin
  • Antineural nuclear antibodies (ANNA-1(=Anti-Hu), ANNA-2 (=anti-Ri), ANNA-3, Purkinje cell cytoplasmic antibodies (PCCA-1 (=anti-Yo), PCCA-2, PCCA-Tr and mGluR1), plasma membrane cation channel antibodies (CV2/CRMP-5, Ma1, Ma2/Ta, amphiphysin, striational, voltage gated calcium channels (VGCC) and voltage gated potassium channels (VGKC), anti-NMDA-R (NR1 and NR2) antibodies.
  • Methylmalonic acid, VLCFA, arylsulphatase, homocysteine

Biopsy

  • Conjunctiva (sarcoidosis),
  • Small bowel (Whipple disease)
  • Skin (SLE, vasculitis, CADASIL)
  • Brain biopsy

COMA Algorithm (ENLS 2017)

Neurologic Etiologies of Coma

Toxic-Metabolic Etiologies of Coma

Reference:

“Acute Encephalopathy Work-Up.” Neuroweb.us. http://www.neuroweb.us/Chapters/acute%20encephalopathy/work_up.htm, 2017. Web. 18 Aug. 2017.

Posterior Cerebral Artery Branches

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4 anatomic segments of the PCA:

  1. P1 segment: from tip of basilar to origin of PComm
  2. P2 segment: from Pcomm to dorsal midbrain
    1. P2A – anterior segment
    2. P2P – posterior segment
  3. P3 segment: from lateral quad cistern at origin of post temporal artery to ant limit of calcarine fissure
  4. P4 segment:  terminal cortical branches of PCA after takeoff of parieto-occipital and calcarine arteries

 

REFERENCE:

AJNR Am J Neuroradiol. 2001 Jan;22(1):27-34. “Aneurysms of the posterior cerebral artery: classification and endovascular treatment.”   Ciceri EF1, Klucznik RP, Grossman RG, Rose JE, Mawad ME.

Digital atlas of MCA territory infarction

The color refers to the frequency of infarction at each voxel. The highest frequency of infarct occurrence is in the centrum semiovale and striatocapsular and insular regions.

 

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Reference:

Phan, T. G. et al. “A Digital Map Of Middle Cerebral Artery Infarcts Associated With Middle Cerebral Artery Trunk And Branch Occlusion”. Stroke 36.5 (2005): 986-991.

Delayed Cerebral Ischemia (Definition)

DEFINITION:

 

Delayed Cerebral Ischemia:

Focal (hemiparesis, aphasia, hemianopia, or neglect) or global (2 points decrease on GCS) neurological impairment lasting for at least 1 hour and/or cerebral infarction, which:
▪ Is not apparent immediately after aneurysm occlusion
▪ Is attributable to ischemia
▪ Is not attributed to other causes (i.e. surgical complication, metabolic derangements) after appropriate clinical, imaging, and laboratory evaluation

 

Cerebral infarction:

Presence of cerebral infarction on CT or MR scan of the brain within 6 weeks after SAH, or on the latest CT or MR scan made before death within 6 weeks, or proven at autopsy; that is:
▪ Not present on the CT or MR scan between 24 and 48 hours after early aneurysm occlusion
▪ Not attributable to other causes such as surgical clipping or endovascular treatment
▪ Not due to a nonischemic lucency related to a ventricular catheter, intraparenchymal hematoma, or brain retraction injury

 

Reference:

Francoeur, Charles L. and Stephan A. Mayer. “Management Of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage”. Critical Care 20.1 (2016): n. pag. Web.

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.

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[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.

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[BELOW] Artist rendering of the circuit diagram.

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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.

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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.

Images of Vasospasm

This is a review of an interesting study from 1997 (published in Stroke) that illustrates how vasospastic arteries in a rat subarachnoid hemorrhage model looks like under the scanning electron microscope.

The researchers injected hemolysate (lysed autologous blood) into the cisterna magna of male Sprague-Dawley rats.  After ten minutes, a polymer resin casting medium was injected intravenously.  Once the resin has casted, the tissue and bones were corroded using NaOH solution, until only the vascular cast remains.  The casts were visualized under scanning electron microscope, and the following images were derived:

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Basilar artery of:  A.  saline-injected control rats;  B. hemolysate-injected rats;  arrowheads = PICA;  note the narrowing and corrugation seen in the basilar artery of the hemolysate-injected rats.

Capture.JPG Other major arteries were also observed to be in vasospasm.  (note corrugation in these arteries)

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Vasospasm (demonstrated as corrugation in the casted vessels) is seen in the major arteries (A) as well as the small arteries (B).

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High magnification showing “corrugation” of the basilar artery.  The arrows point to nuclear indentations which correspond the the endothelial cell nucleus.  (see below0

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The researchers also performed conventional SEM.  A and B are normal vessels while C and D are hemolysate-induced vasospastic blood vessels.   A and C are low magnification, B and D are high magnification.

The normal vessels (A) show that the inner surface is very smooth and the vessel wall is thin, and (B) the endothelial nuclei are clearly observed, projecting into the inner surface at regular intervals of 10-20 um.

The vasospastic vessels (C) shows that the smooth muscle layer is thicker, corrugation is observed and (D) many humps are sandwiched and flattened between hills formed by the endothelial cells.

Cast model shows corrugation, characteristic folds of endothelial cells at regular intervals and indentations of endothelial cell nuclei at each peak of those folds.  These indentations correspond to the humps seen in conventional SEM analysis.  The mechanical force of corrugation compressed the endothelial cells, flattened their nuclei and likely disturbed their function.  These physical alterations cause narrowing of the vessels, disturbs local blood flow, and may disturb blood coagulation and adhesion of WBC and platelets to the endothelium.  This may be a mechanism that explains thrombus inflammation and inflammatory response in these diseased vessels.

Their research also showed that arteries exposed to greater amount of hemolysate exhibit more severe vasospasm.

Reference:

Ono, S. et al. “Three-Dimensional Analysis Of Vasospastic Major Cerebral Arteries In Rats With The Corrosion Cast Technique”. Stroke 28.8 (1997): 1631-1638.