Hypoglycorrhachia Differential Diagnosis

Common and Uncommon Etiologies of Hypoglycorrhachia in the LiteratureCapture


  • Bacterial meningitis (including atypical bacteria like nocardia and brucella)
  • Fungal meningitis
  • Mycobacterial (tuberculous meningitis)
  • Amebic meningoencephalitis
  • CMV-associated progressive polyradiculopathy or meningoencephalitis
  • Carcinomatous meningitis
  • GLUT 1-deficiency syndrome
  • Leukemia/lymphoma with CNS involvement
  • Subarachnoid hemorrhage



  • Syphilitic meningitis
  • Lyme meningitis
  • Viral meningitis
  • Neurocysticercosis5
  • CNS toxoplasmosis
  • Cholesterol-induced leptomeningitis secondary to Currarino syndrome
  • Neurosarcoidosis
  • Rheumatoid meningitis
  • Systemic lupus erythematosus with CNS involvement
  • Neuro-Behcet’s Disease
  • Dermoid cyst
  • Granulomatous angiitis of the central nervous system
  • Malignant atrophic papulosis


Etiologies reported to cause severe hypoglycorrhachia, (CSF glu ≤10 mg/dL)

  • Bacterial meningitis (including atypical bacteria like nocardia and brucella) *
  • Fungal meningitis*
  • Mycobacterial (tuberculous meningitis)*
  • Carcinomatous meningitis*
  • Leukemia/lymphoma with CNS involvement*
  • Subarachnoid hemorrhage*
  • Lyme meningitis*
  • Neurocysticercosis5*
  • Cholesterol-induced leptomeningitis secondary to Currarino syndrome*
  • Neurosarcoidosis*
  • Dermoid cyst*


Frequency of Different Known Diagnoses Seen in Patients with Hypoglycorrhachia

  1. All Patients


2. HIV-Infected Patients


3. Patients with History of Neurosurgery


4. Patients without HIV or Neurosurgical History




Chow, E., & Troy, S. (2014). The Differential Diagnosis of Hypoglycorrhachia in Adult Patients. The American Journal Of The Medical Sciences348(3), 186-190. doi: 10.1097/maj.0000000000000217


Checklist: Bleed post TPA


Half life of TPA is ~5 minutes and only 20% is present and active 10 mins after completion of infusion, but PT and PTT prolongation and fibrinogen levels are decreased x 24 hours or more.


  • STOP alteplase
  • VS q15h, GCS, pupil response, treat BP, increased ICP
  • Neurosurgery consult
  • DIAGNOSTICS: STAT CT head, PT/PTT, platelets, fibrinogen, type and cross 2-4 unit pRBC
  1. Transfuse cryoprecipitate 6-8 units IV
    1. If fibrinogen 50-100mg/dL transfuse 10 bags
    1. If fibrinogen <50 mg/dL transfuse 20 bags
  2. Check fibrinogen level 30-60 mins post transfusion, goal fibrinogen level >100 mg/dL
  3. ALTERNATIVE: transfuse single donor platelets or 6-8 bags of random donor platelets

*each bag of cryoprecipitate contains 200-250 mg of fibrinogen, increases fibrinogen levels by 6-8 mg/dL (in a 70 Kg adult)

*half life of fibrinogen is 3-5 days


Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.

Thrombectomy Inclusion / Exclusion Criteria

Modified from MR CLEAN Trial:

  1. Criteria modified from MR CLEAN trial:
    • Clinical diagnosis of stroke, NIHSS >=2, ASPECTS >=6 on noncontrast CT
    • CT/MRI evidence rule out ICH
    • Intracranial occlusion of distal ICA or M1 M2 or A1 A2 arteries demonstrated with CTA / MRA or DSA
    • Sufficient time to initiate thrombectomy within 6 hours of onset
    • Informed consent
    • >=18y
  2. Exclusion
    • BP >185/110 mm Hg
    • Glu <2.7 or >22.2
    • s/p tPA with dose >0.9mg/Kd or 90mg
    • coagulopathy (Plt <40, INR >3)



A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. (2015). New England Journal of Medicine, 372(4), pp.394-394.

Uptodate: Reperfusion therapy for acute ischemic stroke.  Accessed 09/11/2017.

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
  • 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


  • 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


  • 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


  • 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


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

Checklist: Autoimmune Encephalitis Work-up

Serum studies:

  • C3 C4 CH50
  • ANA
  • RF
  • sjogren’s SSA SSB
  • SPEP
  • Thyroid peroxidase, thyroglobulin antibody
  • Glutamic acid-decarboxylase antibody
  • paraneoplastic panel (includes VGKC and NMDA)


MRI brain w/wo con
CTA head/neck


Lumbar Puncture

  • opening pressure
  • CSF protein, glucose, cell count
  • CSF IgG index, oligoclonal bands (check in serum as well)
  • CSF myelin basic protein
  • Gram stain and bacterial culture
  • Fungal culture

*withdraw at least 30 cc of CSF and save extra for additional studies if necessary



CHECKLIST: tPA Eligibility Criteria + sample consent form

From ENLS / ACC/AHA 2013

Algorithm for TIA/AIS:


  • Diagnosis of ischemic stroke causing measurable neurological deficit. Neurological signs should not be minor and isolated. Neurological signs should not be clearing spontaneously
  • Onset less than 3 h before initiating alteplase
  • Patient is at least 18 years old (see section on special considerations: pediatric stroke)

Absolute exclusion criteria if positive

  • No major head trauma or prior stroke in the previous 3 months
  • Symptoms of stroke should not be suggestive of subarachnoid hemorrhage
  • No arterial puncture at a non-compressible site or lumbar puncture in the previous 7 days
  • No history of previous intracranial hemorrhage
  • No history of intracranial neoplasm, aneurysm, or arteriovenous malformation
  • No intracranial or intraspinal surgery in the previous 3 months
  • Blood pressure not elevated (systolic <185 mmHg and diastolic <110 mmHg)
  • No evidence of active bleeding or acute trauma (fracture) on examination
  • Platelet count <100,000 mm3
  • If receiving heparin in previous 48 h, aPTT must be in normal range
  • Not taking an oral anticoagulant or, if anticoagulant being taken, INR < 1.7 or PT > 15 s
  • No dabigatran, apixaban, or rivaroxaban use for chronic anticoagulation for conditions such as atrial fibrillation. There is still little information on assessing influence or levels of these medications in patients with acute stroke. There are suggestions to check an activated thromboplastin time (aPTT), INR, platelet count, thromboplastin time (TT), ecarin clotting time (ECT) and anti factor 10a level (if available). Without normalized special tests (as listed), use of alteplase is NOT recommended in patients with recent use (within 48 h) of these products
  • Blood glucose concentration <50 mg/dL (2.7 mmol/L)
  • CT does not show a multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Relative exclusion criteria if positive—use caution if recommending alteplase if one or more are positive

  • Stroke symptoms are rapidly improving or only minor
  • Pregnancy
  • Seizure with postictal residual neurological impairments
  • Major surgery or major trauma in the previous 14 days
  • Gastrointestinal or urinary tract hemorrhage in the previous 21 days
  • Myocardial infarction in the previous 3 months

Some additional considerations

  • Caution should be exercised in treating a patient with major deficits
  • Caution using alteplase in patients treated with low molecular weight heparin in the past 24 h
  • Patient or family members understand the potential risks and benefits from treatment. No written consent is required but the conversation should be documented in the clinical notes. Do not delay IV therapy if a surrogate is not readily available as this can lead to worse outcomes
  • Alteplase is not FDA approved for treatment of patients under the age of 18. However, alteplase has been used off-label in selected pediatric patients with strokes, following careful counseling of parents and using identical eligibility and contraindication criteria to those used in adults.


Inclusion criteria

  • Clinical diagnosis of ischemic stroke causing measurable neurologic deficit
  • Onset of symptoms <4.5 hours before beginning treatment; if the exact time of
  • stroke onset is not known, it is defined as the last time the patient was known to be normal
  • Age ≥18 years

Exclusion criteria

  • Historical
    • Significant stroke or head trauma in the previous three months
    • Previous intracranial hemorrhage
    • Intracranial neoplasm, arteriovenous malformation, or aneurysm
    • Recent intracranial or intraspinal surgery
    • Arterial puncture at a noncompressible site in the previous seven days
  • Clinical
    • Symptoms suggestive of subarachnoid hemorrhage
    • Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg)
    • Serum glucose <50 mg/dL (<2.8 mmol/L)
    • Active internal bleeding
    • Acute bleeding diathesis, including but not limited to conditions defined in ‘Hematologic’
  • Hematologic
    • Platelet count <100,000/mm3*
    • Current anticoagulant use with an INR >1.7 or PT >15 seconds*
    • Heparin use within 48 hours and an abnormally elevated aPTT*
    • Current use of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays
  • Head CT scan
    • Evidence of hemorrhage
    • Extensive regions of obvious hypodensity consistent with irreversible injury
  • Relative exclusion criteria¶
    • Only minor and isolated neurologic signs
    • Rapidly improving stroke symptoms
    • Major surgery or serious trauma in the previous 14 days
    • Gastrointestinal or urinary tract bleeding in the previous 21 days
    • Myocardial infarction in the previous three months
    • Seizure at the onset of stroke with postictal neurologic impairments
    • Pregnancy
  • Additional relative exclusion criteria for treatment from 3 to 4.5 hours from symptom onset
    • Age >80 years
    • Oral anticoagulant use regardless of INR
    • Severe stroke (NIHSS score >25)
    • Combination of both previous ischemic stroke and diabetes mellitus

<Eligibility criteria for tPA in PDF format>

Written consent is no longer required for tPA as this treatment is considered standard of care for acute ischemic stroke. That being said, the verbiage on this old consent form is a reminder of the information necessary for informed consent for tPA.

I have been clearly and fully informed by Dr._ that I am having a stroke. It has been explained to me that the Intravenous Thrombolytic Therapy using the drug t-PA, administered promptly after the onset of symptoms of a stroke may dissolve the clot and restore blood flow which may lessen the amount of damage to my brain.

I have been made aware that there are common risks and complications of Intravenous Thrombolytic Therapy as well as risks and complications of not having the therapy done. I have been told that the major risks from the use of t-PA are the possibility of internal bleeding including the stomach or intestinal tract and brain. The risk of bleeding in the brain is about 6%. If bleeding into the brain occurs my condition could worsen and may even result in death. I understand that some of the other possible reactions to t-PA include: temporary bruising or bleeding in the mouth, nose, skin, urinary tract or arm. If I refuse therapy my stroke could worsen or not improve.

I have received no guarantees as to results of Intravenous Thrombolytic Therapy. I understand that the alternative is to not receive t-PA and receive only supportive treatment.

In 1996, t-PA was approved by the Food & Drug Administration (FDA) for treatment of stroke within the first 3 hours after onset. In 2009, national guidelines concluded that this treatment could be helpful up to 4.5 hours after the onset of an acute stroke. Currently, the FDA has not approved t-PA for the treatment beyond 3 hours of symptom onset.

The nature and purpose of this therapy and the risks involved have been explained to me by the physician. I have been given an opportunity to ask any questions I may have, and all such questions or inquiries have been answered to my satisfaction. I have read this form and understand it fully.


1. Use actual body weight

2. Alteplase dose is 0.9mg/Kg, max dose not to exceed 90mg.

3. Mix by swirling, rather than shaking

4. 10% of total dose bolused over 1 min, remainder infused over 1 hour

5. Administer 100ml bag of saline after 1 h infusion to flush IV line and ensure entire dose is administered, use same rate to avoid terminal alert please bolus

Comparison of AHA/ASA acute stroke management guidelines (2013) and 2015 FDA prescribing information for alteplase treatment of acute ischemic stroke

Post TPA Orders:

  1. Neurochecks q15mins x 2h, then q30mins x 6h, then q1h there after
  2. Supplemental oxygen to keep O2 says >94%
  3. Check BP q15mins x2h, then q30mins x 6h, then q6 x 16h
  4. SBP goal <180/105
  5. Bedside swallow test (30 mL water PO) before anything else PO
  6. Keep glucose 140-180mg/dL, consider insulin get if Glu persistently >200 (hyperglycemia worsens outcomes, increases risk of ICH after ischemic strokes)
  7. Administer IV fluids (NS at 1.5 mL/Kg/hr), to goal of euvolemia
  8. Bedside telemetry / cardiac monitoring to detect atrial fibrillation, continue x at least 72h
  9. Treat fever source, avoid hyperthermia
  10. Avoid indwelling urinary catheter, NGT, intra-arterial catheters x 4 hours; avoid urinary catheters unless absolutely needed
  11. No anticoagulant / antiplatelet therapy x 24h



Gross, Hartmut, and Noah Grose. 2017. “Emergency Neurological Life Support: Acute Ischemic Stroke”. Neurocritical Care 27 (S1): 102-115. doi:10.1007/s12028-017-0449-9.

Safety Checklist for Early Mobilization

  • If there is an EVD, is the EVD closed and secure for patient mobilization?
  • Have ICPs been well controlled for 24 h with no administration of mannitol or hypertonic saline?
  • Is there no active titration of parenteral vasopressors or antihypertensives?
  • Is the CAM-ICU negative for delirium?
  • Does the patient have a stable neurologic exam?
  • If patient has an AIS, has it been 24 h after the onset of symptoms?
  • If patient has an aSAH, has the aneurysm been treated?
  • If patient has a spontaneous ICH, has the hemorrhage volume been stable for 24 h?

If all above questions are answered “Yes” or “N/A,” proceed with early mobilization


Olkowski, Brian F. and Syed Omar Shah. “Early Mobilization In The Neuro-ICU: How Far Can We Go?”. Neurocritical Care (2016): n. pag. Web. 4 Jan. 2017.