Description

"Utility of Optic Nerve Ultrasonography in Assessing Cerebral Inflammation and Intracranial Hypertension in Patients with Cerebral Impairment" - briefly, the EICON Study.

Investigators Principal Investigator (1): Bogdan PAVEL, MD, PhD, DESA, "Dr. Victor Babes" Clinical Hospital of Infectious and Tropical Diseases.

Principal Investigator (2): Sebastian ISAC, MD, PhD, DESA, Fundeni Clinical Institute Principal Investigator (3): Prof. Gabriela DROC, M.D., Ph.D., Fundeni Clinical Institute

Study Design Study Type: Observational Estimated Number of Participants: 200 participants Primary Purpose: Evaluation Actual Study Start Date: December 1st, 2025 Estimated Primary Completion Date: December 1st, 2027 Estimated Study Completion Date: December 1st, 2027

Groups and Interventions

Group 1: Infectious Pathology Group

Patients admitted with suspected meningitis or encephalitis will undergo the following investigations:

Assessment of consciousness using validated scales (GCS, RASS).

Optic nerve ultrasound to measure the optic nerve sheath diameter (ONSD), performed according to the following protocol:

The patient is positioned supine at a 20-30° incline. A linear probe (9-10 MHz; depth=40 mm; focus=30 mm) is used. The optic nerve must be visible at least 6 mm posterior to the retina. The retinal artery is identified. The diameter of the optic nerve is measured 3 mm posterior to the retina in both the transverse and sagittal planes; the reported value is the mean of the two measurements.

Measurements are performed independently by two examiners. Transcranial Doppler (TCD) to determine the pulsatility index of the middle cerebral artery.

Computed tomography (CT) to exclude intracranial hypertension. Lumbar puncture with measurement of cerebrospinal fluid (CSF) opening pressure. Blood sampling for C-reactive protein (CRP) and neuron-specific enolase (NSE) levels.

Daily Monitoring During Hospitalization:

Daily assessment of consciousness (GCS, RASS) at 09:00. Daily optic nerve ultrasound at 09:00 following the protocol described above. Daily TCD examination of the middle cerebral artery at 09:10. CT scan if clinical signs of intracranial hypertension develop or if there is a sudden decline in GCS of \>3 points.

Repeat lumbar puncture with CSF pressure measurement at 72 hours and 7 days after admission.

Blood sampling for CRP, NSE, and total antioxidant capacity at admission, 72 hours, and 7 days.

Group 2: Patients With Non-Infectious Neurological Pathology

Patients admitted with suspected stroke (CVA), brain tumors, or metabolic encephalopathy will undergo the following investigations:

Assessment of consciousness using validated scales (GCS, RASS).

Optic nerve ultrasound to measure the optic nerve sheath diameter (ONSD), performed according to the following protocol:

The patient is positioned supine at a 20-30° incline. A linear probe (9-10 MHz; depth=40 mm; focus=30 mm) is used. The optic nerve must be visible at least 6 mm posterior to the retina. The retinal artery is identified. The diameter of the optic nerve is measured 3 mm posterior to the retina in both the transverse and sagittal planes; the reported value is the mean of the two measurements.

Measurements are performed independently by two examiners. Transcranial Doppler (TCD) to determine the pulsatility index of the middle cerebral artery.

Computed tomography (CT) to exclude intracranial hypertension. Lumbar puncture with measurement of cerebrospinal fluid (CSF) opening pressure. Blood sampling for C-reactive protein (CRP) and neuron-specific enolase (NSE) levels.

Daily Monitoring During Hospitalization:

Daily assessment of consciousness (GCS, RASS) at 09:00. Daily optic nerve ultrasound at 09:00 following the standardized measurement protocol.

Daily TCD examination at 09:10 to assess the middle cerebral artery pulsatility index.

CT scan if signs of intracranial hypertension appear or if the GCS decreases abruptly by \>3 points.

Lumbar puncture with CSF pressure measurement at 72 hours and 7 days after admission (if applicable).

Blood sampling for CRP and NSE levels at 72 hours and 7 days after admission.

General Objectives

1. Primary Objectives:

To evaluate the sensitivity and specificity of optic nerve ultrasound in the assessment of cerebral inflammation and cerebral edema.

To establish threshold values for diagnosing intracranial hypertension, according to the specific pathology.

To correlate the optic nerve diameter with the patients' clinical condition. 2. Secondary Objectives:

28-day mortality Quality of life assessment on day 28 Rate of local and systemic complications

Inclusion Criteria:

• Patients admitted into one of the specified wards of the involved hospitals
• Patients aged 18-60 years
• Suspected meningitis, encephalitis, stroke or cerebral tumors

Exclusion Criteria:

• Age under 18 years or over 60 years old
• Ocular lesions preventing ocular ultrasound (palpebral infections, cornean erosions, glaucoma, trauma)
• Conditions preventing lumbar puncture (coagulation disorders, epidural abscesses, local infections)

All data is collected and stored electronically, using a tabular Excel file shared by all investigators.

Ethical Considerations: For this study, we request deferred consent and invoke the emergency consent procedure for medical research, in accordance with Article 6, paragraph 4 of the WMO. This approach is justified for the following reasons:

Patients admitted to infectious disease, neurology, or intensive care units often lack the capacity to provide informed consent. Under the Medical Treatment Act (WGBO), individuals who may serve as legal representatives include: a pre-designated representative, a spouse, a registered or other life partner, a parent or child, a sibling, and, in some cases, a court-appointed guardian. However, legal representatives are frequently not present when patients are admitted to the ICU or when the inclusion criteria are met. Moreover, obtaining informed consent from a legal representative requires sufficient time for them to review and consider the information provided. In the acute phase of admission-particularly in the ICU-legal representatives are naturally focused on the patient's clinical status rather than participation in research.

Procedures for Obtaining Consent Informed consent will be requested from the legal representative as soon as possible and no later than 48 hours after the inclusion criteria are met. If feasible, informed consent will be obtained in advance.

If informed consent from the legal representative is not obtained within 48 hours, or if the representative refuses participation within this period, the patient will be excluded and all collected data will be removed from the study.

The legal representative will receive both oral and written information, provided either in person or via telephone and email. Written informed consent may be returned by email within 12 hours of receiving the information, but always within the 48-hour window following inclusion.

Consent received by email must subsequently be confirmed with a signed paper form as soon as possible, and no later than 48 hours after the emailed confirmation.

Retrospective Consent From the Patient A second informed consent procedure will be conducted retrospectively once the patient regains capacity and is able to adequately understand the situation. At that time, the study information will be provided directly to the patient, and written informed consent will be requested and signed by both the patient and the executive investigator. If the patient declines participation, all data collected up to that point will be permanently deleted.