Diagnostic Accuracy of Imaging Findings in TBM/Spinal Tubercular Arachnoiditis and Correlation With Outcomes

Tuberculous Meningitis Clinical Trial

Official title:

Diagnostic Accuracy of Imaging Findings in Tubercular Meningitis/Spinal Tubercular Arachnoiditis and Correlation With Outcomes in Patients With Tubercular Meningitis, Spinal Tubercular Arachnoiditis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05636254
• Other study ID #: IECPG-36/27.01.2022
• Status: Recruiting
• Start date: January 27, 2022
• Est. completion date: February 2024

Study information

• Verified date: November 2022
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: Arunmozhimaran Elavarasi, MD DM
• Phone: +919013844274
• Email: arun_ela[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this Diagnostic accuracy study is

• To study sensitivity and specificity of sulcal tuberculomas in the diagnosis of tubercular meningitis and

• To study the correlation of imaging findings in tubercular meningitis and spinal tubercular arachnoiditis with clinical outcomes after completion of therapy

• Secondary objectives

• To study the proportion of patients having clinical or imaging features of spinal tubercular arachnoiditis

• To study the factors determining outcomes in patients with spinal tubercular arachnoiditis

• To study the treatment trends in patients with spinal tubercular arachnoiditis

The investigators will include [study Population] Patients with chronic meningitis as per criteria listed below

• Chronic meningitis : Case definition

• Headache with or without fever, nuchal stiffness and systemic symptoms AND

• CSF suggestive of meningitis Pleocytosis (>20 cells per μL) with lymphocyte predominance (>50%) OR Protein concentration greater than age-specific normal value; especially >1•0 g/L OR Glucose concentration less than 60% of concentration in blood OR MRI suggestive of meningeal enhancement on contrast enhanced T1 sequences AND

• Deemed by the treating physician that the syndrome is consistent with chronic meningitis

• Patients who are positive for antibodies to HIV and pregnant females will also be included.

• Willing to undergo periodic assessment clinically and with MRI as per clinical condition demands.

The sensitivity and specificity of the finding of sulcal tuberculomas will be compared to the reference standard diagnostic criteria for the diagnosis of TB meningitis.

Description:

Methodology of the study Study design:Ambispective cohort study; Observational study; Diagnostic accuracy study

Sample size: All consecutive patients in the database will be included in the retrospective study and all new patients registered in the neurology OPD and admitted in the Neurology or General Medicine or Geriatric medicine or Medical oncology wards will be included in the prospective arm

Expecting a sensitivity of 70% of sulcal tuberculomas in tubercular meningitis with a range of 60 to 80, the investigators expect (4*70*30) /10*10=84 patients Expecting sulcal tuberculomas to have a specificity of 80%, with a range of 70 to 90%, the investigators expect (4*80*20)/10*10=64 patients Expecting a 70% prevalence of tubercular meningitis amongst patients with chronic meningitis, sample size of atleast 120 patients (70% of 120=84).

Subjects:

• Study Population: Patients with chronic meningitis as per criteria described

• Inclusion criteria

• Patients attending Neurology OPD or are admitted in General Medicine or Geriatric medicine or Medical oncology wards with chronic meningitis diagnosed on the basis of composite clinical criteria, imaging criteria as well as natural history of the illness

• Atleast 14 years of age of all sexes

• Chronic meningitis : Case definition above

• Willing to undergo periodic assessment clinically and with MRI as per clinical condition demands.

• Diagnostic criteria for Tuberculous meningitis ▪ Described in the diagnostic test section ahead

• Diagnostic criteria for clinical spinal tubercular arachnoiditis

▪ Developed paraparesis/quadriparesis/sphincter dysfunction due to spinal radiculomyelitis OR areflexia OR hyperreflexia with no obvious brain parenchymal lesions (suggestive of spinal meningitis-myelitis) or vision loss due to optico-chiasmatic arachnoiditis with imaging evidence of arachnoiditis

• Sample Size: All consecutive patients presenting with chronic meningitis as described above will be included

Exclusion criteria for prospective arm

● Not willing to provide consent

Conduct of the study

• Study protocol

• Consent: Participants or their legally authorized representatives will be explained about the study and informed written consent will be taken in the language they understand for the prospective study

• Participants will undergo magnetic resonance imaging of the brain and spine with contrast using the standardized protocol for chronic meningitis used at AIIMS as the standard of care in the workup of chronic meningitis.

• The final diagnosis of Tubercular meningitis will be made based on the criteria described above and the sensitivity and specificity of sulcal tuberculomas in the diagnosis of TBM will be determined

• Other imaging findings of spinal tubercular arachnoiditis will be collected on a structured proforma by the radiologist who will be blinded to the clinical information on the presence or absence of clinical features.

• Participants will follow treatment for tuberculosis as per the treating physician's discretion in terms of anti-tubercular therapy, anti-seizure medication therapy, duration and dose of corticosteroids and steroid sparing agents.

• Data collection and analysis will be done as per protocol Follow up and outcomes assessed > Participants of the prospective arm will be carefully assessed with detailed history, clinical examination, necessary laboratory investigations and imaging > Detailed history and clinical and neurologic examination, lab parameters and imaging data will be documented into a database as per protocol > Participants will follow treatment for his/her primary condition as per the treating physician's discretion > Outcomes will be assessed at 3 months, 6 months and at end of therapy > The outcome parameters of interest will be modified Rankin scale, visual acuity at 3 months and end of therapy.

Diagnostic accuracy of imaging parameters in the diagnosis of tubercular meningitis will be assessed by sensitivity and specificity.

The investigators aim to do a descriptive study of the clinical, laboratory and imaging parameters of patients tubercular meningitis and spinal tubercular arachnoiditis and compare with patients with other forms of chronic meningitis.

The treatment strategy, usage of anti-tubercular therapy, usage of corticosteroids, steroid sparing therapy, and surgical interventions offered will be studied.

Outcomes will be assessed and compared those who have sulcal tuberculumas and those who don't. The patients with and without spinal arachnoiditis on imaging also will be compared, and their outcomes assessed. Factors affecting outcomes will be studied and exploratory analysis will be done. Statistical analysis will be performed on the available information. Qualitative data will be presented as the number and the percentage of patients in each treatment group. Quantitative data will be presented as mean and standard deviation, range, median and inter-quartile range by treatment group. The absence of imbalance between groups will be checked on baseline variables. Comparisons of qualitative variables between groups will be performed by a Fisher exact test; comparison of quantitative data will be performed by a t test or a comparison of median when they will not follow a Normal distribution. All statistical tests will be performed with the use of a two-sided type I error rate of 5%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: February 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

• Patients attending Neurology OPD or are admitted in General Medicine or Geriatric medicine or Medical oncologywards with chronic meningitis diagnosed on the basis of composite clinical criteria, imaging criteria as well as natural history of the illness

• Atleast 14 years of age of all sexes Willing to undergo periodic assessment clinically and with MRI as per clinical condition demands.

Exclusion Criteria:

Not willing to provide consent

Related Conditions & MeSH terms

• Arachnoiditis
• Meningitis
• Tuberculosis
• Tuberculosis, Meningeal
• Tuberculous Meningitis

Intervention

Diagnostic Test:
• MRI Brain and spine
MRI Brain Ax T2 TSE 3D Sag T1 Ax DWI 3D Sag Flair Ax SWI Post-gad 3D Sag T1 3D TOF Circle-of-Willis MRI Spine Sag T2 whole spine (2 stations) Post-gad Sag T1 whole spine (2 stations)
• Reference standard diagnostic criteria
Diagnostic criteria-TBM Microbiologic evidence of TB in CSF Microbiologic evidence of TB from pulmonary or extrapulmonary sites Reasonable clinical certainty OR allied investigations such as CXR/CECT chest/abdomen/PET CT as per clinical indication suggestive of tuberculosis Other relevant investigations like CSF analysis not suggestive of alternative diagnosis such as neurocysticercosis/cryptococcal/other fungal infections/other causes of chronic meningitis such as brucella/ nocardia/ syphilis/recurrent viral meningitis/ carcinomatous/ lymphomatous meningitis or non infective causes such as sarcoidoisis/sub-arachnoid hemorrhage etc. Reasonable clinical certainty OR allied investigations such as CXR/CECT chest/abdomen/PET CT as per clinical indication ruling out competing diagnoses Patients who develop features or test results suggestive of alternative diagnosis with will be considered to be not due to tubercular meningitis

Locations

Country	Name	City	State
India	All India Institute of Medical Sciences, New Delhi	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
All India Institute of Medical Sciences, New Delhi

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity and specificity of sulcal tuberculomas in the diagnosis of tubercular meningitis	Sensitivity and specificity of sulcal tuberculomas compared with reference standard clinical composite criteria	Day 1 of diagnosis or imaging acquisition
Primary	Correlation of imaging findings with clinical outcomes	Correlation of imaging findings in tubercular meningitis and spinal tubercular arachnoiditis with clinical outcomes after completion of therapy The outcome parameters of interest will be modified Rankin scale, visual acuity at 3 months and end of therapy.	6 months to 18 months, average 9 months after starting treatment
Secondary	Clinical or imaging features of spinal tubercular arachnoiditis	Proportion of patients having clinical or imaging features of spinal tubercular arachnoiditis	Day 1 of diagnosis or imaging acquisition
Secondary	Factors determining outcomes in patients with spinal tubercular arachnoiditis	Factors determining outcomes in patients with spinal tubercular arachnoiditis	6 months to 18 months, average 9 months after starting treatment
Secondary	Treatment trends in patients with spinal tubercular arachnoiditis	Treatment trends in patients with spinal tubercular arachnoiditis	6 months to 18 months, average 9 months after starting treatment