Referral was sought for a middle aged female patient with CNS relapse post allogeneic stem cell transplant, who had undergone prophylactic cranial irradiation in the past and had history of prolonged cytopenia following BFM protocol. She had a diagnosis of mild meningitis on MRI and had presented with features suggestive of raised ICT (Headache, projectile vomiting). Ophthalmology review had indicated the presence of bilateral papilledema whereas the neurology team had advised anti-edema measures (3 percent saline twice daily and 20 percent mannitol three times daily – day 6).

The utility of the ongoing supportive care measures was a relevant point of discussion with the medical oncology team.

Clinical decision making required engagement with the following issues:

What was the optimal management of raised ICT in this setting, Were anti-edema measures indicated?

Why was dexamethasone not being used?

What was the role of cranial re-irradiation?

The pathogenesis of raised ICT was thought to be obstruction of arachnoid granulations by leukaemic blast cells rather than an intraparenchymal mass. A parenchymal chloroma with coexisting peritumoral edema might be associated with these features, but that seemed less likely.

The fact that her symptoms had reduced despite the absence of dexamethasone provided another diagnostic challenge. In the presence of obstructive hydrocephalus, it was clear that osmotic agents were expected to be of limited utility. In fact, the only measures with some underlying rationale supporting their use in this setting, were lumbar puncture (by reducing the volume) and acetazolamide (by reducing the formation). Shunting was not considered as a palliative procedure, in part due to associated morbidity.

Acetazolamide by extrapolation of its dosing in Idiopathic Intracranial Hypertension was advised in a dose of 500 mg two times daily (up from the 250 mg three times daily which might have proved to be suboptimal). The only other trial on its use in the management of raised ICT outside the setting of IIH in post haemmorhagic ventricular dilatation in infancy had led to an increased shunt requirement and neurological comorbidity. This underlined the fact that though it remained mechanistically more suited to this setting, a lack of evidence was a potential drawback to its proposed off the label usage. The potential harms of metabolic acidosis, renal adverse effects and potassium losses indicated a need for monitoring during its initiation and maintenance.

The use of dexamethasone as an edema lowering measure was also fraught with multiple considerations. The concurrent use of proton pump inhibitors and anti-candida measures was indicated, its effect on muscles (myopathy) offset by the limited prognosis, and it’s better CNS penetration (as compared to prednisolone) a positive. If anti-edema measures had been successful earlier, there was a possibility that dexamethasone might be able to substitute for them.

Olanzapine was advised as the anti-emetic of choice, consideration of cranial re-irradiation was advised, counselling about goals of care was continued, and discharge medications discussed with the oncology team.

Learning point – The fact that MRI grades meningeal enhancement and not CSF outflow needs to be kept in mind, as the burden of CNS disease might be masked by the designation of mild meningitis only.

Dosing of Acetazolamide has been extrapolated from the trials in Idiopathic Intracranial Hypertension where carbonic anhydrase inhibition was shown to reduced CSF production by around 50 percent at clinically relevant doses.
Paraesthesia, dysgeusia and fatigue were the major side effects that warranted discontinuation.
Contemporary society guidance advocates against its role in the setting of infectious meningitis.

References

Damkier, H. H., Brown, P. D., & Praetorius, J. (2013). Cerebrospinal fluid secretion by the choroid plexus. Physiological Reviews, 93(4), 1847–1892. https://doi.org/10.1152/physrev.00004.2013
Luyt, K., Jary, S. L., Lea, C. L., Young, G. J., Odd, D. E., Miller, H. E., Kmita, G., Williams, C., Blair, P. S., Hollingworth, W., Morgan, M., Smith-Collins, A. P., Walker-Cox, S., Aquilina, K., Pople, I., & Whitelaw, A. G. (2019). Ten-year follow-up of a randomised trial of drainage, irrigation and fibrinolytic therapy (DRIFT) in infants with post-haemorrhagic ventricular dilatation. Health Technology Assessment, 23(4), 1–116. https://doi.org/10.3310/hta23040
Mollan, S. P., Davies, B., Silver, N. C., Shaw, S., Mallucci, C. L., Wakerley, B. R., Krishnan, A., Chavda, S. V., Ramalingam, S., Edwards, J., Hemmings, K., Williamson, M., Burdon, M. A., Hassan-Smith, Z. K., Digre, K., Liu, G. T., Jensen, R. H., & Sinclair, A. J. (2018). Idiopathic intracranial hypertension: Consensus guidelines on management. Journal of Neurology, Neurosurgery & Psychiatry, 89(10), 1088–1100. https://doi.org/10.1136/jnnp-2017-317440
American Society of Hematology. (2026). American Society of Hematology 2026 guidelines for management of relapsed/refractory acute lymphoblastic leukemia in adolescents and young adults. Blood Advances.

Cite as

Arora, R. D. (2026). Contemporary Palliatrist Review 4 (CPR4) – Isolated CNS relapse of B-cell ALL – why acetazolamide might prove to be a valuable adjunct in mild leukaemic meningitis?. Zenodo. https://doi.org/10.5281/zenodo.21994113

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