... That Is The Question
Brain Biopsy
Despite the range of investigations available for brain disorders, diagnosis involves detective work and collating evidence from lots of different sources. These include patient symptoms and history, neuro-psychological examinations, electrical measurements, blood tests, lumbar puncture (to extract and test cerebral spinal fluid) and non-invasive imaging techniques such as MRI. For many disorders a combination of these things can give a definitive diagnosis, or at least one with high confidence. However the only way to know for sure what is going on in brain tissue is to examine it under the microscope and do direct laboratory tests on a sample. Hence the on-going need for brain biopsy.
Biopsy For CLIPPERS Diagnosis
One of the current questions for CLIPPERS is whether brain biopsy is required for diagnosis. In the original study, Pittock et al performed brain biopsy in 4 of 8 patients and found nothing to distinguish the biopsied from the unbiopsied in terms of their other investigations or response to treatment. Pittock et al say "Biopsy should be considered in patients when alternative diagnoses remain likely and ... (it) ... may be performed safely." They also suggest that diagnosis can be accomplished without biopsy in cases with clear radiological and clinical findings. However Kastrup et al caution against this, particularly given the problems associated with diagnosing lymphoma and other conditions which can present with a CLIPPERS-like appearance. Jones et al report two case studies presenting as CLIPPERS one of whom was eventually considered to be suffering from glioma. Limousin et al report a patient who presented as CLIPPERS but subsequently became resistant to steroid therapies and was in fact suffering from lymphoma. Both glioma and lymphoma are life-threatening conditions that require different treatment. These authors do not in fact disagree about the need for biopsy - to resolve diagnostic uncertainty - as much as it seems on a first reading; the issue is whether conditions other than CLIPPERS can be rigorously excluded without biopsy. Here is where it gets tricky especially as in the absence of a specific cause for CLIPPERS a direct "test" for it isn't possible even with brain biopsy although the appearance can be checked for consistency.
Living In An Imperfect World
- Brain biopsy has risks associated with it. I have heard a 1% general risk of serious complications (including death) quoted but for the brain regions affected by CLIPPERS I was quoted 2% risk. Ideally you should be able to match this risk against the risk of doing nothing and missing the diagnosis but the figures aren't there.
- The biopsy may be technically successful (i.e. a sample is returned) but uninformative in which case you have accepted the risk for no return.
- At the moment we don't know how common CLIPPERS is (but it's probably not common) or what risk factors are associated with it. Low-grade glioma and lymphoma are very hard to diagnose properly without biopsy and can sometimes look like CLIPPERS - but how often? We don't have enough information to properly play the numbers game saying "you have an 80% chance of CLIPPERS versus a 20% chance of lymphoma" (say) as the statistics don't exist. So it's hard to assess the risk of not having the procedure against the risk of having it in terms of missing the diagnosis.
- For medical understanding of CLIPPERS to advance, brain biopsy of affected patients is vital to help establish the microscopic cause of the disease. However, advancing future medical science may not directly benefit the patient accepting the biopsy risk. Hopefully biopsy decisions are always made to maximise direct benefit to the patient and satisfy ethical requirements.
Declined, For The Moment
In my case, after fairly extensive non-invasive and minimally invasive investigations there was no evidence of alternatives to CLIPPERS. I asked my team if they could present a compelling medical case for proceeding with brain biopsy immediately and was told on balance probably not. However my impression (and it's only my impression) is that, quite rightly as the medical professionals responsible for my care, there is a little residual uneasiness that the diagnosis can't be definitively pinned down. So for me it's a gamble to have the biopsy and a gamble not have it and the odds aren't clearly defined. So I made a judgement based on the best information available and accepted a diagnosis of "presumptive CLIPPERS", or "CLIPPERS until proven otherwise". So far I continue to fit the CLIPPERS pattern of symptoms and treatment response. If I diverge from it in the future then biopsy is likely. This happened to the patient reported by Limousin et al who turned out to have lymphoma, but this patient had already had biopsy before their CLIPPERS diagnosis which found no sign of lymphoma or glioma. So the timing of biopsy is important to balance diagnostic power against the chance to intervene early in the course of disease.
Conclusion
The decision to have brain biopsy is very much dictated by personal circumstances. Often it is the best and only way to figure out what is happening and can literally be a life-saver if it results in the best treatment for an unsuspected condition. As our understanding of CLIPPERS improves it remains to be seen whether brain biopsy is a required part of the diagnostic process or whether other less invasive techniques (e.g. Magnetic Resonance Spectroscopy used by Kastrup et al) can help reduce patient risk.
PS Now you can subscribe to these posts by email so you never miss an update. Click the button on the top right.
Read other articles in this series at Living With CLIPPERS.
Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.
