Regular readers will know that a CLIPPERS diagnosis is neither quick nor simple. A large part of the process is excluding other conditions with similar or overlapping symptoms because it is vital that treatment fits the diagnosis as far as possible. Some of these conditions are more amenable to diagnosis than CLIPPERS because they are more common and better understood. The remainder are conditions about which less is known because of their rarity making differential diagnosis even harder. Here are the conditions I have found mentioned in the research literature which have been considered before diagnosing CLIPPERS. I bet that like me, most of you haven't heard of many of these. There are a frightening number of obscure and less obscure things which can go wrong with the old grey (and white) matter. As always please treat my interpretations of these complex disorders with caution and always go to authoritative sources for more information.
The Big Four
These four were mentioned the most while I was being diagnosed.
- Multiple Sclerosis: A condition where the auto-immune system mistakenly attacks myelin in the brain disrupting communication between nerve cells in the brain and spinal cord. UK prevalence is estimated at 100-140 per 100,000 (source: Multiple Sclerosis Trust).
- Cerebral Vasculitis: Inflammation of blood-vessel walls in the brain. Annual incidence estimated at 1-2 per million (source: Watts RA & Scott DG (1997) Classification and epidemiology of the vasculitides. Baillieres Clinical Rheumatology, 11, 191–217).
- NeuroSarcoidosis: Thought to be another auto-immune disease which results in abnormal particles called granulomas being deposited at sites or organs in the body and disrupting the function there. Prevalence of Sarcoidosis is 1-40 per 100,000 in adults but neurosarcoidosis without involvement elsewhere accounts for only 1% of these cases.
- Primary Central Nervous System Lymphoma: A brain cancer of the white blood cells known as lymphocytes. Incidence estimated to be 30 cases per 10 million and rising (source: Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000?, Benjamin W. Corn,, Sue M. Marcus,, Allan Topham, Walter Hauck, and Walter J. Curran Jr. Cancer Volume 79, Issue 12, 15 June 1997, Pages: 2409–2413). More common in immuno-suppressed populations.
The Elephant in the Room
The first 3 of the above were all seriously considered during my investigation and the fourth was mentioned as a possibility. All of these are hard to diagnose on a single test and imaging alone can't tell the full story. In Limousin et al (Journal of Neuroscience, 2011) a patient diagnosed as CLIPPERS who initially responded to steroids turned out to have PCNSL. In Jones et al (Brain, 2011) a patient diagnosed as CLIPPERS turned out to probably have glioma. Interestingly both patients had brain biopsy as part of their initial diagnostic work-up which was inconclusive emphasising the difficulty of diagnosis even with direct tissue examination.
Other Contenders
A whole host of other possibilities are mentioned in the literature including:
- Bickerstaff Brainstem Encephalitis: Prevalence < 1 per 100,000.
- Chronic Perivascular Infection: (e.g. TB, Neurosyphilis, Whippes Disease, Parasitic Infection).
- CNS Behcet's Disease:
- Devic's Disease: Prevalence unknown but often confused with MS.
- Glioma: a brain tumour of glial cells.
- Lymphomatoid Granulomatosis:
- Paraneoplastic Disease: a consequence of cancer elsewhere in the body.
So far less than 20 cases of CLIPPERS have been described and it's too early to estimate incidence or prevalence although it is likely there are previously undiagnosed cases out there. That said, if CLIPPERS was common it would have been noticed before now which suggests that CLIPPERS will remain unusal. It remains to be seen whether CLIPPERS retains it's own identity or whether it is eventually reclassified as a special case of something else.
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.
