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Archive for April, 2012

The language of peripheral neuropathy

11 Apr, 12 | by Arun Krishnan, Web Editor

 In daily neurological practice, peripheral neuropathy remains one of the most common reasons for neurological referral. The worldwide diabetes epidemic will no doubt ensure that more and more patients are seen with the classic syndrome of length-dependent sensory and motor impairment that inevitably sets in train a range of investigations: nerve conduction studies, blood tests including the usual suspects such as B12, folate, creatinine and possibly an oral glucose tolerance test. In some centres, coeliac serology may be added to that panel, although I suspect that your hit rate will be low 1. Every so often, we are surprised by what we find when we order these tests. I recently had a patient who actually was B12 deficient and who did improve with appropriate treatment. Some of you may have had patients with copper-deficient myeloneuropathy, which again is amenable to therapy 2.

 The occurrence of demyelinating changes on NCS is particularly rewarding as it not only alleviates the inevitable boredom of seeing scores of patients with axonal neuropathy, but also provides an interesting intellectual challenge. Some of these patients may have inherited neuropathy and depending on where you live, this may result in little or no further investigation or potentially a mass of ‘neuropathy panels’ looking for one of the zillion genes that we think may underlie charcot-marie-tooth disease. Without a good family history, the greatest beneficiaries of such intense investigation may be the scores of commercial outfits that provide these investigations. Certainly, in my experience the patient does not always benefit beyond testing for the most common genetic abnormalities (PMP 22, MPZ, mitofusin) and further research may be hampered until another family member  comes along with a similar complaint.

 In terms of acquired demyelination, we all think about chronic inflammatory demyelinating polyneuropathy, a condition that I use as a retort against my friends’ frequent verbal assaults that generally centre on the all pervading therapeutic nihilism that apparently still characterises 21st century neurology. (Neurology can be summed up in two words, they tell me, “Diagnose, adios”: I ask them what the temperature is like on Mars these days). But yes, CIDP is a breath of fresh air: intravenous immunoglobulin, steroids, cyclosporine, methotrexate, mycophenolate, rituximab 3. Wow…. I am not sure if they all work but they certainly sound great in unison.

 Over the years there have been many excellent contributions to JNNP in the area of neuropathy research 1-5 and the trend continues in the May issue of the journal. Two prominent neuropathy groups from Chiba and Rochester suggest that we keep in mind a rare but potentially underrecognised form of demyelinating neuropathy and just when you were coming to grips with DADS, MADSAM, MMNCB 3 and other forms of neuropathy soup, here is another – POEMS syndrome 4,5 (polyneuropathy, organomegaly, endocrinpoathy, M-protein and skin changes).  As noted in both these papers and the accompanying Editorial 6, the papers provide clinicians with some clues as to how to separate POEMS patients from ‘run-of-the-mill’ CIDP. In particular, they highlight the fact that POEMS patients appear to have more uniform demyelination along the peripheral nerve trunk, while the changes in CIDP patients are relatively polarized either to proximal or distal regions of the peripheral nervous system. In addition, the changes of axonal loss appear to be more prominent in POEMS, with greater muscle atrophy particularly in the lower limbs. The papers also provide potential ways of differentiating these two disorders on the basis of nerve conduction abnormalities. As noted in the Editorial 6, there may be a very direct clinical benefit from being able to differentiate these condition as the prognosis of POEMS is largely dependent on early identification and treatment, and as highlighted in these papers, a ‘neuropathy presentation’ of this systemic disorder is a common enough occurrence.

 1. Rosenberg et al. Should coeliac disease be considered in the work up of patients with chronic peripheral neuropathy? J Neurol Neurosurg Psychiatry 2005;76:1415-1419 doi:10.1136/jnnp.2004.048413 http://jnnp.bmj.com/content/76/10/1415.full?sid=27d23c4f-2cc3-459e-bcd8-ff52e2c66545

 2.Goodman BP et al. Clinical and electrodiagnostic findings in copper deficiency myeloneuropathy. J Neurol Neurosurg Psychiatry 2009;80:524-527 doi:10.1136/jnnp.2008.144683 http://jnnp.bmj.com/content/80/5/524.full?sid=a2769e05-41c5-4a16-a551-986d4067440e

 3.Lunn MPT, Willison HJ. Diagnosis and treatment in inflammatory neuropathies. Journal of Neurology, Neurosurgery & Psychiatry. 2009 Mar;80(3):249-58. http://jnnp.bmj.com/content/80/3/249.full?sid=7f5e07bb-96ec-4d0a-9b06-e7cb750886e5

 4. Nasu et al. Different neurological and physiological profiles in POEMS syndrome and chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry 2012;83:476-479 Published Online First: 15 February 2012 doi:10.1136/jnnp-2011-301706. http://jnnp.bmj.com/content/83/5/476.full

 5. Mauermann et al. Uniform demyelination and more severe axonal loss distinguish POEMS syndrome from CIDP. J Neurol Neurosurg Psychiatry 2012;83:480-486 Published Online First: 6 March 2012 doi:10.1136/jnnp-2011-301472. http://jnnp.bmj.com/content/83/5/480.full

 6. Arimura K. Early recognition of POEMS syndrome: what is the role of clinical neurophysiology? J Neurol Neurosurg Psychiatry 2012;83:474 doi:10.1136/jnnp-2012-302477 http://jnnp.bmj.com/content/83/5/474.full.

 

Lithium debunked for ALS

5 Apr, 12 | by Steve Vucic, Web Editor

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of motor neurons in the spinal cord, brainstem, and motor cortex, with ea median survival of 3-5 years.  At present, there is no cure for ALS, and the currently available treatments are of limited  efficacy.  Recently, a neuroprotective benefit of lithium carbonate was reported in animal models of ALS and in humans.  Specifically, it was reported that lithium increases survival and retards disease progression, thereby providing a potential ray of hope for the ALS patients.

 

Since the original studies, a number of large studies have been published refuting any benefits of lithium in ALS.  In this issue of JNNP, a group led by Prof van den Berg, apply the final nail to the notion that lithium may be efficacious in ALS.  Specifically, the authors assessed the efficacy of lithium carbonate in a double blind placebo controlled trial in a large cohort of ALS patients.  the primary outcome measures included survival, defined as death, tracheostomal ventilation or non-invasive ventilation for more than 16 h/day.  In addition, secondary outcome measures consisted of the revised ALS Functional Rating Scale and forced vital capacity.   The study failed to demonstrate any benefits of lithium on primary of secondary outcome measures in ALS.   Given the absence of any effects on survival of functional decline in ALS, this study has helped to resign lithium therapy in ALS to history.

Reference

Verstraete E, Veldink JH, Huisman MHB, et al. Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial. Journal of Neurology, Neurosurgery & Psychiatry 2012;83:557-64.

 

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