17 Sep, 14 | by Steve Vucic, Web Editor
Progression in MS has been associated with cortical atrophy. Consequently, the holy grail of trying to prevent diability development in MS is to slow or even prevent the rate of cortical atrophy. In this issue of JNNP, Zivadinovs groups elegantly demonstrate that cortical atrophy evolves over a 10 year period, being more pronounced in those patients developing disability. This is an important study, especially when drug therapies are considered.
Read more at: http://jnnp.bmj.com/content/85/10/1109.abstract
J Neurol Neurosurg Psychiatry 2014;85:1109-1115 doi:10.1136/jnnp-2013-306906
Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study
- Cecilie Jacobsen1,2,3,
- Jesper Hagemeier2,
- Kjell-Morten Myhr4,5,
- Harald Nyland4,5,
- Kirsten Lode1,
- Niels Bergsland2,
- Deepa P Ramasamy2,
- Turi O Dalaker3,6,
- Jan Petter Larsen3,
- Elisabeth Farbu1,3,
- Robert Zivadinov2,7
15 Sep, 14 | by Steve Vucic, Web Editor
In the new ear of MS drugs, safety has been an important consideration. The risk of cancer in patients treated with IFNs has been raised, although never proven. In this issue of JNNP, a large study from British Columbia categoricaly excludes the association of any cancers with MS. Interestingly, there was a non-signifcant increase in the risk of breast cancer, most likely a chance occurence.
Must read more at: http://jnnp.bmj.com/content/85/10/1096.abstract
J Neurol Neurosurg Psychiatry 2014;85:1096-1102 doi:10.1136/jnnp-2013-307238
Assessment of cancer risk with β-interferon treatment for multiple sclerosis
11 Sep, 14 | by Arun Krishnan, Web Editor
It is no secret that treatment options in Neurology are rapidly evolving. It is also no secret that for many chronic neurological disorders, there is no way we can even begin to think about a cure. For many conditions, the mechanisms that cause the disease are only just being identified and this is of course the start of any journey towards treatments that have curative intent. Although researchers in any field may be buoyed by the speed of progress in their own highly specialised area, it is well known that clinical implementation of any treatment takes on average about 15 years from its initial discovery. For patients, this may not be a lifetime but it certainly can feel like one. This is even more distressing if the condition is progressive, as many patients who have longstanding disease may not be suitable for a particular treatment by the time one is discovered. You can apply this to any degenerative disorder, from motor neuron disease, through to Parkinson’s Disease and Alzheimer’s Disease.
Multiple sclerosis is another such condition. In contrast to many other chronic neurological disorders, MS patients tend to be young, highly informed and heavily engaged with social media. So when a media outlet says that stem cell transplantation in Russia can cure MS, they may very well trigger a stampede. In some cases, you have to wonder if this is indeed the media’s intent and any question about the procedure’s scientific basis is deftly pushed to the side. In light of these reports about ‘stem cell’ treatment in MS, it is nice to see a reputable scientific journal such as JNNP publish a study that provides…wait for it….data!! Yes, it exists!!
In this month’s issue, the journal contains a Swedish study of autologous stem cell transplantation in MS http://jnnp.bmj.com/content/85/10/1116.abstract . A quick word for those who are from a non-medical background. What we are talking about here is not embryonic stem cells injected into a patient with MS, but rather about a procedure that has been used in the treatment of haematological malignancy for decades and which is reliant on initial high dose chemotherapy as a means of ablating the immune system.
In the Swedish study, patients had predominantly relapsing-remitting disease, although some patients with progressive disease were also studied. While retrospective in nature, the study nevertheless shows that this treatment may be effective (and safe) in certain patients with severe disabling MS. As noted by the authors, it sets the scene for future larger prospective clinical trials that may provide important insights into the risks and benefits of this treatment and which may also shed light on the patient characteristics that are most likely to predict a beneficial response.
4 Sep, 14 | by Steve Vucic, Web Editor
Salt intake has been shown to modulate the activity of Th 17 cells, the very cells that drive the inflammatory response in MS. Consequently, the question is raised whether high salt intake is associated with MS activity/relapses. In an upcoming issue of JNNP, Farez and colleagues demonstrate a link between high salt intake and MS exacerbations. In addition, the radiological burden was also increased by high salt intake. So I guess we should advise our patients on a low salt dies.
Must read http://jnnp.bmj.com/content/early/2014/07/23/jnnp-2014-307928.full
J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2014-307928
Sodium intake is associated with increased disease activity in multiple sclerosis
1 Sep, 14 | by Arun Krishnan, Web Editor
HIV and multiple sclerosis (MS) are chronic conditions that, despite a massive amount of research, remain essentially incurable. The marked progress in treatment for these conditions has meant that both are now treatable, with the goal of treatment focussing on maintaining independence and quality of life. In the case of HIV, ensuring prolonged survival is an additional critical endpoint.
In JNNP online first, Gold and colleagues have presented an interesting study that explores the question of why patients with HIV never seem to get MS http://jnnp.bmj.com/content/early/2014/07/16/jnnp-2014-307932.abstract . As they mention in their report, there has only ever been one case reported of MS having developed in an HIV positive individual and that patient’s MS symptoms improved when treatment for HIV was commenced. The question raised in that report was whether there may be a virus linked to MS development that was being successfully treated with HIV medication. If so, could this be an avenue for future treatment?
In their study, Gold et al have undertaken a large cohort study using a British database. The major finding from their study is that HIV infection is associated with a lower risk of developing MS. They propose a number of different reasons for this association, including the fact that immunosuppression due to HIV infection may be reducing MS development. From a treatment perspective, the other possibility is that HIV treatments may also be reducing the impact of other viruses that are associated with the development of MS.
This is an interesting study that explores MS from a completely different angle. Well worth the read.
27 Aug, 14 | by Steve Vucic, Web Editor
Primary progressive MS (PPMS) is the least frequent but possibly the most devastating of the MS phenotypes. The rate of progression and disability accumulation in PPMS has been a matter of debate. In an upcoming issue of JNNP 9Published as first online), Koch and colleagues address the issue of factors governing disability progression. Importantly, older age at onset and bilateral lower limb motor features (spasticity and weakness) seemed to be independent predictors of faster rates of disability accumulation in PPMS. Interestingly, no evidence of distinct phase of disability accumulation were noted in PPMS, contrasting with RRMS. Undoubtedly, this would have impact on the understanding of disease pathogenesis and development of prognostic biomarkers.
Must read more at:http://jnnp.bmj.com/content/early/2014/08/04/jnnp-2014-307948.abstract
Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2014-307948
The natural history of early versus late disability accumulation in primary progressive MS
22 Aug, 14 | by Steve Vucic, Web Editor
Thinning of the motor cortex has been suggested as a biomarker of cortical dysfunction in ALS, although the specificity of the finding remains to be determined. In an upcoming issue of JNNP Walhout and colleagues report on the fact that cortical thinning was a specific feature in ALS, related to pathology of upper motor neurons. Consequently, the possibility of cortical thickness measures serving as potential biomarkers of ALS remains very real.
Must read more at: http://jnnp.bmj.com/content/early/2014/08/13/jnnp-2013-306839.abstract
J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2013-306839
Cortical thickness in ALS: towards a marker for upper motor neuron involvement
22 Aug, 14 | by Steve Vucic, Web Editor
Cervical radiculopathy is a common issue for neurologists. While motor dysfunction has been traditionally assessing using needle EMG techniques, thereby confirming the diagnosis, frequently only sensory symptoms may be evident. In such cases, the diagnostic time may be protracted.
In an upcoming issue of JNNP (ON-LINE FIRST) Lin and colleagues tackle this issue in a novel manner assessing sensory axonal excitability distal to the site of dysfunction. Interestingly, distal axonal hyperpolarisation was noted even in the presence of normal sensory nerve conduction studies, as traditionally expected. This provides a novel pathophysiological insight into this disorder.
Must read more at: http://jnnp.bmj.com/content/early/2014/08/20/jnnp-2014-308088.abstract
J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2014-308088
Sensory axonal dysfunction in cervical radiculopathy
22 Aug, 14 | by Arun Krishnan, Web Editor
Recently, I was talking to a young man in my clinic whom I had recently diagnosed with MS. We went over the potential options for treatment and he said that he would think it over and get back to me. A few weeks later I received an email from him stating that he wanted to start dimethyl fumarate (Tecfidera), a new disease modifying-drug for MS. What was his rationale? Here it goes:
“I feel that its effects on the NF2 oxidative pathway mean that I am more likely to experience a clinical benefit, without the adverse effects of immunosuppression”.
Wow. This from an intelligent person who has absolutely no background in medicine. It is truly amazing what you can learn on the internet. While in this case, the young man did not take it upon himself to make the diagnosis of MS, there are people whom I have seen who are absolutely convinced that they have a particular neurological condition based on reports that they have read on the web. In some cases, patients initiate a process of investigation and then arrive at a neurologist’s office armed with objective data that need interpretation. This of course turns the basic process of diagnostics on its head- it becomes a case of find an abnormality first and then ask the doctor to make sense of what it means clinically.
Those of who you work closely with clinical geneticists would have seen a similar situation arising due to the advent of commercial gene panels, which can screen for pretty much anything you want them to screen for. The panels are expensive and once the results are produced it is up to the clinician to make sense of what it all means. This is a major problem in some situations as these panels can make the diagnostic process much harder, particularly where there is more than one abnormality uncovered. At the end of the day, the clinician will need to make a diagnosis and that means resorting to the traditional clinical method of taking a history and doing a physical examination.
In this issue of JNNP, Foley and colleagues provide an interesting report http://jnnp.bmj.com/content/85/9/1012.abstract on a diagnostic journey that commenced with two patients who had independently decided to obtain whole-genome sequencing. As you will read, the results initially side-tracked diagnostic efforts before the treating team were able to utilise a more traditional pathway of investigation, which ultimately led to the diagnosis.
16 Aug, 14 | by Steve Vucic, Web Editor
The risk of fetal malformations is a considerable therapeutic consideration in pregnant patients that suffer epilepsy. the need to control seizures effectively is counterbalanced by toxicity of medications. While lamotrigine was considered as a safer option than other anti-epiletics, doubt was cast upon this assertion. In this issue of JNNP, an important study conducted by Campbell and colleagues elegantly demonstrate that lamotrigine is safer that than valporate and tegretol. Indeed, valporate seemed to bear the highest risk of malformations. Of relevance, higher dose lamotrigine (>400 mg) did not seem to impart a significant increase of risk. Anyone managing epilepsy patients with the potential of falling pregnant must read this very important article.
J Neurol Neurosurg Psychiatry 2014;85:1029-1034 doi:10.1136/jnnp-2013-306318
Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers
- E Campbell1,
- F Kennedy2,
- A Russell3,
- W H Smithson4,
- L Parsons5,
- P J Morrison6,
- B Liggan7,
- B Irwin1,
- N Delanty8,
- S J Hunt1,
- J Craig1,
- J Morrow1