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Peptic ulcers, Nobel Prizes and Multiple Sclerosis

22 May, 15 | by Arun Krishnan, Web Editor

It has been a decade now since Barry Marshall and Robin Warren from the University of Western Australia (UWA) were awarded the Nobel Prize for Medicine for discovering the link between Helicobacter Pylori (H.pylori) and the development of peptic ulcers. Famously, their discovery involved Marshall ingesting the bacteria himself in order to prove his hypothesis. In keeping with very many Nobel Prize winners, the duo had to contend with fierce opposition from colleagues within the medical fraternity who simply refused to believe that there was any suggestion that ulcers could be due to infectious organisms.

A decade on, the multiple sclerosis (MS) research group from UWA have collaborated with Barry Marshall to investigate the possible connections between H.pylori and MS development. In a paper that appears in this month’s issue of JNNP, the authors have explored the ‘hygiene hypothesis’ in MS . This hypothesis contends that exposure to infections early in life are able to potentially reduce development of allergic and immune disease later in life through priming of the immune system. In their paper, the authors provide evidence that evidence of exposure to H.pylori is lower in MS patients than in controls. They also demonstrate that female MS patients who have evidence of previous exposure to H.pylori have lower rates of disability than those who do not. In terms of future research, the authors suggest that it would be important to work out why this relationship is only noted female patients and not in male patients.

Decision-making and multiple sclerosis: there is hope!

4 May, 15 | by Arun Krishnan, Web Editor

One of the most common concerns that I hear as a clinician from MS patients concerns their ability to organise and look after their lives. MS patients who have even the most mild degrees of physical disability report an alarmingly significant effect of the illness of their ability to multi-task and to just get things done in the course of a day. Due to the rapid rate of progress in developing new drugs for MS, we don’t see the levels of physical disability that we used to compared to patients who developed the condition in decades past. Yet, regardless of which medication an MS patient is taking, almost all report fatigue and some difficulty with decision making. The difficulty as a clinician is diagnosing this as there are no simple bedside tests to assess you go about making the sorts of daily decisions that one needs to as a functioning adult. Treatments? Don’t go there, there is simply nothing out there for this problem.

For any disease, you can’t really develop treatments that work without a very detailed knowledge of the mechanism that cause that disease. That’s my lead-in for telling MS patients that there is little I can offer them for any type of cognitive change that they may experience. Fortunately, Muhlert and colleagues have provided an interesting paper in the current issue of JNNP which provides the first evidence that changes in decision-making in MS patients are related to changes in specific parts of the brain’s grey and white matter. These are the studies that we need to make headway into a very prevalent issue for MS patients and their families.

Medication-overuse headache: finally, we have an intervention that works.

20 Apr, 15 | by Arun Krishnan, Web Editor

Headache. Common, painful, frustrating, exhausting- and that’s just what the neurologist feels when a headache patient walks in the room. The patients themselves are often at their wits end as headache, whatever the cause, is often functional incapacitating and can really ruin quality of life. Of all the headache types that are seen in neurology, medication-overuse headache (MOH) can be particularly challenging. The condition typically occurs in patients who take frequent large quantities of acute headache treatments, including over-the –counter drugs. The problem here is that these patients often are taking these tablets for another headache condition such as migraine. After taking large amounts of these acute treatments over long periods of time, their migraine symptoms often tend to morph with MOH symptoms and it can be very hard to tell the two apart. Getting patients to cut down on these meds is hard. How do keep patients on the straight and narrow, when as a neurologist, you only see them infrequently?

The answer: involve the GP! In this issue of JNNP, Kristoffersen and colleagues from Norway did just that . They undertook a randomised study in which they asked GPs to undergo further training in how to reduce consumption of drugs related to MOH. Patients were randomised to standard care or to the intervention. The study was successful in that allocation to the intervention improved outcomes in patients with MOH.

MOH is a very common problem and this paper sets out a simple intervention that could make a big difference to the care of these patients.

Temozolomide reduces risk of seizures in low grade glioma!

7 Apr, 15 | by Steve Vucic, Web Editor

Low grade gliomas are associated with a higher frequency of seizures.  While antieplipetic medications are utilized to reduced seizure frequency, in this issue of JNNP temozolomide was also associated with a a significant reduction in seizure frequency.  Perhaps temozolomide should be added to therapy of LGGs with intractable seizures.




Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide

Spinal cord injury in multiple sclerosis: why is this important for MS clinical trials?

24 Mar, 15 | by Arun Krishnan, Web Editor

For patients with multiple sclerosis (MS), sustained long-term disability is a problem that elicits considerable concern. There is the impact on independence and the potential burden that it may lead to for caregivers. While treatments for MS seem to multiply by the year, established disability remains the one area that is still refractory to treatment. Most of the current medications are excellent for preventing relapses but it is important to remember there is still no good evidence that these medications prevent long-term disability. The trials have not been done and it seems unlikely that they ever will be. There are global efforts directed at progressive forms of MS,  such as The International Progressive MS alliance which is seeking to bring together groups of researchers who are committed to developing new methods for treating progressive MS ( .

The importance of such endeavours is underscored by a manuscript in this month’s issue of JNNP.  Lukas et al have explored the contribution of cervical spine cord damage to the development of disability in MS . They have assessed radiological parameters in a large cohort of patients and have demonstrated that there is a change in the dimensions of the spinal cord that appears to occur in all forms of MS. These changes also predicted disease progression. Critically, the thinning of the cord occurred not only in patients with progressive MS, but also in patients with relapsing-remitting MS (RRMS). A number of these RRMS patients were on treatment with immunomodulatory mechanisms and it is sobering to think that the changes in the spinal cord occurred despite the potential benefits of being on drug treatment. This study is of importance as it highlights the importance of spinal cord disease in the development of disability. The authors also make the valid point that measures of spinal cord injury need to be incorporated into MS drug trials.

Confused about encephalopathy? Here’s something that may help.

16 Mar, 15 | by Arun Krishnan, Web Editor

Confusion. Agitation. Irritability. A wander around any emergency department or neurology ward will yield an abundance of observations that can fall under these categories and yet these are not all due to long waiting times or general hospital mayhem. All these symptoms are common presentations of neurological dysfunction and they are features of that syndrome that neurologists call encephalopathy, which refers to a state of altered consciousness that is typically accompanied by changes in cognition or perception. Working out why someone has encephalopathy is challenging and can take time. While some diagnoses are easier to pick, such as systemic infection, in other cases symptoms can be so non-specific that finding a unifying diagnosis can be very hard despite the wonders of modern medical technology.

In this month’s issue of JNNP, Sutter and Kaplan have published an outstanding review that addresses neuroimaging in acute encephalopathy . Their paper provides an excellent outline of changes in MRI and CT which occur in various conditions that result in encephalopathy. They have gone through common and even rare causes of encephalopathy, indulging those related to immune and infectious mechanisms, and have complied useful lists of specific changes in brain areas that are characteristically involved in each condition.

This review will prove to be a very useful resource, for neurologists, emergency specialists and general physicians, all of whom will be called upon to manage these patients at one time or another.

Spinal cord injury: another step forward.

16 Feb, 15 | by Arun Krishnan, Web Editor

Around the world, spinal cord injury (SCI) is a common and devastating long-term complication of trauma that can result in lifelong disability or even death. There are frequent media reports of treatments that may help patients with SCI walk again and these range from new drugs, to robotic devices to new developments in stem cell research. Despite the hype, the fact remains that there are no treatments that have been proven to definitively alter outcomes in this condition.

One of the major problems with drug trials in SCI is finding a way to measure the response to the drug. Many drugs that are potentially useful may fail in clinical trials because we are not able to accurately determine which patients benefit the most. In other neurological conditions such as multiple sclerosis, the ability to use biomarkers such as MRI has revolutionised our diagnostic and treatment approach, leading to significant gains for patients.

In the current issue of JNNP, Kuhle and colleagues have published a paper which demonstrates that measuring levels of neurofilaments, structural proteins that are present in neurons, may be useful in determining the degree of spinal cord injury. The exciting fact about this paper is that neurofilament levels correlated closely with acute severity of SCI and with the eventual neurological outcomes. The other benefit with this assay was that levels were measured in the blood of patients with SCI, rather than in the cerebrospinal fluid. This makes the assay for more acceptable in the clinical setting. The authors also provide some evidence that neurofilament levels may be responsive to drug treatments and in this case, they have assessed how levels vary according to treatment with minocycline, a medication that has been previously trialled in SCI.

This is a well-designed study. It represents an important step forward in diagnostic methods and treatments for SCI.

Dementia in Parkinson’s disease: what can we do about it?

4 Feb, 15 | by Arun Krishnan, Web Editor

It has been around 200 years since James Parkinson first outlined the clinical features of the condition that would later bear his name. While his descriptions of Parkinson’s Disease (‘shaking palsy’) may have focussed largely around the motor manifestations of this condition, recent insights have provided strong evidence that non-motor manifestations contribute significantly to poor quality of life for patients with this neurodegenerative condition (for an excellent review see the reference below by Jankovic).

Depression, cognitive impairment, sexual dysfunction and constipation are just some of the problems that these patients can develop and it is a source of immense frustration for both patients and clinicians that these problems are so hard to treat. Our current approaches to treating Parkinson’s disease are focussed on medications that really only improve motor outcomes, so what is a neurologist to do when a patient describes the effects of non-motor manifestations on his/her quality of life?

In this issue of JNNP, Wang and colleagues provide a thorough overview of the role of cholinesterase inhibitors as treatments for cognitive impairment in Parkinson’s Disease . These are drugs that have been used in the setting of Alzheimer’s Disease for a number of years. In addition to suggesting that these medications have benefits in Parkinson’s Disease as well as an excellent safety profile, the paper also highlight the fact that the treatments have only been assessed in small clinical trials and that larger studies in this population may be required before they can become an established part of treatment for this condition. Nevertheless, their study provides hope for a major problem which currently remains untreatable.

(1) Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008;79:368-376 doi:10.1136/jnnp.2007.131045

Infections and cancer: any link to brain tumours?

21 Jan, 15 | by Arun Krishnan, Web Editor

There have been numerous postulated links between the development of cancer following exposure to infectious organisms. In the case of the connection between human papilloma virus and cervical cancer, this association has led to ground-breaking treatments in the form of vaccination. A similar connection has been developed between hepatitis B and liver cancer. While many forms of malignancy carry a poor prognosis, malignant brain tumours are often cited as a particularly aggressive form of cancer and this is borne out in survival rates which are dismal.

A question that has been raised in many previous scientific reports is the putative association between cytomegalovirus infection and the development of glioma, a form of malignant brain tumour. There have been previous studies that have suggested a strong link while others have cast doubt on any association. A recent letter in the New England Journal of Medicine has elicited much controversy regarding the possible benefits of anti-viral drugs for CMV being used as treatments for the most aggressive of brain tumours, glioblastoma. Clearly, this is a contentious area and at some point we need to take an objective unbiased view of the data. To that end, in the current issue of JNNP Dey and colleagues have provided an insightful review of the area and have addressed the arguments for and against a role of CMV in glioma development (2). They have addressed the criteria of Koch’s postulates for causation in developing their argument and have taken a close look at the key studies in this area.

This is a timely and interesting review of a very controversial topic.

  1. N Engl J Med 2013; 369:985-986September 5, 2013DOI: 10.1056/NEJMc1302145
  2. J Neurol Neurosurg Psychiatry 2015;86:191-199 doi:10.1136/jnnp-2014-307727

Fish oil: a treatment for severe epilepsy?

7 Jan, 15 | by Arun Krishnan, Web Editor

Happy New Year to all JNNP readers!

In order to ensure that we start 2015 with an optimistic outlook, I thought that the first post of this year should concern a clinical trial with a positive outcome! Epilepsy is a common and very debilitating condition which leads to significant impairments in quality of life. While a lot of patients with epilepsy can be successfully treated with medication, there remains a significant minority in whom seizures remain resistant to anticonvulsant drugs. There is little consensus on how these patients should be managed. Surgical treatment may be useful if a seizure focus is identified, but in other patients in whom the seizure origin remains elusive, treatment can be problematic.

There has been a vast literature that has focused on the role of dietary strategies in patients with drug resistant epilepsy and most of these studies have focussed on use of the ‘ketogenic diet’. The use of fish oil has also been considered, particularly given studies in animal models that have demonstrated a possible benefit at low doses.

In this issue of JNNP, DeGiorgio and colleagues undertook a randomised placebo-controlled diet of fish oil in 24 patients with drug resistant epilepsy . Their study demonstrated a possible benefit of fish oil at low doses, but no significant benefit at higher doses. This is consistent with studies in animal models which have shown anticonvulsant effects at low doses and proconvulsant effects at higher doses.

As most neurologists would know, drug resistant epilepsy ruins quality of life for sufferers. The present study is encouraging and may provide the impetus for larger randomised studies.

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