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Archive for July, 2014

Genetic mutations: Predisposing but not causative?

31 Jul, 14 | by Steve Vucic, Web Editor

Hereditary IBM is an autosomal recessive myopathy characterized by distal muscle weakness, and the absence of the classical IBM phenotype.  mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene has been linked with development of this myopathy.  However, there has been a paucity of genotype-phenotype correlation studies, critical for understanding disease mechanisms.   In this issue of JNNP, a large Japanese group reports the mutation profile for the GNE gene and find phenotypic variability, underscoring the importance of a clinical context.




Mutation profile of the GNE gene in Japanese patients with distal myopathy with rimmed vacuoles (GNE myopathy)

Thunderclap headache and subarachnoid haemorrhage: yes, it’s as bad as it sounds.

30 Jul, 14 | by Arun Krishnan, Web Editor

Aside from publishing ground-breaking insights into the mechanisms of neurological disease, JNNP also publishes many manuscripts that focus on common hard-to-manage clinical problems, things that neurologists come across on a daily basis. In this issue of JNNP, there is a very interesting paper from Bakker and colleagues that concerns one of the most feared neurological disorders, namely subarachnoid haemorrhage (SAH). This condition is due to rupture of a cerebral aneurysm and the condition is commonly fatal. Many of you would have heard about patients who have had emergency surgery for this condition and survived and possibly of others who died despite treatment or in whom the diagnosis was missed.

In my current cohort of final year medical students, all were able to provide clear descriptions of how SAH presents and how you diagnose and treat this condition, which is reassuring. There does however remain one area of contention. If someone has a CT scan of the brain which does not show any evidence of acute bleeding but has evidence of ‘old blood’ in their spinal fluid (obtained by lumbar puncture), how far do you go looking for an aneurysm?

In this paper, Bakker et al have addressed this very issue . Patients who were CT negative but lumbar puncture positive, were put through a rigorous set of additional tests. This included a CT angiogram and in patients who were CT angio negative, a follow-up formal cerebral angiogram. The key finding was that >40% of patients who were investigated in this way had evidence of an aneurysm. This is a very significant proportion and it demonstrates the lengths to which one needs to go to detect these abnormalities. Overall, patients in this study had a favourable outcome, which underscores the benefits of intense investigations in this potentially fatal condition.

MS and Pregnancy: Control the disease before conception for good outcomes?

29 Jul, 14 | by Steve Vucic, Web Editor

Pregnancy has been traditionally associated with lower frequency of relapses and more quiescent MS disease activity.  Consequently, cessation of medications is encouraged, and is necessary for some of the newer oral therapies.  In this issue of JNNP the Italisn MS group publish an important and elegant paper documenting that the control of disease post-partum is really dependent on what is occurring pre conception.  Fewer relapses before pregnancy and lower disability score 9perhpas reflecting less active disease) is associated with better outcomes, as is early resumption of disease modifying agents.




J Neurol Neurosurg Psychiatry 2014;85:845-850 doi:10.1136/jnnp-2013-306054
  • Multiple sclerosis
  • Research paper

Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs

Stress and Parkinsons disease: A potential link

23 Jul, 14 | by Steve Vucic, Web Editor

The era of the 20th century, while associated with tremendous progress, has also heralded the era of chronic diseases that were not prevalent in our ancestors. Stress has been portrayed, at least in the lay media and amongst patients, as an important factor in this. Stress is associated with definite physiological changes. In this issue of JNNP, Professor Andrew Lees proposes a link between chronic emotional stress and biological abnormalities that may contribute to development of neurodegenerative diseases such as PD. Importantly novel avenues for research are highlighted, that could yet unlock the mystery of PD.

Read more at:

The importance of relaxing

Dont fret!















Neurology is the only real test of clinical acumen: discuss.

22 Jul, 14 | by Arun Krishnan, Web Editor


Of all the medical specialties it may be argued that neurology, more than any other, provides the most exacting test of one’s clinical skill. OK, I am a little biased but that does not mean I’m wrong. I mean, the echocardiogram got rid of the cardiology examination and the respiratory and gastro exams were only ever making up the numbers. And honestly, when your endoscope is your best friend, who cares about anything else. As for rheumatology, well all their patients end up on steroids and methotrexate regardless of the diagnosis so it doesn’t really count and besides when those drugs doesn’t work, you know that the neurology referral can never be far away.


Bravado aside, it is true that until recently, there was very little for a neurologist to go by in terms of making a diagnosis aside from his/her clinical acumen. Even now, neurology clinical meetings are dominated by heated discussion that focuses on ensuring meticulous documentation of clinical abnormalities as a prelude to further investigation and treatment. Even for experienced neurologists, this process is at times difficult. Of all the challenges that are thrown at a neurologist, one of its greatest tests is separating out weakness that is ‘neurological’ from that which is ‘functional’. In other words, working out whether there is a clear neurological diagnosis at hand or whether the symptoms are based in other social and psychological factors, possibly coupled with underlying biological vulnerability.


A few years ago, Stone and colleagues from Edinburgh provided an outstanding review article in JNNP that served as a comprehensive overview of the presenting features, pathophysiological mechanisms and possible treatment strategies for patients with functional disorders. Table 2 in that review showed the many different ways in which clinicians communicate this diagnosis to patients. The authors provided the novel parameter of ‘number needed to offend’ to demonstrate how poorly some of these communication methods were received by patients. At the top of the list was ‘symptoms all in the mind’, followed by ‘hysterical weakness’ and then ‘psychosomatic weakness’. The paper also provided a range of more effective ways of establishing rapport and helping patients overcome their deficits.


In the most recent issue of JNNP, McCormack and colleagues have taken management of these conditions a step further . They have undertaken a retrospective review of the management of motor conversion disorders in an inpatient neuropsychiatry unit. In contrast to the long-term impairment that we often see in this condition, the authors demonstrated that patients treated in their unit experienced marked improvements in functioning. The authors correctly mention that further prospective studies would be useful in providing a reliable evidence base for the management of these conditions.


GBS in Asia: A must read!

21 Jul, 14 | by Steve Vucic, Web Editor

Guillain-Barre syndrome (GBS) is an autoimmune neuropathy with a heterogeneous etiology affecting both the myelin and the axon.  GBS is probably the most frequent cause of a rapidly progressive neuropathy in the Western world.  Although the demyelinating variant is more frequent in Western forms of GBS in Asia, the axonal form (termed AMAN) is more frequent.  The review by Bae and colleagues in this issue of JNNP is an authoritative review on the topic providing novel clinical, physiological, pathological and pathophysiological insights.


Must read at

Guillain–Barré syndrome in Asia

CIDP: Diversity in therapy?

18 Jul, 14 | by Steve Vucic, Web Editor

CIDP is an autoimmune disorder of the peripheral nerves.  As its name implies, the disorder is chronic and long-term treatment (therapeutic dependance) may be frequently observed.  The factors predicting such treatment dependence need to be elucidated in order to achieve a more appropriate patient management.  In this issue of the journal, Rabin and colleagues identify the “treatment-dependent” and ” treatment withdrawal” groups establishing important clinical differences  between the groups.  Of relevance, therapy with IVIg seems to be associated with the former group while the latter groups was more response to steroids, suggesting differences in the underlying immunopathogenic processes.


Read more at:


Chronic inflammatory demyelinating polyradiculoneuropathy: search for factors associated with treatment dependence or successful withdrawal

Pregnancy and MS. The need to commence treatment post-partum?

16 Jul, 14 | by Steve Vucic, Web Editor

While pregnancy is associated with a reduced risk of relapses, caution is required in the post-partum period.  In this issue of JNNP, Portaccio and colleagues elegantly demonstrate an increased risk of relapse in the post-partum period.   Greater disease activity before and during pregnancy were reported as predictors of an increased chance of a relapse in the post-partum period.  Therapy with DMDs in the immediate post-partum period seemed to reduced risk of future relapse.




Neurol Neurosurg Psychiatry 2014;85:845-850 doi:10.1136/jnnp-2013-306054
  • Multiple sclerosis
  • Research paper

Postpartum relapses increase the risk of disability progression in multiple sclerosis: the role of disease modifying drugs

Multiple sclerosis and neuroprotection: is laquinimod the answer?

14 Jul, 14 | by Arun Krishnan, Web Editor

Multiple sclerosis (MS) for most people engenders troublesome images of young people with disability, in wheelchairs, unable to care for themselves. The mere mention of the term elicits these fears. Surprisingly, the potential MS-mimic conditions tend to get a less fearful response. In my own practice, I have noticed that telling patients that their symptoms could be due to rheumatoid arthritis, Sjogrens Syndrome or systemic lupus erythematosus (SLE) does not have the same impact and yet we know that neurological involvement in those disorders can be disastrous, often much worse than MS.

So, why is it so? I guess MS is common and many people will know of someone or will have seen images of someone with MS, most of which will depict some degree of disability. Yes, MS is disabling but it is also now increasingly treatable, with numerous agents on the market and even more in clinical trials. The sobering aspect to most of this is that they all generally do the same thing-reduce clinical relapses and hopefully make the MRI scan look a little prettier. What does this do for long term disability? Well, we don’t really know. What we do know is that these drugs act by reducing inflammation but many years down the track, inflammation will stop and neurodegeneration will set in. We also now have increasing evidence that neurodegeneration-the process of gradual loss of brain cell populations-may start very early in the disease. The race is on to find a drug that can act on neurodegeneration, thereby stopping the very process that causes long-term physical disability.

In this issue of JNNP, there is a very interesting paper that provides a ray of hope in that regard. Fillipi and colleagues ( )have demonstrated that a new oral medication for MS, laquinimod, is associated with a reduction in the loss of brain volume that can accompany MS. This drug has been previously shown to reduce disability progression and this study was aimed at working out how it exactly did this. This is an important study as it is now widely accepted that loss of brain volume may be a marker of neurodegeneration and this measurement is now increasingly being used to assess the effectiveness of newer MS drugs.

What does this mean for patients? To answer that question, long-term follow-up will be needed focussing on patient-orientated parameters, particularly measures of physical function. In the meantime, this study provides hope that we may be entering an exciting new phase in the quest for effective treatments for MS.

New criteria for FTD: They work!

10 Jul, 14 | by Steve Vucic, Web Editor

Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder predominantly affecting the frontal and temporal regions of the brain, although the pathology may be more general.  In the absence of a diagnostic test, the diagnosis of FTD remains clinically and pathologically based.  Recently, novel clinical and pathological criteria have been developed to encompass the heterogeneous nature of FTD.  In this issue of JNNP, Chare and colleagues report on the validity of these new criteria in a large international cohort of FTD/dementia.  In this must read manuscript, the pathological validation of criteria was established and  clinical features such as disinhibition, food preferences and naming, though to be diagnostically useful, did not differentiate different forms of FTD.


Read more at:


New criteria for frontotemporal dementia syndromes: clinical and pathological diagnostic implications

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