Tuesday, 21 August 2018

Parkinson's in Multiple Sclerosis

Neurol Sci. 2018 Aug 16. doi: 10.1007/s10072-018-3531-y. [Epub ahead of print]

Parkinsonism and multiple sclerosis, what is behind?

Uysal Tan F

Letter to the Editor

Dear Editor,

The awareness of the coexistence of both diseases in some patients resulted in an ongoing debate on either causal or coincidental relationship between multiple sclerosis (MS) and parkinsonism. Present data offers some rationale for both theories. In the cases presented in the literature, mostly, Parkinson’s disease (PD) follows the MS.

A 43-year-old man complained of tremor of the left arm in 2010. Neurological examination revealed resting tremor of the left upper extremity with mild bradykinesia and mild rigidity, and hypomimia. He had a normal-based gait, with absent left arm swing. The symptoms markedly improved by administration of pramipexole.

In his history, he had mild vertigo, ataxia, and gait disturbances in 2002. Brain magnetic resonance imaging (MRI) revealed demyelinating lesions of the central nervous system consistent with MS: multiple hyperintense lesions located in periventricular areas, the corpus callosum, and the subcortical white matter of both cerebral hemispheres. There were no plaques in the brain stem or in the cerebellum as the basal ganglia, thalamus, capsula interna, and externa were also spared bilaterally.

The patient refused cerebrospinal fluid (CSF) examination; immunological tests were negative and visual evoked potentials (VEP) were normal. Corticosteroid therapy led to significant improvement of his symptoms. One year later, he had one more attack with same clinical findings and good recovery with pulse steroid treatment. Follow-up for 10 years, including yearly MRI scans, was free of any MS attacks thus immunomodulatory treatment was not started.

The patient’s brain MRI at the time of parkinsonism symptoms revealed multiple supratentorial white matter hyperintensities similar to the 2002 MRI and a relatively less obvious cervical cord lesion at C4 level, without enhancement on gadolinium application. Similarly, there was no involvement of basal ganglia, thalamus, and brain stem.

Considering the stable course of MS (no activation) through years, asymmetric onset of parkinsonism symptoms, slow progression of the disease, absence of plaques in the basal ganglia on MRI scan, and good response to the dopa agonist pramipexole, the diagnosis was PD coincidental with MS. During the following years, PD progressed and pramipexole was switched to levodopa and carbidopa treatment 500 mg/day initially and increased to 1000 mg/day.

Currently, at the age of 47 years, he remains without new MS attacks and has stable Parkinsonism.

Lightening never strikes twice, or so the saying goes. But in reality, it would seem being touched by a debilitating illness once - however rare the condition; doesn't make you immune to being hurt a second time.

It's not the first time that I've come across reports of coinciding parkinson's and MS, in fact I've witnessed this first hand in clinic a couple of times. I've often put it down to coincidence, or MS involvement of the brain structures involved in Parkinson's. But could there be a causal relationship between MS and parkinsonism or vice versa?

The reason for asking this is that although there is involvement of the basal ganglia by MS placques leading to damage of dopaminergic neurons (implicated in parkinson's), this is uncommon. MS typically affects cortical, subcortical, and periventricular regions of the brain proper. In some people, like the one described here, the onset of the parkinson's occurs at a younger age, or younger than you would expect for a sporadic presentation (majority of parkinson's are this), implying a possible genetic link between the two disorders. Moreover, the disorders share common pathways to neuronal damage, including inflammation, oxidative stress and mitochondrial dysfunction.

Studies looking at this are based around hospital registries and may not cover the entire population. However, the Danes have done a nationwide association study (15,557 MS cases) on this and found no link (Nielsen NM, Pasternak B, Stenager E, Koch-Henriksen N, Frisch M (2014) Multiple sclerosis and risk of Parkinson’s disease: a Danish nationwide cohort study. Eur J Neurol 21:107–111).

Although, the mystery may never be solved, a direct causal-association-pathology analysis of these occurrences,  rather than simply looking at population statistics, may yield potential new treatment pathways that were not apparent previously.

Monday, 20 August 2018

Guest post: Primary Progressive MS Research: Treatment Outcomes

This is a repost from MStranslate, with kind permission from Brett Drummond.

PPMS is characterised by a steady worsening of disease or accumulation of disability from onset without any lengthy periods of stability or ‘remission’. Some people with primary progressive MS may also experience acute attacks of active disease, commonly referred to as relapses, during which symptoms are exacerbated or new symptoms develop.

Sunday, 19 August 2018

ProfG a Week in TwitterLand

ProfG has taken to twitter to comment on posts.Should we consider a feature on his comments on the blog as it is is clear many people can't we bothered with Twitter?

Gavin GiovannoniThis study suggest that the anti-JC virus antibody index will be difficult to interpret and use to risk profile MSers on rituximab or ocrelizumab as it affects antibody production.
Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients.
Baber U, Bouley A, Egnor E, Sloane JA. J Neurol. 2018 Aug 14. doi: 10.1007/s00415-018-8996-3. [Epub ahead of print]

Gavin GiovannonAgeing is a big problem in MS. This paper suggest it contributes to falls as well as cerebellar and cognitive dysfunction in MS.
Cerebellum and cognition in multiple sclerosis: the fall status matters.Schreck LM, Ryan SPP, Monaghan PG.J Neurophysiol. 2018 Aug 15. doi: 10.1152/jn.00245.2018. [Epub ahead of print]

Gavin Giovannoni.As a community of MS stakeholders we need to take care to produce better and more practical guidelines, particularly in relation to lifestyle issues such as physical activity. A systematic critical review of physical activity aspects in clinical guidelines for multiple sclerosis. Geidl W, Gobster C, Streber R, Pfeifer K.Mult Scler Relat Disord. 2018 Aug 3;25:200-207.

Gavin Giovannoni MSers with hypertension and/or heart disease have a much greater loss of brain volume than MSers without these comorbid diseases. Not surprising considering what we know about hypertension and brain reserve. Do you know your blood pressure?Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study.Jakimovski D, Gandhi S, Paunkoski I, Bergsland N, Hagemeier J, Ramasamy DP, Hojnacki D, Kolb C, Benedict RH, Weinstock-Guttman B, Zivadinov R.Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13769. [Epub ahead of print]

Gavin Giovannoni‏ Instilling a small amount of ice water into the bladder of MSers and measuring the change in pressure allows urologists to diagnosis overactivity of the detrusor muscle. Low tech but potentially useful. Ice water test in multiple sclerosis: A pilot trail.Hüsch T, Reitz A, Ulm K, Haferkamp A. nt J Urol. 2018 Aug 13. doi: 10.1111/iju.13786. [Epub ahead of print]

Gavin Giovannoni‏ Another piece of dogma bites the dust. #NeuroSpeak Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Akaishi T, Nakashima I. Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13772. [Epub ahead of print]

Gavin Giovannoni Another depressing study showing the impact a diagnosis of MS has on young adults. Why aren't we doing more to prevent this disease. 
Young adults' adjustment to a recent diagnosis of multiple sclerosis: The role of identity satisfaction and self-efficacy. Calandri E, Graziano F, Borghi M, Bonino S. isabil Health J. 2018. pii: S1936-6574(18)30139-0.

Gavin Giovannoni‏  A paper showing that cerebrospinal fluid GAP-43 (a recovery marker) is raised in early multiple sclerosis. Will it be down in more advanced MS?. Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018 4(3):2055217318792931.

Gavin Giovannoni‏ No wonder the early burden of MS is related cognitive impairment. The shredder damages connectivity in the MS brain. Are you surprised? Another reason to treat early and effectivelyMagnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis. Solana E, Martinez-Heras E, Martinez-Lapiscina EH, Sepulveda M, Sola-Valls N, Bargalló N, Berenguer J, Blanco Y, Andorra M, Pulido-Valdeolivas I, Zubizarreta I, Saiz A, Llufriu S.Neuroimage Clin. 2018;20:161-168.

Gavin Giovannoni‏ Another elephant in the room (immunosuppression) is making things crowded. #ClinicSpeak Infectious complications of MS DMTs: implications for screening, prophylaxis, and management. Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management.Epstein DJ, Dunn J, Deresinski S.Open Forum Infect Dis. 2018 ;5(8):ofy174.

Gavin Giovannoni‏ TEVA fights back and shows major physicochemical, biological, functional and toxicological differences between the European follow-on glatiramer acetate compared to Copaxone. Will this impact efficacy?Physicochemical, biological, functional and toxicological characterization of the European follow-on glatiramer acetate product as compared with Copaxone. Melamed-Gal S, Loupe P, Timan B, Weinstein V, Kolitz S, Zhang J, Funt J, Komlosh A, Ashkenazi N, Bar-Ilan O, Konya A, Beriozkin O, Laifenfeld D, Hasson T, Krispin R, Molotsky T, Papir G, Sulimani L, Zeskind B, Liu P, Nock S, Hayden MR, Gilbert A, Grossman I.eNeurologicalSci. 2018 May 30;12:19-30.

Gavin Giovannoni‏ Is creating a walled garden the way to deal with fake news in the MS space? Influencers and health-related professional participation on the Web: A pilot study on a social-network of MS
Fake news, influencers and health-related professional participation on the Web: A pilot study on a social-network of people with Multiple Sclerosis. Lavorgna L, De Stefano M, Sparaco M, Moccia M, Abbadessa G, Montella P, Buonanno D, Esposito S, Clerico M, Cenci C, Trojsi F, Lanzillo R, Rosa L, Morra VB, Ippolito D, Maniscalco G, Bisecco A, Tedeschi G, Bonavita S.Mult Scler Relat Disord. 2018 Jul 31;25:175-178. 

Gavin Giovannoni‏ Mental health is a big problem for MSers. Another hidden problem highlighting how large the burden of disease we are missing by focusing on the physical. Factors associated with perceived need for mental health care in multiple sclerosis. Orr J, Bernstein CN, Graff LA, Patten SB, Bolton JM, Sareen J, Marriott JJ, Fisk JD, Marrie RA; CIHR Team in Defining the Burden and Managing the Effects of Immune-mediated Inflammatory Disease.Mult Scler Relat Disord. 2018;25:179-185
Gyllensten H, Kavaliunas A, Alexanderson K, Hillert J, Tinghög P, Friberg E. Mult Scler J Exp Transl Clin. 2018;4(3):2055217318783352.

 Gavin Giovannoni‏  MRI and CIS outcomes. Surely baseline lesion number simply indicates that CISers have had asymptomatic MS longer, hence the MS-shredder has had more time to reduce brain reserve and hence they do worse? How do we capture the time vector? Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018;4(3):205521731879293

Gavin Giovannoni‏ We now have the biomarkers for microglial activation. The question is whether or not inhibiting microglia will make MS better or worse? I suspect worse. The microglial response in MS may be a positive not a negative.Comparison of two different methods of image analysis for the assessment of microglial activation in patients with multiple sclerosis using (R)-[N-methyl-carbon-11]PK11195. Kang Y, Schlyer D, Kaunzner UW, Kuceyeski A, Kothari PJ, Gauthier SA. LoS One. 2018;13(8):e0201289.

Saturday, 18 August 2018

Evidence against oligoclonal bands being important?

As you may realise, I am sometimes critical of my colleagues who tend to follow dogma, without question.

This of course does me no favours with my colleagues. Maybe I should just say everything is "Great" or "Super", like I'm part of  some 1970s Sitcom :-0

Friday, 17 August 2018

Guest post: Does degradation of brain fats cause MS?

This is to let you know about a research project based on a novel idea of how MS develops. I am a pathologist, and have spent most of my career on medical research. I am returning to researching on MS after a long period of working on the arterial disease that causes heart attacks and strokes. The reason for my return to MS work is that I believe that MS may develop in a way similar to arterial disease when the details of the process, the molecules concerned, are considered. 

Thursday, 16 August 2018

Guest Post: Language and MS: Why Our Words and Stories Matter

Question. Those with multiple sclerosis: do you remember the exact words your neurologist used to break the news of your diagnosis?

Wednesday, 15 August 2018

Neuroinflammation associated with nerve damage in progressive MS

This study looks at neuroinflammation. Specifically the fact that the development of treatments for progressive MS is hampered by the lack of suitable biomarkers that can accurately detect and monitor intrathecal inflammation (inflammation which occurs within the spinal theca, which is a sac containing the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord).

Tuesday, 14 August 2018

How big is your need to exercise?

The evidence that exercise and I mean regular exercise is good for you is so overwhelming that it is hard to argue against the science. What I mean by this is that almost everyone accepts exercise as being good for the general population and for people with MS. The downside is that some MSers are so disabled and/or have so much fatigue that they find it difficult to exercise. I am prepared to accept the latter, but I am not prepared to accept this as a reason not to promote/prescribe exercise to the wider MS community. The question I have 'Is how do we get MSers and healthcare professionals (HCPs) to exercise regularly?'

Are you interested in hearing more about what you can do?

My Tibetan Odyssey: In search of Gods in the highest of places

Mountain climbing as an obsession is a selfish endeavor, and there’s just no way to get around that fact
       -Beck Weathers in ‘Left for Dead' on the 1996 Everest disaster.

Monday, 13 August 2018

ProfG on Twitter

You may have realized that the number of posts have dropped to one a day. 

Some people felt that the haphazard way the posts were done was over-loading people. What do you think?

Anyway, you may want to know that ProfG has been tweeting his views, notably on papers, rather than blogging them.  


Do you want sound bites or words of wisdom?
6 hours ago