2) Box (side) - In this exercise, you step sideways over a box and back again.
3) Hölzle - In this exercise, you step either forwards or sideways over small pieces of wood lying on the floor.
This blog records my journey to Hereditary Spastic Paraplegia (HSP, also known as Familial Spastic Paraparesis or FSP). I was diagnosed with SPG4 in 2009 when my wife became pregnant with our first child. I currently wear insoles, do daily stretches and weekly Pilates. I take medication for my bladder. I tweet about HSP, RareDisease and other things @munkee74.
Annual Review: 2020
Back in November Dr Hande Ozdinler gave a presentation to the UK HSP Support Group via Zoom.
Her work has generally been focussed on ALS, which is another type of motor neuron disease, but she brings a useful broad perspective on the health of upper motor neurons. In HSP it is mainly the upper motor neurons which are affected, whereas with SMA (spinal muscular atrophy) it is mainly the lower motor neurons. People with ALS are affected in both upper and lower motor neurons.
Looking at these conditions which affect the upper motor neurons, we know that those neurons degenerate slowly over time. There are two different areas for that degeneration. Intrinsic issues are those which occur within the neurons themselves, perhaps from a genetic mutation or disruption of messaging. Extrinsic issues occur outside the neuron, perhaps the local environment where the neuron sits is not right.
The majority of the presentation looked at the intrinsic issues. Not only do the upper motor neurons degenerate, there is also degeneration of the connection between the brain and the neuron. This degeneration means that messages cannot pass as easily from the brain to the nerve, preventing or disrupting initiation of movement and the modulation of motor function.
Overall, the degeneration of the neurons accumulates over time, and eventually reaches a point beyond which the neuron cannot function any more. Early detection is useful because it gives the most time to be able to help the cells before they get to the point when they can no longer function.
They have developed a number of mouse models for ALS, and there are similar mouse models available for some types of HSP. The mouse has similar motor neurons as a human, and the functioning of the cells is identical. This makes them good for improving our understanding of the upper motor neurons. Part of the model development has included making the upper motor neurons fluorescent, which allows the cells of interest to be identified more easily, and to look at them in great detail. By looking over time they can see how the neurons degenerate, and see how their behaviour changes over time.
They also have put forward that upper motor neuron survival should be one of the key indicators for studies, and the fluorescence helps measure this. There are drug discovery pathways to seek out those which can improve the health and integrity of upper motor neurons.
Some of the proteins involved in upper motor neuron function are secreted into blood, and this offers the potential for a biomarker. Examination of the proteins in the blood should be able to give information on the timing and extent of function loss in the neuron, and identify the underlying cause of the loss.
With understanding of the cause of the loss comes opportunities to begin to formulate treatment strategies. Existing drugs which help that underlying cause in other conditions can be investigated in the case of upper motor neuron degeneration. It is likely that there would be different drugs for different types of upper motor neuron problems, and this is heading towards personalised medicines.
Another aspect they have been working on is using a big data approach to understand the functions affected by the motor neuron degeneration. Essentially by looking at which proteins interact with each other, they can identify a family tree of protein to protein interactions. This moves the focus away from looking at the mutated/absent/over-produced protein and understanding the resulting impacts on those protein to protein activities. The process identifies important functions rather than important proteins, and that opens up different paths in the drug discovery processes and the gene delivery process. They have come a long with with this process on ALS, and they have just started looking into HSP and PLS.
Overall, this was a really useful presentation. There was a lot of technical information given, but my key take-aways are that work done in one condition which affects upper motor neurons easily has potential for help other similar conditions. I was very pleased to hear about the cross-condition work and these new ways of thinking about drug discovery and the specific targeting of medicines.
The image below is a part of a screen shot from the presentation, showing some of the cross-condition work, and of course HSP is grouped into the 'Other' category on the right!
Today I took part in a lightning talk at the Findacure virtual Rare Disease Showcase.
Findacure have been hosting rare disease events for a number of years, and regular readers may remember that I went to their drug repurposing conference in 2016 (yes, there are posts here about that). One of the support group trustees suggested that I talked about the needs identification which I'm covering in this years survey, and that idea was liked by Findacure, so I was up.
Regular readers will note that I usually write up various points and observations from these meetings, however project commitments at work meant I was only able to attend today. I was working on a range of other support group activities this morning, so I was listening to a few of the other talks in the background.
My key takeaway from those talks were the discussions around how social media can be both a blessing and a curse. A study was being talked about where the participants were sharing their experiences during the trial on social media. The result of all the attention was that even those in the placebo arm of the trial showed changes, and hence the study couldn't demonstrate what it wanted to.
For the lightning talks round I was one of five presenters, and I volunteered to go first. There were a few teething issues with my technology which meant that I went a little faster than I wanted to and finished in 4 mins 26 seconds. It was really good fun to take part in!
I had taken the approach of going for five minutes, five things to say:
The other four presenters were telling the stories of their rare disease experiences, and it was insightful to hear that actually those with rare diseases are often in the same boat - trouble with diagnosis, trouble finding information, trouble finding treatments. Everyone was really friendly, and there were some interesting questions at the end. In summary, great fun!
I'm hoping to get the recording of my five minutes for youtube!
I am quite pleased with my support group network map:
So, this last week or so has seen me being involved in a couple of publicity activities.
One of the other trustees at the support group had recently suggested that we put ourselves forward for a couple of things, and these have been developing nicely recently.
We said that I would be prepared to do a five minute talk in one of the lightning talk rounds at this years rare disease showcase, and out of many, I was selected to do this. In the last week or so I have been working out what to say and what to show. My topic (as suggested by our trustee) was around using technology to identify the needs of those with HSP, so a perfect excuse to draw together lots of HSP strings together, including some of the early results from my survey.
If you wish to watch, you can still sign up for the virtual conference: https://www.findacure.org.uk/rare-disease-showcase/, and my session is on Thursday afternoon. Having had a look at the agenda, there are a load of other excellent sounding talks, a few of which I should be able to attend whilst I am there.
Also, we said that we were happy to take part in the Student Voice competition, and I was paired up with a student to talk about my experiences with HSP. The competition is here: https://www.findacure.org.uk/student-voice-prize/. We had a good chat and I was able to share many aspects (including some other early survey results!), and we should find out soon the result of that competition soon. If that essay is the winner, then HSP will get a mention in https://ojrd.biomedcentral.com/
Since my latest venture becoming a YouTuber, I have been meaning to find time to watch various other relevant HSP things in order to report them here.
Finding that time seems to be somewhat challenging at the moment, so I am putting the various YouTube links here, and I'll come back another time to report them. There are two different channels which I mean to look at first:
The European Reference Network on Rare Neurological Diseases (ERN RND) have run a series of webinars over the summer, several of which are relevant to HSP. Each webinar was broadcast on a separate day.
There are five that caught my attention, which I have put the titles and links to in this table below.
Title |
Link |
Environmental
modifiers in Hereditary Spastic Paraplegia |
|
Gait
rehabilitation in people with HSP |
|
How to assess
and manage spastic gait in rare diseases? |
|
Hereditary
Spastic Paraplegia (HSP) clinical disease course |
|
Treatment of
spasticity in HSP |
There's about 5 hours of watching here. They also have videos on other conditions than HSP, and you can see the full details on their channel: https://www.youtube.com/channel/UCLpEdEyhGnQpdmLLzqNXkTg/videos
The Spastic Paraplegia Foundation ran their annual conference on-line, and have uploaded videos of this onto their channel. Their conference ran over three days, and I have included the relevant links into the table below:
Title |
Link |
SP Foundation:
Virtual Conference Day One June 26, 2020 |
|
SP
Foundation: Virtual Conference Day Two June 27, 2020 |
|
Path to
Improve Upper Motor Neuron Health |
|
Genetic
Topics in HSP & Related Diseases |
|
HSP:
Understanding What's Wrong So That We Can Fix It |
|
Research
Advances in the HSPs |
|
A Multimodal
Strategy to Finding a Cure for an Ultra-rare Disease |
There is a video each for days one and two of the conference, and (as far as I can tell) the third day has been split into separate presentations. Overall there is about 9 hours watching here as well. They also have other videos on their channel: https://www.youtube.com/c/SpasticParaplegiaFoundation/videos
This includes videos from the past three years, and it is worth watching the Q&A with Dr Fink, as these give some great pieces of information.
(p.s. I dont know what happened to October, all of a sudden we have arrived in November! I was planning to put this post up in late October, so that my survey launch post got a long time as most recent post! It makes Oct 2020 only the second month when I have posted just the once - April 2011 being the other one)
Hello - it is that time of year again!
I am pleased to announce that my 2020 survey is now open. This year questions are available in English, Italian, Dutch, French, Spanish and Portuguese. Click on the relevant link in the table to below to access the questions in that language.
Language |
Link |
Responses 3 Jan |
English |
176 |
|
Portuguese |
66 |
|
French |
47 |
|
Dutch |
28 |
|
Italian |
11 | |
Spanish |
6 |
Hello,
I realise that there have been quite a few Symptoms Update posts from me of recent, and I wonder if that in itself is an indicator of a change in my rate of progression, a change in my perception of my progression, or if there is some other factor. I dont suppose I'll know!
Anyway - earlier I had my bi-annual appointment with the HSP clinic at the National Hospital for Neurology and Neurosurgery in London. Travel for this appointment was much easier and much less interesting this time, because it was a telephone appointment!
We generally talked around my symptom changes (more on that below) and about what would be the right change to spot that would warrant me starting to take Baclofen. It appears that this is a bit of a balancing act. It was suggested to me that Baclofen can be used to make me feel more comfortable, indicating that I shouldn't start taking it until I begin to feel some level of discomfort. Looking at various websites Baclofen works by reducing the transmission of nerve signals, thereby reducing any underlying instructions to tense. It appears that many people are affected by side effects from Baclofen, and it seems there is a three-way balancing act:
For the 2020 AGM the technical presentations were held digitally via the Zoom platform, and each one was held on a different day. This blog post covers the third, Rehabilitation and Physical Activity in HSP, presented by Dr Gita Ramdharry from the Queens Square Centre for Neuromuscular Diseases in London.
Gita began by outlining some of the aims of physiotherapy for HSP. A key part of this is understanding walking patterns, and how HSP varies peoples walking pattern. They monitor gait by looking at the amount of movement in muscles and joints, and compare those with HSP against those without. There are two types of muscle stiffness - active stiffness, where there is spasticity and spasms in the muscle, which is caused by issues in the nerve pathway - and passive stiffness, where the muscle tissues become stiff or stuck-down, with stiffer muscles becoming shorter.
They found, as an example, that during walking the knee does not bend as much for those with HSP. One of the factors leading to this was passive stiffness in the calf muscles. Passive stiffness can be relieved by stretches and splinting, whereas medication (e.g. Baclofen) can relieve active stiffness. Another factor affecting the knee movement was weakness of the calf muscle - if you dont get as much of a push up from the calf muscle, the knee doesnt bend as much. Weakness was also found in other muscles as well. Strengthening exercises can be used to regain some strength in muscles, for example using a resistance band (Gita mentioned Theraband: https://www.theraband.com/), weights, other exercises or functional electrical stimulation (FES). Physiotherapy for those with HSP is a combination of managing stiffness with either stretches or medication (depending on the type) and undertaking exercises to keep muscles strong.
Next Gita talked about general fitness and activity, and aerobic exercise, noting that physical inactivity is responsible for 1 in 6 deaths in the UK (https://www.gov.uk/government/publications/physical-activity-applying-all-our-health/physical-activity-applying-all-our-health). Gita also found a study into Charcot Marie Tooth (CMT - a related condition to HSP) showing that there is a relationship between peoples body mass index (BMI) and the amount of time they do nothing (i.e. are sedentary) irrespective of if they had CMT or not. She has found that there hasn't been much research done into the benefits of aerobic exercise in those with HSP. She reported a study undertaken in Norway (https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0469-0) which showed that people with HSP spent more of their day sitting than those without HSP, and the next element is to look at the impact of this inactivity.
A recent study looked at the impact of impact of inactivity on symptoms of those with HSP from Covid-19 lockdowns in the Nederlands (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339095/). The study showed that where people carried on with physical activity as before lockdown there wasnt much change in their symptoms. However, people who said that they were less active during lockdown reported worse symptoms. This provides a backdrop to discussions around why people need to keep themselves active.
The next part of Gitas talk covered the Physical Activities in Rare Conditions Collaboration (PARCC) project. Gita began by defining that physical activity is an all-encompassing term for any physical activity which you might do - sports, household activities, gardening, general movement (etc.) whereas exercise is a sub-set of this, which is planned and structured with an aim to improve as aspect of health.
The PARCC programme began by identifying what was important from those with HSP and other related conditions - Ataxia, Muscular Dystrophy, PSP, Huntingtons, MSA and Motor Neuron Disease. There were a lot common issues between these conditions, both in symptoms and in accessing facilities and difficulties in finding information. The first step was to identify barriers to undertaking physical activity. Common themes were around how healthcare and community facilities are organised, communication with healthcare/fitness professionals, carers and others. There was also common themes for individuals around motivation, worries and knowing what they should be doing.
A scoping review of published works showed no papers around exercise in HSP. So, there is a need to assess this. It was found that from a patient perspective the important aspects to measure for a physical activity scheme are physical wellbeing, psychological wellbeing, and being able to participate in activities. The next stage is to then develop the on-line tool for the project, which will have a range of tools, materials and stories. The project will also offer some one-to-one coaching in how to choose what to do to help with making lifestyle changes to become more active. A grant application has been made for this project, and if the grant is made then work will start!
You can watch the whole presentation on YouTube: https://www.youtube.com/watch?v=VVEi0VZdtS0&t
There were a few interesting things in the Q&A.
In a discussion around muscles, Gita explained that muscles work most effectively in certain range of the joint movement, and that you are more likely to notice stiffness at the extreme ends of the joint movement.
A question was asked about Revitive power plates. Gita explained that these work in a similar way to functional electrical stimulation, and that needs an intact nerve to work well, so can work well for those with pure HSP or where their nerve degradation is only in the spine, but are less likely to work well when you have nerve damage in/near the muscles.
A few questions were asked about PARC, and Gita explained that should the grant be successful the initial work would cover the four conditions: HSP, Ataxia, Muscular Dystrophy and Inherited Neuropathies. It was also asked how PARC would be certain to get a representative spread of the HSP population. This is partly to do with the numbers of participants, but Gita also emphasised that the program will give every person their own intervention, agreed in discussion with the skilled therapists, so all plans may look different to each other.
It was asked if there might be anything useful for HSP patients in the Bridges Self Management site mentioned (https://www.bridgesselfmanagement.org.uk/) - There might be - go and look!!
For the 2020 AGM the technical presentations were held digitally via the Zoom platform, and each one was held on a different day. This blog post covers the second, Insights from a large regional HSP cohort, presented by Dr Channa Hewamadduma from Royal Hallamshire Hospital in Sheffield.
Channa began with a brief introduction to HSP, acknowledging that it is very variable between patients. He described that the SPG genes are numbered in the order of their discovery, and it took a long time to identify the gene for SPG3 and as a consequence this is called At-Last-In or Atlastin!
The spasticity in HSP is due to the degeneration of the motor axons in the spinal cord. He described that, as a parallel, if the diameter of the motor axon were the diameter of a football, then the length of the axon would be 7 football stadia!
Understanding the potential effects of HSP on an individual requires knowing about which type of HSP the person has. In a cohort of HSP patients some will have a family history, but many will not, they are the first person to be affected. The Sheffield cohort has 420 patients, with a clinical dataset for 371 and a gene identified in 211. Of those with a gene identified about 60% are Spast/SPG4 and around a quarter are Paraplegin/SPG7. SPG7 was thought to be rare, but may not be. SPG7 has a later onset. Cerebral palsy has been a common misdiagnosis for younger HSP patients.
More than 40% of patients have bladder involvement and around 40% have pain or spasms. More than half of people with complex HSP have optic atrophy. With optic atrophy problems are spotted when the vision is challenged.
SPG7 is one of the genes which shows the spectra of the different overlaps with other conditions and effects. 10% of those in the Sheffield ataxia clinic have SPG7. SPG7 was discovered in 1998. Sheffield has 55 SPG7 patients, and there is a spread between those with HSP, those with ataxia and those with both. The mean age of onset is 42 years.
Further detail was given on optic atrophy. If people are less able to move their eyes they may have been told they have had a stroke rather than have HSP. Optic atrophy in HSP may mean that people are not able to move their eyes equally in every direction. They are hoping to be able to use this as a biomarker for HSP.
An analysis of published data shows that the age of onset of HSP varies with where the mutation occurs within the gene. If the patient has inherited the same mutation from both parents then their onset may be later than if the patient has inherited different mutations from each parent. If the mutation is sufficient to prevent the protein from working (loss of funciton), the patient would have greater spasticity.
Channa described the in-clinic process for patients, getting an assessment of spasticity, coordination, visual, mood, gait and more. They have a range of interventions available. They are planning to identify the potential for a gait biomarker, to look at the natural progression of HSP and look at the differences between types of HSP.
They have been experimenting with a single sensor gait monitoring, worn on the lower back, which can be used to see how the gait has been affected. Some data was presented looking at a 10m walk test, where a person stands, walks 10m, turns, returns and then sits. Those with SPG4 tend to have more problems standing up, whereas those with SPG7 have more problems sitting down. The gait analysis can also spot effects in mildly affected, which gives them a "trial ready" group of patients.
They are hoping to be able to analyse differences in neuro-imaging to help predict how HSP could progress in an individual.
They are also working on a drug screening programme, looking at the effects of different drugs on cells, from SPG7 , using drugs identified through re-purposing programmes. A high content imaging screen is used to differentiate between cells and controls.
You can watch the whole presentation on YouTube: https://www.youtube.com/watch?v=s3qZqLnNpBY
In the Q&A there were a few interesting points.
There is no difference between the terms paraplegia and paraperisis.
There are differences in the mutations in specific types of HSP around the world.
Some people get benefits from co-enzyme Q10, some from CBD oils and some from gluten free diets. A study is planned around the gluten free diet.
For each type of HSP there can be many different mutations. Some of the mutations are more common than others, and there is some variation in the mutation type/location in particular parts of the world.