Review of 2020

 Annual Review: 2020

Yet another year has passed, and again I take the opportunity to reflect on the various activities throughout the year. I'll only mention Coronavirus a few times!

Knowledge

2020 has been a bit of a hectic year for me, and I have not really been paying much attention to newly published research findings. I also know that many aspects of research have been slowed down as medical staff have been re-deployed to help with Coronavirus. Reviewing the 2020 publications will be on my early 2021 list!

Symptoms

My changes this year have been fairly subtle. I perceive that when looking back over the whole year there have been some changes, but they have occurred slowly and gradually. This year I have noted that my bladder and bowel are becoming more urgent in their demands for me to go to the toilet, which means that I might need to review my medication next year. I perceive that my walking speed is slower (as measured by needing to walk faster when taking my boys to/from school), and I know that I need to sit down after less time standing/walking than I have done previously. I think my flexibility and muscle strength are about the same, but I think they might be on the change soon. I had a telephone appointment with my neurologist this year. My next appointment will be 2021 rather than 2022.

This Blog

I'm really pleased with the continuing growth in readership of this blog. My audience remains broadly the same (predominantly UK, USA, Canada, Australia, and then European countries, particularly France and Netherlands, as well as Brasil and India). The most popular posts continue to be the questions for and results of my survey, as well as my general posts on research and particular HSP symptoms. 2020 also saw a high interest in my Coronavirus post from March.

I'm really pleased that blog posts continue to be linked to and used within other HSP and RareDisease communities and publications. Thank you to all my readers, including those that give comments appreciating what I have to say. Feedback like this gives me another reason why this is a worthwhile thing to do. Thank you to anyone that makes a comment or connects up with me in some other way. 

Survey

The annual pattern of my surveys is well established. My 2020 survey has a similar number of responses to my 2018 and 2019 surveys. The 2020 survey uses the same path as 2019, where the survey is available in several languages, so people can answer in their own language. There has been more collaboration across countries getting the questions right. The new feature for this year is to try to identify needs, and I have tried to capture some Coronavirus perspectives as well. Results will be out on 28th Feb after the majority of analysis during January.

Community Contribution

HSP Community activities for 2020 included:

• Starting up a YouTube channel for the Support Group
• Encouraging digital meetings for the Support Group
• Carrying on with the Enable disability network at work
• Representing the UK at EuroHSP
• Analysing and reporting the results of my survey to share with the HSP world
• Continuing this blog and posting/discussing HSP things on twitter
• Working with PARC on the latest grant application

The main element of my community contribution comes from being chair of the HSP support group. Whilst we are getting various issues resolved, there are still many to go. I'm working with the rest of the trustees to ensure that the group continues to support its members in the most appropriate way.

Understanding Upper Motor Neuron Health - Dr Ozdinler

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!

   

Rare Showcase 2020 Lightning Talk

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:

• What is HSP
• How does HSP affect people
• Available support networks
• The approach to needs identification
• Some early results

You are welcome to look at my slides here: https://drive.google.com/file/d/19kLBCvra33y0Vut5jH9WFxouywd8Kz8C 

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:

A week of publicity!

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/

HSP on YouTube

 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:

ERN RND

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	https://www.youtube.com/watch?v=GlmsbKSLTOA
Gait rehabilitation in people with HSP	https://www.youtube.com/watch?v=xR_7A-JVB-E
How to assess and manage spastic gait in rare diseases?	https://www.youtube.com/watch?v=sqznUcJXGsI
Hereditary Spastic Paraplegia (HSP) clinical disease course	https://www.youtube.com/watch?v=vEh4JXi3f9E
Treatment of spasticity in HSP	https://www.youtube.com/watch?v=NzceL8JDwes

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 

SP Foundation

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	https://www.youtube.com/watch?v=kNxbhCuAOj0
SP Foundation: Virtual Conference Day Two June 27, 2020	https://www.youtube.com/watch?v=IFUBvOZIpbA
Path to Improve Upper Motor Neuron Health	https://www.youtube.com/watch?v=MC6NORfD9uk
Genetic Topics in HSP & Related Diseases	https://www.youtube.com/watch?v=_Zd3Kp5n7eI
HSP: Understanding What's Wrong So That We Can Fix It	https://www.youtube.com/watch?v=C3EmaLMSGTY
Research Advances in the HSPs	https://www.youtube.com/watch?v=61U-Xm42N6o
A Multimodal Strategy to Finding a Cure for an Ultra-rare Disease	https://www.youtube.com/watch?v=nDOyw7qX_uw

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) 

2020 Survey Open

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.

The focus for this years survey is: 

• Participation and Activities
• Needs for those with HSP
• Access to healthcare

Similar to recent years the analysis of answers will take into account both mobility and wellbeing. I will collect answers until approximately the end of 2020, with results published on Rare Disease Day 2021 - Sunday 28th February.

As with previous surveys only "name" and "country" are required questions. Answer all others that you want. The survey is a similar length to those in previous years, so hopefully would take a similar time.

For the "needs for those with HSP" questions, I am seeking your opinions on what types of information are most important, which makes a change from the usual factual style of questions. I hope that these questions work well!

Language	Link	Responses 3 Jan
English	https://forms.gle/GdYMemqa6qwrmEEz5	176
Portuguese	https://forms.gle/rACyCU77c9xvjWa87	66
French	https://forms.gle/wS2ao4quXwU1r9ax7	47
Dutch	https://forms.gle/UtYyGDG4GPBj8hh79	28
Italian	https://forms.gle/yttKzSpfVzfrgpZN9	11
Spanish	https://forms.gle/LBWPcMEz6PA5trnD6	6

3rd January

Just starting to look at analysis now. Compared with last year I have:

More responses from: Netherlands

Similar number of responses from: Belgium/Italy/France/Canada

Fewer responses from: UK/USA/Australia/Spain/Brasil

I am happy to have more results in the next few days - especially from those areas with fewer responses!

23rd December - Brief Analysis of ~200 answers.

Here are some results from ~200 answers in English and Portuguese. I would love more answers, a few more will take me over 300 in total. People in UK, USA and Brasil form the bulk of people in this analysis.

About 80% of people consider themselves to be disabled, with similar proportions in all areas of the world.

Some 15-20% of people consider they know HSP very well, with another 40% knowing it well. Most of the remaining 40-45% know HSP somewhat rather than not at all. People feel that healthcare professionals do not understand what it is to live with HSP very well, with 10-15% understanding very well, 15% understanding well, and almost 75% somewhat (<50%) or not at all (~25%). Understanding of HSP seems lower in Brasil than in UK/USA. Nearly 40% were not given a description of HSP when diagnosed, with fewer in UK getting description than in USA/Brasil.

Some 15% of people have had surgery for their HSP, with the two most common types being tendon release surgery and placement of a baclofen pump. Surgery seems most prevalent in USA and Australia.

Some 60% of people have had fewer appointment as a result of Covid-19, and only 5% having more appointments. The availability of digital appointments has increased as a result of Covid-19. Almost two thirds say they were not available before, reducing to around one third after. Before Covid-19 only 15% were accessing digital appointments, increasing to about 55% after. The availability and take-up of digital appointments has been greatest in USA and smallest in Brasil. The key advantage of digital appointments is reduced effort travelling, and the key disadvantage is having less chance to show symptoms.

25th November - Well over 250 now!

8th November - Just hit 200 results. Here are a few early results:

• Over 50% feel the extent or severity of their symptoms was not believed by medical professionals
• Over 50% feel they did not get adequate support because they have not been taken seriously
• Over 50% did not receive a description of HSP when diagnosed with it.

Nearly 2/3 of people have had fewer healthcare appointments due to Covid-19, but there has been a big uptake in digital appointments. Over 50% feel face-to-face appointments are better than digital. The key benefit of digital appointments is reduced effort travelling. The key disadvantage is less chance to show symptoms.

Living with HSP is the most important category of needs, and the most important need is:

• Stretches and exercises that help. 

Other key needs are: 

• treatment options for spasticity,  
• information on improving mental health/wellbeing, 
• information on accessing relevant healthcare professionals 
• an explanation of HSP on diagnosis
• predicting how HSP will progress in individuals 

22nd October - Well on my way to the first 100 results. Thanks!

Clinic Visit, Baclofen and Symptoms Update

 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:

• Taking enough to cause the muscles to allow themselves to relax
• Not taking so much that the relaxation is more than is wanted
• Balancing these two against negative side effects.

It would seem that if you take Baclofen an hour or so before doing stretches then these stretches would be more beneficial as the Baclofen gives the muscles a chance to stretch longer/deeper.

An initial dose might be 5mg (half a tablet) once a day, so that the body can get used to this new drug, and then increasing the dose up to perhaps 10mg three times a day. The maximum is 100mg over a day, so there is plenty of variation possible in working out the best approach, and when to take those doses in order to get the most out of it.

We talked in general terms about my stretches, and I described that I have been modifying my stretches depending on which muscles feel stiffest. It is probably a good idea to have a review with the physiotherapist, just to make sure that I'm still doing the right sort of thing.

On the stretches front, I said that when I went camping over the summer I didnt do my stretches, and that by the end of that holiday I was starting to feel some discomfort in my legs, particularly my calf muscles. They were feeling tight and uncomfortable. Once I finished camping I re-started my stretches and the discomfort has gone away. It is my view that my stretches are really important to keep my mobility going as long as possible. 

I also explained about the level of activity which I do, and how I do need to stop for a rest every now and again, and I feel I may be on the verge of needing one walking stick. Essentially HSP isn't stopping me do anything I want, sometimes it takes me a little longer to do it. (I noted that I cannot really run, but equally I don't really want to run either). I also think that keeping active and moving about is important in keeping my mobility going as long as possible.

The general conclusion from this chat was that I seem to be doing the right things. Lower back pain was mentioned, which is something which many suffer from. The suggestion was that the lower back pain may come from your body having to use different muscles to walk as mobility decreases and legs become stiffer, so that is another thing for me to look out for. I was advised to keep an eye out on my posture whilst sitting. This is something I'm doing anyway because my job involves using a computer all day, and working at home during coronavirus, has meant that I've reconfigured my desk to be better, and I've bought a better chair to use. Sitting posture has also been mentioned to me before, back at previous consultations, and we pick up on that in Pilates as well.

Summary: Still not ready for Baclofen, Review stretches with Physio, Keep active, Keep stretching, Posture!

  

2020 AGM - Rehabilitation and Physical Activity in HSP - Dr Gita Ramdharry

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.

Physiotherapy 

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.

Fitness and Activity   

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.

Physical Activities in Rare Conditions Collaboration

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 

Q&A

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!!

 

2020 AGM - Insights from a large regional HSP cohort - Dr Channa Hewamadduma

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.

HSP

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.

Inheritance and Optic Atrophy 

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.

The Sheffield Clinic 

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.

Future Plans

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 

Q&A

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. 

  

2020 AGM - A Eureka Moment - Prof Andrew Crosby Dr Emma Baple

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 first, A Eureka Moment, presented by Professor Andrew Crosby and Dr Emma Baple from Exeter University. They presented together, alternating between sections of the presentation. 

Andrew began by explaining that his interest in HSP stems from his belief that its later onset and slower progression make it the kind of condition where it is possible to slow or prevent progression.

HSP

Emma gave an overview of HSP, noting that the differences between the types of HSP is very large. The common feature is progressive lower limb stiffness and weakness, but beyond that it is difficult to draw conclusions about how a person is affected. HSP is a condition which affects the upper motor neurons, which sit in the spine and provide the connection between the brain and the lower motor neurons which then connect to muscles. The symptoms of HSP are progressive because of the gradual deterioration of the upper motor neurons over time.

Over 80 different genes have been identified for HSP. Overall we have some 22,000 genes in our DNA, each making a protein which is responsible for the development or function of an aspect of us. A spelling mistake in a gene can cause it not to function, and HSP is often associated with spelling mistakes in the genes which are part of the operation of the upper motor neurons. 

The team at Exeter have been responsible for identifying 15 different HSP genes to date. They are also looking into commonalities between types of HSP.

When they see someone in clinic with HSP that person often wants to know if they will develop HSP or not. Particularly people want to know when they will develop symptoms, how HSP and symptoms will develop over time, and what will the effect of HSP be on their lives. A genetic test can answer if someone will get HSP, but it is only the first step.

Fat Processing

The function of most of the genes which are affected in HSP are not know. However, the function of the gene which is responsible for SPG5 is well known. SPG5 was discovered by the Exeter team. The function of the gene is known to process fats within a cell in a specific particular way. From this, we can be sure that this fat processing pathway is important in the way that upper motor neurons work, and that disruptions in the pathway can cause HSP.

The next step was then to see if the other HSP genes were also involved with the same or similar fat processing pathways. It was found that many of the other HSP genes are responsible for the same or similar pathways as SPG5, and this hypothesis has been published in Brain: https://academic.oup.com/brain/article/143/4/1073/5679762 

Additionally, there are similarities and overlaps with HSP and other degenerative motor neuron conditions - which means that if a treatment can be developed for HSP it may also benefit those with other similar conditions.

Various work is being undertaken which is showing that the hypothesis is most likely correct. The work has involved cellular models and new methods to analyse fat processing pathways so that the effects of each HSP gene in the fat processing pathway can be investigated.

Future Plans

Their future plans are to allow a completely different approach to testing. At the moment tests are looking for the specific known HSP genes, whereas the new understanding allows the test to look at the fat processing pathways instead, which avoids the uncertainties with interpreting genetic test results. They are hoping to be able to do this from a standard 10ml blood sample. 

The approach to potential treatments also varies. The aim is to look for treatments which have potential to alter the affected fat processing pathway. Any that are found can be tested in a clinical trial. The crux of these two things is that they would expect to see an improvement in the fat processing pathway with a treatment, and that improvement should be detectable from the blood test. The detection of the improvement from the blood test should be more certain than seeing a change in how HSP afffects a person with their day-to-day symptom variation. Essentially the fat processing pathway is a biomarker for HSP.

Q&A

From the Q&A at the end there were some interesting questions.

A question was asked around gene editing - this is a lab-based technique for editing one cell. These techniques cannot be used in the bodies, so it is a tool for studying rather than a tool for altering someones DNA in the body. 

Although this presentation talks about fat processing, this is not the same as the levels of fat in your diet. The management of fat/cholesterol in the blood is not the same as the processing of fats/cholesterols in the cells. There is no evidence which links levels of fat/cholesterol's in the body with HSP, although there are several with HSP who also have issues with digestion. This is an area where further investigation is needed.  

    

Symptoms update: The bowel story

Here's a summary of my bowel story - not so much of an update, but more of a recap.

For a few months prior to my first visit to the National hospital in London (2014) I'd been experiencing some bowel urgency issues - basically not being able to get to the toilet quickly enough. This had been happening about once a month, and had been a symptom which had been getting more often. I'd been devising various coping mechanisms - basically carrying extra pants around with me (generally, as well as the "plus one" rule on packing for trips away). Unlike my bladder problems I'd not been experiencing bowel frequency issues. I mentioned this to my GP, and then again at the National.

Another notable feature of my bowel habits is the "two part poo" - where I have a poo as normal, but after this has come out I know that there is more to come out, but I also know that the sphincter has closed and it will be some time before "part two" is going to make an appearance. So, rather than sitting on the toilet and waiting/forcing the rest out I get on with life, knowing I'll be back in a little while. Back at that time the "little while" might be half an hour or so.

I've mentioned various bits of this previously:
First Nov 2013: http://hspjourney.blogspot.co.uk/2013/11/symptoms-update-illness-tiredness.html
Second Jan 2014: http://hspjourney.blogspot.co.uk/2014/01/a-trip-to-doctor.html

Following the trip to the National I had a referral to the "colorectal" team, which I've also previously described: http://hspjourney.blogspot.co.uk/2014/11/a-trip-to-doctor.html.

I have noticed that since taking my bladder medication the bowel issues are pretty much entirely under control, as noted here: http://hspjourney.blogspot.co.uk/2015/02/bladder-medication-update.html

However, that is not the full story....

At one of the clinics I went to they did an anorectal physiology test. This was way back in 2015, and I'm not entirely sure why I've not blogged about this before. The test measures how well your anal sphincter is functioning, and they do this by measuring the pressure inside the bowel, and after that they inflate a balloon in the rectum and ask you to hold on for as long as possible!

The pressure tests were all good for me. The internal sphincter was well above their ball-park indicator, which is a good sign as I am less likely to develop some problems in the future. There were also no worries on the external sphincter.

However, the sphincter didnt relax as easily when I tried to squeeze, and this was described to me as being a bit like trying to get toothpaste out of a tube but with the lid still on - i.e. no matter how hard you squeeze, nothing is going to come out.

The balloon test (known as a balloon expulsion test) was interesting. Essentially the balloon acts like a stool, and the body should then feel the need to go! My sphincter took longer to sense the balloons presence than average - usually this is done within about a minute, but it took about 2 minutes for me.

The advice I was given was to bring my knees up whilst having a poo. I had a follow-up appointment after this, but as the problem had more-or-less gone away we didnt take things any further. Essentially, if things do start to get worse I have a direct route back.

On reflection I think that I have noticed both of the effects mentioned in the tests - Sometimes I know I need a poo, but I can sit down and nothing will come out. The delay in sensing that a poo is there would appear to me to be the urgency issue explained - i.e. the pressure continues to build up, and I only get 'action' when the pressure is so high that I dont have enough time to get to the toilet and the sphincter is going to operate itself.

In the intervening five years (since I've been taking the bladder medication) the issue has generally gone away. There is still the odd time that I cant get to the toilet quickly enough, but this might be one or twice a year rather than roughly every month. The two part poo is still a regular feature - I think that the gap between the two parts is getting longer, and the half an hour I noted back at that time might now be a delay through to the next day sometimes.

Re-reading my notes from the time I also spot that they recommended that I try to regularise my toilet trips so that I can get into a regular routine. This does happen some of the time, but it is more by luck than design. Perhaps another task to put into my daily routine. 

HSP on YouTube

So, this post is a cross between my blogging life, which you know about from previous posts, and my HSP Support Group hat, which I have mentioned previously here.

A while ago I had found a couple of videos from people with HSP on YouTube. I had bookmarked them with a view to writing a blog post about them one day. Those videos are still relevant, and you can read more about them further down the post!

However, coronavirus came to town, which meant that the Support Group was not able to hold its AGM face-to-face this year. Fortunately we were able to hold it electronically, which we did using Zoom - this was a great success - the digital AGM ranking highly in our all-time number of attendees list. My previous blog post was my usual summary of AGM post - and you can read that here: https://hspjourney.blogspot.com/2020/07/uk-hsp-support-group-agm.html

But, the story doesn't finish there, we had a quick discussion and decided to make a YouTube channel for the group, so in a few clicks I move from being someone who aspires to make a blog post about HSP content on YouTube to actually being one of those people making such content! (note - I'm using this phrase in the loosest possible sense - the AGM is a team effort). As I write the only video is the AGM recording, but we will add more videos as our digital journey develops. For those who wish to jump straight to the channel, go here: https://www.youtube.com/channel/UCkxTfcI4tKYNMYsgzVumpWA

The description of the AGM includes a few time pointers - the full list is here:

03:27 - Chair report

05:05 - Coronavirus and meeting changes

06:43 - Meetings and conferences attended

07:29 - Our new website (feel free to play!)

08:13 - Honorary members

09:05 - The David Pearce bequest

10:53 - Award presentations

12:31 - Ambassador

15:30 - Funding of research

16:10 - Help that the group needs (here!)

17:30 - Secretary report

19:02 - Membership secretary report

22:30 - Treasurer report

28:00 - Voting on reports

29:53 - Trustee elections

32:32 - Any other business

33:40 - The 2021 AGM

34:23 - Upcoming HSP presentations

So - if you wish to go and watch - go here: https://www.youtube.com/watch?v=J1yBY0wPm1o& - and dont forget to like and subscribe!!!

So, back to my original idea about writing a blog post on YouTube content - I had thought that I'm unlikely to be the only person seeking out information on YouTube about HSP, and a couple of people I know with HSP have made or been in such videos. I lost a few hours searching, clicking and watching HSP videos on YouTube, and I have started some playlists on the channel so that others searching for HSP can find them. At the moment there are three playlists, but as new videos come to light I see this changing. The first three are:

Those with HSP: https://www.youtube.com/playlist?list=PLM0_-wMVB0ncw1aG3ONLtJPL9nF_TzrKg - Various personal stories about HSP

HSP information: https://www.youtube.com/playlist?list=PLM0_-wMVB0ndjbS0gk7sHsn-Celr2LjL1 - videos which present more medical aspects of HSP or research into HSP

Potato Pants festival: https://www.youtube.com/playlist?list=PLM0_-wMVB0ncCvH6daKN2v9oMgw7Kxw5m - This festival is run in Dorset by Ian Bennett to both have a good time and to raise awareness about HSP and also raise a little money for the group. The live festival has had to take a coronavirus pause this year, so the videos of previous years seemed like a good reminder.

Finally, the channel also contains links to a load of other relevant channels, so if you're using YouTube to look for further information, then this might be a good place to start: https://www.youtube.com/channel/UCkxTfcI4tKYNMYsgzVumpWA/channels

If you can recommend any other videos or channels with an HSP connection, please drop me a line - the playlist and channels is very much a work in progress.

Enjoy your viewing!!

 

UK HSP Support Group AGM

A couple of weeks ago the UK HSP Support Group held its AGM. Due to the effects of Coronavirus it was held on-line via Zoom. Group members and regular readers will note that the AGM usually has the official business first, followed by a series of presentations. The on-line AGM covered the official business part of the AGM only, with the presentations advertised for later in the summer.

Of course, I write this post wearing my chair of the group hat, and the us/we references are about the Support Group. You can read a summary of activities below, but if you'd prefer to watch a recording of the AGM, read my latest blog post with links and more details: https://hspjourney.blogspot.com/2020/07/hsp-on-youtube.html. Written summary:

Activities as usual:

• Welcoming new members to the group
• Meetings
• Member and researcher grants
• Newsletters (all on website)
• Attendance at HSP and Rare Disease meetings (January 2020 Newslink covers most)
• Asking for people to help (new page on website)

New Activities:

• Digital Meetings - needed to do this due to Coronavirus
• David Pearce bequest - details of the bequest and how we are using it - including two new awards
• New committee structure has started up
• Searching out new honorary members - healthcare professionals who work with HSP patients
• The new group website has gone live
• Existing group profile on FaceBook, and new ones on Twitter and LinkedIn 

Thank You!

It was important to recognise and thank all those who had contributed to the group during the year:

• Members - Without members we wouldn’t be here
• Volunteers - Their valuable time makes this group work
• Fundraisers - Activities raise funds and awareness - Amazing!
• Researchers - Their work gives us hope

Award for fundraising

This year, the award is given to Peter Bateman who over the period 2011 to 2019 raised over £10,000 for the group. He did this by providing HSP Group customised key rings and pens together with collecting boxes at hotels and golf clubs etc. near where he lived, his regular replenishment and cash collection no doubt helped in delivering this fantastic amount for us.

Award for raising awareness of HSP

This award is given to Lily Rice who has used her situation to great advantage in becoming the first European person to complete a wheelchair backflip. She has become a mentor to other young people who are coming to terms with life in a wheelchair and uses these opportunities to raise understanding and awareness of the condition and of the Group. Lily was on BBC1 a couple of weeks ago, and I encourage you to watch her episode of Our Lives, Defying Gravity on BBC iPlayer.

Ambassador - Amber Meikle-Janney. 

Last year at the AGM we made Amber our first ambassador for the group, and Amber was really pleased about this. Amber works with the charity Back-up, which helps people with spinal cord injury. Amber teaches wheelchair skills, and when working for the charity has an honorary spinal cord injury herself. These courses are great because they help people do more with their wheelchairs, and it helps people to see them as a benefit more than a burden. 

Research Grants

We received three grant applications recently and have used our newly developed assessment procedure

to successfully evaluate them. We have been able to provide funding for all 3 applications received:

• University of Exeter – PhD student working on biomarkers, aiming to develop a predictive HSP blood test, applicable to all types of HSP.
• University of Sheffield – PhD student working on biomarkers and gait analysis for SPG7, aiming to develop predictive measures.
• Institute of Molecular Biology and Pathology, Rome – Work on predictive biomarkers for SPG4

Elections

Two Trustees, Adam Lawrence and John Mason were at the end of their present term and are standing for re-election. Mitesh Patel is standing for election for the first time.

• Adam Lawrence was re-elected by a unanimous vote.
• John Mason was re-elected by a unanimous vote.
• Mitesh Patel was elected by a unanimous vote.

Presentations

On-line presentations will be given as follows by speakers we had arranged for the AGM:

• Saturday 25 July - Prof Andrew Crosby and Dr Emma Baple are going to be talking about their work on cholesterol processing which was published in the neurology journal, Brain last year. They will also talk about their plans for the future.
• Saturday 1st August - Dr Channa Hewamadduma is going to talk about the work that him and his team undertake in Sheffield, looking at some of the insights and learning they have gained from their approaches to working with a large cohort of HSP patients. 
• Tuesday 11th August - Dr Gita Ramdharry will be talking about the Physical Activities in Rare Conditions. She will also cover more general aspects of rehabilitation and the importance of physical activity for those of us with HSP.

10 years of blogging!

It was on 23rd June 2010 that I wrote my first blog post here. I didnt know at that time what I was really planning to do. I had decided that two posts a month would be a good level of posting, and 261 posts later I think that was the right decision to make (there have been a few months where I have posted more than twice!).

Interestingly, FaceBook told me earlier that 23rd June was also the date when I put mu my first poster at the Spatax meeting in 2016, so it looks like this may be a memorable date for me!

If you'd like to go back to where it all began - follow this link: https://hspjourney.blogspot.com/2010/06/my-history.html

If you'd like to see about my 2010 Spatax poster - follow this link: https://hspjourney.blogspot.com/2016/06/international-meeting-on-spastic.html

What with Coronavirus taking a fair proportion of my time (in one way or another) since March, I've not really had a chance to make lots of noise about my survey results - I'm planning to do that a bit more after the AGM for the UK Support Group (4th July - https://hspgroup.org/) and before I launch my 2020 survey in September.

My 2019 survey results are here: https://hspjourney.blogspot.com/2020/02/2019-survey-results.html

The key points on medication is that there is no single point source of information for this, and many drugs that people are taking dont have published results showing benefits for those with HSP. Regular travel, music and exercise were shown to suggest better wellbeing, and being lonely/isolated and needing to take many medicines suggested lower wellbeing.

I'd like to thank everyone who has taken the time to read my blog posts over the years - regularly, occasionally or just by chance! I get lovely feedback, and I am pleased to know that what I say helps others on their journey with this Rare Disease!

HSP pain

This post is another one where I explore a symptom of HSP - this time pain.

My 2013 survey showed just under 80% of people with HSP had back pain, with similar results in my 2018 survey. I looked in more detail at pain in my 2017 survey, where around 80% of people get some pain with their HSP. Of these, over 95% have some pain in their legs, over 90% have pain in their feet, and over 80% of have some pain in their back and hips.

There are a few published papers on this:

Out of 109 people with HSP in The Netherlands with pure HSP in 2020, 72% reported leg and/or back pain: Experienced complaints, activity limitations and loss of motor capacities in patients with pure hereditary spastic paraplegia: a web-based survey in the Netherlands - 

https://ojrd.biomedcentral.com/articles/10.1186/s13023-020-1338-4

Depression and pain were significantly increased in a study of 118 SPG4 patients in Germany in 2020: Non-motor Symptoms Are Relevant and Possibly Treatable in Hereditary Spastic Paraplegia Type 4 (SPG4) - https://pubmed.ncbi.nlm.nih.gov/31646384/

A study of 108 people with HSP in Norway in 2016 reports that those with HSP more frequently report musculoskeletal pain compared with controls: Health survey of adults with hereditary spastic paraparesis compared to population study controls - https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0469-0

34 patients with SPG4 in Brazil reported higher pain, fatigue and depression than controls in 2016: Non-motor Symptoms in Patients With Hereditary Spastic Paraplegia Caused by SPG4 Mutations - https://pubmed.ncbi.nlm.nih.gov/26806216/.

My 2017 survey showed that most people use medication (either prescription or over the counter) or physical therapy (either exercise, manipulation or massage) to relieve pain. 

Heat and cold therapy, relaxation techniques and TENS machines are other methods used by at least 10% of respondents. The average number of methods used to treat pain is 3, showing that most people use more than one method to control their pain.

There were no common trends between the choice of medication and use of mobility aids, with all of the most common methods of pain control being used across the full range of mobility scores.

Furthermore, people who do not get pain from HSP have a better wellbeing than those who get pain from HSP.

My 2019 survey looked at medication. Respondents taking medicine for pain form the second largest group of around one fifth of all the medication being taken (the biggest group being medication for spasticity and spasms). The pain medication being taken falls into two main groups, one group is for pain, whereas the other group is for nerve pain, pain from spasms, and other HSP symptoms.

The first group (pain) includes common pain medication, some of which is available over the counter, e.g. paracetamol and ibuprofen, and others are prescription medication like fentanyl and morphine. Further analysis of that group was not undertaken.

The second group includes some medications that are used to treat effects of HSP, and these include:

Pregabalin/ Lyrica, Duloxetine, Pramipexole, Oxycodone, Nabilone and Nabiximols. Whilst there are no papers reporting these drugs for use in HSP all but Nabilone are indicated as potential treatments on some HSP websites.

Links to my surveys mentioned:

2013: http://hspjourney.blogspot.co.uk/2014/02/hsp-survey-results.html
2017: http://hspjourney.blogspot.com/2018/02/2017-survey-results.html
2018: https://hspjourney.blogspot.com/2019/02/2018-survey-results.html
2019: http://hspjourney.blogspot.com/2020/02/2019-survey-results.html

Until recently pain as an HSP symptom was routinely experienced by people with HSP but there were no published papers identifying this as a symptom to the wider healthcare community. 

Fortunately this issue is beginning to be addressed - the 2020 paper from Germany concludes: "We recommend that clinicians regularly screen for depression, pain, and fatigue and ask for bladder, sexual, and defecation problems to recognize and treat non-motor symptoms accordingly to improve quality of life in patients with SPG4." It is my opinion that this approach would work well with other types of HSP as well.