Friday, 16 September 2016

Autumnal Survey 2016

After the success of my previous surveys, and feedback from readers and others, I'm continuing the pattern with another survey this year.

My main focus for this survey is understanding fatigue, which many with HSP suffer from. I have selected 3 different short-form fatigue questionnaires, the 5 question Modified Fatigue Impact Scale (MFIS-5), the 9 question Neurological Fatigue Index (NFI-MS) and the 9 question Brief Fatigue Inventory (BFI). I will be interested to see which questionnaire people prefer.

I also ask questions on bladder and bowel issues using the  ICIQ-OAB questionnaire for over-active bladders and some of the questions from the ICIQ-B questionnaire for bowels. Bladder issues are well known, but whilst bowel issues are reported less frequently there still seem to be many who have them. Finally, I ask about how people find out information about HSP.

Following the previous pattern, I will collect results until early 2017, then analysing these in time to publish the results here on rare disease day, 28th Feb 2017.

Also like before, all questions are optional (apart from your name and country). If you have taken part in any of my surveys before, I'd appreciate you using the same name to allow tracking. This year, I am also collecting e-mail addresses to build up a list of people interested in taking part in these surveys in future years.

I would appreciate any readers with HSP to complete this survey:

Wednesday, 7 September 2016

Spatax Meeting - Poster Sessions Part 2

This post covers some of the posters shown which I thought warranted a little more detail. There are 4:

Full post index:

Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

Canadian HSP Population

Chrestian et al from Canada reported the Canadian experience of HSP. Their poster presented the analysis of 534 patients, of which 160 had a genetic diagnosis. They found that;

  • SPG4 and SPG7 were associated with older age at symptom onset. 
  • SPG4 and SPG3A were less associated with learning  difficulties compared with other types.
  • SPG11 was strongly associated with progressive cognitive deficits.
  • SPG3A was associated with better functional outcome compared with other types
  • The strongest predictor for significant disability was abnormal MRI
  • SPG4 associated with greater risk of bladder dysfunction
  • SPG11 associated with increased pain due to HSP symptoms
  • SPG2 associated with increased risk of speech delay
  • SPG4 less likely to have motor delay
The poster also reported using the SPATAX-EUROSPA disability stage to assess disability. This scale can be seen here, in part E: The poster is based on this:

Gait Training for Ataxia
Huisman et al from The Netherlands reported the effects of a five week c-mill training for patients with ataxia. They were testing if the gait in SCA patients and healthy controls can be improved by training on obstacle avoidance and dynamic stability. The patients had ten one hour sessions over 5 weeks, walking on a treadmill with visual cues and obstacles projected onto the belts surface. The difficulty was adjusted to patients capability. The training showed that healthy controls did not improve gait speed but the SCA patients did. 

I had a chat with some about this, who were saying that the patients found the gait training to be very difficult to do, but actually the improvements in gait stayed for some time after the training had finished. This study seems to reinforce the "use it or lose it"approach to muscles, demonstrating that with some hard work it is possible to improve gait.

Wearable Stabiliser for Ataxia
Leonardi et al from Italy reported a small trial using an Equistasi proprioceptive stabiliser. on people with various types of ataxia who could walk alone or with minimal assistance. The device was worn for 3 weeks and showed improvement in gait without adverse effects. 

It is not clear how the device works, but it appears to generate localised vibrations on the skin which act as a feedback mechanism allowing the brain to modify muscle control. It is not clear how the system is set up to deliver the vibrations. The device is reported elsewhere for use in MS and Parkinsons, and I wonder if there may be applications for HSP.

Gait Patterns in HSP
Casali et al from Italy reported a study of 50 HSP patients, some with genetic diagnoses and others without. They identified 3 distinct gait patterns in patients which correlate robustly with clinical data. The poster showed that many different gait parameters were measured, however the parameters which define the groups are all to do with the range of joint movement in hips, knees and ankles.

Group 1 have a reduced ranges of angular motion for hips, knees and ankles (i.e the joints do not flex much). This group was most affected from a clinical perspective, had the most marked spasticity and walked at the slowest speed.

Group 2 had reduced ankle and knee ranges of angular motion, whereas the range of motion for hips was close to the control values.

Group 3 had an increased hip joint range of angles, with ankle and knee ranges of angular motion, close to the control values. This group was the least affected.

The study is reported as having the potential to help tailor treatments to individual needs.

The study seems to show that the progression of gait begins with increased movement of the hips. the next stage is that the angles of motion of all three joints are reduced, such that hips return to normal and knee and ankles are reduced. The final stage is a reduction (or further reduction?) in all joint ranges.

The poster also showed that progression through the groups leads to reduced walking speed, reduced swing duration, reduced cadence and reduced step length.

Thursday, 25 August 2016

Spatax Meeting - Poster Sessions Part 1

This post covers part of the poster sessions. I've chosen to give a brief summary of posters which I found interesting. I will write another post which goes into some further detail about other posters. Obviously, I'm not going to mention my own poster - thats fully covered here:

Potential HSP treatment - Simvastin
Ylikallio, Auranen, Isohanni, Lonnqvist & Tyynismaa from Helsinki reported new mutations in HSP SPG5A / CYP7B1. This gene is known to encode an enzyme involved in cholesterol metabolism, with patients accumlating 27-OH-Cholesterol. One patient was treated with Simvastin, which reduced the 27-OH-Cholesterol  with no adverse effects.

HSP/ALS Overlap
Denora et al from Inserm, Paris report an overlap with HSP SPG11 and ALS. They report neuropathological overlap and some shared clinical features. This opens up new fields of investigation.

Disease Re-classification
Goizet, Mathis, Tazir, Couratier, Magy & Vallat from France/Algeria describe proposals for re-classifying Ataxias in a more understandable fashion, by mode of inheritance, gross phenotypic and genes/mutations. They also indicate this might be feasible for HSP.

Sobanska et al from Poland report that non-motor nerve tracts are affected in the brains of some patients with HSPs SPG3 and SPG4. They report the potential for finding additional symptoms in such patients with the use of more detailed neurological diagnostic tests. They question if the types of HSP should be divided into "pure" and "complicated" any more.

Balance training
Casali et al from Italy report the investigation of the relationship between trunk and thigh movements for people with Ataxia. They report that the drop in coordination between upper and lower body impairs dynamic balance, and this this should be a target for interventions. They propose the use of elastic suits.

Cakrt et al fom Prague report the use of a Brainport balance device ( with people with ataxia with cerebellar degeneration, and describe an improvement in postural control and 2 weeks of training.

Vavla et al, from Italy report the use of neuroimaging in HSP and Ataxia identifying consistent structural and functional changes which correlate well with disease severity, with the potential for use as biomarkers. 

HSP populations 
Updates/reports on HSP populations around the world were given, with 79 patients from Greece reported as following the patterns of other European populations. 75 patients from Israel have been included in a new database. 746 patients with either Ataxia or HSP are included in a Norwegian database, and 35% of these have a molecular/genetic diagnosis.

Gene Panels
Several reports were given on the use of gene panels for HSP, 243 patients in Italy were tested with one of 2 panels of 126 or 200 genes, finding a match in 22%, and reporting some Ataxia/HSP overlaps. A group of 98 families in Portugal were screened with a panel of 70 genes, finding matches in 21%. A study looking at all 74 known HSP genes couldn't find a match in 36% of 283 HSP patients.

Friday, 19 August 2016

Spatax Meeting - Papers, Day 3

This is the fourth and final instalment of the papers presented, this time the third day. As previously, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

Evan Reid ( talked about discovering some unifying mechanisms within HSP. He noted that that there are more than 50 genes affected by HSP, but there are a few common themes across these different genes, including cell membrane traffic. Evan noted that Spastin (the protein produced by the Spast gene, and affected by SPG4) has two different forms (or isoforms). There is some redundancy between these forms, but both need to be affected for HSP to show.

Tim Newton ( talked about age of onset for HSP, noting that the HSP's with point mutations tend to have later onset than those with deletion mutations. He also reported that the effects of HSP were bigger when the deletions were larger, particularly if the deletion extended to the next gene along.

The second session focused on diagnostics.

Stefania Magri ( gave an overview of next generation sequencing (NGS) panels, noting the potential for mis-diagnosis, given that there are some overlaps between HSP and Ataxia, with the genetic test giving the opposite result to a clinical diagnosis in some cases. A joint HSP/Ataxia panel was suggested.

Sara Morais ( said that 40-60% of  families have unknown diagnoses. They checked 98 families against the most frequent HSP genes and identified the gene in 21 of these.

Lydie Burglen ( reported similar information about testing for ataxias, indicating that a gene panel would only cover about 20% of diagnoses. 

As before, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

My key takeaway points from this session are:
  • Gene panels - with the panels of the common genes still only covering some 20% of the tests, that leaves some 80% without a clear diagnosis. I perceive this to be important - particularly letting people know the likelihood of a match, and defining a process after this.
  • The genetic mutations for HSP (and Ataxia) can vary in size, and potentially affect more than one gene, with potentially more than one consequence. 

The question which came through my mind at this time was: how do the dominant transmission cases start - its fair enough to note that they transmit from one generation to the next, but they must start somewhere.

Thursday, 4 August 2016

Spatax Meeting - Papers, Day 2, part 2

This is the third instalment of the papers presented, this time the afternoon of the second day. As previously, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

Full post index:
Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

The first of the afternoon sessions focused on therapeutic approaches, although all of the papers had an Ataxia spin.

Helene Puccio ( described using computer gait analysis, and using it to investigate gene therapy in mice. One of the aspects they have been looking at is what happens if treatments are given after symptoms are showing - they conclude that if the treatment is given before the death of the neurons then it works.

Eleonora Di Gregorio ( talked about speech communication problems affecting quality of life - The symptom is dysarthria - and this occurs in some HSP's too.

The second of the afternoon sessions focused on therapeutic approaches with biomarkers, and again, most of the papers had an Ataxia spin.

Thorsten Schmidt ( talked about some work involving re-purposing existing drugs for SCA3, and gave 2 examples - Riluzole and Citalopram, both of which were tested on mice - Riluzole was not found to give any benefits and Citalopram was. They are trying to get Citalopram into pre-clinical trials.

Benjamin Cravatt ( similarly talked about drug re-purposing for HSP. He began by describing that some cell pathways for the spread of disease are known, but many are not. They are looking at potentially re purposing diabetes drugs for HSP.

In the discussions at the end of the session it was commented that patient numbers for studies are generally low, and there would be some benefit from regional/continental/worldwide patient registries. As there are overlaps between HSP and Ataxia it is good for the researchers to work together.

As before, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key takeaway points are:
  • Treatments are unlikely to be effective if given after the death of neurons.
  • Some are looking at drug re-purposing for HSP/Ataxia at the moment
  • Several Ataxia symptoms and the way they feature are similar to HSP
  • Researchers are looking for bigger/better patient registries

Thursday, 28 July 2016

Spatax Meeting - Papers, Day 2, part 1

This is the second instalment of the papers presented, this time the morning of the second day. As per day 1, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

Full post index:
Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

Day 2 was opened by Peter Bauer Peter talked about genetic sequencing and genetic testing using gene panels (i.e. a sample from a patient is tested against multiple specific genes for a match). He outlined that there are three main areas for problems in getting a genetic test, obtaining the sample, doing the preparation for sequencing, and in the interpretation of the results. The perfect genetic test would know about all possible variants and test for repeat expansions. There are guidelines for diagnostic testing: Asking predictive questions of tests can be tough when there is only limited data available - results can be ambiguous. There can be diagnostic gaps in the data - which would miss patients out who would otherwise get a diagnosis. Another issue is that such a test can show "incidental" findings - i.e. a gene is matched which was not part of the original search remit - consent is needed from the patient to find an report these findings. Peter indicated that 5-10% of rare disease patients have two different conditions. He also indicated that it would be a good idea for the Spatax network to work with the UK 100,000 genome project

There were a couple of people - Tzoulis Charalampos and Robert Roxburgh who talked about higher incidences of varying conditions in certain areas - Western Norway and Maori / Pacific Islands respectively - due to population bottlenecks in the past, also known as founder effects. Robert was talking about Canvas Syndrome - a type of Ataxia - noting that a chronic cough can be a symptom.

Rebecca Schule gave a really good overview of HSP. She indicated that the recessive HSP's have an age of onset around 1 decade earlier than the dominant types, and that there is some influence on the age of onset with the mutation type for certain HSP's. When looking at the severity of HSP, this is partially explained by the disease duration, but that only accounts for 10% of the range of severity. They have looked at how the Spastic Paraplegia Rating Scale varies with type of HSP in order to look at rate of change. They found that SPG4 progresses relatively slowly, with a change of 0.38 points per year, whereas SPG5 is faster at 0.74 points per year. You can find details here:  However, she noted that there are a load of factors which affect patients which are not assessed in the SPRS. For example, with a family there may be differences with the same mutation - perhaps a 30 year difference in the age of onset. One of the key questions is deciding when the disease starts. Another important factor is that day-to-day changes in mobility and other symptoms can be greater than the progression of the disease over a few years. There are lots of unknowns. New tools include biomarkers, gait paradigms and video gait analysis. SPG4 is a good candidate for looking at the effects of genetics and environment to understand more about the variation.

As last time, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key takeaway points are:

  • Genetic test results can be ambiguous.
  • Changes in health can be indicators of underlying problems - e.g. the chronic cough
  • Day-to-day variation can be bigger than year-to-year progression

Sunday, 24 July 2016

Spatax Meeting - Papers, Day 1

I had wondered how to present my observations from the conference, and my decision was to present by topic, chronologically - so this post covers the papers presented on the first day. The papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

Full post index:
Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

The meeting was opened - Henry Wahlig (of the Tom Wahlig Foundation) indicated that the foundation is awarding a scholarship of €120,000 over 3 years for scientists who are opening up new therapies or treatments into HSP. Further info here:

The first speaker was Harry Orr Harry talked about SCA1 (Spinocerebellar ataxia type 1), noting that the longer the delay in treatment the less able cells are to recover function.  Harry also noted a course in molecular degeneration in 2017 near Cambridge

 Andrea Burgo talked about SPG4, noting that SPG4 accounts for up to 50% of the dominant cases of HSP and up to 15% of the sporadic cases. He observed that the stability and viability of neurons depends on intracellular transport, and that axonal swelling is often associated with axonal transport defects,

Harald Stenmark indicated that SPG10 may no longer be considered an SPG.

Julien Branchu reported on research undertaken in SPG11. They are developing a mouse model of SPG11. This model is a "knockout" model, where the gene is made inactive. They observed that the mice developed gait problems similarly to patients, and they also had cognitive/brain and spinal cord impairments, which are also characteristic of SPG11. The model will allow them to understand more about the condition.

As I write this I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

Key Takeaway points;

  • The longer the delay in treatment the less effective it is
  • Animal models can greatly help the understanding of diseases

One of the terms that cropped up a lot was Purkinje cells - thse are cells that in the cerebellum which are used in processes of motor control and learning. The cerebellum is the part of the brain which has plays an important role coordinating and regulating muscle activity It is more difficult to find an accesible description of the Purkinje cells

Thursday, 30 June 2016

International Meeting on Spastic Paraparesis and Ataxias - Overview

Last week I went to the International Meeting on Spastic Paraparesis and Ataxias organised by the Spatax network and the Ataxia Study Group. The meeting was held over 3 days and there is plenty for me to report on, and this topic will be the subject of my next few blog posts. This first post covers my general observations from the meeting, and I'll get onto specifics from the different presentations and posters in later posts.

Full post index:
Papers Day 1:
Papers Day 2a:
Papers Day 2b:
Papers Day 3:
Posters 1:
Posters 2:

You can also read the spatax blog with plenty of pictures and details about the presentations and various goings on:

Before I get on to those things, a quick update on my survey to find out peoples thoughts on topics for my 2016 survey. The two clear leading topics are Fatigue and "Finding out information about HSP". I'd welcome any further comments and suggestions here, I am starting to work out my question strategy at the moment:

Back to Paris - Firstly some thanks are due. Thanks to the HSP support group for covering my expenses. My employer (Atkins: lets staff take 2 days a year leave to support charities, so thanks to them for giving me the time to attend. Thanks (obviously) to my wife for looking after the boys whilst I was out having fun for a few days!

Since I was going to be at the conference I took the decision to submit an abstract for a poster covering my survey results, which was accepted. You can see that on my research page So, thanks are also due to the people who have answered my surveys the last 3 years. Therefore, I had three topics of conversation with people - My own HSP, the results of my surveys and being part of the UK HSP group. The meeting was attended by over 200 researchers and medical professionals, and I was very pleased to have the results of my surveys up in the room for them all to have a look at. I saw many people looking at it, and I engaged in conversations with a fair few of them!

The meeting was really friendly, and I felt quite at home there. The network of researchers feels really close knit, and I was pleased to see and hear about people chatting with each other and sharing their knowledge and findings. In many respect the coffee breaks, lunches and evening social events are just as important as the presentations as they allow people to go and share ideas.

I spotted that overall there were more posters and presentations on Ataxia than there were on HSP. There was also relatively few posters and presentations on treatment and/or relief of symptoms, although it was acknowledged at the end of a couple of presentations that research on treatments may be more prevalent in the next few years.

All of the presentations (also known as papers) and posters were in English, which I was quite relieved about. It wasnt until sitting there and listening that I realised how lucky I am to be able to think and speak in English, whereas the majority of people there (from 22 countries) and having to think in one language and speak in another. The standard of presentation was high, and language did not seem to be a barrier at all.

There was a wide range of papers presented, in all sorts of fields and I have yet to piece together how all of these wide and varied topics fit into the overall HSP picture. Topics included genetic identification, proteins, bio-markers, animal models, genetic testing, cell biology, diagnostics, muscles, clinical diagnosis, symptom identification, age of onset, disease severity etc. You can probably guess that this is the "agenda" for my next set of blog posts!

I spent some time talking with the people from Euro HSP who are keen for the UK group to join. This is quite the opposite to the EU referendum held in the UK on the first day of the meeting (and reported in the second day) which resulted in the beginning of the UK's EU exit.

I think that the various patient groups need to work together, and not just the HSP groups, but those groups for people with similar conditions - Ataxia, CMT, ALS and others. I'm going to explore this further. I found out that in New Zealand HSP is covered under the group for MS, there is no group for HSP in Turkey. Within Europe the national groups have different focuses, with some focusing on fund raising and other providing support. The ataxia groups I spoke to seem to be very similar to the HSP groups, which makes me think that working together should be easy, and in France this is already done.

Speaking to various people about my 2016 survey, suggested topics include physiotherapy/stretches, bowel issues and anxiety. A few people are also looking to set up surveys of their own in their own countries.

You can see a pic of me here, with my poster - it was the first one up!

Thursday, 16 June 2016

A busy weekend - Three conferences

Next weekend is going to be a busy one.

On Sat 24th June is the UK HSP Support Group AGM, however this is the first year in 4 that I wont be going. Instead, I'm off to the Spatax networks HSP and Ataxia conference in Paris, to represent the HSP support group.

This is a combination of several things, my employer, Atkins, offers 2 voluntary days per employee per financial year, and so they are paying for my time to be there. The HSP support group is covering my conference, travel and accommodation costs. I'll simply be reporting back on what I find out.

I looked at the programme for the conference, and they were accepting abstracts for poster sessions. I put an abstract together covering my three on-line surveys which was accepted. So, for the last week or so I've been busy pulling together a poster which summarises the results of the surveys, which will be up for the worlds leading HSP researchers to have a look at.

I'll share the poster here when it is finished!

20th June Update - link to finished poster
Note. Some browsers dont seem to like this file, but you should be able to download and view in acrobat v8 or v9.
A larger but more compatible file is here:

If that wasn't enough, there is also a findacure event "How Rare Disease Patient Groups Can Work With Researchers" in the afternoon in London

So, thats three interesting and relevant meetings which could be gone to - obviously I've very excited to be going to Paris, sharing my findings and finding out about what else is happening in the world of HSP. I'm hoping to be able to tweet from the conference.

If any readers have any topics they particularly want me to find out about, then post a comment, and I'll do my best to find out.

Friday, 27 May 2016

Collecting Ideas for 2016 Survey

Hello everyone,

I'm starting to think about what to cover in my autumn survey this year. I've got a short survey which I'd welcome anyone to complete if they've got any thoughts.

Time-scale wise, I'm getting my thoughts together over the summer to launch in ~September.