Review of 2017

As we draw to the end of 2017 it is time for me to reflect on this years goings on.

Knowledge

This year has seen less new knowledge going in, but there have been several times when I've needed to look back at knowledge gained previously, thereby fulfilling one of this blogs purposes: to act as a memory dump. During the year I've looked back on my posts on depression and my work on misdiagnosis. I've also been contributing to the knowledge of others in a new way by taking part in the HSP falls study for Plymouth University (UK) and the CREATE Daily Living Scale study.

Symptoms

Generally it has been another year of no significant change. I think that my distance may be becoming limited due to HSP, but I've not tested that properly yet. 2017 has seen the continuation of tracking my cycling with Strava and I've started tracking plenty of things with FitBit, so there is plenty of data for me to look at and see if I can spot any patterns. On the other side of the coin, during the year PatientsLikeMe changed their website so I've lost a couple of trackers I found useful there. The main 'big' thing this year has been the MRI scan, but nothing on the results of that yet.

This Blog

I'm really pleased with the continuing growth in readership of this blog! My audience remains broadly the same (predominantly US, UK, Russia, Ukraine, France, Germany, Canada). The most popular posts continue to be the results of my survey, the various presentations/posters given at meetings and my general posts on research and particular HSP symptoms. I now have a full year of Google Analytics tracking to compare with the blogger tracking, so expect some analysis on that in the new year! Various blog posts are being linked to and used within other HSP and RareDisease publications, so I feel like a bit of an information conduit now. Thank you to all my readers.

I've had various comments from people appreciating what I have to say, which I'm very pleased to receive. 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. A couple of my favourite comments about the blog from this years survey are:

"I'm interested to hear how you are progressing with symptoms as I feel like the only guy on earth that has this condition. Your blogs make me feel like I'm not alone"
"Great to read how you approach every day problems"
"It is superb and very informative - I have gleaned a lot of useful info over the past few months and hope to be able to put much of it into practice now I know what I am dealing with."

Survey

The now annual pattern of my surveys is well established. Each year I get more responses than previously, and this year is no exception. I've now got around 190 responses to start analysing in 2018, which is brilliant! If you're reading this and want to take part then (providing it is still 2017) please do! Results will be out on 28th Feb after the majority of analysis during January.

Similarly, its good to get feedback on this. Two of my favourite comments from this year are:
"I felt like your questions were right on target for capturing most of the issues I'm facing."
"It is nice to be asked relevant questions!"

Community Contribution

HSP Community activities for 2017 included:

• Being elected chairman of the UK Support Group!
• Taking part in research projects (as described above)
• Starting to talk with people from other HSP groups
• Convincing the UK HSP group to join EuroHSP
• Analysing and reporting the results of my survey to share with the HSP world
• Seeking out other on-line HSP communities principally to spread the word of my survey
• Continuing this blog and posting/discussing HSP things on twitter.

Obviously, becoming chair of the HSP group is a big change for me, and I'm working with the rest of the committee to ensure that the group continues to support its members in the most appropriate way. There are several channels of discussion going on.

HSP in the news

There have been a couple of people with HSP in the UK news during 2017, both children. 

Firstly, Lily Rice became the first female from Europe to perform a backflip in a wheelchair - http://www.bbc.co.uk/news/uk-wales-41397992 and https://www.youtube.com/watch?v=ePoFlslWHD4.

Secondly, right at the end of the year, Archie Blomfield has been chosen to play the lead role of William Trundle in the Christmasaurus alongside McFly's Tom Fletcher at the Hammersmith Apollo in London. http://www.whizz-kidz.org.uk/about-us/news/christmasaurus-live-whizz-kidz. My youngest son is a dinosaur fan, and we read this great story last Christmas.

A brief history of HSP

I was having a brief look at papers in the "new research tool" I became aware of at the drug repurposing conference in 2016. http://hspjourney.blogspot.co.uk/2016/03/new-tools-research-and-community.html

This pointed me to this article http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2017001100813&lng=en&tlng=en which is a brief history of HSP.

I have copied and pasted the article below, and shortened for this aspects most of interest to me - which is principally understanding the earlier part of the HSP story. If you're interested in the more recent aspects, the click the link and read away!

The article is called: Hereditary spastic paraplegia from 1880 to 2017: an historical review

It is written by: Ingrid Faber, Eduardo Rafael Pereira, Alberto R. M. Martinez, Marcondes França Jr and Hélio Afonso Ghizoni Teive from Universidade Estadual de Campinas and Universidade Federal do Paraná in Brasil.

The diagnosis of an inherited spastic paraplegia is based essentially on the clinical picture, together with the investigation of other, potentially affected, members of the kindred. 

In the last three decades, advances in molecular genetics have revealed that HSPs constitute a large and heterogeneous group of diseases. These frequently overlap clinically and/or genetically with other degenerative disorders such as ataxias, leukodystrophies, spinal muscular atrophy, amyotrophic lateral sclerosis (ALS) and peripheral neuropathies. Historically, the differentiation between HSPs and inherited ataxias has been the most challenging. The key to differentiating complicated HSP from ataxias with associated corticospinal tract dysfunction is to focus on the patient's main disabilities. As a rule, individuals with HSP are overtly spastic and have mild or no complaints relating to the upper limbs. Whereas, in the ataxia group, there is no pronounced dissociation between upper and lower limbs. 

Hereditary spastic paraplegia - first descriptions

In 1880, the Baltic-German (region known today as Estonia and Latvia) neurologist Ernst Adolf Gustav Gottfried von Strümpell published the first case series of patients with HSP. Strümpell reported on two siblings with a probable AD-HSP whose symptoms manifested at 37 and 56 years of age. Clinically, these patients showed a pure form of spastic paraplegia. After the death of one of the siblings, neuropathology showed degeneration of the lateral corticospinal tract, fasciculus gracilis and spinocerebellar tract. In 1888, Maurice Lorrain, a French neurologist, published a more detailed contribution to the anatomical and clinical study of HSPs; hence HSP also being known as Strümpell-Lorrain disease.

Clinical phenotype

Rhein was the first, in 1916, to drive attention to the exquisite clinical heterogeneity some families with HSP displayed. His observations were accompanied by many case series describing pleomorphic clinical pictures encompassing: retinal degeneration, dementia, extrapyramidal symptoms, mental handicap, hand amyotrophy and other features. The term Strumpell's familial spastic paraplegia was reserved for families that displayed only spastic paraparesis, a condition that was thought to be much rarer. Currently, it is recognized that pure forms are more prevalent than complicated ones, their relatively benign clinical course, not affecting life expectancy, greatly contributed to their underdiagnosis at that time. Most epidemiological studies were based on postmortem or hospitalization records.

Anita Harding, a professor of neurology at the University of London, was an important pioneer in the field of molecular neurogenetics. In the 1980s, she published a series of groundbreaking works addressing HSP. In 1981, she presented what was, at the time, the largest investigation into pure HSP, with 22 families studied. She also reinforced the knowledge that spasticity, and not weakness, is the main source of disability in this scenario, an aspect that remains useful in differentiating HSP from other myelopathies. Harding's major contribution to the field of HSP was published in The Lancet journal in 1983. Entitled “Classification of the hereditary ataxias and paraplegias”, this paper established an accurate differentiation between ataxias and HSP, providing a workable base for the etiological investigations that would come. Harding defined that, besides the spastic paraparesis, additional mild signs such as vibration and segmental position sense deficits, slight distal amyotrophy and sphincter dysfunction were also conceivably present in the pure phenotype. This work also provided refinement of the HSP phenotype, emphasizing the variability of disease progression, even within the same family. Sadly, Harding's outstanding career ended prematurely at the age 42 when she succumbed to a cancer. 

In 2006, the German Network for Hereditary Spastic Paraplegia presented the spastic paraplegia rating scale, developed to quantify the disease progression clinically. Validated measures of disease severity are essential to understanding the disease's natural history. Additionally, by their ability to measure treatment impact, they are decisive in the development of future clinical trials.

Structural characterization

While the clinical descriptions of HSP flourished during the 1980s, the pathological comprehension of the disease saw flourishing moments 100 years before. We return to Adolf von Strümpell, the first to identify the disease clinically, who was also the first to describe its pathological hallmarks six years later, in 1886. An unrelated case was also documented by him in 1904. Both pathological specimens showed degeneration of the corticospinal tract in the spinal cord with a distal-proximal gradient. Since then, the disease has been understood as a distal axonopathy of the longest large myelinated fibers of the spinal tract. 

In 1952, Schwarz gave an extensive review of the pathologic literature, highlighting the contributions of Newmark (1904, 1906, 1911), Jakob and Kahlstorf, that culminated with the differentiation of Strümpell's disease from other conditions such as cerebellar ataxias and motor neuron disorders, establishing that, at first, lesions are restricted to the spinal cord and affecting the corticospinal and posterior tracts. 

Advances in genetics

After the accurate clinical classification developed by Harding, the research involving HSP evolved from anecdotal case descriptions to the systematic study of families alike. Numerous HSP genetic studies have been published since the 1980s. Several genetic subtypes of HSP have been described and numbered sequentially, based on the order of the gene discovery (SPG1, SPG2, SPG3, etc. In 1994, Jouet et al., reported that three disorders; X-linked spastic paraplegia, MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and X-linked hydrocephalus were, in fact, allelic conditions, all resulting from mutations in the gene for neural cell adhesion molecule (L1CAM or SPG1). This was the first gene discovered that caused HSP; Also in 1994, Hazan et al., identified the locus implicated in the majority of cases of dominantly inherited HSP.

In 1998, the first gene for autosomal recessive HSP was identified, when the HSP-SPG7 gene was cloned. In 2007, SPG11 was identified as the gene most commonly related to spastic paraplegia with mental impairment and thin corpus callosum. HSP-SPG11 has been recognized as the most common AR-HSP. Surprisingly, SPG11 mutations can also primarily present with other phenotypes, such as parkinsonism or ALS.

Symptoms Update - Walking

So, it looks like there hasn't been many symptoms updates, and then two come along in quick succession!

Observations from the last couple of months are that my walking speed has dropped, but I'm not really sure over low long this has taken place. Certainly before I was living in Bristol I was quite a fast walker, and easily found myself at the front of groups walking. When I was visiting the Lake District (and other similar places) to go walking I know that I was able to average about 5km/hour overall, the uphill bits being the slower part of the average. I used to be able to comfortably achieve 5km/hour on other walks.

These days I notice that I am now walking slower than most people - a walk along the street will see people passing me, and I have to speed up if I want to keep up with a group of people. Recently I went to meet a friend for a couple of drinks which involved a 1.8km walk which I managed in about 23 mins, slightly downhill - about 4.7km/hr, which felt like quite a pace.

The main new thing to note, however, is that about 3/4 of the way back home at the end of the evening my legs were feeling really tired, and I suspect that I shouldnt say that my walking distance is unlimited any more. According to fitbit I had a 15km day, which is one of my busier days. You should note that I treat the distance on fitbit as a measure of activity rather than a measure of distance because fitbit counts some steps whilst I am cycling, but my average distance/busyness is about 9km per day.