Wednesday, 22 February 2012
Some more website links
During my surfing, I've found a few more links to useful things:
A federation of national HSP support groups covering Denmark, France,Italy, The Netherlands, Norway, Spain and the UK:
http://sites.google.com/site/eurohsp/who-we-are
The HSP entry in the rare diseases community - links to support groups and plenty of recent posts with peoples stories. I'm pleased to see that there's a link to this blog here!
http://www.rarediseasecommunities.org/en/community/hereditary-spastic-paraplegia?
Some 2011 research giving a detailed account of the biochemical workings of atlastin, a protein produced by one of the genes linked to HSP:
http://www.sciencedaily.com/releases/2011/07/110708124544.htm
A blog post reporting some research from 2004 into how spastin is involved in neuronal communication.
http://scienceblog.com/community/older/2004/2/20041849.shtml
Another site with a summary of the condition:
http://www.asktheneurologist.com/hereditary-spastic-paraparesis.html
And just for fun, the misspellin version of wikipedia. p.s. its not may fault of you spend hours just looking up other stuff on this page!
http://www.wikipeetia.org/Hereditari_spastic_paraplegia
Friday, 10 February 2012
Location for variants, and more on genes
Before I undertook my trawl of the different variants of HSP, I had in my mind that I would be able to find a "translation" between the detailed results of genetic tests and the variant of the condition. I thought it would be quite a simple exercise - listing the known genetic variations by SPG number and making something clear which I thought wasn't too clear when I got my test results.
Of course, now I realise that there are over 270 genetic variants for SPG4 and over 70 for SPG 11 I realise that this would be a mammoth table, so not something that is easily undertaken. So, a much simpler question to ask is "which genes are affected" - It would seem that each SPG variant affects a different gene, so there are 48 answers to that question. A brief trawl of the internet identifies that the more commonly occurring variants have had their genes named:
A more detailed trawl (for another day) may get further down this line.
Which leads me to perhaps an even more basic question - which chromosomes are affected. I know the Spast gene is on Chromosome 2, but are all the SPG variants? - Quick answer: No.
This made me realise that I had described my genetic test result, and looked at the chromosomal location for other SPGs without really explaining to myself what was going on. There were various references to 'p's and 'q's, but I didn't really understand. So, here goes:
There are 23 pairs of chromosomes in the human body. The first 22 pairs are the same, whereas the last pair is different - and identifies your sex. The chromosomes are numbered by length, with number 1 being the longest and 22 being the shortest. Each chromosome has two arms either side of a narrowing (or centromere). These are the 'p' and the 'q' arms, the 'p' arm is the shortest arm (coming from the French petit - small). Starting at the centromere the locations on the gene are numbered sequentially, with the first location being given 1, the second 2 etc. etc.
So SPG4 is 2p24-2p21, meaning its on the short arm of the 2nd chromosome, between the 21st and 24th location away from the centromere.
This allows me to do a quick set of stats on my trawl of SPG variants - number of variants on each chromosome:
Of course, now I realise that there are over 270 genetic variants for SPG4 and over 70 for SPG 11 I realise that this would be a mammoth table, so not something that is easily undertaken. So, a much simpler question to ask is "which genes are affected" - It would seem that each SPG variant affects a different gene, so there are 48 answers to that question. A brief trawl of the internet identifies that the more commonly occurring variants have had their genes named:
| SPG4 | Spastin |
| SPG11 | Spastacin |
| SPG3A | Alastin |
| SPG7 | Paraplegin |
| SPG17 | Seipin |
Which leads me to perhaps an even more basic question - which chromosomes are affected. I know the Spast gene is on Chromosome 2, but are all the SPG variants? - Quick answer: No.
This made me realise that I had described my genetic test result, and looked at the chromosomal location for other SPGs without really explaining to myself what was going on. There were various references to 'p's and 'q's, but I didn't really understand. So, here goes:
There are 23 pairs of chromosomes in the human body. The first 22 pairs are the same, whereas the last pair is different - and identifies your sex. The chromosomes are numbered by length, with number 1 being the longest and 22 being the shortest. Each chromosome has two arms either side of a narrowing (or centromere). These are the 'p' and the 'q' arms, the 'p' arm is the shortest arm (coming from the French petit - small). Starting at the centromere the locations on the gene are numbered sequentially, with the first location being given 1, the second 2 etc. etc.
So SPG4 is 2p24-2p21, meaning its on the short arm of the 2nd chromosome, between the 21st and 24th location away from the centromere.
This allows me to do a quick set of stats on my trawl of SPG variants - number of variants on each chromosome:
| Chromosome | Number |
| 1 | 4 |
| 2 | 4 |
| 3 | 3 |
| 4 | 1 |
| 5 | 0 |
| 6 | 1 |
| 7 | 1 |
| 8 | 3 |
| 9 | 2 |
| 10 | 4 |
| 11 | 2 |
| 12 | 3 |
| 13 | 2 |
| 14 | 4 |
| 15 | 3 |
| 16 | 2 |
| 17 | 0 |
| 18 | 1 |
| 19 | 3 |
| 20 | 0 |
| 21 | 0 |
| 22 | 0 |
| x | 5 |
| Unspec | 2 |
| Total | 50 |
This more or less ties up with this search. Perhaps I'll look into the differences at some point!
I have 39 'q's and 13'p's - four variants including both.
Various links that helped me find out more are here:
Saturday, 21 January 2012
Jumping Feet (aka: Clonus)
A re-read of some of the HSP pages brings forward a few words that I've not really looked at. Today's word is clonus.
A quick review indicates that clonus is also known as "jumping feet". This sparked off my interest as I recall having "jumping feet" when I was much younger, at junior school, I think. Interestingly there is also myoclonus. Definitions of each are:
Clonus: A form of movement marked by contractions and relaxations of a muscle, occurring in rapid succession, after forcible extension or flexion of a part.
Myoclonus: A rapid involuntary nonrhythmic spasm that can occur spontaneously at rest, in response to sensory stimulation, or with voluntary movements.
I'm interested to note the similarity of the descriptions between clonus and myoclonus.
Some links:
The description of clonus on the SP foundation website is: Clonus is an uncontrollable, repetitive jerking of muscles that makes the foot jump rapidly up and down. It occurs when the foot is in a position that causes a disruption of the signals from the brain, leading to an automatic stretch reflex. http://www.sp-foundation.org/hsp.html
This latter description accords with my childhood experience where I was able to make my foot jump up and down when in a sitting position. I cant remember what I did to get it started, but I suppose that because I was able to start this off at will then it makes it forced rather than involuntary.
Saturday, 7 January 2012
I actually have two "conditions"...
I had a very interesting discussion over Christmas, and its made me realise that I actually have two separate conditions. One is HSP, and the other is one known as "Getting Older".
I've started to spot grey hairs appearing, and I don't associate these with HSP at all. I need to consider if the various things that I've been noticing and commenting on in the context of possible symptoms of HSP are really such symptoms or if they are just as a result of getting older.
For example, I commented last year about getting my speedometer working on my bike as a measure of leg muscle change. When my speedo was last working (a year or two ago) my cycle-to-work average was 13.7mph. Should I get it working again and find the average to be slower, would that be due to HSP starting to affect my muscles, or would that be because I'm a year or two older and just a little bit less fit. I had similarly thought about finding ways of measuring my flexibility.
Conclusion: I should not be so quick to assume that all changes below the waist are HSP, which ought to end up with me in a more positive mind-frame (presumably with a lower likelihood of depression....)
I've started to spot grey hairs appearing, and I don't associate these with HSP at all. I need to consider if the various things that I've been noticing and commenting on in the context of possible symptoms of HSP are really such symptoms or if they are just as a result of getting older.
For example, I commented last year about getting my speedometer working on my bike as a measure of leg muscle change. When my speedo was last working (a year or two ago) my cycle-to-work average was 13.7mph. Should I get it working again and find the average to be slower, would that be due to HSP starting to affect my muscles, or would that be because I'm a year or two older and just a little bit less fit. I had similarly thought about finding ways of measuring my flexibility.
Conclusion: I should not be so quick to assume that all changes below the waist are HSP, which ought to end up with me in a more positive mind-frame (presumably with a lower likelihood of depression....)
Saturday, 10 December 2011
Review of 2011
Its nearly Christmas again, and I thought I'd just have a quick review and summarise what I've discovered this year, and think about how different my symptoms are since the start of the year.
Knowledge:
I've looked into the different variants of HSP and the prevalence, the different muscles and nerves in the legs, and identified several different websites which contain this and other useful information. I'm beginning to understand in "layman's terms" some of the medical terms about the condition that get used frequently. You can still give blood with HSP. There's some evidence that many people with HSP have depression.
Symptoms:
With such a slowly progressing condition it is very difficult to spot things that are noticeably different. About this time last year I noted that I was having to actively ask my leg muscles to relax, and this has been pretty constant since this time (I noted this 6 months ago, too). I've continued to "trip over flat surfaces" which I've been doing for years. I'm fairly certain that my leg muscles become more tense when my emotions are high. I've now been doing Pilates for 2 years - this has certainly helped my awareness and I think its helped my flexibility.
Symptoms update: (legs muscle behaviour)
In the last couple of weeks, I've found that I've been laying in bed in the evenings and feeling that my legs are more stiff and heavy than they used to be. Of course I know they are the same weight, so that part is a perception thing. Is this the first part of my transition into having two weighty but useless limbs below my waist?
On the same theme, when I get to the morning, the first movements of my legs are stiffer than they used to be, although not consistently. I notice more effort required when swinging my leg over the saddle on my bike much more at the start of the day rather than on the way home, and I think I have to put more effort into making my legs move first thing. Perhaps I need to get my speedometer working again to use a measure of 'leg action'.
Just last week I slipped down a few of the stairs, which I don't normally do - so I make a note to myself to be more careful! I remember that I've felt on the verge of slipping a few times before, but this is my first proper slip.
Knowledge:
I've looked into the different variants of HSP and the prevalence, the different muscles and nerves in the legs, and identified several different websites which contain this and other useful information. I'm beginning to understand in "layman's terms" some of the medical terms about the condition that get used frequently. You can still give blood with HSP. There's some evidence that many people with HSP have depression.
Symptoms:
With such a slowly progressing condition it is very difficult to spot things that are noticeably different. About this time last year I noted that I was having to actively ask my leg muscles to relax, and this has been pretty constant since this time (I noted this 6 months ago, too). I've continued to "trip over flat surfaces" which I've been doing for years. I'm fairly certain that my leg muscles become more tense when my emotions are high. I've now been doing Pilates for 2 years - this has certainly helped my awareness and I think its helped my flexibility.
Symptoms update: (legs muscle behaviour)
In the last couple of weeks, I've found that I've been laying in bed in the evenings and feeling that my legs are more stiff and heavy than they used to be. Of course I know they are the same weight, so that part is a perception thing. Is this the first part of my transition into having two weighty but useless limbs below my waist?
On the same theme, when I get to the morning, the first movements of my legs are stiffer than they used to be, although not consistently. I notice more effort required when swinging my leg over the saddle on my bike much more at the start of the day rather than on the way home, and I think I have to put more effort into making my legs move first thing. Perhaps I need to get my speedometer working again to use a measure of 'leg action'.
Just last week I slipped down a few of the stairs, which I don't normally do - so I make a note to myself to be more careful! I remember that I've felt on the verge of slipping a few times before, but this is my first proper slip.
Saturday, 3 December 2011
Other Bloggers
So, I'm having a couple of "glitches" with my browser this afternoon. I was having a hunt around to find out if there were any other bloggers covering HSP. I found a few and I tried to follow them. It doesn't seem to remember these 'follows' though. I'll try again another day, but in the mean time here are the links, so I can remember where these are:
http://spandme.blogspot.com/
http://markdvorak.wordpress.com/
http://rollercoasterparenting.blogspot.com/
http://tokah.blogspot.com/
http://fsphsp.blogspot.com/
There were also a number of other related blogs I found:
http://glutenfree-wheelchair.blogspot.com/
http://thunderhous-yuri.blogspot.com/
http://neuromonitoring.wordpress.com/2011/03/03/motor-and-somatosensory-evoked-potentials-in-hereditary-spastic-paraplegia/
http://stemcellaware.com/
http://spandme.blogspot.com/
http://markdvorak.wordpress.com/
http://rollercoasterparenting.blogspot.com/
http://tokah.blogspot.com/
http://fsphsp.blogspot.com/
There were also a number of other related blogs I found:
http://glutenfree-wheelchair.blogspot.com/
http://thunderhous-yuri.blogspot.com/
http://neuromonitoring.wordpress.com/2011/03/03/motor-and-somatosensory-evoked-potentials-in-hereditary-spastic-paraplegia/
http://stemcellaware.com/
Thursday, 24 November 2011
A quick look at the 'wiring' of the nervous system
OK,
So, I've read many times that: "The major neuropathologic feature of HSP is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent". (from Wikipedia), and various references on many pages to Pyramidal Tracts.
I was wondering what/where these parts are, and what else is 'nearby' - i.e. some kind of wiring diagram for the nervous system. The BBC website had a nice diagram: http://www.bbc.co.uk/science/humanbody/body/factfiles/nervous_anatomy.shtml and there's a much more complicated picture in the enormous post on Wikipedia: http://en.wikipedia.org/wiki/Nervous_system.
fasciculus gracilis: The " fasciculus gracilis" appears to be part of the Dorsal column, alternatively known as the "Gracile fasciculus" and next to this the "Cuneate fasciculus". The dorsal column is in the centre of the spine and sends messages from the skin and positional information back up to the brain, and there are a number of other tracts which carry similar information up (spinocerebellar tracts, spinothalamic tracts and Spino-olivary fibers).
This page is another goes some way to explain the function of each name mentioned: http://www.becomehealthynow.com/article/bodynervousadvanced/820/.
I cant quite work out if HSP affects the spinal column itself or the nerves which connect to the column.
So, I've read many times that: "The major neuropathologic feature of HSP is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts. These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. The spinocerebellar tract is involved to a lesser extent". (from Wikipedia), and various references on many pages to Pyramidal Tracts.
I was wondering what/where these parts are, and what else is 'nearby' - i.e. some kind of wiring diagram for the nervous system. The BBC website had a nice diagram: http://www.bbc.co.uk/science/humanbody/body/factfiles/nervous_anatomy.shtml and there's a much more complicated picture in the enormous post on Wikipedia: http://en.wikipedia.org/wiki/Nervous_system.
axonal degeneration: From one page: "In layman terms it is a type of degeneration of the peripheral nervous system." I cant find a simple description of this, but there any many complicated pages which seem to indicate that the nerve degenerates from within, and then the nerve casing deteriorates. Here's another page: http://imueos.blogspot.com/2010/11/degeneration-regeneration-of-peripheral.html
terminal portions of the longest descending and ascending tracts: The descending tracts are muscle control (i.e. signals travelling down from the brain) and the ascending tracts are perception and touch information (i.e. signals travelling up to the brain). The longest tracts are those that serve the lower part of the body, and the terminal portion of the spinal column is where the longest tracts stop and nerves descend further. This page shows what happens at different sections of the spine. http://en.wikipedia.org/wiki/Spinal_cord.
Then, given that the nerves 'pop out' at the section nearest the organ/muscles that they control, the longest tracts would appear to be those that are "Lumbar" - control of leg muscles and "Sacral" - bowel, bladder and sexual function. http://www.spinalinjury.net/html/_anatomy_of_the_spinal_cord_co.html. There are descending and ascending versions of these.
corticospinal tracts: The lateral corticospinal tract carries messages from the brain to control the muscles. There are two tracts on opposite sides of the spine, and there are also a number of other tracts which control muscles (Extrapyramidal tracts and the anterior corticospinal tract). These are also known as the pyramidal tracts. I haven't really understood the difference between crossed and uncrossed.
terminal portions of the longest descending and ascending tracts: The descending tracts are muscle control (i.e. signals travelling down from the brain) and the ascending tracts are perception and touch information (i.e. signals travelling up to the brain). The longest tracts are those that serve the lower part of the body, and the terminal portion of the spinal column is where the longest tracts stop and nerves descend further. This page shows what happens at different sections of the spine. http://en.wikipedia.org/wiki/Spinal_cord.
Then, given that the nerves 'pop out' at the section nearest the organ/muscles that they control, the longest tracts would appear to be those that are "Lumbar" - control of leg muscles and "Sacral" - bowel, bladder and sexual function. http://www.spinalinjury.net/html/_anatomy_of_the_spinal_cord_co.html. There are descending and ascending versions of these.
corticospinal tracts: The lateral corticospinal tract carries messages from the brain to control the muscles. There are two tracts on opposite sides of the spine, and there are also a number of other tracts which control muscles (Extrapyramidal tracts and the anterior corticospinal tract). These are also known as the pyramidal tracts. I haven't really understood the difference between crossed and uncrossed.
fasciculus gracilis: The " fasciculus gracilis" appears to be part of the Dorsal column, alternatively known as the "Gracile fasciculus" and next to this the "Cuneate fasciculus". The dorsal column is in the centre of the spine and sends messages from the skin and positional information back up to the brain, and there are a number of other tracts which carry similar information up (spinocerebellar tracts, spinothalamic tracts and Spino-olivary fibers).
This page is another goes some way to explain the function of each name mentioned: http://www.becomehealthynow.com/article/bodynervousadvanced/820/.
I cant quite work out if HSP affects the spinal column itself or the nerves which connect to the column.
Monday, 7 November 2011
Symptoms Update - Emotional effects
Quite an emotional weekend has just happened. My sister got married, and she asked me to give her away as our dad died in 2005. I also made a speech. Very happy, but also very emotional.
The relevance of this? Well, I found that at the more emotional parts of the day my leg muscles became very tense, with all of them tightening together and making my legs shake. I had to bend my knees to stop myself turning into a bouncing ball, both in the church and when making my speech. Who'd have thought that skiing lessons would be so useful?
My sister had recently said that our mums legs have done similar when she was emotional, so I'm minded to mention this here as a symptom, which then opens another avenue for future investigation, and I might add an emotional summary as a commentary on my filming.
The relevance of this? Well, I found that at the more emotional parts of the day my leg muscles became very tense, with all of them tightening together and making my legs shake. I had to bend my knees to stop myself turning into a bouncing ball, both in the church and when making my speech. Who'd have thought that skiing lessons would be so useful?
My sister had recently said that our mums legs have done similar when she was emotional, so I'm minded to mention this here as a symptom, which then opens another avenue for future investigation, and I might add an emotional summary as a commentary on my filming.
Saturday, 22 October 2011
FSP Research
Edit 26th November: I realised that this post says nothing really, but that the links are very interesting, so I've added some summary info for each link.
I had thought for a while about looking up the current research into HSP/FSP, primarily to see if I could find any stories/studies involving stem cells. It would seem that the Australian HSP group are funding such a study - details of which are here:
http://www.hspersunite.org.au/stem-cells-hsp/
http://www.asscr.org/index.php?id=1030
I also found an earlier study which had looked at them here:
http://www.hsp-info.de/Project-reports.32.0.html?&L=1
http://www.hsp-info.de/Project-7.108.0.html?&L=1#c377
I also found another couple of sites giving other research studies into HSP, and have included them here for completeness.
http://www.sp-foundation.org/research-study-groups.html
https://sites.google.com/site/eurohsp/scientific-breakthroughts
I had thought for a while about looking up the current research into HSP/FSP, primarily to see if I could find any stories/studies involving stem cells. It would seem that the Australian HSP group are funding such a study - details of which are here:
Stem Cell Pilot Study 2009/10
What is it?
The National Centre for Adult Stem Cell Research (NCASCR) and the HSP Research Foundation (HSPRF) have collaborated to implement a Pilot Study aimed at:
- Growing and maintaining olfactory stem cell lines
- Differentiating them to other nerve cells and
- Defining biological differences in SPG4 cell lines from normal cell lines.
This can lead to the definition of drug targets, that is, compounds that may promote normal cell function instead of impaired cell function caused by the particular mutation.
http://www.hspersunite.org.au/stem-cells-hsp/
http://www.asscr.org/index.php?id=1030
I also found an earlier study which had looked at them here:
http://www.hsp-info.de/Project-reports.32.0.html?&L=1
HSP Promotion Award
Together with the German Neurolgy Organisation (DGN) the award was donated to young researchers, working in the field of HSP in the broadest sense. Since 2008/2009 caused by our 10 anniversary we changed this award into "advanced scholarship"
http://www.hsp-info.de/Project-7.108.0.html?&L=1#c377
Reconstitution of neural functions in the spinal cord through neural stem cells expressing the neural cell adhesion molecule L1
Neural stem cells have recently been shown to be potent and versatile mediators of regeneration in the lesioned central nervous system. They can integrate into the tissue, differentiate into neuronal cells, and grow axons leading to the formation of new synapses and partial restoration of lost functions. The neural cell adhesion molecule L1 has been shown to be a good neurite outgrowth promoter. L1 is upregulated by neurons and Schwann cells after a peripheral nerve lesion and has been implicated in axon regeneration. We propose to test the effect of L1 expressed by genetically manipulated neural stem cells on neuronal differentiation, survival and neurite outgrowth in a mammalian model of spinal cord regeneration
I also found another couple of sites giving other research studies into HSP, and have included them here for completeness.
SPG4 Genetic Research Study
Researchers at Baylor College of Medicine are enrolling subjects in a genetic research study of type 4 autosomal dominant spastic paraplegia (SPG4). They are studying the way that different types of gene mutations lead to differences in clinical symptoms among SPG4 patients.
If you or your family member has been diagnosed with a "deletion" or "duplication" mutation in the SPG4 disease gene (this gene is also called SPAST), you will likely qualify to participate.
HSP Genetic Study
There is a HSP genetic study currently underway at the University of Miami. If you are interested in participating or finding out more information, please contact Fiorella atmihgHSP@med.miami.edu.
The Miami Institute for Human Genomics Genetic is looking for INDIVIDUALS and their FAMILIES who would like to participate in Hereditary Spastic Paraplegia (HSP) research. The purpose of the research study is to identify genetic factors that contribute to Hereditary Spastic Paraplegia (HSP).
http://www.sp-foundation.org/research-study-groups.html
Dr Jamilé HAZAN's team has demonstrated that in the zebrafish atlastin, the protein encoded by the SPG3Agene, controls the architecture of spinal motor neurons and thus the mobility of the larvae during embryonic development of this small fish.
https://sites.google.com/site/eurohsp/scientific-breakthroughts
Sunday, 9 October 2011
Pins and needles
Looking back over my previous posts I talked a while ago about pins and needles (Feb 11 http://hspjourney.blogspot.com/2011/02/symptoms-update.html), and thought I'd have a look to see what else I could find.
Pins and needles is really called paraesthesia, although it would appear also to be spelt paresthesia on some web pages (wikipedia indicates that the former is the British English spelling) http://en.wikipedia.org/wiki/Paresthesia
There are various website which indicate that paraesthesia is a possible feature in uncomplicated/pure HSP - for example http://neuromuscular.wustl.edu/spinal/fsp.html. But, I don't seem to be able to find any referenced papers/studies describing this. Some sites describe it as affecting "below the knee", others in the "lower legs" whereas others just list the term generally without indicating where it might occur.
My main reason, however, for coming back to this issue was that I don't think I've been noticing the pins and needles as much in the last few months and wanted to note that issue here. It doesn't take much reading to find out that pins and needles can be caused by dehydration, lack of sleep, stress, etc. etc. so, perhaps it was one of those (or indeed something else) which caused that then and not really since.
Pins and needles is really called paraesthesia, although it would appear also to be spelt paresthesia on some web pages (wikipedia indicates that the former is the British English spelling) http://en.wikipedia.org/wiki/Paresthesia
There are various website which indicate that paraesthesia is a possible feature in uncomplicated/pure HSP - for example http://neuromuscular.wustl.edu/spinal/fsp.html. But, I don't seem to be able to find any referenced papers/studies describing this. Some sites describe it as affecting "below the knee", others in the "lower legs" whereas others just list the term generally without indicating where it might occur.
My main reason, however, for coming back to this issue was that I don't think I've been noticing the pins and needles as much in the last few months and wanted to note that issue here. It doesn't take much reading to find out that pins and needles can be caused by dehydration, lack of sleep, stress, etc. etc. so, perhaps it was one of those (or indeed something else) which caused that then and not really since.
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