Researchers - Initial Numbers

So, Thanks to a post from Rob from EURODIS on Rarediseasecommunity, I have been looking at PubMed, which has a directory of medical publications. On 20th April there were 589 different papers listed for HSP. I'm doing a bit of number crunching on this information. There are two simple sets of numbers - number of papers per year and number of papers per journal which are easy to find out:

Papers per year:

Year	Papers
2012	4
2011	35
2010	38
2009	49
2008	45
2007	45
2006	48
2005	28
2004	36
2003	36
2002	30
2001	27
2000	18
1999	25
1998	24
1997	13
1996	4
1995	9
1994	10
1993	16
1992	8
1991	13
1990	18
1989	6
1988	3
1978	1

Papers per journal - note that I've yet to decipher the abbreviations:

PapersByJournal

Journal	Papers	Most Recent
Neurology	48	2010
J Neurol Neurosurg Psychiatry	24	2010
J Neurol Sci	23	2011
J Neurol	22	2011
Arch Neurol	22	2009
Neurogenetics	21	2011
Am J Hum Genet	20	2008
Eur J Neurol	17	2012
J Med Genet	16	2009
Ann Neurol	15	2007
Mov Disord	13	2011
Clin Genet	13	2011
Hum Mutat	12	2011
Hum Mol Genet	12	2010
Brain	10	2010
Hum Genet	10	2010
No To Shinkei	9	2003
Acta Neurol Scand	9	2002
Zhonghua Yi Xue Yi Chuan Xue Za Zhi	8	2009
Am J Med Genet	8	2002
Clin Neurol Neurosurg	6	2011
Eur J Hum Genet	6	2009
Nat Genet	6	2007
Neuromuscul Disord	5	2009
Ryoikibetsu Shokogun Shirizu	5	2001
J Child Neurol	4	2010
Chin Med J (Engl)	4	2009
J Cell Biol	4	2009
Neuropediatrics	4	2006
Rinsho Shinkeigaku	4	2001
Dev Med Child Neurol	4	1993
Can J Neurol Sci	3	2012
Neurol Sci	3	2011
Pediatr Neurol	3	2011
Prenat Diagn	3	2010
Brain Dev	3	2010
Arq Neuropsiquiatr	3	2010
J Neurochem	3	2009
Funct Neurol	3	2007
Curr Opin Neurol	3	2007
Muscle Nerve	3	2007
Eur Neurol	3	2007
Neuroradiology	3	2006
Cell	3	2005
Curr Biol	3	2005
Zh Nevropatol Psikhiatr Im S S Korsakova	3	1991
Clin Neurophysiol	2	2011
Acta Neuropathol	2	2011
Genome Res	2	2011
J Clin Neuromuscul Dis	2	2011
BMC Biol	2	2010
J Clin Invest	2	2010
BMC Neurol	2	2010
Am J Med Genet B Neuropsychiatr Genet	2	2009
Arch Phys Med Rehabil	2	2009
Hong Kong Med J	2	2009
J Inherit Metab Dis	2	2008
Lancet Neurol	2	2008
Neurosci Lett	2	2008
J Biol Chem	2	2008
Expert Opin Pharmacother	2	2007
Int J Obstet Anesth	2	2007
Am J Med Genet A	2	2005
Neuropathology	2	2005
Amyotroph Lateral Scler Other Motor Neuron Disord	2	2005
Neuropathol Appl Neurobiol	2	2004
Nervenarzt	2	2003
Genomics	2	2003
Semin Neurol	2	1999
Nat Med	2	1998
Pediatr Neurosurg	2	1995
Genet Couns	2	1994
Ital J Neurol Sci	2	1993
Eur Arch Psychiatry Neurol Sci	2	1990
Psychosomatics	1	2012
Spinal Cord	1	2011
Eur J Paediatr Neurol	1	2011
Curr Mol Med	1	2011
Eur J Med Genet	1	2011
Orphanet J Rare Dis	1	2011
Nat Rev Neurosci	1	2011
PLoS Genet	1	2011
Genet Med	1	2011
Gait Posture	1	2011
Amyotroph Lateral Scler	1	2011
Rev Esp Anestesiol Reanim	1	2011
Mol Cell Neurosci	1	2011
Neurologist	1	2011
Mitochondrion	1	2011
Zh Nevrol Psikhiatr Im S S Korsakova	1	2010
No To Hattatsu	1	2010
PLoS Biol	1	2010
Toxicol Lett	1	2010
Dis Model Mech	1	2010
J Lipid Res	1	2010
Ann Clin Lab Sci	1	2010
Hum Brain Mapp	1	2010
Neuroepidemiology	1	2009
Rom J Morphol Embryol	1	2009
Clin Rehabil	1	2009
AJNR Am J Neuroradiol	1	2009
Ann Anat	1	2009
Adv Exp Med Biol	1	2009
Synapse	1	2009
Nature	1	2008
Acta Neurol Scand Suppl	1	2008
SEB Exp Biol Ser	1	2008
BMC Med Genet	1	2008
J Neurosci	1	2008
J Neurogenet	1	2008
J Intellect Disabil	1	2008
Neuroscience	1	2008
Med Arh	1	2007
Mol Cell Biol	1	2007
Mol Neurobiol	1	2007
Brain Res Bull	1	2007
Pediatr Radiol	1	2007
Tidsskr Nor Laegeforen	1	2007
Curr Neurol Neurosci Rep	1	2006
Anesth Analg	1	2006
J Hum Genet	1	2006
Trends Mol Med	1	2006
Ren Fail	1	2006
Panminerva Med	1	2006
Proc Natl Acad Sci U S A	1	2006
Pharmacol Ther	1	2006
Cell Mol Neurobiol	1	2005
Ceylon Med J	1	2005
Biochem Biophys Res Commun	1	2005
J Clin Neurosci	1	2004
Ned Tijdschr Geneeskd	1	2004
Parkinsonism Relat Disord	1	2004
Neuroreport	1	2003
IUBMB Life	1	2003
Exp Neurol	1	2003
Nihon Rinsho	1	2002
Masui	1	2002
Int Rev Neurobiol	1	2002
Neurol Clin	1	2002
Curr Opin Genet Dev	1	2001
Rev Prat	1	2001
Pharmacogenomics	1	2001
Retina	1	2000
Rev Neurol (Paris)	1	2000
Neurophysiol Clin	1	2000
Can J Anaesth	1	1999
Biochim Biophys Acta	1	1999
Electromyogr Clin Neurophysiol	1	1999
Physiother Res Int	1	1999
Neurochirurgie	1	1998
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi	1	1998
Schweiz Med Wochenschr	1	1998
Hum Hered	1	1998
Am J Phys Med Rehabil	1	1998
J Clin Epidemiol	1	1997
Epilepsia	1	1997
Acta Paediatr	1	1996
Acta Neurochir Suppl	1	1995
Brain Pathol	1	1995
Aust N Z J Psychiatry	1	1995
Vojnosanit Pregl	1	1993
Electroencephalogr Clin Neurophysiol	1	1993
Paraplegia	1	1993
J Neurosurg Sci	1	1993
Neurourol Urodyn	1	1993
Aust Vet J	1	1993
Orthop Rev	1	1992
Minerva Med	1	1992
Clin Neuropharmacol	1	1991
Clin Exp Neurol	1	1991
Fortschr Neurol Psychiatr	1	1991
J Assoc Physicians India	1	1990
Am J Hematol	1	1990
N Engl J Med	1	1990
Prog Clin Biol Res	1	1989
J Med Assoc Thai	1	1989
Medicina (B Aires)	1	1988
Ann Pediatr (Paris)	1	1978

More details in a later post - the link with all this lovely info is here: http://www.ncbi.nlm.nih.gov/pubmed?term=%22Spastic%20Paraplegia,%20Hereditary%22[Majr]

Spastic Gait

I realised that I've been blogging for a while and haven't really touched upon the primary outcome of FSP/HSP - the spastic gait. This is also identified on some FSP sites as a scissor gait.


There are a number of references which give descriptions of a spastic gait - here's part of one I like:


When a person has a spastic gait, his legs are typically weak and abnormally stiff. As he walks, he holds his legs closer together than normal, drags his feet or toes, and lacks the typical flexibility in his ankles and knees. When a person has a spastic gait, his legs, toes, and feet are stiffer than normal. He typically does not flex his muscles and bend his legs as he walks. Instead, long-term muscle contractions usually  cause him to drag one foot or his toes when he walks. Sometimes medications may also be used to treat this gait problem. For example, medicines may be used to reduce muscle contraction, but the effects of many medications are still being studied. (http://www.wisegeek.com/what-is-a-spastic-gait.htm)


Here is a description of scissor gait http://www.gpnotebook.co.uk/simplepage.cfm?ID=818937856: Scissor gait is the term used to describe the manner of walking that is seen in patients with spastic paraplegia, the features are:

• rigidity and excessive adduction of the leg in swing

• plantar flexion of the ankle

• flexion at the knee

• adduction and internal rotation at the hip

• contractures of all spastic muscles

The individual is thus forced to walk up on tip-toe, the other contractures resulting in the knees rubbing together and crossing in a manner analogous to scissors.

Of course, the shortest definitions are often the best: http://medical-dictionary.thefreedictionary.com/Scissors+gait:
scissors gait a crossing of the legs while advancing with slow, small steps.
spastic gait a walk in which the legs are held together and move in a stiff manner, the toes seeming to drag and catch. A slow, shuffling gait in which the patient appears to be wading in water. Knee and hip movements are restricted.


What I'm looking for is the sequence. It would appear to start like this: Initial symptoms are typically difficulty with balance, stubbing the toe or stumbling. (symptoms: http://en.wikipedia.org/wiki/Hereditary_spastic_paraplegia) but there doesnt seem to be much around which describe the next steps. Perhaps this is something I'll have to note myself in my symptoms updates.


I also found these exercises which claim to improve gait:
http://www.ncpad.org/exercise/fact_sheet.php?sheet=566&section=2632

Symptoms update - beer

Here's one from the 'not sure' category.

I went to the pub one evening this week with a friend for a couple of beers and a chat. That was good, but I think I noticed that I was finding it marginally more difficult to walk  home than on the way there. Certainly I managed to trip up on a perfectly flat surface just outside the pub, but I think I felt that I needed more muscle effort to make my legs walk. I've also been quite tired too this week.

This made me think that my post back in November where I talked about emotional effects might have had an alcohol effect too - after all I had had "a couple" of drinks that night too.

I'm going to have to pay attention to these three factors: alcohol, emotions and tiredness to see if I can decide if one plays a stronger influence than the others.

Booze barometer - this week was a genuine couple - I had 3 pints. In November I had had considerably more than this.

Another Name - Jean-Martin Charcot

One of my objectives is to generate a list of current researchers working with HSP, and I suspect that is going to take a while to do. I've a few starting points, and a vague approach in my mind, but I'm going to need to concentrate so I try not to miss any avenues.

In the mean time my brain was turning to the discovery of the condition, and I remember reading on the SP Foundation website: http://www.sp-foundation.org/hsp.html the reference to another name - a Frenchman called Charcot, with another alternative name for the condition: hereditary charcot disease. This post seeks more info - I Hadn't picked up Charcot before.

More info doesn't seem to be easy to find. I suspect that Charcot would be Jean-Martin Charcot, who was French and lived 1825-1893, so would have been around at the time of Strumpells 1880 paper but not Lorrains 1898 paper. Also in his favour was that he was a neurologist. Charcot is much better known for work in MS and Parkinsons, and for his approach to neurological examination. You can read more at wikipedia: http://en.wikipedia.org/wiki/Jean-Martin_Charcot. These higher profile conditions, and CMT tend to flood the search results.

Another supporting observation is that Pierre Marie was a student of Charcot, who also worked with Adolph Strumpell - leading to Marie–Strümpell disease.


It would be nice to find references to Charcots work, which would be from the last three years of his life. If anyone has details, I would be pleased to receive.

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

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:

SPG4	Spastin
SPG11	Spastacin
SPG3A	Alastin
SPG7	Paraplegin
SPG17	Seipin

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:

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!

http://us-east.omim.org/search?index=geneMap&search=paraplegia&sort=chromosome_number%20asc,chromosome_sort%20asc&start=1&limit=100

I have 39 'q's and 13'p's - four variants including both.

Various links that helped me find out more are here:

http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation

http://www.chromodisorder.org/CDO/General/IntroToChromosomes.aspx

http://en.wikipedia.org/wiki/Chromosome

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:

http://en.wikipedia.org/wiki/Clonus

http://medical-dictionary.thefreedictionary.com/clonus

http://en.wikipedia.org/wiki/Myoclonus

http://medical-dictionary.thefreedictionary.com/myoclonus

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.

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....)

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.

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/