Author: SSAdmin

Not to be taken lightly

This article is by SP Foundation Board Member Jackie Wellman

Just last week I had the second person in my family die from urinary tract infections caused by having HSP and it went systemic. Yes, die from a urinary tract infection that went systemic.

The first was in 2000 and it was my Grandma. She died from a chronic urinary tract infection that went systemic. Last week my 63 year old Uncle John was the second.

This article is to warn you that urinary tract infections are nothing to mess around with.

If you have bladder issues with your HSP or PLS, like urgency, then chances are you have to go all the time because you are not emptying. Our bladders just do not work right; therefore they do not empty completely. Even though you may feel like it is. If you have to urinate within the next hour it is because there is too much in there….because it did not empty completely.

Think of a pond that does not get drained…it gets gross. Unpleasant things start growing in it. Same thing with the bladder…not green algae, but nasty bacteria. Those bacteria can become resistant to antibiotics and then you are in trouble.

I used to get UTIs frequently. The doctor talked me into trying to self-cath morning and night. I have not had an infection since. That was about ten years ago. I now get bladder Botox and self-cath about six times a day. Every day. Yes, I would much rather not do it but the alternative is to die…at least in my family. The bladder Botox is painless also. I feel normal for 6-9 months. It’s worth it in every way to me. Before doing Botox I was visiting the bathroom every fifteen minutes.

I urge you, if you are debating about whether or not to start self-cathing, to bite the bullet and do it. It is painless and easy. Not the most convenient thing but better than the alternative.

Functional improvement possible for HSP

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NMES and FES appear to be safe and well tolerated in children with various disabilities. Reports of direct adverse reactions to electrical stimulation were rare.

 

Abstract

The use of therapeutic electrical stimulation for medical purposes is not new; it has been described in medical textbooks since the 18th century, but its use has been limited due to concerns for tolerance and lack of research showing efficacy.

 

The purpose of this review is to discuss the potential clinical applicability, while clarifying the differences in electrical stimulation (ES) treatments and the theory behind potential benefits to remediate functional impairments in youth.

 

The literature review was performed as follows: A total of 37 articles were reviewed and the evidence for use in pediatric diagnoses is reported. The synthesis of the literature suggests that improvements in various impairments may be possible with the integration of ES. Most studies were completed on children with cerebral palsy (CP).

 

Electrical stimulation may improve muscle mass and strength, spasticity, passive range of motion (PROM), upper extremity function, walking speed, and positioning of the foot and ankle kinematics during walking. Sitting posture and static/dynamic sitting balance may be improved with ES to trunk musculature. Bone mineral density may be positively affected with the use of Functional Electrical Stimulation (FES) ergometry. ES may also be useful in the management of urinary tract dysfunction and chronic constipation.

 

Among all reviewed studies, reports of direct adverse reactions to electrical stimulation were rare.

 

In conclusion, NMES and FES appear to be safe and well tolerated in children with various disabilities. It is suggested that physiatrists and other healthcare providers better understand the indications and parameters in order to utilize these tools effectively in the pediatric population.

 

SOURCE: J Pediatr Rehabil Med. 2016 May 31;9(2):83-99. doi: 10.3233/PRM-160375. PMID: 27285801 [PubMed – in process]

 

Does therapeutic electrical stimulation improve function in children with disabilities? A comprehensive literature review.

 

Bosques G1,2, Martin R3,4, McGee L2, Sadowsky C3,4.

 

1 University of Texas – Health Science Center at Houston (UTHealth), Houston, TX, USA.

2 Shriners Hospital for Children, Houston, TX, USA.

3 Kennedy Krieger Institute, Baltimore, MD, USA.

4 Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Compared with overall population

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Self-reported data from 108 adult HSPers was compared with a sample of almost 50,000 in a Norwegian population study. It was found that HSPers:

• more frequently lived alone

• reported lower life satisfaction

• lower mental well-being

• lower social support

• poorer memory and sleep.

Men with HSP reported higher impact of HSP, lower life satisfaction and less ability to perform daily activities compared to women with HSP.

 

Abstract

BACKGROUND:

Hereditary spastic paraparesis (HSP) is a rare neurodegenerative condition characterized by slowly progressive spastic weakness of the lower limbs and urinary sphincter dysfunction. Complex HSP involves additional neurologic symptoms and signs like ataxia, extra pyramidal signs, polyneuropathy, and cognitive decline. Little is known about the disease burden for adults with HSP beyond the described core symptoms.

METHODS:

A cross-sectional survey of 108 adults aged 30 years and older (Mage = 57.7 years, SD = 11.5, range 30 to 81; 54.2 % females) recruited from a national center of expertise for rare disorders and a patient advocacy organization in Norway. Self-report data from the HSP sample was compared to self-report data from a large Norwegian population study, HUNT3 (N = 46,293), covering health-related variables such as overall life satisfaction, mental wellbeing, memory function, perceived pain, and co-morbid diseases. In addition, the HSP sample reported specific items developed for this study in co-operation with the patient advocacy organization.

 

RESULTS:

The HSP sample more frequently lived alone. Overall, the HSP sample reported lower life satisfaction, lower mental wellbeing and lower social support, as well as poorer memory and sleep, compared to controls. Furthermore, the HSP sample more frequently reported musculoskeletal pain, constipation, and urinary incontinence compared to controls. There was no difference between samples in frequency of physical activity and alcohol and tobacco use. Men with HSP reported higher impact of HSP, lower life satisfaction, and less ability to perform activities of daily living compared to women with HSP.

 

CONCLUSIONS:

Adults with HSP experience disease burden on a larger number of areas than previously documented, and men with HSP may represent a particularly vulnerable group.

 

SOURCE: Orphanet J Rare Dis. 2016 Jul 13;11(1):98. doi: 10.1186/s13023-016-0469-0. PMID: 27412159 [PubMed – in process]

 

Health survey of adults with hereditary spastic paraparesis compared to population study controls.

 

Fjermestad KW1,2, Kanavin ØJ3, Næss EE3, Hoxmark LB3, Hummelvoll G3.

 

1 Frambu centre for rare disorders, Sandbakkveien 18, 1404, Siggerud, Norway. kfj@frambu.no.

2 Department of Psychology, University of Oslo, PO Box 1094 Blindern, 0317, Oslo, Norway. kfj@frambu.no.

3 Frambu centre for rare disorders, Sandbakkveien 18, 1404, Siggerud, Norway.

For children with Duchenne muscular dystrophy

 

Children in England suffering from a rare form of muscular dystrophy will soon be able to access the only drug licensed for their condition after a ground-breaking agreement was reached between NHS England and PTC Therapeutics.

 

Under the five-year commercial agreement, which includes an outcomes-based incentive for the manufacturer as well as a mechanism to monitor how well the medicine has worked in practice before future funding decisions are made, Translarna (ataluren) can be used to treat children aged five and over with Duchenne muscular dystrophy (DMD) caused by a nonsense mutation.

 

The move follows a recommendation by the National Institute for Health and Care Excellence earlier this year that the drug, which costs £222,000 per year (before discount) should be available on the NHS if NHS England and PTC could successfully negotiate an economically acceptable managed access agreement.

 

The Institute noted that, in one clinical trial, none of the children in the most sensitive group taking the drug lost the ability to walk over the 48 weeks of the trial compared with 8 percent on the placebo, and that research predicts that it could delay loss of walking for up to seven years.

 

Translarna won conditional approval from the European Commission in August 2014 to treat nmDMD, and is currently available to patients in 23 countries through either expanded access programs or commercial sales.

 

Read the full article… 

 

SOURCE: PharmaTimes online, July 8 2016

 

NHS England, PTC reach agreement on Duchenne drug

 

Selina McKee

Happier, healthier, stronger

 

There are some very helpful ways of living with HSP. It’s all about attitude! Here are some ‘tricks’:

 

“I walk into the gym as a superhero! I tackle each of the exercises that my physiotherapist recommended as mini challenges, doing my very best, and the next day, doing my very best again. Great for my sense of accomplishment! I might not look like it to others but under my gym gear – I am a superhero!”

 

“When I feel down, I do a quick pick-me-up. Here’s my favorite:

https://www.youtube.com/watch?v=T2yjQ01SVug

It takes just over one minute to do and cheers me up enormously! There are lots of quick and easy ways to feel happier, healthier and stronger and there’s scientific proof that it works!”

 

I didn’t make these things up. I stumbled upon the podcast and then the book “SuperBetter” by Jane McGonigal. The SuperBetter method is designed to make you stronger, happier, braver and more resilient. There are lots of randomized, controlled studies and clinical trials to prove these changes are beneficial but this couldn’t be easy – OR COULD IT?!!!

SuperBetter is like playing a game. In fact it is intentionally and specifically just like playing a game. This methodology was created by the author, an internationally renowned game designer, after a very serious brain injury, to face the stress and personal challenges of a very long and slow recovery. SuperBetter is about taking a gameful approach to life and the challenges we all come across. The SuperBetter process is to:

 

1. Challenge yourself.

2. Collect and activate power-ups, which are things you can easily do in 5 minutes or less that make you feel happier, healthier and/or stronger.

3. Find and battle the ‘bad guys’, which are anything that blocks your progress or causes you anxiety, pain or distress.

4. Seek out and complete quests.

5. Recruit your allies.

6. Adopt a secret identity.

7. Go for an epic win.

 

In her book there’s a lot of science on why playing games, including online games is actually good for us! That rush of success when a player does well in a video game, gives a dopamine feel-good reward which, its been proven, is as powerful as intravenous drugs. With practice, learning to live gamefully and developing these skills can lead to significant neural reorganization, resulting in increased attention, faster decision making and more effective learning. Playing games with your friends or family, any games and especially SuperBetter games, can open doors to communication, understanding and mutual support. Lots of examples were given of how this sort of “game” helped friends/associates/loved ones finally understand how they can be helpful.

More compelling to me though is that people around the world are adopting their own secret identities, using power-ups and battling their own bad guys, taking a gameful approach to challenges including depression, anxiety, chronic pain, loss of work even cancer and neurodegenerative disease – and feeling stronger, braver and more capable! Groups, including Navy officers, teachers, therapists and neighborhood associations have designed SuperBetter adventures.

 

I was especially touched by the fellow who couldn’t find a way to get himself healthier – until he decided his epic challenge was to be the best owner his dog could possibly have! He took his dog for frequent walks and threw balls for his dog to fetch and got outside much more often – thereby getting exercise and reducing his own stress – and it made all the difference.

 

I was touched by the man with two young children and motor neurone disease who took on a superhero identity and had his children help him with gameful physical challenges… wanting to be more to them than their father, sick in bed and dying. Life can be hard and having HSP can be hard. If there’s a challenge you’d like to approach/overcome/have more control over or if you’d like to improve some fundamental life skills in a fun, approachable way, here’s a good place to start.

 

Some resources

 

• Ted Talks 19 minute video by Jane McGonigal:

 

• Jump in and start to play! The SuperBetter website. https://www.superbetter.com/

 

• This website offers a wealth of information and support: Areyougameful.com

 

• The book, SuperBetter by Jane McGonigal, is available in hardcover, paperback, on Kindle or as an audio CD. http://www.amazon.com/SuperBetter-Revolutionary-Approach-Stronger-Resilient-Powered/dp/1594206368

 

• It is also available as an iPhone, iPad and iPod touch app https://itunes.apple.com/au/app/superbetter/id536634968?mt=8

 

• Here is a review article in the New Yorker magazine. http://www.newyorker.com/magazine/2015/09/14/high-score

 

It’s all about attitude!

• You are stronger than you know.
• You are surrounded by potential allies.
• You are the hero of your own story.

What it means for HSPers

 

by Adrienne Sexton, Genetic Counsellor and A/Prof. Michael Fahey, Neurogeneticist (Neurogenetics clinic, Royal Melbourne Hospital)

 

What has changed in genetic testing for HSP?

HSP can be caused by a change in any of 50 or more genes. For many years, single gene testing for a few of the more common genes (spastin, REEP1 and atlastin) was available, and the test would look through the thousands of letters of DNA code in one of those genes, to identify a change. If a change is identified, sometimes it is clear that this will stop the gene from working and cause HSP, but sometimes the scientists and doctors cannot be sure whether it explains the HSP diagnosis.

This same principle of looking through the letters of the DNA code can now be applied to many genes at once, representing a huge increase in capability. This major leap forward in genetic technology is called Next Generation Sequencing (other names are panel testing, whole exome sequencing, and Massively Parallel Sequencing). Testing for most or all of the currently known HSP genes now costs about the same as the old tests for one gene at a time, and although testing still costs more than $1,000, is expected that costs will continue to decrease steadily over time. The testing can also be done more quickly. Some types of gene changes are not detected by this type of testing however, and it is very likely there are still undiscovered genes for HSP that may be able to be tested for eventually.

How do I access genetic testing?

Genetic testing can be arranged via a neurologist or Genetic service. You can find a Genetic service in your area by checking http://www.genetics.edu.au/Genetics-Services/genetic-counselling-services

Genetic testing may be free through a Genetic service, depending on many factors including your personal and family history of the condition. If a specific gene for HSP is already known in your family members, then a genetic test is often free of charge for relatives.

Several labs in Australia and overseas offer testing for many HSP genes at once at competitive prices. This can test many combinations of genes, but usually requires a Clinical Genetics specialist to specify a list of which genes should be analysed.

Why is it helpful to visit a Genetics/Neurogenetics service or Neurologist for advice?

At a genetics clinic, Clinical Geneticists, Neurologists, Neurogeneticists, and Genetic Counsellors work together to look at your particular symptoms and family history, and determine which genes might be most relevant for testing. This can be complex and it is important because HSP overlaps with some other conditions – a single gene problem can sometimes cause HSP or another condition, and it is commonly difficult to get a clear diagnosis from the clinical symptoms. A list of conditions sometimes overlapping with HSP includes:

• Ataxia (problems with balance and coordination)
• Mitochondrial conditions (affecting the ‘energy factories’ of the cells in our body)
• Cognitive decline (problems with memory, thinking and planning)
• peripheral neuropathy (problems with sensation in the hands and feet)
• Amyotrophic lateral sclerosis (motor neuron disease)
• Primary lateral sclerosis
• Charcot-Marie Tooth syndrome

Genetics services can also discuss with you the options for potentially having children who will not have HSP. This can be achieved through genetic testing during early pregnancy or via an IVF process, however these options rely on the exact HSP gene problem in the family to be identified first. Some people want to consider these options while other do not – it’s very personal.

Genetic testing has pros and cons, and a genetic counsellor can give you the right information to help you think about the issues and reach a decision that’s best for you. Different people in the family may feel differently about whether they want to know a genetic cause for HSP. It is important to think about whether now is the right timing for you, the possible implications for your family, and to have support in place as needed.

How can genetic testing for HSP help?

Genetic testing may or may not find a cause of HSP in you or your family. Genetic test results for HSP will not usually change your medical treatment or mean that a cure is available. However, it may be useful if it leads to a genetic cause being pinpointed because:

• It may well give you some peace of mind, especially if you have been misdiagnosed in the past or you have been told that you may have one of several conditions or possibly a complex of more than one condition
• The certainty that a positive genetic diagnosis provides helps your doctor, physio and other health professionals. While a genetic diagnosis helps doctors by categorically identifying whether or not someone has one or more of the particular gene changes being tested for, it needs to be remembered that there is no cure or treatment for HSP discovered as yet.
• It may increase the accuracy of information about symptoms and prognosis (although many types of HSP are quite variable even among members of the same family)
• It identifies the inheritance pattern and the chances of children or relatives inheriting or having HSP
• Relatives can fairly easily find out whether they have inherited HSP or not, as screening for a known family gene change is relatively quick and inexpensive
• If a genetic cause is known, then testing during pregnancy or before pregnancy via IVF becomes a real option.

 

 

 Home modifications, quality-of-life

 

Adam Lawrence, an HSPer from the UK, reports on the latest annual survey of HSPers in different countries. The main focus of this survey is understanding the modifications people make around their homes to live with HSP. He also touches on depression and quality of life.

 

Adam writes: “Just to let you know that I have now published the results of the survey here: http://hspjourney.blogspot.co.uk/2016/02/2015-survey-results.html

Given the wide range of modifications suggested, I’m hoping that readers can get some useful ideas from here or at least think about how and when they may have to make changes.”

 

Here are the findings of the on-line survey undertaken between September 2015 and January 2016. 109 respondents with Hereditary Spastic Paraplegia (HSP) completed the survey, predominantly from the USA and the UK. The survey covered modifications at home, depression and quality of life. Respondents also answered questions about their mobility allowing trends to be spotted with level of mobility.

 

Home modifications

There is a wide range of modifications that people have made around their properties. Modifications tend to be made after an accident or after noticing a change in mobility/symptoms, although some people are making modifications early and are planning for future changes.

Some of the modifications are large-scale, including the installation of stair lifts or the conversion of bathrooms to wetrooms, while other modifications are small. This paper repeats some advice given by respondents to others thinking of making those modifications.

As HSP progresses modifications will need to be made to individual’s properties. Many respondents indicate that living in a single storey dwelling makes life much easier. The requirement to move to a single storey dwelling will depend ultimately on personal preferences and the progression of HSP, and there will be plenty of other factors in any decision to stay or to move house.

Frequently, the first modifications made are the installation of grab rails within the property, and these are often fitted in the bathroom first. Subsequent modifications are made depending on the rate of progression of HSP. The parts of properties which are modified the most after the inclusion of grab rails are the bathroom/toilet with a range of different modifications made. Adjustments to beds are relatively common. Modifications in other parts of properties are made less frequently. Some people prefer to make modifications within their existing property whilst others prefer or have to move into accommodation which has been or can be set up to meet their needs.

 

HSP and depression

People with HSP appear to suffer from depression more than the general population. Respondents completed the PHQ-2 questionnaire, which showed that around a quarter should seek further assessment. Results have been compared with the 2009 Estonian study into depression with HSP, and a similar proportion of people with scores of zero, indicating no depression, is shown.

 

 HSP and quality of life

Respondents also completed a sample of questions from the Patients Like Me Quality of Life survey and it is concluded that HSP appears to affect quality of life and from this data there appears to be two step changes. The first step change is in social functioning at the point when mobility aids are needed and the second step change is in physical functioning when mobility aids need to be relied on most or all of the time.

Important findings about spasticity and weakness

 

This study by Melbourne physiotherapist Brooke Adair characterised the gait patterns of children with HSP. Important questions have emerged about the relative influence of spasticity (muscle spasms or contraction) and muscle weakness to the gait patterns examined. These questions are worthy of further examination.

 

This study received support funding from the HSP Research Foundation.

 

AIM:

To examine the kinematic gait deviations at the trunk and pelvis of children with hereditary spastic paraplegia (HSP).

 

METHOD:

This exploratory observational study quantified gait kinematics for the trunk and pelvis from 11 children with HSP (7 males, 4 females) using the Gait Profile Score and Gait Variable Scores (GVS), and compared the kinematics to data from children with typical development using a Mann-Whitney U test.

 

RESULTS:

Children with HSP (median age 11y 4mo, interquartile range 4y) demonstrated large deviations in the GVS for the trunk and pelvis in the sagittal and coronal planes when compared to the gait patterns of children with typical development (p=0.010-0.020). Specific deviations included increased range of movement for the trunk in the coronal plane and increased excursion of the trunk and pelvis in the sagittal plane. In the transverse plane, children with HSP demonstrated later peaks in posterior pelvic rotation.

 

INTERPRETATION:

The kinematic gait deviations identified in this study raise questions about the contribution of muscle weakness in HSP. Further research is warranted to determine contributing factors for gait dysfunction in HSP, especially the relative influence of spasticity and weakness.

 

SOURCE: Dev Med Child Neurol. 2016 Feb 22. doi: 10.1111/dmcn.13082. [Epub ahead of print] © 2016 Mac Keith Press. PMID: 26910787 [PubMed – as supplied by publisher]

 

Kinematic gait deficits at the trunk and pelvis: characteristic features in children with hereditary spastic paraplegia.

 

Adair B1, Rodda J2, McGinley JL3, Graham HK4, Morris ME5,6.

 

1 Centre for Disability and Development Research, Australian Catholic University, Fitzroy, Vic., Australia.

2 Hugh Williamson Gait Laboratory, The Royal Children’s Hospital, Parkville, Vic., Australia.

3 Department of Physiotherapy, University of Melbourne, Carlton, Vic., Australia.

4 Department of Orthopaedic Surgery, The Royal Children’s Hospital, Parkville, Vic., Australia.

5 School of Allied Health, College of Science, Health and Engineering, La Trobe University, Bundoora, Vic., Australia.

6 Department of Physiotherapy, Cabrini Healthcare, Malvern, Vic., Australia.

Survey on gene testing

Dear HSP community members,

Genetic Alliance Australia (GA) invites you to take a survey that is the first of its kind in Australia.

The project launched by GA is called “Australian patients and families’ perspectives on genome sequencing”. The aim of the project is to produce an “Australian Patient Charter on Genome Sequencing”. This will outline the views and opinions of patients and families regarding genome sequencing in the healthcare system. This will become an important reference guideline for policy and decision-makers when incorporating genome sequencing into the Australian healthcare system.

The project will involve an anonymous online survey for individuals and families affected by genetic conditions, and aims to gather their views and opinions on the use of genome sequencing in a clinical setting. The online survey was launched on 6^th May 2016 and will run for approximately two months. By participating in the survey you will have access to a video “Whole Genome Sequencing & You” which will serve as an education resource. There are various ways to access the survey:

• Invitation PDF Advert: http://www.geneticalliance.org.au/cmsAdmin/uploads/genome-sequencing-advert-v0-8.pdf
• Information on GA Website: http://www.geneticalliance.org.au/genome.php?1
• Direct link to the survey: https://www.surveymonkey.com/r/genomesurvey

The input from families and individuals will be highly valued and appreciated, and will ensure that GA has surveyed the many diverse genetic and rare patient groups across Australia.

The project will also involve a focus group towards the end of the June 2016 to further explore the answers provided in the survey and to gather more robust views. GA welcomes your input to provide any questions pertinent for us to ask the focus group participants.

If you have any questions contact the Genetic Alliance on 02 9295 8359 or email dianne@geneticalliance.org.au.

I would personally like to take this opportunity to thank you for your support in this Australia-wide project.

Kind regards,

Dianne Petrie OAM 

Executive Director

Genetic Alliance Australia

Research study establishes the link

 

It will come as no surprise to many with HSP, their families, loved ones and others who care for them that fatigue, pain and depression occur frequently and often severely in HSPers compared with healthy, non-HSP-affected people.

 

 

The statistical difference between the 2 populations is at a ‘highly significant’ level.

 

 

 

This supports the findings of an earlier study from 2009 where it was found that over half the population of HSPers in the study were depressed. That study also linked severity of depression with loss of mobility.

 

 

Even though these results seem self-evident, don’t underestimate the importance of this research as it establishes an evidence base for these outcomes associated with having HSP. Your doctors as well as allied health professionals such as your physio now have a good clinical reason to treat, or refer for treatment of, these outcomes of fatigue, pain and depression.

 

These results also change the nature of any request you might make of your doctor or allied health professional to investigate these issues when you report them, now that they are medically established by this research as different from non-HSPers reporting fatigue, pain or depression.

 

 

BACKGROUND AND PURPOSE:

Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their frequency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4-HSP).

 

METHODS:

Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student’s t test was used to compare groups and linear regression was used to assess correlations.

 

RESULTS:

Patients had higher fatigue scores than controls (31.0 ± 16.5 vs. 14.5 ± 16.0, P = 0.002) as well as pain (3.4 ± 2.7 vs. 1.0 ± 1.6, P = 0.001) and depression (12.7 ± 8.9 vs. 4.4 ± 3.8, P < 0.001, respectively). Fatigue was associated with depression and possibly with disease severity (P = 0.008 and 0.07, respectively).

 

CONCLUSIONS:

Fatigue, pain and depression are frequent and often severe manifestations in patients with SPG4-HSP.

 

SOURCE: Eur J Neurol. 2016 Feb;23(2):408-11. doi: 10.1111/ene.12839. © 2016 EAN. PMID: 26806216 [PubMed – in process]

 

Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations.

 

Servelhere KR1, Faber I1, Saute JA2, Moscovich M3, D’Abreu A1, Jardim LB2, Teive HA3, Lopes-Cendes I4, Franca MC Jr1.

 

1Department of Neurology, University of Campinas – UNICAMP, Campinas, SP, Brazil.

2Medical Genetics Service, Federal University of Rio Grande do Sul – UFRGS, Porto Alegre, RS, Brazil.

3Neurology Service, Federal University of Paraná – UFPR, Curitiba, PR, Brazil.

4Department of Medical Genetics, University of Campinas – UNICAMP, Campinas, SP, Brazil.