AGM2015: The differences between pure and complex HSP - Prof Henry Houlden

Professor Henry Houlden works at the National Hospital for Neurology and Neurosurgery, in London. His presentation covered three areas:

• The differences between pure and complex HSP
• Genetics and genetic testing
• Shared network and genome sequencing 

Prof Houlden reminded us that HSP is generally described with increased stiffness, muscles becoming weaker and a slow progression. For pure HSP the three main areas are legs, bladder and the back. Pure HSP can also affect spasticity in other areas (including the upper body), but if there are other symptoms present then this becomes complex HSP. There is some variation in what symptoms might be expected, but these might include balance. A few videos were then shown with some examples.

If there is not a clear family history then an MRI scan of the brain and the spinal cord can help the diagnosis. For example, if there are some symptoms and compression in the spine this is not HSP and can be treatable. If the initial scan reveals that HSP is a contender, then blood an be sent for genetic testing, and tests on parents/siblings (etc.) can help in a better identification.

The scan would also show up the corpus callosum (a thick band of nerve fibers that connects the left and right sides of the brain allowing for communication: transfer of motor, sensory, and cognitive information). A thin corpus callosum occurs in some complex forms of HSP. For patients with complex HSP a repeat scan every 5 years would help to measure progress/change over time.

Some patients also experience problems with their feet - for example blisters and high arches (blisters can be a problem for people with HSP and diabetes http://www.nhs.uk/Livewell/foothealth/Pages/Diabetesandfeet.aspx) Examination of these can lead towards a diagnosis.

Prof Houlden indicated that about 30% of HSP diagnoses are not genetic. Simply, not all of the genes which cause HSP have been identified yet. There are some 25,000 genes in the body, and currently (Feb 2015) 74 different HSP genes have been identified. Getting the correct diagnosis can give you confidence - there is confirmation of what you have, and the course of can be anticipated - including potential complications. 

The most common pure HSP types with dominant inheritance are SPG4, which accounts for about 40% of cases, SPG3A which accounts for some 2-3% of cases and SPG 31 which accounts for some 1-2% of cases. The most common complex HSP types are SPG11, SPG7, KIF5A (also known as SPG10) and SPG 35. Prof Houlden did not give prevalence information. 

Types of HSP which have a dominant inheritance pattern carry a risk of 50% of passing HSP to the next generation (assuming only one parent carries the gene). Each child has an equal risk of inheriting the gene. For types of HSP which are recessive, the risk of passing the gene to the next generation is tiny, unless both parents are from the same family. Tests can be done prenatally, by CVS (Chorionic villus sampling) at about 10.5 weeks or by amniocentisis at about 16 weeks - however both tests carry risks of miscarriage and/or infection. Alternatively, Pre-implantation genetic diagnosis can be used (like IVF) to check, however this needs funding and the permission of your GP.

Prof Houlden then talked about management of HSP, by reference to Spastin (SPG4). The main points were:

• Physiotherapy and orthotics
• FES (functional electrical stimulation)
• Baclofen
• Self catheter and Detrusitol (noting Detrusitol works best if the bladder empties fully)
• High walking sticks (these result in a more upright walking position)
• Hip and knee replacement later in life.

On FES, it was observed that relatively few people were using FES 3-4 years ago, and the uptake of this has increased more recently. FES is available for HSP in London, Sheffield and Salisbury.

Prof Houlden talked briefly about bowel issues. The effects are not predictable, and this cannot be used in differentiating between pure and complex HSP. Bowel issues can usually be treated.

Prof Houlden then talked about a potential link between HSP and dementia. There can be some cognitive problems later in the progression of HSP, including SPG4. Sometimes the brain has to focus on walking which it does at the expense of other processing. These problems may also occur as a result of fatigue - which increases as it becomes harder to do more, or they may be a side effect of medicaiton being taken. If there are mental problems with HSP then tools to help cognition may be of limited benefit. In this case it is better to treat the condition.

 A European HSP network is (being) set up, with the objective of sharing information, particularly clinical problems, databases of patients and blood/MRI results. This can help research and the treatment of HSP. The network is looking for biomarkers for HSP which could track the progression of HSP, the effects on bones and/or the benefits of drugs. There is more on biomarkers here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078627/. The shared database of patients can be used to help find candidates to take part in drug trials. It is likely that drug trials will be targeted to specific genes, and it becomes necessary to find a sufficient sample to determine the benefits of the drug.

Lastly, Prof Houlden covered getting access to services. Your GP is able to give a referral, and appointments can be booked using the choose and book system. He advised seeing a specialist in clinic once every few years, noting that it can be difficult for a local neurologist to be knowledgeable of rare diseases, but there is more money available for rare diseases at the moment, and this is leading to increased awareness.