Hereditary spastic paraplegia

The name covers not one illness but a whole family of rare inherited conditions with the same outcome: the long nerve fibres running from the brain down the spinal cord to the legs gradually stop carrying the signal. The legs become stiff and weak and the walk changes, slowly, over years. It also goes by the name familial spastic paraparesis, and older textbooks call it Strümpell-Lorrain disease. Nobody knows exactly how many people live with the diagnosis: it is recognised late and often under someone else's name.

What is actually damaged

The instruction to take a step travels from the brain's cortex to the leg muscle along a single projection of a nerve cell, more than a metre long in an adult. It is the longest structure in the body and it depends on flawless transport inside the cell itself. The genes that fail in this condition are precisely the ones handling that transport, along with the shape of the cell's internal membranes and the handling of fats in nerve tissue.

When the system falters, the projection dies back from its far end and shortens towards the cell body. Two recognisable features follow. It is the legs that suffer, and the further from the trunk the worse: the foot before the thigh, while the hands, speech and swallowing stay out of it in the commonest form because their pathways are shorter. And what dominates is not paralysis but spasticity: the muscle receives a surplus of contract signals and none of the braking ones, so it stays tense. The leg does not so much fail to obey as resist the movement. Less severely, the fibres carrying vibration sense and the position of the foot are affected too, along with those that hold the bladder in check.

How it starts and where it goes

The beginning is almost never a noticeable event. People recall that running went first, that uneven ground became hard work, that the sole started wearing down at the toe. Some spend years being treated for "flat feet" or "a trapped nerve in the back". What brings them to a doctor is usually not pain but accumulated clumsiness: tripping on level ground, falling when they try to speed up. From there the pattern of complaints is fairly consistent:

• stiffness in the legs, worse in the morning, after long sitting and in the cold;
• weakness of the muscles that lift the thigh and pull the foot upwards, hence the scuffing gait and the catching toe;
• tight, shortened calves, so that in time the heel no longer reaches the floor;
• painful night-time spasms and jerks;
• a sudden urge to pass urine, sometimes with no way of holding on;
• blunted vibration sense in the feet, which makes balance harder to keep in the dark.

The first signs can appear at any age: in a child who walked late and goes about on tiptoe, and in someone approaching sixty. The pace cannot be predicted in advance, but the later the onset, the slower the course tends to be. Many people manage a lifetime without support; others come to need a stick, a walking frame or a wheelchair for longer distances. In the "pure" form life expectancy is not shortened and the mind stays clear.

When something else joins the legs

In roughly one person in ten the picture is not confined to the legs. Those variants are called complicated, and they are in truth separate genetic diseases in which leg spasticity is only one feature. Alongside it come damage to the peripheral nerves with numb hands and feet, disturbed balance and coordination, epileptic seizures, learning difficulties and failing memory, hearing loss, damage to the optic nerve or the retina, persistent fish-scale scaling of the skin, and trouble with speech and swallowing.

Complicated forms usually begin in childhood or adolescence, are more often recessive and move faster. For a family the difference matters: the investigations, the outlook and the risk to future children are all different, so pinning down the exact gene is particularly worthwhile here.

What runs in the family

More than eighty genes are known in which a fault produces a similar picture; the commonest of them codes for the protein spastin. In dominant inheritance an altered gene from one parent is enough, and the chance of passing it on to each child is one in two. But inheriting the gene and inheriting the same illness are not the same thing: within one family a mother may walk unaided at seventy and consider herself well while her son takes a stick at thirty. Recessive inheritance needs the altered gene from both parents, who are usually well themselves; the risk for each child is one in four, and those forms are more often complicated. There are also rare X-linked variants, in which men are the ones affected.

Having no relative with the same condition does not rule the diagnosis out: the change may have arisen for the first time in this person, or it may have shown up in relatives so mildly that nobody counted it as an illness.

Look-alike conditions that can be treated

This is the most important part of the conversation. Hereditary spastic paraplegia is a diagnosis of exclusion: no test proves it directly, while there is a list of conditions that look exactly the same, several of them treatable.

• Vitamin B12 deficiency causes spasticity and loss of position sense in the legs, shows up in a blood test and can be replaced. Time lost here becomes irreversible.
• Copper deficiency is uncommon but turns up after stomach surgery and with a long-standing excess of zinc, and the picture is almost indistinguishable.
• Adrenomyeloneuropathy, an inherited disorder of fatty acid handling in men, looks for years like pure spastic paraplegia. The danger is not in the legs: in some patients the adrenal glands fail at the same time, which is life-threatening and fully corrected by hormone replacement. So in a man with spastic legs the very-long-chain fatty acids are always checked.
• Dopa-responsive dystonia starts in childhood with stiff legs that worsen towards evening. On small doses of levodopa the person returns to an ordinary life, so with a childhood onset a trial of treatment is almost always given.
• Compression of the spinal cord: a tumour, a disc prolapse, cervical stenosis, syringomyelia, a tethered cord in children. This is the commonest thing found instead of the inherited disease, and the reason everyone gets a scan.
• Multiple sclerosis, other inflammatory disorders of the cord, and infections that destroy it over years.
• Cerebral palsy: there the picture does not worsen with time, so slow but relentless progression over years argues against it.

Hence the usual order: a neurological examination, questions about three generations of the family, scans of the brain and spinal cord, blood tests and sometimes an examination of the spinal fluid. Genetic testing comes last and confirms what the clinical picture has already built. In the pure form the scans are most often normal, and that is expected: striking changes are, on the contrary, a reason to look for another cause.

What genuinely helps day to day

There is as yet no drug that halts the process itself. But most everyday difficulty comes not from the loss of fibres but from spasticity and its consequences, and those can be influenced, appreciably.

• Daily stretching and physiotherapy are the foundation, and they only work as a permanent routine rather than a course twice a year. The main aim is to stop the calves and the back of the thigh shortening irreversibly.
• Muscle relaxants take the edge off the excess tension. The dose is built up slowly from the bottom, because overshooting brings drowsiness and, oddly enough, worse walking: over the years a person comes to carry part of their weight on those very tense muscles. Baclofen must never be stopped abruptly: sudden withdrawal brings fever, confusion, a sharp rise in muscle tone and seizures.
• Botulinum toxin injections into selected muscles help when the obstacle is not general stiffness but a specific one, such as a foot that turns inwards.
• A pump delivering the drug straight into the spinal fluid is considered in severe spasticity, when tablets at tolerable doses no longer cope.
• Splints, insoles and foot support, and where needed a stick, a frame or a wheelchair for longer distances. These are tools, not a defeat: they save energy and cut the number of falls.
• The bladder: timed voiding, drugs that reduce urgency, treatment of infections. Worth taking to a urologist rather than putting up with.
• Back and knee pain almost always comes from a lopsided gait and is treated through the gait and the footwear.
• Fatigue and mood. Walking on legs like these is constant hard work, and flagging energy is physiological here. Low mood is common and responds to treatment just as it does in anyone else.

Exercise does not speed the disease up: advice to "spare the muscles" is harmful here. Loss of condition through inactivity adds its own weakness to the weakness of the illness, and that second part is reversible.

Signs that do not fit the diagnosis

Even with a confirmed inherited diagnosis a person is not immune to other diseases of the spine. See a doctor the same day if:

• the legs have weakened over days or weeks rather than years;
• weakness or clumsiness appears in the hands;
• numbness rises to a clear line across the trunk, like a belt;
• urine stops coming or, conversely, stops being held, and sensation in the perineum is lost;
• severe back pain appears, especially at night, with weight loss or fever;
• after a missed dose of baclofen there is fever, confused speech and worse muscle cramping than usual.

Weakness building rapidly in both legs together with disturbed passing of urine is a situation counted in hours: there you call an ambulance — across Europe the number is 112 — or go to the emergency department rather than wait for a booked appointment.

Online consultation

A remote appointment covers the questions that come up most in this subject. Before a diagnosis, it helps to work out whether the complaints really do correspond to spasticity and to order the investigations so that treatable causes are ruled out first. Afterwards, it is a good setting to discuss adjusting and withdrawing muscle relaxants, the exercise routine, the choice of splint, seeing a geneticist before planning children, and adapting the home. It is easy to show the doctor a video of your own walking: for judging change over time that is sometimes more useful than any description. The urgent signs in the list above are not dealt with through a screen.

This material is for information only and does not replace medical advice.