Symptoms of MS

• The classic Charcot form eventually combines, after a certain time of evolution, spastic weakness of the lower limbs, a cerebellar syndrome both when standing and walking, speech disorders in the form of difficulties in articulating (slurred, explosive speech) and action tremors when grasping an object. The walk is similar to that of a drunken state, with the feet spread apart, lurching and intermittent leaning.
• The medullary forms are dominated by paraparesis (weakness of both legs, often asymmetric), which progresses gradually, and by spasticity, which may be more significant than muscle weakness. Sphincter disorders are then frequent, in particular urinary urgency and urge incontinence. The loss of deep sensitivity in the lower limbs leads to a disturbance in balance (sensory ataxia), which is aggravated when the eyes are closed or in semi-darkness. More rarely, weakness may be observed in one leg on the same side as the spinal cord injury, and thermal and pain sensitivity disorders in the other leg (Brown-Sequard syndrome).
• In sensory forms, visual impairment is often initial, while sensory disorders in the form of paraesthesia and objective sensory deficits fluctuate in intensity, regressing only to reappear during attacks in the same or different territories. One particular syndrome is typical: the "useless hand" syndrome. The presence of a plaque in the posterolateral part of the cervical cord leads to sensory disorders of the hand on the same side as the lesion, without any motor deficit, but rendering the hand non-functional, unable to grasp the shape, consistency or weight of an object, and unable to handle it. Pain phenomena are also frequent and must be differentiated between pain of inflammatory origin and pain of neuropathic origin.
• In cerebellar forms, signs of incoordination and tremor are in the foreground, which can make walking, writing and eating impossible.
•  seizures are rare in MS, occurring in only 2-5% of cases.

The most visible symptoms of MS involve gait and balance disorders. However, even these symptoms may be discreet or relatively hidden at the onset of the disease, only appearing after more or less prolonged physical effort. For example, a person with MS may walk normally for a few tens or hundreds of metres, or even several kilometres, and then notice the gradual onset of foot rubbing, heaviness in one leg, weakness in the foot lifts and more frequent stumbling. Similarly, when exercising, a balance disorder may become more pronounced and walking may become more unbalanced and unstable. Coordination of one leg may also be impaired during exertion, and the patient must keep a visual check on his feet to ensure they are in the right place. Tingling in the feet can also occur during exercise, even when the effort is reduced, and can spread up the legs. These tingles sometimes only appear when you stop exerting yourself. In all cases, these motor or sensory symptoms disappear after a relatively short period of rest, usually in a seated position. The mechanisms of these phenomena relate to what has been called a " medullary claudication ", i.e. a progressive slowing and blocking of nerve impulses at the level of the spinal cord according to energy demand.

Sphincter disorders are also little noticed by those around them and much better perceived by the persons themselves. These are usually urgent urinary needs that require a very quick and often more frequent trip to the toilet. This urinary urgency can lead to emergency incontinence. They result from hyper-reactivity of the bladder muscle called the detrusor. The bladder may also not empty completely during urination, and in the event of heavy residue, urinary tract infections occur regularly. The maximum tolerated volume of a urinary residue after micturition is 100 ml. Another phenomenon that can occur is the lack of synergy between detrusor contraction and bladder sphincter relaxation. The result is a paradox: an urgent need to urinate but difficulty in initiating urination when going to the toilet. Bladder disorders can have serious consequences, with infections spreading to the kidneys and septicaemia. The person has to live with a bladder that does not fill completely and does not empty completely. The advice of a urologist is often decisive. It should be noted that the same symptoms of urgency and possible incontinence may be present in the anal sphincter.

Another hidden symptom is erectile dysfunction in male MS patients following the presence of spinal cord lesions. Erectile dysfunction is often associated with bladder problems. In women, a decrease in perineal sensitivity and a decrease in vaginal secretions can make the sexual act painful and prevent orgasm. Fear of urinary problems occurring during sexual activity can further inhibit it.

Almost half of MS patients complain of pain. We need to distinguish two types of pain: inflammatory pain and neuropathic pain. Inflammatory pain is the normal response of an intact pain perception system when it is subjected to a painful stimulus. These include osteoarticular pain, which is often localised and increased mechanically by movement or position, visceral pain, muscular pain and skin pain caused by trauma or burns. Conversely, neuropathic pain is the consequence of a dysfunction or structural lesion of the nervous system itself, whether in its peripheral (post-Zoster pain, for example) or central part (post-cerebral thrombosis pain, for example, or on MS plaques). It is experienced by about 50% of MS patients and may be spontaneous without any stimulation. Such is the case, for example, with trigeminal neuralgia, caused by the presence of a plaque in the nerve bundles connected to the sensory nucleus of this nerve. It can also be provoked by stimulation that should produce only a minimal painful sensation (known as hyperalgesia) or by stimulation that is not normally painful, such as a touch (known as allodynia). The characteristics of neuropathic pain are often described as burning, painful cold sensation, tightness or tourniquet, possible electric shocks, tingling, nettle stings, reduced sensitivity, or conversely, hypersensitivity to the sting. The extreme is painful anaesthesia, i.e. pain felt in an area where sensitivity has been lost. 

The mechanisms underlying chronic pain following CNS damage, as in MS, are still poorly understood. However, there is always damage to the nerve pathways with thermoalgesic deficit. This damage can cause hypersensitivity of the pain receptors and disinhibition of the nerve fibres that discharge spontaneously. Thermoalgesic nerve pathways are present throughout the spinal cord, in the thalamus, and in the projections from the thalamus to the cerebral cortex.

Neuropathic pain is difficult to treat. The usual analgesics are not very effective. In practice, we mainly use anti-epileptic drugs. These include carbamazepine (Tegretol), Gabapentin (Neurontin) and Pregabalin (Lyrica). Clonazepam (Rivotril) is also used, but causes severe drowsiness. Older antidepressants such as Amitriptyline (Tryptizol, Redomex) or Duloxetine (Cymbalta) are also used to treat neuropathic pain. The aim is to reduce them. Our medications are more active against painful discharges than against chronic burns. It was long thought that opioids were ineffective in the treatment of neuropathic pain. More recent studies have shown that these substances can have a genuinely beneficial effect, but that the results vary considerably between individuals, with some patients experiencing relief while others do not. In general, however, opiate treatment for neuropathic pain requires a much higher dosage than for inflammatory pain.

In addition to inflammatory and neuropathic pain, we must also consider pain secondary to muscle hypertonia known as spasticity. Damage to what is known as the pyramidal motor pathway between the motor neurons in the cerebral cortex and the motor neuron in the spinal cord causes not only weakness of the muscles involved but also spastic stiffness, which can be painful. It is a latent cramping, contracture or tourniquet sensation, which may develop into intermittent but brief spasms, or the persistent impression of having run a long distance in the days before... This spasticity is sometimes useful to compensate for muscle weakness and stand upright. But it worsens under the effect of stress, cold, dampness, etc. When it is excessive and painful, it is mainly treated by taking Baclofen orally. In the most serious cases, it may be necessary to use an intrathecal pump (a catheter inserted directly into the CSF around the spinal cord) to infuse Baclofen locally and continuously. Such treatment makes the lower limbs more supple, facilitates nursing and prevents bedsores. The bladder muscles (sphincters and detrusor) can also show similar spasticity, which can be treated with local, repeated injections of Botox.

In the event of pain that is resistant to conventional medical treatment, it is necessary to contact a specialist algology centre. This could include a discussion of the benefits of using cannabinoid derivatives (Sativex), as well as performing percutaneous or intrathecal or intracerebral stimulation of the cortex using locally implanted electrodes.

Cognitive disorders disrupt visual and verbal memory (the information provided by language via the auditory pathways) for recent events, learning disabilities, mental flexibility that enables fluid transition from one activity to another, and speed of execution of cognitive tasks. These problems often develop insidiously, and the person may not realise it until several years later, when they are experiencing difficulties in their professional activity or simply in running their household. They are relatively correlated with the number of cerebral white matter lesions and in particular frontal lesions. They correlate even better with atrophy of the thalamus , which is an important relay centre and is involved in general brain activation. Similarly, atrophy of the corpus callosum plays an important role in these cognitive disorders, as it contains all the nerve fibres that connect the two hemispheres of the brain. Demyelinating plaques therefore cause dysconnections between different areas of the brain, since at the level of these plaques, the speed of nerve impulses is greatly reduced and the number of nerve fibres can be reduced by transection and secondary degeneration. More than the total number of plaques, the location of some of them seems to play an important role in what is known as cerebral connectivity. All the nerve bundles in the cerebral hemispheres can be compared to airways, with their hubs and secondary dispersions. Plaques located in highly connected areas will have a greater adverse impact on the brain's ability to function. This is an important field of research that goes beyond MS and focuses on the ' connectome ', i.e. the study of connections between different brain regions.

 Fatigue is a common symptom in MS. Here we need to distinguish between primary fatigue due directly to the disease, and secondary fatigue following sleep disorders, taking analgesic medication, muscle atrophy or prolonged inactivity. Primary fatigue due directly to the disease often occurs in fits and starts, and is likened to extreme lassitude. It consists of a loss of the physical and/or mental energy needed to carry out the usual activities. Here too, atrophy of the corpus callosum could play an important role in this primary fatigue.

Personality changes are also common, even though they may initially go unnoticed. The main symptoms are Impulsive overreaction and a lack of control over emotions. These disorders result from lesions in the frontal lobe and a disruption in emotional self-regulation . This often results in "hot-headed" behaviour, which the patient then blames himself for, and which can damage relationships with family, friends and colleagues. These sudden mood swings are hard on those nearest and dearest, who are the first to suffer. Once again, explaining these extreme reactions by the presence of frontal plaques, introducing a bit of self-mockery, cultivating humour, relieving guilt... are the best ways of putting up with these uncomfortable reactions. The suffering of the partner and close carer must also be taken into account.

Conversely, and more rarely, another facet of frontal syndrome is characterised by apathy, relative euphoria and emotional detachment incomprehensible to those around.

Alongside antidepressants, mood regulators, psychological support and relaxation and "mindfulness" techniques, the best treatment is preventive and consists of slowing down the accumulation of brain damage as much as possible before a critical threshold is reached and these symptoms become evident. Specific psychiatric disorders are discussed in the chapter on comorbidities.