Multiple sclerosis

1- Epidemiology:

– The risk of developing MS depends on the region where prevalence of the first 15 years of his life were spent.

– There is a north-south gradient higher prevalence north.

– Predominance 60% female; the mean age of onset is 30 years. 70% between 20 and 40 years

2- Pathophysiology:

Multiple sclerosis– Demyelination plates arranged without order in the white matter and electively meadows CSF: periventricular and oval center of the cerebral hemispheres-hey, optic nerve, brain stem, cerebellum and spinal cord.

– In early inflammation (mononuclear lymphoplasmacytic infiltrate, perivascular) and disintegration of the myelin (phagocytosed by macrophages).

– Demyelination respects relatively axons: the axons myélino-dissociation.

– The remyelination is more or less complete, accompanied by a reaction astrocytic gliosis.

– Suffering axonal (from the beginning of the disease) resulting in permanent disability. Coexistence of different ages plates (dissemination in time) of a diffusely in the CNS (dissemination in space).

– The gray matter and the peripheral nervous system are generally respected

– Cranial nerves can be achieved in their intranévraxique path (eg: V and VII)

– A secondary axonal damage is possible after several outbreaks explaining the effects between relapses.

– Paroxysmal phenomena are associated with membrane phenomena (conduction block) and not with demyelination.These conduction blocks are aggravated by heat and acidosis.

– On the etiological, many factors are incriminated: viruses (measles Ac ++); environment (childhood); Autoimmunity: intrathecal synthesis of Ig polyclonal; reduction of CD8 + T cells at the time of relapses (which are high in remission).Role of TNFa and IFN.gamma. Production of Ac antimyéline. There is a genetic predisposition, but familial forms are rare.

3- Clinic:

– Evolution marked by regressive attacks (relapsing remitting, the most common).

– Common sensory disorders and sometimes features. paresthesia; Contact dysesthesia; Lhermitte’s sign, which is an equivalent of a later cordonale reached with brief electric shock sensation triggered by the flexion of the neck, down along the back and limbs in-férieurs.

– Motor impairment (pyramidal and cerebellar)

* The achievement of the pyramidal tract is common (80% after 5 years of evolution); different clinical forms (monoplegia hemiplegia …) py-ramidal syndrome (see the course)

* Cerebellar syndrome (50% of cases) with static and kinetic tremor often often disabling intensional

– Optic nerve: almost constant, often with subclinical altered only ENP. It carries a retrobulbar optic neuropathy. 22% of ESP begins with the infringement. It results in a sudden drop in visual acuity, sided with orbital pain. Sometimes incomplete with impaired vision colors (red-green color blindness) and central scotoma. The fundus is normal at first appears secondarily pallor of the temporal segment of the disc.

– Infringement of the brainstem:

* Disorders of oculomotor: diplopia is common, often linked to a internuclear ophthalmoplegia or ISO (III <=> VI).

In case of ISO, the eye in abduction (VI) is not followed by contralateral eye (III), where a horizontal diplopia, while the convergence of the eyes is possible. Bilateral ISO is highly suggestive of September

* Symptomatic Trigeminal V (trigeminal): lightning pains in the V territories, there hypoesthesia and abolition of the corneal reflex on the same side (eliminating an essential neuralgia V).

* Facial paralysis of peripheral type

* Vestibular Syndrome central type (disharmonious, fleeting dizziness, nystagmus multidirectional).

* NB: deafness is rare but subclinical alteration of the PEA is common.

– Sphincter and sexual disorders: frequent, almost constant after a change of more than 10 years. urinary urgency and urinary frequency, dysuria, residual urine. Impotence and frigidity.

– Psychiatric disorders: mood (depression), intellectual impairment on attention, memory, rarely subcortical dementia.

– Other signs:

* General signs: very common asthenia,

* Paroxysmal Events: brief tonic seizures; paroxysmal dysarthria; neuralgia (sensitive Tegretol carbamazepine).

* Important Signs: clinical worsening or appearance of new events related to sustained physical effort, strong heat, a warm bath or during a febrile syndrome (conduction block).

* Negative signs: no cortical involvement (no aphasia or apraxia, epilepsy exceptional); by the reach of the SNP; no extrapyramidal signs; outstanding homonymous hemianopia.

* Possible pupillary abnormalities: Argyll-Robertson (anisocoria with abolition of photomotor and conservation accomodation-convergence reflex); pupillary Marcus-Gunn phenomenon (mydriasis paradoxical to the illumination of the eye affected by retrobulbar optic neuritis

4- Additional tests:

– In consideration’re specific to multiple sclerosis.

– FNS normal, no inflammation, normal ESR.

LCR: Hypergammaglobulinorachie evocative (> 12% of the total protein) due to an intrathecal IgG synthesis with no known antigen specificity. It is oligoclonal distribution (oligoclonal band), absent from the serum. Lymphocytic pleocytosis (<50 cells / mm3) can be observed; normal LCR does not eliminate the Dc; lack of correlation between CSF abnormalities and severity of outbreaks.

MRI: clinicopathological dissociation; in suspension and soustentoriel and marrow; in the white matter and especially periventricular. T1: hypointense taking gadolinium plate when young (<3 months). T2: hyperintense areas. No mass effects. They are not specific in September They vary from one exam to another. Atrophy of the corpus callosum is frequently observed. Taking Gadolinium is a marker of disease activity. CT is less sensitive than MRI (recent isodense plates and take the contrast; the old plates are hypodense and are not enhanced by the product). At a more advanced stage -> ventricular dilatation.

– Multimodal evoked potentials (AEP, EPI, PES PEM) show the same lesions subclinical; multifocal lesions

5- positive diagnosis:

– Dissemination in time; dissemination in space, intrathecal synthesis of Ig (CSF); absence of other causes (MS remains a disposal Dc)

– Two clinical exacerbations with two distinct anatomical lesions sufficient to confirm the diagnosis of MS.

6- Development:

– Onset may be monosymptomatic in 50% of cases

– The development by regressive outbreaks is frequent (80%); is relapsing remitting. Which is characteristic of MS

– The thrust is defined by the appearance of new signs or worsening of pre-existing sign, outside of any intercurrent factor, for more than 24 hours and occurring over a month for the final push.

– Remission is defined by a persistent improvement in signs for at least one month.

– Regression of signs is under at least complete, leaving scars between relapses

– Secondary progressive forms: after 10 years of development, half of the patients present with progressive defined as a progressive worsening of neurological disorders for at least 6 months.

– The primitively progressive (15%) is essentially marrow; after 40 years; without female

– Gait: after 6 years of evolution

– Patient confined to his home: after 18 years of evolution

– Median survival: 35. decubitus complication deaths; urinary infection

– Poor prognosis factors: late onset, progressive forms, short interval between the first two outbreaks, intellectual deterioration.

7- Treatment:

Corticosteroids: Symptomatic treatment at the time of thrust; reduce the length of the thrust; do not prevent subsequent relapses; does not influence the course of the disease.

Antispasmodic: baclofen, dantrolene

Immunosuppressive drugs (DMARDs) are reserved for severe cases. Azathioprine (severe flare to form);cyclophosphamide (secondary progressive).

Immunomodulators (DMARD); interferon beta (IFN beta) which acts by opposing the toxic effects of the IFN.gamma and TNF and activating the suppressor cells.