Multiple sclerosis Multiple sclerosis (MS) is a chronic autoimmune, T-cell-mediated hypersensitivity type4 , inflammatory disorder of the CNS. Multiple plaques of demyelination are found throughout the brain and spinal cord, occurring sporadically over year, MS is a major cause of disability in young adults Multiple sclerosis (MS) is an important treatable cause of long-term disability in adults. The annual incidence is around 7 per , While the lifetime risk of developing MS is about 1 in 400. The incidence of MS is higher in Northern Europeans and the disease is about twice as common in females. Gender. Women outnumber men by 2: 1. There is evidence that ratio is widening with increasing Proportion of women being affected Slew 0 25) eludll 48 auuall gl élAge. Presentation is typically between 20 and 40 years of age. Presentation after age 60 is rare Eitology: 1/ environmental factor : There is also some evidence that low levels of vitamin D and lack of sunlight exposure may be a risk factor for MS. - Epstein-Barr virus (EBV) (EBV seropositivity is higher in patients with MS than in the general population) -Human herpesvirus 6 (HHV-6) 2/ genetic factor 4/ autoimmune factor An autoimmune cause of multiple sclerosis is therefore supported by genetic studies,a prominent role of immune cells in diseasePathology Plaques of demyelination, 2-10mm in size, are the cardinal features, Plaques occur anywhere in CNS white matter but have a predilection for distinct CNS sites: optic nerves,the periventricular region, the corpus callosum, the brainstem and its cerebellar connections, and the cervical cord (corticospinal tracts and posterior columns)Pathophysiology: Initial CNS inflammation in MS involves entry of lymphocytes across the blood-brain barrier, which can be inhibited by monoclonal antibodies like natalizumab which bind a481-integrin. These cells proliferate in perivascular lesions and the resulting inflammatory cascade releases cytokines and initiates destruction of the oligodendrocyte-myelin unit. Histologically, the resultant lesion is a plaque of inflammatory demyelination, most commonly in the periventricular regions of the brain, the optic nerves and the spinal cord (Fig. 28.25), and also found in the cortex. After the acute attack, gliosis and repair by oligodendrocyte precursor cells follows, leaving a shrunken scar Much of the initial acute clinical deficit is caused by the effect of inflammation on transmission of the nervous impulse rather than structural disruption of myelin, and may explain the rapid recovery of some deficits. In the long term, accumulating myelin loss reduces the efifciency of impulse propagation or causes complete conduction block, contributing to sustaineddisruption of myelin, and May CApiaill tile taps recovery of some deficits. In the long term, accumulating myelin loss reduces the efifciency of impulse propagation or causes complete conduction block, contributing to sustained impairment of CNS functions. Inflammatory mediators released during the acute attack, and loss of structural and trophic support from myelinating cells, contribute to axonal damage, which is a feature of the latter stages of the disease and is an important substrate of disability in the later, progressive phase of MS shovsdl - is an inflammatory demyelinating disease of the CNS in which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration, and tissue damageNote. (2a! antigen Gag ees NE GA antigen GN Teed repli bAsic Pe dd Se oe Se oS 3 ae Basi Protein == | Sore SO a ps ® (3) RX oli geclenelro te C1-eye nerve: Unilateral or asymmetric optic neuritis and bilateral internuclear ophthalmoplegia are typical -Central vision is affected more than peripheral vision. 1-Optic neuritis Symptoms may vary from a mild fogging of central vision with colour desaturation to a dense central scotoma, but very rarely complete blindness. Optic neuritis occurs when swelling inflammation damages the optic nerve a bundle of nerve fibers that transmits visual information from your eye to your brain. Common symptoms of optic neuritis include pain with eye movement and temporary vision loss in one eye and blurred vision The most common cause for optic neuritis is multiple sclerosis -optic neuritis may be found in the form of an afferent pupillary deficit (A plaque of demyelination within the optic nerve is the most common cauce )-optic neuritis may be found in the form of an afferent pupillary deficit (A plaque of demyelination within the optic nerve is the most common cause ) -Prognosis is better for patients with optic neuritis and only sensory relapses. 2-Brainstem demyelination demyelination -relapse affecting the brainstem causes combinations of diplopia and vertigo defect in corticobullbar tract and induce pseudobulbar palsy C5 > difficult in chewing and jaw reflex C7 > absent facial expression C9,10,11 > dysphagia: dysphonia C12> spastic tounge and dysarthriaPyramidal signs in the limbs occur when the corticospinal tracts are involved. 1/ weakness 2/ Hyperreflexia 3/ hypertonia 4/+Babinski -A typical picture is sudden diplopia, and vertigo with nystagmus, but without tinnitus or deafness. -Internuclear ophthalmoplegia results if there is a lesion in the medial longitudinal fasciculus connecting the 3rd, 4th, and 6th nerve nuclei. During horizontal gaze, adduction of one eye is decreased, with nystagmus of the other (abducting) eye; convergence is intact. In MS, internuclear ophthalmoplegia is typically bilateral; unilateral internuclear ophthalmoplegia is often caused by ischemic strokerh ee Bilateral internuclear ophthalmoplegia in a 53-year-old man with diplopia on lateral gazes. Loved! Bilateral internuclear ophthalmoplegia is pathognomonic for MS3/ spinal cord demyelination: ‘* cercical myelopathy, Syringomyelia, Diabetic myelopathy Brown squared syndrome: - sce before. + Transvers myelitis:~ acute inflammation of spinal cord may occur at any level, unknown etiology may follow viral infectiony associated also with multiple sderosise Treatment:~ corticosteroid. + Syringimylia s its dilatation of spinal canaly (Spared of posterior column sensation deep Paraparesis developing over days or weeks is a typical result of a plaque in the cervical or thoracic cord, causing difficulty in walking and limb numbness with tingling, often asymmetric. Lhermitte’s sign may be present Sometimes the arms are also involved in high cervical cord lesions. A tight band sensation around the abdomen or chest is common with thoracic cord lesions. -Lhermitte’s phenomenon Electric shock-like sensations radiate down the trunk and limbs on neck flexion. This points to a cervical cord lesion. Lhermitte’s is common in acute exacerbations of MS-Dorsal column defect : Defect in sensation ( gracil and cuneate) -autonamic nervous system defect Bladder and anus -Defect in spinothalamic tract : propriceptives brallg ashok ysluodl Jas - defect in spinocerebellar: AtaxiaClinical picture: Spinal cord lesions Paraparesis developing over days or weeks (see Box 26.62) is a typical result of a plaque in the cervical or thoracic cord, causing difficulty in walking and limb numbness with tingling, often asym- metric. Lhermitte’s sign may be present (see p. 823). Sometimes the arms are also involved in high cervical cord lesions. A tight band ‘sensation around the abdomen or chest is common with thoracic cord lesions. Common symptoms in MS Disability and neurological impairments accumulate gradually over the years. Several symptoms are common and many can be improved with symptomatic treatments. * Visual changes (see p. 810). * Sensory symptoms - often unusual, e.g. a sensation of water trickling down the skin. Sensory symptoms are the presenting feature in 40% of patients. Reduced vibration sensation and proprioception in the feet are among the most common abnor- malities on examination, but examination may be normal despite significant sensory symptoms. * Clumsy/useless hand or limb - due to loss of proprioception (often a dorsal column spinal plaque). * Unsteadiness or ataxia. * Urinary symptoms - bladder hyper-reflexia causing urinary urgency and frequency. Treatment is with antimuscarinics or intravesical botulinum toxin injections. * Pain - neuropathic pain is common. * Fatigue - a common and often debilitating symptom, which can occur in patients with otherwise mild disease. This sometimes responds to amantadine or a fatigue management programme. * Spasticity - may require baclofen or other muscle relaxants. Occasionally, botulinum toxin injections are used for focal spasticity. © Depression. * Sexual dysfunction. * Temperature sensitivity - temporary worsening of pre-existing symptoms with increases in body temperature, e.g. after exer- cise or a hot bath, is known as Uhthoff's phenomenon.> age — 20-50 years 52:9 > 3:2 > Onset — acute or gradual = Course Remission & exacerbation # Mentality: Euphoric - emotional instability # Speech: Slurred , Staccato or ScannedDiagnosis: The diagnosis of MS requires the demonstration of otherwise unexplained CNS lesions separated in time and place - this meant two or more clinical relapses affecting different parts of the nervous system, and the first ever episode is often referred to as a ‘clinically isolated syndrome’ (CIS). However recent changes to diagnostic criteria mean that MS may be diagnosed after an isolated episode because MRI can identify clinically silent lesions of different ages, and the presence of unpaired oligoclonal bands in the CSF can strongly suggest the development of future events As such MS 1 dove! -There is two different areas of CNS are affected in two different time alse yo Jol lesion JI SlicS! i 13] daodbe - clinical isolated syndrome 412 uu! 43320 yo 51 ySo 8 gail yo 0928 a9) 3UI lesion v9 1515 MS ile Silas - the confirm diagnosis is MRITypes of multiple sclerosis: 1/ relapsing-remitting MS : most (85-90%) patients have an initial relapsing and remitting clinical course with variable intervening recovery, although the majority will eventually enter a secondary progressive phase 2/ secondary progression: With gradual worsening over years ,70% Relapsing-remitting leads to secondary progression Relapsing-remitting Secondary progressive phase phase z 3 6 \ Time (years) Primary progressive MS z= 3 3 a Time (years)3/ primary progression: Gradual worsening progression without relapse remission 4/Relapsing progression : It resemble primary progression but progression with added relapses on a background of progressive disability from the outset Byles y2Sig slit! N31 9¢8 Charcot's triad of MS - Nystagmus -dysarthria (staccato speech) - ataxia (intension tremor) (UNsteady gait)Olb>Mo UMNL gs 8)4e pseudobulbar palsy - co cule gly deep sensation 9 superficial 31445 - Lhermitte’s phenomenon «1! MS