4. Demyelinating disorders.pdf

MULTIPLE SCLEROSIS AND OTHER DEMYELINATING DISORDERS Dr Suhail Al-Shammari Aminah Alawadh DEMYELINATING DISEASES OF CENTRAL NERVOUS SYSTEM: CLASSIFICATION • Monophasic/focal demyelinating diseases (clinically isolated syndrome) Comes inonephase notrecurrent • Acute optic neuritis only BAffectson...

MULTIPLE SCLEROSIS AND OTHER DEMYELINATING DISORDERS Dr Suhail Al-Shammari Aminah Alawadh DEMYELINATING DISEASES OF CENTRAL NERVOUS SYSTEM: CLASSIFICATION • Monophasic/focal demyelinating diseases (clinically isolated syndrome) Comes inonephase notrecurrent • Acute optic neuritis only BAffectsonlyoneplaceleg brainstem • Acute transverse myelitis (complete/ incomplete) • Acute brainstem demyelination • Monophasic/multifocal: One phasebutaffectsmore thanonepartoftheCNS • Acute disseminated Encephalomyelitis (ADEM) Usually • Polyphasic/multifocal demyelinating diseases after fluor virus Recurrent Affectsmore • Multiple sclerosis thanonepartofons egpreviouslythe • Neuromyelitis optica spectrum disease eyethenthe brainstem afterafewyears red Aqui MULTIPLE SCLEROSIS (MS) • MS is the most common cause of severe disability in young adults in western societies between 2040 yrs mited • The exact mechanism of disease is unknown ens • Damage to myelin and axons of the brain and spinal cord Autoimmune • Considerable evidence suggests that MS is immune-mediated 2 • T lymphocytes, macrophages, inflammatory cytokines, and perhaps antimyelin antibodies all appear to participate: andotherssuch o recurrent patches of inflammation with damage to myelin (demyelination) with damage to axons of the brain, spinal cord and optic nerves Secondarydamage to theaxondueto tothemyelinsheath immune mediateddamage agate remains Immune systemisactivated a specialtrigger by causes damageto Cnsdue to migrationofinflammatory manners IMMUNOLOGY OF MULTIPLE SCLEROSIS Damage axon is amend to the myelinsheath Neurodegenerationitselfcan trigger theimmune system Acycle or DAMAGE oh willleadto inflammation neurodegeneration MULTIPLE SCLEROSIS: TYPES • MS is not a single disease but several idiopathic demyelinating syndromes • Relapsing-remitting disease: progression is characterized by relapses of Theperiod between active disease with incomplete recovery remission relapse is during the periods of remission (most unknown canbe months or years common form - 80% of cases) • Secondary progressive disease: after 15yrs a patient progression becomes more aggressive so withrelapse remittingMs aggressive more progress in that a consistent worsening of function can secondaryMs occurs • Primary progressive disease: symptoms are progressive from the onset of disease with the early onset of disability (least common form) without remission eg Patientcan have pareisis thendevelops paraplegia withoutremission HOW COMMON IS MS AND WHO ARE MOST AT RISK? It is more • MS is more common in temperate zones in the northern common further and southern hemispheres and very rare in equatorial from the equator regions • Usually begins between ages of 20 and 40 • Affects women>men at a ratio of 2:1 Most commonalthoughno age is immune from developing Ms • In the United States the prevalence of MS is about 50100/100,000 PREVALENCE OF MS y More common in western areas eg USA Not as common in Europe Arabian areas MULTIPLE SCLEROSIS: CAUSES The cause of MS is unknown predisposition A Genetic Environmental Development of disease is influenced by genes and the environment Triggers Genetic • • • Concordance in identical twins is about 25-30% It 1 parenthas Msthereis a 3 chance Affects predominantly Caucasians ofthechild todevelop it Association with HLA antigens: DR 15 bothparents haveMs thereis a 6 If chanceofthechild developing it Environmental • • • • • Viruses: EBV duringinfancy or childhood Vitamin D Mostaccepted Provedtheory Sunlight Smoking Latitudes: much more common at higher latitudes (5 times more common than in the tropics) Spinal cord (50%) Sensory Motor Tingling, numbness, burning, tight bands, altered temperatureElectric snogensan sensation, Lhermitte’s symptom Weakness, heaviness, clumsinessI Paraparesis Sphincter MULTIPLE SCLEROSIS: SYMPTOMS Remember MS is Multiphasic g mug ca mono paresis quadreparesis ca ca Urinary urgency, incontinence, hesitancy, constipation, fecal incontinence, impotence yntedio Optic neuritis Unilateral in 90% of Blurred vision, ‘patch’ of visual (25%) patients loss, reduced color perception, pain on eye movement, oh patientswith phosphenes scotoma in oneeye neuro myelitis optica Brainstem/ Diplopia, dysarthria, vertigo, facial numbness/ weakness, cerebellar deafness, paroxysmal symptoms, e.g. trigeminal (20%) neuralgia, tonic spasms, ataxia EgPatient Other (5%) wiQuadmparesis numbne facial Indicative brainstem lesio of cognitive Hemiparesis, hemianopia, dysphasia, seizures, unilateral BilateralLanaridins pain in trigeminal area impairment 4symptomsmaybe confused with a stroke Recurrent demyelination can lead to brainatrophy SYMPTOMS- VISUAL LOSS: OPTIC NEURITIS • One of the most common presentations of MS 25 • Unilateral visual loss and retrobulbar pain which develops over several days Acute diminution of vision in oneeye Irreversible • Eye movements and bright lights may exacerbate the eye pain Maybe complete blindness • Visual acuity may be decreased to any degree, and color vision is often affected out of proportion to other elements of vision • A relative afferent pupillary defect (RAPD) is present in the affected eye L • Ophthalmoscopic examination is usually normal at presentation (retrobulbar optic neuritis) May be underestimated by GPs Ophthalmologist mmmm msn.n.mn mn mn SYMPTOMS- MYELOPATHY: TRANSVERSE MYELITIS • Is an inflammatory disorder of the white matter of the spinal cord that produces: Mostcommon area of the spinal ordaffected byMs Cervical dorsal spine then lumbar o Acute or subacute weakness o Sensory loss o Gait impairment o Urinary incontinence Eg dragginglegs whenwalking Especially in involvement of cervical dorsal spine • In patients with MS, transverse myelitis is characteristically incomplete and there is a partial myelopathy rather than dense paraplegia more common than quadriplegia • Progression occurs over a few days to weeks rather than beginning suddenly • A sharp sensory level is not typical SYMPTOMS- DIPLOPIA • The best-known pattern of diplopia in MS is internuclear ophthalmoplegia (INO) § A lesion of the medial longitudinal fasciculus ( MLF) disconnects the contralateral abducens nucleus in the pons from the ipsilateral oculomotor nucleus in the midbrain o Adduction of the ipsilateral eye is impaired while there is jerky nystagmus on abduction of the contralateral eye o It is typically bilateral NEUTRAL Adduction fan ASKED TO LookRIGHT of lefteye Jerking Nystagmus INTERNUCLEAR OPTHALMOPLEGIA ofabaneangeye compute movementin ASKEDTOLOOK borneyes LEFT complete conversion Glesion on the left Why The lesion only affects adduction SYMPTOMS- INCOORDINATION • Demyelination involving the cerebellar white matter and its brainstem connections (particularly the middle cerebellar peduncle) may lead to incoordination and ataxia • This is usually accompanied by severe action or For Example to intention tremor If you ask the patient hand followyourfingerwithhis when His hand will startoscillating approaching thetarget MAKING THE DIAGNOSIS a patientisn't If diagnosed it combination • Early diagnosis is valuable because it allows disease-modifying therapy to be early can lead to severe initiated at the beginning of the disease process disease of • Unfortunately, there is no single symptom, sign, imaging finding, or laboratory test that is 100% reliable for diagnosis of MS Symptoms Signs • It is a clinical diagnosis: supported by finding obtained with MRI, CSF and evoked potentials Imaging Multiple conditions y progression disability f • The central criterion for the diagnosis of MS is presence of CNS lesions whitematter greymatter disseminated in time and space • Excluding conditions that imitate MS 19 Ste sarcoidosis vitamin Biz in this place Other hereditary diseases at different • In some cases, the diagnosis is established by history and physical examination, times however, preclinical investigations are often crucial chronic infection PAST HISTORY • Inquire about prior symptoms typical for MS such as: o visual loss optic neuritis o weakness o numbness May I indicate previous attacks o double vision o vertigo and clumsiness • Deficits which lasted longer than 24h support the diagnosis while those which lasted for only several minutes/ hours do not • When reviewing the past history, ask about the evaluation that was performed at the time of each prior symptom and review these results if available PHYSICAL EXAMINATION • Physical examination often discloses evidence of prior episodes of demyelination Eg Patientwith reflexia Hyper oBabinskisign when light is shined • Most useful among these are findings that suggest prior optic neuritis such as red desaturation, optic atrophy, and initially constricts relative afferent pupillary defects (RAPD) thendilates on the eye it • Or those that reflect demyelination of the spinal cord such as hyperreflexia and upgoing toes Indicates posterior columninvolvement But he isn't symptomaticenough to complain aboutthis MULTIPLE SCLEROSIS: INVESTIGATIONS • MRI o High signal T2 lesions o Periventriculr plaques Around lateral ventricles o Dawson fingers: often seen on FLAIR images- hyperintense lesions penpendicular to the corpus callosum • CSF o Oligoclonal bands (and not in serum) o Increased intrathecal synthesis of IgG • Visual Evoked Potentials (VEP) Immunoglobulins only in CSF Indicates inflammation disrupting BBB found in blood as well it If o Delayed, but well preserved waveform Indicates current previous opticneuritis indicates systemic problem nor Ms MAGNETIC RESONANCE IMAGING (MRI) • MRI of the brain and spinal cord are the most useful diagnostic studies for patients with suspected MS • The diagnosis of MS hinges upon demonstrating CNS demyelination separated in both space and time • A diagnosis of MS is highly unlikely when multiple imaging studies are normal • The T2 hyperintense plaque is the characteristic MRI finding of demyelination secondary to MS • Common plaque locations are in: o The periventricular white matter o Corpus callosum o centrum semiovale o Middle cerebellar peduncle • Lesions in the corpus callosum which are oriented perpendicularly to the lateral ventricles are known as Dawson fingers and are particularly characteristic of MS Flare lesion Rings fBYIopny y MRI BRAIN ventricularlesions WhitePeri Rounded longitudinal M R I SP I N E Postcontrastenhancement • MRI with T1, T2, and indicatespresence active of contrast-enhanced lesion sequences is especially important in patients presenting with transverse myelitis • Spine MRI lesions involve the dorsal or lateral spinal cord rather than a dense transverse cross section o Are typically restricted to one or two segments Any more segments Neuro myelitis Optica LUMBAR PUNCTURE : CEREBROSPINAL FLUID (CSF) • Basic Studies cerebrospinal fluid abnormalities may support the diagnosis of MS and help to exclude imitators • The typical CSF profile in MS includes: Anymore Infection p • A mild elevation in lymphocytes (never exceeding 50 cells/mm 3 ) eg.HN • A mildly elevated protein (less than 100 mg/dL) • Neutrophilic predominance, very low glucose, and very high protein levels should prompt consideration of other diagnoses Notspecificto MS • Oligoclonal Bands Patients with MS synthesize abnormal IgG intrathecally can be present • These antibodies can be separated using gel electrophoresis into oligoclonal bands (OCBs) than 95 % of patients with MS will have abnormal OCBs. When evaluating for OCBs, in otherdiseases o More also perform serum protein electrophoresis to verify that the IgG is being synthesized intrathecally Sarcoidosis eg more than2bands present NEUROMYELITIS OPTICA SPECTRUM DISORDERS Patient may • Optic neuritis have 1 or both • Myelitis with long spinal cord lesions at thesametime Does not need to occur at the same time may occur in • Usually, the clinical features restricted to the above • Cranial MRI usually normal or non-specific • Oligoclonal bands are not seen in CSF • Relapsing course is characteristic • Most have specific biomarker: AQP4-IgG TypicallySpinalCord phases MYELITIS IN NMOSD • Typical Myelitis • Longitudinally extensive transverse myelitis MoreSevere than MS • Severe • AQP4+ d Morethan 2 spinal segments Pater Whiterareaon spinalcord OPTIC NEURITIS IN NMOSD • Typical optic neuritis • Unilateral/sequential • Long optic neuritis • Posterior/chiasm • Severe • AQP4 + Again paler Whiterareas ACUTE DEMYELINATING ENCEPHALOMYELITIS (ADEM) • Multifocal condition that typically begins abruptly and progresses over hours • Often associated with fever, headache, neck stiffness and reduced level of consciousness • More common in children than in adults • A Typically preceded by infection (or, less often, vaccination) Patientwillcomewith encephalopathy • Some patients with ADEM subsequently develop MS, but not all beneurodegenerative indicating signsdemyelination FocusesON Treatingacutephase MULTIPLE SCLEROSIS: MANAGEMENT Preventingrelapse Targetingspecific symptoms • Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure Acute relapse: o High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function) UsuallywestartwithIV then moreon to oral DISEASE MODIFYING DRUGS • Beta-interferon has been shown to reduce the relapse rate by up to 30% • reduces number of relapses and MRI changes, however doesn't reduce overall disability • Other drugs used in the management of multiple sclerosis include: o glatiramer acetate: immunomodulating drug - acts as an 'immune decoy’ month o natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on 16weeks the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier o fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph o nodes. An oral formulation is available o B-cell depleting antibodies: o Ocrelizumab o Retuximab Injectiongiven every 6months o Immune reconstitution: Alemtuzumab, cladripine Fatigue once other problems (e.g. anaemia, thyroid or depression) have been excluded à amantadine Spasticity • • • baclofen and gabapentin are first-line Other options: diazepam, dantrolene and tizanidine physiotherapy is important Bladder dysfunction • guidelines stress the importance of getting an ultrasound first to assess bladder emptying anticholinergics may worsen symptoms in some patients: o if significant residual volume → intermittent self-catheterisation o if no significant residual volume → anticholinergics may improve urinary frequency Oscillopsia gabapentin is first-line SPECIFIC PROBLEMS