In The Name In The Name ofof

GodGod

CASE PRESNTATIONCASE PRESNTATION

OPTIC NEUROPATHY OPTIC NEUROPATHY WITH WITH

PROGRESSIVE MYELOPATHYPROGRESSIVE MYELOPATHY

Loghman HospitalLoghman Hospital

Y. KHOLGHI MDY. KHOLGHI MD

HISTORYHISTORY A 51 years old married right handed female that was in A 51 years old married right handed female that was in

good health until 11 years PTA. good health until 11 years PTA. She has history of lower limbs heaviness in She has history of lower limbs heaviness in

combination with feeling of coldness in 11 years PTA, combination with feeling of coldness in 11 years PTA, that persist 1-2 month and then subside without any that persist 1-2 month and then subside without any treatment.treatment.

After 1 year she had complain of visual loss in right After 1 year she had complain of visual loss in right eye and then 3-4 month later in left eye with visual eye and then 3-4 month later in left eye with visual acuity of complete visual loss in right and 6/10 in left acuity of complete visual loss in right and 6/10 in left eye.eye.

Each of visual attacks treated with Methylprednisolone Each of visual attacks treated with Methylprednisolone pulse and oral Prednisolone after it, that lead to pulse and oral Prednisolone after it, that lead to complete recovery.complete recovery.

Concurrent with visual attacks she had sensory Concurrent with visual attacks she had sensory complain as coldness and tingling with feeling of complain as coldness and tingling with feeling of heaviness in lower limbs that persists in subsequent 4 heaviness in lower limbs that persists in subsequent 4 years in the spite of normal living activities.years in the spite of normal living activities.

She had not any urinary complains in 5 years duration. She had not any urinary complains in 5 years duration.

HISTORYHISTORY Since 6 years PTA, she has history of progressive Since 6 years PTA, she has history of progressive

stiffness and weakness in lower limbs with involvement stiffness and weakness in lower limbs with involvement of hands as tingling and heaviness after 2-3 years, that of hands as tingling and heaviness after 2-3 years, that lead to inability to walking without assistance and loss lead to inability to walking without assistance and loss of dexterity in hands in recent 1-2 months respectively.of dexterity in hands in recent 1-2 months respectively.

She has history of fatigue, frequency, urge She has history of fatigue, frequency, urge incontinence and prolonged constipations since 6 years incontinence and prolonged constipations since 6 years PTA.PTA.

Review of Lhermitte’s sign, diplopia, vertigo, unsteady Review of Lhermitte’s sign, diplopia, vertigo, unsteady gait, abnormal speech, difficulty swallowing, and other gait, abnormal speech, difficulty swallowing, and other systems was unremarkable (no joints pain and skin systems was unremarkable (no joints pain and skin lesions). lesions).

She was under treatment of interferon in 2 subsequent She was under treatment of interferon in 2 subsequent years that discontinue it since 2 years PTA.years that discontinue it since 2 years PTA.

She is under treatment of Amantadine, Baclofen, She is under treatment of Amantadine, Baclofen, Asentra, Alprazolam for reliving stiffness, fatigue and Asentra, Alprazolam for reliving stiffness, fatigue and anxiety. She previously treated with MTX.anxiety. She previously treated with MTX.

Positive finding in N/EPositive finding in N/E Norma reaction of both pupils to light.Norma reaction of both pupils to light. Normal visual acuity. Normal visual acuity. Mild pallor of optic disk in both eyes.Mild pallor of optic disk in both eyes. Spastic quadriparesia preferentially (with Spastic quadriparesia preferentially (with

all signs), loss of abdominal reflex, and all signs), loss of abdominal reflex, and muscle force of 4/5+ in lower limbs with muscle force of 4/5+ in lower limbs with flexion deformity of ankles in rest position.flexion deformity of ankles in rest position.

A sensory level at T7-T8 with abnormal A sensory level at T7-T8 with abnormal deep sensation in lower limbs.deep sensation in lower limbs.

Ability to walking without assistance (up Ability to walking without assistance (up to10 m). to10 m).

Abstract of History and N/EAbstract of History and N/E

A 51 years old married right handed female with A 51 years old married right handed female with history of visual blurring, progressive weakness history of visual blurring, progressive weakness and stiffness of lower limbs, fatigue, frequency, and stiffness of lower limbs, fatigue, frequency, incontinence and constipation since 11 years incontinence and constipation since 11 years PTA. PTA.

She has bilateral optic disk changes, spastic She has bilateral optic disk changes, spastic quadriparesia, a sensory level at T8-T9 and quadriparesia, a sensory level at T8-T9 and abnormal deep sensation of lower limbs in N/E. abnormal deep sensation of lower limbs in N/E.

LocalizationLocalization

With a normal cranial exam, causing With a normal cranial exam, causing lesion of spastic quadriparesia is inlesion of spastic quadriparesia is in

cervical region.cervical region. But with visual loss in different time, she But with visual loss in different time, she

has a additional localization sign for has a additional localization sign for correct diagnosis as correct diagnosis as multiple lesions in multiple lesions in multiple sites with dissemination in multiple sites with dissemination in timestimes. .

Differential DiagnosisDifferential Diagnosis

Toxic and metabolic diseases.Toxic and metabolic diseases. Degenerative diseases.Degenerative diseases. Tumor and mass lesions.Tumor and mass lesions. Infectious diseases.Infectious diseases. Vascular diseases.Vascular diseases. Demyelinating diseasesDemyelinating diseases..

Toxic and metabolic diseasesToxic and metabolic diseases

Drugs (Cisplatin, Heroin abuse and rarely Drugs (Cisplatin, Heroin abuse and rarely Cocaine use).Cocaine use).

Toxin (Conzo and lathyrism).Toxin (Conzo and lathyrism).

Metabolic ( Vitamin B12 deficiency, Mercury Metabolic ( Vitamin B12 deficiency, Mercury intoxication, Alcohol/tobacco amblyopiaintoxication, Alcohol/tobacco amblyopia

Central pontine myelinolysis, Marchiafava-Central pontine myelinolysis, Marchiafava-Bignami syndrome).Bignami syndrome).

Degenerative DiseasesDegenerative Diseases

PLS.PLS. HSP.HSP. SCD.SCD. Hereditary disorders of myelin Hereditary disorders of myelin

metabolism (ALD, MLD, Krabbe's).metabolism (ALD, MLD, Krabbe's). Arnold- Chiari malformation.Arnold- Chiari malformation.

Tumor and Mass lesionsTumor and Mass lesions

Spinal cord mass lesion:Spinal cord mass lesion: Intramedullary Intramedullary Extramedullary Extramedullary

Craniocervical junction tumor. Craniocervical junction tumor.

Paraneoplastic Paraneoplastic encephalomyelopathies.encephalomyelopathies.

Infectious DiseasesInfectious Diseases

HTLV I & IIHTLV I & II LYME LYME SYPHILISSYPHILIS HIVHIV TBTB

Vascular DiseasesVascular Diseases

Arteriovenous Malformations.Arteriovenous Malformations. Cavernous Angiomas.Cavernous Angiomas. Isolated CNS Vasculitis.Isolated CNS Vasculitis. Collagen Vascular Diseases.Collagen Vascular Diseases. Stroke.Stroke.

Inflammatory Demyelinating DiseasesInflammatory Demyelinating Diseases

Acute Disseminated Encephalomyelitis.Acute Disseminated Encephalomyelitis.

VARIANTS OF MULTIPLE SCLEROSIS.VARIANTS OF MULTIPLE SCLEROSIS.1.1. Recurrent Optic Neuropathy Recurrent Optic Neuropathy

2.2. Devic's Disease (Neuromyelitis Optica)Devic's Disease (Neuromyelitis Optica)

3.3. Slowly Progressive MyelopathySlowly Progressive Myelopathy

Multiple Sclerosis (PPMS OR SPMS)Multiple Sclerosis (PPMS OR SPMS)..

Recurrent Optic NeuropathyRecurrent Optic Neuropathy

There are patients whose entire clinical illness is There are patients whose entire clinical illness is confined to the optic nerves. confined to the optic nerves.

They may have sequential affection of one nerve, They may have sequential affection of one nerve, then the other, or they may have simultaneous then the other, or they may have simultaneous bilateral vision loss, a state that is quite uncommon bilateral vision loss, a state that is quite uncommon in classic MS. in classic MS.

Children and preadolescent patients are more likely Children and preadolescent patients are more likely than adults to have recurrent or simultaneous optic than adults to have recurrent or simultaneous optic neuropathy. neuropathy.

Rarely there is slowly progressive optic neuropathy, Rarely there is slowly progressive optic neuropathy, similar to that seen with optic nerve sheath tumors, similar to that seen with optic nerve sheath tumors, such as meningioma.such as meningioma.

In bilateral ON, sarcoidosis is commonly a diagnostic In bilateral ON, sarcoidosis is commonly a diagnostic consideration.consideration.

Devic's Disease (Neuromyelitis Optica)Devic's Disease (Neuromyelitis Optica)

A combination of bilateral optic neuropathy and A combination of bilateral optic neuropathy and cervical myelopathy make up this condition. cervical myelopathy make up this condition.

Reported cases indicate that the myelopathy Reported cases indicate that the myelopathy tends to be more severe, with less likelihood of tends to be more severe, with less likelihood of recovery.recovery.

In some patients the optic neuropathy and the In some patients the optic neuropathy and the myelopathy occur at the same time, in others myelopathy occur at the same time, in others one or the other component is delayed (days to one or the other component is delayed (days to weeks). weeks).

The longer the interval, the more like typical MS The longer the interval, the more like typical MS is the pathology and better prognosis.is the pathology and better prognosis.

Devic's Disease (Neuromyelitis Optica)Devic's Disease (Neuromyelitis Optica)

Because the optic nerve and the Because the optic nerve and the cervical spinal cord are two of the cervical spinal cord are two of the locations in the nervous system in locations in the nervous system in which the lesions of MS are typically which the lesions of MS are typically found, many patients could be found, many patients could be classified as having Devic's disease, or classified as having Devic's disease, or syndrome.syndrome.

Devic's Disease (Neuromyelitis Optica)Devic's Disease (Neuromyelitis Optica)

Devic's like syndrome can be a manifestation Devic's like syndrome can be a manifestation of ADEM or rarely of other autoimmune of ADEM or rarely of other autoimmune disease, such as SLE or APAS. disease, such as SLE or APAS.

This seems to be especially true of patients This seems to be especially true of patients with relapsing Devic's syndrome, making up with relapsing Devic's syndrome, making up approximately one half the patients.approximately one half the patients.

In a few patients the distinction between an In a few patients the distinction between an MS variant and SLE (so-called lupoid MS variant and SLE (so-called lupoid sclerosis) is essentially impossible to make, sclerosis) is essentially impossible to make, and some of these are patients with and some of these are patients with neuromyelitis optica.neuromyelitis optica.

How differentiate Devic’s from How differentiate Devic’s from MSMS

Failure to develop Brainstem, Cerebellar or Failure to develop Brainstem, Cerebellar or Cerebral demyelinative manifestations.Cerebral demyelinative manifestations.

Normality of the cerebral white matter on MRI.Normality of the cerebral white matter on MRI. Almost uniform absence of OCB and Almost uniform absence of OCB and

abnormality of IgG in CSF.abnormality of IgG in CSF. Necrotizing and cavitary nature of spinal cord Necrotizing and cavitary nature of spinal cord

lesions, affecting gray and white matter.lesions, affecting gray and white matter. Humoral nature of Devic’s with high titer of Humoral nature of Devic’s with high titer of

antibody in blood in new studies.antibody in blood in new studies.

Slowly Progressive MyelopathySlowly Progressive Myelopathy

If there are no sensory signs or symptoms, the If there are no sensory signs or symptoms, the entity known as primary lateral sclerosis, one of entity known as primary lateral sclerosis, one of the group of motor neuron diseases, may be the the group of motor neuron diseases, may be the cause. cause.

HTLV-l infection, vitamin B12 deficiency, and HTLV-l infection, vitamin B12 deficiency, and human immunodeficiency virus infection all can human immunodeficiency virus infection all can be excluded by appropriate testing.be excluded by appropriate testing.

Spinal dural arteriovenous fistula can cause a Spinal dural arteriovenous fistula can cause a steadily or stepwise progressive myelopathy, steadily or stepwise progressive myelopathy, usually in the lower spinal segments.usually in the lower spinal segments.

Adrenomyeloneuropathy should be considered.Adrenomyeloneuropathy should be considered.

Slowly Progressive MyelopathySlowly Progressive Myelopathy

A number of patients their spinal MRI A number of patients their spinal MRI results are repeatedly negative.results are repeatedly negative.

VERs, CSF OCBs, and MRI of the head VERs, CSF OCBs, and MRI of the head show no sign of demyelination elsewhere.show no sign of demyelination elsewhere.

Slowly Progressive MyelopathySlowly Progressive Myelopathy

Some clues that MS is Some clues that MS is present are Lhermitte's present are Lhermitte's sign, sensitivity to sign, sensitivity to elevated temperature and elevated temperature and optic neuritis.optic neuritis.

Primary progressive MSPrimary progressive MS

Progressive myelopathy caused by MS Progressive myelopathy caused by MS is part of the primary progressive MS is part of the primary progressive MS group and carries the poor prognosis group and carries the poor prognosis typical of that group.typical of that group.

Final DiagnosisFinal Diagnosis

Progressive MyelopathyProgressive Myelopathy

caused by MScaused by MS

(secondary progressive MS) (secondary progressive MS)

The degree of compressionThe degree of compression of the cervical cord by intervertebral disc disease isof the cervical cord by intervertebral disc disease is often an issue in the middle-aged patient, because aoften an issue in the middle-aged patient, because a majority of persons have some degree of disc disease, andmajority of persons have some degree of disc disease, and following trauma there may be a T2 bright signal within thefollowing trauma there may be a T2 bright signal within the cord due to contusion. There is little doubt that somecord due to contusion. There is little doubt that some laminectomies have been carried out for cervical spondylosislaminectomies have been carried out for cervical spondylosis where MS was the final correct diagnosis.where MS was the final correct diagnosis. . The choice of therapy is. The choice of therapy is difficult. Some patients do better for a time with monthlydifficult. Some patients do better for a time with monthly intravenous corticosteroid therapy.intravenous corticosteroid therapy.

Inflammatory diseasesInflammatory diseases Granulomatous angiitisGranulomatous angiitis Systemic lupus erythematosusSystemic lupus erythematosus Sjogren's diseaseSjogren's disease Beh.;:et's diseaseBeh.;:et's disease Polyarteritis nodosaPolyarteritis nodosa Paraneoplastic encephalomyelopathiesParaneoplastic encephalomyelopathies Acute disseminated encephalomyelitis, postinfectiousAcute disseminated encephalomyelitis, postinfectious encephalomyelitisencephalomyelitis Infectious diseasesInfectious diseases Lyme neuroborreliosisLyme neuroborreliosis Human T-celllymphotropic virus type I infection':'Human T-celllymphotropic virus type I infection':' Human immunodeficiency virus infectionHuman immunodeficiency virus infection Progressive multifocalleukoencephalopathy':'Progressive multifocalleukoencephalopathy':' Neurosyphilis"Neurosyphilis" Granulomatous diseasesGranulomatous diseases SarcoidosisSarcoidosis Wegener's granulomatosisWegener's granulomatosis Lymphomatoid granulomatosisLymphomatoid granulomatosis Diseases of myelinDiseases of myelin Metachromatic leukodystrophy (juvenile and adult)':'Metachromatic leukodystrophy (juvenile and adult)':' Adrenomye Ioleukodystroph y.:.Adrenomye Ioleukodystroph y.:. MiscellaneousMiscellaneous Spinocerebellar disorders':'Spinocerebellar disorders':' Arnold-Chiari malformationArnold-Chiari malformation Vitamin Bl2 deficiency"Vitamin Bl2 deficiency"

AutoimmuneAutoimmune Acute disseminated encephalomyelitisAcute disseminated encephalomyelitis Acute hemorrhagic leukoencephalopathyAcute hemorrhagic leukoencephalopathy Multiple sclerosisMultiple sclerosis InfectiousInfectious Progressive multifocalleukoencephalopathyProgressive multifocalleukoencephalopathy Toxic/metabolicToxic/metabolic Carbon monoxideCarbon monoxide Vitamin B12 deficiencyVitamin B12 deficiency Mercury intoxication (Minamata disease)Mercury intoxication (Minamata disease) Alcohol/tobacco amblyopiaAlcohol/tobacco amblyopia Central pontine myelinolysisCentral pontine myelinolysis Marchiafava-Bignami syndromeMarchiafava-Bignami syndrome HypoxiaHypoxia RadiationRadiation VascularVascular Binswanger's diseaseBinswanger's disease Hereditary disorders of myelin metabolismHereditary disorders of myelin metabolism AdrenoleukodystrophyAdrenoleukodystrophy Metachromatic leukodystrophyMetachromatic leukodystrophy Krabbe's diseaseKrabbe's disease Alexander's diseaseAlexander's disease Canavan-van Bogaert-Bertrand diseaseCanavan-van Bogaert-Bertrand disease Pelizaeus-Merzbacher diseasePelizaeus-Merzbacher disease PhenylketonuriaPhenylketonuria Multiple sclerosisMultiple sclerosis

(e.g., vitamin B12 deficiency, compressivee.g., vitamin B12 deficiency, compressive spinal cord lesions, arteriovenous spinal cord lesions, arteriovenous

malformations,malformations, cavernous angiomas, Arnold-Chiari cavernous angiomas, Arnold-Chiari

malformation), infectiousmalformation), infectious causes (syphilis, HTL V-I, human causes (syphilis, HTL V-I, human

immunodeficiencyimmunodeficiency virus), or hereditary disorders (adult virus), or hereditary disorders (adult

metachromatic leukodystrophy,metachromatic leukodystrophy, adrenomyeloleukodystrophy, spinocerebellaradrenomyeloleukodystrophy, spinocerebellar disorders) .disorders) .