Multiple sclerosis - Clinicals, Diagnosis, and Management

Neurology

Clinicals - History

Fact Explanation
Blurring of the vision of one eye or complete blindness Demyelinating plaques are deposited in the optic nerve therefore optic neuropathy occurs. The defect in the vision can vary from blurring to total blindness with slight pain. Can affect both eyes as well. Vision can worsen in fever, hot weather and after exercise and this is known as Uthoff phenomenon. But recovery occurs with time. Blurring of the vision of one eye or complete blindness
Demyelinating plaques are deposited in the optic nerve therefore optic neuropathy occurs. The defect in the vision can vary from blurring to total blindness with slight pain. Can affect both eyes as well. Vision can worsen in fever, hot weather and after exercise and this is known as Uthoff phenomenon. But recovery occurs with time.
Defects in the color vision There's are no residual symptoms but defects in the color vision may persist. Defects in the color vision
There's are no residual symptoms but defects in the color vision may persist.
Diplopia This is a feature of brain stem involvement due to demyelinating plaques and involvement of 3rd, 4th and 6th cranial nerves in the mid brain and pons. Diplopia
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 3rd, 4th and 6th cranial nerves in the mid brain and pons.
Vertigo This is a feature of brain stem involvement due to demyelinating plaques and involvement of 8th cranial nerve in the pons. Vertigo
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 8th cranial nerve in the pons.
Numbness/ Weakness of the face This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons Numbness/ Weakness of the face
This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons
Difficulty in articulating words, imbalance in walking and tremor This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10 th cranial nerves in the medulla oblangata. Additionally there were three cardinal features of MS associated with involvement of the cerebellum, which are dysarthria, intention tremor, and nystagmus. These three symptoms are known as “Charcot’s triad. ” But these are not diagnostic. Difficulty in articulating words, imbalance in walking and tremor
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10 th cranial nerves in the medulla oblangata. Additionally there were three cardinal features of MS associated with involvement of the cerebellum, which are dysarthria, intention tremor, and nystagmus. These three symptoms are known as “Charcot’s triad. ” But these are not diagnostic.
Difficulty in swallowing This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10th cranial nerves in the medulla oblangata Difficulty in swallowing
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10th cranial nerves in the medulla oblangata
Weakness/ Numbness of both legs with difficulty in walking This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis which results difficulty in walking Weakness/ Numbness of both legs with difficulty in walking
This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis which results difficulty in walking
Bladder incontinence This is due to deposition of demyelinating plaques in the spinal cord which compress the autonomic nerve supply to the bladder Bladder incontinence
This is due to deposition of demyelinating plaques in the spinal cord which compress the autonomic nerve supply to the bladder
Seizures Epilepsy is more common in patients with MS, as well as some spasms in the limbs Seizures
Epilepsy is more common in patients with MS, as well as some spasms in the limbs
Severe pain in the face Trigeminal neuralgia is more common in patients with MS Severe pain in the face
Trigeminal neuralgia is more common in patients with MS
Impairment of memory, finding words, attention and concentration Cognitive impairment is a feature of end stage MS due to effect on higher functions Impairment of memory, finding words, attention and concentration
Cognitive impairment is a feature of end stage MS due to effect on higher functions
Psychological symptoms Psychological symptoms such as depression, suicide and self harm can occur. Depression is the commonest psychiatric illness among these patients. Additionally euphoria, mania, pathological laughing, crying can occur Psychological symptoms
Psychological symptoms such as depression, suicide and self harm can occur. Depression is the commonest psychiatric illness among these patients. Additionally euphoria, mania, pathological laughing, crying can occur
Ankle swelling, Anorexia, nausea, Itching, altered level of consciousness These are features of uremia which occurs in end stage MS as a side effect for interferon therapy. Ankle swelling, Anorexia, nausea, Itching, altered level of consciousness
These are features of uremia which occurs in end stage MS as a side effect for interferon therapy.
Cough with sputum production Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS Cough with sputum production
Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS
Worsening of symptoms with heat This is known as Uthoff phenomenon, where the symptoms gets worse with hot baths, hot weather etc.. It's due to further impairment in propagation of electrical impulses in demyelinated nerve fibers due to heat. Worsening of symptoms with heat
This is known as Uthoff phenomenon, where the symptoms gets worse with hot baths, hot weather etc.. It's due to further impairment in propagation of electrical impulses in demyelinated nerve fibers due to heat.

Clinicals - Examination

Fact Explanation
Reduced visual acuity Optic neuropathy results in reduced visual acuity. Reduced visual acuity
Optic neuropathy results in reduced visual acuity.
Papillodema, Optic atrophy Optic neuritis may manifest as disc edema. But retrobulbar neurits is unable to be demonstrated by the ophthalmoscopy. Later disc pallor due to optic atrophy is seen. Papillodema, Optic atrophy
Optic neuritis may manifest as disc edema. But retrobulbar neurits is unable to be demonstrated by the ophthalmoscopy. Later disc pallor due to optic atrophy is seen.
Relative afferent pupillary defect This occurs due to optic neuropathy Relative afferent pupillary defect
This occurs due to optic neuropathy
Defective ocular movements This is a feature of brain stem involvement due to demyelinating plaques and involvement of 3rd, 4th and 6th cranial nerves in the mid brain and pons. Bilateral internuclear ophthalmoplegia could be present. Defective ocular movements
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 3rd, 4th and 6th cranial nerves in the mid brain and pons. Bilateral internuclear ophthalmoplegia could be present.
Reduced sensation of the face and Weakness of the face This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons Reduced sensation of the face and Weakness of the face
This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons
Nystagmus This is a feature of brain stem involvement due to demyelinating plaques and involvement of 8th cranial nerve in the pons and it's pendular nystagmus. Nystagmus
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 8th cranial nerve in the pons and it's pendular nystagmus.
Dysarthria , Ataxia, Intentional tremor This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10th cranial nerves in the medulla oblangata. Additionally there were three cardinal features of MS associated with involvement of the cerebellum, which are dysarthria, intention tremor, and nystagmus. These three symptoms are known as “Charcot’s triad. ” But these are not diagnostic. Dysarthria , Ataxia, Intentional tremor
This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10th cranial nerves in the medulla oblangata. Additionally there were three cardinal features of MS associated with involvement of the cerebellum, which are dysarthria, intention tremor, and nystagmus. These three symptoms are known as “Charcot’s triad. ” But these are not diagnostic.
Spasticity and motor weakness of the lower limbs This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis. Lhermitte's sign may be present. Spastic tetraparesis may be developed later Spasticity and motor weakness of the lower limbs
This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis. Lhermitte's sign may be present. Spastic tetraparesis may be developed later
Numbness of the lower limbs This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis Numbness of the lower limbs
This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis
Exaggerated lower limb deep tendon reflexes and up going planter response This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis and upper motor neuron signs in the lower limbs Exaggerated lower limb deep tendon reflexes and up going planter response
This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis and upper motor neuron signs in the lower limbs
Spastic tongue, Exaggerated jaw jerk In late stage of MS, signs of pseudobulbar palsy may appear Spastic tongue, Exaggerated jaw jerk
In late stage of MS, signs of pseudobulbar palsy may appear
Earthen complexion, Bilateral ankle swelling, pallor These are features of uremia as a side effect for interferon therapy in late MS Earthen complexion, Bilateral ankle swelling, pallor
These are features of uremia as a side effect for interferon therapy in late MS
Reduced breath sounds, coarse crepitations on auscultation of the respiratory system Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS Reduced breath sounds, coarse crepitations on auscultation of the respiratory system
Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS

Investigations - Diagnosis

Fact Explanation
Serum Anti nuclear antobodies, Anti-DNA antibodies, Anti-Sm antibodies and Anti-phospholipid antibodies These tests are done mainly to exclude SLE Serum Anti nuclear antobodies, Anti-DNA antibodies, Anti-Sm antibodies and Anti-phospholipid antibodies
These tests are done mainly to exclude SLE
Serum Vitamin B12 level This is done to exclude vitamin B12 deficiency causing spastic paraparesis Serum Vitamin B12 level
This is done to exclude vitamin B12 deficiency causing spastic paraparesis
Treponema Pallidum Particles Agglutination Test for Syphilis To exclude Syphilis which can cause neurological manifestations Treponema Pallidum Particles Agglutination Test for Syphilis
To exclude Syphilis which can cause neurological manifestations
Antibodies to Borrelia antigens using ELISA and Western immunoblot To exclude Lyme disease Antibodies to Borrelia antigens using ELISA and Western immunoblot
To exclude Lyme disease
Serum Copper, Ceruloplasmin level To exclude Wilson's disease and serum Copper is high in this Serum Copper, Ceruloplasmin level
To exclude Wilson's disease and serum Copper is high in this
Thyroid function tests These are done to exclude hypothyroidism in a patient presenting with fatigue due to MS. And a link has been observed between autoimmune thyroiditis and MS. Also with beta interferon therapy there could be development of hypo or hyperthyroidism. Thyroid function tests
These are done to exclude hypothyroidism in a patient presenting with fatigue due to MS. And a link has been observed between autoimmune thyroiditis and MS. Also with beta interferon therapy there could be development of hypo or hyperthyroidism.
Cerebrospinal fluid examination It shows oligoclonal IgG babnds and CSF cell count can be raised Cerebrospinal fluid examination
It shows oligoclonal IgG babnds and CSF cell count can be raised
Nerve conduction studies These are normal, and are done to exclude other diseases. But some abnormalities might be noted due to a complication in MS and due to co-existing other diseases Nerve conduction studies
These are normal, and are done to exclude other diseases. But some abnormalities might be noted due to a complication in MS and due to co-existing other diseases
Electroencephalogram This can show slow EEG background activity and reduced coherence in patients with cognitive impairment and high load of lesions in MRI Electroencephalogram
This can show slow EEG background activity and reduced coherence in patients with cognitive impairment and high load of lesions in MRI
MRI brain/ spinal cord This is the definitive investigation to diagnose MS in which multiple plaques are seen mainly in the peri ventricular region, corpus callosum, cerebellar peduncles, brain stem and cervical cord. Active lesions my be enhanced by Gadolinium. This helps to exclude other diagnosis as well MRI brain/ spinal cord
This is the definitive investigation to diagnose MS in which multiple plaques are seen mainly in the peri ventricular region, corpus callosum, cerebellar peduncles, brain stem and cervical cord. Active lesions my be enhanced by Gadolinium. This helps to exclude other diagnosis as well
Visual evoked responses In optic neuropathy, visual evoked responses are delayed. Visual evoked responses
In optic neuropathy, visual evoked responses are delayed.

Investigations - Management

Fact Explanation
Full blood count Leukopenia can occur with interferon therapy, therefore it's important to monitor the patient Full blood count
Leukopenia can occur with interferon therapy, therefore it's important to monitor the patient
Liver enzymes Elevation of liver enzymes can occur with interferon therapy, therefore it's important to monitor the patient Liver enzymes
Elevation of liver enzymes can occur with interferon therapy, therefore it's important to monitor the patient
Thyroid function tests With beta interferon therapy, alteration in thyroid function can occur in long term Thyroid function tests
With beta interferon therapy, alteration in thyroid function can occur in long term
Spasticity of muscles This should be assessed in follow up Spasticity of muscles
This should be assessed in follow up
Full blood count To exclude any anemia prior to surgical procedures (such as tendon release) Full blood count
To exclude any anemia prior to surgical procedures (such as tendon release)
Coagulation studies To exclude any coagulopathy before surgical management Coagulation studies
To exclude any coagulopathy before surgical management
Renal function tests- Serum creatinine, Blood urea nitrogen To exclude any renal dysfuction before anesthesia as well as uremia is a recognized complication with high doses of interferons which are used in management Renal function tests- Serum creatinine, Blood urea nitrogen
To exclude any renal dysfuction before anesthesia as well as uremia is a recognized complication with high doses of interferons which are used in management
Brain and spinal cord MRI McDonald criteria is used to categorize MS depending on MRI lesions Brain and spinal cord MRI
McDonald criteria is used to categorize MS depending on MRI lesions
Cerebrospinal fluid examination McDonald criteria is used to categorize MS depending on the presence of oligoclonal bands in CSF examination Cerebrospinal fluid examination
McDonald criteria is used to categorize MS depending on the presence of oligoclonal bands in CSF examination
Visual evoked response McDonald criteria includes this to make a diagnosis of MS along with MRI and CSF examination. Visual evoked response
McDonald criteria includes this to make a diagnosis of MS along with MRI and CSF examination.
Actionable Bladder Symptom Screening Tool (ABSST) Urinary symptoms are common in MS therefore bladder dysfunction screening tool may be helpful to detect early dysfunction Actionable Bladder Symptom Screening Tool (ABSST)
Urinary symptoms are common in MS therefore bladder dysfunction screening tool may be helpful to detect early dysfunction
Patient Health Questionnaire-9 This maybe helpful to Screen for depression in Outpatients With Multiple Sclerosis as it's commonly encountered Patient Health Questionnaire-9
This maybe helpful to Screen for depression in Outpatients With Multiple Sclerosis as it's commonly encountered

Management - Supportive

Fact Explanation
Patient education and family education There's no curative treatment therefore patient education plays a major role. The patient should be educated regarding the nature, course, prognosis, available treatment options and importance of follow up. It's very important to educate regarding the factors which can cause a relapse such as infection and what to do if symptoms suggestive of a relapse appear. Family should also be educated as it's important and support groups are present. Psychiatric referral may be needed. Patient education and family education
There's no curative treatment therefore patient education plays a major role. The patient should be educated regarding the nature, course, prognosis, available treatment options and importance of follow up. It's very important to educate regarding the factors which can cause a relapse such as infection and what to do if symptoms suggestive of a relapse appear. Family should also be educated as it's important and support groups are present. Psychiatric referral may be needed.
Rehabilitation This plays such an important role. Walking aids, wheelchairs are helpful for ambulation as well as home, and office should be modified according to patient's needs. Multidisciplinary approach is needed Rehabilitation
This plays such an important role. Walking aids, wheelchairs are helpful for ambulation as well as home, and office should be modified according to patient's needs. Multidisciplinary approach is needed
Management of swallowing and speaking difficulties To manage swallowing difficulties patient is educated to use their accessory muscles, maintaining the posture to prevent aspiration, adjustment of the texture of food to facilitate swallowing, Naso-gastic feeding may be necessary. Communication aids are helpful for patients having speaking difficulties Management of swallowing and speaking difficulties
To manage swallowing difficulties patient is educated to use their accessory muscles, maintaining the posture to prevent aspiration, adjustment of the texture of food to facilitate swallowing, Naso-gastic feeding may be necessary. Communication aids are helpful for patients having speaking difficulties
Management of bladder dysfunction intermittent self catheterization may help. Oxybutinin may play a role as well Management of bladder dysfunction
intermittent self catheterization may help. Oxybutinin may play a role as well
Physiotherapy This is important to relieve spasticity and improve and maintain functions of the limbs Physiotherapy
This is important to relieve spasticity and improve and maintain functions of the limbs
Occupational therapy This is important for the patient to manage his activities of daily living Occupational therapy
This is important for the patient to manage his activities of daily living
Muscle relaxants Baclofen, Benzodiazapines, Gabapentin, Botilinum toxin, intra thecl Phenol are helpful to relieve the symptoms of spasticity. Muscle relaxants
Baclofen, Benzodiazapines, Gabapentin, Botilinum toxin, intra thecl Phenol are helpful to relieve the symptoms of spasticity.
Prevention of pressure sores As the patient is bed ridden in late stages, prevention of pressure sores is very important. Water-air mattresses, Rolling the patient every 2 hours can be helpful Prevention of pressure sores
As the patient is bed ridden in late stages, prevention of pressure sores is very important. Water-air mattresses, Rolling the patient every 2 hours can be helpful
Treatment of infections Respiratory tract infections, Urinary tract infections need too be treated promptly Treatment of infections
Respiratory tract infections, Urinary tract infections need too be treated promptly
Treatment of fatigue Sudden episodes of fatigue are common. Therefore regular rest periods, short naps, moderate exercise may help as well as drugs such as amantadine, pemoline, and
fluoxetine may help
Treatment of fatigue
Sudden episodes of fatigue are common. Therefore regular rest periods, short naps, moderate exercise may help as well as drugs such as amantadine, pemoline, and
fluoxetine may help
Vaccination Currently it's been thought that vaccinations are not contraindicated in MS therefore, influenza vaccination is offered. However live vaccines are contraindicated if they are on immunosuppressant therapy. Vaccination
Currently it's been thought that vaccinations are not contraindicated in MS therefore, influenza vaccination is offered. However live vaccines are contraindicated if they are on immunosuppressant therapy.

Management - Specific

Fact Explanation
Treatment of acute relapses These are treated with intravenous methyl prednisolone or high doses of oral steroids. Plasmapheresis may be helpful as well. Treatment of acute relapses
These are treated with intravenous methyl prednisolone or high doses of oral steroids. Plasmapheresis may be helpful as well.
Treatment of relapsing MS Beta interferons are helpful in relapsing and remitting disease and help to prevent relapses. But these are expensive and given as injections. Flu like symptoms can occur as side effects. Glatiramer acetate also has a role as an immunomodulator and helpful to prevent relapses in relapsing and remitting disease. Natalizumab is one monoclonal antibody which prevents the migration of antibodies to CNS. It's helpful in severe disease which doesn't respond to other treatments. Alemtuzumab may be useful as well. Treatment of relapsing MS
Beta interferons are helpful in relapsing and remitting disease and help to prevent relapses. But these are expensive and given as injections. Flu like symptoms can occur as side effects. Glatiramer acetate also has a role as an immunomodulator and helpful to prevent relapses in relapsing and remitting disease. Natalizumab is one monoclonal antibody which prevents the migration of antibodies to CNS. It's helpful in severe disease which doesn't respond to other treatments. Alemtuzumab may be useful as well.
Treatment of aggressive MS Azathioprine, high dose Cyclophosphamide, Mitoxantrone which are immunosuppressants may be beneficial. Intravenous Ig may have a role as well. Treatment of aggressive MS
Azathioprine, high dose Cyclophosphamide, Mitoxantrone which are immunosuppressants may be beneficial. Intravenous Ig may have a role as well.
Treatment of progressive MS The main aim is to prevent progressive worsening of the disease. Drugs used are beta inetrferons and traditional immunosuppressants Treatment of progressive MS
The main aim is to prevent progressive worsening of the disease. Drugs used are beta inetrferons and traditional immunosuppressants
Treatment of MS in pregnancy Steroids are not contraindicated. However use of immunomodulatory drugs in pregnancy should be decided after careful analysis of risks and benefits. Pregnancy does not adversely affect the course of disease. Treatment of MS in pregnancy
Steroids are not contraindicated. However use of immunomodulatory drugs in pregnancy should be decided after careful analysis of risks and benefits. Pregnancy does not adversely affect the course of disease.
Other emerging therapies Daclizumab, Rituximab are monoclonal antibodies which are emerging as therapies. Laquinimod has immunomodulatory properties. Cladribine is a purine nucleotide analogue. Fingolimod is isolated from a fungus. BG00012 (Dimethyl Fumarate) is thought to increase the production of Th2 cytokines. Epidemiological association has been noted between higher geographic latitudes, sunlight exposure, and MS. therefore Vitamin D maybe helpful as well. Other emerging therapies
Daclizumab, Rituximab are monoclonal antibodies which are emerging as therapies. Laquinimod has immunomodulatory properties. Cladribine is a purine nucleotide analogue. Fingolimod is isolated from a fungus. BG00012 (Dimethyl Fumarate) is thought to increase the production of Th2 cytokines. Epidemiological association has been noted between higher geographic latitudes, sunlight exposure, and MS. therefore Vitamin D maybe helpful as well.

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