History

Fact Explanation
Blurring of the vision of one eye or complete blindness [7] [8] [9] 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. [7] [8] [9]
Defects in the color vision [7] [8] [9] There's are no residual symptoms but defects in the color vision may persist. [7] [8] [9]
Diplopia [10] 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. [10]
Vertigo [10] This is a feature of brain stem involvement due to demyelinating plaques and involvement of 8th cranial nerve in the pons. [10]
Numbness/ Weakness of the face [10] This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons [10]
Difficulty in articulating words, imbalance in walking and tremor [11] [19] 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. [11] [19]
Difficulty in swallowing [11] This is a feature of brain stem involvement due to demyelinating plaques and involvement of 9th and 10th cranial nerves in the medulla oblangata [11]
Weakness/ Numbness of both legs with difficulty in walking [12] 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 [12]
Bladder incontinence [13] This is due to deposition of demyelinating plaques in the spinal cord which compress the autonomic nerve supply to the bladder [13]
Seizures [14] Epilepsy is more common in patients with MS, as well as some spasms in the limbs [14]
Severe pain in the face [15] Trigeminal neuralgia is more common in patients with MS [15]
Impairment of memory, finding words, attention and concentration [16] [20] Cognitive impairment is a feature of end stage MS due to effect on higher functions [16] [20]
Psychological symptoms [16] 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 [16]
Ankle swelling, Anorexia, nausea, Itching, altered level of consciousness [17] These are features of uremia which occurs in end stage MS as a side effect for interferon therapy. [17]
Cough with sputum production [18] Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS [18]
Worsening of symptoms with heat [21] 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. [21]
References
  1. WOOTLA BHARATH, ERIGUCHI MAKOTO, RODRIGUEZ MOSES. Is Multiple Sclerosis an Autoimmune Disease?. Autoimmune Diseases [online] 2012 December, 2012:1-12 [viewed 07 September 2014] Available from: doi:10.1155/2012/969657
  2. THE MULTIPLE SCLEROSIS GENETICS GROUP . Genetic basis for clinical expression in multiple sclerosis. [online] 2002 January, 125(1):150-158 [viewed 07 September 2014] Available from: doi:10.1093/brain/awf009
  3. HAFLER DAVID A.. Multiple sclerosis. J. Clin. Invest. [online] 2004 March, 113(6):788-794 [viewed 07 September 2014] Available from: doi:10.1172/JCI21357
  4. ALROUGHANI R., AL HASHEL J., LAMDHADE S., AHMED S. F.. Predictors of Conversion to Multiple Sclerosis in Patients with Clinical Isolated Syndrome Using the 2010 Revised McDonald Criteria. ISRN Neurology [online] 2012 December, 2012:1-6 [viewed 07 September 2014] Available from: doi:10.5402/2012/792192
  5. LIU S., KULLNAT J., BOURDETTE D., SIMON J., KRAEMER D. F., MURCHISON C., HAMILTON B. E.. Prevalence of brain magnetic resonance imaging meeting Barkhof and McDonald criteria for dissemination in space among headache patients. Multiple Sclerosis Journal [online] December, 19(8):1101-1105 [viewed 07 September 2014] Available from: doi:10.1177/1352458512471874
  6. REJDAK K., JACKSON S., GIOVANNONI G.. Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin [online] December, 95(1):79-104 [viewed 07 September 2014] Available from: doi:10.1093/bmb/ldq017
  7. OSBORNE B. J., VOLPE N. J.. Optic neuritis and risk of MS: Differential diagnosis and management. Cleveland Clinic Journal of Medicine [online] 2009 March, 76(3):181-190 [viewed 07 September 2014] Available from: doi:10.3949/ccjm.76a.07268
  8. PFEFFER G., BURKE A., YU-WAI-MAN P., COMPSTON D. A. S., CHINNERY P. F.. Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. Neurology [online] December, 81(24):2073-2081 [viewed 07 September 2014] Available from: doi:10.1212/01.wnl.0000437308.22603.43
  9. THOUVENOT ERIC, MURA FRéDéRIC, DE VERDAL MARIE, CARLANDER BERTRAND, CHARIF MAHMOUD, SCHNEIDER CHRISTELLE, NAVARRE SOPHIE, CAMU WILLIAM. Ipsilateral Uveitis and Optic Neuritis in Multiple Sclerosis. Multiple Sclerosis International [online] 2012 December, 2012:1-4 [viewed 07 September 2014] Available from: doi:10.1155/2012/372361
  10. THOMKE F., LENSCH E., RINGEL K., HOPF H. C.. Isolated cranial nerve palsies in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry [online] 1997 November, 63(5):682-685 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.63.5.682
  11. BROWN SHIRLEY A.. Swallowing and Speaking Challenges for the MS Patient. International Journal of MS Care [online] 2000 October, 2(3):4-14 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-2.3.4
  12. BLIGHT AR. Treatment of walking impairment in multiple sclerosis with dalfampridine Ther Adv Neurol Disord [online] 2011 Mar, 4(2):99-109 [viewed 07 September 2014] Available from: doi:10.1177/1756285611403960
  13. LENSCH E., JOST W. H.. Autonomic Disorders in Multiple Sclerosis. Autoimmune Diseases [online] 2011 December, 2011:1-6 [viewed 07 September 2014] Available from: doi:10.4061/2011/803841
  14. ALLEN ALEXANDER N, SEMINOG OLENA O, GOLDACRE MICHAEL J. Association between multiple sclerosis and epilepsy: large population-based record-linkage studies. Array [online] 2013 December [viewed 07 September 2014] Available from: doi:10.1186/1471-2377-13-189
  15. GASS A., KITCHEN N., MACMANUS D. G., MOSELEY I. F., HENNERICI M. G., MILLER D. H.. Trigeminal neuralgia in patients with multiple sclerosis: Lesion localization with magnetic resonance imaging. Neurology [online] 1997 October, 49(4):1142-1144 [viewed 07 September 2014] Available from: doi:10.1212/WNL.49.4.1142
  16. JEFFERIES K.. The neuropsychiatry of multiple sclerosis. Advances in Psychiatric Treatment [online] 2006 May, 12(3):214-220 [viewed 07 September 2014] Available from: doi:10.1192/apt.12.3.214
  17. ARRAMBIDE G.. Thrombotic thrombocytopenic purpura-haemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon beta. Multiple Sclerosis Journal [online] 2014 April [viewed 07 September 2014] Available from: doi:10.1177/1352458514529614
  18. ROFES LAIA, ARREOLA VIRIDIANA, ALMIRALL JORDI, CABRé MATEU, CAMPINS LLUíS, GARCíA-PERIS PILAR, SPEYER RENéE, CLAVé PERE. Diagnosis and Management of Oropharyngeal Dysphagia and Its Nutritional and Respiratory Complications in the Elderly. Gastroenterology Research and Practice [online] 2011 December, 2011:1-13 [viewed 07 September 2014] Available from: doi:10.1155/2011/818979
  19. KUMAR DR, ASLINIA F, YALE SH, MAZZA JJ. Jean-Martin Charcot: The Father of Neurology Clin Med Res [online] 2011 Mar, 9(1):46-49 [viewed 10 September 2014] Available from: doi:10.3121/cmr.2009.883
  20. ACHIRON A. Cognitive patterns and progression in multiple sclerosis: construction and validation of percentile curves. Journal of Neurology, Neurosurgery & Psychiatry [online] 2005 May, 76(5):744-749 [viewed 10 September 2014] Available from: doi:10.1136/jnnp.2004.045518
  21. FLENSNER GULLVI, EK ANNA-CHRISTINA, SöDERHAMN OLLE, LANDTBLOM ANNE-MARIE. Sensitivity to heat in MS patients: a factor strongly influencing symptomology - an explorative survey. Array [online] 2011 December [viewed 10 September 2014] Available from: doi:10.1186/1471-2377-11-27

Examination

Fact Explanation
Reduced visual acuity [1] [2] [3] Optic neuropathy results in reduced visual acuity. [1] [2] [3]
Papillodema, Optic atrophy [1] [2] [3] 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. [1] [2] [3]
Relative afferent pupillary defect [1] This occurs due to optic neuropathy [1]
Defective ocular movements [4] 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. [4]
Reduced sensation of the face and Weakness of the face [4] This is a feature of brain stem involvement due to demyelinating plaques and involvement of the 5th and 7th cranial nerves in the pons [4]
Nystagmus [6] 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. [6]
Dysarthria , Ataxia, Intentional tremor[5] [12] 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. [5] [12]
Spasticity and motor weakness of the lower limbs [7] [8] 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 [7] [8]
Numbness of the lower limbs [7] [8] This is due to deposition of demyelinating plaques in the spinal cord which compress the spinal cord and causes a spastic paraparesis [7] [8]
Exaggerated lower limb deep tendon reflexes and up going planter response [7] 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 [7]
Spastic tongue, Exaggerated jaw jerk [11] In late stage of MS, signs of pseudobulbar palsy may appear [11]
Earthen complexion, Bilateral ankle swelling, pallor [9] These are features of uremia as a side effect for interferon therapy in late MS [9]
Reduced breath sounds, coarse crepitations on auscultation of the respiratory system [10] Aspiration due to bulbar palsy can cause bronchopnemonias in end stage MS [10]
References
  1. OSBORNE B. J., VOLPE N. J.. Optic neuritis and risk of MS: Differential diagnosis and management. Cleveland Clinic Journal of Medicine [online] 2009 March, 76(3):181-190 [viewed 07 September 2014] Available from: doi:10.3949/ccjm.76a.07268
  2. PFEFFER G., BURKE A., YU-WAI-MAN P., COMPSTON D. A. S., CHINNERY P. F.. Clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. Neurology [online] December, 81(24):2073-2081 [viewed 07 September 2014] Available from: doi:10.1212/01.wnl.0000437308.22603.43
  3. THOUVENOT ERIC, MURA FRéDéRIC, DE VERDAL MARIE, CARLANDER BERTRAND, CHARIF MAHMOUD, SCHNEIDER CHRISTELLE, NAVARRE SOPHIE, CAMU WILLIAM. Ipsilateral Uveitis and Optic Neuritis in Multiple Sclerosis. Multiple Sclerosis International [online] 2012 December, 2012:1-4 [viewed 07 September 2014] Available from: doi:10.1155/2012/372361
  4. THOMKE F., LENSCH E., RINGEL K., HOPF H. C.. Isolated cranial nerve palsies in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry [online] 1997 November, 63(5):682-685 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.63.5.682
  5. BROWN SHIRLEY A.. Swallowing and Speaking Challenges for the MS Patient. International Journal of MS Care [online] 2000 October, 2(3):4-14 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-2.3.4
  6. BARTON J J, COX T A. Acquired pendular nystagmus in multiple sclerosis: clinical observations and the role of optic neuropathy.. Journal of Neurology, Neurosurgery & Psychiatry [online] 1993 March, 56(3):262-267 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.56.3.262
  7. JARRETT L. Managing severe lower limb spasticity in multiple sclerosis: does intrathecal phenol have a role?. [online] 2002 December, 73(6):705-709 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.73.6.705
  8. BLIGHT AR. Treatment of walking impairment in multiple sclerosis with dalfampridine Ther Adv Neurol Disord [online] 2011 Mar, 4(2):99-109 [viewed 07 September 2014] Available from: doi:10.1177/1756285611403960
  9. ARRAMBIDE G.. Thrombotic thrombocytopenic purpura-haemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon beta. Multiple Sclerosis Journal [online] 2014 April [viewed 07 September 2014] Available from: doi:10.1177/1352458514529614
  10. ROFES LAIA, ARREOLA VIRIDIANA, ALMIRALL JORDI, CABRé MATEU, CAMPINS LLUíS, GARCíA-PERIS PILAR, SPEYER RENéE, CLAVé PERE. Diagnosis and Management of Oropharyngeal Dysphagia and Its Nutritional and Respiratory Complications in the Elderly. Gastroenterology Research and Practice [online] 2011 December, 2011:1-13 [viewed 07 September 2014] Available from: doi:10.1155/2011/818979
  11. SCHIFFER R.. Review of Pseudobulbar Affect Including a Novel and Potential Therapy. Journal of Neuropsychiatry [online] 2005 November, 17(4):447-454 [viewed 07 September 2014] Available from: doi:10.1176/appi.neuropsych.17.4.447
  12. KUMAR DR, ASLINIA F, YALE SH, MAZZA JJ. Jean-Martin Charcot: The Father of Neurology Clin Med Res [online] 2011 Mar, 9(1):46-49 [viewed 10 September 2014] Available from: doi:10.3121/cmr.2009.883

Differential Diagnoses

Fact Explanation
Other causes of optic neurits [1] There are other causes for optic neuritis as well. Leber's hereditary optic neuropathy (LHON) which causes bilateral simultaneous or rapidly sequential optic neuritis unilke in MS is one such disease entity. Also toxins (tobacco amblyopia and methanol), vitamin B-12 deficiency, inflammatory disorders such as sarcoidosis, vasculitis, and lupus, infections, ischaemia, tumors should be kept in mind. [1]
Transverse myelitis [3] This is similar to spinal cord involvement in MS. But the paralysis is rapidly progressive Also sensory loss, incontinence, back pain, fever and meningism can be seen [3]
Devic's disease or neuromyelitis optica [2] It is an acute or subacute optic neuritis associated with myelitis [2]
Foix-Alajouanine syndrome [4] It's mainly seen in adult males and a subacute necrotic myelitis. It also causes a spastic paralysis, sensory loss, and incontinence initially. [4]
Acute disseminated encephalomyelitis [5] This could be either post-infectious encephalomyelitis or post-vaccination encephalomyelitis. Initially it starts with fever, myalgia, and malaise, later evolving into neurological features such as focal neurological signs, transverse myelitis, and cranial palsies including bilateral optic neuritis and cerebellar ataxia may occur with varicella. [5]
Adrenoleucodystrophy and metachromatic leucodystrophy [6] This is slowly progressive but can be remitting and often gives a family history, abdominal symptoms, and features of Addison's disease such as skin pigmentation. [6]
HTLV-1 related myelopathy [7] It causes a tropical spastic paraperesis due to human T-cell leukemia virus 1 but other features of MS are not seen [7]
Lyme disease [8] This causes a spastic paraparesis, cerebellar ataxia, and cranial nerve palsies which are recurrent. MRI changes can mimic MS. [8]
Neurosyphilis [9] Pupillary abnormalities are mainly seen with headache and seizures. Optic neuritis in Syphilis is painless [9]
Cerebral involvement in Systemic Lupus Erythromatoses [10] Cerebral lupus cause neurological feayures such as ataxia, brain stem abnormalities, and cranial nerve palsies. Other features in SLE such as fever, malaise, malar butterfly rash and/or photosensitivity rash, arthritis should be inquired [10]
Sjögren's syndrome [11] Optic neuropathy is seen as it's an inflammatory disorder and other features such as keratoconjunctivitis sicca, xerostomia usually along with another connective tissue disorder such as rheumatoid arthritis. [11]
Neurosarcoidosis [12] Optic nerve involvement is seen with involvement of other cranial nerves such as facial nerve. Also brain stem and spinal cord involvement is seen. However peripheral nerves and muscles are involved unlike in MS [12]
Behçet's disease [13] It's a multisystem inflammatory disorder with recurrent genital ulceration, uveitis, retinal vasculitis, skin lesions such as erythema nodosum [13]
Whipple's disease [14] It's caused by Tropheryma whippelii and neurological symptoms such as pyramidal signs,cognitive changes, supranuclear gaze palsy, hypothalamic signs, seizures, ataxia and cranial nerve palsies are seen [14]
Malignancy [15] [16] Hodgkin's disease can cause CNS angiitis, as well as Lymphomatoid granulomatosis (T lymphoma) can cause neurological features [15] [16]
Wilson's disease [17] It is an autosomal recessive disease with hepatic and neurological manifestations due to accumulation of copper in the liver, basal ganglia and appearance of Kayser-Fleischer rings in the eye [17]
Central pontine myelinolysis [18] This is an osmotic demyelination syndrome which occurs as a complication of treatment of severe hyponatraemia. With chronic hyponatremia, their cells are adapted to this low tonicity but with treatment there's rapid rise in serum tonicity which causes this. Clinical features may be difficult to distinguish from MS [18]
Spinal cord infarction [19] Acute ischemic stroke of the spinal cord causes paraplegia and flaccid paralysis initially due to spinal shock but later there's development of upper motor neuron signs in the upper limbs with lower limbs developing spasticity, hyperreflexia and extensor plantar responses similar to MS. Also there's anesthesia to pain and temperature below the level of infarct with preservation of dorsal column functions. [19]
References
  1. OSBORNE B. J., VOLPE N. J.. Optic neuritis and risk of MS: Differential diagnosis and management. Cleveland Clinic Journal of Medicine [online] 2009 March, 76(3):181-190 [viewed 07 September 2014] Available from: doi:10.3949/ccjm.76a.07268
  2. OH JIWON, LEVY MICHAEL. Neuromyelitis Optica: An Antibody-Mediated Disorder of the Central Nervous System. Neurology Research International [online] 2012 December, 2012:1-13 [viewed 07 September 2014] Available from: doi:10.1155/2012/460825
  3. AL DEEB S.. Acute transverse myelitis. A localized form of postinfectious encephalomyelitis. [online] 1997 July, 120(7):1115-1122 [viewed 07 September 2014] Available from: doi:10.1093/brain/120.7.1115
  4. KRISHNAN PRASAD, BANERJEE TAPASKUMAR, SAHA MANASH. Congestive myelopathy (Foix-Alajouanine Syndrome) due to intradural arteriovenous fistula of the filum terminale fed by anterior spinal artery: Case report and review of literature. Ann Indian Acad Neurol [online] 2013 December [viewed 07 September 2014] Available from: doi:10.4103/0972-2327.116931
  5. BENNETTO L. INFLAMMATORY/POST-INFECTIOUS ENCEPHALOMYELITIS. Journal of Neurology, Neurosurgery & Psychiatry [online] 2004 March, 75(90001):22i-28 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.2003.034256
  6. VAN GEEL B. M, ASSIES J., WANDERS R. J A, BARTH P. G. X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy. Journal of Neurology, Neurosurgery & Psychiatry [online] 1997 July, 63(1):4-14 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.63.1.4
  7. ARAúJO ALEXANDRA P. Q. C., FONTENELLE LUCIA M. C., PáDUA PAULA A. B., FILHO HEBER S. MAIA, ARAúJO ABELARDO DE Q. C.. Juvenile Human T Lymphotropic Virus Type 1–Associated Myelopathy. CLIN INFECT DIS [online] 2002 July, 35(2):201-204 [viewed 07 September 2014] Available from: doi:10.1086/341251
  8. HILDENBRAND P., CRAVEN D.E., JONES R., NEMESKAL P.. Lyme Neuroborreliosis: Manifestations of a Rapidly Emerging Zoonosis. American Journal of Neuroradiology [online] December, 30(6):1079-1087 [viewed 07 September 2014] Available from: doi:10.3174/ajnr.A1579
  9. MEHRABIAN SHIMA, RAYCHEVA MARGARITA RADOSLAVOVA, PETROVA ELENA PETROVA, TSANKOV NIKOLAY KONSTANTINOV, TRAYKOV LATCHEZAR DINTCHOV. Neurosyphilis presenting with dementia, chronic chorioretinitis and adverse reactions to treatment: a case report. Array [online] 2009 December [viewed 07 September 2014] Available from: doi:10.4076/1757-1626-2-8334
  10. MANSON JESSICA J, RAHMAN ANISUR. . Orphanet J Rare Dis [online] 2006 December [viewed 07 September 2014] Available from: doi:10.1186/1750-1172-1-6
  11. TOBóN GABRIEL J., PERS JACQUES-OLIVIER, DEVAUCHELLE-PENSEC VALéRIE, YOUINOU PIERRE. Neurological Disorders in Primary Sjögren's Syndrome. Autoimmune Diseases [online] 2012 December, 2012:1-11 [viewed 07 September 2014] Available from: doi:10.1155/2012/645967
  12. NUNES HILARIO, BOUVRY DIANE, SOLER PAUL, VALEYRE DOMINIQUE. Sarcoidosis. Array [online] 2007 December [viewed 07 September 2014] Available from: doi:10.1186/1750-1172-2-46
  13. KIDD D.. Neurological complications in Behcet's syndrome. [online] 1999 November, 122(11):2183-2194 [viewed 07 September 2014] Available from: doi:10.1093/brain/122.11.2183
  14. BUREš JAN, KOPáčOVá MARCELA, DOUDA TOMáš, BáRTOVá JOLANA, TOMš JAN, REJCHRT STANISLAV, TACHECí ILJA. Whipple’s Disease: Our Own Experience and Review of the Literature. Gastroenterology Research and Practice [online] 2013 December, 2013:1-10 [viewed 07 September 2014] Available from: doi:10.1155/2013/478349
  15. GRIMM SEAN, CHAMBERLAIN MARC. Hodgkin's Lymphoma: A Review of Neurologic Complications. Advances in Hematology [online] 2011 December, 2011:1-7 [viewed 07 September 2014] Available from: doi:10.1155/2011/624578
  16. STRAVODIMOU A., CAIROLI A., RAUSCH T., DU PASQUIER R., MICHEL P.. PTLD Burkitt Lymphoma in a Patient with Remote Lymphomatoid Granulomatosis. Case Reports in Medicine [online] 2012 December, 2012:1-4 [viewed 07 September 2014] Available from: doi:10.1155/2012/239719
  17. GOW P J. Diagnosis of Wilson's disease: an experience over three decades. [online] 2000 March, 46(3):415-419 [viewed 07 September 2014] Available from: doi:10.1136/gut.46.3.415
  18. MARTIN R J. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. Journal of Neurology, Neurosurgery & Psychiatry [online] 2004 September, 75(suppl_3):iii22-iii28 [viewed 10 September 2014] Available from: doi:10.1136/jnnp.2004.045906
  19. GHANDEHARI KAVIAN, GERAMI SARABI MOHAMMAD REZA, MAARUFI PARHAM. Clinical Evaluation of Patients with Spinal Cord Infarction in Mashhad, Iran. Stroke Research and Treatment [online] 2010 December, 2010:1-4 [viewed 10 September 2014] Available from: doi:10.4061/2010/942417

Investigations - for Diagnosis

Fact Explanation
Serum Anti nuclear antobodies, Anti-DNA antibodies, Anti-Sm antibodies and Anti-phospholipid antibodies [5] These tests are done mainly to exclude SLE [5]
Serum Vitamin B12 level [4] This is done to exclude vitamin B12 deficiency causing spastic paraparesis [4]
Treponema Pallidum Particles Agglutination Test for Syphilis [3] To exclude Syphilis which can cause neurological manifestations [3]
Antibodies to Borrelia antigens using ELISA and Western immunoblot [2] To exclude Lyme disease [2]
Serum Copper, Ceruloplasmin level [1] To exclude Wilson's disease and serum Copper is high in this [1]
Thyroid function tests [12] [13] 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. [12] [13]
Cerebrospinal fluid examination [6] [8] It shows oligoclonal IgG babnds and CSF cell count can be raised [6] [8]
Nerve conduction studies [10] 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 [10]
Electroencephalogram [11] This can show slow EEG background activity and reduced coherence in patients with cognitive impairment and high load of lesions in MRI [11]
MRI brain/ spinal cord [6] [7] [8] [9] 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 [6] [7] [8] [9]
Visual evoked responses [8] In optic neuropathy, visual evoked responses are delayed. [8]
References
  1. GOW P J. Diagnosis of Wilson's disease: an experience over three decades. [online] 2000 March, 46(3):415-419 [viewed 07 September 2014] Available from: doi:10.1136/gut.46.3.415
  2. WEINSTEIN ARTHUR. Array. CLIN INFECT DIS [online] 2008 July, 47(2):196-197 [viewed 07 September 2014] Available from: doi:10.1086/589316
  3. SEñA ARLENE C., WHITE BECKY L., SPARLING P. FREDERICK. Novel Serologic Tests: A Paradigm Shift in Syphilis Screening for the 21st Century . CLIN INFECT DIS [online] 2010 September, 51(6):700-708 [viewed 07 September 2014] Available from: doi:10.1086/655832
  4. ALLEN L. H. How common is vitamin B-12 deficiency?. American Journal of Clinical Nutrition [online] 2009 January, 89(2):693S-696S [viewed 07 September 2014] Available from: doi:10.3945/​ajcn.2008.26947A
  5. MANSON JESSICA J, RAHMAN ANISUR. . Orphanet J Rare Dis [online] 2006 December [viewed 07 September 2014] Available from: doi:10.1186/1750-1172-1-6
  6. OSBORNE B. J., VOLPE N. J.. Optic neuritis and risk of MS: Differential diagnosis and management. Cleveland Clinic Journal of Medicine [online] 2009 March, 76(3):181-190 [viewed 07 September 2014] Available from: doi:10.3949/ccjm.76a.07268
  7. THOMKE F., LENSCH E., RINGEL K., HOPF H. C.. Isolated cranial nerve palsies in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry [online] 1997 November, 63(5):682-685 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.63.5.682
  8. REJDAK K., JACKSON S., GIOVANNONI G.. Multiple sclerosis: a practical overview for clinicians. British Medical Bulletin [online] December, 95(1):79-104 [viewed 07 September 2014] Available from: doi:10.1093/bmb/ldq017
  9. LIU S., KULLNAT J., BOURDETTE D., SIMON J., KRAEMER D. F., MURCHISON C., HAMILTON B. E.. Prevalence of brain magnetic resonance imaging meeting Barkhof and McDonald criteria for dissemination in space among headache patients. Multiple Sclerosis Journal [online] December, 19(8):1101-1105 [viewed 07 September 2014] Available from: doi:10.1177/1352458512471874
  10. WARABI YOKO, YAMAZAKI MIKIHIRO, SHIMIZU TOSHIO, NAGAO MASAHIRO. Abnormal Nerve Conduction Study Findings Indicating the Existence of Peripheral Neuropathy in Multiple Sclerosis and Neuromyelitis Optica. BioMed Research International [online] 2013 December, 2013:1-6 [viewed 07 September 2014] Available from: doi:10.1155/2013/847670
  11. LEOCANI L.. Electroencephalographic coherence analysis in multiple sclerosis: correlation with clinical, neuropsychological, and MRI findings. [online] 2000 August, 69(2):192-198 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.69.2.192
  12. WOOTLA BHARATH, ERIGUCHI MAKOTO, RODRIGUEZ MOSES. Is Multiple Sclerosis an Autoimmune Disease?. Autoimmune Diseases [online] 2012 December, 2012:1-12 [viewed 10 September 2014] Available from: doi:10.1155/2012/969657
  13. TAVAKOLI M, POUR MANSHADI SM, NADERI N, DEHGHAN A, AZIZI S. Unusual Side Effects of Interferon Beta-1a in Patient with Multiple Sclerosis Mater Sociomed [online] 2012, 24(3):203-205 [viewed 10 September 2014] Available from: doi:10.5455/msm.2012.24.203-205

Investigations - Fitness for Management

Fact Explanation
Full blood count [1] [2] To exclude any anemia prior to surgical procedures (such as tendon release) [1] [2]
Coagulation studies [1] [2] To exclude any coagulopathy before surgical management [1] [2]
Renal function tests- Serum creatinine, Blood urea nitrogen [1] [2] [3] 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 [1] [2] [3]
References
  1. KUMAR A, SRIVASTAVA U. Role of routine laboratory investigations in preoperative evaluation J Anaesthesiol Clin Pharmacol [online] 2011, 27(2):174-179 [viewed 07 September 2014] Available from: doi:10.4103/0970-9185.81824
  2. SHULMAN M. A., THOMPSON B. R.. I. Not fit for a haircut ... how should we assess fitness and stratify risk for surgery?. British Journal of Anaesthesia [online] December, 112(6):955-957 [viewed 07 September 2014] Available from: doi:10.1093/bja/aeu003
  3. ARRAMBIDE G.. Thrombotic thrombocytopenic purpura-haemolytic uremic syndrome in relapsing-remitting multiple sclerosis patients on high-dose interferon beta. Multiple Sclerosis Journal [online] 2014 April [viewed 07 September 2014] Available from: doi:10.1177/1352458514529614

Investigations - Followup

Fact Explanation
Full blood count [1] Leukopenia can occur with interferon therapy, therefore it's important to monitor the patient [1]
Liver enzymes [1] Elevation of liver enzymes can occur with interferon therapy, therefore it's important to monitor the patient [1]
Thyroid function tests [3] With beta interferon therapy, alteration in thyroid function can occur in long term [3]
Spasticity of muscles [2] This should be assessed in follow up [2]
References
  1. CHIARION-SILENI VANNA, DEL BIANCO PAOLA, ROMANINI ANTONELLA, GUIDA MICHELE, PACCAGNELLA ADRIANO, DALLA PALMA MAURIZIO, NAGLIERI EMANUELE, RIDOLFI RUGGERO, SILVESTRI BARBARA, MICHIARA MARIA, DE SALVO GIAN LUCA. . BMC Cancer [online] 2006 December [viewed 07 September 2014] Available from: doi:10.1186/1471-2407-6-44
  2. THOMPSON A J. Clinical management of spasticity. Journal of Neurology, Neurosurgery & Psychiatry [online] 2005 April, 76(4):459-463 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.2004.035972
  3. Effects of Interferon Beta-1a in Patient with Multiple Sclerosis Mater Sociomed [online] 2012, 24(3):203-205 [viewed 10 September 2014] Available from: doi:10.5455/msm.2012.24.203-205

Investigations - Screening/Staging

Fact Explanation
Brain and spinal cord MRI [3] McDonald criteria is used to categorize MS depending on MRI lesions [3]
Cerebrospinal fluid examination [3] McDonald criteria is used to categorize MS depending on the presence of oligoclonal bands in CSF examination [3]
Visual evoked response [3] McDonald criteria includes this to make a diagnosis of MS along with MRI and CSF examination. [3]
Actionable Bladder Symptom Screening Tool (ABSST) [1] Urinary symptoms are common in MS therefore bladder dysfunction screening tool may be helpful to detect early dysfunction [1]
Patient Health Questionnaire-9 [2] This maybe helpful to Screen for depression in Outpatients With Multiple Sclerosis as it's commonly encountered [2]
References
  1. BURKS JACK, CHANCELLOR MICHAEL, BATES DAVID, DENYS PIERRE, MACDIARMID SCOTT, NITTI VICTOR, GLOBE DENISE, SIGNORI MANUEL, HUDGENS STACIE, ODDERSON IB, PANICKER JALESH, ROSS AMY PERRIN. Development and Validation of the Actionable Bladder Symptom Screening Tool for Multiple Sclerosis Patients. International Journal of MS Care [online] 2013 December, 15(4):182-192 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073.2012-049
  2. FERRANDO STEPHEN J., SAMTON JULIA, MOR NIV, NICORA STEPHANIE, FINDLER MARIANNE, APATOFF BRIAN. Patient Health Questionnaire-9 to Screen for Depression in Outpatients With Multiple Sclerosis. International Journal of MS Care [online] 2007 May, 9(3):99-103 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-9.3.99
  3. POLMAN CH, REINGOLD SC, BANWELL B, CLANET M, COHEN JA, FILIPPI M, FUJIHARA K, HAVRDOVA E, HUTCHINSON M, KAPPOS L, LUBLIN FD, MONTALBAN X, O'CONNOR P, SANDBERG-WOLLHEIM M, THOMPSON AJ, WAUBANT E, WEINSHENKER B, WOLINSKY JS. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria Ann Neurol [online] 2011 Feb, 69(2):292-302 [viewed 10 September 2014] Available from: doi:10.1002/ana.22366

Management - General Measures

Fact Explanation
Patient education and family education [9] [10] [11] 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. [9] [10] [11]
Rehabilitation [8] 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 [8]
Management of swallowing and speaking difficulties [3] 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 [3]
Management of bladder dysfunction [4] [7] intermittent self catheterization may help. Oxybutinin may play a role as well [4] [7]
Physiotherapy [5] This is important to relieve spasticity and improve and maintain functions of the limbs [5]
Occupational therapy [6] This is important for the patient to manage his activities of daily living [6]
Muscle relaxants [1] [2] Baclofen, Benzodiazapines, Gabapentin, Botilinum toxin, intra thecl Phenol are helpful to relieve the symptoms of spasticity. [1] [2]
Prevention of pressure sores [7] 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 [7]
Treatment of infections [7] Respiratory tract infections, Urinary tract infections need too be treated promptly
Treatment of fatigue [7] 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 [7]
Vaccination [11] 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. [11]
References
  1. JARRETT L. Managing severe lower limb spasticity in multiple sclerosis: does intrathecal phenol have a role?. [online] 2002 December, 73(6):705-709 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.73.6.705
  2. THOMPSON A J. Clinical management of spasticity. Journal of Neurology, Neurosurgery & Psychiatry [online] 2005 April, 76(4):459-463 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.2004.035972
  3. BROWN SHIRLEY A.. Swallowing and Speaking Challenges for the MS Patient. International Journal of MS Care [online] 2000 October, 2(3):4-14 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-2.3.4
  4. O'LEARY MARGIE, ERICKSON JANET R., SMITH CHRISTOPHER P., CANNON TRACY W., FRASER MATTHEW, BOYD MARLENE, HEYMAN ROCK, CHANCELLOR MICHAEL B.. Changes in Voiding Patterns in Patients With MS and Extended-Release Oxybutynin. International Journal of MS Care [online] 2002 January, 4(3):116-124 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-4.3.116
  5. CHAN A, HECK CS. Mobility in Multiple Sclerosis: More than just a Physical Problem. International Journal of MS Care [online] 2000 March, 2(1):51-61 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-2.1.51
  6. FALK-KESSLER JANET, KALINA J. TAMAR, MILLER PAMELA. Influence of Occupational Therapy on Resilience in Individuals with Multiple Sclerosis. International Journal of MS Care [online] 2012 October, 14(3):160-168 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-14.3.160
  7. HALPER J. The Evolution of Nursing Care in Multiple Sclerosis. International Journal of MS Care [online] 2000 March, 2(1):14-22 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-2.1.14
  8. HUTCHINSON BRIAN, FORWELL SUSAN J., BENNETT SUSAN, BROWN THEODORE, KARPATKIN HERB, MILLER DEBORAH. Toward a Consensus on Rehabilitation Outcomes in MS: Gait and Fatigue. International Journal of MS Care [online] 2009 June, 11(2):67-78 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-11.2.67
  9. RAE-GRANT ALEXANDER, KIMMEL SHARON R., ECKERT NANCY, SCHALL RICHARD, BEILMAN MAUREEN, KIMMEL DEBORAH. Professional Education in Multiple Sclerosis Care Through a Multidisciplinary Program for Health Care Practitioners. International Journal of MS Care [online] 2007 June, 9(4):148-153 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-9.4.148
  10. JURASKOVA ILONA, CHAPMAN JULIE, BUTOW PHYLLIS N., JOLAN AFSANEH, ZORDAN RACHEL, KIRSTEN LAURA T., SEDGWICK CHRISTINE. Challenges, Needs, Rewards, and Psychological Well-Being of Multiple Sclerosis Support-Group Facilitators. International Journal of MS Care [online] 2008 July, 10(3):85-93 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-10.3.85
  11. LEARY S M. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medical Journal [online] 2005 May, 81(955):302-308 [viewed 07 September 2014] Available from: doi:10.1136/pgmj.2004.029413

Management - Specific Treatments

Fact Explanation
Treatment of acute relapses [1] [2] These are treated with intravenous methyl prednisolone or high doses of oral steroids. Plasmapheresis may be helpful as well. [1] [2]
Treatment of relapsing MS [2] [3] [5] [6] [7] [8] [9] [10] 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. [2] [3] [5] [6] [7] [8] [9] [10]
Treatment of aggressive MS [2] [4] Azathioprine, high dose Cyclophosphamide, Mitoxantrone which are immunosuppressants may be beneficial. Intravenous Ig may have a role as well. [2] [4]
Treatment of progressive MS [2] [4] The main aim is to prevent progressive worsening of the disease. Drugs used are beta inetrferons and traditional immunosuppressants [2] [4]
Treatment of MS in pregnancy [12] 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. [12]
Other emerging therapies [11] 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. [11]
References
  1. LEARY S M. Multiple sclerosis: diagnosis and the management of acute relapses. Postgraduate Medical Journal [online] 2005 May, 81(955):302-308 [viewed 07 September 2014] Available from: doi:10.1136/pgmj.2004.029413
  2. POLMAN CH, UITDEHAAG BM. Drug treatment of multiple sclerosis West J Med [online] 2000 Dec, 173(6):398-402 [viewed 07 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071194
  3. PATY D. W., LI D.K.B.. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis: II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology [online] 1993 April, 43(4):662-662 [viewed 07 September 2014] Available from: doi:10.1212/WNL.43.4.662
  4. MOORE LINDA, KAUFMAN MICHAEL, CONWAY JILL. Response to Mitoxantrone for Secondary Progressive Multiple Sclerosis in African Americans Compared with Whites. International Journal of MS Care [online] 2010 July, 12(4):156-159 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-12.4.156
  5. KAUFMAN MICHAEL. Combining Therapies With Interferon Beta for Relapsing and Early Progressive MS: A Review. International Journal of MS Care [online] 2002 January, 4(2):50-69 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-4.2.50
  6. JALILIAN BABAK, EINARSSON HALLDóR, VORUP-JENSEN THOMAS. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?. IJMS [online] 2012 November, 13(12):14579-14605 [viewed 07 September 2014] Available from: doi:10.3390/ijms131114579
  7. SVENNINGSSON ANDERS, FALK EVA, CELIUS ELISABETH G., FUCHS SIEGRID, SCHREIBER KAREN, BERKö SARA, SUN JENNIFER, PENNER IRIS-KATHARINA, FOR THE TYNERGY TRIAL INVESTIGATORS , INFANTE-DUARTE CARMEN. Natalizumab Treatment Reduces Fatigue in Multiple Sclerosis. Results from the TYNERGY Trial; A Study in the Real Life Setting. PLoS ONE [online] 2013 March [viewed 07 September 2014] Available from: doi:10.1371/journal.pone.0058643
  8. BRYANT J. Systematic review of immunomodulatory drugs for the treatment of people with multiple sclerosis: Is there good quality evidence on effectiveness and cost?. [online] 2001 May, 70(5):574-579 [viewed 07 September 2014] Available from: doi:10.1136/jnnp.70.5.574
  9. O'LEARY SHIRLEY, BEAVIN JILL, BISHOP CYNTHIA, CAPOLINO LISA, GREINEL ELIDA, HUDSON ELIZABETH. Practical Guidelines for Administering Natalizumab: A Nursing Perspective. International Journal of MS Care [online] 2007 March, 9(1):1-8 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-9.1.1
  10. CAON CHRISTINA, MEYER CATHY, MAYER LORI, SMITH M. SHELTON. Efficacy and Safety of Alemtuzumab in Multiple Sclerosis and Impact on Nursing Role. International Journal of MS Care [online] 2013 December, 15(4):159-168 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073.2013-004
  11. SYC STEPHANIE, SCHIESS NICOLINE. Emerging Therapies for Multiple Sclerosis. International Journal of MS Care [online] 2010 April, 12(1):17-20 [viewed 07 September 2014] Available from: doi:10.7224/1537-2073-12.1.17
  12. LORENZI A R. Multiple sclerosis and pregnancy. [online] 2002 August, 78(922):460-464 [viewed 10 September 2014] Available from: doi:10.1136/pmj.78.922.460