Demyelinating diseases consists of a group of disorders characterized by the loss of myelin with relative axonal sparing. Primary demyelinating disorders may be attributed to autoimmune mechanisms. Demyelination is often secondary to infectious, metabolic, ischemic, or hereditary disorders or exposure to a toxin.
Presentation
Symptoms of demyelinating disorders are variable and depend on the neurologic deficits in the affected portion of the nervous system. Primary demyelinating disorders should be considered in patients presenting with diffuse or multifocal neurologic deficits of acute onset that wax and wane; in particular those that onset shortly after a vaccination or infection. The most common presenting symptom of demyelinating diseases are sensory disturbances of the limbs, vision loss, and subacute motor symptoms (e.g, weakness, spasticity, hyperreflexia, gait and balance disturbance) [1].
Common demyelinating disorders and presenting symptoms include:
- Multiple sclerosis - Common presenting features of multiple sclerosis include weakness, paraesthesia or focal sensory loss, diplopia, optic neuritis, ataxia, dizziness, muscle spasms, trigeminal neuralgia, depression, weakness, fatigue, seizures, and/or mild cognitive impairment. Bladder, bowel, and sexual dysfunction often occur as well [2].
- Acute disseminated encephalomyelitis - Patients with acute disseminated encephalomyelitis commonly have ataxia, headache, weakness, slurring of words, speech impairment, cranial nerve palsies, seizures, lethargy, delirium, stupor, and/or vomiting [3] [4].
- Progressive multifocal leukoencephalopathy - Common symptoms of progressive multifocal leukoencephalopathy include insidious onset of neurological deficits related to speech, vision, motor function, personality, and cognition [5] [6].
- Central pontine and extrapontine myelinolysis is characterized by acute onset of confusion, weakness of the extremities, and/or mutism. Other symptoms may include ataxia, difficulty swallowing, and low blood pressure. Some patients may also complain of movement disorders (e.g., dystonia, choreoathetosis, shuffling).
Hematological
- Hemophilia A
Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia. Discontinue using vitamin E 1 month before any surgical procedure. [nursece.com]
Entire Body System
- Collapse
She has come a long way since she was found collapsed on a Mendocino beach, severely emaciated and barely alive. [marinemammalcenter.org]
She is a mature adult northern fur seal who was found collapsed on a beach on the Mendocino coast, severely emaciated and barely alive. [web.archive.org]
Markowitz GS, Nasr SH, Barry Stokes M, et al. (2010) Treatment with IFN-α, -β, or -γ is associated with collapsing focal segmental glomerulosclerosis. Clin J Am SocNephrol 5: 607–615 Noris M, Remuzzi G (2009) Atypical hemolytic–uremic syndrome. [omicsonline.org]
[…] protein facilitates oligodendrocyte differentiation and process outgrowth early in the myelination process ( 45, 46 ), whereas MAG is important in oligodendrocyte–neuron signaling, such that it regulates axon caliber and contributes to axon growth cone collapse [doi.org]
Apnea and hypopnea may be caused by a collapse of the tissues and muscles in the pharynx (obstructive apnea/hypopnea) or a failure in the medullary respiratory signal (central apnea/hypopnea). [jcsm.aasm.org]
- Unconsciousness
GBS can also affect the nerves involved in unconscious body functions -- leading to abnormal heart rhythms, blood pressure fluctuations and difficulties with passing urine. [livestrong.com]
It rarely affects unconscious actions, such as breathing and blood pressure. Senses and feeling: A person may experience numbness, burning, or prickling sensations in their arms, legs, or feet. They may also feel pain when touched lightly. [medicalnewstoday.com]
- Congestive Heart Failure
Adverse events associated with anti-TNF strategies are tuberculosis, demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased. download article [poj.peeters-leuven.be]
The syndrome of latent cerebral venous thrombosis: its frequency and relation to age and congestive heart failure. Stroke (1973) 4 (3):419–30. doi:10.1161/01.STR.4.3.419 CrossRef Full Text | Google Scholar 13. [journal.frontiersin.org]
Gastrointestinal
- Hiccup
Symptoms include: Blurred vision Loss of eyesight Eye pain Weak or numb arms and legs Bladder and bowel problems Vomiting Uncontrollable hiccups Neuromyelitis optica doesn’t have a cure or FDA-approved medications to treat it. [webmd.com]
NMO has diverse clinical manifestations besides optic neuritis and transverse myelitis, including intractable vomiting unresponsive to antiemetics, hiccups, cranial nerve abnormalities, narcolepsy, diencephalic syndrome (endocrinopathy, water balance [neuropathology-web.org]
Takahashi, T., et al., Intractable hiccup and nausea in neuromyelitis optica with anti-aquaporin-4 antibody: a herald of acute exacerbations. Journal of neurology, neurosurgery, and psychiatry, 2008. 79(9): p. 1075–8. PubMed CrossRef 45. [springermedizin.de]
Cardiovascular
- Vascular Disease
Myelin damage can also occur with: alcoholism liver damage electrolyte imbalances Hypoxic-ischemic demyelination occurs due to vascular disease or a lack of oxygen in the brain. MS is the most common demyelinating condition. [healthline.com]
- Heart Failure
These diseases have rarely been associated with de novo heart failure and only in the setting of bladder dysfunction have they been linked to renal failure. [omicsonline.org]
Adverse events associated with anti-TNF strategies are tuberculosis, demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased. download article [poj.peeters-leuven.be]
The syndrome of latent cerebral venous thrombosis: its frequency and relation to age and congestive heart failure. Stroke (1973) 4 (3):419–30. doi:10.1161/01.STR.4.3.419 CrossRef Full Text | Google Scholar 13. [journal.frontiersin.org]
Musculoskeletal
- Muscle Spasm
Common demyelinating disorders and presenting symptoms include: Multiple sclerosis - Common presenting features of multiple sclerosis include weakness, paraesthesia or focal sensory loss, diplopia, optic neuritis, ataxia, dizziness, muscle spasms, trigeminal [symptoma.com]
Symptoms: The most common symptoms of demyelinating disorders are: Vision loss Muscle weakness Muscle stiffness Muscle spasms Changes in how well your bladder and bowels work Causes: in many cases, doctors aren’t sure what causes these conditions. [webmd.com]
Other manifestations can include painful muscle spasms, trigeminal neuralgia, fatigue and depression, subtle cognitive difficulties, psychiatric disturbances and seizures. [ncbi.nlm.nih.gov]
Eyes
- Blurred Vision
You may have blurred vision or lose your eyesight. If it’s in your spinal cord, your legs and arms might not work well. If you have one attack of neuromyelitis optica, you’ll probably get another. [webmd.com]
MS symptoms vary widely and include blurred vision, weak limbs, tingling sensations, unsteadiness and fatigue. For some people, MS is characterised by periods of relapse and remission while, for others, it has a progressive pattern. [msif.org]
[…] functions, so a wide range of symptoms can occur when nerves are affected by demyelination, including: numbness loss of reflexes and uncoordinated movements poorly controlled blood pressure blurred vision dizziness racing heart beat or palpitations memory [healthline.com]
Urogenital
- Sexual Dysfunction
Bladder, bowel, and sexual dysfunction often occur as well. [symptoma.com]
Sexual Dysfunction Because multiple sclerosis can affect not only the spinal nerves but also the autonomic nervous system, erectile dysfunction may be a symptom encountered by the male patient. [nursece.com]
[…] noise. 5 Patients with MS face a high risk of insomnia of around 40%. 1, 6 Awakening too early in the morning is the most common symptom (58%). 7 Primary symptoms of MS which can be associated with insomnia are neurogenic bladder (nocturia), spasticity, sexual [jcsm.aasm.org]
Neurologic
- Memory Impairment
If thiamine is given and death averted, Korsakoff's syndrome may develop in some patients, who suffer from memory impairment that leaves them unable to remember events for a period of a few years before the onset of illness (retrograde amnesia) and unable [the-medical-dictionary.com]
Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis. [jcsm.aasm.org]
Google Scholar | Crossref | Medline | ISI Benedict, R., Ramasamy, D., Munschauer, F., Weinstock-Guttman, B., Zivadinov, R. (2009) Memory impairment in multiple sclerosis: correlation with deep grey matter and mesial temporal atrophy.J Neurol Neurosurg [journals.sagepub.com]
J Neurol 259 : 139–146 [ PubMed ] Benedict R., Ramasamy D., Munschauer F., Weinstock-Guttman B., Zivadinov R. (2009) Memory impairment in multiple sclerosis: correlation with deep grey matter and mesial temporal atrophy. [ncbi.nlm.nih.gov]
- Neglect
Neglected tumours may reach large proportions. More examples of dermatofibrosarcoma protuberans How is dermatofibrosarcoma protuberans diagnosed? The absence of symptoms often leads to a delay in diagnosis of d ermatofibrosarcoma protuberans. [dermnetnz.org]
Consequently, patients frequently tend to neglect their problem and presentation can be late. Most patients have this tumor either as a stable lesion or growing over years. [ncbi.nlm.nih.gov]
Not surprisingly, this tumor's indolent behavior was often the cause for initial neglect. Therefore, in many cases, treatment was sought only after the onset of symptoms. [acsjournals.onlinelibrary.wiley.com]
- Spastic Gait
We describe herein the case of a 57 year old man who, over the last five years, has presented ataxic and spastic gait on the right side, a reduction in fine motor movement of the fingers mainly on the right side, superficial right side brachiocrural hypoesthesia [ncbi.nlm.nih.gov]
On first evaluation she had an atrophic optic disc on the left side, mild spastic gait and increased muscle stretch reflexes. [scielo.br]
- Speech Disorder
[…] or speech disorder Hand paralysis Clumsiness Hemiparesis or paralysis of one side of the body Lack of coordination Paresthesia or tingling, twitching and burning sensations on the skin Ocular paralysis Neurological symptoms Loss of sensation Genital [hxbenefit.com]
- Burning Sensation
The demyelination of nerves seriously affects the movements, cognition, sensation and other functions of patients. [hxbenefit.com]
Workup
The diagnosis of demyelinating disease consists of a history of present illness, physical exam, laboratory, neuromuscular and imaging tests. A history of any recent infections and/or vaccinations should be noted.
Laboratory tests that should be done include complete blood count, syphilis test (e.g., RPR), antinuclear antibodies, fluorescent treponemal antibody test, lyme titer, sedimentation rate, and angiotensin converting enzyme level [7].
A cerebrospinal fluid (CSF) exam may demonstrate pleocytosis (slight elevation of mononuclear white blood cells), oligoclonal immunoglobulin G (IgG) bands, and an elevated globulin to albumin ratio [8]. Patients with myelin damage will have elevated CSF myelin protein levels, which is indicative of myelin damage.
A magnetic resonance imaging (MRI) scan may show subclinical demyelinated lesions and/or enhancement of nerve roots with the use of gadolinium [9].
The "hot bath test" works by elevating the body's temperature, which leads to exacerbation of symptoms and worsened deficits in persons with demyelinating disease.
Neuromuscular testing including an electromyography (EMG) can be used to help determine presence of peripheral neuropathy and demyelination [10].
A sural nerve biopsy can be performed to add to the evidence for the diagnosis of a demyelinating disease.
MR
- Brain MRI Abnormal
On brain MRI, the MOG group had fewer brain abnormalities, fewer periventricular lesions, and fewer ovoid lesions perpendicular to the ventricle than the MS group. [nn.neurology.org]
Radiologically isolated syndrome (RIS) affects patients who have incidental brain MRI abnormalities suggestive of MS, but without any sign or symptom attributable to the disease. [jcsm.aasm.org]
Other Test Results
- Slow Nerve Conduction Velocity
Tests that can be of diagnostic help include nerve conduction testing and electromyography looking for very slow nerve conduction velocities, lumbar puncture looking for elevated spinal fluid protein without many inflammatory cells and MRI imaging of [rarediseases.org]
Treatment
Carroll WM 1, Saida T, Kim HJ, Kira J, Kermode AG, Tsai CP, Fujihara K, Kusunoki S, Tanaka M, Kim KK, Bates D ; Pam-Asian Committee on Treatment and Research of Multiple Sclerosis. [ncbi.nlm.nih.gov]
Prognosis
Prognosis of Demyelinating Diseases Prognosis of Demyelinating Diseases depends on the condition. [epainassist.com]
Prognosis The prognosis is excellent for low grade lesions but a poorer prognosis is associated with the FS variant due to a higher risk of recurrence and metastases. Overall, the rate of mortality is low (< 3% at 10 years). [orpha.net]
MRI T1: low signal T2 high signal usually higher than or equal to adjacent subcutaneous fat fat saturation sequences: suppressed T1 C+ (Gd): enhances Treatment and prognosis Dermatofibrosarcoma protuberans has an excellent prognosis after complete resection [radiopaedia.org]
Demyelinating Disease Prognosis The outcome of treatment depends on what type of demyelinating disorder is present in the patient. [hxbenefit.com]
Etiology
Abstract Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. [ncbi.nlm.nih.gov]
Epidemiology
SNP Genetics, Inc., Seoul, Republic of Korea. 5 Department of Life Science, Sogang University, Seoul, Republic of Korea; Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Republic of Korea. [ncbi.nlm.nih.gov]
Pathophysiology
This review discusses clinical, pathophysiological, radiological and therapeutic concepts of demyelinating disease of the CNS in SLE, focussing on its differentiation from MS and its relation with other CNS demyelinating processes, such as transverse [ncbi.nlm.nih.gov]
Cause & pathophysiology Cause- exactly not known Genetic propensity- HLA-DR15 & DQ6 increase risk Infection- possible trigger of inflammatory response- HHV, MMR Other- decreased sunlight exposure, smoking, stress, vaccinations, toxins Pathophysiology [slideshare.net]
A randomized, controlled, clinical trial Krøll et al. 2018 Migraine and its psychiatric comorbidities Minen et al. 2016 Pathophysiology of Migraine Pietrobon and Moskowitz 2013 The effects of aerobic exercise for persons with migraine and co-existing [herlevhospital.dk]
Prevention
Treatment Aims- returning function after an acute attack, preventing new attacks, preventing disability Acute attack- IV methylprednisolone ± plasmapheresis Disease modifiers- Interferon β-1a/1b Glatiramer Mitoxantrone Natalizumab Supportive [slideshare.net]
However, it cannot be prevented in individuals with genetic factors causing nerve demyelination. Researches are being carried out to find out whether it is possible to prevent nerve demyelination in such people. [hxbenefit.com]
However, very often the oligodendrocytes are also destroyed which delays or prevents remyelination from happening. Additionally, another kind of glial cell, called astrocytes, cause scar tissue to form in place of the myelin. [mult-sclerosis.org]
References
- Olek, 2005 - adapted from Paty et al., 1994 and Studney D et al., 1993, MS COSTAR: A computerized patient record adapted for clinical research purposes. J Neurol Rehab; 7:145.
- McAlpine D, Lamsden CE, Acheson ED. Multiple Sclerosis - A Reappraisal, ed. 2, Edinburgh, Churchill and Livingstone, 1972.
- Gupte G, Stonehouse M, Wassmer E, et al. Acute disseminated encephalomyelitis: a review of 18 cases in childhood. J Paediatr Child Health. 2003;39:336–42
- Leake JA, Albani S, Kao AS, et al. Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features. Pediatr Infect Dis J. 2004;23:756–64.
- Sugimoto C, Ito D, Tanaka K, et al. Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy. Arch Virol 1998;143:249–62.
- Hammarin AL, Bogdanovic G, Svedhem V, et al. Analysis of PCR as a tool for detection of JC virus DNA in cerebrospinal fluid for diagnosis of progressive multifocal leukoencephalopathy. J Clin Microbiol 1996;34:2929–32.
- Jones CT. Childhood autoimmune neurologic diseases of the central nervous system. Neurol Clin. 2003;21:745–64.
- Park SJ, Jeong IH, Kong BS, et al. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS. PLoS One. 2016;11:e0166277.
- Balashov K. Imaging of Central Nervous System Demyelinating Disorders. Continuum (Minneap Minn). 2016 Oct;22(5, Neuroimaging):1613-35.
- Hanewinckel R, Ikram MA, Van Doorn PA. Peripheral neuropathies. Handb Clin Neurol. 2016;138:263-82.