Continuing Education Activity
White matter lesions (WMLs) are areas of abnormal myelination in the brain. These lesions are best visualized as hyperintensities on T2 weighted and FLAIR (Fluid-attenuated inversion recovery) sequences of magnetic resonance imaging. They are considered a marker of small vessel disease. However, there are numerous non-vascular causes, as well. An increase in WMLs increases the risk of stroke, cognitive decline, depression, disability, and mortality in the general population. This activity reviews the evaluation and treatment of patients with WMLs and highlights the role of the interprofessional team in evaluating and treating patients with this condition.
Identify the etiology of white matter lesions.
Describe the typical imaging findings associated with various diseases presenting with white matter lesions.
Outline the management options available for patients with white matter lesions.
Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients with white matter lesions.
The white matter (WM)constitutes the network of nerve fibers that serves to allow the exchange of information and communication between different areas of the gray matter (GM). It lies beneath the GM inthe brainand superficial to GM in the spinal cord. It has evolved more than GM and occupies almost half of the brain. From the comparison of several cross-sections of the spinal cord performed in different regions, it is evident thatthe size of the area occupied by the WM varies from region to region, depending on the extent of the central GM. In particular, the GM/WM ratio grows from the cervical region to the lumbar region as the WM is decreasing as it proceeds towards the terminal portion of the spinal cord.
The WM contains neural networks formed by bundles of axons to mediate essential connectivity between different key motor and cognitive cortical regions. It comprises of myelinated and unmyelinated axons along with glial cells, including myelin-producing oligodendrocytes, microglia, astrocytes, and oligodendrocyte progenitor cells.
Myelin acts as electrical insulation for axons and is responsible for rapid saltatory impulse propagation and protects the nerve fibers from injury. It has a water content of about 40%. The remaining dry mass (60%) is mainly composed of proteins (15%to 30%) and lipids (70%to 85%), with phospholipids, cholesterol, galactolipids, and plasmalogens in a molar ratio of 2:2:1:1.
The chapter of WM lesions (WMLs) or leukoaraiosis encompassessmall vessel vascular brain diseases and non-vascular conditions. Any process leading to change in chemical composition, damage, or ischemia of myelinated fibers can present as WMLs on magnetic resonance imaging (MRI) that represents the gold standard for WMLs investigation. The term WM hyperintensity (WMH) is quite a descriptive expression used on MRI. These lesions are best seen as hyperintensities on T2 weighted and FLAIR (fluid-attenuated inversion recovery) sequences of MRI. FLAIR sequences have a particular role in assessing WMLs close to the ventricular margin by nullifying the cerebrospinal fluid (CSF) signal.
While the WMHs are well-described on MRI, the lesions were firstlyillustrated based onbrain computed tomography (CT). In 1985,Hachinski in 1985 described "leukoaraiosis" as "diminished density of white matter which is seen on brain computed tomography."
Concerning small vessel vascular brain processes, WMLs are commonly present in MRI of asymptomatic elderly individuals typically located in periventricular (PV-WMH) and deep subcortical regions (DS-WMH). For instance, WMLs arefrequently detected in people with untreated chronic hypertension. The volume of WMLs tends to increase with age from small punctate lesions to large confluent lesions. Nevertheless, although the occurrence of WMLs was initially considered a normal, age-related finding, recent investigations proved thatlarge areas of disease in the WM of the brainmust be considered as neuroimaging markers of brain frailty.Of note, various longitudinal studies described WMLs as a predictor for future risk of stroke, cognitive decline, depression, disability, and mortality in the general population.The clinical significance of the lesions is confirmed by the results of a meta-analysis thatdemonstrated three times increased risk of dementia and stroke, and a doubled risk of death in people with WMLs.For instance,the ischemic microvascular disease, vascular cause of WML, maycause about 45% of dementia cases and 20% of strokes. Again,WMLs are associated with poor post-stroke outcomes and increased risk of parenchymal hematoma following mechanical thrombectomy.
Apart from WMLs secondary to small vessel disease, however, these lesions are also common features of demyelinating inflammatory disorders, leukodystrophies, and degenerative disorders. Clinical aspects, prognosis, management varies according to the distribution and spread of the WM damage.
This group of lesions and diseases, therefore, includes very different clinical conditions in terms of etiology, pathogenesis, pathological features, clinical presentations, imaging, and therapy.Thisarticle is aimed at discussing the clinical features and treatment of patients with severaltypes ofWMLs. The role of the interprofessional team in evaluating and treating patients is also highlighted.
The etiology of white matter lesions (WMLs) is heterogeneous. Based on etiology,WMLs can be divided into vascular and non-vascular causes.
Vascular causes of WMLs include:
Microvascular ischemic disease or small vessel disease (SVD)
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Non-vascular causes for WMLs include:
Inflammatory: Multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD)
Infectious: HIV encephalopathy, progressive multifocal leukoencephalopathy (PMLE), neuroborreliosis, HSV and CMV encephalitis, neurosyphilis, CNS cryptococcal infection, Whipple disease, Lyme encephalopathy, subacute sclerosing panencephalitis (SSPE).
Toxic: Chronic alcohol abuse, carbon monoxide (CO) intoxication, inhalation of toluene, heroin, and cocaine, methotrexate-related leukoencephalopathy.
Metabolic: Vitamin B12 deficiency, copper deficiency, acute intermittent porphyria, hepatic encephalopathy, Hashimoto encephalopathy.
Neoplastic: Glial tumors, CNS Lymphoma
Traumatic: Radiotherapy, post-concussion(traumatic axonal injury, TAI)
Lysosomal Storage Diseases: Metachromatic leukodystrophy (MLD), Krabbe disease, Fabry disease, gangliosidosis, mucopolysaccharidosis
Peroxisomal Disorders: X linked adrenoleukodystrophy, Zellweger syndrome, Refsum disease
Mitochondrial Disorders: MERF (myoclonic epilepsy with ragged red fibers), MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes), Leigh disease, Kearns-Sayre disease.
Aminoacidopathies and Organic Acidopathies: Canavan disease, glutaric aciduria, urea cycle disorders
Unknown Etiology: Alexander disease, Vander Knapp encephalopathy
Others: Vanishing white matter disease, myotonic dystrophy
Another nosographic approach distinguishes primary WMLs, derived from an unknown etiology, from secondary ones; these latter due to a great variety of known etiologies.
In the general population, the prevalence of age-related vascularWMLs is approximately 10% to 20% at 60 years and approaches 100% in those older than 90 years.Studies have reported that WMLs are common in Japanese, Chinese, Caucasian, African-American, and Caribbean Black populations.
MS represents the most common inflammatory neurologicalcondition in young adults. Again, it has been estimated that the disease affects approximately 2,500,000 people worldwide.In the United States (US), the rate is 57 to 78 cases per 100,000 people in the southern states and 100 to 140 cases in the northern states.The prevalence of NMOSD is approximately 1/100,000 in the White population and up to 10/100,000 in Blacks. In East Asians, the prevalence is about 3.5/100,000 population.
PMLE is present in 1% to 4% of patients with AIDS. Furthermore, gliomas account for up to 35% of the CNS tumors in adolescents and young adults.
The incidence of WMLs secondary to heritableWM disorder is approximately 1 per 8,000 live births.However, for acquiredWM disorders in children, it is estimated to be 1.66 per 100,000 children.
Cerebrovascular risk factors such as age, hypertension, diabetes mellitus, hyperlipidemia, hyperhomocysteinemia, and hypersensitive C-reactive protein are well-known risk factors for vascular WMLs.Genetic factors also play an essential role in the development of WMLs as many genetic loci have been identified, and twin studies have suggested 55-80% heritability.
Pathophysiology for the development of vascular WMLs in elderly patients is thought to be secondary to chronically reduced blood flow by arteriosclerosis, lipohyalinosis, or fibrinoid necrosis of small vessels. Incomplete infarction secondary to persistent hypoxia leads to altered cerebral autoregulation promoting the transcription of many inflammatory genes, leading to the breakdown of the blood-brain barrier (BBB) and entry of pro-inflammatory proteins into the brain parenchyma and vessel wall. This will lead to demyelination, axonal loss, vacuolation, and reduced glial density. Some studies also suggest the role of venous collagen deposition in the pathogenesis of ischemic WMLs.
The different distribution of the lesions could be linked to different pathogenetic mechanisms. PV-WMH is featured by gliosis, loosening of the WM, loss around convoluted venules in perivascular spaces. In contrast, theprimarycharacteristics of DS-WMH are demyelination, gliosis, andaugmentedtissue loss as the lesions become more serious. By summarizing, the pathological characteristicsof WMLsmay encompass myelin rarefaction, reactive gliosis, axonal loss, infarction, venular collagenosis, arteriosclerotic small vessel alterations. Moreover, BBB impairment plays a pivotal role in the genesis of WM damage, and a different pattern involvesPV-WMH and DS-WMH.
In WMLs secondary to non-vascular diseases like MS, demyelination is caused by autoimmune inflammation-mediated primarily by T cells againstmyelin proteins.While the cause of MS is still unknown, it probably presupposes a combination of genetic susceptibility and nongenetic factors such as viral infection, low vitamin D levels. This combination results in an autoimmune disorderthat leads to myelin loss, destruction of oligodendrocytes, and reactive astrogliosis. However,the axon is usually undamaged; in some patients, it is aggressively destroyed.
NMOSD is a group of inflammatory disorders of the CSN featuring severe immune-mediated demyelination and axonal damage, involving optic nerves and spinal cord mostly. Although these disorders werestudied as avariant of MS, they have distinct pathophysiology.Theautoimmune pathogenesis for NMOSD, indeed, involves IgG autoantibody against the aquaporin-4 (AQP4) water channelor the myelin oligodendrocyte glycoprotein. In a subset of NMOSD, no antibodies (double-seronegative disease).
The exact mechanism of the pathophysiology of ADEM is still unknown. However, it has been related to inflammation initiated by infection or vaccination in genetically susceptible individuals causing demyelination. PMLE is a central demyelinating disease caused by reactivation (usually occurs at CD4 count less than 200/cmm) of latent JC polyomavirus (or John Cunningham virus or Human polyomavirus 2) in oligodendrocytes, in HIV patients. Leukodystrophy causes WMLs secondary to substrate accumulation due to enzymatic defects causing demyelination.
The TAI refers to a severe axonal mechanical damage due toa rotational acceleration of the brain. Although its pathophysiology is complicated, the injury damage is firstlydue to amechanical break involving axonal microtubules. This stretchinducesaxonal damages through undulations and breaks and direct membrane mechanoporation with calcium influx. This mechanism leads to the activation of several injurious pathways, including the caspase-mediated proteolysis and the cytokine-mediated microglia recruitment with impairment of axonal transport and theagglomeration of transported proteins in varicose swellings.
History and Physical
Clinical presentation can vary from asymptomatic to patients with disabling disease as per the WMLs etiology. Elderly patients with small punctate cerebral vascular white matter lesions (WMLs) are usually asymptomatic, but they progress to large confluent lesions and can present with subtle functional decline, cognitive impairment, dementia, urinary incontinence, or gait and balance impairment and neuropsychiatric disorders.
Within the group of vascular WM diseases,the distribution of lesions varies greatly, and consequently, the clinical aspects. For instance, in SVD, the WMHs are mainly found in basal ganglia and frontotemporal and periventricular WM. It may induce cognitive impairment, loss of balance or coordination, vision loss, and dizziness. Severe headachescan be present in different types of WMLs.
Patients with non-vascular etiology of WMLs like MS can have heterogeneous presentations, including fatigue, unilateral visual blurring, sensory changes, motor abnormality, urinary incontinence, speech and swallowing difficulties, pain, anxiety, depression, numbness and tingling, cognitive dysfunction. Nevertheless,the clinical scenario varies from patient to patient as well as the evolution of the disease. In some patients, indeed, there is a progressive and rapid deterioration, while in others, an alternation between relapses and remissions can be observed.
Clinical aspects of NMOSD include acute attacks of bilateral optic neuritis with significant visual loss or transverse myelitis, inducing limb weakness, sensory loss, and bladder dysfunction. Other symptoms can include episodes of intractable nausea, vomiting, hiccups, excessive daytime somnolence or narcolepsy, and seizures. There are a commonlyrelapsing course and variable degrees of recoverywithinweeks to months.
Children with WMLs presenting with progressive symptoms of declining developmental milestones, cognitive impairment, and motor abnormalities should be suspected for leukodystrophy. However, patients in their first or second decade with WMLs secondary to ADEM present with acute onset and rapidly progressive symptoms of fever, headache, vomiting, confusion, or altered sensorium.Although migraine was associated with structural changes in the brain WM, these lesions are generally not linked to any neurological issuesas well as an increased risk of cognitive decline.
Evaluation of patients presenting with white matter lesions (WMLs) depends on the age of the patient, clinical scenario, and pattern of white matter lesions on MRI.
WMLs on MRI are common manifestations of cerebral small vessel disease and are associated with vascular risk factors. These patients should be screened for vascular risk factors by routine laboratory tests, including complete metabolic panel, lipid profile, and HbA1c. Also, in these patients, it is worthwhile to quantify WMLs to monitor their progress with time. Various grading scales like the Fazekas scale, age-related white matter changes (ARWMC) rating scale, and Van Swieten scale can be used to assess the extent and progression of WMLs.
Patients with non-vascular WMLs require further evaluation to identify the etiology of the lesions. CSF analysis is helpful in cases of suspected MS (oligoclonal bands), ADEM (lymphocytic pleocytosis with raised proteins), and infectious demyelination (antiviral antibodies). MR spectroscopy can help in the etiological diagnosis of WMLs to differentiate lesions based on different metabolites peaks.
Additional tests like serology for autoantibodies in case of suspected vasculitis, anti-MOG antibodies in ADEM, and anti AQP4 antibodies in NMOSD. Also, metabolic and toxicology screens can be helpful in suspected cases. Children with WMLs and clinical scenarios for leukodystrophy require genetic testing.
Treatment / Management
White matter lesions (WMLs) detected incidentally or in MRI of elderly patients with a transient ischemic attack (TIA) require management of vascular risk factors by:
Intensively controlling the blood pressure
Strict diabetes control
Promoting physical fitness
Use of antiplatelets
Prophylaxis of migraine with aura can also help decrease the risk of WMLs. The use of B vitamins to lower homocysteine levels is useful in managing patients with SVD.
Management of patients with non-vascular WMLs is individualized as per etiology. WMLs secondary to MS flares are treated with steroids. However, patients need long term maintenance therapy with disease-modifying treatment to halt disease progression. Furthermore, in patients with ADEM, immunosuppression with high-dose intravenous glucocorticoids is used. Acyclovir has also been reported to have benefits in some cases. Leukodystrophies do not have a specific treatment, and treatment is supportive and symptomatic only.
Pattern recognition of white matter lesions (WMLs) in MRI is crucial as it may make the diagnosis in many conditions.
The differential diagnosis for symmetric WMLs:
Bilateral Hemispheres: Toxic encephalopathy, HIV encephalopathy, autoimmune encephalopathies, and Vitamin B12 deficiency
Periventricular Lesions: Small vessel disease, HIV encephalopathy, vitamin B12 deficiency, metachromatic leukodystrophy, X-linked adrenoleukodystrophy, and vanishing white matter disease
Subcortical Including Arcuate Fibers: Alexander disease, Kearns-Sayre syndrome, and CADASIL
Frontal Predominance: Alexander Disease, and metachromatic leukodystrophy
Parietal/Temporal/Occipital Lobes: PRES (posterior reversible encephalopathy), heroin abuse, and Krabbe disease.
Corpus Callosum: Marchifava-Bignami disease, metachromatic leukodystrophy, and Krabbe disease
Cerebellum: Toxic encephalopathy, and mitochondriopathies
Central Pons: Central pontine myelinolysis (CPM)
The differential diagnosis for asymmetric WMLs:
Patchy Multifocal Confluent Lesion: MS, autoimmune encephalopathies, and CADASIL
Parieto-Occipital Regions: PMLE
The prognosis of patients with white matter lesions (WMLs) depends on the etiology of the lesions. Patients with age-related WMLs are irreversible and progressive. Large and confluent WMLs have a poor prognosis and lead to cognitive impairment and global functional decline. A study by Hassan et al. confirmed the association of severity of white matter lesions with mortality.
WMLs secondary to MS have interpatient variability in prognosis. Severe disabilities are present in 5% of patients within the first five years of onset, and 10–20% of patients of MS remain unimpaired without therapy even after 20 years. NMO and ADEM have a variable prognosis from complete recovery to the development of permanent physical disability, especially in post measles ADEM.Acute demyelinating disease prognosis depends upon the severity of the initial illness. Patients responding to treatment have a favorable prognosis. However, leukodystrophies have poor prognosis. Reversible causes, including metabolic and toxic encephalopathies, have a good prognosis.
Severe white matter lesions (WMLs) are associated with cognitive impairment, global functional decline, cerebrovascular accident, mood disorders,gait, and balance dysfunction. WMLs are also associated with grey matter atrophy and accelerate neurodegeneration.Furthermore, severe, extensive involvement of white matter by non-vascular causes like MS, ADEM, and NMO causes disability.
Deterrence and Patient Education
Patients with vascular risk factors should be identified early and counseled on lifestyle changes as well as control of comorbid conditions. Self-monitoring of blood pressure and blood sugar, dietary modifications, weight reduction, and improving physical fitness has proven to decrease the progression of white matter lesions.Involvement in cognitively complex leisure activity to improve cognitive reserve has been associated with a protective effect on cognitive functioning and late-life depression in patients with WMLs.
Enhancing Healthcare Team Outcomes
As described, white matter lesions (WMLs) have varied clinical presentations, differential diagnoses, and complications. Managing these patients requires extensive collaboration and coordination among a team of professionals, which consists of neurologists, radiologists, internists, ophthalmologists, psychiatrists, neurosurgeons, rheumatologists, microbiologists, pain specialists, nurse specialists, mental health nurses, pharmacists, physical therapists, and nutritionist. It is compulsory to identify the right set of professionals depending on the etiology of a case. Clear and effective communication between these professionals while monitoring the progression and complications of WMLs can decrease mortality.
Fazekas grade three white matter lesions in a case of stroke. Contributed by Sunil Munakomi, MD
Muzio MR, Cascella M. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Nov 14, 2022. Histology, Axon. [PubMed: 32119275]
Nave KA, Werner HB. Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol. 2014;30:503-33. [PubMed: 25288117]
Hachinski VC, Potter P, Merskey H. Leuko-araiosis: an ancient term for a new problem. Can J Neurol Sci. 1986 Nov;13(4 Suppl):533-4. [PubMed: 3791068]
Firbank MJ, Teodorczuk A, van der Flier WM, Gouw AA, Wallin A, Erkinjuntti T, Inzitari D, Wahlund LO, Pantoni L, Poggesi A, Pracucci G, Langhorne P, O'Brien JT., LADIS group. Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study. Br J Psychiatry. 2012 Jul;201(1):40-5. [PubMed: 22626634]
Debette S, Beiser A, DeCarli C, Au R, Himali JJ, Kelly-Hayes M, Romero JR, Kase CS, Wolf PA, Seshadri S. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke. 2010 Apr;41(4):600-6. [PMC free article: PMC2847685] [PubMed: 20167919]
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010 Jul 26;341:c3666. [PMC free article: PMC2910261] [PubMed: 20660506]
Kang HJ, Stewart R, Park MS, Bae KY, Kim SW, Kim JM, Shin IS, Cho KH, Yoon JS. White matter hyperintensities and functional outcomes at 2 weeks and 1 year after stroke. Cerebrovasc Dis. 2013;35(2):138-45. [PubMed: 23406918]
Atchaneeyasakul K, Leslie-Mazwi T, Donahue K, Giese AK, Rost NS. White Matter Hyperintensity Volume and Outcome of Mechanical Thrombectomy With Stentriever in Acute Ischemic Stroke. Stroke. 2017 Oct;48(10):2892-2894. [PMC free article: PMC5659291] [PubMed: 28887393]
Smith EE, Saposnik G, Biessels GJ, Doubal FN, Fornage M, Gorelick PB, Greenberg SM, Higashida RT, Kasner SE, Seshadri S., American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Functional Genomics and Translational Biology; and Council on Hypertension. Prevention of Stroke in Patients With Silent Cerebrovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2017 Feb;48(2):e44-e71. [PubMed: 27980126]
GBD 2016 Multiple Sclerosis Collaborators. Global, regional, and national burden of multiple sclerosis 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Mar;18(3):269-285. [PMC free article: PMC6372756] [PubMed: 30679040]
Hor JY, Asgari N, Nakashima I, Broadley SA, Leite MI, Kissani N, Jacob A, Marignier R, Weinshenker BG, Paul F, Pittock SJ, Palace J, Wingerchuk DM, Behne JM, Yeaman MR, Fujihara K. Epidemiology of Neuromyelitis Optica Spectrum Disorder and Its Prevalence and Incidence Worldwide. Front Neurol. 2020;11:501. [PMC free article: PMC7332882] [PubMed: 32670177]
Diwanji TP, Engelman A, Snider JW, Mohindra P. Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. Adolesc Health Med Ther. 2017;8:99-113. [PMC free article: PMC5624597] [PubMed: 28989289]
Bonkowsky JL, Nelson C, Kingston JL, Filloux FM, Mundorff MB, Srivastava R. The burden of inherited leukodystrophies in children. Neurology. 2010 Aug 24;75(8):718-25. [PMC free article: PMC2931652] [PubMed: 20660364]
Langer-Gould A, Zhang JL, Chung J, Yeung Y, Waubant E, Yao J. Incidence of acquired CNS demyelinating syndromes in a multiethnic cohort of children. Neurology. 2011 Sep 20;77(12):1143-8. [PMC free article: PMC3265045] [PubMed: 21865580]
Fornage M, Debette S, Bis JC, Schmidt H, Ikram MA, Dufouil C, Sigurdsson S, Lumley T, DeStefano AL, Fazekas F, Vrooman HA, Shibata DK, Maillard P, Zijdenbos A, Smith AV, Gudnason H, de Boer R, Cushman M, Mazoyer B, Heiss G, Vernooij MW, Enzinger C, Glazer NL, Beiser A, Knopman DS, Cavalieri M, Niessen WJ, Harris TB, Petrovic K, Lopez OL, Au R, Lambert JC, Hofman A, Gottesman RF, Garcia M, Heckbert SR, Atwood LD, Catellier DJ, Uitterlinden AG, Yang Q, Smith NL, Aspelund T, Romero JR, Rice K, Taylor KD, Nalls MA, Rotter JI, Sharrett R, van Duijn CM, Amouyel P, Wolf PA, Gudnason V, van der Lugt A, Boerwinkle E, Psaty BM, Seshadri S, Tzourio C, Breteler MM, Mosley TH, Schmidt R, Longstreth WT, DeCarli C, Launer LJ. Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium. Ann Neurol. 2011 Jun;69(6):928-39. [PMC free article: PMC3122147] [PubMed: 21681796]
Fennema-Notestine C, McEvoy LK, Notestine R, Panizzon MS, Yau WW, Franz CE, Lyons MJ, Eyler LT, Neale MC, Xian H, McKenzie RE, Kremen WS. White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin. 2016;12:737-745. [PMC free article: PMC5071546] [PubMed: 27790395]
Wardlaw JM, Valdés Hernández MC, Muñoz-Maniega S. What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc. 2015 Jun 23;4(6):001140. [PMC free article: PMC4599520] [PubMed: 26104658]
Papadopoulos D, Magliozzi R, Mitsikostas DD, Gorgoulis VG, Nicholas RS. Aging, Cellular Senescence, and Progressive Multiple Sclerosis. Front Cell Neurosci. 2020;14:178. [PMC free article: PMC7338849] [PubMed: 32694983]
Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004 Dec 11-17;364(9451):2106-12. [PubMed: 15589308]
Mohammadian M, Roine T, Hirvonen J, Kurki T, Posti JP, Katila AJ, Takala RSK, Tallus J, Maanpää HR, Frantzén J, Hutchinson PJ, Newcombe VF, Menon DK, Tenovuo O. Alterations in Microstructure and Local Fiber Orientation of White Matter Are Associated with Outcome after Mild Traumatic Brain Injury. J Neurotrauma. 2020 Dec 15;37(24):2616-2623. [PubMed: 32689872]
Hasan TF, Barrett KM, Brott TG, Badi MK, Lesser ER, Hodge DO, Meschia JF. Severity of White Matter Hyperintensities and Effects on All-Cause Mortality in the Mayo Clinic Florida Familial Cerebrovascular Diseases Registry. Mayo Clin Proc. 2019 Mar;94(3):408-416. [PubMed: 30832790]
Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010 Jul;133(Pt 7):1914-29. [PMC free article: PMC2892939] [PubMed: 20534650]
Habes M, Erus G, Toledo JB, Zhang T, Bryan N, Launer LJ, Rosseel Y, Janowitz D, Doshi J, Van der Auwera S, von Sarnowski B, Hegenscheid K, Hosten N, Homuth G, Völzke H, Schminke U, Hoffmann W, Grabe HJ, Davatzikos C. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain. 2016 Apr;139(Pt 4):1164-79. [PMC free article: PMC5006227] [PubMed: 26912649]
Sexton CE, Betts JF, Demnitz N, Dawes H, Ebmeier KP, Johansen-Berg H. A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain. Neuroimage. 2016 May 01;131:81-90. [PMC free article: PMC4851455] [PubMed: 26477656]
Lin C, Huang CM, Fan YT, Liu HL, Chen YL, Aizenstein HJ, Lee TM, Lee SH. Cognitive Reserve Moderates Effects of White Matter Hyperintensity on Depressive Symptoms and Cognitive Function in Late-Life Depression. Front Psychiatry. 2020;11:249. [PMC free article: PMC7158948] [PubMed: 32322221]
Disclosure: Roopa Sharma declares no relevant financial relationships with ineligible companies.
Disclosure: Sandeep Sekhon declares no relevant financial relationships with ineligible companies.
Disclosure: Marco Cascella declares no relevant financial relationships with ineligible companies.
White matter lesions (WMLs) are areas of abnormal myelination in the brain. These lesions are best visualized as hyperintensities on T2 weighted and FLAIR (Fluid-attenuated inversion recovery) sequences of magnetic resonance imaging. They are considered a marker of small vessel disease.Are white matter lesions always MS? ›
DIFFERENTIAL RADIOLOGICAL DIAGNOSIS OF WHITE MATTER LESIONS. White matter T2 hyperintensities in the brain are not specific to MS and are seen in a number of other disorders. They can even be seen in otherwise normal individuals, particularly with increasing age.Are white matter lesions in brain normal? ›
Cerebral white matter lesions (WML) are common in the aging brain and are associated with dementia and depression. They are associated with vascular risk factors and small vessel disease, suggesting an ischemic origin, but recent pathology studies suggest a more complex pathogenesis.What causes white matter lesions on brain MRI? ›
White spots on a brain MRI are not always a reason to worry. There are many possible causes, including vitamin deficiencies, infections, migraines, and strokes. Other risk factors for white spots include getting older, race/ethnicity, genetics, obesity, diabetes, hypertension, and high cholesterol.Are white matter lesions serious? ›
Some white matter lesions may not cause noticeable symptoms and can be considered almost “normal” with aging. However, some of these lesions can damage important pathways (highways) within your brain and can cause problems with memory, balance and walking.What is it when you have lesions of white matter in an MRI? ›
White matter lesions (WMLs) are areas of abnormal myelination in the brain. These lesions are best visualized as hyperintensities on T2 weighted and FLAIR (Fluid-attenuated inversion recovery) sequences of magnetic resonance imaging. They are considered a marker of small vessel disease.What are the 4 stages of white matter disease? ›
Four stages were defined by dividing individuals into simple quartiles corresponding to those with the lowest total WMSA (Quartile I, n = 25), mid-low total WMSA (Quartile II, n = 25), mid-high total WMSA (Quartile III, n = 25), and highest total WMSA (Quartile IV, n = 22) (Fig.How do you treat white matter brain lesions? ›
There isn't a specific treatment. The goal is to treat the cause of the damage and stop the disease from getting worse. Your doctor may prescribe medicines to lower your blood pressure or cholesterol. If you smoke, you should quit.Can stress cause white matter lesions? ›
Several lines of evidence have reported white matter dysfunction in psychiatric conditions, including depression, stress- and anxiety-related disorders.What is the life expectancy of a person with white matter disease? ›
In general, the prognosis is grave, with the majority of patients dying after a few years. However, some die only after several months, and some manage to survive for several decades .
White matter disease doesn't have a cure, but there are treatments that can help manage your symptoms. The primary treatment is physical therapy. Physical therapy can help with any balance and walking difficulties you may develop.Can brain lesions be harmless? ›
Brain lesions are areas of abnormal tissue that have been damaged due to injury or disease, which can range from being relatively harmless to life-threatening.Should I worry about white matter hyperintensities? ›
These changes in the white matter are predictors of a future risk of stroke, even after adjusting for the presence of vascular risk factors; decline in global cognitive performance, executive function, and processing speed; dementia (Alzheimer type, vascular, and mixed); and death, particularly due to cardiovascular ...Can white matter lesions cause anxiety? ›
The altered white matter may be a vulnerability marker in individuals at high risk of clinical anxiety.Can depression cause white matter lesions? ›
Depressive disorder has been linked to changes in the white matter. White matter changes in depressive disorder could be a result of impaired cerebral blood flow (CBF) and CBF self-regulation, impaired blood-brain barrier function, inflammatory factors, genes and environmental factors.What do white matter lesions indicate? ›
White matter lesions (WMLs) or leukoaraiosis indicate small vessel vascular brain disease as well as degenerative or inflammatory processes. WMLs appear as hyperintense periventricular or subcortical patchy or confluent areas on T2 or fluid-attenuated inversion recovery MRI sequence.How fast does white matter disease progress? ›
This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years.What diseases can cause lesions on the brain? ›
- Brain tumors (including cancer).
- Congenital disorders (conditions you have at birth) and metabolic disorders.
- Degenerative brain diseases (especially age-related ones), such as Alzheimer's disease, Lewy body dementia, Multiple system atrophy, and Parkinson's disease.
Unlike Alzheimer's disease, which shrinks the hippocampus causing progressive memory loss, white matter disease is a more diffuse mind-robbing condition that targets small blood vessels deep within the brain's white matter.Is white matter disease the same as MS? ›
“In general, white matter disease causes acute MS symptoms, like numbness and weakness," Stone says. "Gray matter disease causes progressive symptoms, like fatigue and memory loss. These higher brain functions are called cognitive functions. Most MS disability actually comes from cognitive dysfunction."
White matter changes (WMCs) have been reported to be associated with a decline in motor function in speed and fine motor coordination, and with many diseases including AD [2,5,6], vascular dementia, dementia with Lewy bodies, and psychiatric disorders .What does white matter disease feel like? ›
While white matter disease has been associated with strokes, cognitive loss, and dementia, it also has some physical and emotional symptoms such as balance problems, falls, depression, and difficulty multitasking (e.g., walking and talking).Do brain lesions need to be removed? ›
Common approaches for treating brain lesions include the following: "Wait and see;" if the lesion is not causing problems and is not growing, you may only need periodic checkups. Surgical removal of the lesion, if possible; new surgical techniques may make it possible to remove even hard-to-reach lesions.Is white matter disease same as dementia? ›
The difference between sub-cortical and white matter dementia occurs with procedural memory, which is impaired in subcortical dementia, but normal in white matter dementia as it is in cortical dementia. Thus, white matter dementia is seen as a memory retrieval deficit with normal procedural memory.Do white matter lesions cause fatigue? ›
Brain white matter (WM), and more specifically neuronal connectivity, is thought to perform a crucial role in the central processing of fatigue .Are white matter lesions migraine or MS? ›
If you have migraine or MS, it may show brain lesions called white matter lesions or T2 hyperintensities, although the pattern is usually different in each. This is why these lesions need to be interpreted carefully on an MRI and considered along with your symptoms.Can high blood pressure cause white matter lesions? ›
Several studies have suggested that people with high blood pressure have a greater chance of accumulating white matter lesions and experiencing later-in-life cognitive impairment and dementia.What vitamins help with white matter disease? ›
Vitamin D, Folate, and Cobalamin Serum Concentrations Are Related to Brain Volume and White Matter Integrity in Urban Adults.Is white matter disease a stroke? ›
In traditional stroke subtyping, subcortical or white matter stroke includes infarcts in the white matter deep to the cortex in humans, and also small basal ganglia, thalamus, and brainstem strokes or “lacunar” infarctions.Can the brain recover white matter? ›
White matter injuries are very serious, but, depending on the type and extent of the injury, extensive recovery may occur. As long as the neuron cell bodies remain healthy, axons can regrow and slowly repair themselves.
In addition, white matter hyperintensities (WMH), for example in the spinothalamic tract, also referred to as the anterolateral pathway, may lead to an increase in pain experience; this type of pain is paraphrased as deafferentiation pain.Do white spots on the brain mean dementia? ›
Increased numbers and size of the intense-white spots seen on the mostly gray images of the brain have long been linked to memory loss and emotional problems, especially as people age.Do brain lesions always mean MS? ›
Not all lesions seen in an MRI are caused by MS. Lesions can be caused by other diseases such as migraine or stroke, and they can also develop with age. They can be detected in MRI scans before you experience any symptoms. Sometimes, a lesion might be detected in a scan that was done for another reason.Can you live a long life with brain lesions? ›
Some brain tumours grow very slowly (low grade) and cannot be cured. Depending on your age at diagnosis, the tumour may eventually cause your death. Or you may live a full life and die from something else. It will depend on your tumour type, where it is in the brain, and how it responds to treatment.What happens if a brain lesion is left untreated? ›
If left untreated, any type of glioma may grow and press on other structures within the brain. Pressure on the brain can be harmful as it forces the brain against the skull, causing damage to the brain and hampering its ability to function properly.What age do people get white matter hyperintensities? ›
Background. White matter hyperintensities (WMH), visible on T2-weighted MRI scans, are frequent in the elderly population, being in patients with cognitive impairment but also in cognitively unimpaired adults older than 60 years old.Do white matter hyperintensities mean MS? ›
White matter hyperintensities (WMH) seen on T2WI are a hallmark of multiple sclerosis (MS) as it indicates inflammation associated with the disease. Automatic detection of the WMH can be valuable in diagnosing and monitoring of treatment effectiveness.Are white matter lesions the same as white matter hyperintensities? ›
White matter hyperintensities (WMHs) are brain white matter lesions that are hyperintense on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans. Larger WMH volumes have been associated with Alzheimer's disease (AD) and with cognitive decline.Can white matter lesions cause vertigo? ›
White matter lesions (WMLs) are often seen on magnetic resonance imaging (MRI) scans of elderly people and are related to various geriatric disorders, including dizziness. The cause of this correlation could be the disruption of neuronal networks that mediate higher vestibular cortical function.Can emotional trauma cause white matter disease? ›
Trauma exposure may result in disruption of cerebral white matter in individuals with or without PTSD, particularly in the frontal fibers.
Significance. Psychological stress is linked to multiple sclerosis (MS) severity (e.g., to a heightened risk of brain lesion development).What disease affects the white matter in the brain? ›
White matter disease, or leukoaraiosis, means there is damage to white matter in the brain. It can lead to problems with thinking, problem solving, balance, and other symptoms. White matter is tissue that includes nerve fibers (axons), which connect nerve cells. A fatty tissue called myelin covers the axons.What psychiatric disorders are associated with white matter hyperintensities? ›
White-matter hyperintensities have been associated with both schizophrenia and mood disorders, particularly bipolar disorder, but results are inconsistent across studies.Can tension headaches cause white matter lesions? ›
Results: Individuals with tension-type headache were more likely to have extensive white matter hyperintensities than headache-free subjects, with this being the case across all methods of white matter hyperintensities assessment (Scheltens scale: Odds ratio, 2.46; 95% CI, 1.44-4.20).Can you have lesions and not have MS? ›
The diagnosis of MS cannot be made solely on the basis of MRI because there are other diseases that cause lesions in the CNS that look like those caused by MS. And even people without any disease — particularly the elderly — can have spots on the brain that are similar to those seen in MS.Do lesions on the brain always mean MS? ›
Not all lesions seen in an MRI are caused by MS. Lesions can be caused by other diseases such as migraine or stroke, and they can also develop with age. They can be detected in MRI scans before you experience any symptoms. Sometimes, a lesion might be detected in a scan that was done for another reason.Can you still have MS if MRI is clear? ›
There are rare cases where someone can have MS but their MRI will look clear. This happens. That doesn't mean they can't get a diagnosis of multiple sclerosis, but it does make it significantly more difficult.How do I know if my brain lesions are MS? ›
More than 90% of people with MS have scar tissue that shows up on an MRI scan. A spinal tap can check for abnormalities in the fluid that bathes the brain and spinal cord. Tests to look at electrical activity of nerves can also help with diagnosis.
It is also known as neuromyelitis optica (NMO) or Devic's disease. Some of its symptoms are similar to the symptoms of multiple sclerosis, so it may be misdiagnosed as such.What triggers MS lesions? ›
In MS, the term lesion refers to an area of damage or scarring in the central nervous system. Lesions are caused by inflammation or the immune system attacking the myelin sheath on nerves in the brain, spinal cord or optic nerve.
Migraines are one of the most common mimicker diseases that can be misdiagnosed for MS. Migraine causes intense throbbing headaches, light sensitivity, and nausea. Many migraine sufferers have also experienced blurred vision similar to the kind caused by optic neuritis in MS patients.Where do MS lesions appear first? ›
Signs and Symptoms
Characteristic lesions are located in the periventricular and juxtacortical regions, in addition to the brainstem, cerebellum, spinal cord, and optic nerve.
- numbness and tingling.
- loss of balance and dizziness.
- stiffness or spasms.
- bladder problems.
- bowel trouble.
- Brain tumors (including cancer).
- Congenital disorders (conditions you have at birth) and metabolic disorders.
- Degenerative brain diseases (especially age-related ones), such as Alzheimer's disease, Lewy body dementia, Multiple system atrophy, and Parkinson's disease.
These include fibromyalgia and vitamin B12 deficiency, muscular dystrophy (MD), amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), migraine, hypo-thyroidism, hypertension, Beçhets, Arnold-Chiari deformity, and mitochondrial disorders, although your neurologist can usually rule them out quite easily.Does MS show up on blood work? ›
While there is no definitive blood test for MS, blood tests can rule out other conditions that cause symptoms similar to those of MS, including lupus erythematosus, Sjogren's syndrome, vitamin and mineral deficiencies, some infections and rare hereditary diseases.What age does MS usually start? ›
MS can appear at any age but most commonly manifests between the ages of 20 and 40. It affects women two to three times as often as men. Almost one million people in the United States have MS, making it one of the most common causes of neurological disability among young adults in North America.What is the life expectancy of someone with multiple sclerosis? ›
MS itself is rarely fatal, but complications may arise from severe MS, such as chest or bladder infections, or swallowing difficulties. The average life expectancy for people with MS is around 5 to 10 years lower than average, and this gap appears to be getting smaller all the time.What percentage of MS patients have brain lesions? ›
It's not clear how common brain lesions are with MS. According to researchers, they occur in 6% to 82% of MS cases. 1 A brain magnetic resonance imaging (MRI) scan and occasionally evoked potential tests are used to detect MS lesions in the brainstem.What does MS fatigue feel like? ›
Fatigue in MS is not just an ordinary tiredness, like you might get at the end of a hard day's work. People describe it as an overwhelming sense of tiredness with no obvious cause. You may wake up feeling as tired as you did when you went to sleep.