How Malaria-Like Protozoa May Trigger Micro-Bleeds And Brain Lesions In MS

Most people with multiple sclerosis (MS) have been told the same basic story: 

MS starts in the brain. The immune system suddenly attacks myelin, and leaves scars called lesions scattered throughout the brain and spinal cord.

But what if that story is missing the real starting point?

What if MS lesions actually start in the brain’s smallest blood vessels—before they ever show up on an MRI? And what if something living inside red blood cells has been quietly damaging those blood vessels this entire time?

For more than 100 years, researchers and clinicians have reported clues that point in exactly this direction. These clues are buried in old case reports, autopsies, vascular studies, and forgotten treatment trials. Very few people with MS have ever been told about them.

This post will walk you through:

• What these organisms are
• What they do in the blood
• How they damage small vessels and may help explain micro‑bleeds and brain lesions in MS
• Why antimalarial drugs have helped MS, past and present
• And why this matters for anyone living with MS today

The goal is to give you a different way of looking at MS—one that opens up new questions, new hope, and a new sense of possibility.

The Overlooked Suspects: Malaria‑Like Parasites in Red Blood Cells

The organisms we are talking about are malaria‑like protozoa.

These are tiny, single‑celled parasites that:

• Infect red blood cells
• Live and multiply inside those cells

This is very different from bacteria that float freely in the bloodstream. These parasites hide inside the very cells that carry oxygen throughout the body. That means everywhere your red blood cells go, they go too—including into the smallest blood vessels that feed the brain and spinal cord.

Two important examples of these red‑blood‑cell parasites are:

• Plasmodium species, which cause malaria
• Babesia species, which cause babesiosis

Both are well‑documented to live inside red blood cells and to cause serious disease in humans.

What if, in at least a subset of people with MS, similar malaria‑like organisms are present at low, chronic levels—undetected by standard tests, but slowly damaging the tiny blood vessels that feed the brain and spinal cord?

 

What These Parasites Do Inside the Blood

We can learn a lot by looking at malaria and babesiosis, where scientists have studied these parasites in detail.

When malaria‑like parasites infect red blood cells, several key things happen:

1. Red blood cells become stiff and “sticky.”
   Infected red blood cells lose their normal flexibility. They are more likely to clump together and to stick to the inner wall of blood vessels.
2. They trigger inflammation in vessel walls.
   These parasites provoke an inflammatory response in the lining of blood vessels (the endothelium), which makes vessels more fragile and more likely to leak or clog.​
3. They block the tiniest vessels.
   The smallest blood vessels—capillaries and venules—are only just wide enough for a normal red blood cell to squeeze through. When those cells are stiff and sticky, they can obstruct blood flow, especially in highly delicate networks like those in the brain and spinal cord.

In cerebral malaria, for example, researchers have shown that parasitized red blood cells adhere inside brain microvessels, reduce blood flow, disrupt the blood–brain barrier, and cause local swelling, micro‑infarcts, and focal brain injury.​

Now think about where some of the most densely packed and delicate small vessels are located:

• The brain
• The spinal cord

If infected red blood cells are moving through those tiny vessels, causing inflammation, obstruction, and damage, you would expect to see:

• Micro‑bleeds
• Patchy, localized tissue damage
• Areas of iron deposition from leaking red blood cells
• And eventually, white matter changes and lesions

This picture starts to look uncomfortably similar to what we actually see in MS.

 

From Blood Vessel Damage to MS‑Type Lesions

Modern MRI and pathology studies have shown over and over that MS lesions are not randomly scattered in the brain. They are closely tied to small veins and venules.

 

The “Central Vein Sign”

Advanced MRI has revealed a striking pattern called the central vein sign. In most MS lesions, a small vein can be seen running right through the center of the lesion.

Key findings:

• MS lesions are characteristically venocentric—centered around small veins.
• When at least 40–50% of white‑matter lesions contain a central vein, this pattern can help distinguish MS from other conditions that mimic it on MRI.

In other words, the blood vessel is not an innocent bystander. It appears to be the organizing center of the lesion.

 

Early Blood–Brain Barrier Breakdown

MRI has shown that new MS lesions start with very focal breakdown of the blood–brain barrier around small veins.​

Researchers observed:

• Ring‑like enhancement around a tiny vein, representing early, localized leakage from that vessel
• Enhancement then fills in toward the center over time, consistent with damage expanding outward from the vessel wall into the surrounding tissue​

This is a “vascular‑first” lesion pattern: the small vessel is damaged, it starts to leak, and only then does a full lesion develop.

 

Micro‑Bleeds and Iron

Brain tissue studies in people with MS have found:

• Abnormal iron build‑up around tiny blood vessels
• Signs that red blood cells have leaked out of damaged vessels into the brain tissue
• Direct damage to the walls of these small blood vessels inside MS lesions

More recently, susceptibility‑weighted MRI has found that people with MS—especially older patients—have a higher prevalence of cerebral micro‑bleeds compared to healthy controls.

In a large case‑control study:

• About 20% of MS patients over age 50 had cerebral micro‑bleeds, versus about 7% of healthy controls
• More micro‑bleeds were associated with greater physical and cognitive disability

Other longitudinal studies have shown that new micro‑bleeds can appear over time in MS, and that they are more common with longer disease duration and older age.

Taken together, this shows that:

• Small blood vessels are damaged
• They leak, causing micro‑bleeds and leave iron behind
• Surrounding tissue is injured
• Lesions form around the damaged vessels

Instead of only asking, “Why is the immune system attacking myelin?”, we should also ask a deeper question:

What is damaging the blood vessels that supply the brain?

 

A Century of Clues: Malaria‑Like Infection and MS

The idea that a chronic, malaria‑like infection could contribute to MS is not new. It appears in the medical literature as far back as the late 1800s.

A 2001 historical review by Kissler pulled together more than 100 years of observations. These included:

• Case reports where malaria infections were followed by MS‑like illnesses, or where malaria itself produced neurological syndromes nearly indistinguishable from MS
• Autopsy cases in which tiny parasites were found in the small vessels of the brain and spinal cord in patients labeled with “disseminated sclerosis” (an older term for MS)
• Geographic and seasonal patterns hinting at an infectious or vector‑related influence
• Reports of quinine, an antimalarial drug, improving MS symptoms in some patients

Across multiple early‑to‑mid‑20th‑century datasets (as summarized by Kissler), investigators reported that:

• Roughly 30–40% of MS patients had antibodies to malaria‑like organisms
• Around 20% had detectable parasites (when they were specifically looked for)
• These findings were rarely or never seen in the control groups used in those studies

Importantly:

• Many of these patients had never traveled to classic, tropical malaria regions.
• The infections appeared to be low‑grade, chronic, and often clinically silent in terms of typical malaria symptoms.

This suggests we are not dealing with dramatic, acute malaria. We may be looking at chronic, low‑level, malaria‑like infections that can quietly persist inside red blood cells—hard to detect, but still capable of damaging the microvasculature over time.

 

Patterns That Don’t Fit a Simple Autoimmune Story

When researchers stepped back and looked at larger patterns, more clues emerged.

Geography and History

Historical analyses compared:

• Older maps of malaria and malaria‑like infections in Europe and other temperate regions
• With maps of MS prevalence that developed later

They observed overlaps between areas with prior malaria exposure and later MS clusters, especially when considering time periods before modern public health campaigns treated malaria in many temperate zones.

This does not prove causation, but it raises an important question:
Did regions with a history of malaria‑like infections “seed” more chronic, low‑level infections that later contributed to MS in some individuals?

Seasonality

Modern studies have also found seasonal variation in MS relapses:

• Relapse rates often peak in spring in some cohorts​
• Relapses correlate with environmental factors such as sunlight exposure and other seasonal changes​

Infectious diseases—including malaria in certain settings—are also known to show seasonal patterns. When you see a disease that flares at particular times of year, it is reasonable to ask whether environmental or infectious triggers are playing a role.

Together, these geographic and seasonal patterns suggest that something more than a purely “random” autoimmune process may be at work.

 

Modern Treatment Clues: Hydroxychloroquine in MS

Fast‑forward to the 21st century.

Hydroxychloroquine (HCQ) is a modern antimalarial drug. It is widely used today for autoimmune and inflammatory conditions like lupus and rheumatoid arthritis because it modulates certain immune pathways. But its original purpose was to target parasites inside red blood cells.

A team at the University of Calgary decided to test HCQ in primary progressive MS (PPMS)—the form of MS that typically responds the least to standard immunomodulating drugs.

The 2021 PPMS Trial

In this early‑stage trial, where everyone received the same treatment:

• 35 people with PPMS received 200 mg of hydroxychloroquine twice a day for 18 months.
• Participants with actively enhancing lesions were excluded, to focus on non‑relapsing, progressive disease.
• The primary outcome was whether patients experienced at least 20% worsening on the Timed 25‑Foot Walk between 6 and 18 months.

Based on previous data, the researchers expected about 40% of this group to worsen over that time period.

What actually happened?

• Only 8 of 35 participants (about 23%) showed that level of walking deterioration—significantly fewer than the expected 40%.
• The trial met its predefined success threshold, indicating that HCQ reduced the proportion of patients with significant disability worsening and should be studied further in randomized trials.

Additional work from the same study looked at biomarkers like neurofilament light and GFAP (markers of neurodegeneration and astrocyte activation), suggesting that HCQ may have measurable effects on underlying neurodegenerative processes in PPMS.​

Remember:

• Hydroxychloroquine is not a classic MS immunosuppressant.
• It was not developed to repair myelin.
• It was originally designed to target intracellular parasites in red blood cells, and later found to have immune‑modulating and microglia‑calming effects.

Yet in this PPMS study, it slowed disability progression in a group that is usually very hard to treat.

Is it helping because of its immune‑modulating effects, its impact on infection, or some combination of both?

We don’t have final answers yet—but the signal is strong enough that this drug, born in the world of antimalarial therapy, is now being considered as a serious candidate in progressive MS.

 

The Forgotten Quinine Stories: Early Malaria Drugs in MS

Long before modern MS drugs existed, physicians tried another antimalarial: quinine.

Quinine is a classic antimalarial compound that specifically targets protozoa living inside red blood cells. It is not a myelin repair drug. It is not a steroid. And it is not a conventional immunosuppressant.

Yet, in reports from the late 1800s through the early 1900s, multiple clinicians observed that MS patients treated with quinine experienced notable neurological improvements.

Across different case series and reports (as reconstructed and summarized by Kissler and other historians):

• Patients with spastic weakness, tremors, and difficulty walking often improved with quinine therapy.
• Some reports described dramatic functional recoveries, especially when treatment was started earlier in the course of disease.

In one five‑year observation of dozens of MS patients treated with quinine, the author concluded that quinine appeared most helpful in early‑stage MS, based on global clinical impressions and function.

Quinine does essentially one main thing in this context:

• It targets red‑blood‑cell parasites—the same type of organisms we have been discussing.

So when an MS patient’s neurological symptoms improve on a drug like quinine, it naturally raises a question:

What, exactly, is that drug acting on?

Many of these improvements were temporary. When quinine was stopped, symptoms often returned. This is exactly what you would expect if the underlying problem were a chronic infection that was suppressed but not eradicated.

 

Malaria‑Like Neurological Disease That Looked Just Like MS

At the same time that quinine was being used in MS, physicians were describing the flip side:

Patients with malaria—especially cerebral or chronic forms—who developed neurological syndromes that looked very much like what we now call MS.

These patients had:

• Spastic paralysis
• Abnormal gait
• Intention tremor – shaking that appears when reaching for something
• Eye movement problems
• Speech disturbances

In some cases, symptoms improved, then flared again, creating a relapsing pattern. This pattern is strikingly similar to relapsing–remitting MS.

Diagnostic tools were limited at the time. MRI, modern CSF testing, or today’s serologies were not available. But to those early neurologists and pathologists, the overlap in clinical pictures between certain malaria‑related conditions and MS‑like syndromes was too strong to ignore.

Some authors explicitly suggested that:

• Malaria and MS might represent different expressions of a similar underlying process—chronic, microvascular damage driven by infection of red blood cells.

Others argued that “true MS” should be reserved for cases that did not respond to quinine, while MS‑like cases that improved markedly with antimalarials were more accurately described as malarial or malaria‑like disease.

 

Why This Connection Has Been Missed

So why hasn’t this infection‑and‑blood‑vessel angle been seriously explored in modern MS research, despite more than a century of clues?

There are several deeper reasons.

1. A shift in medical thinking toward autoimmunity

Before the 1950s and 1960s, most doctors were trained to look first for infections as the cause of chronic disease. Over the last 70 years, that has changed dramatically. As the modern theory of autoimmunity took hold, conditions like MS were reclassified as “the immune system attacking the body,” and the older infection‑based explanations quietly faded into the background.

Medical schools and specialist training programs now largely teach MS as a primarily autoimmune disease of “unknown trigger,” rather than as a condition that might be driven, at least in part, by chronic infection and blood‑vessel injury. That means today’s neurologists and researchers are often not even trained to look for malaria‑like parasites, chronic infections, or low‑grade vascular damage as possible starting points.

2. A profit‑driven research system that sidesteps cheap drugs and cures

Modern healthcare is also a very expensive industry, and research funding is heavily shaped by how our drug system is built.

Pharmaceutical companies recover their high research and development costs and generate profits largely by developing patent‑protected, high‑priced drugs. They have far less financial incentive to invest in potential cures that rely on older, inexpensive, or non‑patentable medicines.

Some of the newer MS drugs are now priced well above $100,000 per year per patient.

 

A New Framework for Understanding MS

When you step back and connect the dots, a powerful pattern emerges:

• Organisms that infect red blood cells
• Measurable changes in blood flow, vessel integrity, and microvascular health
• Micro‑bleeds, perivascular iron, and venocentric lesions on MRI
• Neurological syndromes in malaria that mirror MS
• Historical and modern evidence that drugs targeting these organisms can improve or slow MS symptoms in at least some patients

This combination of evidence is not random. It strongly suggests that infection and blood‑vessel damage play a major role in MS, at least in a subset of people.

That does not mean:

• MS is only caused by a malaria like protozoa

But it does mean standard of care is looking narrowly at only the immune system, while virtually ignoring what is happening in the blood and the microvasculature that feeds the brain.

If organisms living in red blood cells are quietly driving small‑vessel damage in MS, then:

• The immune system is reacting to injury, not initiating it
• Vascular protection and infection‑targeted strategies could be crucial parts of a comprehensive recovery approach
• And new diagnostic tools that can detect chronic, low‑level parasite infections—especially those hiding inside red blood cells—are urgently needed.

 

What This Could Mean for People Living With MS

For someone living with MS, this line of research offers three important things:

1. A different story about your illness
   Instead of “your immune system is attacking your body for no reason,” consider that chronic infection and vascular damage  explain why lesions form where they do.
2. New directions for research and treatment
   The hydroxychloroquine PPMS trial is a concrete modern example of a drug with antimalarial roots slowing disability in the least treatable form of MS, and it deserves much more follow‑up. Future work might explore other agents, better detection of chronic malaria‑like infections, and ways to protect and repair the microvasculature.
3. Real grounds for hope
   If at least part or all of the damage in MS is driven by chronic, low‑grade infections causing microvascular injury—then MS is not a mysterious, unstoppable autoimmune fate. It becomes an infectious disease that can be treated and recovery is possible.

This dramatically expands the conversation about what MS is and the best ways to treat it.

 

A Call to Rethink – and to Share

If this is even partly true, it changes how we see MS:

From a purely immune‑driven brain disease to a infectious disease that involves blood vessels, infection, and the immune response.

It makes us consider that:

• Damage may start in the blood and microvasculature
• The immune system may be responding to early injury around tiny veins
• And antimalarial and infection‑focused strategies might play a role in future MS treatment and recovery, especially when combined with integrative approaches.

For people living with MS, this perspective offers hope:

• Hope that there is a cause of this disease.
• Hope that new diagnostic tools and therapies could emerge as we revisit and update this forgotten line of research.
• Hope that MS symptoms are not “just random,” but there is a real cause that must be addressed.

If this resonates with you, please do not keep it to yourself.

• Share this article with friends, family, and support groups.
• Share it with practitioners, researchers, and anyone involved in MS care.
• Ask questions. Start conversations.

The more people who understand that MS may involve hidden infections and blood-vessel damage—not an unexplained immune attack—the more pressure there will be to properly investigate these questions.

There are real solutions to recover from parasites today!

To restore health, we must focus on treating the cause of inflammation, which are parasites. First, identify the enemy (parasites), then support the body and treat the parasites while following a holistic approach. When parasitic infections are treated effectively, we can overcome inflammation or disease.

If you’re frustrated with the fact that our standard of care STILL doesn’t offer a real solution for treating MS and other diseases, then click on the link below to watch Pam Bartha’s free masterclass training and discover REAL solutions that have allowed Pam and many others to live free from MS and other diseases.

CLICK Here to watch Pam’s masterclass training

References:

Hydroxychloroquine in PPMS

1. Koch M, Kaur S, Fransen NL, et al. Hydroxychloroquine for primary progressive multiple sclerosis. Ann Neurol. 2021;90(6):940-948. doi:10.1002/ana.26239.

Single‑arm, phase II futility trial (35 PPMS patients, 200 mg HCQ BID for 18 months) found that only 24% had ≥20% worsening on the Timed 25‑Foot Walk, which was less than the expected 40% threshold, suggesting HCQ reduced disability worsening and is a promising candidate needing randomized trials.
Link: https://pubmed.ncbi.nlm.nih.gov/34590328/​

2. Hydroxychloroquine in primary progressive multiple sclerosis. ClinicalTrials.gov identifier: NCT02913157.

Trial registry describing design: open‑label, single‑arm PPMS study testing whether 400 mg/day HCQ can prevent worsening of walking ability, excluding patients with enhancing lesions to focus on non‑inflammatory progression.​
Link: https://clinicaltrials.gov/study/NCT02913157​

3. Petracca M, Kaur S, Whitehouse L, et al. Serum neurofilament-light and glial fibrillary acidic protein levels in primary progressive multiple sclerosis treated with hydroxychloroquine. Mult Scler Relat Disord. 2023;68:104234. doi:10.1016/j.msard.2022.104234.

Biomarker analysis from the HCQ PPMS trial showing associations between treatment, neurofilament light, and GFAP, supporting a potential effect of HCQ on neurodegenerative processes in PPMS.​
Link: https://pubmed.ncbi.nlm.nih.gov/36214614/​

 

Central Vein Sign and Venocentric Lesions

4. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12(12):714-722. doi:10.1038/nrneurol.2016.166.

Reviews evidence that MS lesions are characteristically venocentric, containing a small central vein, and proposes the central vein sign as an MRI biomarker to improve diagnostic specificity versus MS mimics.​
Link: https://www.nature.com/articles/nrneurol.2016.166​

5. Maggi P, Absinta M, Grammatico M, et al. Central vein sign differentiates multiple sclerosis from central nervous system inflammatory vasculopathies. Ann Neurol. 2018;83(2):283-294. doi:10.1002/ana.25154.

Demonstrated that when ≥50% of white matter lesions show a central vein, MS can be distinguished from inflammatory vasculopathies with very high diagnostic accuracy, reinforcing the perivenular origin of MS lesions.​
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC5901412/​

 

Blood–brain Barrier Evolution and Vascular Damage

6. Gaitán MI, Shea CD, Evangelou IE, et al. Evolution of the blood–brain barrier in newly forming multiple sclerosis lesions. Ann Neurol. 2011;70(1):22-29. doi:10.1002/ana.22472.

Using dynamic contrast‑enhanced MRI, showed that new MS lesions start with perivenular ring‑like enhancement that fills in centripetally, reflecting early, focal BBB breakdown around small veins, consistent with a vascular‑first lesion pattern.​
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3143223/​

7. Adams CW. Perivascular iron deposition and other vascular damage in multiple sclerosis. J Neurol Neurosurg Psychiatry. 1988;51(2):260-265. doi:10.1136/jnnp.51.2.260.

Classic pathology paper documenting perivascular iron deposition, vessel wall damage, and evidence of red blood cell extravasation in MS plaques, supporting a role for micro‑bleeds and vascular injury in lesion development.​
(Access via iron chelation review) Link: https://www.tandfonline.com/doi/full/10.1042/AN20130037 (cites Adams 1988 extensively)​

 

Malaria‑like Infection and MS (Historical Research)

8. Kissler H. Is multiple sclerosis caused by a silent infection with malarial parasites? A historico-epidemiological approach: Part I. Med Hypotheses. 2001;57(2):180-187. doi:10.1054/mehy.2000.1171.

Link: https://pubmed.ncbi.nlm.nih.gov/11516218/

Part I reviews historical MS and malaria data and argues that the geographic and temporal patterns of MS (early clusters, latitude effects, and migration patterns) can be re‑interpreted as compatible with a long‑standing, often silent malarial or malaria‑like infection. It highlights early case descriptions where malaria and “disseminated sclerosis” overlapped and suggests that the spread of MS in Europe and North America may have followed the earlier spread and partial eradication of malaria, supporting the idea that at least some MS could reflect chronic intra‑erythrocytic parasitic infection rather than a purely spontaneous autoimmune disease.

9. Kissler H. Is multiple sclerosis caused by a silent infection with malarial parasites? A historico‑epidemiological approach. Med Hypotheses. 2001;56(3):329-335. doi:10.1054/mehy.2000.1182.

Part 2 reviews more than 100 years of observations (geography, seasonality, case reports, autopsies, quinine responses) and argues that silent malarial or malaria‑like infection could underlie MS in a subset of patients, citing data on antibodies and parasites found in MS cohorts.​
(Full text often behind paywall; your Live Disease Free website summary.)

Link: https://livediseasefree.com/the-lost-malaria-ms-link-over-140-years-of-forgotten-research-that-changes-everything/​

 

10. Spelman T, Gray OM, Trojano M, et al. Seasonal variation of relapse rate in multiple sclerosis is associated with sunlight exposure. J Neurol Neurosurg Psychiatry. 2017;88(11):1075-1079. doi:10.1136/jnnp-2017-315689.

Large registry‑based analysis showing significant seasonal variation in MS relapse rates, with peaks in spring and associations with monthly sunshine hours, supporting an environmental/infectious or seasonal trigger component.​
Summary: https://climahealth.info/resource-library/seasonal-variation-in-multiple-sclerosis-relapse/​

 

Malaria, Microvasculature, and Brain Injury

11. Pikor D, Hurła M, Banaszek-Hurła N, Drelichowska A, Paul M. Neurovascular pathophysiology and emerging biomarkers in cerebral malaria: an integrative perspective. Neurol Int. 2025;17(9):149. doi:10.3390/neurolint17090149.

This cerebral malaria review reinforces a neurovascular model that looks strikingly similar to what we see in MS. It shows how parasites inside red blood cells sequester in tiny brain vessels, activating the endothelium, disrupting the blood–brain barrier, and causing microvascular congestion, perivascular hemorrhages, and microinfarcts—lesions that closely resemble the perivenular damage, iron deposition, and microbleeds described in MS. It also highlights endothelial and inflammatory biomarkers (like adhesion molecules, Ang‑2/Ang‑1, and CXCL10) and argues that effective treatment must stabilize the microvasculature and protect the BBB, not just kill parasites—exactly the kind of vascular‑focused thinking that could be applied to MS as well.​

Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC12472603/

12. Deplaine G, Safeukui I, Jeddi F, et al. The sensing of poorly deformable red blood cells by the human spleen can be mimicked in vitro. 2011;117(8):e88-e95. doi:10.1182/blood-2010-10-312801.

Shows that Plasmodium‑infected RBCs become less deformable and more likely to be sequestered or cause microcirculatory problems, providing a mechanistic basis for microvascular blockage in malaria.
Accessible review: https://pubmed.ncbi.nlm.nih.gov/21163923/​

 

Babesia and MS 

13. Haberli N, Coban H, Padam C, et al. Babesia microti infection in a patient with multiple sclerosis treated with ocrelizumab. Mult Scler Relat Disord. 2021;48:102731. doi:10.1016/j.msard.2020.102731.

Case report of severe babesiosis in an MS patient on anti‑CD20 therapy, highlighting how malaria‑like RBC parasites can cause significant hematologic and systemic disease in this population and the need for vigilance in endemic areas.​
Link: https://pubmed.ncbi.nlm.nih.gov/33450528/​

 

Early Clinical and Pathological Observations (MS–malaria Overlap)

14. Prince AD. Multiple sclerosis following malarial infection: report of nine cases observed in soldiers. J Nerv Ment Dis. 1889;16.

Neurologist Prince described at least six, later nine, cases in which malaria was followed by a chronic neurological illness compatible with disseminated sclerosis, suggesting a temporal association between malaria and MS‑like syndromes.​
(Details summarized in: Kissler H. Med Hypotheses. 2001.)​

15. Spiller WG. A case of malaria simulating disseminated sclerosis. Univ Penn Med Bull. 1897;10.

Reported a malaria case with unilateral spastic weakness and other signs closely resembling disseminated sclerosis, explicitly noting how similar the neurological picture was to MS.​

16. Spiller WG. Disseminated sclerosis with unsuspected malarial infection: report of an autopsy case. J Nerv Ment Dis. 1900;27.

Autopsy case of an 8‑year MS‑like illness in a man with no history of malaria attacks, where motile malarial parasites were found post‑mortem in small vessels of brain and spinal cord, implying long‑standing, clinically silent malarial infection.​

17. Mannaberg J. Ueber die Beziehungen zwischen Malaria und multipler Sklerose. Wien Klin Wochenschr. 1899;12.

Argued, based on clinical and pathological similarities, that disseminated sclerosis could be caused by malarial parasites, and that MS‑like symptom complexes played an important role in malaria.​

18. Müller F. Ueber die Pathogenese der multiplen Sklerose und ihre Beziehung zur Malaria. Dtsch Med Wochenschr. 1904;30.

Proposed that both malaria and MS involved obstruction of small brain vessels by parasitized red blood cells, and recommended quinine as a useful remedy in all cases of MS, particularly when vertigo was a major symptom.​

19. Dürck H. Ueber die pathologische Anatomie der Malaria: Granulome und Leptomeningitis. Beitr Pathol Anat. 1917;62.

Described malaria granulomas and leptomeningitis in cerebral malaria and compared them to similar granulomatous and meningeal findings reported in MS brains, suggesting these could represent early stages of MS plaques.​

20. Frerichs F. Ueber multiple Sklerose mit kapillaren Blutungen. Arch Pathol Anat Physiol Klin Med. 1849;2.

One of the earliest MS pathology descriptions, noting multiple small hemorrhages in association with demyelinating lesions, supporting the idea of capillary hemorrhages as part of MS lesion formation.​

21. Dawson JW. The histology of disseminated sclerosis. Trans R Soc Edinb. 1916;50:517‑740.

Classic MS pathology monograph; included description of small capillary hemorrhages and perivenular demyelination in MS, which later authors compared to hemorrhagic changes seen in cerebral malaria.​

22. Unnamed authors (two neuropathologists). Cerebral malaria lesions producing multiple areas of sclerosis. Arch Neurol Psychiatry. 1942;47.

Reported that hemorrhages, necrotic foci, and granulomatous nodules in cerebral malaria all healed as “patches of sclerosis,” and concluded that multiple scattered areas of sclerosis from malaria could disturb brain function similarly to MS.​

 

Early Quinine Treatment Reports

23. Unnamed authors. On three cases of coexisting malaria and multiple sclerosis treated with quinine. Med Klin Wochenschr. 1892;9.

Described three clinical situations where malaria and MS‑like disease overlapped (symptoms during fever, after fever, or without fever) and noted that quinine treatment was beneficial in two MS cases.​

24. Marburg O. Über die Behandlung der multiplen Sklerose mit Chinin. Wien Klin Wochenschr. 1920s;33.

Reported that small doses of quinine improved overall health and neurological function in MS patients, especially in early stages, and recommended its continued use.​

25. Brickner RM. The treatment of multiple sclerosis with quinine: results in forty‑nine patients over five years. Arch Neurol Psychiatry. 1935;33.

Systematic 5‑year observation of 49 MS patients treated with quinine; concluded that quinine therapy was beneficial, particularly in early MS, based on global clinical impressions and functional outcomes.​

26. Conklin SD. Multiple sclerosis treated with quinine hydrochloride: report of a complete functional recovery. J Nerv Ment Dis. 1937;85.

Detailed case of a 27‑year‑old woman diagnosed with MS who received continuous quinine hydrochloride from 1934–1937 and experienced rapid, near‑complete, and sustained recovery of neurological function, with only nystagmus remaining.​

27. Castellani A. Malaria closely simulating disseminated sclerosis: four cases cured by quinine. 1917;190(4911).

Reported one Balkan and three tropical cases of a malarial condition with scanning speech, intention tremor, nystagmus, spastic gait, and hyperreflexia—clinically indistinguishable from MS—all completely cured with quinine; Castellani concluded they were not “true MS” precisely because they responded to antimalarial therapy.​

28. Craig CF. The diagnostic value of quinine reaction in chronic malaria with neurological manifestations. Am J Trop Med. 1917;1.

Observed that administration of quinine in suspected chronic malaria could provoke fever and clinical reactions even when no parasites were seen, using this as evidence to attribute central nervous system lesions to malarial infection.​

29. Mühlens P. Die Chininprobe zur Aufdeckung latenter Malariainfektionen. Dtsch Med Wochenschr. 1921;47.

Described the “quinine test” method: small quinine doses triggering reappearance of parasites or fever, used as a diagnostic tool to unmask latent malaria when blood smears were repeatedly negative.​

30. Perret‑Gentil M. Beobachtungen über Malariaplasmodien bei Beginn der Chinintherapie. Schweiz Med Wochenschr. 1945;75.

Recommended examining blood specifically at the start of quinine therapy, when he most often observed malarial parasites and fever in chronic or silent malarial infections.​

 

Cerebral Micro-bleed Studies

31. Zivadinov R, Ramasamy DP, Benedict RHB, et al. Cerebral microbleeds in multiple sclerosis evaluated on susceptibility-weighted images and quantitative susceptibility maps: a case-control study. 2016;281(3):884-895. doi:10.1148/radiol.2016160060.

445 MS patients, 45 CIS, 51 other neurological disease, 177 healthy controls; using SWI and QSM, they found a higher prevalence of cerebral microbleeds in MS/CIS than in healthy controls, especially in older patients, and more microbleeds were associated with worse physical and cognitive disability.
URL: https://pubmed.ncbi.nlm.nih.gov/27308776/​

32. Subramanian K, Haacke EM, Li X, et al. Longitudinal magnetic resonance imaging of cerebral microbleeds in multiple sclerosis patients. Brain Sci. 2020;10(11):815. doi:10.3390/brainsci10110815.

In 2 MS cohorts (100 RRMS; 112 MS + 25 controls) scanned with SWI and QSM, 14–19% of MS subjects had at least one microbleed; new microbleeds appeared over time, and longer disease duration and older age increased the chance of developing microbleeds, confirming that CMBs can accumulate and change over time in MS.
URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC7697968/​

33. Cerebral microbleeds in MS patients are associated with increased risk for physical, cognitive disability. News release. University at Buffalo press summary of Zivadinov et al.

Summarizes the Radiology case‑control study: “20% of MS patients over the age of 50 have cerebral microbleeds compared to 7% of healthy controls;” among those under 50, 14% of CIS patients had microbleeds vs 3% of healthy controls, and microbleeds were associated with increased physical and cognitive disability.
URL: https://www.buffalo.edu/news/releases/2016/06/022.html

 

 

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