Introduction

Pernicious Anaemia (PA), sometimes called Biermer’s or Addison-Biermer anaemia, is a rare type of anaemia caused by your immune system attacking certain stomach cells. These cells are important because they help your body absorb vitamin B12, a nutrient vital for making healthy red blood cells. Without enough B12, your red blood cells can become abnormally large and shaped incorrectly, which can cause health problems.¹

PA mostly affects people over 60, and studies suggest around 1.9% of people in this age group have undiagnosed PA. Globally, it is responsible for 20–50% of adult vitamin B12 deficiencies.¹

PA can be hard to diagnose. People are sometimes mistakenly told they have anxiety or depression because early symptoms—like feeling tired, having trouble concentrating, or forgetting things—can be vague.2 PA can affect your gut, your thinking, and your nervous system, and diagnosis can take up to five years.²

Recognising neurological signs alongside blood tests is key to confirming PA. In this article, we’ll explore the main neurological symptoms so you can better understand what to watch out for.

How does PA develop at the cellular level?

To understand why PA affects the nervous system, it helps to know what happens inside the body.

PA usually occurs when your body cannot properly absorb vitamin B12 from food. This is often because a protein called intrinsic factor(IF), which is needed to absorb B12, is missing or not working correctly.³ 

You might wonder which foods provide vitamin B12. B12, or cobalamin, is found mainly in animal products such as meat, fish, and dairy. When you eat these foods, B12 is protected in the stomach by a protein called haptocorrin before binding to intrinsic factor (IF). This B12–IF complex is then absorbed in the small intestine and enters the bloodstream. Inside your cells, B12 is turned into active forms called methylcobalamin and adenosylcobalamin, which play key roles in keeping your body healthy.⁴ 

These active forms of B12 are important for several functions: they help your body make DNA, keep the protective myelin coating around your nerves healthy, and break down substances like homocysteine and methylmalonic acids (MMA) that can be harmful in large amounts.

Without enough B12:

• Your body struggles to make DNA, leading to unusually large red blood cells (megaloblastic anaemia)
• Nerves can become damaged because the protective myelin coating is lost, causing neurological problems
• Harmful substances like homocysteine and MMA can build up, potentially harming brain cells and structures, which may contribute to memory problems, brain shrinkage, cognitive decline^4,5

How does paresthesia ensue?

A lack of vitamin B12 can cause a condition called combined myeloneuropathy. This means the nerves in your spinal cord and throughout your body start to break down, which can lead to various neurological symptoms.

The damage mostly affects the back part of the spinal cord, which is responsible for movement coordination, sensing touch, and knowing the position of your limbs. Because B12 is needed to make DNA, a deficiency can damage your nerves and lead to the tingling, numb, or “pins and needles” sensations in your hands and feet known as parasthesia.⁶

Another condition caused by B12 deficiency is called sub-acute combined degeneration (SCD), which affects the spinal cord and gradually worsens. Paresthesia is often one of the first symptoms, followed by vision problems, muscle weakness, thinking difficulties, sexual issues, and bladder reflex changes.⁶

How does PA cause Ataxia?

Ataxia is not a disease itself, but a sign that something is affecting the nervous system. It shows up as a lack of coordination in your body and can be caused by different factors, including illness or injury. People with ataxia may notice changes in how they walk, how their eyes move, or even how they speak, depending on which parts of the brain, especially the cerebellum, are affected.⁷

In pernicious anaemia, ataxia happens because the nerves that control movement start to break down. This disrupts the normal signals that help your body move smoothly and in coordination. The pathways often affected include the pyramidal tracts and the dorsal columns, which are key for sending movement and position information to the brain.⁸

People with ataxia caused by B12 deficiency may notice:

• Trouble walking steadily
• Frequent falls or stumbling
• Difficulty keeping balance when standing still (sometimes checked by a doctor using the Romberg test)

What are the cognitive changes associated with PA?

Pernicious anaemia can also affect your thinking and behaviour, which can impact daily life. People may experience memory problems, difficulty concentrating, changes in mood, or even psychiatric symptoms such as depression or confusion.⁶ These issues mainly happen because the body lacks enough vitamin B12, which is vital for keeping the brain and nerves healthy. High levels of substances like homocysteine and methylmalonic acid (MMA) can also add to these problems. 

Some cognitive and brain-related problems that may occur with B12 deficiency include:

• Memory loss or difficulty remembering things
• Seeing or hearing things that aren’t there (hallucinations)
• Believing things that aren’t true (delusions)
• Dementia or confusion
• Seizures in babies
• Poor brain development in unborn babies
• Shrinkage of brain tissue^5,6,9

How is PA diagnosed?

The evaluation and diagnosis of PA can be a bit tricky due to the disappearance of the Schillings test. It involves a combination of clinical features, biochemical markers, and confirmatory antibody testing.⁴ 

Tests that can help confirm pernicious anaemia include:

• Blood counts and other routine blood tests to check vitamin B12, folate, iron, and the production of new blood cells
• Looking at your blood under a microscope to see if red blood cells are abnormal
• Measuring vitamin B12 levels and related markers like holotranscobalamin and methylmalonic acid
• Checking how your stomach is working, including levels of certain digestive substances
• Testing for antibodies that may attack the stomach’s vitamin B12 absorption process
• Sometimes, a camera test (endoscopy) may be done to look at the stomach lining and check for cancer risk¹⁰

If tests show antibodies against the stomach’s intrinsic factor and your vitamin B12 level is below 200 ng/L, this strongly suggests you have pernicious anaemia. If you notice any symptoms mentioned earlier, it is important to speak with your doctor for proper diagnosis and treatment.

According to the British Committee for Standards in Haematology, anyone with anaemia, nerve problems, or an inflamed tongue (glossitis) who might have pernicious anaemia should be tested for anti-IF antibodies, even if their vitamin B12 levels seem normal.

Treatment and prognosis

Pernicious anaemia requires lifelong treatment. The main treatment is vitamin B12 injections, which are usually the first step. At the start, you may receive 1000 micrograms of B12 (either hydroxocobalamin or cyanocobalamin) every day or every other day for one to two weeks. After this initial stage, injections are usually given once a week for one to two months.⁴

Once the initial treatment is complete, a maintenance dose of 100–1000 micrograms of B12 is given every month or every two to three months, depending on your needs. This helps keep your vitamin levels stable and prevents symptoms from coming back.

See for more information on treatment options.

It’s important to attend regular check-ups while receiving maintenance treatment. Your doctor may adjust your doses and carry out tests to ensure your B12 levels remain healthy.¹¹ Starting treatment early can reverse many of the symptoms, sometimes fully. However, if treatment is delayed, some nerve or brain damage may become permanent.

FAQs

Can a B12 deficiency cause Alzheimer’s disease?

A lack of vitamin B12 can increase certain substances in the blood that may affect the brain. Low B12 and the buildup of homocysteine are linked to memory problems and dementia in some people. Getting your B12 levels checked can help protect your brain health.⁶

Can vegetarians or vegans develop a B12 deficiency?

Yes, vegetarian or vegan diets can sometimes lead to low B12 because this vitamin is mainly found in animal products. Without enough B12, harmful substances like homocysteine can build up in the body. Taking B12 supplements or fortified foods can prevent deficiency and keep you healthy.¹²

Can vegetarians or vegans develop a B12 deficiency?

Yes, vegetarian or vegan diets can sometimes lead to low B12 because this vitamin is mainly found in animal products. Without enough B12, harmful substances like homocysteine can build up in the body. Taking B12 supplements or fortified foods can prevent deficiency and keep you healthy.

Can I take B12 tablets instead of injections?

In some cases, oral B12 tablets can work, especially if injections are difficult. Your doctor will advise the best method depending on how severe your deficiency is and how well your body absorbs B12.

Is pernicious anaemia inherited?

Pernicious anaemia is usually caused by the immune system attacking the stomach, not inherited directly. However, having a family history of autoimmune diseases can slightly increase the risk.

Summary

Pernicious anaemia can cause a wide range of symptoms, which sometimes makes it hard to diagnose. Neurological signs like difficulty walking, tingling in the hands or feet, memory problems, irritability, or even hallucinations may appear first and can be overlooked.

Spotting symptoms early is important because prompt treatment can prevent permanent nerve or brain damage. Maintaining a balanced diet with all essential vitamins and minerals is also important to avoid deficiencies. Regular check-ups can help ensure that any problems are caught and treated in good time.