Vitamin B₁₂ deficiency presenting as neck pain and cervical radiculopathy

Abstract

Vitamin B₁₂ is required for the formation of haematopoietic cells and the synthesis of myelin. Deficiency typically presents with fatigue and megaloblastic anaemia. Prolonged deficiency can cause neurological symptoms such as paresthesia, which can progress to subacute combined degeneration of the spinal cord. We describe an unusual presentation of B₁₂ deficiency in a young man who was initially diagnosed and treated for cervical radiculopathy. This case highlights the challenges of diagnosing B₁₂ deficiency in patients with neurologic but without haematologic, abnormalities. While the current incidence of B₁₂ deficiency in developed countries is low, cases are likely to rise with the increased adoption of veganism. Clinicians should be aware of the variable presentations of B₁₂ deficiency because delayed diagnosis and treatment increases morbidity and can cause irreversible neurological deficits.

Background

Vitamin B₁₂ is required for the formation of haematopoietic cells and the synthesis of myelin.^{1 2} Low B₁₂ impairs nucleic acid metabolism in the bone marrow, causing megaloblastic anaemia.² Patients typically present with fatigue, pale skin, decreased appetite and irritability. Prolonged deficiency can cause neurological symptoms, most commonly stocking and glove paresthesia. Further progression can lead to subacute combined degeneration of the spinal cord. These patients present with progressive weakness and ataxia progressing to spasticity and paraplegia.^{2 3}

Promptly identifying a B₁₂ deficiency is critical as the neurological manifestations are disabling and often irreversible.³ Despite an inexpensive and non-invasive diagnostic process, B₁₂ deficiency is often missed by clinicians due to its variable and non-specific presentation.^4–6 Diagnosis is especially challenging in unusual cases where patients have neurological symptoms but lack haematological abnormalities.

Case presentation

A man in his early 20s presented with 4 weeks of bilateral arm paresthesia and recent-onset cervical pain with burning radiations from his shoulders to his hands. Medical history and family history were unremarkable and the patient denied drug use. MRI cervical spine without contrast was significant for multilevel degenerative disc disease and facet arthropathy without significant spinal canal or neural foraminal stenosis as seen in figure 1.

Figure 1.

(A) Sagittal T2-weighted, (B) axial T2-weighted, (C) axial GRE MRI cervical spine sequence depicting minimal multilevel disc degeneration without cord compression or cord signal abnormality. There are no indications of subacute combined degeneration of the spinal cord.

Following the imaging results, the patient was referred to a physical medicine and rehabilitation specialist. By the time of his physiatry appointment, the patient had progressed to have bilateral forearm weakness and muscle spasms, new-onset low back pain, tingling in the right big toe and intermittent right quadricep spasms. He denied any bowel or bladder incontinence. Physical exam was significant for limited neck flexion and diminished strength in the left extensor hallucis longus, ankle evertor and hip abductors. The patient was diagnosed with C6–C7 and L5 radiculopathies, advised to take ibuprofen and given posture improvement exercises. 

Over the subsequent 4 weeks, the patient grew weaker, had more frequent paresthesia and began to feel the sensation of electrical shocks running down his spine triggered by cervical flexion (Lhermitte’s sign). He slept more than 16 hours a day despite minimal physical exertion. He presented to the emergency room for emergent reassessment. Imaging showed no significant nerve impingement and the patient was referred to neurology for outpatient follow-up.

Investigations

MRI of the brain (not shown) was remarkable only for an arachnoid cyst. Laboratory workup was significant for low B₁₂ at 200 pg/mL (ref: 211–911 pg/mL), elevated methylmalonic acid at 1120 nmol/L (ref: 87–318 nmol/L) and low vitamin D at 8 ng/mL (ref: 20–80 ng/mL). Red cell count, haemoglobin, haematocrit and mean corpuscular volume were all within reference ranges. A more detailed history revealed that the patient was a lifelong vegetarian and had followed a vegan diet for the past 18 months. After completing an extensive workup to rule out infectious, inflammatory and autoimmune aetiologies, the patient was diagnosed with a vitamin B₁₂ deficiency.

Treatment

The patient was instructed to take a 2500 µg oral B₁₂ supplement three times per week. In addition, he received subcutaneous injections of 1000 µg B₁₂ daily for 5 days, weekly for 1 month and monthly for 5 months.

Outcome and follow-up

Cobalamin levels were 961 pg/mL 7 months after treatment initiation. The patient was symptom-free at 10 months and remained so at his 2-year follow-up. The patient’s symptomatic response to B₁₂ supplementation provided further support for his diagnosis and made disc degeneration an unlikely aetiology of his presentation.

Discussion

Vitamin B₁₂ is most abundant in animal-derived foods. On ingestion, B₁₂ binds to gastric-produced intrinsic factor, and this B₁₂-intrinsic factor complex is absorbed by the ileum. The most common cause of B₁₂ deficiency is pernicious anaemia, an autoimmune condition where the body produces antibodies against intrinsic factor, preventing adequate absorption.⁵ Medical conditions which compromise the function of the stomach and intestines such as prior bariatric surgery, Crohn’s disease, proton pump inhibitors and Diphyllobothrium latum infection are also known to cause deficiency.⁷ Vitamin B₁₂ deficiency can also be the result of recreational nitrous oxide use and genetic aetiologies such as mutations in the gene encoding TCN1.^{8 9} While low B₁₂ in the general population is rare, high rates have been reported among vegetarian, elderly and infant populations.^{10 11} Our patient’s vegetarianism, and subsequent veganism, led to his deficiency. 

This case highlights the challenges in making a diagnosis due to the condition’s non-specific presentation. The most common initial symptom of B₁₂ deficiency is fatigue, but nearly 38% of US workers report fatigue—making linking the symptom to B₁₂ deficiency difficult.^{12 13} Current guidelines recommend clinicians obtain complete blood counts, chemistries (glucose, electrolytes, calcium, renal and hepatic function tests), thyroid-stimulating hormone and creatine kinase in patients with fatigue. While B₁₂ deficiency often results in abnormal complete blood count results, our patient lacked notable haematological abnormalities. Hence, he was not diagnosed until cobalamin and methylmalonic acid levels were collected.

The neurological symptoms of B₁₂ deficiency are also non-specific and can range from vocal cord paralysis to seizures.^14–18 This patient initially had upper extremity paresthesia and cervical pain, which following an MRI was misdiagnosed as cervical radiculopathy despite an absence of significant spinal canal or neural foraminal stenosis. It was only after progressive neurological symptoms beyond cervical dermatomes and a negative MRI thoracic and lumbar spine that other aetiologies were considered. This case highlights the risks of prematurely attributing clinical symptoms to potentially non-specific spinal imaging. A review of 3110 asymptomatic individuals found 37% of 20 years old had disk degeneration, 29% had disk protrusion and 19% had an annular fissure.^{19 20} Misattributing neurological symptoms to spinal disc injuries is especially dangerous in patients with B₁₂ deficiency because delayed treatment can cause permanent spinal cord injury resulting in lifelong disability. Our patient began treatment 9 weeks after symptoms began and after receiving three MRIs. If he was diagnosed earlier, he would have likely experienced a milder disease course and a faster recovery. 

In addition to paresthesia, this patient experienced muscle spasms, cervical pain, Lhermitte’s sign and hypersomnia. Lhermitte’s sign is one of the rarest manifestations of vitamin B₁₂ deficiency and is considered a classic sign of multiple sclerosis.²¹ We recommend clinicians consider B₁₂ deficiency in patients with Lhermitte’s sign and testing inconsistent with multiple sclerosis. Hypersomnia is another rare symptom that can be caused by vitamin B₁₂ deficiency.²² While the finding is non-specific and 8%–25% of adults report excessive daytime sleepiness, clinicians should consider B₁₂ in patients with unexplained hypersomnia.²³ To our knowledge, there are no studies in the literature linking neck pain directly to B₁₂ deficiency. It is unclear whether this patient’s cervical pain was caused by low B₁₂ levels, or if the acute onset was coincidental. 

Learning points.

• Vitamin B₁₂ deficiency remains a diagnostic challenge due to its variable and non-specific presentation.

• While B₁₂ deficiency remains rare in developed countries, it is plausible cases will rise with the increased adoption of veganism.

• Clinicians trained in diagnosing B₁₂ deficiency using markers other than megaloblastic anaemia may prevent the onset of potentially irreversible symptoms.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).