What is Myeloneuropathy

Myeloneuropathy also called myelopathy is any disease affecting the spinal cord and peripheral nerves in the lower limbs 1). Myeloneuropathy signs and symptoms include difficulty in walking, weakness of lower limbs, ataxic gait, and sensory manifestations in glove and stocking distribution 2). On examination, there are myelopathic signs such as hyperreflexia, spasticity, extensor plantar responses, and infrequently, bladder bowel disturbances 3). Romberg sign indicates involvement of the posterior column 4). Classical neuropathic signs include glove and stocking sensory loss, absent or diminished ankle jerk, and distal limb atrophy 5). Cognitive impairment and vision loss, because of optic nerve damage may occasionally dominate the clinical picture in a patient with myeloneuropathy 6). All of these patients have gait difficulty primarily due to severe sensory ataxia 7), 8).

A correct diagnosis of myeloneuropathy is often challenging. Vitamin B12, folate, copper, and vitamin E deficiencies can lead to myeloneuropathy. The clinical picture in all these conditions is similar to that of mimics subacute combined degeneration of the spinal cord. The pattern of neurologic involvement and results obtained from biochemical tests and imaging studies can help in establishing the correct diagnosis.

Figure 1. Myeloneuropathy causes

myeloneuropathy causes
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Figure 2. Common nutritional, metabolic, and toxic causes of myeloneuropathy

Common nutritional, metabolic, and toxic causes of myeloneuropathy
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Figure 3. Copper deficiency myeloneuropathy

Copper deficiency myeloneuropathy

Footnotes: Sagittal and axial fast spin-echo MRI T2-weighted images of the cervical spine. Sagittal (A) and axial (B) fast spin-echo MRI of the cervical spine before treatment demonstrate diffuse increase in signal intensity (arrows) involving the dorsal columns of the cervical spinal cord extending from C1 to C7. The thoracic levels (not shown) were not involved. Findings of MR imaging of the brain were normal.

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Figure 4. Nitrous oxide induced myeloneuropathy

Nitrous oxide induced myeloneuropathy

Footnotes: A 20 year old female with a history of nitrous oxide abuse, she used about 5-10 canisters of nitrous oxide per week. She presented with tingling sensation in all extremities and burning sensation in bilateral soles; weakness and difficulty walking for 1 week. Physical exam reveals decreased light touch and pinprick sensation in all extremities with distal to proximal gradient. Decreased vibration sense in both feet. Hyporeflexia in upper limbs and absent reflexes in both lower limbs. Rhomberg sign weakly positive. No bladder or bowel incontinence. Her blood tests revealed: vitamin B12 = 279pg/mL, homocysteine = 58 nmol/mL and methylmalonic acid (MMA) = 1.59 nmol/mL. MRI of her spinal cord showed patchy increased signal intensity from C1-C5 affecting dorsal column. Axial T2 mid-cervical demonstrates bilateral hyperintensity in the dorsal column (inverted V sign). No cord compression or edema seen.

[Source 12) ]

Myeloneuropathy causes

A variety of nutritional, toxic, metabolic, infective, inflammatory, and paraneoplastic disorders can present with myeloneuropathy 13). Deficiencies of vitamin B12, folic acid, copper, and vitamin E may lead to myeloneuropathy with a clinical picture of subacute combined degeneration of the spinal cord 14). Chikungunya virus has been shown to produce a syndrome similar to myeloneuropathy 15). Vacuolar myelopathy seen in human immunodeficiency virus (HIV) infection is clinically very similar to subacute combined degeneration 16). A paraneoplastic myeloneuropathy, an immune-mediated disorder associated with an underlying cancer, may rarely be seen with breast cancer 17). Tropical myeloneuropathies are classified into two overlapping clinical entities — tropical ataxic neuropathy and tropical spastic paraparesis 18).

Copper deficiency myeloneuropathy

Copper deficiency is a rare and potentially treatable cause of myeloneuropathy 19), 20). Copper is an essential mineral that function as a cofactor (a compound that is essential for the activity of an enzyme) for several enzymes known as copper-dependent enzymes (cuproenzymes) involved in energy (ATP) production, iron metabolism, neuropeptide activation, connective tissue synthesis, and neurotransmitter synthesis 21), 22), 23), 24), 25). One abundant copper-dependent enzyme is ceruloplasmin, which plays a role in iron metabolism and carries more than 95% of the total copper in healthy human plasma 26). Copper is also involved in many physiologic processes, such as angiogenesis; neurohormone homeostasis; and regulation of gene expression, brain development, brain and nervous system physiological processes including neurotransmitter synthesis and formation and maintenance of myelin, pigmentation, and immune system functioning 27), 28), 29). In addition, defense against oxidative damage depends mainly on the copper-containing superoxide dismutases 30), 31).

Clinically evident, or frank, dietary copper deficiency is relatively uncommon in humans 32). Based on studies in animals and humans, the effects of copper deficiency include anemia, hypopigmentation, hypercholesterolemia, connective tissue disorders, osteoporosis and other bone defects, abnormal lipid metabolism, central nervous system demyelination, ataxia, polyneuropathy, myelopathy, inflammation of the optic nerve, and increased risk of infection 33), 34), 35).

The harmful effects of copper deficiency 36):

  • Increased cholesterol, decreased glucose tolerance and abnormal electrocardiograms (ECGs) 37).
  • Increased LDL and triglycerides and decreased HDL 38)
  • Increased susceptibility of lipoproteins and tissues to oxidation 39).
  • Increased apolipoprotein B 40).
  • Increased blood pressure 41).
  • Increased plasminogen activator inhibitor type 1 42)
  • Increased early and advanced glycation end-products 43)
  • Increased inflammation43 and increase in the expression of genes involved in inflammation and fibrinogenesis 44)
  • Ultrastructural irregularities of elastin and abnormal endothelial cells, subendothelial space, collagen fibres and smooth muscle cells 45)
  • Increased atherosclerosis 46)
  • Myelodysplastic syndrome 47)
  • Hepatic iron overload 48)
  • Fatty liver disease 49)
  • Cardiac hypertrophy 50), cardiomyopathy 51), 52)
  • Optic neuropathy, myeloneuropathy, anemia and neutropenia 53)
  • Atrial thrombosis, abnormal ECGs and sudden death 54)

Common causes of acquired copper deficiency include 55):

  • Malabsorption of copper
  • Gastric surgery, including gastric bypass or gastrectomy
  • Enteropathies such as inflammatory bowel disease, cystic fibrosis, and celiac disease
  • Excessive use of copper chelators
  • Zinc supplement overuse, parenteral overdosing, denture cream ingestion
  • Chronic total parenteral nutrition, prolonged jejunal enteral feeding
  • Diet low in copper
  • Cause unknown

The most common causes of acquired copper deficiency include malabsorption as a consequence of prior gastric surgery or enteropathy (e.g., celiac disease, cystic fibrosis, and inflammatory bowel disease) and excessive zinc supplementation 56), 57), 58), 59). Given that most dietary copper is absorbed in the duodenum, the potential harmful effect of gastric surgery on absorption is obvious. Furthermore, zinc and copper compete for absorption across the intestinal brush border through the binding of an intracellular protein called metallothionein. Consequently, excessive zinc supplementation can impair the absorption of copper into enterohepatic circulation.

The following groups are most likely to have inadequate copper status 60), 61), 62), 63):

  • People with celiac disease. In a study of 200 adults and children with celiac disease, of which 69.9% claimed to maintain a gluten-free diet, 15% had copper deficiency (less than 70 mcg/dL in serum in men and girls younger than 12 years and less than 80 mcg/dL in women older than 12 years and/or ceruloplasmin less than 170 mg/L) as a result of intestinal malabsorption resulting from the intestinal lining alterations associated with celiac disease 64). In its 2009 clinical guidelines for celiac disease, the American College of Gastroenterology notes that people with celiac disease appear to have an increased risk of copper deficiency and that copper levels normalize within a month of adequate copper supplementation while eating a gluten-free diet 65).
  • People with Menkes disease. Menkes disease is a rare, X-linked, recessive disorder of copper homeostasis caused by ATP7A mutations, which encode a copper-transporting ATPase 66). In individuals with Menkes disease, intestinal absorption of dietary copper drops sharply, leading to signs of copper deficiency, including low serum copper and ceruloplasmin levels 67), 68). The typical signs and symptoms of Menkes disease include failure to thrive, impaired cognitive development, aortic aneurysms, seizures, and unusually kinky hair 69), 70). The life span of patients with Menkes disease is difficult to predict, although the majority of these children do not live past the age of three years, but subcutaneous injections of copper starting in the first few weeks after birth can reduce mortality risk and improve development 71), 72).
  • People taking high doses of zinc supplements. High dietary intakes of zinc can interfere with copper absorption, and excessive use of zinc supplements can lead to copper deficiency. Reductions in erythrocyte copper-zinc superoxide dismutase, a marker of copper status, have been reported with even moderately high zinc intakes of approximately 60 mg/day for up to 10 weeks 73). People who regularly consume high doses of zinc from supplements or use excessive amounts of zinc-containing denture creams can develop copper deficiency because zinc can inhibit copper absorption. This is one reason the Food and Nutrition Board established the Tolerable Upper Intake Level (UL) for zinc at 40 mg/day for adults 74), 75).

The pathophysiology underlying the myeloneuropathy of copper deficiency remains unclear 76). It has been theorized that copper may play an integral role in methylation via methionine synthase, a necessary step in the production of purines and myelin proteins 77). Copper is also a cofactor for the enzyme superoxide dismutase, which is involved in the scavenging of free radicals. Additionally, copper is a known cofactor in cytochrome C oxidase-driven electron transport and oxidative phosphorylation, both crucial processes in the production of adenosine triphosphate (ATP). It remains unclear whether copper deficiency in a combination of the above processes are responsible for the damage that precipitates myelopathy 78).

Currently, there is not a sensitive and specific biomarker that accurately and reliably assess copper inadequacy in humans 79), 80), 81), 82). Copper status is not routinely assessed in clinical practice 83). Human studies typically measure copper and copper-dependent enzymes (cuproenzyme) activity in plasma and blood cells because individuals with known copper deficiency often have low blood levels of copper and ceruloplasmin 84). However, both the plasma ceruloplasmin and copper levels can be influenced by other factors, such as estrogen status, pregnancy, infection, inflammation, and some cancers, therefore limiting the usefulness of these assays to estimate body copper status 85), 86). Normal serum copper concentrations are 10–25 mcmol/L (63.5–158.9 mcg/dL) and 180–400 mg/L for ceruloplasmin 87). Experimental work has recently identified other copper-related biomarkers, including erythrocyte copper Cu/Zn superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase 88), 89), 90), but further experimental validation is required, including clinical testing in humans.

Oral copper supplementation is efficacious, acceptable and practical mode of therapy for copper deficiency myeloneuropathy. In some cases, oral copper maintenance therapy was preceded by parenteral supplementation, presumably in order to rapidly replenish copper stores and avert any further deterioration. Although some reports refer to copper parenteral treatment only 91), 92), 93), the efficacy of oral copper supplements should make prolonged parenteral therapy unnecessary.

Typical daily copper doses were equivalent to 2–4 mg of elemental copper. In one case attributed to non-weight loss gastrointestinal surgery, administration of 2 mg of oral copper per day normalised blood parameters and improved neurological symptoms. However, a subsequent symptomatic and biochemical relapse necessitated that the dose be incremented to 4 mg and then 6 mg, which achieved sustained remission 94). Another patient with idiopathic zinc overload was poorly compliant with oral copper supplementation at 2 mg/day. His serum copper levels remained low and the neurological deficit progressed, though serum caeruloplasmin increased to a value at the low end of the normal range and the anaemia resolved. The copper dose was gradually escalated to 8 mg/day but compliance remained poor and he continued to deteriorate neurologically. Subsequently, the patient reported better compliance and his neurological status improved. However, his highest recorded serum copper level remained below the normal range, and it was unclear whether this reflected insufficient dosage, poor compliance or other factors. Copper doses of up to 9 mg per day have been reported 95).

Treatment may need to be continued indefinitely where the underlying risk factor cannot be eliminated. Regular follow-up is necessary to ensure normalisation of biochemical and haematological parameters and stabilisation or improvement of neurological features.

Therapeutic efficacy does not appear to be influenced by the type of copper compound administered. Oral copper gluconate did not influence serum copper levels in normal volunteers 96). Whilst this finding was previously interpreted as signifying poor bioavailability 97), 98), it appears to merely reflect intact copper homeostasis through biliary excretion in a copper-replete study population.

Since zinc can interfere with copper absorption, care must be taken to avoid copper preparations that also contain significant quantities of zinc, as may be the case with multivitamin tablets.

Nitrous oxide induced myeloneuropathy

Nitrous oxide (N2O) also known as laughing gas misuse through use of whipped cream chargers or ‘whippets’ bought from ‘head shops’ or online can cause a severe but potentially reversible nitrous oxide induced myeloneuropathy through interference with vitamin B12 metabolism, leading to megaloblastic anemia (characterized by large, abnormally nucleated red blood cells as well as low counts of white and red blood cells, platelets; glossitis of the tongue; fatigue; palpitations; pale skin; dementia; weight loss; and infertility) and subacute combined degeneration of the spinal cord 99), 100), 101), 102), 103), 104), 105), 106), 107), 108), 109), which itself can be irreversible 110). Progressive demyelination or degeneration of the spinal cord can cause neurological signs and symptoms such as sensory disturbance in the lower (± upper) limbs, areflexia (absence of neurologic reflexes such as the knee-jerk reaction) and the loss of proprioception (the sense that lets you perceive the location, movement, and action of parts of you body) and vibratory sense along with gait abnormalities. Areflexia can be permanent if neuronal death occurs in the posterior and lateral spinal cord tracts 111), 112), 113), 114). Dementia-like disease, including episodes of psychosis, is possible with more severe and chronic vitamin B12 deficiency 115), 116).

Vitamin B12 also known as cobalamin is required for the development, myelination, and function of the central nervous system (brain and spinal cord); healthy red blood cell formation; and DNA synthesis 117), 118), 119). Vitamin B12 functions as a cofactor (a compound that is essential for the activity of an enzyme) for two enzymes, methionine synthase and L-methylmalonyl-CoA mutase 120), 121), 122), 123), 124). Methionine synthase catalyzes the conversion of homocysteine to the essential amino acid methionine 125)126). Methionine is required for the formation of S-adenosyl-L-methionine (SAMe), a universal methyl donor for almost 100 different substrates, including DNA, RNA, proteins, and lipids 127), 128), 129). L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the metabolism of propionate, a short-chain fatty acid 130).

The mechanism involves nitrous oxide-induced inactivation of vitamin B12 and inhibition of methionine synthetase, disrupting methylation and DNA synthesis and leading to injury of the neuronal axons. Patients with a pre-existing B12 deficiency are particularly prone to developing acute life-threatening neurological symptoms on exposure to nitrous oxide, which can be fatal 131), 132).

Non-functioning vitamin B12 leads to accumulation of methylmalonic acid (MMA) and homocystine, which can be tested in the patient serum when B12 levels appear normal, suggesting a ‘functional’ B12 disorder. Serum B12 and active B12 levels may be normal because in this situation the myeloneuropathy is triggered by functional rather than absolute B12 deficiency.

A high index of suspicion is required to prompt appropriate investigation, make the diagnosis and commence treatment early.

MRI imaging of the spine showed the characteristic features of dorsal column hyperintensity on T2 weighted sequences strongly suggest the diagnosis.

The management of patients with nitrous oxide induced myeloneuropathy includes educating them about the risks of nitrous oxide and vitamin B12 replacement using high-dose intramuscular hydroxocobalamin (1 mg on alternate days until no further neurological improvement, followed by 1 mg every 2 months) 133). Guidelines from the British Society for Haematology recommend injections three times per week for two weeks in patients without neurologic deficits 134). If neurologic deficits are present, injections should be given every other day for up to three weeks or until no further improvement is noted 135). In general, patients with an irreversible cause should be treated indefinitely, whereas those with a reversible cause should be treated until the deficiency is corrected and symptoms resolve 136). If vitamin B12 deficiency coexists with folate deficiency, vitamin B12 should be replaced first to prevent subacute combined degeneration of the spinal cord 137). The British Society for Haematology does not recommend retesting vitamin B12 levels after treatment has been initiated, and no guidelines address the optimal interval for screening high-risk patients 138).

A 2018 Cochrane review involving 108 patients with vitamin B12 deficiency found that high-dose oral vitamin B12 replacement (1 mg to 2 mg per day) was as effective as high-dose intramuscular administration for correcting anemia and neurologic symptoms 139). However, oral therapy does not improve serum methylmalonic acid (MMA) levels as well as intramuscular therapy, although the clinical relevance is unclear 140). There is also a lack of data on the long-term benefit of oral therapy when patients do not take daily doses 141). There is insufficient data to recommend other formulations of vitamin B12 replacement (e.g., nasal, sublingual, subcutaneous) 142). The British Society for Haematology recommends intramuscular vitamin B12 for severe deficiency and malabsorption syndromes, whereas oral replacement may be considered for patients with asymptomatic, mild disease with no absorption or compliance concerns 143).

Neurological deficits can improve with abstinence and vitamin B12 supplementation, even in the most severely affected patients.

Folic acid deficiency

Folic acid deficiency can also produce a clinical picture similar to that of subacute combined degeneration of the spinal cord caused by vitamin B12 deficiency. Many other deficiencies such as vitamin B12 deficiency are concomitantly present. Folic acid deficiency is usually caused by dietary deficiency, malabsorption syndromes, pregnancy and lactation, usage of anticancer, antiepileptic, or oral contraceptive drugs, and long-term alcoholism. Folic acid deficiency-associated myeloneuropathy partially responds to folic acid supplementation 144), 145).

Vitamin E deficiency

Vitamin E deficiency is classically characterized with a spinocerebellar syndrome; however, it can also present with myeloneuropathy. Ataxia with vitamin E deficiency is an autosomal recessive disorder. The clinical features of vitamin E deficiency are similar to Friedreich’s ataxia. Patients present with cerebellar ataxia, loss of deep jerks, loss of vibration sense, dysarthria, and Babinski sign. Head titubation, retinopathy and dystonia are more common in these patients. Early diagnosis is crucial for successful treatment 146), 147), 148).

Chlorpyrifos poisoning

Chlorpyrifos is an organophosphate insecticide, which can cause delayed neurological toxicity following a high dose exposure 149), 150). A delayed myeloneuropathy following chlorpyrifos poisoning has been reported in an isolated case 151).

Chikungunya virus

Chikungunya virus in India has been shown to produce a syndrome similar to myeloneuropathy. A study during a chikungunya epidemic noted that among 90 laboratory-confirmed cases, 12 patients had myeloneuropathy, with or without encephalitis. The outcome of the neurological complications was good. In an another report of 300 patients with chikungunya, in 2006, 14% (7/49) patients had myeloneuropathy 152), 153).


Vacuolar myelopathy in HIV infection is clinically very similar to subacute combined degeneration. Vacuolar myelopathy manifests with a posterolateral spinal cord syndrome with bladder and bowel disturbances. HIV myelopathy appears in the late stages of HIV infection when CD4+ cell counts are very low. Most of these patients concomitantly have other complications of HIV infection such as encephalopathy, opportunistic infections, or malignancies. Spinal cord pathology, including vacuolar myelopathy, has rarely been reported in Indian HIV-infected patients 154), 155).

Paraneoplastic myeloneuropathy

A paraneoplastic myeloneuropathy is an infrequent immune-mediated disorder that is associated with an underlying cancer. In some case reports, paraneoplastic myeloneuropathy has been reported with breast cancer. Antineuronal nuclear antibody 1 (anti-Hu) is frequently positive in these patients and they respond well to corticosteroids 156), 157). Reports on paraneoplastic myelopathies have demonstrated a characteristic magnetic resonance imaging (MRI) pattern of longitudinally extensive signal changes in the spinal cord.

Sjögren’s syndrome

Sjögren’s syndrome can manifest with myeloneuropathy 158). Sjögren’s syndrome is an autoimmune disorder characterized by decreased secretions of lacrimal and salivary glands (sicca symptoms). The central and peripheral nervous systems’ involvement in Sjögren’s syndrome is a result of vasculitis as well as direct immunological injury to neurons. Clinical spectrum of Sjögren’s syndrome-associated neuropathy includes sensory ataxic neuropathy, trigeminal neuropathy, multiple mononeuropathy, radiculoneuropathy, painful sensory neuropathy without sensory ataxia, autonomic neuropathy with anhidrosis, and multiple cranial neuropathy. Neurological symptoms occur in approximately 20% of patients with Sjögren’s syndrome, and may be the presenting manifestations of the disease 159).

Hashimoto’s disease

In Hashimoto’s disease, antithyroid antibodies can also be associated with acute myeloneuropathy or myelopathy 160), 161). The exact role of antithyroid antibodies in the pathogenesis of the myelopathy is not precisely clear; however, a vasculitic process has been suggested. There is often a good response to corticosteroids 162), 163).


Sarcoidosis is a granulomatous disorder that can affect virtually any organ of the human body and nearly any component of the nervous system. A variety of neurological manifestations are possible including myelopathic signs and symptoms, and signs of segmental radiculopathy at the affected levels. Polyradiculopathy, including cauda equina syndrome and peripheral neuropathy, may accompany myelopathic finding. The diagnosis of sarcoidosis is quite challenging in such patients.

Tropical myeloneuropathies

Tropical myeloneuropathies were described initially in tropical countries and are classified into 2 overlapping clinical syndromes that can have overlapping features — tropical spastic paraparesis (TSP) and tropical ataxic neuropathy (TAN) 164). Tropical spastic paraparesis (TSP), a chronic cause of myeloneuropathy, has frequently been reported from South India. It is caused by an infection with human T-cell lymphotropic virus-1 (HTLV-1). Tropical ataxic neuropathy (TAN) is a slowly progressive cause of myeloneuropathy seen in cassava-eating countries. This disease characteristically occurs in an endemic form and is clinically characterized by sensory polyneuropathy, gait ataxia, optic atrophy, and nerve deafness. Tropical ataxic neuropathy often starts with dysesthesias in the lower limbs followed by unsteadiness of the gait. Romberg test is characteristically present. Reflexes in the lower limbs are either diminished or absent. Plantar response is usually flexor. Tropical ataxic neuropathy is seen in populations that use large quantities of cassava in their diets for very long periods 165), 166).

Inherited myeloneuropathies

A variety of hereditary myeloneuropathies have been described. Adrenomyeloneuropathy, a variant of adrenoleukodystrophy, is a noninflammatory involvement of the spinal cord that involves the descending corticospinal tracts, dominantly in the thoracic and lumbosacral regions, and the posterior columns, in the cervical spinal segments. The clinical features of adrenomyeloneuropathy include a slowly progressive spastic paraparesis and mild polyneuropathy in adult men, with or without sensory manifestations and sphincter disturbances 167).

Recently, Motley et al 168) from Belgium described five siblings in a family with dominantly inherited myeloneuropathy. All affected family members had a mild axonal neuropathy and three out of four family members had lower extremity hyperreflexia, suggestive of a superimposed myelopathy. A nerve biopsy showed evidence of chronic axonal loss. All affected family members had a heterozygous missense mutation in the alanyl-tRNA synthetase gene 169).

Myeloneuropathy symptoms

Myeloneuropathy symptoms vary depending on the underlying cause and the relative degree of involvement of the corticospinal tracts, spinocerebellar tracts, the dorsal columns, and peripheral nerves. Paresthesias (pins-and-needles sensation) and numbness involving the digits of the upper and/or lower limbs represent the most common complaints. In addition to spinal cord and peripheral nerve involvement, patients may also have visual deficits, and neuropsychiatric disease (depression and dementia).

Dorsal column involvement leads to impaired tactile discrimination, proprioception, and vibration sense. The earliest symptoms of dorsal column involvement are paresthesia, observed in the form of tingling, burning, and sensory loss of the distal extremities. Either the upper or lower limbs are involved first, or all four limbs are affected simultaneously. In addition, Lhermitte’s sign which is a transient sensation of an electric shock that extends down the spine and extremities upon flexion and/or movement of the neck may be present. Loss of proprioception usually presents as a difficulty in maintaining balance in the absence of visual cues (e.g., in the dark or with closed eyes).

Lateral corticospinal tract dysfunction causes muscle weakness, hyperreflexia, and spasticity. Stiffness is often the initial symptom of lateral cord involvement. Diffuse hyperreflexia can occur, although ankle reflexes are usually absent. Other signs of upper motor neuron damage such as ankle clonus and Babinski sign may be present. Spasticity can progress to paraplegia or quadriplegia if the condition remains untreated. Sphincter involvement in advanced cases can lead to bowel and bladder incontinence.

Spinocerebellar tract degeneration causes gait abnormalities in the form of sensory ataxia. Romberg’s test is a simple bedside test to determine the integrity of the dorsal column pathway of your brain and spinal cord (the neural pathways that carry proprioception sense by which sensory information from the peripheral nerves is transmitted to the cerebral cortex), which controls proprioception 170). Proprioception is the sense that lets you perceive the location, movement, and action of parts of your body 171). Proprioception encompasses a complex of sensations, including perception of joint position and movement, muscle force, and effort 172). These sensations arise from signals of sensory receptors in your muscle, skin, and joints, and from central signals related to motor output. Proprioception enables you to judge limb movements and positions, force, heaviness, stiffness, and viscosity. It combines with other senses to locate external objects relative to the body and contributes to body image. Romberg sign is positive in a patient who can stand with his feet placed together and eyes open but paradoxically sways or falls while closing his eyes, thereby eliminating his visual cues 173), 174). During a Romberg test, your doctor will ask you to close your eyes while standing with your feet together and your arms to your side, this removes the visual and vestibular components that contribute to maintaining balance. If you feel unbalanced or unsteady, positive Romberg’s sign, it could mean that you have an issue with your central nervous system (your brain or spinal cord) 175).

Physical examination may reveal decreased sensation to light touch and pain/temperature, hyperreflexia, spasticity, increased tone, disorders of gait, and the emergence of an extensor plantar response. Urinary and/or fecal incontinence or retention may also be seen 176).

Myeloneuropathy diagnosis

If you have myeloneuropathy symptoms, your doctor will look for a treatable cause. Besides conducting a physical exam and a neurological exam, including checking your vision, balance, coordination and reflexes, your doctor might request tests, including:

  • Blood tests. Blood levels of vitamin B12, folic acid, methylmalonic acid (MMA), homocysteine, vitamins A, D, E, and K, iron, and calcium should be assessed to detect other nutritional deficiencies
  • Imaging studies. Imaging of the brain and spinal cord, with contrast, is always needed.
  • Lumbar puncture (spinal tap). In some cases of myeloneuropathy, this may be a helpful test. A needle is inserted into the lower back (lumbar region) between two lumbar bones (vertebrae) to remove a small sample of cerebrospinal fluid. The fluid, which surrounds and protects your brain and spinal cord, is sent to a laboratory for testing.
  • Genetic testing. Your doctor might recommend genetic testing to determine whether a gene mutation causes one of the inherited myeloneuropathy conditions.
  • Electromyography (EMG) and nerve conduction study. Electromyography and nerve conduction study results are often consistent with axonal sensorimotor polyneuropathy in the legs; somatosensory evoked potentials may provide an electrophysiological evidence of dysfunction in the central pathways.

Myeloneuropathy treatment

Myeloneuropathy treatment involves treating the underlying cause such as vitamin B12 supplements for nitrous oxide induced vitamin B12 deficiency and copper for copper deficiency.

Because there are so many causes of myeloneuropathy and each case is different, your doctor is the best person to tell you what kind of treatments are possible and likely to help you. The information they provide will be the most relevant to your particular situation.

Myeloneuropathy prognosis

Myeloneuropathy prognosis depends on the underlying cause. Some patients are left with a permanent deficit, including lifelong paraparesis despite optimal treatment.

Neurological deficits can improve with nitrous oxide abstinence and vitamin B12 supplementation, even in the most severely affected patients. Neurological recovery may be incomplete, particularly when patients continue to use nitrous oxide (N2O) 177).

In patients with copper deficiency myeloneuropathy, copper supplementation can arrest further neurological deterioration and even reverse symptoms and imaging findings 178).

The life span of patients with Menkes disease is difficult to predict, although the majority of these children do not live past the age of three years, but subcutaneous injections of copper starting in the first few weeks after birth can reduce mortality risk and improve development 179), 180).

References   [ + ]

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