Comment; good review of the various nutritional neuropathies, how they present, how to resolve them and long-term prognosis
Nancy Hammond, MD, Yunxia Wang, MD, Mazen Dimachkie, MD, and Richard Barohn, MD
University of Kansas Medical Center, Kansas City, KS
Yunxia Wang: ywang@kumc.edu
Keywords
Neuropathy; Thiamine; Vitamin B12; Copper; Vitamin B6; Bariatric Surgery
Introduction
Malnutrition can affect all areas of the nervous system. Risk factors for malnutrition include
alcohol abuse, eating disorders, older age, pregnancy, homelessness, and lower economic
status. Any medical condition that affects the GI tract can also impair absorption of essential
vitamins. Nutritional deficiencies have been described in patients with inflammatory bowel
disease, fat malabsorption, chronic liver disease, pancreatic disease, gastritis, and small
bowel resections. Patients receiving total parental nutrition (TPN) are also at risk for vitamin
deficiency and TPN formulations should be carefully formulated to include supplemental
vitamins and trace minerals. Neurological complications following gastric bypass surgery
are increasingly recognized. Nutritional neuropathies manifest either acutely, subacutely, or
chronically. They can be either demyelinating or axonal.
A unique class of peripheral neuropathy with coexistent myelopathy, also called
myeloneuropathy, can also been seen with nutritional neuropathies. Myeloneuropathy has
been described with deficiencies of vitamin B12 and copper.
Patients with myeloneuropathy will present with both upper motor neuron and lower motor
neuron signs. Peripheral neuropathy may mask the symptoms and signs of the myelopathy
presenting a diagnostic challenge. Hyper reflexia may be difficult to assess in the presence
of severe peripheral neuropathy and ankle jerks may be absent. Muscle weakness may
impair the toe extensors, so Babinski sign may not be present. Besides spinal cord/cauda
equina arteriovenous malformation, the clinician should suspect myeloneuropathy when the
predominant complaint is gait impairment or bowel or bladder dysfunction in the setting of a
peripheral neuropathy.
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Thiamine Deficiency
Pathogenesis
Thiamine (vitamin B1) is a water-soluble vitamin present in most animal and plant tissues.
Neuropathy due to thiamine deficiency, known as beriberi, was the first clinically described
deficiency syndrome in humans. Beriberi may manifest with heart failure (wet beriberi) or
without heart failure (dry beriberi). Thiamine deficiency is also responsible for Wernicke’s
encephalopathy and Korsakoff’s syndrome. Thiamine is absorbed in the small intestine by
both passive diffusion and active transport and rapidly converted to thiamine diphosphate
(TDP). TDP serves as an essential co-factor in cellular respiration, ATP production,
synthesis of glutamate and γ-aminobutyric acid[1] and myelin sheath maintenance. Only
about 20 days of thiamine are stored in the body, and thiamine deficiency can start to
manifest in as little as three weeks. The recommended daily allowance (RDA) for thiamine
ranges from 1.0 mg per day for young healthy adults to 1.5 mg per day for breastfeeding
women[2]. Athletes and patients with higher metabolic needs as seen during pregnancy,
systemic infections, and certain cancers need a higher daily intake of thiamine. Thiamine
deficiency is rare in industrialized countries and is most commonly seen in the setting of
chronic alcohol abuse, recurrent vomiting, AIDS, long-term total parenteral nutrition, eating
disorders and weight reduction surgery.
Clinical Features
Symptoms usually develop gradually over weeks to months, but sometimes they may
manifest rapidly over a few days mimicking Gullain Barré Syndrome[3, 4]. Fatigue,
irritability, and muscle cramps may appear within days to weeks of nutritional deficiency[5].
Clinical features of thiamine deficiency begin with distal sensory loss, burning pain,
paraesthesias or muscle weakness in the toes and feet[6]. There is often associated aching
and cramping in the lower legs. Left untreated, the neuropathy will cause ascending
weakness in the legs and eventually evolve to a sensorimotor neuropathy in the hands.
Beriberi may include involvement of the recurrent laryngeal nerve, producing hoarseness
and cranial nerve involvement manifesting as tongue and facial weakness [7]. Oculomotor
muscle weakness and nystagmus have been attributed to beriberi, but these manifestations
are more likely due to coexistent Wernicke’s disease. Approximately 25% of patients with
thiamine deficient polyneuropathy may also have Wernicke’s encephalopathy which
manifests as ophthalmoplegia, ataxia, nystagmus and encephalopathy[6].
Diagnosis
Blood and urine assays for thiamine are not reliable for diagnosis of deficiency.
Measurement of thiamine pyrophosphate by high-performance liquid chromatography[8] or
erythrocyte transketolase activation may be preferred for assessment of thiamine status[9].
However, the precise sensitivity and specificity for those assays has not been established.
Testing must be performed before thiamine supplementation is given. Electrodiagnostic
testing shows an axonal sensorimotor polyneuropathy worse in the lower extremities and
nerve biopsies demonstrate axonal degeneration [6].
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Management
When a diagnosis of thiamine deficiency is made or suspected, thiamine replacement should
be provided until proper nutrition is restored. Thiamine is usually given intravenously or
intramuscularly at an initial dose of 100 mg followed by 100 mg per day. Cardiac
manifestations may improve within hours to days while neurological improvement may take
3–6 months with motor manifestations responding better than sensory symptoms[10]. Some
improvement is expected in most patients, but this typically occurs slowly, and in patients
with severe neuropathy, there may be permanent deficits[11].
Vitamin B12
Pathogenesis
Vitamin B12 (cobalamin) is present in animal and dairy products and is synthesized by
specific microorganisms. Humans depend on nutritional intake for their vitamin B12 supply.
Vitamin B12 deficiency has been observed in 5% to 20% of older adults and up to 40% of
older adults have low serum vitamin B12 levels[12]. The RDA for vitamin B12 is 2.4 mcg
daily[2].
Vitamin B12 is an integral component of two biochemical reactions in human. The first is
the formation of methionine by methylation of homocysteine. A byproduct of this reaction is
the formation of tetrahydrofolate, an important precursor of purine and pyrimidine synthesis.
The second important reaction is the conversion of L-methylmalonyl coenzyme A into
succinyl coenzyme A which is essential for formation of the myelin sheath.
Vitamin B12 is liberated from food by stomach acid and pepsin. Liberated B12 then binds to
R proteins secreted in the saliva and gastric secretions. Cobalamin is released from the R
protein in the small intestine and binds to intrinsic factor. The vitamin B12-intrisic factor
complex is then absorbed in the terminal ileum.
Cases of vitamin B12 deficiency can be due to malabsorption, pernicious anemia,
gastrointestinal surgeries and weight reduction surgery. As vitamin B12 is only found in
animal products strict vegan diets lack vitamin B12 and must be supplemented. Certain
medications may contribute to vitamin B12 deficiency namely proton pump inhibitors[13]
and metformin[14]. An underappreciated cause of Cbl deficiency is food-cobalamin
malabosrption. This typically occurs in older individuals and results from an inability to
adequately absorb Cbl bound in food protein. These patients can absorb free Cbl without
difficulty. Therefore, Schilling tests will be normal. No apparent cause of deficiency is
identified in a significant number of patients with Cbl deficiency.
The most common cause of B12 deficiency is pernicious anemia. This autoimmune disorder
is characterized by destruction of the gastric mucosa, and the presence of parietal cell and
intrinsic factor antibody leading to impaired B12 absorption. The disorder is more common
in African-Americans and in patients with Northern European background.
Chronic exposure to nitrous oxide has been associated with subacute combined degeneration
[15]. The mechanism by which nitrous oxide induces vitamin B12 deficiency is by
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inactivation of methyl-cobalamin thereby inhibiting the conversion of homocysteine to
methionine and methyltetrahydrofolate (MTHF) and 5-methylene-tetrahydrofolate (THF),
which are required for myelin sheath protein and DNA synthesis.
Clinical Features
Vitamin B12 (cobalamin) deficiency is associated with hematologic, neurologic, and
psychiatric manifestations. Subacute combined degeneration, neuropsychiatric symptoms,
peripheral neuropathy and optic neuropathy are the classic neurological consequences of
B12 deficiency. Patients may present with neurological symptoms regardless of a normal
hematological picture. The neuropathy associated with B12 deficiency usually begins with
sensory symptoms in the feet.
Differentiating vitamin B12 deficiency-related polyneuropathy from cryptogenic sensory
polyneuropathy (CSPN) can be difficult on clinical grounds only. Clinical features useful to
identify vitamin B12 deficiency related peripheral neuropathy are the acuteness of
symptoms onset, and concomitant involvement of upper and lower extremities[16].
Sometimes the sensory symptoms and signs first appear in the upper extremities or the
“numb hand syndrome” [17–19]. When this occurs with other findings of a
myeloneuropathy, immediately consider B12 as well as copper deficiency (see below). The
myeloneuropathy findings often consist of significant proprioception and vibration,
increased tone, weakness in a corticospinal tract distribution, (ex. hip and knee flexors),
brisk knee and arm reflexes, Hoffman’s signs in the fingers, and extensor plantar responses
in the toes.
Histopathological studies have showed breakdown and vacuolization of central nervous
system myelin under B12 deficiency states [20]. In contrast to the demyelinating features
seen in the spinal cord, axonal neuropathy is seen on nerve biopsies and nerve conduction
studies in vitamin B12 polyneuropathy.
Diagnosis
Diagnosis of B12 deficiency is usually made in the presence of typical neurological
symptoms, hematological abnormalities, and serum vitamin B12 levels less than 200 pg/ml,
though a significant proportion of vitamin B12 deficiency patients may have serum levels
that are within the low normal range up to 400 pg/ml. Measurement of the serum
metabolites methylmalonic acid (MMA) and homocysteine (Hcy) can improve the
sensitivity significantly in patients with low normal range of B12 (300–400 pg/ml) when
there is high clinical suspicion [21]. Though elevated MMA and Hcy suggest B12
deficiency, it is necessary to rule out other conditions associated with such abnormal levels,
such as renal insufficiency and hypovolemia. Isolated Hcy elevation may also be seen in
hypothyroidism, deficiency of folic acid and pyridoxine, cigarette smoking, and advanced
age.
Historically, the Schilling test was used to diagnose pernicious anemia. Today, it is difficult
to obtain a Schilling test due to the unavailability of the radioisotope. Anti-intrinsic factor
and anti-parietal cell antibodies can be helpful in the diagnosis of pernicious anemia with
high specificity and low sensitivity for the former and high sensitivity and low specificity
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for the latter. In typical cases with myelopathic symptoms, increased T2 signal intensity is
seen in the posterior column on magnetic resonance imaging studies (see imaging below for
copper deficiency which is similar).
Treatment [17]
Early diagnosis is critical since patients with advanced disease may be left with major
residual disability. Common treatment regimen includes administration of 1000 mcg
intramuscularly daily for 5–7 days, followed by 1000 mcg IM monthly. Other approaches
are a once-a-week injections for four weeks, and then monthly injections. Either is probably
acceptable. B12 levels should be monitored occasionally to prevent inadequate treatment or
non-compliance. Initial severity and duration of symptoms, and the initial hemoglobin
measurements correlate with the residual neurological damage after cobalamin therapy. This
inverse correlation between severity of anemia and neurologic damage is not understood. If
a neurologic response occurs, it does so within the first six months of therapy, although
further improvement may occur with time. On the other hand, sometimes treatment only
prevents further neurologic impairment, and often patients are left with the neurologic
deficits found prior to treatment.
Patients with food-cobalamin malabsorption can absorb free cobalamin and, therefore can be
treated with oral cobalamin supplementation. Oral cobalamin replacement therapy may also
be an option for patients with pernicious anemia. The daily requirement for cobalamin is 1
to 2 μg, and approximately 1% of orally administered cobalamin can be absorbed by patients
with pernicious anemia. Therefore, theoretically, an oral cobalamin dose of 1000 mg per day
should be sufficient. Although oral cobalamin may seem preferable to intramuscular
injections, parenteral therapy is actually less expensive (if it is self-administered). Given the
absence of convincing data regarding oral replacement in patients with neurologic deficits,
the authors’ practice is to use intramuscular cobalamin therapy when the etiology is
pernicious anemia. However, a reasonable compromise may be to switch to oral therapy
after several months and periodically monitor MMA or Hcy levels.
There is no clear evidence that folic acid therapy precipitates or exacerbates B12 deficiency-
related neuropathy, however pharmacological doses of folic acid may reverse the
hematological abnormalities of cobalamin deficiency, masking early recognition of
symptoms, therefore, resulting in the development or progression of neurological symptoms.
Vitamin E Deficiency
Pathogenesis
Vitamin E is abundantly available in the diet and is present in animal fat, nuts, vegetable oils
and grains. Alpha- tocopherol is the biologically active form of vitamin E in humans. The
RDA of vitamin E is 15 mg per day of alpha-tocopherol[22]. Dietary vitamin E is
incorporated into chylomicrons and passively absorbed in the intestines. This process
requires bile acids, fatty acids, and monoglycerides for absorption[9]. Vitamin E is delivered
to tissues via the chylomicrons and then chylomicron remnants when vitamin E is
transferred to very low-density lipoproteins (VLDL) via alpha-tocopherol transfer protein
(TTP). Most vitamin E deficiencies occur in patients with malabsorption or transport
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deficiencies. Patients with cystic fibrosis who have malabsorption can develop vitamin E
deficiency.
The pathogenesis of vitamin E deficiency is poorly understood. Vitamin E is an antioxidant
and a free radical scavenger, and it is postulated that the neurological manifestations of
vitamin E deficiency are primarily related to the loss of this protective function. Fat
malabsorption is the main cause of vitamin E deficiency. Isolated vitamin E deficiency is a
rare autosomal recessive disorder caused by a mutation in the alpha-tocopherol transfer
protein gene on chromosome 8q13 [23]. Another hereditary disorder leading to vitamin E
deficiency is abetalipoproteinemia, a rare autosomal dominant disorder resulting from
mutations in the microsomal triglyceride transfer protein[24]. Patients with this disorder
have fat malabsorption and deficiencies of many fat soluble vitamins. If left untreated,
patients with this disorder develop pigmented retinopathy, loss of vibration and
proproprioception, loss of deep tendon reflexes, ataxia and cerebellar degeneration as well
as generalized muscle weakness[25].
Clinical features
Because alpha- tocopherol is stored in adipose tissues, symptoms of vitamin E deficiency
may take 5–10 years to manifest. The onset of symptoms is usually slow and progressive.
Clinical features of vitamin E deficiency mimic that of Friederich’s ataxia and include
ataxia, hyporeflexia, and loss of proprioception and vibration. Other findings on
neurological examination may include dysarthria, nystagmus, ophthalmoparesis,
retinopathy, head titubation, decreased sensation, and proximal muscle weakness. Pes cavus,
and scoliosis may be present. Nerve conduction studies in vitamin E deficiency show a
sensory predominant axonal neuropathy. Nerve biopsy shows loss of large myelinated fibers
with evidence of regeneration. [26]. Electromyography is often normal, although mild signs
of denervation may occur. SSEP may show abnormalities consistent with posterior column
involvement [27].The principal pathologic features of vitamin E deficiency include swelling
and degeneration of large myelinated axons in the posterior columns, peripheral nerves, and
sensory roots[9].
Diagnosis
Diagnosis is made by measuring alpha-tocopherol levels in the serum. Serum vitamin E
levels may be normal even when deficiency is present. The ratio of total serum vitamin E to
the total serum lipid concentration has been suggested as a superior assessment of vitamin E
status[28].
Management
Treatment of Vitamin E deficiency may reverse or halt the progression of the neurological
symptoms. Treatment begins with oral supplementation of Vitamin E 400 international units
twice daily, with a gradual increase in the dose until normalization of serum vitamin E
levels. Patients with abetalipoprotienemia may require very large doses of vitamin E to
normalize serum vitamin E levels. Malabsorption syndromes may require treatment with
water-miscible or intramuscular preparations of vitamin E.
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Vitamin B6
Pathogenesis
Vitamin B6, or pyridoxine, is unique in that either a deficiency or an excess can cause a
neuropathy. Pyridoxine is readily available in the diet and dietary deficiency of B6 is rare.
Humans are not able to synthesize B6, so dietary intake is essential. After absorption,
pyridoxine is converted into pyridoxal phosphate which is an important co-factor in
numerous metabolic reactions. The RDA for pyridoxine is 1.3 mg daily with the upper limit
of 100mg daily[2]. Doses of 50mg to 100mg of vitamin B6 should mainly be used in certain
conditions such as pyridoxine deficient seizures and patients taking certain medications to
avoid toxicity.
Vitamin B6 deficiency is most commonly seen in patients treated with the certain
medications that are B6 antagonists, namely isoniazid, phenelzine [29], hydralazine [30],
and penicillamine. B6 deficiency can also be seen in patients receiving chronic hemodialysis
[31]. Vitamin B6 deficiency may also result from the malnutrition due to chronic alcoholism
and in patients with high metabolic needs such as the pregnant or lactating woman. Risk
factors for vitamin B6 toxicity are excessive intake of supplements [32,33].
Clinical Features
In infants, pyridoxine deficiency is a cause of seizures. In adults neuropathy due to B6
deficiency starts with numbness, paresthesias, or burning pain in the feet which then ascends
to affect the legs and eventually the hands. Neurological examination reveals a length
dependent polyneuropathy with decreased distal sensation, reduction of deep tendon
reflexes, ataxia and mild distal weakness.
Vitamin B6 toxicity produces a sensory ataxia, areflexia, and impaired cutaneous sensation.
Patients often complain of burning or paresthesias. Electrodiagnostic testing usually shows a
sensory neuronopathy, but with severe toxicity motor nerves can be affected as well[33].
Symptoms of toxicity can be seen with doses as low as 100 mg per day[34].
Diagnosis
Vitamin B6 deficiency can be detected by direct assay of blood or urine. Pyridoxal
phosphate can also be measured in the blood. Nerve conduction studies reveal severely
reduced sensory nerve action potentials with preserved CMAP. Sural nerve biopsy confirms
axonal degeneration of small and large myelinated fibers.
Management
Vitamin B6 supplementation with 50mg per day is suggested for patients being treated with
isoniazid or hydralazine. Daily B6 doses of 10 mg to 50 mg are recommended for patients
undergoing hemodialysis[31].
The treatment for B6 toxicity is to stop the exogenous B6. Patients may continue to have
symptom progression for 2–3 weeks following the discontinuation of vitamin B6 before a
gradual improvement starts, a phenomenon known as coasting.
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Pellagra (Niacin Deficiency)
Pathogenesis
Pellagra is the clinical manifestation of nicotinic acid (niacin or B3) deficiency. The classic
clinical triad of pellagra is dermatitis, dementia, and diarrhea. Pellagra was once endemic in
the United States and Europe and is still occasionally encountered. Most modern patients
with pellagra have other risk factors for malnutrition such as homelessness[35],
anorexia[36–38], certain cancers, or malabsorption[39].
Niacin is absorbed in the intestine by simple diffusion. The RDA for adults for niacin is
14mg to 16mg a day[2]. Niacin and its derivatives are important in carbohydrate metabolism
Clinical Features
Early neurological symptoms are predominantly neuropsychiatric including apathy,
inattention, irritability, and depression. Without treatment symptoms can progress to stupor
or coma. Isolated niacin is not known to be a cause of neuropathy and most patients
deficient in niacin have other nutritional deficiencies as niacin alone will not improve
neuropathy [9].
Diagnosis
There is no reliable measure of serum niacin.
Management
Oral replacement of nicotinic acid of 50 mg two or three times a day is recommended for
treatment, but dose may be limited due to flushing. Nicotinamide can be used as a substitute
in patients unable to tolerate nicotinic acid. Pellagra should be considered in any patient
deficient in vitamin B12 or thiamine whose cognition does not improve with
supplementation.
Copper Deficiency
Pathogenesis
Copper deficiency has long been recognized as a cause of hematologic abnormalities in
humans, but neurological abnormalities due to copper deficiency were not reported until
2001 [40]. Since then copper deficiency has been reported to cause either myelopathy or a
myeloneuropathy[41]. Copper deficiency has also been reported in association with
peripheral neuropathy[42, 43], but it is not clear from these case reports if the neuropathy
was isolated or in association with other neurological manifestations. Copper sources are
common in most western diets and copper rich foods include seafood, nuts, wheat and
grains. The RDA for copper for adults is 900 mcg daily[44].
Copper is essential in many oxidative reactions in the body. These reactions can generate
free radicals which are toxic to the cell and so both the absorption and excretion of copper
are tightly regulated by cells.
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Gastric acid is needed to solubilize dietary copper. Afterward, it is absorbed by both active
and passive mechanisms in the intestines. The active transport mechanism predominates
when dietary copper is low and augmented by passive diffusion when dietary copper is high.
Gastric acid is needed to solubilize dietary copper. Once copper enters the serum it is bound
to plasma proteins and transported via the portal vein to the liver. Here copper is
incorporated into ceruloplasmin for delivery to cells. If copper supplies are high, the liver
excretes excess copper into the bile.
The most common cause of copper deficiency is prior gastric surgery. Exogenous zinc
intake from either excessive intakes of zinc supplements [45]or use of older zinc containing
denture creams[46, 47]has also been postulated as a cause of copper deficiency with
neurological manifestations. Both zinc and copper bind to metallothionein in the
enterocytes. Excessive zinc intake leads to up regulation of these complexes and copper has
a higher affinity for these receptors than zinc leading copper to displace zinc. The zinc is
then absorbed into the bloodstream and the copper/metallothionein complex remains in the
enterocyte and is excreted in the feces following normal sloughing of these cells. Copper
deficiency can also be seen in association with excess iron consumption and malabsorption
syndromes.
Clinical Features
The majority of patients present with gait difficulty and lower limb paresthesias.
Neurological examination reveals loss of proprioception and vibration due to dorsal column
dysfunction and sensory ataxia. Upper motor neuron signs such as bladder dysfunction,
brisk knee jerks, and extensor plantar reflexes can also be elicited[41]. A motor neuron
disease-like presentation has also been reported [48, 49].
MRI studies of the spinal cord are reportedly abnormal in 47% of cases showing increased
T2 signal in the posterior columns in both the cervical and thoracic spinal cord[50] [Figure
1]. Neurophysiologic studies are abnormal in most patients with a copper myelopathy.
Nerve conduction studies are compatible with mixed, motor and sensory axonal
polyneuropathy[41].
Diagnosis
Hematologic abnormalities are common in patients with copper deficiency, particularly
anemia or occasionally myelodysplastic syndrome. In copper deficiency serum copper,
ceruloplasmin and urinary excretion of copper will be low, and zinc often will be high.
Ceruloplasmin is an acute phase reactant, so this may not be an adequate marker in certain
patients.
Management
In patients with copper deficiency due to excessive zinc intake, it is important to discontinue
the exogenous zinc. Replacement with 2 mg of elemental copper three times a day orally is
the preferred method of copper replacement. Our clinic combines oral replacement with a 2
mg weekly IV infusion for one month. Copper salts (copper gluconate or copper chloride)
may be given intravenously. Hematologic abnormalities due to copper deficiency often
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respond completely and promptly. While copper replacement will stop progression of
neurological abnormalities patients are often left with residual symptoms[41].
Neuropathy Following Bariatric Surgery
Obesity is an increasing medical challenge in both developed and developing counties. In
2010, more than 35 % of Americans were obese, and 5% of Americans were morbidly
obese. Bariatric surgery is an effective procedure for weight loss in morbidly obese patients
refractory to a diet and exercise program. More than 200,000 bariatric surgeries were
performed in 2008. The number expected to rise with the increase obesity population.
Neurological complications have gained attention in association with bariatric surgery.
Neurological complications can involve the entire nervous system ranging from diffuse
encephalopathy to peripheral neuropathy to myopathy. Among the neurological
complications seen after bariatric surgery, peripheral neuropathies were the most common
and may affect up to 16 % of operated patients[51]. There were three dominant peripheral
neuropathy patterns seen after bariatric surgery: sensory-predominant polyneuropathy
(acute, subacute and chronic), mononeuropathy and radiculoplexopathy, with the first two
being more common than the radiculoplexopathy[51]. Onset of symptoms could be subacute
to insidious; the time of onset varies from months to years, post-surgery [52,53]. Protracted
vomiting and fast weight loss were risk factors to develop peripheral neuropathy after
bariatric surgery[51, 54].
Malnutrition was not uncommon for morbidly obese patients prior to their bariatric surgery.
Twenty nine percent patients were thiamine deficiency among 379 consecutive patients
undergoing bariatric surgery reported by Flancbaum[55]. The most common nutrient
deficiencies following bariatric surgery are deficiencies of thiamine, vitamin B12, vitamin
E, vitamin D, and copper[56]. Bariatric procedures cause or worsen malnutrition by
restriction of intake or combined restriction of intake and impaired absorption. Peripheral
neurological complications after bariatric surgery are probably related to multiple nutritional
deficiencies. Thiamine deficiency often was seen in painful polyneuropathy post bariatric
surgery, which can present without central involvement (encephalopathy). B12 or copper
deficiencies were the cause of myeloneuropathy, though data was not consistent [51].
Thiamine, B12 and copper should be a part of baseline metabolic work-up for patient
undergoing bariatric surgery, especially patients who were on a diet prior to surgery.
Education regarding the importance of adherence to nutritional supplements after surgery is
the key to prevent peripheral neuropathy developed post bariatric surgery.
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