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• Schilling test: The Schilling test is used to determine the etiology of vitamin B-12 deficiency in patients with normal IF antibodies.

• Stage 1: Administer radiolabeled cobalamin 0.5-2.0 mCi PO to fasted patients. One to 6 hours later, administer unlabeled cobalamin 1000 mcg IM to saturate transcobalamin and flush hepatic storage. Measure the percentage of radiolabeled cobalamin in a 24-hour urine specimen. Urinary excretion within the reference range is 10-35% over 24 hours. Reduced urinary excretion of cobalamin, ie, less than 7-9% based on individual laboratory reference range values, in persons with normal renal function supports decreased absorption of oral cobalamin. If excretion is low, proceed to stage 2.

• Stage 2: Stage 1 is repeated with coadministration of porcine IF 60 mg. If the absorption of cobalamin is normalized, the presumptive diagnosis is PA. If poor absorption persists after administration, proceed to stage 3.

• Stage 3: Tetracycline is administered for 5 days prior to reperformance of stage 1 to exclude blind loop as the etiology.

• Stage 4: Pancreatic enzymes are administered with repetition of stage 1 to test for pancreatic disease.

• Caveats: If vitamin B-12 is administered 48 hours before the Schilling test, dilution of the radiolabeled cobalamin and spuriously low apparent urinary excretion and false-positive results occur. False-negative values occur in food-bound malabsorption due to achlorhydria. True negative results are from dietary deficiencies (vegan) and cobalamin binding–protein abnormalities.

• Routine hematologic and chemistry tests

• Hematologic abnormalities may be absent at the time of neurologic presentation.

• Vitamin B-12 deficiency produces the classic picture of macrocytic anemia, with a mean corpuscular value (MCV) greater than 100 fL. The MCV correlates with estimated vitamin B-12 level:
  • MCV of 80-100 fL (normal) indicates less than 25% probability of vitamin B-12 deficiency.

  • MCV of 115-129 fL indicates a 50% probability.

  • MCV greater than 130 fL indicates a 100% probability.

• Peripheral blood smear shows macro-ovalocytosis, anisocytosis, and poikilocytosis, as well as basophilic stippling of the erythrocytes and Howell-Jolly bodies. Reticulocyte count can be within the reference range or low. Hypersegmentation (>5% of neutrophils with >5 lobes or 1% with >6 lobes) of polymorphonuclear cells may occur without anemia. Thrombocytopenia is observed in approximately 50% of patients, and platelets often have bizarre size and shape.

• Serum indirect bilirubin and lactate dehydrogenase (LDH) may be elevated because PA can have a hemolytic component.

• Achlorhydria is present in many patients with PA.

• Laboratory parameters after administration of vitamin B-12

• Anemic patients
  • Reticulocytosis starts in 3-4 days and peaks at 1 week.

  • Hemoglobin concentration rises in 10 days and returns to the reference range in 8 weeks.

  • LDH falls within 2 days.

  • Hypersegmented neutrophils disappear in 1-2 weeks.

• Patients with severe anemia and borderline-to-low iron stores
  • Serum iron level falls within 24 hours because of increased erythropoiesis.

  • Hypokalemia may develop because of increased potassium utilization in hematopoiesis.

Imaging Studies:

• Because of the increased incidence of gastric cancer in PA, gastric radiographic series are suggested at the first visit.

• In patients with myelopathy, MRI may reveal regional T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities mainly in the thoracic posterior columns with possible extension into the brain stem. In patients with chronic disease, atrophy of the spinal cord is observed.

• Brain MRI may show T2 and FLAIR hyperintensities in the cerebral white matter and around the fourth ventricle.

• Brain MRI of infants with vitamin B-12 deficiency may show delayed myelination.

Other Tests:

• Abnormal evoked potentials may be the first electrodiagnostic finding, even in asymptomatic patients with normal neurologic examination findings. The abnormalities are often referable to a central conduction defect; however, peripheral nerves are also affected.

• Somatosensory evoked potentials (SSEP) may reveal prolongation of L3-P27 latency, reflecting a defect in conduction in the large-fiber sensory pathway between the cauda equina and the contralateral sensory cortex.

• Visual evoked potential (VEP) findings are as follows:

• VEP findings may be abnormal even without visual symptoms or signs.

• Prolongation of the P100 waveform can be unilateral or bilateral.

• P100 may normalize after cobalamin replacement.

• Nerve conduction study (NCS)/EMG findings are as follows:

• In 1943, Dynes and Norcross found evidence of neuropathy in 23% of patients with PA.

• In a recent study, up to 65% of untreated patients had peripheral neuropathy.

• Axonal sensorimotor polyneuropathy is present in up to 80%. Demyelinating or mixed forms are less frequent.

• Typical features are decreased conduction velocities and motor or sensory amplitude and denervation on EMG.

• In 1991, Healton et al found decreased motor nerve conduction velocities (NCV), absent or reduced sensory potentials, and fibrillations in the distal muscles indicating mixed demyelinating-axonal disease in 7 of 9 cases of vitamin B-12 deficiency and neuropathy.

• In 1998, Steiner et al described 5 patients with demyelinating polyneuropathy.

• Sensory nerves are usually more affected than motor nerves and are more severely affected distally than proximally. Proximal focal conduction block has been reported, which reversed on treatment.

• Electroencephalography (EEG) findings may be normal or show nonspecific slowing. Follow-up EEG findings may be improved in response to treatment.

Procedures:

• Bone marrow aspiration may be performed for histologic examination.

Spinal cord findings

• Macroscopic: It may be shrunken in anteroposterior diameter. The posterior and lateral columns may be gray-white in color.

• Microscopic: Multifocal vacuolated and demyelinated lesions exist in the white matter of the posterior and lateral columns. Early in the course, myelin sheaths are swollen, but axons appear normal; the largest fibers are predominantly affected. Demyelination starts in the center of the posterior columns of the upper thoracic cord. Then, lesions spread laterally and cranially to the lateral corticospinal tracts in the cervical segments and the medulla. Myelin breakdown, foamy macrophages, and occasional lymphocytes are characteristic, predominantly in a perivascular location. As demyelination and vacuolation increase, axons degenerate. Gliosis may be present in older lesions.
  • Electronic microscopic findings have only been used in nonhuman primates, not in humans. In the rhesus monkey model, the posterior and lateral spinal cord shows myelin degeneration characterized by separation of myelin lamellae and formation of intramyelin vacuoles leading to complete destruction of the myelin sheath and later to degeneration and loss of axons and gliosis.

  • Vitamin B-12 deficiency myelopathy is virtually indistinguishable from vacuolar myelopathy in AIDS, which is also characterized by vacuolation between the myelin sheaths accompanied by macrophage infiltration. However, the presence of multinucleated giant cells is characteristic of AIDS and not of vitamin B-12 deficiency.

Brain findings

• Macroscopic: The brain appears normal.

• Microscopic: Findings resemble the spinal cord pathology with scanty small perivascular foci of demyelination within the white matter featuring myelin swelling and axon degeneration. The optic nerve typically shows degeneration, predominantly in the papillomacular bundles.

Peripheral nervous system findings

• Unlike EMG/NCS findings, which indicate predominantly axonal or mixed axonal-demyelinating neuropathy, histologic examination suggests either primary demyelinating or axonal neuropathy with secondary demyelination. However, most studies were performed before the introduction of semithin, teased fiber, and electron microscopy analysis.
  • A biopsy of the anterior tibial nerve recorded loss of myelin sheath and no loss of axons (Greenfield, 1934).

  • A sural biopsy revealed loss of myelinated fibers and no demyelination in teased fibers, indicating secondary demyelination (McCombe, 1984).

  • In 1959, Coers and Woolf found endplate and preterminal axon abnormalities in muscle biopsies of patients with cobalamin deficiency, suggesting axonal damage.

• The pathology is better described in animal models. In cobalamin-deficient rats, electron microscopy revealed intramyelin and endoneural edema, with no or minimal axonal damage (reversible on administration of cobalamin) in nerves, dorsal root ganglia, and the ventral and dorsal roots.

Nonneurologic findings

• Bone marrow hyperplasia

• Mild-to-moderate splenomegaly

• Increased iron deposits in the reticuloendothelial system

• Atrophy in all layers of the stomach, sparing the pyloroduodenal region

-- Cyanocobalamin is used to replenish the deficiency caused by any of the etiologies described. Drug Name Cyanocobalamin or vitamin B-12 (Berubigen, Cyanoject) -- Most stable and available form of vitamin B-12. Absorbed rapidly to the organism from IM or SC applications. Oral cyanocobalamin can replace parenteral formulations. Is effective in PA because 1% of free cobalamin is absorbed via diffusion rather than requiring the presence of IF. Adult Dose Parenteral administration: 1000 mcg/d IM/SC for 5 d or 1000 mcg IM 2 times per wk for 2 wk, then 1000 mcg/wk IM/SC for 5 wk, then 100-1000 mcg IM/SC every mo Oral administration: 1000-2000 mcg PO qd for life Pediatric Dose Parenteral administration: 1000 mcg IM qd for 2 wk; congenital disorders require lifelong replacement of 1000 mcg every mo Oral administration:<12 years: Not established >12 years: Administer as in adults Contraindications Documented hypersensitivity; Leber disease, ie, hereditary optic nerve atrophy (patients may experience severe and swift optic atrophy when treated with vitamin B-12); severe megaloblastic anemia (hypokalemia and sudden death may occur) Interactions Colchicine, paraaminosalicylic acid, and excessive ingestion of alcohol may produce malabsorption of vitamin B-12; chloramphenicol may reduce cobalamin efficacy through interference with erythrocyte maturation Pregnancy A - Safe in pregnancy Precautions Pregnancy category C if dose exceeds RDA; very rarely patients report adverse effects (most commonly asthenia, headache, pruritus, diarrhea, and dizziness); serious reactions such as anaphylaxis and vascular thrombosis may occur; severe hypokalemia may result after correction of megaloblastic anemia because of increased cellular potassium requirements Drug Name Folic acid (Folvite) -- Folate supplementation can reverse the hematologic abnormalities, but the neurologic manifestations only respond to cobalamin. Adult Dose 1 mg PO/IM/SC qd Pediatric Dose <12 years: Not established >12 years: 1 mg PO/IM/SC qd Contraindications Documented hypersensitivity Interactions Increase in seizure frequency and subtherapeutic levels of phenytoin reported when used concurrently Pregnancy A - Safe in pregnancy Precautions Pregnancy category C if dose exceeds RDA; benzyl alcohol may be contained in some products as a preservative (associated with a fatal gasping syndrome in premature infants); resistance to treatment may occur in patients with alcoholism and deficiencies of other vitamins   [8]ページ先頭 ©2009-2026 Movatter.jp