2. Vitamin B12 and Anemia
3. Vitamin B12 and Neurological Disorders
4. Vitamin B12 Deficiency and Hyperhomocysteinemia
Conflicts of Interest
|ADMA||8-isoprostaglandin F2α dimethy larginine|
|DRS-R-98||Delirium Rating Scale—Revised-98|
|MICD||metformin induced cobalamin deficiency|
|MADRS||Montgomery Asberg Depression rating scale|
|MCV||mean corpuscular volume|
|MMSE||Mini-Mental State Examination|
|MTHFR||5,10-methylenetetrahydrofolate reductase gene|
|RDAs||recommended dietary allowances|
|RBCs||red blood cells|
|SCD||sub-acute combined degeneration|
|SDMA||arginine and symmetric dimethyl arginine|
|TPHA||Treponema pallidum hematoglutinin assay|
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|References||Laboratory and Clinical Investigation||Main Changes after Treatment|
|Socha et al. ||Full blood profile, Folate levels, Vitamin B12 levels|
Parietal cell antibody, Conventional cytogenetics,
Hematologic neoplasm next-generation-sequencing panel (62 genes) for disease-associated mutations.
|Case 1: Abnormal complete blood cell count findings improved, as did neurologic symptoms.|
Case 2: rapid improvement of hematologic symptoms and slower but complete resolution of neurologic symptoms.
|Garcia et al. ||Hb, MCV, Folate levels, iron, ferritin, vitamins B2, B6, and B12 levels, gastroduodenoscopy and gastric biopsy, Antibodies against intrinsic factor and Helicobacter pylori detection||At 12 months the patient was free of the Recurrent aphthous stomatitis with normal levels of hemoglobin, MCV, and vitamin B12.|
|Pontes et al. ||Full blood count, Folate levels and vitamin B12 levels||After 14 days of treatment complete remission of all symptoms.|
|Pahadiya et al. ||Full blood profile, vitamin B12 levels, LDH, bilirubin|
Bone marrow aspiration, antinuclear antibody and Coomb’s test, Coagulation profile, iron profile Renal function tests, urinalysis and electrolytes Gastroscopy, electrocardiograph, ultrasonography of abdomen, and chest X-ray
|At the follow-up of 1 month, hematological parameters were within normal limits and ecchymosis disappeared.|
|Surani and Sharma ||Full blood profile, Folate levels, vitamin B12 levels||Hemoglobin improved to 10.3 gm/dL after four days. Complete blood count showed a complete resolution of pancytopenia at two months follow up. Vitamin B12 and folate level normalized.|
|Hussain et al. .||Full blood profile, Vitamin B12, Folate, Haptoglobin, MMA, Intrinsic factor antibody||At six-month follow-up clinical and laboratory analysis improvement (e.g., hemoglobin improved to 11.9 gm/d).|
|Sasi and Yassin .||Full blood profile, B12 level, Bilirubin, LDH|
Haptoglobin, direct antiglobulin (DAT)
Serum iron, thyroid functions
|Blood cell counts started showing an upward trend on day 4 after starting the treatment. On discharge, after 10 days of hospital stay, improvement of blood profile and vitamin B12 (from values <37 pmol/L to 369 pmol/L), remission of all symptoms.|
|References||Laboratory and Clinical Investigations||Main Changes after Treatment|
|Ralapanawa et al. ||Full blood profile, serum creatinine, plasma glucose, thyroid stimulating hormone levels, vitamin B12 levels, nerve conduction studies||After 3 months, clinical improvement, with repeated B12 levels being elevated up to 308.6 pg/mL. Follow up at 1 and 3 years showed improvement of nerve conduction.|
|Ekabe et al. ||Full blood profile, HIV test, Treponema pallidum hematoglutinin assay (TPHA), erythrocyte sedimentation rate and peripheral blood smear analysis, stool exam and urinalysis||At 1 months follow up good clinical recovery, improvement in neurological symptoms and a follow up MCV of 97 fl, red blood cell count of 4.1 million/µL, and reticulocyte count of 0.95%.|
|Maamar et al. ||Full blood profile, Somatosensorial evoked potential (SEP), MRI, vitamin B12 levels, Folate levels, bone marrow biopsy||Correction of the neurological signs (paresthesis and sphincter disorders).|
|Senol et al. ||Blood glucose, AST, ALT, blood urea nitrogen, creatinine, Hb, MCV, white blood cell count, sedimentation rate, Vitamin B12 levels, HbA1C level, Somatosensorial evoked potential (SEP), Electromyography, Gastric endoscopy and biopsy, Brain MR, Cervical spine MR imaging||At two months follow up complete resolution of symptoms, MR imaging abnormalities significantly improved; impairment of the Somatosensorial evoked potential continued.|
|Srikanth et al. ||Full blood profile, bone marrow biopsy, Visual evoked potential and brain stem evoked potential studies, Gastric endoscopy and biopsy, workups for infections, para infectious myelitis, multiple sclerosis and connective tissue disorders, Folate levels, vitamin B12 levels, cervical MR examination||At 10 months follow-up, MRI revealed total resolution of cord abnormality.|
|Kumar ||Full blood profile, bone marrow biopsy, vitamin B12 levels, Folate levels, Anti-intrinsic factor antibody Gastric endoscopy and biopsy, Brain CT scan, EEG||At 24 months follow-up resolution of seizure and functional independence.|
|Mavromati & Sentissi ||Full blood profile, Electrolytes, vitamin B12 levels, Folate levels, Lyme’s test brain MRI, Neuropsychiatric tests||At 1 week normalization of vitamin B12 level (330 pmol/L); at 2 weeks important diminution of the cognitive deficiency and a partial remission of the depressive symptoms (MADRS score 22, MMSE 28/30 and DRS-R-98 4; the clock test was normalised). Four weeks after the episode total remission of the depressive symptoms (MADRS score: 4) and stable mental status.|
|References||Laboratory and Clinical Investigation||Main Changes after Treatment|
|Tanaka et al. ||Full blood profile, prothrombin time, protein C, protein S levels, total homocysteine, folic acid, vitamin B12 (Antinuclear antibody (fluorescent antibody technique), immunoglobulin G anticardiolipin antibodies (IgG ACA), phospholipid (GPL), Lupus anticoagulant (diluted Russell’s viper venom time rate). Tumor marker, carcinoembryonic antigen (CEA carbohydrate antigen 19-9, and a-fetoprotein (AFP), CT||Serum homocysteine level decreased (total homocysteine: 12.4 mmol/L), and swelling of his leg improved with significant resolution of thrombus by CT.|
|Kapur ||Full blood profile, Peripheral blood film, serum cobalamin levels, prothrombin time, protein S, antithrombin III, fibrinogen levels, factor V Leiden assay and prothrombin gene mutation, fasting total serum homocysteine levels, neurological examination, Cerebrospinal fluid examination, CT, MRI||Significant improvement of neurological symptoms. At 6 months normal serum cobalamin 364 pg/mL (200–600) and fasting total homocysteine levels 8.4 μmol/L (5.0–13.9). The rest of the thrombophilia profile was within normal limits.|
|Ammouri ||Full blood profile, prothrombin time, partial thromboplastin time, fibrinogen level, protein C, protein S levels, antithrombin III function, genetic testing for factor V Leiden and factor II mutation, plasma homocysteine level, cobalamin plasma level, folate plasma, antibodies to intrinsic factor, bone marrow biopsy, chest radiographs, ECG, TC, Ultrasonography||Case 1: After a 1-year follow up total remission of psychiatric disorders and thrombotic events. Hemoglobin and homocysteine plasma levels were within normal range.|
Case 2: At 6-month follow-up period, hemoglobin and homocysteine plasma levels were within normal range. No thrombotic events for 3 years after the follow-up.
Case 3: At 6-month follow-up period, hemoglobin and homocysteine plasma levels were within normal range. No thrombotic events during 4 years of follow-up.
Case 4: At 3-year follow-up no psychiatric disorders and thrombotic events. Homocysteine plasma level was within normal range.
|Ulrich .||Full blood profile, holotranscobalamin plasma levels, total homocysteine, MMA, Folate, zinc and copper, Electroneurography, CT, MRI.||Cyanocobalamin, MMA and homocysteine levels continuously decreased, and were normal again after 1 month; improvement of sensory disturbances and gait ataxia; At 2 months follow-up MRI showed significant regression of the dorsal column hyperintensities.|
|Kovalenko et al. ||Full blood profile, troponin, blood urea nitrogen, creatinine, serum electrolytes, B-type natriuretic peptide level, Factor V Leiden, prothrombin mutation, cardiolipin antibody, lupus anticoagulant, anti-B2 glycoprotein, protein C, protein S levels, Homocysteine level, vitamin B12, folate levels, chest radiographs, ECG, echocardiogram, Pulmonary angiography||Serum Hcy levels did not decrease to normal values.|
|Goette et al. .||Full blood profile, lipid profile, Liver function tests (γ-glutamyl transpeptidase, Alanine transaminase and aspartate aminotransferase, bilirubin), activated partial thromboplastin time, international normalized ratio, thrombin time, activated recalcification, fibrinogen, clotting factors II, XII and VIII levels, protein C, protein S, anti-phospholipid antibodies, vitamin B12, folate, Hcy, analyses of cofactors and enzymes involved in homocysteine metabolism, serum levels of 8-isoprostaglandin F2α dimethy larginine (ADMA), Plasma concentrations of arginine and symmetric dimethyl arginine (SDMA), serum level of creatinine, urine analysis 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, TC, computed tomography angiography, ultrasound, echocardiogram||At 2 weeks follow-up level of homocysteine had decreased to 57.6 μmol/L. Three weeks later homocysteine level was 18.1 μmol/L, and after 3 months it was 5.5 μmol/L. After completing his the following metabolites had decreased: ADMA, to 0.363 μmol/L; SDMA, to 0.32 μmol/L; arginine, to 62.8 μmol/L; light reflex rheography and oscillography shown normal perfusion; improvement of pain, paraesthesia in right leg and increasing of pain-free walking distance.|
|Ruscin et al. ||Full blood profile, vitamin B12, methylmalonic acid (MMA), total serum homocysteine, serum folate, serum creatinine, renal function test.||At first follow-up vitamin B12 has increased, MMA and HCYS was reduced at 351 nmol/L and 23.7 µmol/L respectively. At second follow-up vitamin B12 was normal; MMA and HCYS were further reduced but remain slight elevated.|
|McCaddon ||Full blood profile, vitamin B12, serum and red cell folate, plasma folate, parietal cell antibodies, total serum homocysteine, cognitive tests.||Case 1: improvement in memory and cognitive tests.|
Case 2: Within one month tHcy fell to 7.5 μmol/L; no significant cognitive deficits.
Case 3: No improvement; the patient died from a bronchopneumonia several weeks later.
Case 4: At six-months follow up tHcy fell to 6.6 μmol/L; marked improvement in general behaviour observed also three years later.
Case 5: improvement in cognitive tests.
Case 6: tHcy fell to 9.6 μmol/L; improvement in cognitive tests.
Case 7: At one month follow-up tHcy fell to 8.3 μmol/L; improvement in cognitive tests. At one year follow up MRI scan showed no significant progression in the extent or size of the focal areas of abnormality in the deep white matter, and no change in ventricular configuration.
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