. 2021 Sep 7;22(18):9694. doi: 10.3390/ijms22189694

Table 3.

Laboratory and clinical investigations of the reported cases in the section on vitamin B₁₂ deficiency and HHcy, with main changes after treatment.

References	Laboratory and Clinical Investigation	Main Changes after Treatment
Tanaka et al. [43]	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 [44]	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 [45]	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 [46].	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. [47]	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. [48].	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. [49]	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 [50]	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.