Complete clinical and functional recovery following low-dose methotrexate related paraparesis in a patient with compound c.1298A>C AND c.677C>T MTHFR polymorphism: A case report

Gianantonio Saviola, Lul Abdi-Ali, Silvano Sacco, Laura Comini, Katrin Plewnia, Maja Rossi, Alfredo Orrico

Research output: Contribution to journalArticle

Abstract

RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine.

PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit.

DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity).

OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene.

LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.

Original languageEnglish
Pages (from-to)e13350
JournalMedicine
Volume97
Issue number49
DOIs
Publication statusPublished - Dec 2018

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Paraparesis
Methylenetetrahydrofolate Reductase (NADPH2)
Methotrexate
Psoriatic Arthritis
Folic Acid
Arthritis
Thymidylate Synthase
Antidotes
Tetrahydrofolate Dehydrogenase
Methylprednisolone
Neurologic Examination
Therapeutics
Vitamin B 12
Neurology
Gait
Adenosine
Genes
Rheumatoid Arthritis
Anti-Inflammatory Agents
Rehabilitation

Keywords

  • Adult
  • Antirheumatic Agents/administration & dosage
  • Arthritis, Psoriatic/drug therapy
  • Diagnosis, Differential
  • Female
  • Humans
  • Methotrexate/administration & dosage
  • Methylenetetrahydrofolate Reductase (NADPH2)/genetics
  • Paraparesis/chemically induced
  • Polymorphism, Genetic

Cite this

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title = "Complete clinical and functional recovery following low-dose methotrexate related paraparesis in a patient with compound c.1298A>C AND c.677C>T MTHFR polymorphism: A case report",
abstract = "RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine.PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit.DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity).OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene.LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.",
keywords = "Adult, Antirheumatic Agents/administration & dosage, Arthritis, Psoriatic/drug therapy, Diagnosis, Differential, Female, Humans, Methotrexate/administration & dosage, Methylenetetrahydrofolate Reductase (NADPH2)/genetics, Paraparesis/chemically induced, Polymorphism, Genetic",
author = "Gianantonio Saviola and Lul Abdi-Ali and Silvano Sacco and Laura Comini and Katrin Plewnia and Maja Rossi and Alfredo Orrico",
year = "2018",
month = "12",
doi = "10.1097/MD.0000000000013350",
language = "English",
volume = "97",
pages = "e13350",
journal = "Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries",
issn = "0025-7974",
publisher = "Lippincott Williams and Wilkins",
number = "49",

}

TY - JOUR

T1 - Complete clinical and functional recovery following low-dose methotrexate related paraparesis in a patient with compound c.1298A>C AND c.677C>T MTHFR polymorphism

T2 - A case report

AU - Saviola, Gianantonio

AU - Abdi-Ali, Lul

AU - Sacco, Silvano

AU - Comini, Laura

AU - Plewnia, Katrin

AU - Rossi, Maja

AU - Orrico, Alfredo

PY - 2018/12

Y1 - 2018/12

N2 - RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine.PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit.DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity).OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene.LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.

AB - RATIONALE: The mechanisms of action of MTX (methotrexate) in the treatment of RA (rheumatoid arthritis) and PsA (psoriatic arthritis) is related to its antifolic activity, due to the high affinity for enzymes that require folate cofactors as dihydrofolate reductase and to the anti-inflammatory activity derivated from the inhibition of thymidylate synthetase that leads to the over-production of adenosine.PATIENT CONCERNS: Our patient was a 41-year-old female, affected by PsA in treatment since 2 years with low-dose methylprednisolone and low-dose subcutaneous MTX. The treatment was effective. The patient subacutely developed a severe paraparesis with impossibility of gait or standing without aid and was admitted to a Neurology Department where the cause of the paraparesis was not clear in spite of accurate radiological neurophysiologic and laboratory tests. Therefore, she was admitted in a rehabilitation unit.DIAGNOSIS AND INTERVENTIONS: Paraparesis in PsA patient in treatment with methotrexate. MTX toxicity was hypothesized; therefore the drug was discontinued while i.m. folic acid and cyanocobalamin were administered for 20 days. The diagnosis was clinical, based on neurological examination (paraparesis) and on the chronic use of MTX (hypothesis of toxicity).OUTCOMES: The patient obtained a complete resolution of paraparesis. Genetic analyses showed associated a compound heterozygosity for the c.1298A>C and c.677C>T variants of methylenetetrahydrofolate reductase (MTHFR) gene.LESSONS: Neurological side effects of MTX are uncommon. In literature no previous case of MTX induced paraparesis in patients treated with low-dose MTX for chronic arthritis has been described. The association between the gene polymorphisms of MTHFR (c.1298A>C and c.677C>T) and MTX toxicity in arthritis patients is confirmed. The case also confirms that folates are a precious antidote of MTX toxicity.

KW - Adult

KW - Antirheumatic Agents/administration & dosage

KW - Arthritis, Psoriatic/drug therapy

KW - Diagnosis, Differential

KW - Female

KW - Humans

KW - Methotrexate/administration & dosage

KW - Methylenetetrahydrofolate Reductase (NADPH2)/genetics

KW - Paraparesis/chemically induced

KW - Polymorphism, Genetic

U2 - 10.1097/MD.0000000000013350

DO - 10.1097/MD.0000000000013350

M3 - Article

C2 - 30544400

VL - 97

SP - e13350

JO - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

JF - Medicine; analytical reviews of general medicine, neurology, psychiatry, dermatology, and pediatries

SN - 0025-7974

IS - 49

ER -